[Biology of a newly isolated agent of the Chlamydia group]. The results of identification of the agent ("Progress" strain) isolated from the organs of a calf sacrificed in the early stage of pneumonia are presented. The agent adapted to yolk sacs of chick embryos was pathogenic for white mice by the intracerebral route and for monkeys infected with aerosol. The infected animals developed specific complement-fixing antibody. The antigen of the agent reacted in the CFT with homologous immune sera and with sera against ornithosis and other members of the ornithosis-lymphogranuloma-trachoma (OLT) group. In cell cultures the agent multiplied well and produced cytoplasmic inclusion bodies characteristic of the OLT group members.


[Properties of mouse hemocytoblastosis-reticulosis (Mazurenko) virus]. The results of molecular biological study of the properties of hemocytoblastosis-reticulosis virus (Mazurenko) are presented. The virus was found to have buoyant density of 1.16 g/cm3 in sucrose density gradient. Virions contain 70S RNA possess reverse transcriptase activity.


[Experiences in the determination of thyroxine iodine in serum in various functional conditions of the thyroid gland]. A report is given on the method of the thyroxine iodine determination in the serum. Of 213 patients the result of the thyroxine iodine determination was compared with the clinically and radiologically established functional condition of the thyroid gland. The findings are discussed. Similar results were also reported of other in-vitro-tests (T3-test, T4-test, BEJ and PBJ). According to our experiences we consider the thyroxine iodine determination in the serum siutable as screening test which - when there is a suspicion of a hypo- or hyper- thyroidism - needs the supplementation by the radio-iodine functional and localisation tests.


[Frequency and type of arrhythmias in patients with chronic coronary disease]. Serious arrhythmias are accepted to be the main cause of sudden death in acute coronary artery disease (CAD). The purpose of this study was to evaluate the frequency and type of cardiac arrhythmias in patients with chronic CAD. 67 patients with suspected chronic CAD, documented by history and/or Ecg-changes, were investigated by means of a dynamic Ecg (Holter Avionics) with an average of 11 hours monitoring. On the basis of concomitant ST-segment depressions the patients were divided into 3 groups (A: greater than 0.1mV; B: 0.05-0.09mV; C: less than 0.05mV). The frequency of serious arrhythmias increased significantly with a greater degree of ST-segment depression. Serious arrhythmias were observed in 54% in group A, in 46% in group B, but only in 24% in group C. The frequency of minor arrhythmias such as occasional (less than 12/min atrial or ventricular premature contractions was essentially the same in all 3 groups. In 12 patients more than one serious arrhythmia were documented. Of the serious arrhythmias observed, 94% were tachycardias and/or secondary to increased myocardial irritability and therefore could respond favourably to beta-blocking agents. We believe that arrhythmias in patients with known chronic CAD should be taken seriously and longterm treatment with beta-blockers considered.


[The significance of inner ear fluid (perilymph) in forensic medicine (author's transl)]. An original method for collecting the perilymph in the inner ear by chiselling the pyramid of the temporal bone is presented; From 300 to 350 mul of fluid may be obtained each time. Various types of determination were performed on 399 human cadavers. The alcohol level was tested in 140 cases, the ABO(H) group antigens were determined in 89 cases, the phenotypes of the gamma-globulin (1) group system in 152 cases, and the alpha1-antitrypsin (Pi) system in 18 cases. Determinations of the alcohol level in the perilymph has been confirmed to be useful, as they allow not only determination of the degree of intoxication in cadavers in an advanced state of decomposition, but also by comparing the alcohol concentration in the cerebrospinal fluid, the vitreous humour, and the blood, the phases of elimination and absorption of alcohol may be more precisely determined. It was also found that the perilymph is a good medium for the determination of the group antigens of the red blood-cells and the gamma-globulin system, the serum and the alpha1-antitrypsin enzyme. These data suggest that the method may be more widely used in various forensic medical tests.


[Problem in the partial separation of X- and Y-carrying human spermatozoa]. The introduction of a fluorescent staining technique for identification of Y chromosome made possible the distinction of X- and Y-bearing human spermatozoa. Using this fluorescence analysis the isolation of Y- and X-bearing human spermatozoa were investigated employing two different methods for separation of spermatozoa. 1. The migration of human spermatozoa in cervical mucus obtained from women shortly before mid-cycle was studied, using an in-vitro method for horizontal sperm penetration. Basing on the progressive sperm motility in cervical mucus, a fraction rich in Y-bearing spermatozoa in the frontal zone of sperm migration was found. 2. Gradient centrifugation at different rotor speeds using a discontinous sucrose gradient has been employed for separation of human spermatozoa. A significant trend for separation of Y- and X-bearing spermatozoa was demonstrated. The results were shortly discussed.


[Changes in heparinocytes during the administration of Depositon and Sequenz-Ovosiston]. During hormonal contraception with Deposiston (once a week pill) and with Sequenz-Ovosiston (14 days mestranol 0.1 mg, 7 days mestranol 0,08 mg and 2 mg chlormadinone acetate) doesn't take place a change of basophil granulocytes (heparinocytes) in blood. Under Deposiston the small elevation is somewhat lengthened, under Sequenz-Ovosiston the elevated phase is similar to those of the normal menstrual cycle. The smaller risk of thromboembolia under heparinocytopenia preventing contraceptives is discussed.


Antigenic variation of neuraminidase of human type A influenza (H3N2) viruses isolated in Berlin (West). After the emergence of the A/Hong Kong/1/68 (H3N2) strain of influenza virus antigenic variation of the hemagglutinin and neuraminidase antigens have been demonstrated leading to the identification of the variants A/England/42/72,a/Port Chalmers/1/73 and A/Scotland/840/74. This study describes antigenic changes of neuraminidases in influenza viruses isolated since 1968 in Berlin (West). A collection of 13 isolates of human type A influenza was studied in neuraminidase inhibition tests. The results are in line with data from other laboratories indicating a major change in the neuraminidase antigen as early as December 1969. The strains isolated at that time cross-reacted with an antiserum against the N2-Hong Kong enzyme to less than 50%. During the following years (1970 to 1972) the neuraminidase remained fairly stable. Serological cross-reactions showing 47 to 38% inhibition as compared to the homologous N2-antigen. The neuraminidase of the A/Berlin/3/72 strain revealed a close antigenic relationship to the later appearing A/Port Chalmers 1/73 variant. Two strains isolated in 1975 (January) showed an even further drift away from the then representative A/Port Chalmers/1/73 strain. The fact that the neuraminidase antigens of the Berlin viruses had changed in December 1969 may account for the severe 1969/70 influenza epidemic in Berlin affecting a large proportion of the population. Prevalent anti-neuraminidase antibodies may play a role in restricting a variant carrying a new hemagglutinin to primarily infected individuals by cross-reacting with a closely related enzyme.


[LE cells in the synovial fluid].

[LE cells in the synovial fluid]. The occurence of LE cells in the synovial fluids of two patients is reported. The demonostration of LE cells in synovial exudate is clinically valuable. Examination of joint fluid should therefore pay attention to the search for LE cells and their precursors. Reoccurrence of E-cells in the synovial fluid indicates their origin in the joint cavit. They could still be found even after multiple intraarticular injections of triamcinolone acetonide.


Cross-protection induced in mice by immunizations with proteins of related bacteria species. Groups of mice were immunized with detoxified protein from S. typhimurium, S. paratyphi B and S. paratyphi C. Consecutive infections with different concentrations of the homologous and heterologous strains showed that: 1. Immunizations with proteins from S. typhimurium induced protections in 65% of the mice infected with 50 LD100 of their natural pathogen, and in 80% of the mice infected with 50 LD100 of S. paratyphi B; the infection with S. paratyphi C of mice in this group afforded protection against 20 LD100 in 75% of the animals. 2. Immunization with proteins from S. paratyphi B induced protection in the mice against the infection with 20 LD100 of S. typhimurium (survival of 80% of the mice) and against 20 LD100 of the homologous S. paratyphi B (survival of 90% of the mice). 3. Immunization with proteins from S. paratyphi C protected the mice against the infection with 20 LD100 of S. typhimurium in a proportion of 80-85% of the animals; infection with the homologous S. paratyphi C did not result in protection against more than 20 LD100 of the bacteria (80-85% survivals). The survivors, in each group, when reinfected 30 days later with 50 LD100 of S. typhimurium resisted in a proportion of 100%, as a consequence of antibodies induced against more specific proteins released in the mice during the infections by the related pathogens.


The unfortunate role of precedent in bacteriology. I. The main antigens of salmonellae: the proteins. Proteins from S. paratyphi B were found to be better immunogens, in rabbits, than the bacteria from which they were extracted. Likewise, proteins from S. newport induced antibodies which reacted in agar gel, against proteins from many species of Salmonella. The immunogenicity of the bacterial proteins, as well as their many biological activities are ignored because the classic techniques used lose these main antigens of Enterobacteriaceae. The contrasting overemphasized role attributed to the lipopolysaccharides has created a precedent which is not to the advantage of bacteriology.


[The tetralogy of Fallot: surgical treatment. 145 cases (author's transl)]. 1. The overall operative risk for the palliative procedures for Tetralogy was 3,2% (93 cases). The Blalock-Taussig shunt remains the intervention of choice in older children. The Waterston shunt gives optimal results in the infants under six months of age but on long term the hasard of pulmonary hypertension still exists. 2. Before 1965, the mortality rate for the total repair was 43,7% (16 cases). During the last 8 years, the mortality rate decreased to 5,7% (36 cases). One operative death after total correction with a Potts shunt is not included in this figure. This type of shunt was replaced by the Waterston shunt after 1966, because of the high operative risk total correction and the high frequency of pulmonary hypertension on long term. 3. The long-term results were excellent in 85% of the survivors (mean follow-up of 4,1 years). A pulmonary insufficiency was found on clinical examination in 35% of the cases. This insufficiency was well tolerated by all patients. The long-term consequences, however, are uncertain. 4. It seams rational to proceed to an earlier total correction in these cases when well defined criteria are fullfilled, as the mortality figures of the palliative and corrective procedures have a tendency to reach each other: (3,2 versus 5,7%).


[Treatment of perforated gastroduodenal ulcer with gastrectomy using a "T" tube. Preliminary report (author's transl)]. Perforation of gastro-duodenal ulcers is followed by a 10% mortality rate. Surgery remains the first choice treatment. A series of 27 cases treated as emergencies by a gastrostomy with a "T" tube of Kehr is reported. The technique is simple and operative time minimal. It is especially indicated in perforations of more than 8 hours or happening in old or diseased patients. It is safer than simple sutures and makes an efficient postoperative intensive care possible. Its purpose is to save the patient while postponing elective surgery.


[Mediastinoscopy and bronchial carcinoma. Experience with 600 mediastinoscopies (author's transl)]. Of 600 mediastinoscopies carried out from 1966 to 1973, 479 were performed to assess the operability of a pulmonary carcinoma. Of these, (43%) were positive and (57%) negative. Of the 161 patients found positive during an initial period, 14 were considered candidates for operation. The tumour was irresectable in one patient, who died after 3.5 months; curative resection was possible in one and palliative resection in 12 patients. These 12 patients all died within a year. Of the 184 patients found negative during an initial period, 149 were treated by operation. The tumour proved irresectable in 5%, while curative resection was possible in 76% and palliative resection in 19%. Comparison with the period 1957-1963, when in the same hospital resection was performed after a negative Daniels biopsy, shows that the tumour was irresectable in 20%, while curative resection was possible in 35% and palliative resection in 45%. During a second period, patients with a positive mediastinoscopy were refused operation. Of 89 negative patients, 81 were treated by operation. No tumour was found to be irresectable; curative resection was possible in 78% and palliative resection in 22%. A survival study was made of 100 operated patients with a follow-up from a minimum of two years and four months to a maximum of four years and four months. The early mortality averaged 10%. The late mortality was 31% after curative lobectomy, 43% after curative pneumonectomy, and 100% after palliative resection. The survival was 49%


Studies on guinea pig skin cell cultures. V. Co-culture of pigmented melanocytes and albino keratinocytes, a model for the study of pigment transfer. Mixed cultures of melanocytes (M) and keratinocytes (K) are easily obtained from pigmented guinea pig ear skin. They are suitable for the study of pigment transfer from M to K. However, quantitation is difficult because many K are already loaded with pigment prior to cultivation. A technique is presented in which pigment-producing M are co-cultured with K of albino origin. Pigmented guinea pig ear skin is split with trypsin and basal cells including M are harvested. The cell suspension is treated with sodium citrate which prevents the attachment of K (but not of M) to the culture substrate. Ninety per cent pure M cultures are obtained. Five to seven days later, another basal cell suspension is prepared, this time from albino ear skin. This second suspension is seeded on top of the pigment-forming culture of M. The number of contacts between albino K and pigment-forming M increases as a direct function of time. Contrarily, the number of K which become pigmented increases until the fifth day of co-culture and decreases thereafter.


Biosynthesis of prostaglandins by human inflamed skin. The biosynthesis of prostaglandins by human inflamed skin was studied in 8 patients with primary irritant dermatitis induced by benzalconium-chloride. Inflamed skin from these patients evidenced an increased ability to synthesize prostaglandins. In the presence of exogenous arachidonic acid in the incubation medium, the activity formed was about 80% greater in inflamed skin than in non-inflamed control skin. In prostaglandin E1-equivalents the concentration amounted to 8.09 +/- 1.59 ng/mg protein nitrogen and 4.51 +/- 1.24 ng/mg protein nitrogen, respectively (mean values +/- S.E.). When inflamed skin was incubated without excess of exogenous precursor acids in the incubation medium the activity formed was about 80 times lower and the values were similar to those of non-inflamed skin. Thus, the present results support the view that the prostaglandin system is activated in primary irritant dermatitis, thereby providing a basis for future therapeutic attempts to control this disorder.


Immunological phenomena induced by UV rays. Antiserum against UV-irradiated DNA was prepared and used as a specific reagent in an indirect immunofluorescence (IF) technique for the detection of photochemically damaged DNA in the epidermis of hairless mice. Fluorescence of cell nuclei was found in sections of dorsal epidermis of mice immediately after the irradiation. It persisted for 24 hours. The IF reaction became negative after 48 hours, irrespective of the duration of UV exposure to which the mice were subjected. This may indicate: either (a) the occurrence of DNA repair processes, or (b) the relation of DNA repair to the life cycle of the epidermal cell. Mice exposed to UV radiation similar to the erythema spectrum of sunlight do not show any changes in the cellular DNA, even after a dose of 40 MED.


Dissociation of human adult epidermal cells by disulfide-reducing agents and subsequent trypsinization. Primary cultures of epidermal cells from human adult skin were dissociated by dithiothreitol (DTT) with subsequent trypsinization. After treatment with disulfide reducing agents, the desmosomes were either destroyed or showed a homogeneous ultrastructure. Trypsin separated the homogeneous desmosomes, whereas cell membranes, organelles, and nuclei remained undamaged. Trypsin did not influence normal desmosomes. A suspension of human epidermal cells was recultivated in new flasks. Two types of cells grew in the cultures--polygonal and spindle-shaped. The polygonal cells were maintained for 30 to 60 days and grew slowly. The spindle-shaped cells were leucine-amino-peptidase negative, grew actively, and were subcultured.


Demonstration of 3-methoxytyrosine in the urine of melanoma patients. With the aid of gas chromatography and mass spectrometry a metabolite of dopa, 3-methoxytyrosine, has been demonstrated in the urine of 2 patients with melanoma metastases, the amounts excreted being 4.0 mg and 8.5 mg/24 hours, respectively. 3-Methoxytyrosine could not with certainty be identified in the urines of two normal subjects.


Benign and malignant proliferative response. Dermal infiltration, origin and importance. Lymphoreticular infiltration (LRI) is the most common type of dermal infiltration. The LRI is made up of two main components: (i) a dermal skeleton, and (ii) the infiltration in a strict sense. (i) The dermal skeleton consists of the blood vessel involved, most probably a post-capillary venule, and activated fibroblasts (Fig. 3). The activated fibroblasts contain "paraplasmatic granules" in their processes (Fig. 4). Since the fibroblasts are in mutual contact by their ramifications (Fig. 3), they are reticulum cells by definition (Bessis). In our opinion they are the only local reticulum cells in the dermis. They are not stem cells, nor do they belong to the reticulo-endothelial system and they do not give rise to histiocytes. (ii) In the skeleton of LRI, other cells infiltrate, predominantly monocytes and lymphocytes. The LRI may specialize and contain various amounts of neutrophilic, basophilic, or eosinophilic leukocytes and plasma cells. If enough B-lymphocytes and plasmacells are involved, abnormal globulins may be produced (e.g. syphilis II). The lymphomas are considered to be malignant proliferative disorders of LRI-type. LRI is found in allergic spreading reactions mediated by stimulated lymphocytes. A similar spreading of lymphocytes is to be expected if the allergen sensitizes a lymphocyte with neoplastic information (e.g. tumor virus) (Fig. 6). The degree of dedifferentiation and the response of the organism to the dedifferentiated lymphocytes is the reason for the variety of lymphomas.


The activation of antigens of the basement membrane zone by proteolytic enzymes in vitro. Following brief exposure of cryostat sections of human skin to the action of proteolytic enzymes (papain or trypsin), there was a pronounced increase in the antibody binding sites of the basement membrane zone, shown in indirect immunofluorescence by an increased intensity in fluorescence of the basement membrane zone as compared with preparations which had not previously undergone incubation, and by an increase of 5-6 (papain) or 4-5 (trypsin) titre dilution steps. This effect was practically absent when guinea-pig tongue was used as the antigenic substrate. In conjunction with findings published in the literature, our results can be interpreted as indicating that the activation of the basement membrane zone antigens by proteolytic enzymes is associated with an increase in antigenicity which results in the formation of "auto-antibodies" of the basement membrane zone antibody type.


Studies on T and B lymphocytes in the peripheral blood of discoid lupus erythematosus patients with and without chloroquine treatment. The proportions of T-B cells of peripheral lymphocytes in DLE patients as well as the effect of chloroquine treatment on T cell count were studied. In DLE, both the active and the total rosette-forming cell counts decreased, whereas the B cell count did not differ from normal values. Long-term chloroquine administration causes a further reduction in T cell count.


Keratinized cells as a possible yellow-stain receptor for gold-orange. Using a previously described staining procedure, it was found that gold-orange stains some epithelial cells yellow, both in skin sections and in cytologic smears from skin and various other epithelia. A correlation seems to exist between the degree of keratinization and the yellow colour obtained with this staining method.


Study of some minerals in normal Egyptian scalp hair. Scalp hair of 128 normal individuals of both sexes and of differing ages was examined for its mineral content by flame photometric and colorimetric procedures. The results obtained revealed that sodium and potassium may be considered as sex specific and of value as a medico-legal sign, while no marked difference was observed between male and female calcium content. The values of scalp hair copper were found to be slightly higher in females than in males. Similarly the mean value of scalp hair iron was found higher in females than in males, especially during the female reproductive period. Regarding the scalp hair phosphorus content, it has been found that a relationship between phosphorus and calcium does exist.


Treatment of hereditary angioneurotic edema with tranexamic acid and cinnarizine. Six out of 7 Finnish patients suffering from hereditary angioneurotic edema were helped during attacks, by treatment with tranexamic acid (AMCA, Cyklokapron, Kabi) in doses of 1.5 g 3 times daily, follow-up time 3-25 months. 3 of these patients also had continuous AMCA treatment, in the course of which 2 remained nearly symptom-free on a dosage of 1 g 2-3 times daily. Even the third one had shorter and milder attacks. One patient, however, had to stop taking AMCA after 6 weeks' treatment, because of fatigue and nausea. Follow-up time for the others was 9-11 months. For comparative purposes, 3 patients were given continuous treatment with an antihistamine, cinnarizine in a dosage of 20-30 mg daily. Two of the patients were helped by it, one becoming nearly symptom-free and the other having fewer and milder attacks; follow-up time 9-10 months.


Erythema nodosum and erythema multiforme associated with milker's nodules. An epidemic of 44 cases of milker's nodules was recorded in the Tampere Central Hospital catchment area in Finland during the autumn of 1974. Exanthema or erythema multiforme-like secondary eruptions were seen in 10 cases. One female patient is reported in detail because of the simultaneous occurrence of erythema nodosum and erythema multiforme. The virological diagnosis was confirmed by electron microscopy.


Exaggerated onychodermal band associated with unilateral racket thumb nail. Exaggerated onychodermal bands and a unilateral racket thumb nail occurred in a healthy 36-year-old primiparous female. Each condition is described and the relationship of exaggerated onychodermal bands to chronic renal disease (systemic disease) is reviewed. We are reporting this patient since we have been unable to find a similar reported case with both abnormalities and because of the paucity of information on these conditions in the dermatology literature.


Subacute thyroiditis. Eleven cases with histological confirmation and thyrotrophic response to thyrotrophin releasing hormone. Eleven cases are reported of subacute thyroiditis with histopathological study; there were 9 females and 2 males. Bacteriological studies were inconclusive. Different stages of pathological involvement were observed at the same time in all patients. The clinical course followed the classical pattern in most cases: hyperthyroid-like, hypothyroid-like phase and recovery. Blood TSH assessment before and after TRH stimulation revealed an early phase of depression unresponsive to TRH, followed by high levels with marked stimulation; during the first phase, radioiodine uptake was low, but was enhanced by exogenous TSH administration; accordingly the low uptake seems to be due to low TSH levels and not to complete destruction of the thyroid gland. Failure of TSH levels to rise after TRH stimulation is typical of this stage of the disease. Although the final outcome is not yet predictable in some patients, definitive myxoedema appears to be probable in two cases.


[Differential diagnostic procedures in localized liver diseases]. Liver scintigraphy by means of 99mTc-sulphur colloid (n = 430) and 67Gallium-citrate (n = 180) were carried out on selected patients, on a follow-up study. This study was undertaken to prove the possibility of early diagnosis of primary hepatic carcinomas. Only autoptically verified cases (n = 119) were used for the evaluation of the accuracy of liver scans. 99mTc-s.c. -scans predicted the presence or absence of focal liver diseases in 78% of the cases. Scan data were falsely positive in 10% and falsely negative in 28%.


Kurloff cells. 1. Histochemical characteristics of the Kurloff bodies. Kurloff cells, characterized by a large inclusion body in ill-defined lymphoreticular cells, were induced in male guinea pigs by oestrogen administration. The inclusion body material was characterized by way of light- and electron microscopy and histochemical staining reactions. Nucleo-protein were not detected, but certian tests for amino acids were observed and, at the peripheral parts of the inclusion bodies, phospholipid tests were positive. However, forced proteolysis of lipid extractions failed to abolish the reactions for detection of carbohydrate-rich compounds in the inclusion bodies thus confirming that their main characteristics were those of glycoproteins. Series of histochemical tests demonstrated the presence of periodate-reactive 1, 2-glycol groups and sulphate radicals. Periodate-reactive material and sulphomucins represented two separate substances, as demonstrated by extractions and combined staining tests. Some characteristics common with chondroitin sulphates were observed but, on the other hand, the observed differences suggested a different type of sulphation. The inclusion body failed to show any hydrolytic, dehydrogenase or oxidative enzyme activities, thus being metabolically inactive, although the cells showed certain enzyme activities in their cytoplasm and cell organelles.


Kurloff cells. 2. Histochemical and morphological characteristics of the Kurloff cells. Kurloff cells (KB cells) containing a glycoprotein inclusion body appear in femal guinea pigs and can be induced in males by oestrogen administration. These cells are found in bone marrow, thymus, and in the red pulp of the spleen, but not in the lymph nodes. Gradually growing inclusion bodies were observed in a series of cells in these organs. Morphological and histochemical features suggested an active synthesis of the inclusion body material: cisternae of the endoplasmic reticulum fused with the membrane surrounding the inclusion body and by way of electron histochemical methods periodate reactive material was demonstrated in the endoplasmic reticulum, in the Golgi cisternae, and in the inclusion body. Enzymatic activities were not observed in the inclusion body, but otherwise the KB cells showed enzymatic activities of oxidative and glycolytic pathways. Marker enzymes for the granulocytes series, the plasma cells, the mast cells, and the monocyte-reticulum cell group were negative in the KB cells and thus, classification of the KB cells into a particular cell type was not possible, although these cells obviously belong to the lymphoreticuar system. Phagocytosis was not observed, either. The possible role of the KB cells in the immune system are discussed.


Studies on the 14C-histamine release induced by noradrenaline in mouse neoplastic mast cells. Murine neoplastic mast cells incubated with labelled histamine released 14C-histamine when exposed to increasing concentrations of noradrenaline. This process was blocked by low temperature, by inhibiting oxidative metabolism and glycolysis, by calcium deprivation and by cytochalasin B. Electron microscope observations of cells exposed to noradrenaline revealed an increase of the Juxtanuclear Golgi Apparatus, and the appearance of a pronounced peripheral vacuolization. Cells exposed simultaneously to noradrenaline and cytochalasin B were characterized by a further increase of the Golgi apparatus, and by the appearance of many electron dense cytoplasmic granules. The possible mechanisms of the noradrenaline induced histamine release were discussed.


Sudden death following intravenous sodium diphenylhydantoin. A well-documented (by ECG as well as autopsy) case of fatal ventricular asystole secondary to intravenous administration of sodium diphenylhydantoin is presented. The possible role of ventricular conduction disturbances, hypoxemia, and metabolic abnormalities as precipitating factors are discussed.


Blood viscosity and oral anticoagulant therapy. During administration of bishydroxycoumarin, hematocrit, viscosity of whole blood, and viscosity of plasma decreased in samples from nine healthy volunteers and 31 patients who had coronary heart disease. The relationships between viscosity of blood and intensity of anticoagulant therapy varied from patient to patient. Discontinuation of the drug was followed by return of viscosities to pretreatment levels in two to four days. The decrease of viscosity of blood by anticoagulant therapy may explain the relief of anginal pain in patients who have coronary heart disease.


Pharmacy exhibits in medical staff education. The use of hospital pharmacy exhibits as a means of educating physicians about pharmacy services and improving physician-pharmacist relationships is discussed. Two exhibits concerning potassium supplementation and total parenteral nutrition are described.


Pharmacokinetics in drug therapy. I: Propranolol hydrochloride as adjunct therapy in the treatment of thyrotoxicosis. A case study in which propranolol hydrochloride was used as adjunct therapy in the treatment of atrial fibrillation with rapid ventricular response, thyrotoxicosis and high output heart failure is presented to illustrate the pharmacokinetics of this drug. The relationship of propranolol dosage to blood levels, the effect of blood levels on pharmacological response, the metabolism and elimination of propranolol, and determination of rational dosage of the drug, are discussed.


The reflex sympathetic dystrophy syndrome. I. Clinical and histologic studies: evidence for bilaterality, response to corticosteroids and articular involvement. Eleven consecutive patients fulfulling criteria for the reflex sympathetic dystrophy syndrome (RSDS) were studied by quantitative clinical methods, providing measurements of swelling (ring size), tenderness (dolorimeter) and functional capacity (grip strength). The predominantly affected extremity was clearly identified by these technics and its serial progress determined in six patients. Corticosteroid therapy predictably resulted in improvement of all treated patients. Greater tenderness was found in the joints than in the interjoint areas, indicating a possible accentuation of the disease process in juxta-articular tissues. Synovial biopsy specimens in four patients were abnormal, and the histology was presented in detail for the first time. All patients showed bilateral involvement during the study, providing evidence for a central neural mechanism in the RSDS.


The reflex sympathetic dystrophy syndrome. II. Roentgenographic and scintigraphic evidence of bilaterality and of periarticular accentuation. Patchy osteoporosis is the primary roentgenologic manifestation of the reflex sympathetic dystrophy syndrome (RSDS). As recent clinical and histologic data suggested articular changes in RSDS, fine-detail roentgenograms were obtained in eight consecutive patients. Juxta-articular and soft-tissue swelling, osteoporosis and erosions of the subchondral bone were found. 99mTcO4 and 99mTc-EHDP scintigraphy showed localization of nuclide predominantly in the juxta-articular tissues. Serial roentgenographic, scintigraphic and quantitative bone densitometric measurements showed changes that reflected the clinical course of the disease.


Alpha-fetoprotein.

Alpha-fetoprotein. Despite all the information about AFP presented, a great deal still needs to be discovered especially in pregnancy. Geographical and racial differences remain to be elucidated. Similarly, differences in obstetric population in Helsinki and Baltimore, for example, are only now being studied. Sex differences may exist; Lardinois and associates195 cited a higher level of AFP in male than female fetuses. The important questions that need to be answered are whether AFP assays can help improve the other half of prenatal care- that directed to the fetus- and whether the AFP model can help enhance our understanding of the similarities and differences of fetal and cancer cells.


Serum prolactin concentrations in women treated with chlormadinone acetate. Serum prolactin concentrations were measured serially in eight normal women who used continuous chlormadinone acetate treatment (500 mug per day) for six months as part of an investigational new drug contraceptive study. Circulating prolactin was also measured in women using several additional oral contraceptive steroid preparations including a sequential mestranol-mestranol + chlormadinone acetate regimen. No increase in basal serum prolactin concentration was produced by chlormadinone acetate treatment, either alone or when added to estrogen therapy. These results suggest that chlormadinone acetate may not alter human mammary tissue through a prolactin mechanism.


Fetal syphilis in the first trimester.

Fetal syphilis in the first trimester. Evidenc of first-trimester fetal syphilis was sought in the products of conception in a therapeutic abortion clinic. During two collection periods of one week, five patients with serologic and clinical data consistent with recent syphilitic infection were identified. Their conceptuses were carefully examined by silver and immunofluorescent stains for the presence of Treponema pallidum. Two of these five conceptuses (9 and 10 weeks' gestation) were found to contain T. pallidum by these methods. The literature supporting the Langhans layer/five months' placental barrier theory is reviewed and discussed in view of these two first-trimester cases.


Bilateral adrenalectomy in treatment of disseminated breast cancer. Forty-three patients underwent bilateral adrenalectomy for advanced breast cancer at the Hospital of the University of Pennsylvania from 1960 to 1974. Fourteen patients (32 per cent) experienced an objective remission. There was no difference in the initial free interval between the responders and nonresponders. Premenopausal patients who improved after surgical castration or androgen therapy and postmenopausal patients who responded to estrogen therapy and its subsequent withdrawal had a greater response to adrenalectomy. Twenty-three of the forty-three patients who underwent bilateral adrenalectomy had evidence of metastatic involvement in at least one of the excised adrenal glands. Results show that patients who responded to previous therapy had a longer survival after adrenalectomy.


[The effect of 6% hydroxyethyl starch, 45% dextran 60 and 5.5% oxy-poly-gelatine on blood volume and circulation in human volunteers (author's transl)]. Studies in 30 volunteers showed that the volume increasing effect of a 2.5% Oxypolygelatine-solution is rather short (90 to 240 min), whereas the volume effect of a 4.5% Dextran 60 solution remained stable over a period of 240 min hydroxethyl-starch solution 6% caused a distinct increase in blood volume after a period of 90 min and of 240 min in five volunteers, while the blood volume of the other volunteers remained rather constant. The parameters we measured provide no explanation for this effect.


[The influence of hydroxyethyl starch solutions on circulation and on kidney function in hypovolaemic patients (author's transl)]. In a group of 12 hypovolemic patients some parameters of circulation and kidney function were measured before and after an infusion of 1000 ml 6% hydroxyethyl starch solution (HES) was given. There were found increases in cardiac output, centralvenous pressure and endogenous creatinine clearance, and decreases of total peripheral resistance and shock index. Under the conditions of this investigation HES solution showed good properties as a plasma substitute.


[Hydroxyethyl starch as plasma substitute: experiments in isovolamic haemodilution (author's transl)]. Isovolaemic haemodilution to a hematocrit of 10% was achieved by stepwise exchange of blood against 6% hydroxyethyl starch (HES) in 11 splenectomized dogs. All animals survived the actuely performed extreme haemodilution; one animal died 5 days later due to massive bilateral pneumonia. Blood volume as determined by 51Cr-tagged red cells was unchanged at hematocrit 10%; 2 and 5 hours after reaching the minimum haematocrit, blood volume was reduced by 7 and 15% of control. At day 3 after dilution, blood volume was normal again. Thus under conditions of extreme isovolaemic haemodilution the volume effect of hydroxyethyl starch was found inferior to that of dextran 60. Haemodilution with HES was associated with a presistent augmentation of the serum concentration alpha-amylase.


Audiotape-slide teaching. An assessment of group and individual presentation. A series of fourteen audiotape-slide presentaiions on clinical physics and measurement were produced for self instruction by junior anaesthetists. A comparison of group and individual teaching carried out on fifteen trainees indicated no difference between the effectiveness of the two methods. In both cases almost 90% of the lecture points could be immediately recalled. Most students however preferred individual tuition. The assessment also allowed a comparison of individual lectures so that upgrading, modifying and rewriting of the appropriate lectures or parts of lectures could be carried out. The tapeslide technique and the format used was found to be very acceptable to the anaesthetists taking part. The flexibility of audiotape-slide lectures as a teaching medium is discussed.


[Circulatory changes during preoperative isovolaemic haemodilution with a mixed solution of hydroxyethyl starch and 5% human albumine. A clinical study (author's transl)]. The influence of preoperative isovolaemic haemodilution on the circulation was examined in a clinical study. Heart rate, mean arterial pressure, mean pulmonary arterial pressure, cardiac output as well as haemoglobin and haematocrit values were determined. Stroke volume, total peripheral resistance, and the modified tension-time-index were calculated. A mixture of human albumin 5% and hydroxy-ethyl-starch was used as a solution for dilution. During the dilution phase the cardiac output increased compensatorily to the decrease of haemoglobin and the haematocrit values. While the heart rate and the mean arterial pressure remained unchanged the total peripheral resistance was reduced. Considering the described conditions and contraindications, preoperative isovolaemic haemodilution is a suitable method to replace an intraoperative blood loss of up to 2000 ml autologously. Thus a posttransfusion hepatitis can be avoided. In addition, preoperative isovolaemic hemodilution improves the microcirculation and may have a prophylactic effect on the thrombosis in the postoperative phase.


[Comparative investigations of hydroxyethyl starch and dextran 60 in Isovolaemic haemodilution and haemorrhagic shock of rats (author's transl)]. Isovolaemic blood volume replacement down to a haematocrit value of 20% by commercial dextran 60 or hydroxyethyl starch has been survived by male rats of the Wistar strain without significant deviations from the initial blood volume. The haemoglobin and haematocrit values were found to be practically within the normal range 14 days after treatment. In a second series of male rats of the Wistar strain haemorrhagic shock was maintained over a period of 60 min. The 48 hour survival rate amounted to 100% after retransfusion or replacement by hydroxyethyl starch or dextran 60 of the bleeding volume. The kidneys of both series when examined by the light microscopy showed no pathological changes. On the basis of the findings presented hydroxyethyl starch may be considered to be as effective in blood volume replacement as dextran 60.


[The influence of hydroxyethyl starch on blood clotting (author's transl)]. It has been shown in clinical experiments that blood coagulation was delayed by Dextran 60 and Hydroxyethylstarch (HAS). During the postoperative period up to the 2nd postoperative day the measured clotting factors were decreased within the physiological range. Platelet adhesiveness was mainly reduced in the group of Dextran 60 and in the male Hydroxyethylstarch group. A similar effect of haemodilution as seen by haematocrit and blood viscosity results was produced by Dextran 60 and Hydroxyethylstarch. In the electrolyte group the values obtained did not show any significant influence on blood coagulation apart from a light and temporary trend to hypercoagulation during the day of operation.


[The influence of the plasmaexpander hydroxyethyl starch on the serological blood grouping tests as compared to dextran 60 and whole blood (author's transl)]. The influence of HES on serological blood grouping (ABO. Rh. crossmatch) was tested in comparison with dextran. It was shown out that a previous volume substitution up to 20% did not influence the reading of blood grouping determination. Higher dilutions of blood led to rouleaux formation which however could be easily distinguished from agglutination by addition of isotonic saline solution. Crossmatching brings difficulties, as weak antibodies might be missed even using the AHG test due to too high a degree of dilution of the patient's serum by plasma expanders. Increasing the sensitivity be enzyme technics (Papain, Eldon) is not advisable as irreversible non-specific reactions can be found already at low degrees of volume substitution.


[Plasma histamine levels in man following infusion of hydroxyethyl starch: a contribution to the question of allergic or anaphylactoid reactions following administration of a new plasma substitute (author's transl)]. In contrast to the effects of rapid infusion of gelatin and dextran preparations, no histamine release was observed in 10 human subjects (volunteers) following rapid infusion of hydroxyethyl starch. This was measured by fluorometric histamine determination in venous plasma. Furthermore no clinical symptoms of an allergic or anaphylactoid reaction could be detected in any of the volunteers.


[The effect of the plasma substitutes hydroxyethyl starch and dextrane-60 on the kidney function of dogs in acute haemorrhagic shock (author's transl)]. In 14 dogs during experimentally induced haemorrhagic shock the effects of 6% solutions of hydroxyethyl starch and Dextran-60 were compared. As main parameters of the renal function the arterial and venous pressures, renal blood flow, creatinine-clearance as measure of the glomerular filtration rate, urinary flow rate and urinary excretion of sodium and potassium were estimated. After complete substitution of the lost blood volume both plasma substitutes increased the renal blood flow by 50%. Glomerular filtration rate returned to control values, urinary volume and potassium output increased whereas sodium output decreased slightly. If only 50% of the lost volume was substituted, the renal blood flow and filtration rate remained at or below control values. Hydroxyethyl starch and Dextran-60 proved to be almost equally effective in restoring renal function.


[On the lacking teratogenic effect of the plasmaexpander hydroxyethyl starch in the rat and mouse (author's transl)]. Hydroxyethyl-starch (HES) has been tested for teratogenic activity in BD-strain rats and Swiss mice. HES in both species was shown not to be teratogenic. High doses of 50 g/kg/day given by intraperitoneal injection lead to abortion in all pregnant rats. This report in concerned with the important question of, whether development and normal life of the progeny of rats and mice is affected when treated with HES during pregnancy. Special attention has been given to potential teratogenic effects.


[Liberation of histamine by anaesthetics (author's transl)]. Injection of Epontol (7 mg/kg i.v.) to male healthy students caused a brief increase in plasma histamine concentration from 0.7 ng/ml to 3.0 ng/ml. Combined injection (7 mg/kg) and infusion of Epontol (21 mg/kg during 15 min) or combined injection of Epontol (7 mg/kg) and suxamethonium (0.5 mg/kg) caused a more prolonged appearance of histamine in plasma without higher maximum concentrations. During anaesthesia with ketamine (Ketanest), halothane or nitrous oxide the histamine concentrations in plasma remained unaltered.


Localization of rabbit gamma globulins in the mouse visceral yolk sac placenta. The yolk sac placenta has been implicated previously in transmission of passive immunity to the fetus. This work uses an immunohistochemical technique devised by Sternberger et al. ('69) to study this problem. Rabbit serum containing gamma globulins was injected into the uterine lumen of the White Swiss mouse during the last third of pregnancy. Two or four hours later yolk sacs were removed and fixed in 2% paraformaldehyde or freeze-dried and fixed with paraformaldehyde vapors. Finely chopped tissue was treated with (1) sheep antiserum to rabbit serum gamma globulin, (2) an antigen-antibody complex consisting of horseradish peroxidase and rabbit anti-horseradish peroxidase and (3) hydrogen peroxide and 3,3'-diaminobenzidine. Reaction product was heavily concentrated in visceral yolk sac endodermal cells, frequently deposited in endothelial cells of vitelline vessels, and rarely in the serosal basement membrane and mesothelial cells which border the exocoelomic cavity. This supports evidence of other workers that the yolk sac membrane rapidly absorbs substances with which it comes in contact, transport into vitelline vasculature is a route of transfer from mother to fetus, and possible transfer into the exocoelomic cavity and thence to the amniotic cavity may occur in mice.


Changes in serum protein values of sheep infected with Fasciola gigantica. Serum protein values were determined in 6 lambs given 1 dose of 200 metacercariae of Fasciola gigantica. Over the 22 weeks of the experiment, total serum protein values in these lambs were only moderately increased over those of control lambs (n = 6). The increase was mainly associated with the change in alpha2-globulin and gamma-globulin fractions. The highest value of gamma-globulin (39.03%) of total serum protein was observed at 18 weeks after infection. Mean albumin concentration in the exposed lambs decreased considerably, starting in week 8 and persisting until the end of the experiment. The lowest level (39.28%) was seen at week 16.


Inhibition of dihydrostreptomycin binding to Mycobacterium smegmatis by monovalent and divalent cation salts. To better understand salt antagonism of dihydrostreptomycin (DSM) action on Mycobacterium smegmatis, the effects of monovalent and divalent cation salts on drug uptake were studied in relation to the lethal activity of DSM. In Sauton liquid medium NaCl, MgCl(2), and SrCl(2) inhibited the initial instantaneous binding of [(3)H]DSM to the organism and suppressed secondary uptake. These data correlated well with the capacity of each salt to prevent the lethal activity of DSM. It was concluded that monovalent and divalent cation salt antagonism of DSM action on M. smegmatis involves nonspecific interference with drug uptake.


A new actinomycin complex produced by a Micromonospora species: fermentation, isolation, and characterization. A species of Micromonospora, Micromonospora floridensis NRRL 8020, has been found to produce an actinomycin complex consisting of at least 25 active components. After solvent extraction of the complex, separation of the individual components was carried out by preparative thin-layer chromatography. Hydrolysis and subsequent electrophoretic and chromatographic identification of the amino acid content of each of the isolated components have shown differences from known actinomycins, and the probability exists that these contain a number of amino or imino acids not previously found in other members of this group of antibiotics.


Interrupted aortic arch: factors influencing prognosis. From January, 1969, to June, 1974, 11 infants with interrupted aortic arch were operated upon. Eight of them died in the perioperative period. Their cases were reviewed in an attempt to find factors influencing the prognosis. Age, weight, preoperative hemodynamics, angiographic findings, and the type of arch anomaly did not influence the outcome. The operation, whether palliative or involving intracardiac repair, did not affect the prognosis. The only factor related to the outcome was the size of the conduit: in all infants who died, the vessel used to bridge the gap (carotid or subclavian artery) was of narrow diameter. In the 3 patients who survived it was of much larger bore. We conclude that in the repair of interrupted aortic arch, an adequate conduit is essential for success.


[Palliative surgery of transposition of great vessels associated with pulmonary stenosis]. Palliative treatment for transposition of the great vessels with pulmonary stenosis (combined or not with ventricular septal defect) was studied in relation with 24 patients operated upon at Laennec's Hospital in Professor Mathey's section between January 70 and January 74. Three therapeutic attitudes are possible according to whether or not an atrial septal defect is created (Blalock-Hanlon's operation) in combination with the systemic-pulmonary artery anastomosis, and according to whether the operations are performed in one or many steps. It seems that for the badly-tolerated forms of the new-born, combination of both operations seems to be the best attitude, the curative treatment being impossible at this age.


[Tachycardia caused by reciprocal rhythm between normal pathways and a rapid atrial-His pathway]. Report of one unhabitual case of reciprocal rhythm with anterograde conduction through James' fibres and retrograde conduction through the normal nodal pathways. The reality of an anterograde nodal short-circuit is indicated by many arguments, and in particular by the presence of a double ventricular response, after induced atrial premature beats reaching the ventricle once by the rapid pathway and the second time by the slow pathway.


Metabolic products of microorganisms. 155. Modes of action of rinamycin and derinamycin. Rinamycin interfered with DNA-polymerase I of Escherichia coli in cell-free systems more effectively than actinomycin C. Its inhibitory action could be relieved by increasing the concentration of polymerase. The rinamycin concentrations that caused effective inhibition of the RNA-polymerase reaction in vitro were approximately 10 times higher than those required to inhibit the DNA-polymerase reaction in vitro.


Structural and enzymatic characterization of viper C-type virus. The structural polypeptides of purified viper range in molecular weight from 11,000 to 97,000 daltons and consist of 3 major and about 13 minor polypeptides. The virus contains both protein kinase and reverse transcriptase activities. Several of the structural polypeptides are phosphorylated in vitro by the virus-associated protein kinase. However, most (possibly all) of the viral structural polypeptides are not phosphorylated in vivo. DeoxyATP is as efficient as ATP in donating phosphate for in vitro phosphorylation of viral proteins. In vitro protein phosphorylation always precedes transcription and the virus-associated protein kinase and reverse transcriptase activities can be partially separated by sedimentation in a sucrose gradient.


Chemically-induced temperature sensitive mutants of dengue virus type 2. I. Isolation and partial characterization. Temperature sensitive (ts) mutants of dengue virus type 2 (DEN-2, TH-36 isolate) were induced by replication in primary hamster kidney cells treated with 5-azacytidine. Seven ts mutants were obtained from 138 clones isolated by an immunofluorescent cloning technique. Of these 7 ts mutants, 5 were sufficiently stable to permit partial characterization. Complementation was detected at very low but statistically significant levels between some ts mutants at 40 degrees C. Viral double-stranded RNA production was evaluated in LLC-MK2 cells at 30 degrees and 40 degrees C by micro-quantitative complement fixation. The results of complementation tests and RNA production tests indicated that the 4 of 5 stable ts mutants constitute 3 separate complementation groups (2 RNA+ and 1 RNA-groups), while a fifth ts mutant was RNA- but non-complementable. The data presented here indicate that a genetic system can be developed without employing traditional plaque or cytopathology methods. Further, the 5 DEN-2 ts mutants are believed to represent the only set of complementation-positive flavivirus mutants so far isolated.


Absence of neuraminidase from influenza C virus. Influenza C viruses did not possess neuraminidase activity when examined using either fetuin or sialyllactose as substrate. Purified preparations of influenza C virus inhibited hemagglutination by NWS hemagglutinin. The hemagglutination inhibiting activity was abolished by treatment of influenza C virus with neuraminidase. These findings indicated the absence of neuraminidase activity on influenza C virus particles.


[Experimental analysis of the interactions between heparin and a duodenal heparinoid]. It is shown that positive synergism exists between the clarifying, hypocholesterolaemising, hypolipidaemising and fibrinolytic effects of heparin sodium and a duodenal heparinoid. The results of pharmacokinetic and chemicophysical investigations are also presented.


[The picture and significance of alcholic hyalin (the Mallory body)]. The structure and significance of Mallory bodies in alcholic chirrhoses of the liver were studied by means of histochemical and electron-microscopy methods.  It is established that alcoholic hyaline is a protein-polysaccharide-lipid complex and on the ultrastructural level has a dual structure:  fibrillar and electron-dense lipid-like.  Deposits of hyalyne is one of indications to the gravity of the liver structural disorders.


[A means of combining the histochemical and neurohistologic method for study of axo-muscular synapses]. An indoxyl method for identification of esterase with the use of the classical method of argentation after Campos of nerve elements is described. As a result, the nerve trunks, adducting nerve fibres and terminal ramifications of the axon being impregnated with silver nitrate become brown-black, whereas the sites of distribution of axo-muscular synapses acquire bleu colouration.


Glycoprotein catabolism in rat liver: Lysosomal digestion of iodinated asialo-fetuin. (125)I-labelled asialo-fetuin, administered intravenously, rapidly accumulates in rat liver and the radioactivity is subsequently cleared from the liver within 60min. Plasma radioactivity reaches a minimum between 10 and 15 min after injection and rises slightly during the period of liver clearance. Free iodide is the only radioactive compound found in plasma during this latter period. Fractionation of rat liver at 5 and 13min after injection of (125)I-labelled asialo-fetuin supports the hypothesis that asialo-glycoprotein is taken into liver by pinocytosis after binding to the plasma membrane and is then hydrolysed by lysosomal enzymes. At 5min, radioactivity was concentrated 23-fold in a membrane fraction similarly enriched in phosphodiesterase I, a plasma-membrane marker enzyme, whereas at 13min the radioactivity appeared to be localized within lysosomes. Separation of three liver fractions (heavy mitochondrial, light mitochondrial and microsomal) on sucrose gradients revealed the presence of two populations of radioactive particles. One population banded in a region coincident with a lysosomal marker enzyme. The other, more abundant, population of radioactive particles had a density of 1.13 and contained some phosphodiesterase, but very little lysosomal enzyme. These latter particles appear to be pinocytotic vesicles produced after uptake of the asialo-fetuin bound by the plasma membrane. Lysosomal extracts extensively hydrolyse asialo-fetuin during incubation in vitro at pH4.7 and iodotyrosine is completely released from the iodinated glycoprotein. Protein digestion within lysosomes was demonstrated by incubating intact lysosomes containing (125)I-labelled asialo-fetuin in iso-osmotic sucrose, pH7.2. The radioactive hydrolysis product, iodotyrosine, readily passed through the lysosomal membrane and was found in the external medium. These results are not sufficient to account for the presence of free iodide in plasma, but this was explained by the observation that iodotyrosines are deiodinated by microsomal enzymes in the presence of NADPH.


Two-dimensional immunolectrophoresis as a diagnostic tool for heavy chain disease. 8 sera from patients with three types (gamma, alpha, mu) of heavy chain disease were tested by two-dimensional immunoelectrophoresis (Td. IEP) in order to assess the potential usefulness of such a technique as a routine diagnositc tool for heavy chain disease. Rocket immunoselection of the same sera was also performed by comparison. Characteristic, though not pathogomonic patterns were obtained by Td. IEP of the sera from patients with alpha chain disease. The main differential ciriteria by which heavy chain disease proteins could be differentiated from myeloma immunoglobulins were as follows: a) marked heterogeneity of the precipitin lines, ascribeable to the formation of polymers of different sizes; b) decreased sharpness, sometimes blurred delimitation, of the precipitin lines; c) frequent occurrence of spurs of the myeloma proteins over the deleted immunoglobulins in Kroll's tandeum variant, or between deleted immunoglobulins and small amounts of normal immunoglobulins present in the same serum. In our experience, rocket immunoselection does not show appreciable advantages as compared with Td. IEP.


Serum and synovial fluid inhibitors of antibody-mediated lymphocytotoxicity in rheumatoid arthritis and systemic lupus erythematosus. Many sera from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) inhibit lymphocyte-dependent antibody cytotoxicity (LDAC). RA synovial fluids also inhibit LDAC. RA serum inhibition was present in high molecular weight and 5S serum fractions, whereas in SLE it was confined to 7S fractions. A correlation between rheumatoid factor activity and LDAC inhibition was noted, and there was some evidence for inhibition of SLE serum acting on effector cells. Inhibition in RA synovial fluid was found in both high molecular weight and very low molecular weight fractions (less than 4S.)


'Supernormal' phase in hemiblock conduction. A case is described where the basic sinus rhythms is associated with an advanced degree of left anterior hemiblock. The rhythm is complicated by atrial extrasystoles, associated with a lesser degree of left anterior hemiblock. This paradox of 'supernormality' is explained on a critical interplay of differential refractoriness within the divisions of the left bundle-branch.


Lupus erythematosus in a patient with amyloidosis, adrenal insufficiency, and subsequent immunoblastic sarcoma: demonstration of the LE phenomenon in the lung. A patient with systemic lupus erythematosus of long duration developed secondary amyloidosis and finally died after the additional complication of malignant lymphoproliferative disease. Multiple system involvement, typical serologic findings, and postmortem evidence substantiated the diagnosis of lupus erythematosus. Amyloid deposition was found in several organs, but was notably extensive in the adrenal cortex. This extensive deposition resulted in adrenal insufficiency, which was diagnosed clinically and treated until the patient's death from lymphoma. The particular nature of the malignant lymphoma is emphasized; a distinctive feature was the disappearance of positive lupus erythematosus cells from the buffy coat and the reduction in titers of relevant serologic tests toward the end of the illness. In spite of this reduction, many hematoxylin bodies and abundant complete lupus erythematosus cells were found in the lungs on postmortem examination.


[An uncommon pseudo tumoral skin disease; the so-called Papillomatosis cutis carcinoides. A review (author's transl)]. The review of the current literature on the subject is followed by the exposure of the clinical and histopathological data concerning a case of papillomatosis cutis carcinoides. The Authors conclude on the opportunity to maintain this nosographic pattern, to be enclosed among the cutaneous pseudo tumoral affections.


Anaesthesia for cardioversion: a comparison of diazepam, thiopentone and propanidid. Three groups of 50 patients were anaesthetized with diazepam 0.32 mg/kg or thiopentone 3.7 mg/kg or propanidid 4.6 mg/kg for elective carfioversion. Propanidid caused more hypotension than diazepam or thiopentone. Apnoea was most frequent following thipentone and excitatory side-effects were most prominent following propanidid; the electric countershock worsened the excitatory phenomena. The success rate of conversion was higher in the diazepam group than in the other groups, but the difference was not statistically significant. Diazepam failed to produce amnesia in about 33% of the patients. Thiopentone is suitable and pleasant for cardioversion. Diazepam is recommended in poor-risk patients and in emergency situations.


[A case of epidermodysplasia verruciformis with neoplastic degeneration and demonstration of viral particles in warts (author's transl)]. A case of epidermodysplasia verruciformis, already described by Borelli in 1946, was presented. The electron microscopy showed viral intranuclear particles in the verrucous lesions. A Bowen-like tumor was found on the forehead. The connections are described between virus and tumor.


A proposed role for alpha1 macroglobulin in the promotion of alpha1 acute-phase globulin synthesis by the perfused rat liver. The effects of intravenously administered rat alpha1 macroglobulin (alpha1M), alone and in combination with pancreatic trypsin, on the synthesis of alpha1 acute-phase globulin (alpha1AP globulin) have been measured in the isolated perfused rat liver 24 h after injection. Maximum promotion (approximately five-fold) of alph1AP globulin synthesis was observed after administration of alpha1M complexed with trypsin or alpha1M alone, which after purification had lost most of its trypsin-protein-esterase (T.P.E.) activity. Slightly lesser but still significant degrees of enhancement (approximately four-fold) of alpha1AP globulin synthesis resulted from the injection of alpha1M alone or complexed with trypsin, which after purification had retained sitnificant T.P.E. activity. All these responses were greater than those generated by injection of trypsin or plasma alone, or rabbit plasma complexed with trypsin. However, the synthetic response did not reach the maximum rate observed 24 h after an intramuscular injection or sterile turpentine. An hypothesis is proposed for the role of alpha1 macroglobulin (and its homologue in man, alpha2 macroglobulin) in the mediation of the acute-phase synthetic response by the liver. This predominantly intravascular glycoprotein serves as the principal circulatory porteinase binder. Proteinases released in response to tissue injury, necrosis or inflammation would be bound and inactivated by alpha1M, and in turn the alpha1M-proteinase complex would stimulate the liver to synthesize a number of acute-phase proteins. Certain of these, e.g. alpha2 acute-phase globulin also possess proteinase binding activity and, being of low molecular weight, would be more effective than alpha1M in the inactivation of released tissue enzymes at extravascualr sites. The data presented in this paper are compatible with this biphasic role for plasma proteinase inhibitors in the biological response to injury.


Detection of monocyte specific antigen on human acute leukaemia cells. Heteroantisera with specificity for human monocyte and macrophage antigens (HuMa) have been tested for activity against peripheral blood cells from patients with acute leukaemia. Using indirect immunofluorescence, blast cells from 25/27 patients with acute myelomonocytic leukaemia were reactive with anti-HuMa antisera, whereas blasts from 19/20 patients with acute myeloblastic leukaemia and 13/13 patients with acute lymphoblastic leukaemia were not reactive. The F(ab1)2 fragment of the antibody retained specific activity. Activity of whole serum against myelomonocytic blast cells was specifically removed by absorption with macrophages. These observations indicate that circulating blast cells from patients with acute myelomonocytic leukaemia may carry differentiation antigens characteristic of monocytes and macrophages.


Dental complications of cytotoxic therapy in Hodgkin's disease--a case report. A case of trigeminal zoster in a patient with disseminated Hodgkin's disease is described. Although one case of maxillary tooth loss in a comparable patient has previously been recorded, this is the first report of mandibular tooth loss. The aetiological significance of Beomycin and I-(2-chloroethyl)-3-cyclohexyl-I-nitrosourea (C.C.N.U.) is discussed and an hypothesis for post-zoster tooth exfoliation is suggested.


Ionophorous polymers. Interaction with polynucleotides and effects on RNA-directed DNA polymerase activity. Poly(vinylbenzo-18-crown-6), a water-soluble polymer endowed with ion-binding crown moieties as pendent groups, forms insoluble complexes with polyadenylate in the presence of K+; the corresponding monomeric benzo-18-crown-6, does not form a precipitate under the same conditions. In the presence of Na+ and Mn2+ which in aqueous solution complex weakly to crown compounds, no coprecipitation of the crown polymer and polyadenylate occurs; nevertheless, the crown polymer strongly binds to immobilized polyadenylate even under these conditions. The interactions of crown polymer with the poly-nucleotide result in a loss of templating ability of the latter. Using RNA-dependent DNA polymerase of murine leukemia virus it was found that (1) enzymatic action is efficiently inhibited even in the absence of ions which coprecipitate crown polymer and template, (2) inhibition is reversed by addition of excess polynucleotide and (3) monomeric crown does not inhibit the reaction.


A study of zinc distribution in human serum. The partition of zinc in human serum between two major zinc-binding proteins, albumin and alpha2-macroglobulin, was studied in 28 control subjects and in 156 hospitalized patients. Albumin-bound zinc was both the major and the more dynamic of the serum zinc components. Over a wide range of values the concentrations of albumin-bound zinc and total serum zinc were highly correlated (r=0.91) with each other, as were concentrations of albumin and albumin-bound zinc (r=0.69). alpha2-Macroglobulin-bound zinc was not strongly correlated either with total serum zinc or with the serum concentration of alpha2-macroglobulin. Twenty-four hour urinary excretion of zinc was not correlated with any of the serum zinc parameters. To a large extent it appears that total serum zinc concentration reflects serum albumin concentration.


Current questions on the tumour-associated antigens of chemically-induced tumours. I. In search of their characterization. The main methods for detecting the tumour associated antigens of chemically-induced tumours, and the significance of the results given by these methods are briefly reviewed. The possibility of finding several sorts of tumour antigens is discussed more specifically. The origin of the antigenically unique (non-crossing) antigens found in the chemically-induced tumours, as compared to the frequently cross-reacting antigens found in the virus-induced tumours, gives rise to speculation. The biological significance of these antigens is discussed.


[Ultramicromethod of determining antigens]. A method of alpha-fetoprotein (AFP) ultramicrodetection, permitting to reveal up to 10(--8) mg of AFP with its concentration of 1--2.10(--6) mg/ml was suggested. The antigen ic concentrated in a capillary tube during the electrophoresis in polyacrylamide gel. The compressed zone moves into the gel plate, containing antiserum. Free diffusion of the antigen is followed by the formation of precipitation rings, whose area is in proportion to the amount of the antigen. The precipitins are revealed by the treatment with I125-labeled antibodies to gamma-globulin of the immune serum, with subsequent radioautography.


[Study of the reproduction conditions of the avian myeloblastosis virus for separation of the "reverse transcriptase" enzyme]. Sensitivity of eight chick lines to the avian myeloblastosis virus as the main source for RNA-dependent DNA-polymerase recovery was studied in the course of the "revertase" project. The virus (0.1 ml) was inoculated intracardially or intraperitoneally to one-day chicks, and then the virus titer was determined according to the ATP-activity. C and D-lines of the Enya-cross were shown to be most sensitive (sensitivity 75%) among the lines studied.


[Distribution of alpha-fetoprotein and albumin in paraffin sections of cells of Zaidel's ascitic hepatoma]. The alpha-fetoprotein (AFP) and albumin localization were studied in the cells of rat Zaidel's ascitic hepatoma. It was shown in the paraffine sections of the hepatoma cells fixed by mixture of 96 degrees ethanol with 1% glacial acetic acid that 9.3% of hepatoma cells contained AFP and 0.6% of the cells--serum albumin. Small quantities of the tumour cells had both of these proteins simultaneously. There was no definite regularity in the distribution of the AFP and albumin-containing cells in the tumour islands.


[Immunoautoradiographic determination of beta-1 gamma globulin in the blood serum of patients with trophoblastic tumors]. The authors determined beta1-G-globulin (beta1GG) in the sera of patients with different malignant tumours and of normal donors by means of the immunodiffusion method (ID) and immunoautoradiography (IAR). In the ID-negative sera beta1GG was revealed by means of IAR in 7 out of 8 patients with chorionepithelioma of the uterus and in 1 out of 7 patients with teratomblastoma of the testis before the treatment. After the treatment the beta1GG was determined in 7 out of 21 patients with chorionepithelioma of the uterus. At the early stage of trophoblastic tumours of the uterus beta1GG could be found in 77.7% of cases by means of IAR and in 16.8% of cases by means of the ID method.


Phagocytosis in human platelets: localization of acid phosphatase-positive phagosomes following latex uptake. Incubation of human platelets in plasma containing a suspension of latex particles for 1-90 min resulted in progressive accumulation of particles in the open-channel system, followed by localization of latex in electron-opaque vacuoles. After 60 min, acid phosphatase was localized within latex-containing vacuoles. The periodate-alkaline-bismuth reaction intensely stained external membranes and membranes of the open-channel system. Membranes of latex-containing organelles were not stained. Latex phagocytosis was independent of both anticoagulant choice and aspirin effects. Our results indicate that the platelet can act as a true phagocyte, and we suggest that the phagocytic process is chronologically similar to that reported for polymorphonuclear leukocytes.


[Preliminary studies on the argyrophilic cells of the human hypophysis]. Appropriate technics such as Bodian's method prove the presence of very numerous argyrophilic cells in the human adenohypophysis in the enfant as well as in the adult. This population of argyrophilic cells is heterogenous, cytoimmunological tests demonstrate that a lot of them belong to the groups of gonadotropic cells. On the other hand, no argyrophilic cell stains positively with Falck's technic. The exposure of human lyophilised hypophysis to formaldehyd vapours reveals the existence of many fluorescent cells but comparisons prove certainly that these elements square only with the beta cells, in fact with the cells responsible for corticotropin secretion.


[Cytoimmunological detection of corticotropic and melanotropic cells in the human fetal adenohypophysis in early stages of development]. The corticotropic and melanotropic cells of eight human adenohypophyses from eight to twelve weeks-old foetuses were identified with immunofluorescent and immunoenzymatic procedures. Anti-ACTH (1-24), anti-ACTH (17-39), anti-beta-LPH and anti-beta-MSH immunsera were electively fixed by the same cell type. These cortico-melanotropic cells, localized on the edge of glandular cords in contact with vascular mesenchym, both in the anterior and posterior walls of Rathke's pouch, were PAS-positive, cyanophilic, and plombic hematoxylin positive.


[Value of histospectrophotometry for the study of glycoproteins, glycosaminoglycans, and anionic polyglycans after staining with pseudo-isocyanine]. Pseudo-isocyanine, a basic stain, shows a characteristic metachromasia when associated with biological polyanions. The maximal absorption peak is very narrow and its wavelength is specific for the substances tested, in vitro as well as in tissue sections.


[Chromosome aberrations induced by bleomycin in human lymphocytes in vitro]. The authors tried to determine a dose-effect relation between the concentration of Bleomycin and the number of chromosomal aberrations "in vitro" in human lymphocytes during 48 h cultures. Concentrations of 1 gamma/ml, 2 gamma/ml, 10 gamma/ml and 20 gamma/ml were used. The number of normal cells seems to decrease according an exponential function; at a concentration of 20 gamma/ml, 15 p. 100 of the cells were apparently normal and this rises the problem of chemotherapeutic agent resistance. The number of one hit and two hit damages increases according to the dose of Bleomycine but it was not possible to determine a mathematic relation of the phenomenon. Like viruses and others chemicals, Bleomycin was responsible for "pulverisation" of chromosomes in several cells.


e antigen in acute hepatitis B.

e antigen in acute hepatitis B. To examine the association between e antigen and hepatitis-B surface antigen (HBs Ag) we studied 90 inpatients with acute viral hepatitis type B. e Antigen was present in 24 of the patients; these patients had detectable levels of HBs Ag for significantly longer than the 66 with no e antigen in their serum. The HBs Ag subtypes D (adw) and Y (ayw) were similarly distributed among patients with e antigen and among those without, and no differences in the results of biochemical liver function tests were observed between the two groups during the acute phase of illness. Three of the five patients who developed clinical and histological signs of chronic liver disease were positive for e antigen, a finding which supports the hypothesis that e antigen has a prognostic value in hepatitis B.


Reappraisal of Gram-staining and cultural techniques for the diagnosis of gonorrhoea in women. A retrospective study of 209 consecutive cases of gonorrhoea showed that more than 98 per cent. of cases were detected by two sets of examinations at weekly intervals. This was compared with earlier results obtained at this clinic when only 86 per cent. of cases were detected by two examinations. It is believed that modifications in culture techniques were responsible for the improvement and that two tests are now sufficient to screen for gonococcal infection in the majority of patients when an efficient microbiological service is available. Because of the high incidence of infection in contacts of men with gonorrhoea, a third test is recommended for the small number of such patients who have negative results of their first two tests. This also serves to monitor the efficiency of the culture techniques. The majority of women with gonorrhoea attended because they were believed to be contacts of men with the disease but many attended of their own accord because they had symptoms. Mild symptoms were described by as many as 53-5 per cent. of all infected women. Nine cases of gonorrhoea were detected during the follow-up period. Three of the four cases which were thought to be due to treatment failure were detected at the first test, in contrast to the cases which were thought to be due to re-infection, the majority of which were diagnosed at subsequent tests. Constant surveillance of the accuracy of the diagnostic methods used in the detection of gonorrhoea in women is of great importance if errors are to be reduced to a minimum.


Axonal transport in the efferent pathways of the hippocampus: labeling of projection areas after (3H)valine injections. [3H]Valine was injected into the medial and lateral CAI of the dorsal hippocampus and the radioactivity accumulated in areas of some of its efferent projections was measured by scintillation counting. The labeling of the septum, thalamus, hypothalamus, corpus mammillare, preoptic area and basal telencephalon significantly exceeded the corresponding background activities. Fimbria transection before [3H]valine injection reduced the labeling of these areas to background levels. Differences were observed between medial and more lateral CAI injection sites in the distribution of 3H label among projection areas. The dynamics of axonal transport were studied in 4 of these projection areas: septum, thalamus, hypothalamus and corpus mammillare. A rapidly moving wave of radioactivity began to arrive in all areas 1--3 h after injection. The rate was roughly estimated to be around 100 mm/day in the fibers projecting to the corpus mammillare after injections into the medial CAI. When the brain  areas were fractionated into crude nuclear, mitochondrial-synaptosomal and microsomal fractions, projection areas were found to contain more label per milligram of protein in the mitochondrial-synaptosomal fraction than control areas.


Development of the Canadian Home Fitness Test. The Canadian Home Fitness Test is a self-administered procedure in which the participant steps at an age- and sex-specific rhythm controlled by recorded music, then palpates the pulse immediately following activity. Validation of the test has shown a correlation of 0.72 with the results of a standard submaximum bicycle ergometer test, while the directly measured maximum oxygen intake is correlated even more closely (r = 0.88) with the attained stepping rate, body weight and recovery heart rate. Given modest training, subjects could measure their immediate postexercise heart rate (correlation with electro-cardiographic data, r = 0.94), although 10-second counts underestimated the true rate by an average of 7 beats/min. The safety of the test will be established ultimately by experience in its use in a large population; nevertheless, both theoretical considerations and results of trials in over 14 000 adults suggest the procedure can be self-administered without serious consequences. It is also well accepted by the general public and arouses considerable interest in most homes. The test can thus be recommended as providing an approximate measure of an individual's physical fitness in order to stimulate an increase in personal physical activity. It also has potential as a simple screening procedure that would allow paramedical personnel to record fitness levels and standardized exercise electrocardiograms in large segments of the population.


BACON (bleomycin, adriamycin, CCNU, oncovin and nitrogen mustard) in squamous lung cancer. Experience in fifty patients. Fifty patients with inoperable squamous carcinoma of the lung. 38 with extensive, and 12 with limited disease, were treated with BACON. Tumor regression greater than 50% was observed in 17 patients (45%) with extensive, and four patients (33%) with limited disease. Stabilization of disease for greater than or equal to 8 weeks was seen in four extensive and eight limited patients, and had the same prognostic importance with regard to survival as response: in extensive disease, responding and stable patients had median survival (MST) of 26 weeks from start of therapy, while MST for non-responders was 9 weeks. MST in limited disease (all patients responding or stable) was 32 weeks. Analysis of survival in extensive disease by performance status showed improvement in each category over historical control results for supportive care alone. BACON was better tolerated and probably more effective when CCNU was given every 8 weeks, rather than every 4 weeks.


Intracytoplasmic hyaline globules in hepatocellular carconomas. Intracytoplasmic hyaline globules (IHG) were found in 16 out of 105 hepatocellular carcinomas (15.2%). In all cases, there was a male preponderance, most of the patients were Black, and the mean age was in the fifth decade. IHG were mostly noted in the better-differentiated tumors. Bile production was present in 12% of all tumors. Over 80% of tumors with globules showed necrosis as compared with 40% of the tumors without globules. Cirrhosis was present in almost half the cases, with liver cell dysplasia in 15%. These globules are possibly alpha-fetoprotein. Some of them may be giant lysosomes. Their role in carcinogenesis and prognosis is uncertain.


Mesenchymal tumors of the uterus. VI. Epithelioid smooth muscle tumors including leiomyoblastoma and clear-cell leiomyoma: a clinical and pathologic analysis of 26 cases. Twenty-six cases of atypical smooth muscle tumors of the uterus, including leiomyoblastoma, epithelioid leiomyoma, clear-cell leiomyoma, and plexiform tumorlet, are presented. The characteristic microscopic feature serving as the basis for inclusion in this study is the rounded to polygonal shape of the majority of cells instead of the elongated blunt-ended shape of smooth muscle cells seen in the typical leiomyoma. Mixtures of epithelioid, clear-cell, and plexiform patterns occurred with sufficient frequency to indicate that such patterns are variants of a single entity. A transition to typical smooth muscle cells was found in most instances, confirming the smooth muscle origin of these tumors. Features related to a favorable prognosis include the presence of clear cells, an expansile tumor margin, extensive hyalinization, and absence of extensive necrosis as seen microscopically. Until additional evidence has been accumulated it is proposed that neoplasms having five or more mitotic figures per ten high-power fields (HPF) be tentatively termed epithelioid leiomyosarcoma or leiomyosarcoma with epithelioid features and those with less than five mitotic figures per ten HPF, epithelioid leiomyoma.


Solitary cecal plasmacytoma: electron microscopic, immunologic, and cytochemical studies. A case of solitary cecal plasmacytoma is described with strong evidence of IgGk paraprotein production demonstrated by immunofluorescence and electromicroscopy. This is the ninth case of colonic plasmacytoma reported in the English literature and the first to show positive immunofluorescence.


Ultrastructural studies of human prostatic neoplasia. Forty-two specimens of human prostatic neoplasia (32 carcinomas, eight benign hyperplasia, two bladder tumors infiltrating prostatic tissue, and 15 tissue cultures derived from prostatic neoplasia) were examined by electron microscopy. Intracisternal viruslike particles, 150-200 nm in diameter and budding, were found in epithelial cells of four carcinomas. In some of these particles, an electron-dense central core or two concentric layers were discernible. In addition, particles resembling type C virus particles, 90-130 nm in diameter, were observed in intracytoplasmic vacuoles in five cases of carcinomas and in one case of benign prostate hyperplasia. Thus, viruslike particles were found in 9 of 32 cases of prostate carcinoma and in one of eight cases of benign prostate hyperplasia. Virus particles have, so far, not been found in any of the tissue culture specimens. Further studies are required to determine the nature of these particles and their relationship to the origin of human prostatic neoplasia. Additional observations in both benign hyperplasia and carcinoma include intranuclear mitochondria, multilayered nuclear inclusions, bundles of intranuclear fibrils, intracytoplasmic tubules, extracellular tubulo-filamentous structures, and cilia.ltilayered nuclear inclusions, bundles of ilo-filamentous structures, and cilia.


A malignant tumor of the vagina resembling synovial sarcoma: a light and electron microscopic study. A malignant tumor arising in the upper lateral vaginal mucosa in a 24-year-old white woman, hitherto undescribed in the literature, was studied by light and electron microscopy. The main part of the tumor was epithelioid, forming a tubular or acinar pattern. At the periphery, the tumor cells were more spindly and formed sheets resembling fibrosarcoma. The tumor cells contained occasional material positive for mucicarmine, alcian blue, and PAS stains, and the nests of the cells forming acini were surrounded by reticulin fibers. The tumor ultrastructure consisted of a single type of cell with large cytoplasmic vacuoles and occasional perinuclear intracytoplasmic filaments. Slender long microvilli projecting into the lumina were also characteristic. Basal laminae were occasionally present around the acini. The findings suggested that the tumor was of mesenchymal origin, closely related to synovial sarcoma.


Primary intracranial yolk sac tumor: immunofluorescent demonstration of alpha-fetoprotein synthesis. An autopsy case of 20-year-old male with primary intracranial yolk sac tumor (endodermal sinus tumor) is reported. Whereas the biopsy specimen obtained from the pineal region showed diffuse proliferation of atypical tumor cells, the metastatic subdural tumor removed from lumbar spinal region had the characteristic histologic appearance of yolk sac tumor. The histologic diagnosis was intracranial yolk sac tumor originating in the pineal gland. The elevated amount of alpha-fetoprotein in the cerebrospinal fluid and in the serum further supported the diagnosis. At autopsy, only metastatic tumor was present in the posterior fossa. The immunofluorescence study demonstrated the presence of intra- and extracellular alpha-fetoprotein globules in the tumor tissue. The intra- and extracellular distribution of alpha-fetoprotein, in general, appeared to coincide with that of the PAS-positive hyaline globules in the tumor.


Enhanced pulmonary toxicity with bleomycin and radiotherapy in oat cell lung cancer. In a recently completed study, combination chemotherapy consisting of bleomycin, adriamycin, cyclophosphamide, and vincristine was given to 29 patients with oat cell lung cancer. There were no cases of pulmonary fibrosis in these 29 patients. Although several of these patients had prior radiotherapy, none had concomitant radiotherapy and chemotherapy. This same four-drug chemotherapy regimen was combined with concomitant radiotherapy in 13 patients with oat cell lung cancer. There were three cases of fatal pulmonary fibrosis and two other cases of clinically significant pulmonary fibrosis. All five cases of pulmonary fibrosis occurred several weeks after completion of a six-week course of bleomycin (total dosage 90 units). It is concluded that bleomycin cannot be safely administered while patients are receiving radiotherapy to the lung.


Removal of inhibitors against RNA-directed DNA polymerase activity in human milk. Milk from a number of species (e.g., man, mouse, rat, dog, and cow) contains inhibitors of the RNA-directed DNA polymerase. When attempts are made to isolate virions from the milk, part of the inhibitors follow the virions in the purification. The amount of inhibitors varies in different milk samples. These inhibitors can probably account for the large discrepancies reported in studies of the presence of oncornaviruses in human milk. Phosphatases bound to subcellular particles or fragments seem to be the most important inhibitors in the milk interfering with the RNA-directed DNA polymerase assay. It is shown that the inhibitory enzymes can be completely removed by sedimentation of the milk through a Metrizamide gradient.


Production of antisera with specificity for malignant melanoma and human fetal skin. Complement-dependent cytotoxic antibodies to common cell surface antigens of cultured melanoma cells were produced in guinea pigs. At appropriate dilution, melanoma antisera were cytotoxic only to melanoma target cells. Following absorption with pooled lymphoid cells, additional absorption with melanoma cells but not absorption with fibroblasts or carcinoma cells was found to remove all cytotoxic activity from melanoma antisera. Absorption with human fetal skin cells but not with autologous fetal visceral cells was found to remove cytotoxicity from melanoma antisera. Tissue type-specific antigens may be shared by human malignant melanomas and fetal skin of black racial origin (at 16 to 18 weeks of gestation). The methods may be useful in the production of xenogeneic antisera with "operational monospecificity" for common melanoma-specific antigens. Sera from 47 patients with malignant melanoma failed to evidence specific cytotoxicity for melanoma target cells.


Phase I study of 5-azacytidine (NSC-102816) using 24-hour continuous infusion for 5 days. The biologic and antitumor activity of 5-azacytidine has been well demonstrated in the past. The drug at present is thought to be primarily cell cycle phase specific. This study was designed to eliminate undesirable side effects (mainly nausea and vomiting) occurring with a bolus dose and to confirm the recent findings of the relative stability of 5-azacytidine's solution with preserved biologic and antitumor activity. In the study we determined that a dose of 150 mg/m2/day given as a 120-hour continuous iv infusion and repeated at 28-day intervals produced safe, manageable, and reproducible toxicity. The drug was freshly prepared at 4-hour intervals. Eleven courses were administered to seven patients at this dose level and no patient experienced nausea or vomiting. Leukopenia was the major toxic effect. Antitumor activity was shown in one patient with colon cancer and another with American Burkitt's lymphoma.


Effect of anti-alpha1-fetoprotein on alpha1-fetoprotein-producing rat tumors in vivo and in vitro. Active or passive immunization of rats to alpha1-fetoprotein (AFP) does not consistently inhibit the growth of AFP-producing transplantable hepatomas in vivo, and anti-AFP does not kill these hepatomas in vitro. However, 3 of 14 rats in 1 experiment responded to passive immunization by reversal of tumor growth as evidenced by normalization of elevated AFP serum concentrations, and 1 of 9 rats actively immunized with rat AFP in complete Freund's adjuvant had suppressed growth of transplantable hepatoma 7777.


Isolation and characterization of an antigen of the bovine C-type virus. By means of gel filtration and isoelectric focusing, an antigen of the bovine C-type leukemia virus was isolated in a highly purified form from extracts of infected cells. The antigen has a molecular weight of approximately 25,000 daltons and an isoelectric point of 6.4 to 6.6. In immunodiffusion experiments, the antigen forms a line of identity with an antigen extracted from highly purified bovine C-type leukemia virus by treatment with ether or Triton X-100. As determined by immunodiffusion analyses, the bovine C-type leukemia virus antigen does not have antigenic determinants in common with the murine or feline leukemia viruses, the foamy-like bovine syncytia virus, or the Mason Pfizer monkey virus.


Bleomycin (NSC-125066) and CCNU (NSC-79037) in the combination chemotherapy of mopp-resistant hodgkin's disease. Twenty-two patients with MOPP-resistant stage IVB Hodgkin's disease were treated with a combination of bleomycin and CCNU. The response rate in 18 patients surviving at least 1 month was 72% with 11 partial and two complete responses. The mean duration of response and survival in partial responders were 12.2 and 17.5 months respectively. The two complete responses resulted in survivals of 20 and 36 + months. Bleomycin toxicity contributed to two deaths, one pulmonary and and one hypotensive. Severe CCNU toxicity occurred after three of 82 administrations but there were no CCNU-related deaths. The majority of patients in the study tolerated the regimen without serious toxicity. Although highly effective in the temporary control of advanced resistant Hodgkin's disease, the program will hopefully be improved by the addition of longer-acting agents.


Ultrastructural study of pulmonary bleomycin toxicity. Ultrastructural manifestations of bleomycin A2 toxicity in the human lung were studied in three patients. In addition to the appearance of nucleolar fibrillar centers, an increase in membranous, beaded, and granular nuclear bodies was found in nuclei of type 1, type 2 alveolar epithelial cells, and interstitial fibroblasts in all treated patients. Few such nuclear bodies were found in specimens of untreated patients.


Effects of Poly(1-vinyluracil) and Poly(9-vinyladenine) on viral RNA-directed DNA polymerase. The effects of poly(1-vinyluracil) [poly(vU)] and poly(9-vinyladenine) [poly(vA)] on the RNA-dependent DNA polymerase activity of murine leukemia virus (Moloney strain) were studied. Vinyl polymers themselves cannot act as templates for the polymerase. However, if a vinyl polymer is added to a polymerase reaction mixture in which a complementary polynucleotide serves as the template, the reaction is inhibited: thus with polyribocytidylic acid as template and oligodeoxyguanylic acid as primer, neither poly(vU) nor poly(vA) had a significant effect; when polyribouridylic acid was used as template and oligodeoxyadenylic acid as primer, poly(vA) inhibited polymerase activity while poly(vU) had little effect; when polyriboadenylic acid was a template and oligodeoxy thymidylic acid was a primer, poly(vU) was an inhibitor. Complex effects were noted with the latter system and poly(vA); either stimulation or inhibition of the reaction was observed, depending on the concentration of poly(vA). The stimulation brings about a decrease in the amount of lower-molecular-weight materials in the product and is caused by the interaction of poly(vA) with the template-primer. Thus vinyl polymers differ from polynucleotides in their mechanism of inhibition of viral polymerase, since the latter inhibit the enzyme by binding to it.


In vitro synthesis of immunoglobulins and other proteins by dysplastic and neoplastic human mammary tissues. The synthesis of several proteins in human mammary carcinomas and in dysplastic breast tissues was studied by tissue culture and by immunofluorescence. The synthesis of immunoglobulins showed marked quantitative and qualitative variations from one specimen to another, and a preferential synthesis of immunoglobulin G and C'3 in the carcinomas with lymphocytic infiltration. Fixation of immunoglobulins G and M on the surface of neoplastic cells was noted in some carcinomas. Secretory component was detectable in some cases by immunofluorescence, but no synthesis could be found in vitro, presumably because of unfavorable culture conditions. The synthesis of lactoferrin, casein, and some serum alpha- and beta-globulins was significantly greater in noncancerous tissues than in carcinomas. Synthesis of lactoferrin was also more frequent in the well differentiated carcinomas than in the poorly differentiated carcinomas. The tissue culture technique used in this study, although in need of better adaptation to the requirements in vitro of human mammary tissues, proved to be a useful tool for investigating the synthesis of several protein components by the epithelial cells of cancerous and dysplastic tissues of the human breast. Whether a preferential synthesis of 1 class of immunoglobulins or of other proteins might influence the evolution of a mammary lesion could not be determined in this material but it should be studied further.