[Use of colposcopic examinations in the determination of the birth term]. The authors have determined with the help of colpo-cytological examination the birth's time wich can be expected in 375 pregnancy. Their experiences: 1. With colpo-cytological examination in 76,8% of the cases they could determine the time of the expected delivery. 2. This method can offer precious facts to diagnose overcarrying. 3. This method is simple, quick, cheap, and can be performed everywhere.


[Urocytogram in the treatment with bleomycin]. Even though Bleomycin is excreted in the urine in high concentrations, side effects in the urinary tract due to the chemical nature of this compound are seldom observed. With respect to treatment of gynecological carcinomas, it is, therefore, important to examine the effect that Bleomycin when treatment involves the use of Endoxan. Cytologically, one finds an increase in desquanmation of the transitional epithelium and an increase in degenerate cell forms. The homogenous eosinophilic cellular inclusions which are observed, are specific for neither Endoxan nor for Bleomycin treatment. The antibiotic effect of Bleomycin results in an aseptic cystitis. The urocytogramm is suitable for examining the epithelial changes of the urinary tract in context with the gynecological carcinoma treatment and also for determing tumor breakthough into the bladder.


[Studies on mobility and prognosis in spondylitis ankylosans]. 278 patients with ankylosing spondylitis have been studied in order to find a basis for prognosis by setting a mobility function index of the vertebral column. This index does not depend on manifestation age or on the blood sedimentation rate. It increases with progression of x-ray findings. A coincidence of impaired mobility and overweight is relatively frequent and function index and electrophoresis are correlated. In contrary to this study a study of the course gives probably more prognostic indications.


[Cytotopochemistry of lipids in vaginal smears of pregnant women]. The author presents a preliminary paper upon cytotopochemical evaluation of lipids in the vagina epithel in physiological and pathological gravidity to the Vth lunar month. The staining has been carried out by the method with Red Oil O. Besides that the vaginal smears have been evaluated also on the base of their pycnotic and eosinophilic index by staining after Shorr. There have been examined 94 women divided into two groups, i.e. with physiological and pathological course of gravidity and evaluated 282 smears in total. The author means that the occurence of irregularly located bigger lipid inclusions in the cytoplasma of cells is a signalisation of cytotopochemically estimated structural changes caused most probably by a disturbance of the hormonal balance. The results have been worked out statistically.


Serum and synovial fluid concentrations of alpha2 macroglobulin and alpha2 neuroamino-glycoprotein in rheumatoid arthritis. The serum and synovial fluid concentrations of alpha2 macroglobulin and alpha2 neuramino glycoprotein of patients with rheumatoid arthritis have been studied. For, both protein fractions have antiprotease activity and inhibit, though to different degrees, many factors concerning inflammation. Even though both fractions have certain activities in common, in rheumatoid arthritis, we neither see a parallel increase nor antagonistic actions in the case of alpha2 macroglobulin and alpha2 neuramino-glycoprotein.


[Study of human secretory immunoglobulin A. I. Obtaining monospecific antiserum to human secretory immunoglobulin A]. A method of obtaining monospecific antiserum to the human secretory IgA is described. Immunochemically pure secretory IgA (isolated from human colostrum by fractionation with ammonium sulfate and gel-filtration on Sephadex G-200) was used for immunization of rabbits or sheep. Heterologous antibodies were removed by adsorption with commercial gamma globulin, normal serum, the serum of a patient suffering from A-myeloma with the IgA polymere and purified lactoferrin. Monospecific antiserum to the secretory IgA gave a reaction of complete immunological identity with the secretory IgA and a free secretory component.


[Use of the oblique illumination method for characterizing N. meningitidis cultures]. The authors used the method of oblique illumination for detection of the state of the population of meningococcus cultures. In studying 48 strains there were revealed three types of fluorescence of the colonies: bright orange with a transition into greenish-light blue along the lower margin (the I type), bright light blue with a narrow orange or green upper margin (the II type) and greyish-light blue colonies (the III type). The type of fluorescence was not associated with the sero-group specificity. Populations of meningococcus cultures, depending on conditions and duration of growth on the nutrient medium could consist both of the colonies with the same type of fluorescence, and also represent a combination of colonies with a different type of fluorescence. The colonies of the I and II types of fluorescence had marked group specificity, but mutation occurred during passage and the III type of fluorescence formed with a loss of serological specificity. Continuous selection of the colonies of the I and the II types of fluorescence permitted to preserve the population with specific properties necessary for production of diagnostic and vaccine preparations for a long time.


[Study of the antigenic structure of Salmonella by means of immunoelectrophoresis]. The method of immunoelectrophoretic analysis was applied to the study of the antigenic structure of 180 freshly-isolated and laboratory cultures of salmonellae belonging to 29 serological types. A complicated set of specific and common antigens of bacteria was revealed in direct and cross experiments with the use of homologous and heterogenous antisera; immunophoregrams were drawn for each of the serological type under study. General regularities in immunophoretic, diffuse and serological characteristics of the individual antigens of salmonellae were established. It was shown that different serological types of salmonellae possessed surface K antigens along with the O and H antigens. On immunophoregrams K-antigens of salmonellae were revealed in the form of a bright precipitation arch in the central or the anode zone; O antigens gave a characteristic two-component precipitation line in the cathode zone of the phoregram.


[Heparin and the heparin-precipitated human blood plasma fraction in the rosette formation reaction]. Experiments were conducted on CBA mice. The effect of heparin and of the fraction of human blood plasma precipitated by heparin (FPH) on the course of the specific immunity reaction, i.e. of rosette-formation, was studied. Inhibition of the mentioned reaction by FPH was revealed. No such effect was produced by heparin. Experiments were carried out in vitro. The results of the mentioned experiments were compared with literature data on the effect of heparin and FPH on other immunological reactions. A supposition was put forward that these substances interacting with lymphocytes had different points of application: heparin-cellular membrane, FPH-superficial cell receptors.


[Study of the role of type-specific antigen in the process of Shigella flexneri interaction with epithelial cell and macrophage cultures]. Epithelial cells of the HEp-2 line infected in parallel by genetically connected strains of Sh. flexneri, differing in the capacity to synthesize the type antigen were studied morphologically. The type antigen proved to show no significant influence on the penetration of dysentery bacilli into the cell. A study of the process of phagocytosis of the mentioned strains by a culture of peritoneal macrophages of guinea pig demonstrated that the presence of a type antigen communicated to the bacteria some selective advantages within the macrophages increasing their resistance to the action of the digestive enzymes.


[Obtaining purified preparations of individual Shigella newcastle K- and O-antigens by using an ultracentrifugation method]. A modified method of obtaining the purified K- and O-antigens of Sh. newcastle with the use of ultracentrifugation is described. Serologically individual K- and O-antigens were obtained and their chemical composition was studied. Polysaccharide of the K-antigen consisted of the galacturonic acid, galactose, glucose, rhamnose xylose and hexosamine; it contained no heptoses. The O-antigen contained galactose, glucose, mannose, rhamnose, heptose and hexosamine; in difference to K-antigen was equal to 150000--160000. Thus, the K- and the O-antigen differed not only in the electrophoretic and diffuse mobility and immunological specificity, but also in the chemical composition.


[The role of microsocial and psychological factors in the development of stable psychological changes in children]. The author conducted a clinical study of 305 children with epilepsy, the results of which were correlated with stable psychic changes, microsocial, psychological factors and identical heredity. It was established that pathological personality traits in the parents, a situation of conflicts in the family and a wrong rearing were significantly higher in mentally changed epileptic children. An identical hereditary loading does not form significant correlations with stable mental changes. The conclusion is being made that an unfavourable situation may exert a certain impact on the formation of a character in children with eilepsy.


[Isolation of carcinoembryonic antigen]. A method employed in the authors' laboratory for isolating the carcinoembryonic antigen (CEA) from tumours of the entodermal digestive tract and their metastases is described. The main step is fractionation of the preparations obtained by perchloric acid extraction using gel filtration on Sephadex G-200, Sepharose 4 B, and Sepharose 6 B at pH 4.5 and 7.0. The peaks with CEA-specific antigeneity were characterized by the distribution coefficient of the CEA between the mobile and the stationary phases (Kav), and by the relative elution volume (ve/vo). The CEA purified by gel filtration could not reliably be enriched through preparative electrophoresis in Sephadex G-25 gel, polyacrylamide gel or Pevikon powder. The isolation procedures used were compared with those reported in the literature, and the results obtained are discussed.


[Total resection of prostate and vesicle. Sacrococcygeal approach (author's transl)]. The author's technique is illustrated with 10 cases. It is an enlarged approach compared to the classical sacrococcygeal approach, that supposes opening of the sacral canal and location of the last sacrococcygeal nerve endings. The sacrum is divided as high as possible, usually at the level of the middle of S4. This yields excellent view of the junction between prostatic apex and membranous urethra. Section of the urethra at the chosen level can be very precise and completely preserves the innervation and vascularisation of the membranous urethre together with the sphincter function. Resection originates with division of urethra followed by uplifting of prostate and vesicles after ligation and division of the vascular pedicles. The anterior aspect of the bladder is opened and the trigone located. This makes possible the circumscription of the cervix and finally the division of the vas deferens and their vasculatures. This removes the prostate, seminal vesicles, vas ampullae and Denonvilliers aponeurosis en bloc, while scrupulously following the classical rules of carcinologic resection. Reconstruction is obtained either by direct anastomosis between anterior bladder wall and urethra, if enough tissue is available, the opening being closed like a racket; either by inserting a tube flap of reversed Boari type, taken from the anterior and lateral bladder wall. Urinary continency was complete within 3 months in 7 of the 10 operated patients. Two had stress incontinency. They both had extensive lesions and one had invasion of the membranous urethra and bladder cervix, the other had osseous sacrococcygeal matastases. A third patient contends he is incontinent 6 months after operation without obvious functional or neurological disturbance. The author advocates the present technique for its good results concerning continency. However it is still a preliminary work comprising only 10 cases.


Clinical and haemostatic parameters related to thromboembolism and low-dose heparin prophylaxis in major surgery. In a study of 112 patients undergoing elective major surgery clinical and haemostatic data was followed in connection with a double-blind investigation on the effect of subcutaneous low-dose heparin prophylaxis. None of the patients developed severe thromboembolism but according to lung photoscanning and leg scanning 41 of the patients had deep vein thrombosis and/or pulmonary embolism. Clinically thromboembolism appeared within 4 days after operation. In 22 patients with epidural anaesthesia the incidence of thromboembolism was lower than in the patients with general anaesthesia. The extension of the operation was positively correlated to a higher incidence of thromboembolism. The surgical trauma was reflected in most of the routine haemostatic laboratory parameters, hiding possible minor changes caused by subclinical thromboembolic complications. The low doses of heparin could only be detected with more sensitive methods. A comparison of sodium and calcium heparin administered subcutaneously revealed no significant differences.


The extraction and partial purification of the deoxycholate-soluble matrix protein from human plantar horny layer. The electron-dense, amorphous matrix protein in human horny cells was extracted with deoxycholate. The deoxycholate-soluble material was partially purified by differential centrifugation and molecular sieve chromatography. Approximately 44% of the total protein was extracted into the 270,000 g supernatant fraction. Macroaggregates with histochemical characteristics indentical with those in situ keratohyalin granules were formed upon dialysing the 270,000 g supernatant fraction against redistilled water. Antibody was raised to the purified material of the initial peak from the Sepharose 6B column. The resulting antiserum yielded a single precipitin line when tested against the immunizing antigen. Electrophoresis in the presence of sodium dodecylsulfate showed this antigenic material to be heterogeneous. It was immunologically homogeneous when this antigenic material was examined by immuno-electrophoresis. Since the antibody was localized on the keratohyalin granules of human planter skin by indirect immunofluorescence, the partially purified, deoxycholate-soluble material from human plantar horny layers is considered to originate from keratohyalin granules. Amino acid analysis revealed a high content of glycine, glutamic acid and aspartic acid, and a low content of histidine and leucine.


Surface ultrastructure of human skin.

Surface ultrastructure of human skin. The normal human skin surface was studied with a combination of scanning electron microscope, surface replication method, and transmission electron microscope. All specimens were prepared with the critical point drying (CPD) method. Horny cells were found to stack up in columnar fashion with their peripheries overlapping. The surface of a non-nucleated horny cell, therefore, showed a dome-shaped elevation in the center, transmitting the nuclear bulge of the underlying granular cells; parallel double lines at the periphery representing its true cell border and depressed, step-like imprint of the cell border of the cell which once overlapped; and on high magnification the true surface of the separated desmosomes. The surfaces of the horny cells showed many bizarre marks but were relatively smooth. The underside of the surface horny cells, however, bore villi except in areas overlapping the periphery of the underlying cell. Tissue cultured keratinocytes also stacked up when the keratinized and the cell periphery also overlapped. However, the overlapped cell border did not leave the imprint on the underlying cell, probably because of the lack of pressure from above.


A comparative study of tumor cells from metastatic carcinoma of the breast in effusions. Fluids caused by metastatic tumors in body cavities were reviewed for the 20 year period of 1953 through 1972. Presented is a study of 115 cases of effusions secondary to metastatic breast carcinoma with emphasis on recognizing cytologic criteria for various breast tumors and determining which cells occur with consistency. Utilizing various characteristics of both individual and aggregates of malignant cells, specific guidelines were established. Delineating characteristics include cell size, individual cell morphology, and pattern of cellular adherence. These criteria allowed the differentiation between infiltrating ductal carcinoma, medullary carcinoma, and lobular carcinoma as well as metastatic tumors from other sites.


Embryology of the epidermis: ultrastructural aspects. III. Maturation and primary appearance of dendritic cells in the mouse with mammalian comparisons. The epidermis of mice ranging in age from prenatal day 17 through postnatal day 4 and, in addition, postnatal day 18, was studied with the electron microscope. In the 17 day fetus, the periderm may or may not be present and a stratum corneum is developing in the latter case. The cells of the strata spinosum and granulosum contain much glycogen and many keratinosomes and homogeneous keratohyalin granules which appear to line up in a row near the distal cell membranes, fuse and form keratinized cells which contain material similar in density to that of the individual keratohyalin granules. In the 18 to 20 day fetuses, no periderm is present. The stratum corneum becomes well-developed. The quantity of glycogen decreases but the number of keratinosomes and keratohyalin granules increases. Some cells in the basal region contain necrotic phagocytosed cells. Few changes occur in the epidermis of the neonate, although the stratum corneum increases in thickness. In the early postnatal period, the mouse epidermis is mature in appearance and resembles that of man. By postnatal day 18, the whole epidermis is much thinner, although all classical strata can usually be identified. The primary appearance and subsequent maturation of epidermal dendritic cells was also studied in the mouse during the embryonic, fetal, early postnatal and 18 day postnatal periods. Melanocytes which lacked cell processes were first identified in the 15 day fetus. Melanocyte cell processes and an increasing number of melanosomes, as well as melanocytes, are present between prenatal day 18 and postnatal day 3. On postnatal day 4, fewer melanocytes are present and they contain vacuoles. Phagocytosed melanocytes are also present within basal keratinocytes. Undifferentiated dendritic cells or indeterminate cells are observed beginning on prenatal day 16. These cells do not appear to increase significantly in number subsequently. On postnatal day 18, Langerhans cells and indeterminate cells are present but no melanocytes can be identified. No Merkel cells were observed. Mitotic dendritic cells or dendritic cells traversing the basal lamina were not observed.


Ultrastructural features of mast cells in systemic mastocytosis. A 3-year-old boy with systemic mastocytosis has been observed since the age of 4 months when he was first diagnosed as suffering from urticaria pigmentosa. Involvement of skin, liver, spleen and bones was observed. The electron microscopy of skin and liver revealed varied alterations in the morphology of mast cells. The most important findings were irregularly-shaped cells and unusual long and interdigitated cytoplasmic villi, with consequent aggregation of mast cells which was more prominent in the dermis. Proliferation and accumulation of mitochondria in one part of the cell and deeply indented nuclei were frequent. The problem, whether the morphological changes encountered--especially the complex interdigitation of villi--should be interpreted as a sign of expected neoplastic development, is discussed.


Evaluation of the different techniques utilized in diagnosing breast lesions. This study demonstrates the practical advantage of using more than one technique in evaluating breast tumors. Thionin stained, frozen sections and H & E stained, paraffin-embedded, permanent sections yielded a high degree of accuracy in differentiating benign from malignant lesions. Papanicolaou stain is essential for evaluating cytologic material. Special stains, enzyme histochemistry, and examination by SEM and transmission microscopy are essential in identifying the various cellular components of mammary tumors. On the basis of these techniques, fibroadenomas were defined as tumors of stromal cells of the lobule and sclerosing adenosis as a benign proliferation of myoepithelial cells; and it was suggested that mammary cancers may arise from myoepithelial ductal epithelial, or ductular epithelial cells. The behavior of the tumor is related to its cell of origin.


Ultrastructural changes in scleromyxedema. Skin biopsy specimens from a 60-year-old patient with paraproteinemia and generalized changes of the skin typical of scleromyxedema were studied with the electron microscope. The dermis was dominated by collagen fibrils and accumulations of peculiar connective tissue cells, while elastic tissue was sparse and in some areas completely absent. Large, sharply demarcated areas of a filamentous material were occasionally observed. The collagen fibrils were often surrounded by thin filaments with a periodic segmentation and by many glycosaminoglycan (mucopolysaccharide) filaments. The elastic fibres contained large amounts of elastic fibrils and small amounts of a homogenous matrix. The cytoplasm of the above-mentioned cells was dominated by lysosomes in different stages of development, often occupying almost all the cytoplasmic area. The collagen fibrils were found in close relation to these cells, frequently inside invaginations of the cells. Furthermore, collagen fibrils were observed free in the cytoplasmic area and inside the lysosomes, indicating lysosomal degradation of collagen.


Treatment of generalized scleroderma with inhibitors of connective tissue formation. 103 patients suffering from generalized scleroderma were studied in order to assess the effect of treatment with inhibitors of connective tissue formation. 93 patients with generalized scleroderma were given D-penicillamine, benzyl-penicillin-diethylamino-ethyl-ester hydroiodide, adrenal glucocorticoids, dextro-thyroxine, hydralazine, and "mixed treatment" (one or several of the drugs in consecutive courses, or concurrently). The effect of dextrothyroxine could not be evaluated in this study. No improvement could be seen after adrenocortical steroid therapy. Hydralazine seemed to be effective. D-penicillamine improved 25 of 34 treated patients; penicillin hydroiodide 12 out of 16. The dermal sclerosis of 6 patients regressed completely; in 16, sclerosis regressed with the exception of finger sclerosis; in 32, partial regression was registered; 20 had their progression arrested, but there was no regression; in 19 cases, there was no effect whatsoever. The prognosis seemed to be better for young than for old people. The age at onset was lower in the better groups. The higher the total dose, the better the results. The length of the treatment course is probably of some significance. The short-lasting cases had better prospects than the longer lasting. Ten untreated patients of this material and 11 patients seen earlier showed continued progression. Side effects leading to discontinuation of the drugs were seen in a substantial number of patients, especially after D-penicillamine. Twelve deaths could not be related to the treatments.


Cytologic studies of malignant melanoma of the vagina. Four cases of primary malignant melanoma of the vagina are described and discussed with respect to vaginal smears. Two cases treated with radiotherapy began to increase the amount of the melanin pigment during the course of irradiation. Characteristic cytologic features found in the four cases are summarized as follows: a) Distribution of cell 1) Scattering, no tendency of grouping 2) Moderate anisocytosis and anisokaryosis b) Cytoplasm 1) Cyanophilic wispy cytoplasm 2) Indistinct cytoplasmic rim 3) Relatively clear cytoplasm 4) Relatively low N/C ratio c) Melanin pigment 1) In melanoma cells-finely granular and diffusely packed in cytoplasm 2) In histiocytes-coarsely granular and densely packed in cytoplasm d) Nucleus 1) Extremely eccentric nucleus 2) Thin and irregular nuclear membrane 3) Relatively regular chromatin distribution 4) Finely or moderately granular chromatin pattern 5) Prominent nucleolus 6) Giant malignant cells (3-4 nuclei) 7) Intranuclear vacuole (punched out).


T- and B-cells and IgE in mycosis fungoides. The role of T- and B-lymphocytes and serum IgE was studied in 22 patients with mycosis fungoides. The distribution of B-cells in peripheral blood was normal, while the mean percentage of T-cells was significantly lower than in 14 healthy controls. Four patients with mycosis fungoides in stages I to IV had a highly elevated serum IgE, while serum IgE in remaining patients was slightly elevated, normal, or subnormal. The mean serum IgE level was not significantly elevated. Our results tend to show that a reduced ability to react with cellular immunity may be an important factor in mycosis fungoides. This may have therapeutic aspects.


Deposition of fibrinogen (FR-antigen) in skin diseases. II. Pustulosis palmaris et plantaris (with special reference to heparin-precipitable fraction). Ten out-patients with pustulosis palmaris et plantaris were examined with direct immunofluorescence (IF) technique for deposition of fibrinogen, fibrin or its degradation products (FR-antigen) in affected and unaffected skin, together with heparin-precipitable fraction (HPF), cryoglobulin and total plasma fibrinogen in the blood.  FR-antigen was found in all cases in affected skin as a uniform pattern of a continuous ramification below the dermo-epidermal junction. This IF picture was absent in unaffected skin, but in other parts of the dermis in affected and unaffected skin, scattered streaks of IF could be seen. In one case, however, unevenly distributed IF was found in unaffected skin in the junction area. The scattered IF was also present in a minor degree in affected and unaffected skin in a control material of other dermatoses. Only one patient had slightly elevated values of HPF (0.33 mg/ml). Total plasma fibrinogen was insignificantly elevated, and no cryoglobulin could be found.


Attempts to induce sensitization in guinea pigs with nickel complexes. A technique for the induction of sensitization in pigs with a nickel-alanine conjugate has been reported by other investigators. Similar results were observed in our experiments in mini-pigs. However, using the identical technique, we were unable to induce sensitization in guinea pigs with NiSO4, with nickel-alanine or other nickel-amino acid complexes, or with a complex of nickel with soluble guinea pig skin extract. These results indicate that nickel-amino acid complexes and nickel-guinea pig skin complex were not antigenic in guinea pigs with this technique. Hypotheses for the apparent failure to induce sensitization are proposed.


Lentiginosis profusa syndrome. IV. Giant pigment granules (light microscopy). Ionically separated epidermal sheets from pigmentations of two patients with lentiginosis profusa were incubated in dopa (3,4 dihydroxyphenylalanine) and slide-mounted. Light microscopy revealed intracellular giant pigment granules which appeared like those seen with von Recklinghausen's disease.


Acanthoma fissuratum--spectacle frame acanthoma. The development of a cutaneous nodule at the site of friction of spectacles has been discussed by several authors. In all but one case the lesion occurred behind the ears. The only previous report of this acquired tumour occurring on the nose is that of Farrell & Wilson (4). It is suggested that this problem is relatively common and most frequently presents when mistaken for basal cell epithelioma or when identified in medical personnel. A further six cases of this neglected tumour occurring on the nose are described.


Plasma cell granulomas in non-lipemic xanthomatosis: apparent induction by indomethacin. A 71-year-old man with non-lipemic, generalized, plane xanthomas developed nodules and tumors within one month of starting indomethacin therapy. These enlarged and spread during 5 months of daily indomethacin but promptly and spontaneously involuted when the indomethacin was discontinued. Within 4 months, the nodules and tumors were completely gone. The process is viewed as an "indoderma", i.e. a granulomatous drug reaction, analogous to an iododerma.


Large doses of glucocorticoid in the treatment of alopecia areata. Severe extensive alopecia areata (totalis) was treated with prednisolone as a single 2 g dose i.v. (22 patients) or 0.5 g daily for 5 days orally (13 patients). Four of the patients responded well, 12 had a poor response and 19 had no response. There was a relapse in some at about 6 months, which could be arrested by a further single i.v. dose, but the risks of this form of therapy are unclear and it cannot be recommended for general use. The clinical response to a single dose of corticosteroid implies, however, that there may be a 'switch' mechanism in certain auto-immune diseases, with an all-or-none response.


Venous leg ulceration: skin and serum zinc concentrations. Zinc was measured in serum and in thigh skin in patients with venous leg ulceration and also in controls. Skin zinc concentrations were expressed in terms of area and dry weight. The mean serum zinc concentration was significantly lowered in the ulcer group. The thigh skin zinc concentration was elevated in patients with chronic venous leg ulceration. The difference was more marked if the zinc concentration was calculated per surface area of skin, but did not reach statistical significance.


Asymptomatic male and female gonorrhoea. Three hundred and ninety-nine patients attending the out-patient clinic of the Department of Dermatology and Venereology, Rigshospital, Copenhagen, for various venereal complaints were examined during a three-month trial. Neisseria gonorrhoeae was found in 75 female and 89 male patients. 43 women (57%) and 13 men (15%) were asymptomatic at the first visit. The duration of the asymptomatic period exceeded 3 weeks in 25 female (33%) and 7 male (8%) patients. The asymptomatic period in the male group varied from 15 to 90 days and from 4 to 180 days in the females. The majority of the patients with asymptomatic gonorrhoea had been exposed to a sexual contact with proven gonococcal infection, thus emphasizing the importance of contact investigation.


Progesterone-binding globulin and testosterone-binding activity in guinea pig serum during pregnancy: relationship to progesterone and oestrogens. Progesterone levels in serum have been determined throughout pregnancy in guinea-pigs by a competitive protein-binding technique, using pregnant guinea pig plasma protein as binding agent. The concentrations of this protein (progesterone-binding globulin, PBG) as well as the testosterone-binding activity (TBA) have been quantitated by means of equilibrium dialysis. In order to correlate these parameters to the endogenous oestrogen production, the urinary oestrogen excretion was recorded. The concentration of progesterone, PBG and TBA showed a sharp rise on days 14-18 of gestation, reaching a maximal level on days 30-44. The progesterone level thereafter declined significantly towards parturition, followed by a sharp drop post partum. PBG and TBA followed a similar course, the decline towards parturition, however, being non significant. Neither progesterone, PBG nor TBA were significantly correlated to the urinary oestrogen excretion. The concentration of PGB was remarkably high, amounting to 1-2 x 10(-5) M during most of the guinea pig pregnancy. This binding capacity generally exceeded the endogenous progesterone concentration by a factor of 20, as calculated on a molar basis. A mean of 64% of the binding sites was available for testosterone binding, corresponding to a free binding capacity of 400 mug testosterone per 100 ml.


Demonstration of analogues to the human pregnancy zone protein in animals. The pregnancy zone protein (PZ) is known to occur in increased amounts during pregnancy and hormonal treatment. Analogues of this human serum alpha2-globulin were demonstrated in animals by double gel diffusion and immunoelectrophoresis. Direct cross-reactions were found for Rhesus monkey and beagle dog against anti-human pregnancy zone protein. After preparation of an "anti-dog PZ" serum it was possible to demonstrate analogues also in cow and sheep. Thus, the present investigation demonstrated animal analogues to the human pregnancy zone protein, which should be valuable for studies of the biological role of this protein.


Binding of iodinated angiotensin congeners to angiotensin II antibodies. Antibodies against angiotensin II (A II) were generated in rabbits by immunization with val5-angiotensin II coupled to albumin. All antisera bound significant amounts of 125I-labelled A II hepta (2-8) and hexapeptide (3-8), but angiotensin I (A I) was not bound. High specificity for A II was found in 3 sera out of 10. The other sera showed above 50% cross-reaction with hepta- or hexapeptide, or both. No sera were found to cross-react with A I. The amino acids in position 1 and 2 may become additional immunological determinants, providing the basis for the generation of antibodies highly specific for A II. Labelling with 125I using the chloramine method may alter the immunoreactivity of angiotensin congeners. Selected antisera against A II may be used for radioimmunoassays of the biologically active angiotensin "III" (2-8 heptapeptide) and the 3-8 hexapeptide fragment of A II.


Porosity and surface area of anionic resins: limitations in the employment of model substrates for the colloidal iron reaction. Quantitative evaluations of the uptake of an acid ferric hydroxide sol revealed the iron binding of model substrates unrelated to their ion binding capacity. Electron microscopy showed iron particles bound exclusively or mainly to the surfaces of model substrates. Morphometric estimations resulted in a good agreement of the surface/volume ratio with the amount of bound iron. The results are discussed with regard to the steric hindrance of the colloidal iron reaction resulting in a nonstoichiometric interaction.


Absorbances of hematoxylin solutions at varying pH levels. An alum hematoxylin was prepared (0.5 g hematoxylin, 8 g potassium alum, distilled water 477.5 ml and Na10(3) solution, 1 mg/ml, 22.5 ml) and divided into 50 ml aliquots. The pH of these aliquots was adjusted with 2 1/2% NaOH or 10% H2SO4. As soon as the pH of a sample was adjusted the absorbance from 400 to 700 nm was recorded with a Cary 15 spectrophotometer using specially designed cuvettes and undiluted samples. The following day the absorbances at peak were measured on a Coleman Jr. spectrophotometer and three days later a variety of tissues was stained with each solution. The pH and peak of absorbance of the aliquots were pH = 2.0 450 NM, 2.5 505, 2.6 507, 2.7 515, 2.8 520, 2.9 530, 3.0 540, 3.1 550, 3.3 560, 3.5 560. In the stained material in the intensity of nuclear staining was about the same at all pH levels but non-specific staining was greatest in slides stained at pH = .5 and virtually absent in slides stained at pH = 2.0. At intermediate pH levels the amount of non-specific staining was intermediate.


Feulgen staining of mammalian tissues fixed in picro-formol-acetic acid. The paper describes a highly satisfactory method for in situ localization of DNA in tissues fixed in picro-formol-acetic acid or picro-formol-acetic-chromic acid mixtures following a technique in the Feulgen procedure as devised by the author. Mammalian tissues fixed in these fixatives can be hydrolysed in 6N HCl at 35 degrees C for 10 min, rinsed in water, stained with Schiff reagent after exposing the sections under UV light for 10 min, washed in water, dehydrated through a graduated series of ethanol, cleared in xylol and mounted in DPX. Sections of tissues fixed in picro-formol-acetic-chromic acid mixtures after acid hydrolysis when stained with an aqueous solution of basic fuchsin are also found to be very satisfactory for in situ localization of DNA.


Immunological studies on bronchial secretion. II. Antibodies against bronchial secretion in systemic lupus erythematosus and asthmatic patients. Bronchial secretion was tested by double gel-diffusion with sera from 100 asthmatic patients, 72 systemic lupus erythematosus patients, 29 patients with other diseases and 31 normal individuals. Positive gel-diffusion reactions were observed only in the sera from two patients with S.L.E. Sera from 100 asthmatic patients, 29 non-allergic patients and 31 normal individuals, tested with bronchial secretion by the passive haemagglutination and inhibition test, showed only three positive reactions with sera from asthmatic patients. Two problems were discussed: the immunological relationship between antigenic determinants found in the sputum and serum in S.L.E. patients; and the possibility that the bronchial secretion being reabsorbed might act as an auto-antigen.


Stereometric observations on the hypothalamic neurosecretory system of the spotted owlet, Athene brama Temminck, in total preparations. The configuration of the HNS of the spotted owlet, Athene brama Temminck, was studied by employing the bulk-staining technique. This enabled a three-dimensional view of the HNS. The neurons of the SON are distributed into three divisions, namely, the preoptic, median and lateral. The PVN is U-shaped; the distal portion of the arms of the U extends laterally to form the lateral division of the PVN, which remains in continuity with the lateral division of the SON. The periventricular division of the PVN joins ventrally the median division of the SON. Unlike in the passerine birds, in the spotted owlet the PVN is more prominently developed than the SON. Since the axonal pathways are not stained, the proximal portion of the hypothalamo-hypophysial tract could not be demonstrated in bulk-stained preparations. Hence it was not possible to trace with certainty the origin of the axonal terminations in the ME and in the NL. Anterior of the ME, the tract branches into two; one branch enters the zona externa to the ME and the other is continued into the NL. The ME is divisible into an AF-positive anterior region and an AF-negative posterior region. The NL is saccular and heavily loaded with the NSM. Studies on the HNS of the spotted owlet by the bulk-staining technique reveal that the general configuration of the system is comparable to that of the HNS of birds studied previously.


Brain involvement in Whipple's disease: a case report. A man of 22 with Whipple's disease suffered from a acute febrile state and unconsciousness. Focal inflammatory lesions accompanied by large numbers of peculiar macrophages occurred in thalamus and basal ganglia. The electron microscopic findings conform to previous reports on brain involvement in Whipple's disease.


The distribution of intravenously administered peroxidase in the optic nerve head of rabbit and monkey. Peroxidase was used as an histologic tracer to study the permeability properties of the tissues in the optic nerve head of rabbit and monkey. The distribution of the tracer was observed by light microscopy. Within a short time after intravenous injection peroxidase was located extravascularly in the optic nerve head. The present study confirms earlier reports of a defect in the blood-optic nerve barrier in the region of the optic nerve head. The tracer was found to have reached the connective tissue of the optic nerve head, and to a lesser degree the optic nerve tissue proper. The observations made it probable that peroxidase had reached the connective tissue of the optic nerve head by diffusion from the perineural chorid and sclera.


Effect of anti-alpha-fetoprotein serum on growth and plating efficiency of alpha-fetoprotein-producing hepatoma cells in vitro. The effect of a specific rabbit antiserum to rat alpha-fetoprotein (AFP) was examined on the growth and the plating efficiency of AFP-producing rat hepatoma cells (AH70Btc Clone 10-5) in cultures. The addition of anti-AFP serum to the culture medium inhibited cell growth moderately and inhibited plating efficiency markedly, although no inhibitory effect of complexes of AFP and antibody to AFP was observed on cell growth. Anti-AFP globulin in the immune serum was demonstrated on the cell surface by fluorescent antibody technique. Several clones producing low levels of AFP were obtained by long-term treatment of the original Clone 10-5 cells with anti-AFP serum. These treated clones showed characteristics that differed from the untreated original clone 10-5 cells: The relative plating efficiency of the treated clones on agar plates containing 5% anti-AFP serum was higher than the original Clone 10-15 cells and the amount of AFP secreted by the treated clones was lower.


Effects of long-term treatment with procaine amide. A prospective study with special regard to ANF and SLE in fast and slow acetylators. During 1970-75 a total of 42 patients have been subjected to long-term treatment with procaine amide (PrA) because of different cardiac arrhythmias and have been observed up to over 5 years. Among these patients 35 (83%) developed a significantly increased titer of ANF and of these, 12 patients (29%) developed a "classical" drug-induced SLE syndrome. In the SLE group all but 2 improved rapidly after cessation of PrA, and the ANF titer decreased continuously but slowly in both groups. Acetylation test with sulphamidine and/or isoniazid in 11 patients among the SLE cases showed 8 slow and 3 fast acetylators. Among 12 patients who also had received PrA for a long time, but had not shown any signs of an SLE syndrome, there were 10 fast and 2 slow acetylators.


The influence of phosphatidyl serine on the release of histamine from isolated rat mast cells induced by different agents. The influence of phosphatidyl serine (PS) on histamine release from isolated rat mast cells induced by antigen, compound 48/80, adenosine-5'-triphosphate (ATP), the ionophore A23187, and decylamine was studied. PS enhanced antigen-induced release but inhibited the release caused by compound 48/80, A23187, and decylamine. PS did not influence the release induced by ATP. The different effects of PS on the action of the various histamine releasing agents do not conform to a unifying model for the action of PS on the release process. Possible interactions between PS and the agents in the incubation medium as well as at specific reactive sites on the plasma membrane might explain some of the effects of PS. Consequently, the results cannot be used as evidence for the existence of basic differences in the release process induced by various calcium- and energy-dependent releasing agents.


The effects of histamine liberators and exogenous histamine on wound healing in rat. The effects of compound 48/80, adenosine-5-triphosphate (ATP) and exogenous histamine (Hi) on the healing of excised surface wound and tensile strength of surgical skin wound in rat were studied. The chemicals were injected directly into the wound area. 48/80, ATP and exogenous Hi were found to stimulate the wound healing as measured by collagen formation, tensile strength examination and a measurement of the surface circular wound. When given separately, the order of activities was: 48/80 is greater than ATP is greater than Hi; when administered together as a mixture, compound 48/80, ATP and exogenous Hi also accelerated the wound healing. The mixture shortened the healing process by about 5 days as compared with 17 days in control.


Screening in child care.

Screening in child care. For a disease to be susceptible to screening, it should be definable, important and treatable. Treatment begun earlier on the basic of discovery through screening must have some advantage. The period between first possible detection and optimal time for treatment must be substantial. Adequate facilities and resources for evaluation and care must be available. Finally, there must be a valid, low-cost test for the disease and there must not be a high cost associated with false-positive or false-negative results.


Periodic fibrillar material in intracellular vesicles and in electron-dense bodies in chondrocytes of rat costal and tracheal cartilage at various ages. The occurrence of intracellular fibrillar material (frequently banded) has been studied in normal costal and tracheal chondrocytes of rats at various ages ranging from 1 to 90 days. The study methods have included digestion with collagenase, electron histochemical techniques and routine electron microscopy. Banded fibrillar material has been observed intracellularly in vesicles or in electron-dense bodies in perichondrial and subperichondrial chondrocytes from rats of all ages. These fibrils and extracellular collagen fibrils are partially and equally degradable by collagenase, they are positive after staining with phosphotungstic acid or with silver nitrate methenamine, and their lucency corresponds with that of collagen when they are stained only with lead citrate. They have not been observed in intracellular clefts. They, therefore, seem to be formed intracellularly and to be exocytosed subsequently. Large vesicles and electron-dense bodies seem to be derived from Golgi saccules. A mechanism whereby banded intracellular fibrils could be formed from tropocollagen molecules is postulated. The frequency of occurrence and the diameter of intracellular fibrils seems to increase with increasing age.


The stimulatory effects of diethylstilbestrol and diethylstilbestrol diphosphate on the reticuloendothelial cells of the rat spleen. The effects of the estrogenic compounds, diethylstilbestrol (DS) and diethylstilbestrol dophosphate (DSP) on morphologically demonstrable characteristics of reticuloendothelial (RE) cells were studied in rat spleen. These included metalophilia, acid phosphatase, nonspecific esterase and phagocytosis. Routine histological and histochemical techniques were used to determine the distribution of metalophilic cells, hydrolytic enzymes, the presence of intracytoplasmic PAS-positive material, hemosiderin sequestration, and the ability to phagocytose injected carbon particles and bacterial organisms. Changes in these parameters associated with increased RE function were observed in several regions of spleens of DS or DSP-treated animals. The marginal metalophils at the periphery of the nodule, normally not phagocytic in animals of the age studied, became phagocytic and demonstrated increased metalophilic and enzymatic activity. The red pulp was characterized by increased densities of cells in pulp cords demonstrating metalophilia, hydrolytic enzyme activity, PAS positivity and hemosiderin. Phagocytosed material was limited to cells in the pulp cord. The reactions of the sinus-lining cells were not affected by this treatment. Results indicated that the marginal metalophils have the capacity to become fully functional RE cells under the influence of these drugs.


Electrophoretic abnormalities in chronic lymphocytic leukemia and cancer sera. It was previously shown (Am J Clin Pathol 55: 65-67, 1971) that sera from patients with chronic lymphocytic leukemia (CLL) produce a characteristic pattern on disk-acrylamide gels. Other observations indicating the presence of immunosuppressive proteins in the sera of patients with cancer suggested the search for characteristic protein patterns employing the same technic. Utilizing sera from patients with various types of malignancies and appropriate controls, the results appear to indicate that there is a consistent and distinctive pattern to the gels. The nature of the (different) protein(s) remains to be elucidated.


Serum antithrombin in coronary-artery disease. Serum antithrombin activity (AA) was correlated with coronary angiographic findings in 69 patients with documented angina. There was excellent correlation between normal values and normal coronary circulation or only one-vessel stenosis in 30 of 35 patients (86%). When AA was above 90%, 90% of patients (20 of 22) had normal circulation or one-vessel occlusion. In 24 patients AA values were significantly decreased. Coronary angiography in this group revealed three with normal circulation or only one-vessel involvement (10%); 21 of 24 had two or three vessels occluded (90%). The correlation between severe CAD and low AA is probably coincidental to a "triggered" or "turned-on" clotting system. The most practical clinical contribution of AA estimation relates to this capacity to identify angina patients in whom clot-preventive measures (aspirin; dipyridamole; anticoagulants) might prove beneficial.


Neutrophil granules: A review.

Neutrophil granules: A review. Hematologists are familiar with the granules of leukocytes because they serve as a means of identification of certain white blood cells.19 It is now generally appreciated that the granules of neutrophilic polymorphonuclear leukocytes (PMN) store antibacterial agents and lysosomal enzymes until they are needed for the killing and digestion of phagocytized microorganisms.16 Within the framework of this well-known setting, this article presents some new data on the mode of formation and chemical content of PMN granules. In particular, the traditional view that azurophil (nonspecific) granules change into specific granules will be challenged.


A quantitative study of the pregnancy zone protein in sera of woman taking oral contraceptives. By means of a single radial immunodiffusion the concentration of "the pregnancy zone protein" (PZ) was measured in sera from women taking oral contraceptive drugs. Woman taking only 0.3 mg. of norethisterone were found not to induce measurable amounts of PZ, whereas women taking combined contraceptive drugs showed a significant rise in concentration of PZ. After six months' treatment, 1 mg. of norethisterone and 0.1 mg. of meastranol daily were found to give an average concentration of PZ amounting to 59 mg. per 100 ml., that is, approximately half of the concentration of PZ in sera from women during the last trimester of pregnancy. Different combined contraceptive pills gave rise to different concentrations of PZ.


Localization of hepatitis B surface antigen in conventional paraffin sections of the liver. Comparison of immunofluorescence, immunoperoxidase, and orcein staining methods with regard to their specificity and reliability as antigen marker. Hepatitis B antigen (HBAg) has been demonstrated in conventional formalin-fixed paraffin-embedded liver tissue by peroxidase and fluorescent immunostaining as well as by orcein. Complete locational and morphologic identity is seen between material stained by specific immunologic methods and by orcein. The antigen is restricted to the cytoplasm and is generally observed in the hepatocyte; it is present in three morphologic forms. Certain morphologic forms can even be identified in hematoxylin and eosin-stained tissue. Results of immunostaining procedures indicate that the antigen demonstrated in this study consists entirely of surface coat of hepatitis B virus (HBsAg). This seems to be the only component revealed by orcein staining. The latter is considered to be a good marker of the surface antigen and to have certain advantages over immunostaining. It is suggested that suitability of conventional paraffin sections for the detection of HBAg has wide and important implications.


Ultrastructural localization of histones in chronic erythremic myelosis. The localization of histones was studied ultrastructurally with the use of the ammoniacal silver stain in erythroid precursors from 6 patients with chronic erythremic myelosis (Di Guglielmo syndrome), 3 patients with severe untreated pernicious anemia, 2 patients with untreated autoimmune hemolytic anemia, and 4 presumedly normal individuals. Silver deposits, indicative of sites of arginine-rich histone within nuclei, were not observed in proerythroblasts from any of the individuals. Small deposits of silver were seen in the heterochromatin in very early intermediate normoblasts. Differences in the amount and distribution of the silver deposits in the various types of erythroid precursors first became recognizable in the intermediate normoblast stage. In all of the individuals, the silver deposits were localized predominantly in the heterochromatic regions of the nucleus. In 6 patients with chronic erythremic myelosis, unusually, dense deposits of silver were observed in erythroid precursors having amounts of heterochromatin comparable to that found in intermediate normoblasts of intermediate megaloblasts in other conditions. In these chronic erythremic myelosis erythroid precursors, the silver deposits were larger and, in many instances, appeared to be more aggregated than in erythroid precursors obtained from 3 patients with untreated pernicious anemia, 2 patients with autoimmune hemolytic anemia, and 4 presumedly normal persons. It is possible that the findings described in this study are involved in the pathogenesis of megaloblastoid erythropoiesis as found in chronic erythremic myelosis.


Ba++ as a gastric stimulant: release of histamine. Ba++ added to the serosal solution bathing a resting frog stomach increased transmucosal resistance and induced acid secretion. The increase in acid secretion was associated with an increased leak of histamine from the mucosa into the serosal solution. Pretreatment with burimamide inhibited the secretory response to Ba++. After a pulse treatment with Ba++ (2 mM for 5 min), the effects on resistance were transient but the effects on acid secretion were sustained. A pulse treatment with histamine also led to a sustained increase in acid secretion, and this increase was blocked by burimamide. It is concluded that Ba++ releases histamine which then stimulates acid secretion.


Behavioral characteristics of children with chronic nonspecific diarrhea. The authors obtained early case histories of 16 children with chronic nonspecific diarrhea and 16 control subjects and found that the index subjects had a significantly higher frequency of sleep problems, crying and irritability, digestive problems excluding diarrhea, overactivity, resistance to discipline, and family history of gastrointestinal problems. They conclude that these behavioral characteristics represent temperamental traits based on physiological factors, perhaps an imbalance of autonomic nervous system function. They speculate that chronic nonspecific diarrhea may occur in association with certain temperamental traits because both the somatic and psychic components stem from a common disturbance in autonomic nervous system function.


Cancer of the cardia.

Cancer of the cardia. The records of 157 patients with cardioesophageal carcinoma were reviewed. It is evident that although the prognosis of patients with squamous carcinoma is better than that of patients with adenocarcinoma, neither lesion is compatible with substantial long-term survival. Palliative resection of squamous carcinoma provides satisfactory short-term relief of symptoms. Palliative resection of adenocarcinoma, however, does not afford a similar response. Alternative modes of therapy are suggested.


Differentiation of the neural plate and neural tube in the young chick embryo. A study by scanning and transmission electron microscopy. The differentiation of the presumptive neural plate, the neural plate and the neural tube have been investigated in the chick embryo by SEM, TEM and histochemical techniques. The relationship of these tissues to neighbouring structures, including extracellular materials, has also been studied. When SEM micrographs of primitive streak stage embryos were examined in stereo, it was found that cells which had been invaginating at the time of fixation were similar in shape to fibroblasts migrating in vitro. It was concluded that SEM stereo pairs could provide evidence about the mode and direction of cell migration. Many more mid-bodies have been found associated with the developing neural tissue than with the lateral ectoderm. It was found possible to recognise mid-bodies not only by TEM but also by SEM. It is therefore proposed that SEM montages may be used for assessing which regions of a tissue have recently undergone extensive mitosis. The beads on the specialised threads seen in the early stages of development are now considered to be formed from mid-bodies. Similar, but unbeaded threads have been described which span the gap between the neural folds just prior to the dorsal closure of the neural tube and it seems probably that these threads help to close the neural tube. It is suggested that the beaded threads arise by incomplete separation of two daughter cells at mitosis, whereas the unbeaded threads form by outgrowth of cell processes.


Removal of blood group determinants from bovine erythrocyte membranes. 2. Degradation of ghosts by butanol and pyridine. Ghosts produced from erythrocytes collected from six different cattle were degraded with butanol and pyridine. Of a total of 38 different antigenic determinants available for investigation among the six cows, F, V, J and L were the only specificities detected in the subfractions resulting from either method of degradation. After butanol degradation V, J and L antigens were found in the soluble protein fraction, while F was found in the insoluble protein. Pyridine digestion resulted in all four determinants being detected in the sialoprotein layer, while J was found in the lipoprotein as well. All antigens were relatively weak, being detected in inhibition strengths of 10.0 to 1.25 mg/ml.


Immunologic release of histamine from bovine polymorphonuclear leukocytes. Blood from calves sensitized to horse serum was fractionated to yield a suspension containing 94% granulocytes. These cells released up to 90% of their total histamine when exposed to the antigen. This is a noncytotoxic reaction similar to that observed in human beings, rabbits, and guinea pigs. Higher concentrations of antigen caused inhibition of histamine release. This immunologic reaction may be important in bovine hypersensitivity, especially in the lungs, where intravascular aggregations of granulocytes are found at the height of the anaphylactic response.


Arterial infusion chemotherapy for palliation in far-advanced malignant neoplasms. For patients with far-advanced regionally localized malignancies, arterial infusion chemotherapy offers reasonable palliation with minimal complications. High locoregional concentration of the antineoplastic drugs is obtained with relatively little systemic toxicity.


Significance of histopathological findings in Dupuytren's contracture. Clinical and histopathological data were compared in a series of 59 patients with Dupuytren's contracture (DC) from the years 1946-1971 in order to clarify whether histopathological findings were in accordance with the clinical development of the disease. All well known histopathological features were inspected. The most valuable prognostic sign seemed to be the appearance of several active nodules, indicating rather rapid development of DC, with a high frequency of postoperative recurrence in these patients. Lack of active nodules did not exclude this possibility but made it less likely. Other occasional findings typical of DC such as the number of mitoses, microhaemorrhages, perivascular lymphocytic infiltrations and hypertrophied corpuscles of Vater-Paccini seemed to be of minor prognostic value. Mucopolysaccharides from DC tissue showed metachromasia with toluidine blue did not stain with HID-AB (high iron diamine-alcian blue) as HID positive in specimens preserved embedded in paraffin blocks for several years.


[Do immunization of rabbits by N-acetylgalactosamine and a disaccharide linked to a protein produce anti-microbial antibodies (author's transl)]. Rabbits were immunized with N-acetylgalactosamine linked to bovalbumine. They produced antibodies which precipitated this same sugar linked to human gamma-globulins but did not agglutinate Salmonella johannesburg which carry a side chain of N-acetylgalactosamine. The same immunization enhanced the titre of "natural" antibodies agglutinating human A red cells (which carry a terminal N-acetylgalactosamine) but they did not evoke such antibodies in rabbits with no "natural" hemagglutinins. These negative results, when compared to the positive one obtained with 0-acetyl-3,6-dideoxygalactose suggest that rabbit antibody-sites limited to one sugar may exist but that they can be detected only under certain conditions. Another group of 8 rabbits was immunized with a disaccharide alpha-Glc-(1 leads to 6)-GalNAc linked to a protein. All produced antibodies agglutinating S. johannesburg (1,40) which carry this disaccharide and S. senftenberg which carry the disaccharide alpha-Glc-(1 leads to 6)-Gal. The titres of these antibodies decreased after a second course of immunization.


[Surgery of cancer pain. Section of the IX and V nerves in the ontocerebellar space, section of Andersch's ganglion and Jacobson's verve. Indications and results]. The authors describe their experience involving 30 patients treated surgically for stubborn algesia during the development of cancers of the face and neck. Sectioning Jacobson's nerve which they suggested for 72 cases exclusively or mainly involving otalgia especially where the tumours was tonsillar, proved of great therapeutic value and took little toll of the patients. - Resection of Andersch's ganglion, difficult and often ineffective, should not be attempted. - On the other hand, when there is stubborn pharyngeal pain with otalgia, sectioning the IXth is remarkably successful. Likewise, where there is pain in the face or tongue and the floor of the mouth which fails to respond to opiates, partial microcoagulation of the pre-pontile root of the trigeminal nerve is an excellent solution. - Neurotomies of the IXth and the Vth, carried out in the cerebellopontile angle, are operations with simple sequelae. They have the outstanding advantage of permanently relieving the pain of these unfortunate patients.


[Reactivity of a purified antigen of Paracoccidioides brasiliensis with paracoccidioidomycosis and histoplasmosis sera]. The immunoelectrophoretic reactivity of a "crude" and a "purified" antigens of Paracoccidiodes brasiliensis against the sera of confirmed cases of paracoccidioidomycosis and histoplasmosis was evaluated. The "crude" antigen revealed precipitating antibodies in both the homologous and the heterologous human sera; the number of precipitating systems being higher with the former. The "purified" antigen reacted only with the homologous sera. It is postulated that the use of such "purified" antigen may significantly reduce the non specificity of the serologic tests in the immunodiagnosis of paracoccidioidomycosis.


[Effect of gramicidin C on the formation and germination of Bacillus brevis var. GB (P+-variant) spores]. The effect of gramicidin C added to the medium at various periods of cultivation in concentrations of 20, 40 and 100 gamma/ml on sporulation of P+-variant of Bac. brevis var. GB was studied. The most effective increase in the sporulation rate and percentage of the cells germinating into the spores was observed on addition of the antibiotic to the medium in amounts of 20 and 40 gamma/ml in 13 hours of the culture development. The amount of gramicidin C during sporulation decreased and partially passed into the spores which did not differ after germination from those of P+-variant grown on the synthetic medium with glucose and without preliminary addition of the antibiotic. Addition of gramicidin C in an amount of 100 gamma/ml at the end of the lag phase, i.e. 4 hours after the culture inoculation suppressed sporulation and had no effect on growth of the cells of its own producing organism.


Inhibition of murine plasmocytoma tumours with antibody activity by their respective specific antigens. Three murine plasmocytoma tumour which secrete specific antibodies have been studied for the effect of specific antigens (pneumococcal C polysaccharide and dinitrophenylated bovine gamma globulin) on the growth of these tumours in vivo. In each case, the effect of the specific antigen was to inhibit the growth of that tumour which synthesized the specific antibody. Low molecular weight haptens had no effect on tumour growth. We suggest that this antigen specific growth inhibitory effect is a function of the antigen's binding to membrane bound antibody resulting in defective membrane function.


Cross-reactive antigens and lectin as determinants of symbiotic specificity in the Rhizobium-clover association. Cross-reactive antigens of clover roots and Rhizobium trifolii were detected on their cell surfaces by tube agglutination, immunofluorescent, and radioimmunoassay techniques. Anti-clover root antiserum had a higher agglutinating titer with infective strains of R. trifolii than with noninfective strains. The root antiserum previously adsorbed with noninfective R. trifolii cells remained reactive only with infective cells, including infective revertants. When adsorbed with infective cells, the root antiserum was reactive with neither infective nor noninfective cells. Other Rhizobium species incapable of infecting clover did not demonstrate surface antigens cross-reactive with clover. Radioimmunoassay indicated twice as much antigenic cross-reactivity of clover roots and R. trifolii 403 (infective) than R. trifolii Bart A (noninfective). Immunofluorescence with anti-R. trifolii (infective) antiserum was detected on the exposed surface of the root epidermal cells and diminished at the root meristem. The immunofluorescent crossreaction on clover roots was totally removed by adsorption of anti-R. trifolii (infective) antiserum with encapsulated infective cells but not with noninfective cells. The cross-reactive capsular antigens from R. trifolii strains were extracted and purified. The ability of these antigens to induce clover root hair deformation was much greater when they were obtained from the infective than noninfective strains. The cross-reactive capsular antigen of R. trifolii 403 was characterized as a high-molecular-weight (greater than 4.6 times 10(6) daltons), beta-linked, acidic heteropolysaccharide containing 2-deoxyglucose, galactose, glucose, and glucuronic acid. A soluble, nondialyzable, substance (clover lectin) capable of binding to the cross-reactive antigen and agglutinating only infective cells of R. trifolii was extracted from white clover seeds. This lectin was sensitive to heat, Pronase, and trypsin. inhibition studies indicated that 2-deoxyglucose was the most probable haptenic determinant of the cross-reactive capsular antigen capable of binding to the root antiserum and the clover lectin. A model is proposed suggesting the preferential adsorption of infective versus noninfective cells of R. trifolii on the surface of clover roots by a cross-bridging of their common surface antigens with a multivalent clover lectin.


Palliative treatment with oral Estracyte in disseminated prostatic carcinoma. In Roswell Park Memorial Institute, between 1969 and 1974, a total of 32 patients with widespread metastasized carcinoma of the prostate were treated with oral Estracyt. Objectively demonstrable remissions were achieved in eight patients (8/32 equals 25%). Subjective improvement of their general condition was experienced by 15 patients (15/32 equals 47%). The toxicity of Estracyt manifests itself with gastrointestinal disorders, which in most cases are amenable to anti-emetic treatment.


A case of embryonal sarcoma (rhabdomyosarcoma) of the prostate treated with combined surgical and cytostatic therapy. The case history of a 22-months old boy with a malignant embryonal tumor of the prostate is given. Five years after initiation and three years after termination of a combined therapy with cytostatic drugs (actinomycin D, vincristine sulfate and cyclophosphamide) and surgery he is in good health without any signs of recurrence or metastatic disease. On this moment it is still impossible to be certain whether this therapy is the key for treatment of these tumors, but the successes published and the result till now in this case can be an indication that we are going in the right direction. Perhaps we may even hope that in the future we will have cytostatic drugs and combinations of therapy which will enable us to avoid mutilating operations.


Juvenile hyalin fibromatosis.

Juvenile hyalin fibromatosis. A boy had multiple large tumors on the scalp, whitish nodules on the nape and both sides of the neck, hypertrophic gingiva, and severe flexural contractures of hip and knee joints. The histopathologic structure of the tumor was characteristic of juvenile hyalin fibromatosis. The tumor cells were embedded in an amorphous eosinophillic ground substance. X-ray films revealed numerous osteolytic and osteociastic lesions that are important findings in the study of this disease.


[Eosinophilic leucocytes in the skin lesions of psoriasis and atopic dermatitis (author's transl)]. Using specific techniques (Leder; and Schaefer u. Fischer) we examined the presence of eosinophilic leucocytes (EGr) in sections of various forms of psoriasis, some under treatment with methotrexate. We compared the results with findings in atopic dermatitis. The number of EGr was calculated in proportion to the remaining cells in the relevant section of the horny layer and of the dermis (papillary body, subpapillary dermis). The proportion of eosinophilic leucocytes was found to be considerably smaller than the supposed number seen in H.-E. sections. Also, in psoriasis pustulosa the proportion was relatively small, whereas in the dermis of atopic dermatitis it was 2 times higher. In atopic dermatitis of patients, who acquired the dermatitis as adults, the proportion was lower, although it was possible to examine the tissues of only three such patients. Treatment with methotrexate had no significant influence on the percentage of EGr in the psoriatic infiltrates.


[Continuous electrocardiographic recording. Clinical, diagnostic and therapeutic value]. The interest of permanent electrocardiographic recording in ambulatory patients is not restricted to the demonstration of the cardiogenic origin of some functional disturbances. This method provides the proof of the often non fiable character of anamnesis for the diagnosis of arrhythmias. It shows the close relationship between "minor" (extra-systoles) and "major" (tachycardias) arrhythmias, and consequently the prognostic value of the former in relation with the latter. Continuous ECG follow-up affords in the assessment of anti-arrhythmic drugs efficiency a higher safety than that provided by the conventional simple clinical follow-up.


Terminal dilution purification of adenovirus prototypes, and the antigenic relationship between types 4, 16 and 14. Two terminal dilution purifications in HEK cells were performed with adenovirus prototypes of types 1 to 7, 12, 16, 19 and 9-15, and one terminal dilution with a freshly isolated type 8 strain. The antisera prepared against viruses after terminal dilution neutralized the original and the purified virus to the same extent, indicating the antigenic purity of the respective prototypes. Cross-reactions in neutralization with other types within the subgroup were also identical. Only the prototype of type 16 (Ch 79) showed a cross-neutralization with type 4, while four type 16 wild strains showed cross-neutralization with type 14, but none with type 4. The prototype (CH 79) is a "prime strain" in relation to the type 16 wild strains.


[Tumorscanning of the head and neck malignomas (author's transl)]. Tumorscanning of malignomas and their metastatic nodules in head and neck is an enrichment of diagnostic possibilities. For the examination such substances can be used, which are tumoraffine and well to mark with a radio-isotope. Therefore we have marked the cytostatic drug Bleomycine with 57Co. Scans were performed with the Anger-Camera 4 to 6 hrs after intravenous injection of 1 mCi 57Co-Bleomycine. 60 patients with different malignomas have been examined, 46 with tumor-localization in head and neck, the others in thoraxabdomen. 34 (85%) of the head and neck malignomas could be demonstrated; 21 (81%) were squamous cell carcinomas, 13 (69%) sarcomas. The possibilities of this method are shown; its clinical importance lies in the identification of primary tumors and their metastatic nodules, of relapses and tumorrests as well as the localization of distant metastasises.


Vestibular end organ mapping in the squirrel monkey. Vestibular end organ mapping (surface preparation) was performed in squirrel monkeys by using succinic dehydrogenase staining. Comparing sensory hair cell counts and surface area measurements of the squirrel monkey to those of man and the guinea pig, the values obtained from the squirrel monkey were between those of man and the guinea pig. When regional (central versus peripheral) cell density was compared, the density of the peripheral area was 1.62X more on the average than that of the central portion.


Endodontic education.

Endodontic education. Undergraduate endodontology is taught in Australian Universitiies in Restorative or Conservative departments. Courses generally consist of twelve lectures, three seminars and technique courses. Average clinical experience is six to eight endodontic treatments in anterior and posterior teeth. Comparison with American and Scandinavian teaching, staff and facilities indicates that this subject is receiving considerably less emphasis in Australia. As endodontic therapy is eseential in any dental health programme based on preventive dentistry there is a considerable need to upgrade undergraduate endodontic teaching in Australia.


Pull-through resections for carcinoma of the rectum. Pull-through operations have been undergoing evaluation as a treatment for carcinoma of the rectum in several centres. Functional results at one and two years have been between 1960 and 1970, which enables a five-year follow-up. Forty-eight of these were palliative procedures, with a mean survival time of nine months. Only 11 patients were Dukes A cases and none of these have died from their disease. One hundred and five were Dukes B, with a 73% five-year survival. The Dukes C cases had only a 22% five-year survival. The main problems have been related to the blood supply to the exteriorized distal colon.


Immunochemical relationship between alpha-amylases of rat liver, serum, pancreas and parotid gland. 1. Rabbit antisera to purified rat parotid alpha-amylase were prepared. 2. The relationships between rat parotid-gland, pancreatic, serum and liver amylase were investigated by using the antisera in immunodiffusion, immunoelectrophoresis and immunoinhibition experiments. 3. Serum and liver amylase were identical, and very similar to parotid-gland amylase; pancreatic amylase was, however, quite distinct, and showed only some of the determinants present on parotid-gland amylase. 4. The data strengthen the suggestion that the liver is the main source of serum amylase.


Chloride-dependent restoration of coupling by oligomycin in rat liver mitochondria. In rat liver mitochondria suspended in KC1 medium, oligomycin interfered with the effect of uncouplers on energy conservation. It antagonized the effect of uncouplers that are weak acids (2,4-dinitrophenol etc.), but enhanced that of the lipid-penetrating cation NN-dimethyl-N'N'-dibenzylammonium. Oligomycin caused none of the above effects when Br- or NO-/3 was substituted for C1- as the major anionic species in the assay medium. The concentration of oligomycin that exerted the above-mentioned effects was lower than that necessary for the inhibition of energy transfer, but was in the range that induced C1- permeation through the cristae membrane. The possible connexion between the effect of oligomycin on C1- permeation and its interference with the action of uncouplers is discussed.


Tumour antigenicity in ovarian cancer.

Tumour antigenicity in ovarian cancer. The blastogenic response to a crude cell extract of ovarian cancer cells has been studied in 48 patients with ovarian cancer (9, autologous, 39 allogeneic), in 26 female controls matched for age and in 18 female patients with other types of cancer in remission from disease. The responses in ovarian cancer patients in remission and relapse were considered separately. The blastogenic responses to cell extracts of foetal ovary, foetal lung, foetal liver and normal adult ovary were also assessed in a proportion of all 3 groups. The blastogenic responses to ovarian cancer and foetal ovary cell extracts were found to be significantly greater in the ovarian cancer patients in remission than in the controls, but the responses to ovarian cancer extract were not greater in the relapse group or in patients with other cancers. As a blastogenic response to normal ovarian extract was also present in some of these patients, the data so far do not support the hypothesis of a tumour specific antigen. This tumour associated response may be occurring to determinants in foetal or adult ovarian tissue to which the patient becomes sensitized in malignant disease. The response is complex and the nature of the antigen requires further analysis.


The effect of steroid hormones on the growth pattern and RNA synthesis in human benign prostatic hyperplasia in organ culture. The effect of testosterone, dihydrotestosterone, 3 beta-androstanediol and oestradiol-17 beta on the morphology and RNA synthesis in human benign prostatic hyperplasia (BPH) in organ culture has been investigated. In hormone treated and untreated explants alike, the epithelium multiplied to form several layers. This effect was most marked after exposure to dihydrotestosterone. In explants grown in non-supplemented medium the epithelium showed some squamous changes; testosterone or dihydrotestosterone preserved the secretory character of the epithelium while oestradiol-17 beta caused cellular degeneration. The incorporation of 3H-uridine into RNA was studied by autoradiography. In the epithelium, testosterone or dihydrotestosterone raised the uptake significantly over that measured in the control explants, oestradiol-17 beta reduced it while 3 beta-androstanediol produced similar values to those found in the control explants. The incorporation of 3H-uridine in the smooth muscle cells was increased by testosterone and decreased by oestradiol-17  beta. A comparison with normal rat prostatic epithelium in organ culture showed that in the absence of androgens the incorporation of 3H-uridine was lower than in BPH and the effect of testosterone correspondingly greater. The results suggest that although the growth of human BPH in organ culture appears to be androgen dependent, it still remains hormone sensitive and can be influenced by steroid hormones in a similar manner to that in rat prostatic gland. They further show that the smooth muscle of the stroma is also hormone sensitive, a point which should be considered in the hormonal management of benign prostatic hyperplasia.


[Evaluation of methisoprinol+ in the treatment of infectious hepatitis. Negative results]. The usefulness of metisoprinol was evaluated by a double blind study and at random in the treatment of mild infectious hepatitis in a group of 42 children. Twenty-one patients were given the drug at the dose of 50 mg/kg/day, divided t.i.d., by mouth and for 12 days. The other twenty-one patients made up the control group and were given placebo. No modifications nor clinical differences were found in the parameters evaluated; laboratory results were also negative in the studies carried out that might be attributed to the administration of the drug.


Studies of "potentially lethal damage" in EMT6 mouse tumour cells treated with bleomycin either in vitro or in vivo. Studies have been carried out into the effect usually referred to as "repair to potentially lethal damage" following the treatment of cells with bleomycin. In vitro, increased survival was seen with delayed subculture of cells in both exponential phase and plateau phase. It was unimportant whether the medium present during the delay period had been previously used to support cell growth. Exposure of cells growing as a solid tumour in vivo to bleomycin (4 mg/kg), gave a surviving fraction of 2 X 10(-3) if assay was carried out at 30 min but a surviving fraction of virtually 100% if assay was delayed until 6 h. Various possible artefacts have been eliminated as reasons for the observations but doubts are raised regarding the nature of the mechanism involved.


The synthesis and properties of the complete complementary DNA transcript of ovalbumin mRNA. The synthesis of a complementary DNA copy (cDNA) of hen ovalbumin mRNA using AMV RNA-directed DNA polymerase was studied under different conditions of salt, deoxyribonucleotide concentrations, temperature, and time. It was observed that in the absence of monovalent cation at 46 degrees C a complete transcript of ovalbumin mRNA could be effected by the enzyme. The minimum deoxyribonucleotide requirement for complete synthesis was 35 muM for dATP, dGTP, and dCTP and 200 muM dTTP. By a number of different experimental criteria which included sedimentation on alkaline sucrose gradients and electrophoresis in polyacrylamide gels containing 98% formamide, direct electron microscope visualization, and protection of ovalbumin [25I]mRNA from nuclease digestion it could be demonstrated that a considerable fraction of a complete mRNA transcript was indeed synthesized. The cDNA/ovalbumin mRNA hybrid had a Tm on hydroxylapatite of 92 degrees C, indicating the synthesis of a RNA transcript with a high fidelity. When such a complete ovalbumin [3H]cDNA was synthesized with a specific activity of 10(8) cpm/mug and hyfridized to an excess of chick DNA, the kinetics of hybridization indicated that the cDNA was comprised of a nonrepetitive sequence.


Mechanism of phosphonoacetate inhibition of herpesvirus-induced DNA polymerase. Phosphonoacetate was an effective inhibitor of both the Marek's disease herpesvirus- and the herpesvirus of turkey-induced DNA polymerase. Using the herpesvirus of turkey-induced DNA polymerase, phosphonoacetate inhibition studies for the DNA polymerization reaction and for the deoxyribonucleoside triphosphate-pyrophosphate exchange reaction were carried out. The results demonstrated that phosphonoacetate inhibited the polymerase by interacting with it at the pyrophosphate binding site to create an alternate reaction pathway. A detailed mechanism and rate equation for the inhibition were developed. For comparison to phosphonoacetate, pyrophosphate inhibition patterns and apparent inhibition constants were determined. Twelve analogues of phosphonoacetate were tested as inhibitors of the herpesvirus of turkey-induced DNA polymerase. At the concentrations tested, only one, 2-phosphonopropionate, was an inhibitor. The apparent inhibition constant for it was about 50 times greater than the corresponding apparent inhibition constant for phosphonoacetate. DNA polymerase alpha of duck embryo fibroblasts, the host cell for the herpesviruses, was inhibited by phosphonoacetate. The apparent inhibition constants for the alpha polymerase were about 10-20 times greater than the corresponding inhibition constants for the herpesvirus-induced DNA polymerase. Duck DNA polymerase beta, Escherichia coli DNA polymerase I, and avian myeloblastosis virus reverse transcriptase were not inhibited by phosphonoacetate.


Species-specific aggregation factor in sponges. V. Influence on programmed syntheses. Isolated cells from the siliceous sponge Geodia cydonium as well as small primary aggregates (diameter: 70 mum) consisting of them show no increase in rates of programmed syntheses and mitotic activity with time. After addition of a highly purified aggregation factor to a culture with primary aggregates which subsequently form secondary aggregates (diameter: larger than 1000 mum), a dramatic increase of DNA, RNA and protein synthesis occurs. Together with this increase, the cells show a high mitotic activity. The values for the mitotic coefficient reach a first maximum 8 h after the beginning of the secondary aggregation process. The stimulation of the mitotic activity of cells during the aggregation factor induced secondary aggregation process can be suppressed by inhibitors of RNA and protein synthesis as well as by a blocker of DNA synthesis. This finding may indicate that cells from the G0-population enter the proliferating cell pool via the G1-phase.


Single-channel parameters of gramicidin A,B, and C. The single-channel conductance lambda and the mean channel lifetime gamma of natural and synthetic gramicidins A, B, and C has been studied. Significant differences in delta were found between gramicidin A and B; both gramicidins differ only in one amino acid (tryptophan replaced by phenylaline). The distribution of lambda is narrow in glycerylmonooleate membranes but considerably broader in dioleoyl phosphatidylcholine and dioleoyl phosphatidylethanolamine membranes. The ratio of the single-channel conductances in glycerylmonooleate and dioleoyl phosphatidylcholine membranes is only about two and is considerable smaller than the conductance ratio of nonactin-mediated cation transport. This finding suggests that dipolar potentials at the membrane/solution interface have little influence on the conductance of the gramicidin channel.


Experimental autoimmune demyelinating diseases: experimental allergic encephalomyelitis and experimental allergic neuritis. Experimental allergic encephalomyelitis (EAE) and experimental allergic neuritis (EAN) are reproducible models of auto-allergic demyelinating diseases of central and peripheral neurons tissue respectively. EAE bears a close resemblance to naturally-occuring post-infectious encephalomyelitis and EAN to Laundry-Guillain-Barré polyneuritis, in humans. In the experimental models the antigen responsible for disease induction is a different myelin basic protein in each disease. Although a variety of humoral antibodies to various neural fractions are found in both disorders, it has been shown that disease results from cell-mediated immune reactions to specific myelin antigens.


Antigenic identity of alpha-macrofetoprotein and acute phase protein in the rat. Antisera were raised in rabbits against rat embryonic blood and inflammatory serum. The antisera, made specific by absorption procedures, were cross reacted with embryonic blood and inflammatory serum. A reaction of identity between alpha-macrofetoprotein and acute phase protein was demonstrated.


Interference with proliferative activity in the CNS and its relation to facial abnormalities. In considering craniofacial abnormalities, possible caused by factors interfering with cell proliferation, it is important to keep in mind the central nervous system. The CNS produces specific cell types throughout gestation and interference with cell proliferation may cause permanent cell loss. In this study it is shown that brief insults may damage some brain structures and spare others. Which structures sustain damage depends on which cells are proliferating at the time of insult. The varied lesions produced by interference at different stages of development were found to be accompanied by different syndromes of behavioral abnormalities.


[The effect of heparin and a human heparin precipitable plasma fraction on antibody producing cells in vitro]. A study was made of the effect of heparin and heparin-precipitable fractions of human blood plasms (HPF) on the capacity of the cells of mouse spleen immunized with sheep erythrocytes to plaque-formation in vitro. It was found that heparin and HPF produced an inhibitory effect on the reaction of plaque formation as a result of interaction with lymphocytes. It is supposed that a possible point of application of heparin and HPF action are surface cell membranes of the antibody-forming cells.


[Ultrastructural analysis of preparations impregnated with silver salts]. The work was devoted to the ultrastructural analysis of the neurohistological preparations. Sections of the tissue from the precardial parts of the pulmonary and caval dog veins were impregnated with silver salts after Campos and embedded in the araldite by a special method. Electronmicroscopi studies showed reduced silver adsorbed by the tissue of the impregnated preparations to exhibit a granular structure (the granules were 30-400 A in size). The largest of them were revealed in the axoplasm of the myelinated and unmyelinated nerve conductors, whereas the smaller ones found in various cellular and fibrous formations of the tissue substrate; silver granules were as a rule absent within the thickness of the myelin sheath. The noted regularities of adsorption and distribution of the silver granules in the impregnated preparations caused a morphologically expressed phenomenon of argentophilia.


[Histochemical characteristics of the secretory elements of the vermiform appendix following surgical trauma, circulatory hypoxia and immunization]. Histochemical methods were applied to determination of salomycin, dermatansulfate, keratosulfate and neutral mucopolysaccharides in the goblet cells of rabbit appendix. Sialomycin and neutral mucopolysaccharides were found in the glands. Immunization with human gamma globulin was followed in the productive phase of immunogenesis by a rise of the secretory activity of the mucosa of the appendix. An increase of the mucus formation in the appendix occurred after laparatomy and during the initial period of experimental appendicitis. However, surgical trauma caused an opposite effect against the background of increased functional activity of the secretory elements of the immunized animals, and during experimental appendicitis no activation of mucus formation was seen. The influence of the abovementioned factors on the secretory activity of the mucous membrane was accompanied by qualitative changes in the synthesized mucus.


[Isolation of the pregnancy specific beta-glycoprotein (SP1) and antigen-related proteins by means of immunoadsorption]. Purification of human pregnancy-specific beta1-glycoprotein (SP1) and antigenically related proteins of sub-human primates (chimpanzee, rhesus monkey, cynomolgus and baboon) was achieved by means of an immunoadsorbent technique. The immunoglobulins of a rabbit antiserum to human SP1 were isolated on DEAE-cellulose and coupled to CNBr-activated Sepharose. This immunoadsorbent was used to bind human SP1, respectively monkey proteins immunochemically related to SP1 from placental extract fractions. After extensive washing the proteins were eluted by an acidic glycine buffer. Contaminating serum proteins could be removed by chromatography on hydroxyapatite columns. With this method it was possible to obtain SP1 and the antigenically related proteins of monkeys in good yield and in highly purified form. The proteins thus isolated from human and sub-human primate placentae were compared in their physicochemical and immunochemical properties. The amino acid and carbohydrate compositions of human SP1 and rhesus SP1 have been determined. In a biological test certain inhibitory effect of human SP1 on the mixed leukozyte culture (MLC) could be demonstrated.


[Can azur-B eosin replace the May-Grünwald-Giemsa stain?]. A new method is described for staining blood and bone marrow smears. It is characterized by the presence of only two dyes, purified azure B and eosin in methanol, as stock solutions. Staining results are equivalent to those obtained by using the traditional dye mixtures according to May and Grunwald, Giemsa, Leishman or Wright. Different from these azure B-eosin staining can be standardized and is easier to be handled. Correlations between the azure-B-eosin and May-Grunwald-Giemsa (MGG) staining methods are briefly discussed.


[Electronmicroscopic and immunohistochemical studies on human lymphocytes]. Lymphocytes from the blood of healthy individuals and of patients suffering from CLL were investigated by electron microscopy and peroxidase-immunohistochemistry. B-lymphocytes were labelled by heterologous, peroxidase-conjugated antisera directed against the Id-determinants of their membranes. T-lymphocytes were labelled by an indirect method: specific incubation with a specific anti-T-cell-globulin from the rabbit; labelling-incubation with a peroxidase-conjugated anti-rabbit-IgG-globulin from the sheep. In addition, T-lymphocytes were identified by their ability to form rosettes with sheep erythrocytes spontaneously. The quantitative results were: about 80% T-lymphocytes and about 24% B-lymphocytes in normal persons, the opposite results in CLL. T- and B-lymphocytes were photographed electron microscopically; the number of organelles in the single cells was evaluated: lysosomes in the average are more numerous in T-lymphocytes, ergastoplasm in B-lymphocytes, mitochondria are equally distributed in both groups of cells. There is so much overlapping, however, that the single cell only with the aid of immunochemistry or rosette formation can be identified as a B- or T-cell. In both, the T- and the B-cell-series, different forms of lymphocytes can be distinguished according to the degree of cell differentiation. Some further problems, as specificity of the antisera and labelling of the cells by means of their Fc-receptor are discussed.


Bleomycin in advanced squamous cell carcinoma: a random controlled trial. Report of Medical Research Council Working Party on Bleomycin. Bleomycin was compared with conventional cytotoxic drugs in the treatment of 70 patients with advanced squamous cell carcinoma; the primary deposit was in the head and neck in 50 patients and in the perineum or skin in 20. Thirty-four patients received bleomycin while 36 received other cytotoxic drugs. No significant difference was detected between the two groups either in the proportion showing tumour regression or in the survival rates. If bleomycin is to advance the treatment of squamous cell carcinoma it can be only in combination with other drugs or with radiotherapy.


Rapid retrograde transport of dopamine-beta-hydroxylase as examined by the stop-flow technique. We have studied the retrograde axonal transport of dopamine-beta-hydroxylase (DBH) with the aid of a new stop-flow technique. Rabbit sciatic nerves in vitro were incubated in chambers which exposed different regions to oxygenated physiological saline solution at different temperatures. These chambers contained no mechanical barriers that could generate local compression or anoxia. When the proximal halves of nerves were cooled to 2 degrees C while the distal halves were kept at 37 degrees C, a peak of DBH activity began to accumulate in the middle. Accumulation was detectable after 1.5 h of proximal cooling, and the amount of activity in the peak increased linearly with time for up to 4.5 h. The rate of this accumulation was only about 20% of the rate at which DBH activity accumulates proximal to locally cooled regions. Retrograde accumulation of DBH activity is not an artifact that depends upon the simple juxtaposition of cooled and warmed regions; it does not occur when nerves are locally warmed to 37 degrees C while being kept elsewhere at 2 degrees C. When nerves that had been proximally cooled for 3h were rewarmed, the accumulated DBH activity was asymmetrically displaced toward the proximal end. The migrating wave lacked a definite peak, but appeared as a shoulder with a well-defined front that moved steadily at about 12mm/h. We take this as direct evidence for retrograde axonal transport of DBH. The maximum velocity of this transport is very similar to the velocity of orthograde transport previously determined by stop-flow techniques.


[Classification by the Golgi technique of several categories of neurons in the mouse paraventricular nucleus]. Using the rapid Golgi technique four types of neurons have been observed in the paraventricular nucleus : magnocellular neurosecretory neurons, parvocellular neurons with "extrahypophyseal" axon, parvocellular neurons with recurrent axon (possibly inhibitory interneurons) and neurons of reticular type.


Calcium localized in juxtanuclear granules of epiphyseal chondrocytes with a dilute glyoxal bis(2-hydroxyanil) solution. The glyoxal bis(2-hydroxyanil) (GBHA) method for staining labile calcium deposits in chondrocytes was modified. Fresh blocks of epiphyseal cartilage stained in this dilute GBHA solution revealed calcium in the juxtanuclear Golgi vesicles, each approximately 1 mu in diameter. Prolonged staining revealed previously described 0.5 mu granules throughout the cytoplasm which tended to mask the juxtanuclear reaction. The red GBHA reaction product was believed to be a chelate of calcium since it was removable with EGTA, and stable in Na2CO3 and KCN solution. When the tissue blocks stained with the dilute GBHA solution were restained with the original concentrated GBHA solution, refractile bodies containing red GBHA-positive granules were revealed at the periphery of the hypertrophied chondrocytes. The presence of calcium in the juxtanuclear Golgi vesicles and in the pericellular refractile bodies may indicate that the Golgi is involved in the transport of minerals to the matrix.


Blood group MN precursors as human breast carcinoma-associated antigens and "naturally" occurring human cytotoxins against them. Blood groups MN active substances were found in benign and malignant human mammary glands. However, the precursor T (Thomsen-Friedenreich) antigen, as determined with human sera, occurred in all cancerous breast tissues tested but not in the benign mammary glands. Anti-T antibody, which is present in all human sera, was severely depressed in 21.16% of 189 breast carcinoma patients, compared with 3.62% of 470 persons of similar age without cancer. Of 720 persons tested approximately 85% of those with severely depressed anti-T had carcinoma; their IgG, IgM and IgA concentrations were of normal range. A greater than 25%-90% increase in anti-T titer score was found in 65.6% of 32 patients bled 1-14 months after mastectomy for carcinoma as compared with 3.1% of 32 patients with breast biopsy who had no carcinoma. All differences in anti-T titer score changes reported are statistically highly significant. Injection of T antigen from human erythrocytes increased anti-T titer scores.