In vitro DNA synthesis on smooth membranes observed by fluorescence. Smooth membranes have been isolated from a human diploid line of lymphocytes. These membranes exhibit an endogenous DNA-synthesizing capability which is partially destroyed by prior treatment with RNase. In order to ascertain the role of the membranes in the DNA synthesis we have examined the conformation of the membrane proteins by observing fluorescence changes of the intrinsic probe, tryptophan. We have observed that on addition of the deoxynucleoside-5'-triphosphates, which permits DNA synthesis, there are fluorescence changes due to the tryptophan residue; when DNA synthesis is prevented by omitting some of the precursor triphosphates, fluorescence changes are absent. These effects have been observed with plasma and nuclear membrane fractions; the former may contain a small fraction of the latter. Similar membrane preparations from non-lymphoid cells do not process the endogenous DNA-synthesizing system, as shown by the lack of incorporation of radioactive precursors of fluorescence changes.


[The histochemical evidence of the cholinesterase in the integument by means of the copper ferro cyanide methode (author's transl)]. With the aid of the Ferrocyanidmethod from KARNOVSKI und ROOTS ChE-positiv structures in the skin of various laboratory animals and of man were located. Specific cholinesterase is found in verves, around apocrine sweat glands and around eccrine sweat glands of some species. In the stratum basale of the epidermis from the rat you can demonstrate a high concentration of acetylcholinesterase. Unspecific cholinesterase is detectable in nerves, in the blood vessels, in the lumen of apocrine sweat glands and sebaceous glands.


[Methods of the histochemical detection of biogenic amines (author's transl)]. Histochemical and ultrahistochemical methods for the demonstration of biogenic amines are investigated with regard to their efficiencies and limitations. For the purposes of the light microscopy fluorescent histochemical methods at present are sufficient. Hereby beta-arylethyl-amines and indolalkylamines are demonstrable with formaldehyde or glyoxylic acid whilst histamine is traceable with o-phthaldialdehyde. In this connection those chemical and physical conditions of this methods are shown, under which the demarcation and quantitative determination of the several amines is possible. Ultrahistochemically biogenic amines can be demonstrated by means of the chromaffine and the argentaffine reaction, the reaction with permanganate and the REINECKE-salt precipitation technique. Apart from the latter one, all these methods are based on an initially reaction between glutaraldehyde and amines. Thus these techniques might be founded on one and the same principle. Besides, the demonstration of adreanline as a secondary amine might be hindered also by the fact that the product of its reaction with glutaraldehyde is soluble in water. On the other hand the reaction product of primary amines with glutaraldehyde is insoluble in water. When using REINECKE-salt the correctly localizated precipitation of amines is the first step of the reaction. After that the treatment with glutaraldehyde is only serving for the fixation of the tissues. But the ultrahistochemical methods mentioned above altogether are showing a deficiency as far as they do not allow to make the several amines selectively visible. Therefore a quantitative ultrahistochemistry of biogenic amines is still impossible at present.


Distribution of ruthenium red staining material in the cerebral cortex of rat. The ultrastructural distribution of ruthenium red staining material is studied in the cerebral cortex of rat. It is established that the material is located equally along the cell surface of the neurons, glial and endothelial cells, and within a number of cell organelles: mitochondria, smooth endoplasmic reticulum, synaptic vesicles and throughout both membranes of the nuclear envelope. Using digestion with hyaluronidase and trypsin, and lipid extraction an attempt is made to determine the participation of some chemical compounds such as acid mucopolysaccharides, glycoproteins, glycolipids and acid polypeptides in the composition of the ruthenium red-positive material. Moreover, the problem of the optimal conditions for the carrying out of ruthenium red staining in the CNS  is discussed.


Analytical electron microscopic identification of cytochemical products in thin sections. A cytochemical technique utilizing a chromium complex to localize biogenic amines in tissue has been studied using energy dispersive X-ray analysis. The X-ray analysis procedure shows that chromium is indeed involved in the complex at the biogenic amine locus. This demonstrates intraneuronal sites for neurotransmitter agents and shows that the combined methodologies of histochemistry, cytochemistry, electron microscopy and energy dispersive X-ray analysis can provide new methods and insights into cellular metabolic activity.


Light and electron microscopic studies of the pulmonary alveolar surfactant. 22 methods of light and electron microscopy have been tested for the identification of the pulmonary alveolar surfactant. Among the non electron microscopic methods Romhányi's anisotropic staining with toluidine blue was the most serviceable. In addition to simple performance it allows the identification of the smallest alteration -- not to be identified by other methods -- of the alveolar surfactant. Among the electron microscopic technics Ruthenium Red staining and Dermer's tricomplex method yielded the best results. Given that different chemical components of the alveolar surfactant will be identified by these 2 methods they supplement each other favourably. In the study of human cadaver material Baker's phospholipid reaction and Romhányi's anisotropic toluidine blue reaction is being used.


Studies on the integument of cestodes. II. The nature of protein component in the integument of gravid proglottides of Taenia hydatigena. The main cuticle of the gravid proglottides shows differences in their chemical make up, in that there is a transformation of SH groups into -S-S bonding resulting in the refractivity of the cuticle. Another feature is the coexistence of dityrosine linkages with -S-S bondings. The mode of dityrosine formation from tyrosine residues is found to be possible by the presence of a peroxidase enzyme system in the cuticle. The evolutionary and physiological significance of the occurrence of -S-S bonding and dityrosine links have been discussed.


Studies on metachromasia. III. Toluidine blue-substrate interaction and metachromasia. With salts as substrates the metachromatic responses of the thiazine dye, Toluidine blue are studied. It is found that generally salts produce a gamma-metachromatic response. The substrate-dye interaction is studied in detail and the results are discussed in the light of various interpretations of previous workers. It is suggested that toluidine blue may have two sites that are responsible for the exhibition of green and red metachromatic responses. The influence of water on metachromasia has been studied and is reported to bring about an oscillation of spectral colours. Spectrophotometric studies were also carried out.


Selective staining of animal chromosomes with synthetic dyes following iodine-dye-procedure. The paper embodies results of the use of 51 synthetic dyes, belonging to different chemical groups for staining of animal chromosomes following iodine-dye procedure. It has been found that some of these dyes can replace gentian violet, crystal violet and safranin when used after this procedure. It has further been found that the fluorescent dyes, acriflavine and acridine yellow can also be used to stain animal chromosomes and that some of the dyes belonging to one chemical group can be successfully used whereas others of the same group are of no use. Dyes of the monoazo group are absolutely useless. Amongst the dyes successfully used, the preparations remain stable when stained with most of them except methyl green, malachite green, brillant green, iodine green and cresyl violet and amongst acid dyes, acid fuchsin. Cytochemical studies presented herein indicate that the components of the animal chromosomes stainable with crystal violet are the nucleic acids and that these substances should be highly polymerised and should not be even in a semi-degraded state. Removal of any one of these nucleic acids makes the chromosomes unstainable with iodine-crystal violet.


Influence of carbonates and other salts in tissues on the Schiff's reagent. Application of the Schiff's reagent on fresh and undecalcified cuticle of crustaceans such as Emerita asiatica and Ocypoda platytarsis showed positive results with their calcified layer which led to suggest that salts of calcium account for the staining. In vitro studies with carbonate and other salts furnished confirmatory evidence. It is suggested that in tests involving the Schiff's reagent proper removal of resident salts must be carried out.


Neurological investigation of 5-year-old children with low birthweight. 139 children with a low birthweight (LBW), i.e. not more than 2 500 g, were examined at 5 years of age in respect of their neurological status, with special reference to motor coordination according to Touwen & Prechtl. 5 (3.6%) children had cerebral palsy; 13 (9.4%), minimal brain dysfunction; 38 (27.3%), delayed motor maturation; and 83 (59.7%), normal motor development and normal neurological status. Impairment of hearing and of vision, epilepsy and mental retardation were more common in children with cerebral palsy and MBD. Children with MBD and delayed motor maturation had a lower IQ, as judged from the draw-a-mantest according to Goodenough than children with normal neurological status. Cerebral palsy was found in children with a very low birthweight and short gestational age. Other findings were equally distributed among groups classified by weight and duuration of gestation.


Serum alpha-foetoprotein as a marker for endodermal sinus tumour (yolk sac tumour) or a vitelline component of "teratocarcinoma". The correlation between serum alpha-foetoprotein (AFP) and the clinical pathological finding of 24 germ cell tumours arising from the testes (14 cases), the ovaries (3 cases), the mediastinum (3 cases), the retroperitoneal region (2 cases), and the sacrococcygeal region (2 cases) are presented. Irrespective of marked differences in age and sex of the patients, primary site of the tumours and clinical outcome, the 24 cases constituted a homogeneous group in fundamental histological patterns and in AFP synthesis. In all cases of endodermal sinus tumour or teratocarcinomas with a distinct vitelline component an increased serum AFP concentrations was found in the pre-operative serum samples. AFP was also demonstrated in the tumour tissue by quantitative determination of AFP in tumour homogenate (5 cases) and, by immunofluorescence technique, positive staining of the cells lining the endodermal sinuses and of the hyaline globules was found (3 cases). In 12 germ cell tumours without vitelline components in the tumour tissue sections, a normal AFP concentration below 20 mug/1 was found in preoperative serum samples.


Glycol methacrylate embedding of renal biopsy specimens for light microscopy. Thirty-five consecutive renal biopsy specimens were evaluated by light histology using paraffin and glycol methacrylate embedding. The clarity of the renal structures was found to be much better, and the renal lesions better defined, using glycol methyacrylate embedding.


Short stature in an adolescent due to spondyloepiphysial dysplasia tarda. A 15-year-old boy had normal growth until age 7 years and decreased growth velocity thereafter. His upper segment/lower segment (U/L) ratio was 0.8. Anterior pituitary function was normal. Roentgenograms revealed characteristic findings of spondyloepiphysial dysplasia tarda (SDT). The sitting height measurement or U/L segment ratio is important in identifying this condition. This condition should be considered in the differential diagnosis of short stature in males.


Slide- tape sequence: a teaching aid in instrumentation. A study at Wayne State University involving 34 medical technology students was conducted in an effort to provide supportive evidence for the use of selected audiovisual material in the teaching of instrumentation. The study did not conclusively demonstrate the effectiveness of a slide-tape sequence in this university instrumentation course. However, the methodology and evaluative procedures may prove helpful to universities and hospital-based programs in determining the usefulness of their audiovisual material.


Hepatitis B antigen - an incomplete history. Hepatitis B virus still cannot be grown in an in vitro system; therefore, research into hepatitis B antigen (HB Ag) is limited to laboratory methods such as serology, electron microscopy, and biochemistry. These have established the presence of two distinct antigenic  components of HB Ag, that associated with the small forms and the outer covering of the Dane particle (HBs Ag), and that of the Dane particle core (HBc Ag). Current findings make it almost certain that the Dane particle represents the hepatitis B virus (HBV), the smaller forms of the antigen representing excess viral lipoprotein. The group of individuals positive for the antigen are considered and the immunopathology of the disease is discussed. Present understanding of the antigen has made it possible to consider the use of HBs Ag as a means of vaccination. However, further information on the immune mechanisms associated with HB Ag are required before this can be accepted as a general means of protection. Finally, looking at currently available techniques, it would appear that passive hemagglutination and radioimmunoassay are both highly specific and sensitive methods of screening for HB Ag.


Biophysical and biochemical characterization of hepatitis B antigen. Hepatitis B surface antigens specified by the genome of the hepatitis B virus are shared by various particulate forms which circulate in the sera of chronic HBs Ag carriers. As purified from sera, HBs Ag consists of at least seven polypeptides, two of which appear to be glycoproteins. Most or all of these polypeptides contain both group-specific (a) and subtype-specific (d or y) determinants aspart of their structure. One particulate form, the Dane particle, is present as a minor component in most sera and may actually represent the virus of type B hepatitis.


Biophysical and biochemical properties of purified preparations of hepatitis B surface antigen (HBs Ag). Two antigenically distinct subtypes, adw and ayw, of hepatitis B surface antigen (HBs Ag), have been purified from the plasma of anicteric hepatitis patients. Biophysical studies of these purified preparations revealed considerable heterogeneity in their overall surface charge, morphology and molecular weights. Chemical studies revealed that the composition of the particles is complex in that four to six different polypeptides and three glycoproteins were identified. In addition, cholesterol, three polar lipids, and two glycolipids were detected in purified HBs Ag preparations. Antisera, prepared in guinea pigs to individual polypeptides derived from HBs Ag subtypes adw and ayw, reacted with both the group- and type-specific antigenic determinants associated with the intact particles. The potential of these purified preparations of HBs Ag and of the individual subunits derived from them as possible vaccines is discussed. Specific antipolypeptide sera will be utilized to determine whether HBs Ag components are synthesized as specific viral products or are composed of components of modified host-cell molecules.


Structural and immunoreactive characteristics of hepatitis B core antigen. The ultrastructural study of liver tissues from 38 patients with type B viral hepatitis consistently showed the presence of hepatitis B core antigen of 21-25 nm size in the liver cell nuclei and to a lesser extent in the cytoplasm. This finding and the demonstration of the tubular form of hepatitis B surface antigen in the proliferative degranulated endoplasmic reticulum constituted the etiologic criterion for the diagnosis of the disease. The double-shelled Dane-like particles were frequently found in association with the tubular form of the surface antigen. The core particles were found in the protoplasmic processes of hepatocytes and this correlated with the immunofluorescent microscopic findings that the antigen may be shed into circulation  with the protoplasm. The core antigen was found to resist digestion by various enzymes such as protease, DNase, RNase, phospholipase C, lipase, lysozyme, diastase, neuraminidase and hyaluronidase, all of which did not destroy the immunoreactivity as demonstrated by immunoelectron and immunofluorescent microscopy. Similarly, sodium dodecyl sulfate, Tween 80 and mercaptoethanol also had no effect. The formalin-fixed paraffin-embedded liver tissue sections could be treated with protease to facilitate the immunofluorescent staining for the core antigen in tissue.


Hepatitis B antigen subtypes-history, significance and immunogenicity. Initial work showed that all hepatitis B surface antigens (HBs Ag) were identical. Subsequent, additional studies revealed that hepatitis B surface antigens have a group reactive determinant, a, plus additional specificities which are not universally present on all antigens. Four well-defindd subtypes of HBs Ag exist (HBs Ag/adw, HBs Ag/ayw, HBs Ag/adr, HBs Ag/ayr) but additional subtypes will be forthcoming as newly described determinants are confirmed. The subtype specificities are determined by the hepatitis B virus and not the host. Subtypes of HBs Ag are already of great use in the epidemiology of hepatitis B virus infections; yet they may have additional significance. Current work on HBs Ag subtypes is limited by the ability to find or produce antibodies to other than the a or group reactive determinant. The other determinants appear to be less immunogenic than a.


Serotypes of hepatitis B antigen (HBs Ag): the problem of "new" determinants, as exemplified by "t". The principal antigenic determinants of hepatitis-B surface antigen (HBs Ag) are specified by distinct genotypes of hepatitis-B virus (HBV). This hypothesis still stands undisproven. These specificities include the common antigen(s), called a, and two pairs of subdeterminants, d/y and w/r. The members of each pair are in general mutually exclusive, resulting in four "primary" phentoypes of HBs Ag: adw, adr, ayw, and ayr. The newer "a(w) subcategories" probably also reflect differences in viral genotype; if so, the number of "subtypes" rises to eight. Further subdivision into independent strains of HBV may eventually become feasible on the basis of one or more of the following "new" HBs Ag reactivities, once these have been shown to be virus-coded: g, n, q, x, and t. The requirements for accepting new reactivities as HBV-specific, and for comparing them among themselves, are discussed, using t as an example. A peculiar feature of t is its variable physical behaviour: "overt" t reactivity is correlated with the adw phenotype; "cryptic" [t], with ayw; while adr and ayr have so far been t-negative. Pending the indispensable tests of experimental transmission, this uneven distribution would seem to suggest that expression of t is regulated by the HBV genome.


Hepatitis B surface antigen and human serum proteins. The purification of HBs Ag is briefly discussed with emphasis on the immunochemical characterization of the resulting preparations. Results of experimental work in various laboratories aimed at establishing presence or absence of human serum proteins as integral parts of (highly purified) HBs Ag particles do not yet allow definite conclusions.


Antibody to hepatitis B core antigen.

Antibody to hepatitis B core antigen. Two distinct antigen-antibody systems are associated with the hepatitis B virus (HBV): hepatitis B surface antigen (HBs Ag) and antibody (anti-HBs) and the more recently described hepatitis B core antigen (HBc Ag) and antibody (anti-HBc). Testing of serial serum samples from patients with type B hepatitis demonstrates the regular occurrence of anti-HBc during the course of this disease. In general, highest titers of anti-HBc are seen with prolonged circulation of HBs Ag as in the chronic carrier state. Titers of anti-HBc begin to fall with recovery from HBV infection and anti-HBc appears to be shorter lived than anti-HBs. As such, anti-HBc testing is important in documenting the occurrence of infection with HBV and is of great value in epidemiologic studies and in evaluating the safety and efficacy of hepatitis B immune globulin and HBV vaccines.


Hepatitis B surface antigen and liver cell carcinoma. The frequency distribution of HBs Ag in different parts of the world reveals a relatively high frequency among healthy members of population groups inhabiting areas of high incidence of liver cell carcinoma. Similar high frequencies of HBs Ag are also found in those areas where macronodular cirrhosis is relatively common and is usually complicated by liver cell carcinoma. In geographic areas with low incidence of liver cell carcinoma and macronodular cirrhosis, a relatively low frequency of HBs Ag is usually encountered in the population. The frequency of HBs Ag is relatively higher in patients with liver cell carcinoma with or without cirrhosis than in comparable controls. The subtypes of the antigen do not correlate with the incidence of liver cell carcinoma and there is also no correlation between alpha fetoprotein and HBs Ag in the presence of liver cell carcinoma. HBs Ag is very rarely detected in patients with micronodular cirrhosis or in liver cell carcinoma which may be its complication. It would appear that HBs Ag is necrogenic in the liver and is capable of producing hepatic necroses or hepatitis which may progress to macronodular cirrhosis. The areas of hepatic necroses may either progress to liver cell carcinoma or the resultant macronodular cirrhosis may be complicated by carcinoma. The oncogenic potential of HBs Ag requires further studies.


Relationship of hepatitis A antigen to viral hepatitis. Progress in research on hepatitis type A has begun to accelerate because of the recent discovery of an antigen associated specifically with hepatitis type A infection and the development of tests for antibody to the antigen. Hepatitis A antigen is associated with 27 nm virus-like particles found in the liver and stool of animals experimentally infected with hepatitis type A and in the stool of humans experimentally or naturally infected with the virus. The density of the particulate antigen when isolated from the liver is 1.34, but antigen particles with densities ranging from 1.32 to 1.40 have been detected in stool. However, antigens from the liver and from the stool appear to be antigenically related. Using immune electron microscopy as a serologic tool for detecting antibody to hepatitis A antigen, we detected antibody in convalescent sera from 100 per cent of patients experimentally or naturally infected with hepatitis type A. In contrast, patients with hepatitis type B or non-B hepatitis not epidemiologically compatible with a diagnosis of hepatitis type A did not have a serologic response to hepatitis A antigen. Antibody was found in approximately 50 per cent of normal individuals tested; the frequency was directly related to age. By the use of immune electron microscopy for the detection of hepatitis A antigen and antibody, the temporal relationship of antigen, antibody and liver damage was determined in experimentally infected humans and chimpanzees. On the basis of serologic comparisons, hepatitis type A does not appear to be related to experimental hepatitis caused by the GB agent of Deinhardt, nor is the hepatitis A antigen serologically related to the fecal antigen of Cross.


The influence of genotype on the development of glomerular lesions in mink with Aleutian disease virus. In an attempt to document progression rate differences in the development of glomerular lesions in mink infected with Aleutian disease virus (ADV), the glomeruli of Aleutian and non-Aleutian mink experimentally infected with ADV were evaluated by light, fluorescent, and electron microscopy. The animals were also examined for the presence of interstitial infiltrate, neutrophils, and arterial lesions. One hundred percent of the Aleutian mink had glomerular cell proliferation and interstitial infiltrate, while 95% of the Aleutian and 41% of the non-Aleutian mink had neutrophilic infiltrates and arteritis, respectively. Of the non-Aleutian mink, 91, 83, 42, and 12.5% had glomerular cell proliferations, glomerular neutrophils, interstitial infiltrate, and arterial lesions in, that order. All the Aleutian mink had glomerular depositions of gamma-globulin (IgG) and complement (C3), whereas 75% of non-Aleutian mink had deposits of IgG and C3. One hundred percent of both genotypes had glomerular deposits of immunoglobulin M (IgM). Ultrastructural glomerular changes consisting primarily of depositions of granular electron-dense material on basement membranes were observed in Aleutian mink 6 weeks after infection and 12 weeks after infection in non-Aleutian mink. These findings document progression rate differences in the development of glomerular lesions in Aleutian disease-affected Aleutian and non-Aleutian mink. Further, they emphasize the need for exploration of pathogenetic mechanisms involved in progression rate differences in lesion development.


Development and utilization of complement-fixation and immune adherence tests for human hepatitis A virus and antibody. The reliable propagation of CR326 strain of human hepatitis A virus in Saguinus mystax marmosets has permitted the development of specific serum neutralization, complement-fixation (CF), and immune adherence (IA) assays for hepatitis A antigen and antibody. The CF and IA assay were made possible by the use of livers of CR326-infected marmosets as a source of hepatitis A antigen. All assays were shown to be specific for hepatitis A. Patients with hepatitis B did not show development of hepatitis A antibody. Hepatitis A antibody appeared following onset of illness, and, in the longest time period studied, has persisted for seven years. Epidemiologic studies have been performed on several Costa Rican families with outbreaks of hepatitis, with the IA and CF assays. Also, several populations in the U.S.A. were studied. These indicated a high incidence of hepatitis A at an early age in Costa Rica and a relatively low incidence of hepatitis A antibody among adults in the U.S.A. It was shown that human immune globulin can be standardized for hepatitis A antibody content by the IA assay. Finally, the IA assay indicated probable hepatitis A antibody in uninoculated chimpanzees, grivet monkeys, and rhesus monkeys.


Reduced beta-adrenergic responsiveness in hypothyroid rats. The beta-adrenergic agonist isoproterenol (100-200 mug/kg body wt sc) induces vasodilation and an increase in skin temperature of the tail of the euthyroid but not the hypothyroid rat. Administration of thyroxine (25 mug/kg body wt per day) to rats made hypothyroid by means of the antithyroid drug aminotriazole (0.5 g/kg of foof) returned responsiveness to control level. Reduced responsiveness to isoproterenol occurred between 1 and 5 wk of treatment with aminotriazole. Increase in tail skin temperature induced in euthyroid rats by isoproterenol was blocked by administration of propranolol (7.5 mg/kg ip). Other beta-adrenergic-induced responses, including increased water intake and increased plasma glucose concentration, also were reduced in hypothyroid rats and returned to control level by administration of thyroxine. Thus,  hypothyroidism appears to be accompanied by a reduced beta-adrenergic responsiveness as assessed by changes in tail skin temperature, water intake, and plasma glucose concentration after injection of isoproterenol. Since administration of thyroxine returned the responses of hypothyroid rats to control levels, it appears that thyroxine is important in maintaining beta-adrenergic responsiveness under these conditions.


Nonspecific reactions with the intradermal test for hydatidosis in persons with other helminth infections. A partially purified Echinococcus antigen solution, prepared by boiling hydatid cyst fluid, was used in the intradermal test for hydatid disease in a Peruvian population. An unexpectedly high rate of positive reactions and poor agreement with serological tests suggested the presence of some agent(s) which produced cross-reactions with Echinococcus granulosus antigens in the intradermal test. Testing of hospital patients infected with a variety of helminths demonstrated nonspecific reactions in persons with Hymenolepis nana, Taenia spp., and Fasciola hepatica infections, mixed parasitisms, and several non-helminth pathological conditions. The findings contraindicated the use of the intradermal test for epidemiological surveys of hydatid disease. It is pointed out that intradermal test positivity rates cannot be used as synonymous with infection prevalence and regional differences do not necessarily reflect differences in the prevalence of E. granulosus infection. The greater specificity of some serological tests favor their use for epidemiological purposes.


The ultrastructure of a characteristic spermhead-defect in the boar: the SME-defect. Semen samples from an eight-month-old landrace boar showing poor sperm motility were investigated at the boars' arrival to an A.I. centre. Sperm morphology was found abnormal in +/- 30% of the sperm heads, which contained a rounded, often circular hypochromatic body (eosin-nigrosin stain) about 2 mum in diameter. The body was located in the front half of the sperm head, i.e. within the region of the acrosomal cap. Later a similar defect (+/- 50%) was found in an imported 2 1/2-year-old Yorkshire boar with decreased fertility. Electron microscopy of ejaculates and testis tissue showed that the hypochromatic body was a cyst containing a body of variable size but of moderate electron density. Usually the cyst was located within the nucleus and sometimes with direct communication to the acrosonal system. During spermiogenesis the abnormal spermids may show a deep invagination into the nucleus of the acrosomal granule. Inbreeding experiments are planned in order to determine if a possible hereditary factor is involved in the defect.


[Bioclinical study of the electro-immunodiffusion technic for the assay of serum alpha fetoprotein]. The author discusses the result that may be expected in clinical medicine from an electro-immunodiffusion method for the detection of alpha-foetoprotein. The samples studied were obtained from pregnant women, patients with liver cell carcinoma or severe digestive diseases, whether malignant or not, and a few amniotic fluids and sera obtained from the umbilical cord. This simple, rapid method is characterized by a sensitivity threshold of about 300 ng/ml and permits one to detect about 75% of cases of liver cell carcinoma.


Experimentally induced canine toxocariasis: laboratory examinations and pathologic changes, with emphasis on the gastrointestinal tract. Eght dogs were orally superinfected for 1 month with 50,000 embryonated Toxocara canis ova. Results of laboratory examinations during inoculation and for 2 weeks postinoculation revealed moderate leukocytosis, marked absolute eosinophilia, hypoalbuminemia, increased concentrations of serum glutamic pyruvate transaminase, and in 2 dogs, precipitating humoral antibodies. Other changes were moderate ascites, hepatomegaly, lymphadenopathy, and focal lesions (0.5 to 3.0 mm) in liver, lung, kidney, intestine, abdominal lymph node, heart, diaphragm, and spleen. Microscopically, focal eosinophilic gastroenteritis was produced. Eosinophils and globule leukocytes were increased throughout the intestinal mucosa. Eosinophil-infiltrated and granulomatous lesions were in the same organs listed as having focal lesions, as well as in the pancreas. The importance of serum beta-globulin content as a potential diagnostic tool was emphasized, and the experimentally induced infection was compared with naturally occurring eosinophilic gastroenteritis in the dog.


Regulation of the secondary antibody response in vitro. III.--inhibitor-containing cells of antigen stimulated rabbit lymph node organ cultures. The existence of inhibitor cells influencing the immune response has been inferred in many recent studies employing mice or chickens. The mechanism of this presumed suppression is unknown. The present report describes the isolation of AIM (antibody inhibitory material) from migrant lymphoid cells which normally escape from fragements of rabbit lymph mode cultures. The RNAse activity of AIM was demonstrated and the implications of this property discussed.


Variations in the capacity of the steroid binding beta globulin (SBbetaG) in plasma from normal young twins. The capacity of human plasma to bind specifically dihydrotestosterone (DHTBC) has been determined in normal monozygotic and dizygotic twins less than 20 years old. The total variation in DHTBC was analysed by stepwise multiple regression, combined with variance analysis, applied to the pair sums in DHTBC, body height and body weight, as well as to age. A significant part of the variation in DHTBC was explained. Due to the strong interwining between body weight, body height and age in growing children it was impossible to make out which one of the latter variable contributed most to the negative correlation which was observed. Previous studies in adults did, however, show that only body weight and not body height or age correlated negatively with DHTBC. By doing the same calculations for the within-pair differences in DHTBC, body height and body weight it was hoped to delineate the within-family part of the environmental variation in DHTBC. Body weight and body height did, however, not offer any significant explanation as to this part of the variation in DHTBC. The upper limit of heritability (h2) for DHTBC was estimated by comparing intraclass-correlation coefficients in monozygotic and dizygotic twins. According to the method used to calculate the latter intraclass-correlation coefficients h2 estimates for DHTBC of 0.774 and 0.960 were arrived at. However, due to the rather small number of dizygotic twins available the confidence limits of these estimates were rather large.


[Proceedings: Pituitary thyroid axis in subacute thyroiditis (author's transl)]. We studied 10 patients with subacute thyroiditis. All had an increase in free thyroxine index, PBI, T4 and PBI/T4 ratio, an absence of thyroidal radioiodine uptake and no increase in plasma TSH after TRH injection. Exogenous TSH increased the uptake in 6/9 patients. The three patients who did not respond to TSH had higher PBI/T4 ratio than others. After treatment for one month there was either a normalization of laboratory tests either a subnormal thyroid function associated with an absence of response to TRH. All tests became normal two months later.


Occurrence of slowly sedimenting components with mu chain antigenicity in normal adult and cord serum. The occurrence of trace amounts of slowly sedimenting components with mu chain antigenicity was investigated in 8 normal adult sera and 4 sera from cord blood of new-born infants. Separation of these components from 19S IgM was obtained by density gradient ultracentrifugation. The fractions were studied by radioimmunoassay. The results suggest that slowly sedimenting components with mu chain antigenicity occur in normal adult serum in amounts located in the mug/ml range. Several components sedimenting with various speeds were identified, although their sedimentation coefficients were not measured. This fact suggests that not only the already described 7S IgM monomer exists in normal blood but that other modes of association between mu and L chains or mu chains fragments also occur. Sera from cord blood showed patterns similar to that of adults.


Studies on the antigenic structure of tetanus toxin. The isolation and purification of split-products from tetanus toxin after freezing is reported. Antigenically defective and non-defective fragments exhibiting reduced molecular weights with respect to that of intact toxin were investigated as to their biological and immunological properties. The results obtained are discussed in relation to other data from the literature.


Specificity of the antiviral agent calcium elenolate. Calcium elenolate, an antiviral agent which inhibits reverse transcriptases, inhibits the growth of chicken embryo fibroblast cells, as well as Echerichia coli and Bacillus subtilis strains. The drug in vitro inhibits E. coli deoxyribonucleic acid (DNA) polymerase II and DNA polymerase III holoenzyme, as well as several unrelated enzymes. The usual DNA polymerase assay components, with the exception of spermidine, have no effect on the observed inhibition. Inhibition of DNA polymerase II by the drug appears to be due to a direct and irreversible effect on the enzyme. However, DNA synthesis in E. coli is no more susceptible to the drug than is the increase in cell mass. These results suggest that calcium elenolate is an inhibitor of rather low specificity.


In vitro culture of the proximal tubule of the bovine nephron : the fate of the histiospecific antigens and neosynthesis of an alpha-foetoprotein. The isolation of pure tubules of the outer cortex of the foetal bovine kidney, using a previously described methods, has shown that the tubule suspension obtained is almost entirely constituted of proximal tubule fragments. The proximal cells obtained from this suspension were grown in vitro. The previously called "nephrospecific" antigens NS1-2 were shown to be strictly specific for the cells of the proximal tubule, which is an "histion" of the kidney, that is to say an ultimate unit of differentiation of this organ. The fate of these antigens, henceforth termed "histiospecific antigens" (of the proximal tubule), was followed in primary monolayer cultures of the proximal tubules, using immunodiffusion tests and immunofluorescence. A rapid decrease in this antigen content of the cells was observed during the in vitro culture. An immunoautoradiographic study demonstrated that the synthesis of these antigens was switched off in the confluent cultures. A similar autoradiographic study demonstrated that these same proximal cells at confluence synthesized a bovine alpha1-foetoprotein, which had been detected in earlier studies of kidney cortex cultures. This double antigenic shift is correlated with the in vitro evolution of some morphological markers of the proximal cells, as studied with the transmission and the scanning electron microscope. The factors responsible for these results are discussed.


Lich myxedematosus. A dermal infiltrative disorder responsive to cyclophosphamide therapy. Lichen myxedematosus is an uncommon, chronic, cutaneous disease of mucin deposition that has resisted a variety of therapies. The discovery of a unique, basic, homogeneous globulin in the sera of many of the patients with this disorder raised questions concerning the relationships between lichen myxedematosus, multiple myeloma, and amyloidosis. Our patient, who lacked the abnormal serum globulin, was successfully treated with cyclophosphamide.


[Neoantigens on cells transformed by SV40. IV. - A quantitative study of antigenic sites in a cell line (TSV5C12) (author's transl)]. The antigenic sites at the membrane of SV40-transformed hamster fibroblasts (TSV5C12) were studied using isotope techniques. A specific fixation of antibodies directed against SV40 coded antigen had previously been shown using a cytotoxicity test in presence of fresh guinea pig complement. Using the "paired-label" technique, described by Boone et al., approximatively 7.2. 10(7) fixing site for the specific antibodies against SV40 coded antigen(s), were found. The fixation of antibodies onto the cells varied with the time of culture of cells. It was not possible to determine whether the number of antigenic sites, or their accessibility to the antibodies, or their susceptibility to complement, was dependent on the cell cycle.


Chemotherapy for advanced Kaposi sarcoma. Kaposi sarcoma is a rare disorder, usually controlled with conservative localized treatment. However, prognosis is serious for patients with aggressive cutaneous disease, and aminous for those with visceral involvement. Two cases of advanced Kaposi sarcoma are reviewed to illustrate a chemotherapeutic approach to patients with this disease. The first case represents a verified response of visceral Kaposi sarcoma to chemotherapy. The second provides an example of the control of aggressive dermatologic disease.


Metiamide: an antagonist of histamine-stimulated gastric acid secretion. Metiamide, 25 mg, antagonized the action of histamine on acid and pepsin secretion from both denervated pouches and innervated stomachs in dogs. In the same preparations its action on pepsin following food, pentagastrin or 2 deoxy-d-glucose was nonsignificant. Following pilocarpine or secretin, metiamide augmented pouch pepsin. The action of every acid stimulant was depressed by metiamide including the direct vagal action of deoxy-d-glucose on the innervated stomach. H2 receptors seem, therefore, to be involved in some form in acid stimulated by the vagi, histamine, pentagastrin and pilocarpine. Pepsin stimulation does not seem to be via H2 receptors with the esception of stimulation by histamine itself.


[Effect of chlormandinone acetate upon seizures in epileptic children with latent signs of hyperandrogenism]. The effect of chlormadinone acetate (24 mg/day) upon the plasma levels of pituitary gonadotropins and gonadal hormones on the number of generalized convulsions and spike EEG density was investigated in a group of epileptic children with intractable seizures and with clinical signs suggestive of hyperandrogenism. In each case, the effect of chlormadinone was evaluated in relation to hormonal levels and seizures observed during a control period and under the effect of placebo as follows: Control (PC)-Chlormadinone acetate (PCL1)-Placebo (PP)-Chlormadinone acetate (PCL2). In a male child (4MS), the number of convulsive attacks observed in the control period (26/month) was reduced during PCL1 (2/month) increased during PP (12/month) and was reduced again during PCL2 (0/month). Spike EEG density showed a parallel course to the clinical attacks. In this case, control levels of testosterone were markedly elevated (40 ng/ml) and were decreased during PCL1 to 4.0 increased again during PP to 34.0 and decreased again during PCL2 to 1.2 ng/ml. Plasma levels of pituitary gonadotropins were unchanged throughout the entire period of study. In other cases, neither the number of epileptic attacks nor spike EEG density were apparently affected by this regime and plasma levels of pituitary gonadotropins and gonadal hormones were also unmodified. These results suggest that a latent state of hyperandrogenism may be detected in some epileptic patients with intractable seizures and that chlormadinone may reduce convulsive attacks in these patients, probably by decreasing testosterone plasma levels.


Physiological and DNA characterization of Candida maltosa, a hydrocarbon-utilizing yeast. Selected yeast classified as Candida sake van Uden et Buckley were examined for their physiological, morphological and immunological properties and their DNA relatedness. Candida maltosa Komagata, Nakase et Katsuya is herein recognized as a species separate from C. sake, Candida maltosa was distinguished from C. sake and from C. tropicalis by insignificant DNA reassociation. In addition, C. maltosa was distinguished from C. sake by its higher maximal growth temperature and lower guanine plus cytosine content of its DNA and from C. tropicalis by its failure to utilize soluble starch for growth and its resistance to cycloheximide. The species C. cloacae and C. subtropicalis are placed in synonymy with C. maltosa.


Mutants of Myxococcus xanthus insensitive to glycerol-induced myxospore formation. Mutants of Myxococcus xanthus FBt unable to form myxospores in response to 0.5 M glycerol arise spontaneously with a frequency of 1--3 X 10(-5). These mutants are designated glc. Ultraviolet mutagenesis increases the frequency to a maximum of 7% of the survivors. The reversion frequency following ultraviolet irradiation of spontaneous glc mutants is less than 10(-3). Of four glc mutants examined, none form myxospores in response to the alternative inducers, ethylene glycol and dimethyl sulphoxide. One glc mutant is induced by 1.5 M glycerol; strain FBt responds to this glycerol concentration with low efficiency myxospore formation. Strain FBt and glc mutants all produce myxospores with low efficiency in response to phenyl ethanol. Of 117 glc mutants tested, 109 form fruiting bodies containing mature myxospores; thus, mutations to the glc phenotype do not normally block myxospore formation within the fruiting cycle of the organism.


Cytochemical localization of catalase activity in methanol-grown Hansenula polymorpha. The localization of peroxidase activity in methanol-grown cells of the yeast Hansenula polymorphia has been studied by a method based on cytochemical staining with diaminobenzidine (DAB). The oxidation product of DAB occurred in microbodies, which characteristically develop growth on or methanol, and in the intracristate space of the mitochondria. The staining of microbodies was H2O2 dependent, appeared to be optimal at pH 10.5, diminished below pH 10 and was inhibited by 20 mM 3-amino 1,2,4 triazole (AT). In contrast to these observations, the reaction in the mitochondria was not H2O2 dependent and not notably affected by differences in pH in the range of 8.5 to 10.5. Microbodies and mitochondria were also stained when H2O2 was replaced by methanol. Appropriate control experiments indicated that in this case methanol oxidase generated the H2O2 for the peroxidative conversion of DAB by catalase. These results suggest  that catalase is located in the microbodies of methanol-grown yeasts. A model for a possible physiological function of the microbodies during growth on methanol is put forward.


Sexual experience and sexual responsiveness: sex differences. Male (30) and female (30) college undergraduate subjects were shown five photographic slides depicting different heterosexual behaviors and one slide depicting solitary masturbation by a person of the same sex as the subject. Subjects rated the extent to which they found each of the slides sexually arousing and pleasant or unpleasant and indicated how many times they had personally engaged in each of the depicted activities. Following exposure to the slides, sexual arousal and emotional reactions were assessed. Contrary to the propositions of Kinsey et al. (1953), female heterosexual experience was equal to or superior to masturbation experience as an indicant of female sexual reactivity to the erotic materials. Among males, masturbation experience was superior to heterosexual experience as an indicant of sexual reactivity. The role of affective reactions to sexual experiences as determinants of sexual responsiveness is discussed.


Radionuclide photoscanning. Usefulness in preoperative evaluation of melanoma patients. The results of radionuclide scans (liver, bone, and brain scans and whole-body scans using bleomycin tagged with radioactive indium [111In]) performed on 100 melanoma patients during their initial evaluation were reviewed to determined whether or not they effected a change in clinical staging or therapeutic decision. Patients were classified as stage I (primary disease) or stage II (regional disease) on the basis of regional lymph node dissections. Only one patient (stage II) of 73 stage I and II patients had an abnormal finding on the initial radionuclide scan. Fifteen of 26 patients thought to be stage III (disseminated disease) on clinical grounds had abnormal findings on at least one scan. A therapeutic change as a result of scanning occurred in the stage II patient after abnormal bone and whole-body scans. As an initial routine screening test for stage I and II melanoma patients, radionuclide scanning was unproductive and rarely influenced therapeutic decisions.


Blood viscosity, plasma proteins, and Raynaud syndrome. The rheology of the blood was studied in 20 patients with Raynaud syndrome. Sixteen patients had scleroderma, two had nonspecific angiitis, one had systemic lupus erythematosus, and one had Raynaud disease. Viscosity measurements were performed on whole blood, plasma, and suspensions of 45% red blood cells (RBCs). In autologous plasma, over a wide range of shear rates. The relative viscosity, an index of RBC aggregation, was obtained by dividing the RBC viscosity in autologous plasma (at a hematocrit value of 45%) by the plasma viscosity. Concentrations of the plasma globulins and fibrinogen were also measured. The mean plasma viscosity was significantly (P less than .01) elevated over established normal controls. The mean RBC viscosity and the relative viscosity were significantly (P less than .01) elevated over normal controls, as were fibrinogen and the globulins. These studies demonstrate increased blood viscosity and red blood cell aggregation, which may constitute an important hindrance to flow.


Palliation of tricuspid atresia. Potts-Smith, Glenn, and Blalock-Taussig shunts. Aortopulmonary (Potts-Smith), subclavian-pulmonary (Blalock-Taussig), and cavopulmonary (Glenn) shunts are the commonly performed operations for palliation of tricuspid atresia. A total of 104 patients with tricuspid atresia have undergone these procedures, either alone or in combination over a 28-year-period at the Hospital for Sick Children, Toronto. Operative risk is high in the first six months of life (44%), reasonable after six months of age (7.4%), and low for reoperation (3.5%). Long-term palliation of the 75 survivors (mean follow-up, 8,5 years) is compared for the three operative groups and charted on an actuarial table. Potts shunt offers superior long-term palliation. Therefore, as an overall plan of management, a Potts shunt with restriction of its anastomotic growth is the initial procedure of choice. When the patient outgrows the Potts shunt, a Glenn anastomosis is constructed. Ideally, the combination of these two shunts will produce a balanced circulation offering excellent long-term palliation.


[Complex application of stains in the histochemical study of proteins]. The paper proposes a complex of methods for the histological study of protein which allosw revealing heterogeneity of its compostitions, determining the protein discharge and obtaining the data on the presence and distribution of a number of aminoacid residues. The schedule of the study includes reactions with dichlortriazine basic and acid stains (of both low and high affinity). The proposed schedule is convenient for detection and characterization of protein both in the structure, containing mainly proteins, and in the structures whose biopolymeres are represented mainly by carbohydrates.


[Peculiarities of the staining of neural tissue with procion yellow]. The application of protion yellow allowed to reveal nerve cells of different size, and their dendrites and axons, bundles of nerve fibres for a considerable length. Staining with protional yellow resembles to impregnation of the nervous tissue with silver salts. Combination of protion yellow with dyes of other groups and silver nitrate impregnation improves the stability of staining.


Luxol Fast Blue MBSN-Levafix Red Violet E-2BL. A combined stain for myelin sheaths and glia fibers. During investigations of reactive dyes, Levafix Red Violet E-2BL was found suitable for staining of glia fibers. Experiments were carried out on 37% formaldehyde-fixed human autopsy material. Paraffin sections were treated with Luxol Fast Blue MBSN as usual, differentiated until glia fibers were decolorized, and counter-stained in a 0.25% solution of Levafix Red Violet E-2BL in 0.25% acetic acid. Myelin sheaths were colored blue. Gila fibers, smooth muscle cells, and nuclei were stained red violet. Axons and connective tissue remained unstained; occasionally, coarse bundles of collagen showed patchy coloration. Polarization microscopic studies proved that Levafix Red Violet E-2BL is bound to well-oriented fibrous proteins in glia fibers. The similar staining and polarization microscopic properties of glia fibers and smooth muscle support previous findings that glia fibers contain a myosin-like protein.


The mechanism of unresponsiveness in lymphocytes specifically selected by antigen in normal rats. The immunological potentialities of populations of thoracic duct lymphocytes collected from rats recently challenged with sheep erythrocytes were compared with those of lymphocytes from rats immunologically tolerant of this antigen. Both "selected" and tolerant populations fail to mount immune responses to sheep erythrocytes in irradiated syngeneic hosts but can do so if transferred to semi-allogeneic recipients. If co-cultivated with normal lymphocytes in irradiated hosts, both types of population can modulate the responsiveness of the former to sheep erythrocytes. Supplementation of normal lymphocytes with "selected" populations collected earlier than 28 hours after challenge of the donors tends to result in augmented responses while later collections are more likely to be associated with suppression. Consequently, it is suggested that "selected" populations are unresponsive because of the presence of specifically activated cells rather than as a result of their depletion. The influence of "selected" populations on the responsiveness of normal lymphocytes is attributed to this content of activated cells.


Effects of thymus-independent (B) cells and the H-2 gene complex on antiviral function of immune thymus-derived (T) cells. Antiviral activity in vivo exerted by ectromelia virus-immune spleen cells transferred to ectromelia-infected recipients and cytotoxicity against virus-infected target cells in vitro were both properties of non-immunoglobulin (Ig)-bearing cells (which included T cells). Ig-bearing cells, including thymus-independent (B) cells and antibody-secreting cells, were much less active in vivo when injected alone and tended to block rather than amplify the effect triggered by T cells. Ig-bearing cells were also slightly active in vitro, possibly because some T cells have detectable Ig. Antiviral effects in cell transfer experiments were seen only when immune cell donors and infected recipients shared the same H-2 gene complex. These results are consistent with the hypothesis that the T cell response to ectromelia infection is directed against specific virus-induced change(s) in antigen(s), specified by gene(s) in the H-2 complex, which appear in virus-infected cells.


Repair (or recovery) effects in quiescent Chinese hamster cells: an attempt at classification. Increased survival of density-inhibited Chinese hamster cells after a variety of treatments is analyzed in terms of half-time of "repair," magnitude of repair, and dependence upon nutrient medium during the repair interval. At least three different systems are identified: X-ray-like, UV-like, and an entirely different system after heat shock. Repair after methyl methanesulfonate and after visible light (in bromodeoxyuridine-substituted cells) may be interpreted as a superposition of the X-ray and UV-like repair systems.


[Disodiumcromoglycate and histamine liberation by cotton dust extract in the rat (author's transl)]. 1. Disodiumcromoglycate (DSCG) had no influence on the microscopical appearance of rat peritoneal mast cells either by i.p. injection (2 times 10(-5) g/ml) or by i.v. infection (10 mg/kg) nor by local application (2 times 10(-5)/1 times 10(-4) g/ml). 2. A particular effect of DSCG (2 times 10(-6)/2 times 10(-5) on the tonus of guinea pig ileum or an interaction with contractor activity due to histamine (3 times 10(-8)/1 times 10(-7) g/ml) has not been established. 3. Histamine liberation from rat peritoneal mast cells by i.p. injection of aqueous cotton dust extract was not inhibited by DSCG (2 times 10(-8)/2 times 10(-7) g/ml), histamine liberation was rather increased.


Nitroglycerin and premature ventricular complexes in myocardial infarction. Because of clinical observations suggesting that nitroglycerin may suppress premature ventricular complexes during acute ischaemia, a study was undertaken to assess the effect of nitroglycerin on the incidence of premature ventricular complexes in patients with acute myocardial infarction. Forty patients with acute myocardial infarction were studied. Twenty-six patients received 0.4 mg nitroglycerin sublingually every 4 hours for the first 24 hours after admission to the coronary care unit. The total premature ventricular complex count for the 26 patients for 15 minutes before nitroglycerin was 592, and 276 for the 15 minutes after the drug (P less than 0.005). In the remaining 14 patients on the same nitroglycerin schedule, a single electrocardiographic lead was continuously recorded on tape. During the first hour after nitroglycerin, the premature ventricular complex count decreased by 58 per cent, and the second and third hours showed a decrease from control count of 71 and 65 per cent respectively. By the end of 4 hours the ectopic count was back to control level. The data indicate that nitroglycerin may decrease the number of premature ventricular complexes for up to 3 hours in patients with acute myocardial infarction. The mechanism of action of nitroglycerin is not elucidated by this study, but the observation may be of value in further studies of specific antiarrhythmic therapy and prevention of arrhythmias in patients with coronary artery disease.


Relation between infarct size and ventricular arrhythmia. In order to determine whether ventricular arrhythmia is quantitatively related to infarct size estimated enzymatically we studied 31 patients with acute myocardial infarction without cargiogenic shock. Infarct size index was estimated from hourly serum creatine kinase (CK) changes during periods of 48 to 72 hours. Ventricular arrhythmia was quantified by automated analysis of continuous electrocardiographic recordings over a period of 20 hours with the use of the Argus/H computer system. Patients were classified into three groups according to infarct size index. Patients in all groups had similar average heart rate, blood pressure, serum potassium, and arterial pH and PCO2 values during the first 10 hours after admission. The total number of ventricular ectopic beats (VEB), frequency of couplets, and ventricular tachycardia, and peak rate of ventricular ectopic beats during the first 10 hours after admission were all related to infarct size index. For example, patients with small, medium, and large estimated infarct size averaged 26, 104, and 405 ventricular ectopic beats, respectively. These results suggest that the severity of ventricular arrhythmia early after myocardial infarction is related to the extent of myocardial injury as estimated enzymatically. Thus the apparent efficacy and therefore the evaluation of antiarrhythmic agents early after myocardial infarction may be influenced by the magnitude of injury sustained by the heart.


Effects of disopyramide on electrophysiological properties of specialized conduction system in man and on accessory atrioventricular pathway in Wolff-Parkinson-White syndrome. Seven patients with normal specialized conduction system and three patients with the Wolff-Parkinson-White (WPW) syndrome were studied using programmed stimulation of the heart before and after the administration of intravenous disopyramide. The principal effect of this drug was to prolong the effective refractory period of the atria and ventricles, and to prolong the effective refractory period of the anomalous pathway in the WPW syndrome. In addition, it prolonged the conduction time in the anomalous pathway in the WPW syndrome. These findings suggest that disopyramide would be a useful and safe drug in the management of certain atrial and ventricular arrhythmias and in the management of the Wolff-Parkinson-White syndrome with atrial fibrillation.


Escape-capture bigeminy caused by blocked atrial extrasystoles. A further mechanism of escape-capture bigeminy is described, viz, blocked atrial extrasystoles.


Binding of tubocurarine to specific serum protein fractions. The binding of tritium-labelled tubocurarine to separate protein fractions of sera from normal subjects and patients with hepatic disease was measured by an electrophoretic technique. The binding of the drug to gamma globulin and albumin solutions also was studied using equilibrium dialysis. The major portion of the drug, 82-90%, was bound to the gamma globulin electrophoretic fraction of both normal and patient sera. However, as measured by equilibrium dialysis, only 15.8% of the drug was bound to the gamma globulin and 23.8% to albumin. Equilibrium dialysis yields the data by which the validity of other methods for measuring drug-protein binding can be judged. Since in a previous study we also found no difference in binding of the drug between healthy individuals and patients with hepatic disease, equilibrium dialysis measurements may reflect better the binding of the drug in vivo.


The differential binding of antibody from the sera of patients with pemphigus and pemphigoid to isolated guinea-pig epidermal cells. A method for preparing isolated epidermal cells using trypsin is described. The isolated cells retain the ability to bind antibody from patients with pemphigus or with pemphigoid in a disease-specific.


Observations on a factor-V inhibitor.

Observations on a factor-V inhibitor. A 67-year-old man developed a potent inhibitor of factor V shortly after undergoing blood transfusions and surgery. The inhibitor reacted in a time-dependent manner with factor V and gave a non-linear concentration graph. Studies with specific antisera indicated that it contained gamma and mu heavy chains and both kappa and lambda light chains. The plasma from two patients with congenital factor-V deficiency did not neutralize the inhibitor.


A new assay for the measurement of total progressive antithrombin. A new rapid method for assaying total antithrombin activity has been developed based on the inactivation of thrombin incorporated into an agarose gel, during the radial diffusion of plasma in the gel. The area of thrombin inactivation is subsequently observed by the coagulation of fibrinogen in a separate agarose gel layer poured over the thrombin gel. The method is described in detail and its accuracy assessed with respect to other antithrombin assays. Using specific antisera to alpha2-globulin (antithrombin III), alpha2-macroglobin and alpha1-antitrypsin, total antithrombin activity measured by this assay consisted of 47% alpha2-globulin, 29% alpha2-macroglobulin and 26% alpha1-antitrypsin.


Serum inhibitors in fibrinolysis.

Serum inhibitors in fibrinolysis. Four protease inhibitors have been identified in human serum and methods for their isolation are described. After removal of the euglobulin fraction, serum was submitted to ion exchange chromatography and gel filtration, and fractions were tested for inhibition of the lysis of plasminogen-deficient fibrin clots by plasmin, trypsin and elastase. In addition inhibitors of plasminogen activation were sought by studying the effects of separated fractions on the lysis of plasminogen-rich fibrin clots by urokinase. Examination by immunophoresis showed that three of the separated inhibitors were alpha2-macroglobulin, alpha1-antitrypsin and inter-alpha-trypsin inhibitor. The fourth antiprotease was a powerful inhibitor of both urokinase-induced and plasmin-induced clot lysis, and was identified as an inter-alpha-globulin from its electrophoretic mobility in agarose gels.


A simple two-step isolation procedure for human and bovine antithrombin II/III (heparin cofactor): a comparison of two methods. Human and bovine antithrombin II/III have been isolated by a simple procedure essentially using only affinity chromatography on heparin-agarose and polyethylene glycol precipitation. An additional ammonium sulphate step removes polyethylene glycol and trace contaminants. The final preparation is homogeneous by SDS-, disc- and agar slide electrophoresis. End group analysis of human antithrombin II/III shows histidine as the N-terminal amino acid. The pure preparation showed both progressive antithrombin activity and heparin cofactor activity.


Cellular immunity to human basic myelin protein in women with dysplasia and carcinoma in situ of the cervix. Sensitization to human myelin basic protein or encephalitogenic factor (EF), and antigen thought to be analogous to different human tumours, can be measured by the macrophage migration inhibition test (MMI). The MMI test was done on one occasion in 51 women with dysplasia and carcinoma in situ of the cervix; 20 women with non-malignant gynaecological conditions served as controls. Sensitization to EF was found in 71 per cent of women with carcinoma in situ and 42 per cent of women with dysplasia. None of the controls showed sensitization. Sensitization could not be related to histological evidence for cellular infiltration within the cervix.


Raised alpha-fetoprotein levels in amniotic fluid and maternal serum in a triplet pregnancy in which one fetus had an omphalocoele. During the second pregnancy of a 31-year-old patient, who already had a child with hydrocephalus, the ultrasonic scan at 16 weeks gestation demonstrated the possiblity of triplets. Raised amniotic fluid and maternal serum alpha-fetoprotein concentrations were observed at 16 and 17 weeks gestation. The pregnancy was terminated at 17 weeks gestation and one of the fetuses had an extensive omphalocoele, radial aplasia and digital abnormalities.


On the interaction of 3,4,5,6-tetrahydrouridine with human liver cytidine deaminase. In contrast to the rapid inhibition of bacterial cytidine deaminase by 3,4,5,6-tetrahydrouridine, the onset of inhibition of the enzyme from human liver was found to be relatively slow. Inhibition was found to be reversible, and the corrected rate constants for binding (kon = 2.4 x 10(4) M-1 sec-1) and release (koff = 5.6 x 10(-4) sec-1) were in reasonable agreement with a Ki value (2.9 x 10(-8) M) measured separately under steady-state conditions, which was several orders of magnitude lower than estimates previously reported in the literature. Rates of binding and release of this potential transition state analogue were not appreciably affected by the substitution of deuterium oxide for solvent water. The slow onset of inhibition, which was also observed for cytidine deaminase from HeLa cells, suggests that structural reorganization precedes the formation of a stable enzyme-inhibitor complex. 6-Azacytidine, which favors a "high-anti" configuration at the glycosidic bond, was found to be active as a substrate for cytidine deaminase, with a turnover number exceeding that of cytidine. 2,2'-Anhydro-1-beta-D-arabinofuranosylcytosine, which is restricted to the "syn" configuration, was found to be without activity as a substrate or an inhibitor.


A new inhibitor of coupled oxidative phosphorylation, 5-hydroxynaphthalenedicarboxylic anhydride, a derivative of a carcinogenic polynuclear hydrocarbon. 5-Hydroxy-1,2-naphthalenedicarboxylic anhydride is closely related to its precursor dibasic acid which is a metabolite of the carcinogenic polynuclear hydrocarbon dibenz[a,h]anthracene. The anhydride inhibited respiration of coupled mitochondria. This inhibition was relieved by 2,4-dinitrophenol. Several mitochondrial volume change processes energized by ATP were also inhibited by the anhydride. Both the mitochondrial ATPase activity induced by 2,4-dinitrophenol and the ATPase activity of submitochondrial particles induced by magnesium ion were inhibited by the anhydride. The spectrum of inhibitory activity was not associated with acetic anhydride, succinic anhydride, or phthalic anhydride. The data indicate that 5-hydroxy-1,2-naphthalenedicarboxylic anhydride inhibits the machinery of oxidative phosphorylation in a manner similar to rutamycin. 5-Hydroxy-1,2-naphthalenedicarboxylic anhydride is the first molecule derived from a carcinogen with such inhibitory properties.


Mode of inhibition of herpes simplex virus DNA polymerase by phosphonoacetate. Phosphonoacetate is a highly specific inhibitor of herpes simplex virus-induced DNA polymerase. Sensitivity of herpesvirus type 1 or type 2 induced DNA polymerase to the drug was similar. However, DNA polymerases from other sources such as the host cells (Wi-38), Micrococcus luteus, and hepatitis B virus were highly resistant. In addition, Escherichia coli RNA polymerase and reverse transcriptase of Rous sarcoma virus were also insensitive to the drug. Enzyme kinetic studies showed that inhibition was noncompetitive with respect to deoxyribonucleotide triphosphates. The Ki value was about 0.45 muM. The apparent Km values for dTTP, dATP, dCTP, and dGTP were 0.71, 0.75, 0.42, and 0.39 muM, respectively. The base composition of template has no profound effect on the extent of inhibition. The drug caused uncompetititve inhibition with respect to template which indicated that phosphonoacetate did not bind directly to template DNA. Results are presented which suggest that phosphonoacetate did not affect the formation of the enzyme-DNA complex but probably inhibited the elongation step of DNA polymerase reaction.


Immunochemical study of beta-glucuronidase inhibitor from porcine sublingual gland. Interaction of beta-glucuronidase inhibitor with alpha2-macroglobulin. Antiserum to the inhibitor of beta=glucuronidase isolated from porcine sublingual gland was prepared in rabbits. Double immunodiffusion with the inhibitor produced a single precipitin line. However, neutralization of the inhibitor was produced by the antiserum and also by normal serum. Anti-beta-glucuronidase inhibitor isolated from human serum, by fractionation with (NH4)2 SO4 followed by DEAE-cellulose, Sephadex G-200 and Sepharose 4B chromatography, was identified as alpha2-macroglobulin by using ultracentrifuge analysis and immunoelectrophoresis. The mechanism of interaction of beta-glucuronidase inhibitor with alpha2-macroglobulin was also studied.


Isolation of two forms of rat alpha-fetoprotein and comparison of their binding parameters with estradiol-17beta. In polyacrylamide gels, highly purified rat alpha1-fetoprotein shows a molecular heterogeneity, i.e. a "slow" and a "fast" moving fraction. We have isolated by electrophoretic fractionation and subsequent elution these two forms of alpha1-fetoprotein, and we have studied comparatively the binding parameters for estradiol-17beta of whole alpha1-fetoprotein preparations and of the isolated forms. We have shown that the number of binding sites per molecule of whole alpha1-fetoprotein is always, in our experimental conditions, a fractional number, inferior to unity (0.3). Furthermore, the analysis of the binding parameters of the "two forms" of alpha1-fetoprotein allows discrimination between different classes of binding sites. For the "slow" fraction, the number of predominant binding sites per molecule of protein is close to unity (0.7-0.9), whereas for the "fast" fraction, a very low fractional value is found (0.1). The corresponding association constants are reproducibly different for the two fractions: Ka = 0.1.10(8) M-1 for the "slow" alpha1-fetoprotein, and Ka = 0.7.10(8) M-1 for the "fast" alpha1-fetoprotein. Traces of a very high affinity (10(9) M-1) minor class of binding sites are demonstrated in the "slow" fraction. These results point to the existence of a molecular population of alpha1-fetoprotein, some forms of which have a strong or very strong affinity, and some a negligible affinity, for estrogens.


Reversed transport of amino acids in Ehrlich cells. Gramicidin induces a marked Na+-dependent efflux of amino acids from Ehrlich cells. In absence of Na+, gramicidin does not alter the efflux. In presence gramicidin, glycine efflux is inhibited by methionine and less so by leucine. Glycine efflux caused by HgCl2 is neither Na+ dependent nor inhibitable by amino acids. Neither efflux of inositol which is transported by an Na+-dependent route, nor efflux of several other solutes which are transported by Na+-independent routes, is affected by gramicidin. The antibiotic appears to permit a reversal in the direction of of the operation of the Na+-dependent amino acid transport system. The increased efflux is partly, but not entirely, due to an increase in the cellular Na+ concentration and a reduction of the electrochemical potential difference for Na+.


Some characteristics of the DNA-tyrocidine complex and a possible mechanism of the gramicidin action. 1. The cyclic peptide antibiotic tyrocidine which inhibits RNA synthesis in vitro by forming a complex with the DNA (Schazschneider, B., Ristow, H. and Kleinkauf, H. (1974) Nature 249, 757-759) induces hypochromicity of the DNA. The complex dissociates at elevated temperatures but which are below the melting temperature of the DNA. 2. The linear peptide antibiotic gramicidin which reverses the inhibitory effect of tyrocidine (Ristow, H., Schazschneider, B., Bauer, K. and Kleinkauf, H. (1975) Biochim. Biophys. Acta 390, 246-252) does not bind to DNA and does not induce hypochromicity of the DNA. However, the DNA-tyrocidine complex dissociates at lower temperatures when gramicidin is present. Thus gramicidin weakens the binding of tyrocidine to DNA. 3. The presence of DNA quenches the fluorescence of tyrocidine but not that of gramicidin. This quenching of tyrocidine fluorescence is reduced in the presence of gramicidin. 4. Tyrocidine inhibits transcription of single-stranded DNA as well. This inhibition too can be reversed by gramicidin. Thus the action of the peptides is not dependent on a double-stranded DNA conformation.


[2-colored fluorescence of differentially condensed chromosomes stained with acridine orange]. Metaphase chromosomes of the Chinese hamster differentially-condensed under the influence of a) 5-bromdeoxyuridine, b) colcemide, and c) cold, were stained with acridine-orange (AO) in concentrations of 1.5 X 10(-7) to 3 X 10(-5) g/ml at pH 4.1 to 8.5. It was found that stretched chromosomal segments fluoresced in the orange/red part of the spectrum, whereas normally condensed ones--were green. The colour distribution along the chromosome depended mainly on the AO concentration and the exposure in the UV-light, and was independent of pH and molarity of the buffer. Apparently this phenomenon cannot be attributed to the uneven denaturation of the chromosomal DNA, but rather depends on structural and/or chemical differences between euchromatin and heterochromatin.


Interpersonal relationships and child-rearing practices in 214 parents of battered children. The self-reported child-rearing practices of 214 parents of battered babies were characterized in a few but not all respects by demanding behaviour which exceeded that to be expected in relation to their social class and age. Inconsistency in child management was noted in the comparison between lack of demonstrativeness and emotional over-involvement, and between physical punishment and a tendency to be lax in the supervision of the child, and was reminiscent of parents of delinquents. Unhappiness and hostility in relationships with members of their families of origin, with unsupporting partners and with people in general were other important features. Generally, identified perpetrators were characterized by features significant for the sample as a whole.


A clinical comparison of the tumour-imaging radiopharmaceuticals 67Gallium-citrate and 111Indium-labelled bleomycin. Two tumour-imaging agents, 67Gallium-citrate and 111Indium-bleomycin have been assessed in a clinical trial. Both the quality of tumour image and correlation with known sites of disease has been compared by scanning with the two agents in a variety of malignant diseases. In addition, comparative uptakes of the agents have been measured in biopsy samples. In 28 scanning examinations using the agents sequentially, 67Gallium-citrate provided a more satisfactory tumour image and had closer clinical correlation with known sites of disease in 14 cases. Scans were felt to be of similar quality in 14 cases. There were no examples where 111Indium-bleomycin scans were found to be superior to 67Gallium-citrate. A number of biopsy samples of spleen, liver and lymph nodes were obtained from patients undergoing staging laparotomies for lymphomas in whom small doses of 67Gallium-citrate and 111Indium-bleomycin had been injected shortly before operation. Seven of the spleen samples were infiltrated with tumour and five of these contained less 67Ga than 111In; in contrast four of the five tumour-infiltrated lymph nodes showed 67Ga concentrations greater than those of 111In. It is concluded that 67Gallium-citrate is a more useful tumour-imaging agent than 111Indium-bleomycin, at least for lesions situated above the diaphragm. The value of 111Indium-bleomycin in the demonstration of abdominal malignancies has not been fully assessed in this study. Trials of new tumour imaging agents should as far as possible be compared directly with the best available alternative agent in a controlled study.


Is a 'second look operation' justified in suspected recurrences after abdominal cancer surgery? Seventy-three patients have been submitted to 74 further laparotomies for suspected recurrent malignant abdominal disease over a period of 13 months. The original tumour was situated in the large bowel in 42, oesophagus or stomach in 24, ovary in 3, small intestine in 2 and pancreas and retroperitoneum in 1 instance each. There were 10 examples of benign lesions, 16 of further primary cancer and 24 of resectable local recurrences or metastases. Seventeen patients underwent some palliative procedure, and only 7 were beyond any surgical help.


Antigenic heterogeneity in patients with reactions in borderline leprosy. Fifteen patients with borderline leprosy who developed "reversal" reactions were studied from the inception of treatment. Thirteen showed an appreciable increase in lymphocyte transformation (LT) when preparations of Mycobacterium leprae were used as antigen. The LT responses to either "whole" or "sonicated" preparations of the bacillus in these 15 patients and in nine others also in reaction correlated with the clinical presentation. Those with skin disease predominating in the reaction showed an appreciable increase in LT when whole M leprae was used as antigen. Those with nerve disease predominating showed an increase with sonicated M leprae. In those with both skin and nerve disease there was an increase with both antigen preparations. The ratios of the LT test results (whole to sonicated M leprae) showed highly significant differences between the three groups.


A study of the dynamics of retrograde transport and accumulation of horseradish peroxidase in injured neurons. The phenomenon of retrograde intraaxonal transport of extracellular markers introduced at the level of the axon terminal has been suggested as a possible mechanism of communication between the axon terminal and the neuron cell body. We tested the hypothesis that communication after axotomy might consist of a change in the rate of uptake or of transport of material by injured neurons. Small lesions were made with a needle in one retinal quadrant of chicks and immediately afterwards horseradish peroxidase (HRP) was injected into the vitreous body of the eye. The amount of HRP accumulated by some of the neurons of the isthmo-optic nucleus (ION) which project to the damaged area was clearly different from that of nearby cells which project to the non-damaged portions of the retina. The uninjured cells accumulated enzyme marker beginning at 3.5 h after injection. The injured neurons did not accumulate significant amounts of HRP until between 4 and 6 h after injection. Between 6.75 h and 18 h the injured cells in the ION accumulated greater amounts of HRP than cells in other regions, but by 24 h the cells of the ION in the region of injury contained distinctly less label. This pattern of enzyme accumulation was confirmed by counts of the number of HRP-positive granules within cells of chicks fixed 4, 11.75, 12.25, 27.6 and 72 h after injury. In another series of experiments, the axon terminals of the ION were first exposed to HRP, and 1 h later some of the axons were damaged with a needle. In these cases, there was no difference between the injured and control neurons in the time of first appearance of labeled cells in the ION within the first 4 h after injection of HRP. These findings suggest that injury initially results in a decrease in the uptake of the marker rather than a decrease in the rate of retrograde transport. The amount of marker found in the injured neurons later is greater than that found in the control neurons. This subsequent difference may represent an increase in the rate of uptake, transport, or both or a decrease in the rate of degradation of HRP within the cell body as a response to injury of the axon.


Effect of pretreatment with local corticosteroids on antibody-forming cells in the eye and draining lymph nodes. To study the effect of pretreatment of rabbits with locally administered steroids, unilateral subconjunctival injections of 10 mg. triamcinolone suspension were given 10 and 3 days before intracorneal injection of the same eye with bovine gamma globulin. We killed the rabbits 6, 9, 12, 15, and 21 days after the BGG injection, and determined the number of antibody-producing cells in the homolateral lymph nodes, corneas, and uveal tracts. Corticosteroids did not significantly affect the PFC response in the draining lymph nodes, but the number of plaque-forming cells in the corneas and uveal tracts was reduced. Steroid-treated eyes were less inflammed than control eyes. The possible mechanisms for the effect of steroids on the ocular immune response are discussed.


Absence of 'superfast' axonal transport in rat sciatic nerve. Axonal transport of labelled protein was studied in rat sciatic nerve by analyzing nerve segments at intervals after injection of L-[3H]leucine into the lumbar spinal cord. Some nerves were sectioned before injection so that material in transit accumulated proximal to the section. The segments distal to the section served as controls for incorporation into the nerve of blood-borne label. An analysis of TCA-soluble and TCA-insoluble activity in cut and intact nerve segments was also made. No evidence was found for the existence of a 'superfast' component of axonal transport (velocity 2000 mm/day). Results showed that the most rapidly transported protein derived from the neuron soma had a conventional 'fast' velocity of 350-420 mm/day. There was no transport of TCA-soluble material. It is suggested that 'superfast' transport, detected in mice by other investigators, is an artefact resulting from failure to control for incorporation of circulating label into the sciatic nerve.


A p-nitrophenyl alpha-galactoside hydrolase from Pseudomonas atlantica. Localization of the enzyme. A p-nitrophenyl alpha-galactoside hydrolase is partially released when whole cells of Pseudomonas atlantica are converted to spheroplasts. The p-nitrophenyl alpha-glactoside hydrolase is completely inactivated by treatment of whole cells with diazonaphthalene -- disulfonic acid (NDS), a reagent which does not penetrate the cytoplasmic membrane. Under the conditions used no inactivation of lactic acid dehydrogenase was observed. A specific staining procedure for this enzyme for use in electron microscopy was developed. The results with this technique in conjunction with the results of spheroplasting and NDS localization suggest that p-nitrophenyl alpha-galactoside hydrolase is located in or on the double-track membranes, primarily on the outer double track.


The oxyphil and C cells of the human thyroid gland. A cytochemical and histopathologic review. The C and oxyphil cells of the human thyroid are analyzed in the light of recent advances in cellular biology, cytochemistry, and histopathology. The C cell is present in the normal human thyroid, where its identification is cardinally by means of argyrophilic cytoplasmic granules. The morphology, topography and argyrophilia of C cells are discussed with reference to tumor, cyst, and teratoma formation in the thyroid gland. Oxyphil cells of the thyroid are cytochemically akin to C cells but arise from follicular cells. They occur in the thyroid and other protein-producing organs, but are themselves inefficient producers of proteins and glycoproteins. Speculation is made on their morphological characteristics, and consideration is given to DNA-RNA involvement in the functional and morphological alterations of this follicular cell type.


Primary adenocarcinoma of the jejunum and ileum. A clinicopathologic study. The clinical and pathologic features of 43 primary adenacarcinomas of the small intestine (32 jejunal and 11 ileal) are reported. Seventy-four percent of the patients presented with partial or complete small bowel obstruction, 56% complained of abdominal pain, 37% had symptoms of anemia (weakness, easy fatigability), and 35% had lost weight. Anemic hemoglobin levels occurred in 69%, and a palpable abdominal mass in 25%. Treatment consisted of a "curative" or "palliative" resection, or a bypass procedure. Seventy-nine percent of the tumors showed an annular, constricting pattern, while the remaining 21% had a predominantly fungating or polypoid appearance. Three individuals currently free of clinical recurrence have been followed less than 5 years. Of the remaining 40 patients, a 5-year cure was achieved in 11 (28%), including 6 (15%) who at present have no recurrence and 5 (13%) who subsequently died of other causes. Within 5 years, 28 of these 40 patients (70%) were known or presumed dead tumor, and 1 had succumbed to other causes (2%). Various pathologic features were correlated with the clinical course. Documented lymph node metastasis proved to be the most valuable prognostic finding, 88% of these individuals dying of tumor, as contrasted to 45% of those with tumor-free nodes. A few cases of superficially invasive carcinoma found in an otherwise benign adenomatous lesion had a good prognosis when symptoms were produced mainly by the adenoma, the carcinoma being a relatively minor component.


Nutrition and experimental carcinogenesis: a review. Restriction of the total diet or the number of calories fed to rats and mice inhibits the formation of tumors in several tissues. Unless animals are fed equivalent levels of food, or attain equivalent body weights, it is difficult to assess the significance of the effect of other nutritional modifications on carcinogenesis. The effects of altering the levels of protein or fat are much less than those seen with dietary restriction. Feeding a protein-free diet is tolerated for a limited period and can alter the metabolism of carcinogens. It may thus affect the tumor incidence induced by one-shot carcinogens. Vitamins have specific effects on the activity of certain carcinogens, the fullest information being available for vitamin A, which has been shown to inhibit or enhance carcinogenesis, and vitamin C, which by reducing sodium nitrite, prevents nitrosation of secondary and tertiary amines occurring in acidic conditions of the stomach. Inorganic substances, such as iodine (thyroid) and copper (liver), may affect the tumor incidence in specific tissues. The metabolic activation of carcinogens is modified by enzyme induction and the administration of antioxidants. The relevance of these results to the induction of cancer in humans is briefly discussed.


Dietary effects on chemical carcinogenesis in animal models for colon and liver tumors. Studies of dietary effects on chemical carcinogenesis in rats have demonstrated that colon tumor induction is enhanced by increased dietary fat intake or dietary deficiency of vitamin A in some but not all cases. The enhancing effect of a high-fat diet is augmented by lipotrope deficiency. Induction of hepatic tumors by several different carcinogens also is enhanced in rats fed a high-fat diet marginally deficient in lipotropes. The dietary effects may be exerted through alteration of metabolism of carcinogens, which has been demonstrated in lipotrope-deficient rats, through immunological mechanisms, which influence induction of colon tumors, or through effects on gastrointestinal bacteria and bile acid metabolism. Demonstration of dietary effects on carcinogenesis may require utilization of combined dietary stresses that alter metabolic loads but do not seriously impair growth.


Gomori-positive elementary granules in inner and outer layer of the infundibulum. With the gallocyanine technique (Wittkowski, Bock and Franken, 1970) Gomori-positive substances of the infundibulum can be stained for light- and electron-microscopic examination. In various mammalian species, the size of Gomori-positive elementary granules in the outer layer is markedly different from that in the inner layer of the infundibulum. In general, the granules of the outer layer have less then half the diameter of those of the inner layer. In birds and fish, however, only small differences were found between the granules of both layers. The significance of the results is discussed.


Studies on the transport of secretory granules in the magnocellular hypothalamic neurons of the rat. II. Action of vincristine on axonal flow and neurotubules in the paraventricular and supraoptic nuclei. Intrathecal administration of 20 mug of vincristine sulphate in the rat induced in vivo the formation of paracrystalline inclusions mainly in axonal processes. This is associated with an impairment in the migration of neurosecretory granules as shown by their accumulation in the perikarya of the magnocellular neurons. The granules are intermixed with numerous dense bodies of various shape, sometimes with a fibrillar content, and probably of lysosomal origin. In addition to the impairment of the flow of neurosecretory granules, there is also a striking accumulation of mitochondria and synaptic vesicles, and an apparent proliferation of the smooth endoplasmic reticulum. In the posterior lobe, the axonal endings contain a large number of neurosecretory granules, intermingled with bodies of varying shapes and electron density. Occasionally, a dense membrane surrounding a group of elementary granules is observed, reacting positively for acid phosphatase. This suggests an attempted crinophagia.


Identification of the vasopressin producing and of the oxytocin producing neurons in the hypothalamic magnocellular neurosecretroy system of the rat. Immuno-enzyme histochemical investigations showed that, in the magnocellular hypothalamo-hypophysial neurosecretory system of the rat, vasopressin and oxytocin are synthetized in separate neurons. Both the vasopressin neurons and the oxytocin neurons are present in both the supraoptic and the paraventricular nuclei in about the same number. Preferential location of the two kinds of rat neurosecretory neurons is not as obvious as in the bovine hypothalamus. Their perikarya do not show distinct morphological differences. The two kinds of neurosecretory perikarya are the origin of separate vasopressin-containing and oxytocin-containing axons respectively. In the neural lobe, the distribution of the two different types of axons is described.


[Immunopathology of a model inflammation]. A series of 32 healthy individuals has been examined, in whom a large number of model inflammatory lesions of the "skin window" type had been produced. Physiological salina solution and diptheriac toxoid were administered by dropping as well as by intradermal injection into the lesioned areas of these individuals. The cover slips were removed after 12, 24 and 48 hours. The control inflammation without antigenic stimulation was characterized by the presence of neutrophilic granulocytes, monocytogenic macrophages and, later, also by epitheloid cells and foreign body giant cells. Celluization of the immune conditioned inflammation mainly consisted of rather small mononuclear cells related to the lymphatic series on the basis of their morphological and cytochemical features. In addition, neutrophils were also found, as well as typical macrophages, epitheloid and foreign body gaint cells. In the 24 and 48 hour preparations, particularly in those obtained from lesions following intradermal antigen administration, basophilic and eosinophilic granulocytes were a regular finding. The ftndings show a variability of the mutual proportions of immunocompetent and immunoneutral cells in the inflammatory cellulization under various condition.


[Histopathological picture of acute disseminated intravascular coagulation]. The paper deals with histological analysis of 72 cases characterized by the finding of capillary microthromboses characteristic of acute disseminated intravascular coagulation (DIC). It has been stressed that, in addition to the usual fibrillary fibrin deposits, DIC is also characterized by the occurrence of globular fibrin formations, most frequently found within the hepatic and hypophyseal sinusoids. In the present series, microthromboses were obviously more frequent within the capillaries of organs such as the renal glomeruli or plexus chorioideus, wherein significant amounts of water are lost from circulating blood.


[Proposition of a reference serum for the immunochemical assay of human serum proteins]. Sera of healthy students (from Academy of Paris) aged between 18 and 30 years were collected with a view to routine clinical testing. 50 samples each representing the pooled sera of 400 individuals were investigated by evaluating 7 proteins for each pooled sample. Calculations of standard deviations showed that there existed a significant reproductibility of less than 2% for the population as a whole. These pooled sera representing 20 000 individual blood samples are proposed as a standard of human serum proteins.


35-S-antithyroid drug concentration and organic binding of iodine in the human thyroid. 35S-methimazole (MMI), 35S-carbimazole or 35S-propylthiouracil (PTU) were given orally to fifty-five patients at various times up to 12 h before surgical thyroidectomy. The amount of 35S radioactivity and labelled drug in thyroid and plasma samples was measured. Intrathyroidal inhibition or organic binding of iodine by MMI, carbimazole and PTU was measured after intravenous administration of 131I, 132I or 125I-iodide. After administration of 35S-carbimazole or 35S-MMI the thyroid to serum (T/S) ratio of 35S radioactivity was greater in thyrotoxic glands than in non-toxic adenoma tissue. 35S-MMI was found in thyroid and plasma samples after administration of 35S-carbimazole. The T/S 35S-MMI was greater than 1 in most but not all patients. 35S radioactivity was also concentrated in the thyroid after administration of 35S-PTU. In thyrotoxic glands there was an 80% inhibition of iodine organification in patients receiving MMI and 60% for those receiving PTU. It is suggested that carbimazole and MMI can be given once or twice daily in some patients but PTU would be less suitable for this dose schedule.


[Immunologic comparison between some Wolbachiae and research of antigentic community with other members of the order of Rickettsiales]. The antigenic relationship between some rickettsiae of arthropods, which do not transmit germs pathogenic to vertebrates was investigated by agglutination and immunofluorescence techniques. The comparison of R. melolonthae, R. tipulae, R. cetonidarum, R. grylli and of the rickettsiae of the scorpion Buthus occitanus shows that the Wolbachiae are divided into three serological groups. The insect crystallogen rickettsiae belong to the first group, R. grylli and the scorpion Rickettsia are antigenically distinct (tables I and II). No antigenic relationship was found between these arthropod microorganisms and the following agents of vertebrate rickettsioses and chlamydioses : historical typhus, murine typhus, pustulous fever, Q-fever, epizootic absortion of sheep and psittacosis (tables III and IV). Bacteria of OX2 and OX19 strain of P. vulgaris when mixed with anti-Wolbachiae serums of I, II, III groups, give a negative Weil a Felix reaction. The OXK Proteus are however agglutinated by 4 out of 6 rabbit anti-Rickettsiella serums of the group. This fact calls for a further investigation regarding the comparison of these Rickettsiella with various strains of R. tsutsugamushi.


Basophilic leucocytes: structure, function and role in disease. We have attempted to review the current state of our knowledge concerning the human basophilic leucocyte, drawing on experimental data derived from animals when necessary. Long neglected, a great deal has been learned about these cells in recent years, about their morphology, their biochemical constitutents and their ability to synthesize certain of these constitutents, their interactions with homocytotropic antibodies, their release of mediators in anaphylaxis, their response to chemotatic stimuli, their participation and progressive degranulation in cell-mediated hypersensitivity reactions, and their capacity for ingesting and releasing certain exogenous tracers. Despite this vast accumulation of new information, much more must be learned before we can confidently describe the role of basophils, or of the closely related mast cells, in health or disease. It seems most unlikely that either cell exists for the purpose of destroying the organism in anaphylactic shock. Nonetheless, it is highly probably that basophil/mast cell function is closely related to the potent chemicals stored within their cytoplasmic granules. One likely possibility holds that small amounts of these chemicals are required for homeostasis (e.g., for regulation of the tone of the microvasculature) and that these cells function by releasing such substances continuously, as they are needed, in small aliquots rather than by explosive discharge. This hypothesis requires that basophils be capable of releasing their contents in piecemeal fashion. Such gradual release apparently occurs in delayed-type hypersensitivity reactions, but the mechanisms responsible for this form of degranulation have not yet been identified. This hypothesis also requires that physiological, rather than pharmacological, roles be found for histamine, heparin and possibly for other components of the basophils/mast cell granules. Progress in this direction has been extremely slow.