Active enhancement in the primate by bone marrow I. Ia-like determinants on nucleated bone marrow cells. This study investigates the possibility that the active enhancing properties of bone marrow (BM) cells may be related to Ia-like determinants on their surface membranes. Less chromium was released on a cell per cell basis from nucleated baboon BM cells used as targets in complement-dependent cytotoxicity than from labelled lymph node lymphocytes. On the other hand, BM cells stimulated allogeneic lymphocytes in culture more vigorously than lymph node lymphocytes. BM cells with lymphocyte-activating properties could be enriched by fractionation on a discontinous bovine serum albumin gradietnt. BM cells responded poorly to allogeneic cell stimulation in mixed culture. Platelet absorption studies of an alloantiserum supported the conclusion that nucleated BM cells, and particularly BM fractions collected from the less dense interfaces of a bovine serum albumin gradient, express relatively more lymphocyte-activating or Ia-like determinants than "serologically defined" determinants.


Counter immunoelectrophoresis for detection of human prostatic acid phosphatase. An immunochemical method for detection of prostatic acid phosphatase is described. Acid phosphatase was obtained from benign human prostatic tissue. A specific antiserum to this enzyme was produced in rabbits. A counter immunoelectrophoretic method utilizing the specific antiserum with a chemical staining technique has been developed. Clinical trials have indicated the usefulness of this method for the specific determination of prostatic acid phosphatase.


[Sensitivity of microorganisms isolated from swine to aqueous and proteinic solutions of gentamycin]. Employing a microbiologic method (in vitro) the activity was investigated of Gentamicin DSO Pharmachim, dissolved in water, in normal swine gamma-globulin, and in normal swine polyglobulin with regard to swine strains of Escherichia coli, Salmonella choleraesis Bordetella bronchiseptica, and Pseudomonas aeruginosa as well as Mycoplasms. A strong sensitivity was found to exsist in all tested strains (except for the Mycoplasms) to gentamycin both in a water and in a protein solution. The in vivo testing of the therapeutic effect of the two types of solutions in an experimental infection in albino mice revealed that the differences found in the activity of the various gentamicin solutions were statistically insignificant. The step agglutination test was used to follow up the effect of gentamycin on the OK agglutinating antibodies of a gamma-globulin preparation against oedema disease in pigs. Results showed a slight increase in the agglutinating activity of the gamma-globulin antibodies under the effect of the antibiotic.


A histochemical and ultrastructural study of stored material in neuronal ceroid lipofuscinosis. A histochemical and ultrastructural study of five cases of neuronal ceroid lipofuscinosis (NCL) revealed the existence of two related lipopigments differing in some tinctorial properties and ultrastructure. Type I pigment is present in all the tissues affected and corresponds to the pigmentary tertiary lysosomes of well known ultrastructure. Type II pigment occurs exclusively in the neurones of lipophilic cerebral grisea, as a component of the so called protein-myoclonic bodies. It shares with type I certain basic tinctorial properties of lipopigment and its lysosomal localization, but differs in other respects. It stains poorly if at all with the PAS and PAF techniques and is markedly metallophilic, azurophilic and positive for protein. Type II pigment is extremely electron-opaque after staining with heavy metals to the extent that they appear practically amorphous. The possibility that type II material is derived from type I pigment is considered. The amount of type II pigment is highly variable. Both types of pigments are present in residual bodies of various shape and size, including spheroids.


[Heterochromatin of the rat-like hamster Tscherskia triton de Winton (Rodentia, Cricetinae), II]. Differential staining of rat-like hamster chromosomes revealed: 1) C- and G-banding of chromosomes depending upon the Giemsa solvent (distilled H2O and phosphate buffer correspondingly) in case of ordinary staining; 2) dependence of C-banding pattern on the C-method; 3) different resistance of C-bands to trypsin action; 4) dependence of Q-bands on the fluorochroms employed (A, 33258 H, AO), the second non-fluorescent (A, 33258 H) near-centrometric heterochromatic region is brilliantly fluorescing when AO is employed; 5) heterogeneity of C-, G- and Q-bands, i.e. similarly stained region, may differ in their structural-functional peculiarities.


[Changes of platelet function, coagulation and fibrinolysis during induction of labour at term by prostaglandin F2alpha and oxytocin (author's transl)]. Platelet function (induced and spontaneous aggregability according to Born and Breddin respectively) and some parameters of coagulation and fibrinolysis have been investiagted during induction of term labour by PgF2alpha i.v. (n = 9) and oxytocin i.v. (n = 9). During infusion of PgF2alpha there was a slight decrease of platelet aggregation with both methods. Desaggregation in the Born-test was increased. On the contrary there was no change of platelet function except a small increase of the speed of aggregation if one applicates oxytocin. The parameters of the plasmatic coagulation system remained almost unchanged in both groups and hint only at a slight increase of the fibrinolytic activity in the oxytocin group. The clinical importance of the results is discussed.


[Multiple cartilaginous exostoses and neoplastic degeneration: review of the literature (author's transl)]. In about 10% of patients suffering from multiple osteochondroma a malignant degeneration of one osteochondroma occurs. Data of 59 patients are collected from the literature. The malignant degeneration occurs at the age of 31 in average, mostly on the pelvic girdle, less frequently on the shoulder girdle and on the ribs. The development is slow in most cases, at times interrupted. The first clinical signs are an increase in swelling, rarely pain or neurological symptoms. Radiological findings and prognosis correspond well with those of a proliferative chondroma or a primary chondrosarcoma. Recurrences after local treatment are frequent, metastases are rarely found. Regular check-ups and good information of patients suffering from multiple osteochondroma are recommended.


[Demonstration of early local vital reactions by combination of morphological investigation methods (author's transl)]. In extension of earlier Scanning Electron Microscopical findings on local vital reaction, we initially tried conventional microscopic histology. By standard staining methods--generally used in demonstrating fibrins (Ladew IG, PTAH, PAS etc.) fresh fibrinous mashing was hardly demonstrable. Tryptophan reaction as per Adams brought positive results. By modifying Scanning Electron Microscopic preparation techniques, the surface transverse striation could be shown. For dissolution of the complex morphological structural patterns on the wound surface, Transmission Electron Microscopy was used. Identification of fibrinous filaments was done by their interior transverse striation. Mashing of shaped structure components of the blood in vital and post mortal injuries should be more closely analyzed. Advantages and disadvantages of Scanning and Transmission Electron Microscopic techniques are discussed in view of forensic problems and a tentative judgement passed.


[Management of acute oesophageal fistulas (author's transl)]. The observation of 75 patients with acute oesophageal fistulas indicate their great multiformity of etiology, pathogenesis, morphology, clinical course, complications, underlying oesophageal pathology. Most frequently the fistulas resulted from injuries inflicted during bouginage, cardiodilatation, external and intraoperative trauma. Drug therapy should be started immediately with the making of diagnosis of the suspected oesophageal injury, and then surgery is undertaken if indicated. Drug therapy proved effective only in cases of non deeply penetrating injuries. Palliative interventions as sole procedures permitted to eliminate the acute fistulas in 12 patients, to turn them into chronically behaving--in 17; in the rest of the patients they were ineffective. Twenty-one patients were operated radically, 9 of them following ineffective drug therapy and palliative surgery. The result of radical surgery depends on several factors, and especially on its technique, on the reinforcement and isolation of the sutures by the adjacent tissues with blood supply preservation--diaphragm, pericardium, pleura, muscle-pleural flap, muscles, etc.


[Risks in amniocentesis for prenatal diagnosis of genetic defects]. In 139 patients for prenatal diagnosis 186 amniocenteses were required. The repetiion of amniocentesis followed in 12.3% due to failure of cell growth, in 1.1% due to failure to obtain fluid, and in 10.2% to performe the fetography. In 3 pregnant women 2 repetitions were indicated. Although the amniocentesis were performed without ultrasound, in 92% the first insertion of needle were already succeeded in obtaining fluid. In repeated amniocenteses no significant differences were found. Brownish fluid were observed in 4.7% of the first amniocentesis. With 24.4% it was significantly more frequent in the repeated amniocenteses. Bloody taps appeared in each fifth puncture, but only in 2.8% blood fluid were also withdrawed for cell culture. 82.9% of the first amniocentesis followed between 16 and 19 week's gestational age and the result was present after 20.3 days on an average. The abortion rate was 4.3%. Among the newborns one hydrocephalus with questionable needle mark, one microcephalus and one further child with questionable needle mark were found. In one duodenal atresia and in one achondroplasia an inconclusive result was obtained. Two erroneous diagnoses of sex occurred and no diagnosis was obtained in two women.


A retrospective study of carcinoma of the pancreas with special reference to the results of surgical treatment. 469 patients treated for carcinoma of the pancreas in the County of Stockholm in 1963--73 were analysed for mean survival time, mean hospital-stay, post-operative complications and mortality. The results of treatment with palliative biliary by-pass procedures and radical surgery were compared. The mean survival time after by-pass operation was 5,7 months and after radical surgery 12,8 months. The mean hospital-stay was 39 and 83 days respectively. The post-operative mortality after palliative biliary by-pass procedures was 16%, and the frequence of major post-operative complications 10%. The corresponding figures after radical surgery were 25% and 30% respectively. Despite the longer survival time, it is doubtful if patients benefit from radical surgery.


HLA antigens in allergic contact dermatitis. The relationship between HLA factors and allergic contact dermatitis was examined in a series of 149 patients with unequivocal positive reactions to one or several allergens on epicutaneous testing. Nine statistically significant associations involving 6 different HLA antigens and 6 different allergens were found. Four allergens (chromium, formalin, balsam of Peru and wool alcohol) were positively associated with the B7 antigen. Furthermore chromium allergy was associated with A3, formalin allergy with A2 (negative association) and A9, nickel allergy with B8 and colophony allergy with B27. The B7 antigen and the combination A3+B7 showed significant regressions on number of allergies. The results fit the hypothesis that some HLA factors (like B7) may predispose for multiple contact allergy and others for allergen specific reactions.


The Langerhans cell: its origin, nature, and function. This is the biography of a cell--a cell as elusive and as deceiving as any in medical literature. This is the biography of the Langerhans cell, literally a cell at our fingertips, yet seemingly always beyond our intellectual grasp. Here is the story of a foundling within our epidermis, yet outside our pathologist's daily view. It is the history of a cell whose stain and form belied its function. It is a biography of a cell which virtually hid from us until it came under the revealing beam of the electron microscope.


Neurohistological observations on the kidney of Rattus rattus rufescens (Indian black rat) as revealed by cholinesterase technique. The intrinsic innervation of the kidney in Rattus rattus rufescens (Indian black rat) has been studied by cholinesterase technique, under various temperatures, incubation periods and different pH values. The percentage of myelinated nerves was rather high in the medulla region, whereas the non-myelinated nerves dominated in association with the uriniferous tubules and their branches, glomerulus and renal vein in the cortex region. Periarterial AChE-positive ganglia were recorded in the medulla region. The perivenous and periglomerulus plexuses were formed by the non-myelinated nerves and their branches.


Proteins secreted by platelets: significance in detecting thrombosis. Because platelet survival measurements are time-consuming and may not completely reflect platelet involvement in hemostasis and thrombosis, other tests have been sought. Measurement of two proteins released by platelets, platelet factor 4 (PF4) and beta-thromboglobulin (betaTG), may provide simpler, more direct means of quantitating platelet involvement. The radioimmunoassays for these proteins reviewed in this paper are sensitive and specific. Although there are technical problems still to be resolved in their clinical application, clinical studies to date suggest that such assays will be useful in studying the pathogenesis and course of thromboembolic disorders. PF4 and betaTG levels apparently do reflect in vivo platelet release. Because release of PF4 and betaTG parallels release of platelet-derived growth factor, plasma PF4 and betaTG levels should also reflect release of that protein. The PF4 and beta TG assays along with an assay for fibrinopeptide A in clinical samples should help elucidate the relative importance of platelet release and fibrin formation in thromboembolic disorders.


The mechanism of histamine release induced by the ionophore X537A from isolated rat mast cells. II. The relationship between increase of cell volume and histamine release. The ionophore X537A induced swelling of isolated rat mast cells parallel to histamine release. Both actions were depressed by extracellular calcium and BSA, temperatures below 37 degrees C, NEM, PMSF, and TTX, and were enhanced by high potassium and pretreatment of the cells with ATP. DSCG, theophylline, and DFP enhanced the histamine release noted after 10 min of incubation without influencing the swelling action of X537A. The swelling action could not be separated from histamine release and it is suggested that it might be inherent in the mechanism of secretion induced by X537A. The present results further distinguish histamine release induced by the two ionophores X537A and A23187.


Modulation of the spontaneous histamine release by adrenergic and cholinergic drugs. Experiments have been reported on the possible modulation of the spontaneous histamine release by adrenergic and cholinergic drugs. Adrenergic drugs increase the spontaneous histamine release in vivo, and in neoplastic mast cells, in vitro. The mechanism of histamine release appears to be dependent upon the activation of alpha-adrenoceptors. Cholinergic drugs activate the release of histamine in many secretory processes in vivo; in vitro, acetylcholine is one of the most powerful histamine releasers in isolated purified rat mast cells. The release of histamine evoked by acetylcholine in rat mast cells is a calcium-requiring, temperature-dependent exocytosis. The physiological relationship of the sympathetic, parasympathetic and histamine-containing cells are discussed.


[Induction of immune tolerance to protein antigens in mice by 6-mercaptopurine (author's transl)]. The tolerance induction in mice to human serum albumin (HSA) and bovine gamma globulin (BGG) by combined injections of antigen and 6-mercaptopurine is studied. After pretreatment with antigen and mercaptopurine specific unresponsiveness or hyporesponsiveness are observed both in inbred (CBA) and outbred mice. Under the experimental protocol HSA is more tolerogenic than BGG. In CBA-mice tolerance to BGG was only found on the level of IgG-antibodies. The factors which influence the development of a drug-induced immunological unresponsiveness (mice strain, quality of antigen and antigen dosage) and the role of test system are discussed.


Early quantification of experimental myocardial infarction with technetium-99m glucoheptonate: scintigraphic and anatomic studies. Recent advances in understanding of the pathophysiology of myocardial necrosis indicate the need for a noninvasive method that will allow detection and quantification of infarcts in the first few hours after the onset of infarction. Myocardial infarct scintigraphy using technetium-99m glucoheptonate is capable of detecting infarction in dogs and man within 4 to 6 hours of onset. Studies were performed in 45 dogs with acute myocardial infarction: 28 with with an anterior infarct, 5 with an inferior infarct, 6 with an anterior infarct studied after infusion of mannitol and 6 with ligation of the left anterior descending coronary coronary artery and reperfusion of the ischemic area. The dogs were given 20 m Ci of technetium-99m glucoheptonate 1 hour after coronary occlusion, subjected to imaging 5 to 9 hours later and then killed. The experiments revealed that (1) scintigraphic infarct size correlated with infarct weight for anterior (r = 0.85) and inferior (r = 0.88) infarcts; (2) technetium-99m glucoheptonate also concentrated in a rim of myocardium around the infarct that probably represented the ischemic zone; and (3) technetium-99m glucoheptonate uptake by infarcted myocardium could be greatly increased with mannitol and reperfusion.


Precordial mechanical stimulation for exposing electrical instability in the ischemic heart. Sequenital mechanical pulsing of the chest wall with three stimuli failed to induce arrhythmias in normal dogs. After coronary arterial occlusion, this technique evoked in 11 of 12 animals repetitive ventricular tachycardia in 2. These responses corresponded closely to those elicited by electrical testing. In four conscious animals after recovery from myocardial infarction, precordial pulsing induced repetitive ventricular arrhythmias. The type of arrhythmia produced depended on the degree of prematurity of the third pulse in the sequence. The use of precordial mechanical stimulation can perhaps be modified and adapted as a method of detecting persons at high risk for sudden cardiac death.


Hyperglycinuria and hyperglycinemia in two siblings with mild developmental delays. Two preschool-age siblings with similar histories of encephalopathy were examined for developmental retardation and found to have elevated levels of urinary and blood glycine. Their inability to convert glycine into serine in the absence of elevated blood and urinary ketone levels was suggestive of a defect in the glycine-cleavage enzyme system (or serine hydroxymethyl transferase). These patients differ significantly from the majority of reported cases of nonketotic hyperglycinemia in that they did not manifest life-threatening neonatal illness, severe mental retardation, or neurological deficits. However, during an oral glycine load, alterations in the electroencephalographic pattern occurred that suggested a relationship between elevated blood glycine levels and pathological involvement of the central nervous system. The ratio of CSF-blood glycine was found to be in the range expected for nonketotic hyperglycinemia.


Value of B-scan ultrasonography in the diagnosis of liver cancer. Accuracy compared to scintigraphy and angiography. Seventy-one patients with liver cancer were examined by B-scan ultrasonography. The presence of liver cancer was assumed through the irregularity and increased intensity of echos. The accuracy of ultrasonography in the diagnosis of liver cancer was 72%, while the diagnostic accuracy of scintigraphy was 85% and angiography 93%. No obvious correlation could be demonstrated between the ultrasonographic patterns and serum alpha-fetoprotein (AFP) levels. Ultrasonography is a useful method of detecting liver cancer.


Meconium aspiration syndrome. Neonatal and follow-up study. One year's experience with MAS in a neonatal intensive-care unit is analyzed with follow-up information. Seventeen patients or 3.7% of all admissions had MAS. Four patients (23.5%) died of acute respiratory failure. Two patients with MAS and persistence of the fetal circulation required cardiac catheterization to exclude cyanotic congenital heart disease. No survivors had persistent chronic lung disease. However, two of three patients with MAS and seizures had significant psychomotor retardation at follow-up examination.


The chemical mediation of delayed hypersensitivity skin reaction. II. Characterization of a macrophage-chemotactic factor from bovine gamma-globulin-induced skin reaction in guinea pigs. Macrophage-chemotactic factors were extracted from delayed hypersensitivity skin lesions induced by bovine gamma-globulin in guinea pigs. The most active factor, MCFS--1, was highly purified and found to be a heat-labile protein with a molecular weight of 150,000 and to possess in vivo as well as in vitro activity. This factor was homogeneous during polyacrylamide gel electrophoresis, and the chemotactic activity was associated exclusively with this band. Further characterization revealed that its isoelectric point was 6.7 to 6.9 and made a single arc in the beta-globulin region with rabbit antiserums against guinea pig serum on immunoelectrophoresis. This factor seemed to be antigenically different from immunoglobulin G (IgG) by immunodiffusion and immunoadsorption. On the other hand, the chemotactic activity of MCFS-2 was adsorbed by neither anti-IgG nor anti MCFS-1 and that of euglobulin fraction was partially adsorbed by anti-IgG. These indicate the presence of at least three types of antigenically different chemotactic factors for macrophages in the extracts of delayed hypersensitivity skin lesions.


Evidence of complement catabolism in acute pancreatitis. Active proteolytic enzymes are released into the gland parenchyma and surrounding tissues during episodes of acute pancreatitis. Since complement components are potential substrates for active proteases and may be the source of biologically active peptides capable of mediating tissue injury, we have examined sera obtained from 12 patients during 13 episodes of acute pancreatitis for evidence of complement catabolism. In 8 of 13 acute phase sera, there were decreased levels of CH50, C3, C4, or some combination thereof as well as degradation products of C3 (revealed by crossed immunoelectrophoresis). In convalescent sera, levels of complement components were normal or elevated. Measurements of alpha1-antitrypsin, alpha2-macroglobulin, and trypsin inhibitory capacity failed to reveal evidence of protease-antiprotease imbalance. These findings provide evidence of complement catabolism in acute pancreatitis and suggest the possibility that activated complement components may play a role in the pathogenesis of some systemic pathologic changes which occur in this disease.


Adverse reactions to practolol: some observations on the possible relevence to immune mechanisms. HLA antigen frequencies were determined in patients who had suffered adverse reaction to the beta-adrenergic blocking agent, practolol. No statistically significant differences were observed between these patients and control groups. The latter were selected to include two separate groups, normal random healthy population controls, and controls who had taken practolol with no apparent adverse effects. Patients suffering from the very severe form of reaction, sclerosing peritonitis, were analysed separately from those with other lesion e.g. ocular symptoms, but did not show any significant differences. Altered HLA antigen frequencies were observed for those control patients whose primary diagnosis was hypertension but this was considered to be due to selection bias.


The anti-anaphylactic action of tiaramide hydrochloride. Tiaramide hydrochloride (THC) is a new basic, non-steroidal, anti-flammatory drug. Its anti-anaphylactic action has been investigated using rat mast cells. It was found that THC exerts a strong inhibitory action on antigen-induced and compound 48/80-induced histamine release from rat peritoneal mast cells in a fluorometric assay. Compound 48/80-induced vasodilatation in rat skin is inhibited by prior intradermal injection of THC, as measured by blueing of skin due to intravascular Evans blue dye. THC also inhibits radio-labeled serotonin release from compound 48/80-challenged rat mast cells. In these experimental systems a similar action was exerted by disodium cromoglycate, but higher drug concentrations were needed. Further studies are needed to determine the exact mode of action of this drug and its eventual clinical use in the field of allergic diseases.


Electron microscopic toluidine blue staining of the erythrocyte membrane. Incubation in ferricyanide medium of toluidine blue stained erythrocytes produces opaque precipitates lining either aspect of the cell membrane. In addition, granular and needle-shaped precipitates occupy an intra- or extracellular position. Staining of the outer aspect of the membrane may reflect toluidine blue binding of the erythrocyte glycocalyx. Precipitates at the inner leaflet resemble Ca2+ affinity sites which were considered phosphorylated spectrins. Comparison with the light microscopic topo-optical toluidine blue reaction proved most of the electron dense precitates noncontributive to anisotropic staining.


Improved homogenization techniques for sputum cytology counts. Liquefaction of sputum with dithiothreitol induces regular distribution of cells and facilitates total and differential counting without affecting morphology or staining characteristics. The reagent is cheap and stable. The process is predictable, reasonably quick and obviates the need for examination of multiple preparations, otherwise mandatory in quantitative studies of inflammatory conditions of the lower respiratory tract.


Viral infections and IgE levels.

Viral infections and IgE levels. Six non-atopic patients with respiratory infections to a variety of viruses demonstrated a consistent drop in IgE levels (35% to 87%) in the convalescent phase compared to the acute phase of infection, suggesting that the viral agent affects T lymphocytes to suppress and hence B lymphocytes to secrete IgE immunoglobulin.


[Hereditary bisalbuminemia. Study of a new familial case in France (author's transl)]. A case of bisalbuminemia of slow type was discovered in a 41 year old woman with obesity, diabetes mellitus and hypertension. This abnormality was discovered in six other members of the family and was thus hereditary. After a description of the laboratory tests used, the various forms of bisalbuminemia are described together with the circumstances of onset of the acquired forms, the biochemical and metabolic characteristics of the hereditary forms and their mode of transmission. Bisalbumin is present in all races. The mother of our case was of Italian origin, which permitted us to classify this case with others of Italian origin.


Precipitation of fibrin monomers and fibrin degradation products by ristocetin. Ristocetin, at relatively low concentrations (1.0 mg/ml-1.5 mg/ml), can selectively precipitate fibrin monomers and fibrin degradation products (fdp) from plasma without effect on fibrinogen or fibrinogen degradation products (FDP). 125I-labeled fibrin monomers and fibrin degradation products were precipitated by ristocetin when their plasma concentrations were greater than 0.25 microgram/ml and 50 microgram/ml, respectively. In order to obtain a visible precipitated, 2 microgram/ml of fibrin monomers of 50 to 100 microgram/ml of fibrin degradation products were necessary. These effects were optimally observed under the following conditions: (1) temperature, 20 C to 37 C; (2) pH, 7.0 to 7.5; and (3) incubation time, 15 to 60 minutes. Late-fibrin degradation products are approximately eight times less sensitive to ristocetin-induced precipitation than early-fibrin degradation products. Plasma medium is essential for the differentiation of fibrin monomers and fibrin degradation products from fibrinogen and fibrinogen degradation products by ristocetin. These results suggest that the specific detection of fibrin monomers and fibrin degradation products in plasma may be easily performed by ristocetin.


[Discussion of the interest of estimation of hydroxyprolinuria in chronic alcoholism (author's transl)]. 24 hour hydroxyprolinuria was measured in 50 chronic alcoholics divided up into those with simple alcoholism and those complicated by cirrhosis. All the patients had a significant increase in hydroxyprolinuria. Without there being any difference between cirrhotics and alcoholics without cirrhosis. Comparison between hydroxyprolinuria and the tests usually used to follow the course of hepatic involvement in chronic alcoholism: IgA, transferrin, electrophoresis of serum proteins, alkaline phosphatase, show that there is no correlation between hydroxyprolinuria and the diagnostic or prognostic tests of an alcoholic liver among which the variable IgA is the most significant. On the other hand, hydroxyprolinuria has a linear correlation with the calciuria, which suggests that the increase in hydroxyprolinuria in chronic alcoholics is more related to changes in the collagen of bone tissue than with those in liver tissue.


[Effects of TSH on thyroid ribonucleic acids (author's transl)]. Bovine thyroid slices were incubated with TSH (20 mU/ml) in the presence of 0.04 microgram/ml actinomycin D. The incorporation of 3H Adenosine or 3H Uridine in the microsomal RNA fraction was studied. TSH enhanced the labeling of this RNA. After gel electrophoresis in 100% formamide, the distribution of the radioactivity showed a relatively larger incorporation of the precursors in the region corresponding to heavy molecular weight RNA (3 X 10(6) daltons). These data suggest that TSH could exert a specific effect on transcription in the thyroid gland.


[Search for new antitumor antibiotics in the bleomycin group]. The culture of Penicillium avellaneum 444 and its bleomycin resistant variant may serve a rather valuable specific test for detecting organisms producing new antitumor antibiotics of the bleomycin group. The organisms producing antitumor antibiotics of the group of anthracyclines (rubomycin and carminomycin), actinomycins and other chemical groups do not inhibit the growth of these test-organisms. Such tests are also resistant to the effect of antibacterial antibiotics.


Hyperpigmentation after bleomycin therapy. Ultrastructural study. Pigmentation in a Causasian male, resulting from bleomycin therapy for Hodgkin's disease, has been studied ultrastructurally. The melanocytes, though present in normal numbers, showed several abnormalities; the endoplasmic reticulum and the Golgi apparatus were were well developed and the mitochondria were enlarged. Lipid inclusions in the endoplasmic reticulum and numerous autophagocytic vacuoles, some containing lipids were observed. Transfer of melanosomes to keratinocytes appeared to be increased. The melanosomes, which measured less than 0.55 mu were dispersed in the cytoplasm and did not form complexes, as has been observed with nitrogen mustard. The increase of melanocytic activity and the disturbance of melanosome transfer are discussed.


Histochemistry of the intercellular substance of the normal and psoriatic human epidermis. The intercellular substance of skin samples obtained from normal subjects and from psoriatic patients has been studied with histochemical methods for carbohydrate containing substances and checked with enzymatic extractions. The surface coat which makes up most of the intercellular substance was stained with colloidal iron and with Alcian Blue solutions containing up to 0.20 M magnesium chloride; the stainings were heavily affected by the previous treatment of the sections with testicular hyaluronidase, but not with neuraminidase. The staining of the intercellular substance with Alcian Blue solutions containing up to 0.20 M magnesium chloride and the action of the hyaluronidase gives strength to the hypothesis that hyaluronic acid is contained in the substance. In the skin of psoriatic patients intercellular spaces wider than in normal skin and a reduced surface coat, particularly in the higher layers, has been observed.


Heterogeneous keratohyalin formation in warts. The heterogenecity of keratohyalin (KH) has been demonstrated in rats, then in human warts where similar morphological features have been found and among them, dense homogeneous ovoïd single granules (SG) and composite granules (CG) apparently made up of single granules "coated" with a matrix. This work compares the ultrastructure of the KH of the tongue of newborn rats with that of common warts with and without post-fixation by OsO4, after oxydation by H2O2 and after pepsin treatment. The osmiophily of the SG is confirmed as well as the absence of osmiophily of the matrix of the CG. In man, however, the SG are resistant to oxydation by H2O2 and the CG matrix is oxydation sensitive whereas the opposite is observed in the case of rats. These differences show that it is impossible to deduce the composition of the KH in human warts from that of the rat despite their close ultrastructural resemblance but that important modification of the keratogenesis and KH formation are induced in the cells parasited by the virus of common warts.


Particles from mouse melanoma B16 containing reverse transcriptase and 70S RNA related to human melanoma cytoplasmic RNA. The mouse melanoma B16 contains particles encapsulating high molecular weight RNA of 60--70S size associated with a reverse transcriptase. The [3H]DNA synthesized by these particles possesses homology with RNA isolated from a hamster melanoma and from three human malignant melanomas.


Type C oncornavirus isolation studies in systemic lupus erythematosus. II. Attempted detection by viral RNA-dependent DNA polymerase assay. Isolation of type C oncornavirus was attempted from 20 tissues and cell cultures of patients with systemic lupus erythematosus. Chemical inducers, cocultivation and fusion with cells from multiple other species, prolonged subculturing, and the RNA-dependent DNA polymerase assay for virus detection were used. A type C virus was isolated, but was shown to be the endogenous rat virus. Thus the methods, although generally appropriate, were not specifically permissive for  replication of a human type C virus. This agrees with the failure of other investigators to isolate a virus of undisputed human origin. Combining available evidence, a fundamental role for type C viruses in lupus erythematosus remains an attractive hypothesis.


Type C oncornavirus isolation studies in systemic lupus erythematosus. III. Isolation of a putative retravirus by triple cell fusion. A putative retravirus was isolated from a cell culture derived by fusion of mink and dog cell lines with cultured placental cells from a patient with systemic lupus erythematosus. The virus was detected by reverse transcriptase assay of supernatant medium after prolonged subculturing. Its characterisation, including species of origin, is in progress, but it is probably a new type C virus. Its role, if any, in lupus erythematosus in unknown.


Plasma and urinary levels of beta2 microglobulin in rheumatoid arthritis. Plasma and urinary levels of beta2 microglobulin have been investigated in 21 patients suffering from rheumatoid arthritis (RA). Despite a normal renal glomerular function in all patients 50% of them had supranormal plasma beta2 microglobulin levels and 30% had a higher than normal urinary output of beta2 microglobulin generally related to the high plasma level. Plasma beta2 microglobulin levels paralleled closely the lymphocytosis and the 'joint count' both indexes of the severity of the disease. beta2 Microglobulin was normally secreted by the lymphoid tissue and it is suggested that it reflects the increase of the total mass and/or membrane turnover of the lymphoid tissue in RA. beta2 Microglobulin may be considered as a good parameter of the degree of severity of the joint and extra-articular involvement as well as a useful tool for the evaluation of drug efficacy in rheumatoid arthritis.


Major hepatic resection for neoplasia: personal experience in 108 patients. One hundred eight patients have undergone major hepatic resection by the senior author during the eight year period April 1970 to April 1978. Primary liver cancer was present in 36; metastatic colorectal cancer in 25, miscellaneous metastatic cancers in 15, hepatoblastoma in 5, gallbladder cancer in 4, and bile duct cancer in 3. Benign tumors, principally giant hemangioma, were resected in 20 additional patients. The 30 day operative mortality rate was 9% overall. Prior to 1975, 41 of the resections were done using the vascular isolation perfusion technique. The operative mortality rate of 17% for this technique is a reflection of early experience and the advanced stage of disease of many patients. The operative mortality for the standard resection has been only 4%. Subphrenic abscess has developed in only 13% of patients during the past three years. Postoperative hospitalization has been shortened, being a median of 13 days. The resectability rate for malignant disease was 33%. Forty-six percent of the resections were performed with curative intent. Fifty-four per cent were palliative, performed in individuals with regional spread or distant metastasis. After curative surgery, three year survival was 88% for individuals with primary liver cancer and 72% with metastatic colorectal cancer. After palliative resection, the rates were 31 and 0%, respectively. The three year survival rate is 46% overall, being 81% for the curative resection group and 18% for the palliative group. Tumor markers proved useful in monitoring patients after hepatic resection.


Histamine release in rats after administration of five neuromuscular blocking agents. The effect of five neuromuscular blocking agents on histamine levels of various tissues was studied. Blood and tissue samples were taken from male rats previously treated intravenously with neuromuscular blocking agents. d-Tubocurarine proved to be the most potent histamine liberator. Alcuronium, gallamine and succinylcholine were only moderate histamine liberators, whereas pancuronium released practically no histamine. The results  from the individual tissues suggest that the possible sources of increased blood histamine concentrations are tongue and skin with high histamine content. No release of histamine was found from the lung.


Functional role of the cerebral nystagmogenic area in the cat. A nystagmogenic area has been identified in the occipital lobe of the cerebral cortex of the cat. The electrical stimulation of this area induces a horizontal eye nystagmus directed toward the opposite side. The chronic lesion of both cerebral nystagmogenic areas provokes dramatic modifications of the eye nystagmus elicited by optokinetic stimulations. In particular, it has been observed that following the ablation of the two nystagmogenic areas the optokinetic eye nystagmus is abolished being replaced by pendular oscillations of the eyes with intercalated eye jerks in the same direction of the normal optokinetic eye nystagmus.


[Statistical investigation into the methodology at various centres of the microbiological diagnosis of the cerebro-spinal fluid (author's transl)]. To survey statistically the bacteriological methods used in the culture of the cerebro-spinal fluid in Italian hospitals, we sent a questionnaire nearly 400 laboratories in various regional, provincial and zonal hospitals. We received 36 replies, which, although not numerous, have furnished the data for present paper.


Spectra of glutamate dehydrogenase with diethylstilbestrol. Glutamate dehydrogenase displays hyperchromicity at 256 nm and at 276 nm upon binding of diethylstilbestrol. Increase in absorbancy is linear at both regions up to 250 micrometer DES, and becomes parabolic at higher concentration of DES. ADP in the presence of DES causes decrease in absorbancy at 256 nm; absorbancy at 276 nm increased by DES is not affected by ADP. DES prevents spectral effects produced by GTP (decrease in absorbancy at 254 nm and at 276 nm). ADP still decreases absorbancy at 254 nm, leaving the 276 nm region unchanged. ADP enhances spectral effects produced by GTP. GTP, however, prevents changes produced by ADP.


[Isolation and characterization of beef thyroid giant RNA]. Total HMW-RNAs were prepared by three different methods (method with phenol, method with NaClO4, method without phenol using Ultrogel AcA 22 filtration). Giant RNAs were obtained in the void volume by filtration on Sepharose 2B. The giant RNAs/total HMW-RNA ratio is higher (6.77%) with the gel filtration method than with phenol or NaClO4 methods (1.41% and 1.00% respectively). The nucleotide composition of these RNAs is DNA-like and the sedimentation constants are approximately 70-100 S.


[Plasma proteins in young and adult Spermestes c. cucculatus (Swainson) (Aves - Ploceidae - Estrildinae)]. The blood plasma of Spermestes c. cucullatus (Swainson) analysed electrophoretically on agar shows seven fractions. Immunoelectrophoresis against an antispermestes rabbit serum reveals 16 fractions. Individual variation of the plasma protein fractions is very low, as is also the case for the mobility of the fractions. With age, the alpha-globulins disappear gradually. In the newly hatched bird, the protein variations are more pronounced than in adults. Most important are the lower relative content of albumin and a corresponding relatively higher content of beta- and gamma-globulins. There seems to exist a slight sexual dimorphism in albumin level, which is higher in males than in females. During the reproduction period, both sexes show a fall of the relative concentration of albumin. Injections of gonadotropine hormone produce an increase of the plasma-proteins level and a marked decrease of the relative concentration of albumin. The overall figure is comparable with that of birds in natural breeding condition.


Interaction between vagal and chemoreceptors afferents in ventilatory response to transient hypercapnia (awake rabbits). The ventilatory response to a transient hypercapnia was studied in four awake rabbits maintained in a volume displacement plethysmograph : the increase in inspiratory volume (VI) was associated or not with an increase in inspiratory and expiratory durations (TI and TE). These ventilatory variations were consistent with the activation of the peripheral chemoreceptors by carbon dioxide (short latency of the initial response). After vagal blockade by local anaesthesia, relative ventilatory variations were not significantly different from those previously measured. Central activity seems an important factor reducing inhibitory vagal input and favouring peripheral chemoreceptor afferents.


Post-natal development of brown adipose tissue in the rat bred at 23 degrees C or 28 degrees C. In view to study the effects of thermal environment on the development and the thermogenic activity of interscapular brown adipose tissue (BAT), young rats born at 23 degrees C or 28 degrees C were sacrificed at 1, 3, 7, 11, 14 or 21 days after birth. The rate of increase in animal weight was quite the same at both temperatures up to the 14th day. The development of BAT and its contents in lipids, in water and in noradrenaline indicate that the energetic activity of the tissue is greatly stimulated in rats kept at 23 degrees C up to the 11th day. It is concluded that in rats bred in the habitual thermal conditions (23 degrees C), the occurrence of non shivering thermogenesis (NST) is important during the period of ten days after birth; in the following period NST could be progressively replaced by other thermoregulatory processes.


Body temperature and oxygen uptake in the kinkajou (Potos flavus, Schreber), a nocturnal tropical carnivore. Two kinkajous (Potos flavus, Procyonidae) showed marked nycthemeral variations in their rectal temperature. The mean Tr at night was 38.1 +/- 0.4 degrees C SD and 36.0 +/- 0.6 degrees C SD while resting during the day. Body temperature and O2-consumption were measured at ambient temperatures from 5-35 degrees C. With one exception at 35 degrees C, hypo- or hyperthermia was never observed. At air temperatures above 30 degrees C the bears reacted with behavioural responses. O2-consumption was minimal at Ta's from 23-30 degrees C. The mean basal metabolic rate was 0.316 ml O2 g-1 h-1 which is only 65% of the expected value according to the Kleiber formula. Below 23 degrees C heat production followed the equation : y (ml O2 g-1 h-1) = 0.727--0.018 Ta. The minimal thermal conductance was 90% of the predicted value according to the formula : C (ml O2 g-1 h-1 degrees C-1) = 1.02 W-0.505 (HERREID & KESSEL, 1967). Kinkajous are another distinct exception to the mouse to elephant curve.


White platelet arterial thrombus formation is inhibited by indomethacin in vivo. White platelet thrombi induced after electrical current application followed by ADP superfusion can be inhibited by indomethacin. These findings suggest that the synthesis of PGG2 and PGH2 is inhibited, which results in less local platelet aggregating activity.


Osmotic thirst suppression elicited by electrical stimulation of the basal forebrain in the dog. Reactivity of the thirst mechanism to osmotic stimuli was measured in conscious dogs chronically implanted with electrodes in the basal forebrain. It was found that the thirst threshold to the osmotic stimulus increases markedly during electrical stimulation of the preoptic area, septum, nucleus accumbens septi, and to smaller degree during stimulation of the nucleus caudatus. The possibility of existence of some inhibitory components in the neural system controlling thirst in the dog is suggested.


Saralasin and SQ 20881 : their effects on central nervous system norepinephrine. The effects of the infusion of Saralasin and SQ 20881, two drugs that inhibit the renin-angiotensin system, on the norepinephrine (NE) concentration in hypothalamus and medulla oblongata were studied in male Wistar rats. NE content increased in hypothalamus in response to both drugs, without changes in medulla oblongata catecholamine concentration. These results showed that the NE concentration of certain areas of the central nervous system can be modified, in a short time, by the inhibition of the renin-angiotensin system. Results observed after the infusion of Saralasin could indicate that the receptors, on which the angiotensin acts to produce this alteration, are similar to those of the peripheral blood vessels.


Comparison of long term lipogenic effects of two different medium-chain triglycerides (tri C8: O and tri C12 : O) in the growing rat. During the growth (35 g-340 g), and as compared to results obtained with a lipid-free diet or a diet containing long-chain fatty acids, high levels of Tri C8 : O or Tri C12 : O did not change the quantitative aspects of proteinogenesis and lipogenesis balances. The incorporation of Tri C8 : O into the diet did not change the fatty acid composition of body lipid stores while the incorporation of Tri C12 : O induced a lipogenesis characterized by the disappearance of about 50% of the n-9 and n-7 unsaturated fatty acids, the emergence of an equivalent amount of saturated fatty acids in C12 and C14, and the decrease of hexadecanoic or palmitic acid concentration. Titers of saturated fatty acids with a melting point higher than 40 degrees C increased from 34% to 64%. Results suggested an efficient inhibition of fatty acid biosynthesis de novo by C12 : O, associated with an impossibility for microsomal enzymes to assume the elongation of a sufficient amount of C12 : O to maintain C16 : O concentration and to furnish an important amount of substrate (C18 : O) to delta-9-stearoyl coenzyme A desaturase for oleic acid synthesis. Introducing dodecanoic acid into the diet of growing animals appears to be the most efficient method for increasing the degree of saturation of body lipids without changing the concentrations of long-chain saturated fatty acids.


Subcellular structure of bovine thyroid gland. VII. A study on the distribution of bovine thyroid plasma membranes by density gradient centrifugation in zonal rotors. In order to obtain plasma membrane-rich fractions two methods were tried. Approach A was based on differential pelleting followed by discontinous gradient centrifugation in a B-XIV zonal rotor. In approach B homogeneization was performed in buffered water (NaHCO3, pH 7.4). The 73 300 X g pellet from this homogenate was subjected to buoyant density equilibrium in a HS zonal rotor (continuous sucrose gradient). Using approach A, the highest relative specific activity for plasma membrane markers was found at the 30-37% sucrose interphase. However, an increase for glucose 6-phosphatase (endoplasmic reticulum marker) was also found at that interphase. Using approach B marker profiles different from approach A were found. Approach B results in a subdivision of membrane material in four distinct regions. These regions do not contain completely pure membrane species, although region I seems to be essentially derived from plasma membranes. It is also concluded from approach A that plasma membranes from bovine thyroid tissue are heterogeneous.


Does the nucleus raphes participate in the regulation of resting and stress-induced hypothalamic-pituitary-adrenocortical activity in the pigeon? Extensive multiple electrolytic lesions were placed into the nucleus raphes of the brain stem in the pigeon. Diurnal pituitary-adrenocortical rhythmicity appeared not to be altered and basal plasma corticosterone level remained quite normal in raphe lesioned birds. Electrical stimulations through permanently implanted electrode were delivered in various central nervous structures in unanaesthetized, freely moving pigeons. Stimulations of nucleus raphes and of various parts of formatio reticularis led to a significant rise in plasma corticosterone within 16 to 19 min after the beginning of the stimulating session. Then, plasma B came again to initial level within 15 minutes. Stimulations of the corticotropic area of the hypothalamus (n. posterior medialis hypothalami) and of archistriatum dorsalis induced an early plasma corticosterone increase occurring immediately after the stimulating burst (10 min). Stimulating the n. septum medialis also had an immediate, but reverse (decrease) effect on plasma corticosterone level. Stress-induced pituitary-adrenal cortical activation exhibited a temporal pattern quite similar to that observed after brain stem (n. raphes or formatio reticularis) stimulation. It is suggested that these various limbic and brain stem areas might be involved in some "limbic system-midbrain circuit" with two components : The forebrain component might be involved in the regulation and diurnal modulation of basal hypothalamic-pituitary-adrenocortical function, the brain-stem component interferring with stress-induced responses.


Effects of ammonia on monoamine oxidase and enzymes of GABA metabolism in mouse brain. Acute and chronic ammonia toxicity was produced in the mice by intraperitoneal injection of ammonium chloride (200 mg/kg) and by exposure of mice to ammonia vapours (5% v/v) continuously for 2 days and 5 days respectively. The ammonia content was elevated in the cerebellum, cerebral cortex and brain stem and in liver. In acute ammonia intoxication there was a decrease in the monoamine oxidase (MAO) activity in all the three regions of brain. In chronic ammonia toxicity (2 days of exposure) a significant increase in the activity of MAO was observed in the cerebral cortex while in cerebellum and brain stem there was a significant decrease. In cerebral cortex and cerebellum there was a rise in the activity of MAO as a result of exposure to ammonia vapours for 5 days. A significant decrease was observed in the activity of glutamate decarboxylase (GAD) in all the three regions of the brain both in acute and chronic ammonia toxicity (2 days). There was a decrease in the activity of this enzyme only in the cerebral cortex in the animals exposed to ammonia for 5 days. The activity of GABA-aminotransferase (GABA-T) showed a significant rise in cerebellum and a fall in the brain stem in acute ammonia toxicity. In chronic ammonia toxicity GABA-T showed a rise in all the three regions of brain. Chronic ammonia toxicity produced a significant decrease in the content of glutamate in all the three regions without a significant change in the content of aspartate. GABA and glutamine. The content of alanine increased in all the three regions of brain under these experimental conditions. The ratio of glutamate + aspartate/GABA and glutamate/glutamine showed a decrease in all the three regions as a result of ammonia toxicity.


Spectrum analysis of transient phenomena of the left ventricular pressure. The application of "real time" spectrum analysis to left ventricular pressure during transient phenomena is described. Transient phenomena generated by the injection of drugs (norepinephrine-isoproterenol), anoxia and occlusion of aorta and carotids show sudden changes in the frequency of heart contraction. Propranolol stabilizes the heart rate in similar circumstances.


Effect of increasing duration of denervation on the rate of entry of inorganic phosphate into rat gastrocnemius muscle. The increased inorganic phosphate flow, characteristic of denervated gastrocnemius muscle, is shown to have no direct relation with either the loss of muscle mass or with the concentrations of the acid-soluble phosphate fractions. It is shown to increase hyperbolically with the time elapsed since the nerve section. The asymptotic value reached after thirty days suggests the presence of a saturable mechanism.


Decoupling of the excitation-contraction link by glycerol procedure in volume-clamped muscle fibers. The role of "osmotic shock" and vesiculation in the mechanism of disconnection of the T-system tubules by the glycerol procedure was studied in volume-clamped muscle fibres of the crayfish. The transient dilatation of fibres during the wash-out of glycerol was prevented by application of hypertonic sucrose solutions of decreasing osmolarity to hold the fibre volume constant. Under these conditions the fibres were decoupled only partially; the twitch tension was decreased to a steady level of about 40% of the control tension. The decay in tension developed without the transient potentiation observed in fibres allowed to dilate. The decoupling could not be reversed by reapplication of glycerol saline. The structure of volume-clamped fibres differs from the dilated ones in two respects; the vesicles appear smaller and are absent in continuous layers (about 4 micrometer in width) just under the surface and the cleft membranes. Electron microscopy of these regions has revealed the presence of normal T-system tubules communicating with the fibre exterior. The results provide evidence for the secondary role of the osmotic factor and the essential role of the vesiculation in the induction of the detubulation by glycerol procedure.


[Cytological classification of lung carcinomata (author's transl)]. By comparing the cytological examinations and the final histological classification, the author discusses the possibilities of cytological type judgement. Using a staining method invented by himself, he was able to achieve a conformity of the cytological and of the final histological classification in 80 per cent of all cases. Abstaining from the differences in the judgement of maturity, the results of both methods were in conformity even in 89 per cent of all cases. As compared to the biopsy during bronchoscopy the cytological type classification was more exact. The difference had, however, proved to be insignificant (p greater than 0,05). The advantage of the author's own staining method is particularly obvious at the detection of mucus-forming carcinomata. In this way, two out of three mixed forms of epidermoid carcinomata and of adenocarcinomata could be correctly diagnosed.


Pituitary adenomas in Cushing's disease. A histologic, ultrastructural, and immunocytochemical study. Twenty-two pituitary adenomas in Cushing's disease were removed by transsphenoidal surgery. In six patients the pituitary tumor had become manifest following adrenalectomy (Nelson's syndrome). Sixteen tumors were microadenomas measuring from 2 to 9 mm, while two were diffuse invasive adenomas verified at postmortem examination. Light microscopy showed that the tumors were made of basophillic cells containing PAS-positive granules that stained blue with Herlant tetrachrome and lead hematoxylin. Immunocytochemical studies showed that the granules stained positively with antiserum to adrenocorticotrophic hormone (ACTH) or to beta-lipotropic hormone (beta-LPH) and the peroxidase-antiperoxidase complex. Electron microscopic study of the tumor cells showed ACTH and beta-LPH containing granules varying in size, shape, and amount. Perinuclear bundles of 70 A microfilaments constituted a specific ultrastructural finding.


[Rapid method of combined staining of myelinated fibers and brain cells]. A modification of the method of combined staining of myelin fibers and nerve tissue cells (Klüver and Barrera) is offered. Deparaffinised sections are stained for 1--2 hours in 0.01% acid alcohol solution of luxol blue fast, differentiated in 0.1% sodium tetraborate solution, and poststained with cresyl violet fast according to Nissl. The proposed method considerably shortens the time of staining and simplifies the process of differentiation of stained myelin fibers. The prescription for staining of the brain tissue sections silver-impregnated by the method of Holmes with luxol blue fast and cresyl violet is presented.


[Morphological variants of alcoholic hyalin and possible ways of its evolution]. Possible ways of alcohol hyalin evolution were studied by repeated electron microscopic examinations of the livers of 2 patients with acute alcoholic hepatitis Four types of ultrastructure of alcoholic hyalin were found: parallely oriented fibrillae, randomly oriented fibrillae, fine granular and large granular (spotlike) substance. Examinations of the material from repeated biopsies showed fibrillar hyalin to be "young" and to turn into "old" hyalin of granular structure. The evolution of alcoholic hyalin from fibrillar to granular is accompanied by hepatocyte necrosis and leukotaxic effect.


[Study of the specific antigen of amyloid fibrils in secondary amyloidosis]. Amyloid fibrillae yere isolated from the spleen of a patient with secondary amyloidosis and their antigenic specificity was demonstrated. Pure antibody to the specific amyloid antigen was obtained. The possibility of mmunomorphological detecton of amyloid in tissues was proven. Amyloid protein was found to be absent in normal organs of adults and embryos.


[Method of preparation and staining of microscopic sections in emergency biopsy]. To obtain a distinct and sufficiently standard staining of sections in urgent biopsy Harris hematoxylin should be used the preparation of which is based on oxidation of aluminous hematoxylin by mercuric oxide. This solution stains nuclei of the preparations quite rapidly (within 1/2-1 min) and very electively. The use of a fan for drying of sections on slides and other devices described by the author shorten the time of express biopsy preparation to 5-7 minutes.


[Method of counterstaining preparations for immunofluorescent studies of the pituitary]. To elucidate nonfluorescent structural elements of the hypophyseal parenchyma for immunofluorescent investigations, properties of some dyes most commonly applied for hypophysis staining have been studied. Such dyes as paraldehide-fuchsin, light green, orange G, chromotrop 2R, hematoxylin, eosin, fuchsin, azocarmin possess their own intensive luminescence and block immunofluorescence completely. Some other dyes (trypan blue, bromthymol blue, aniline blue, malachite green, methyl green) though not blocking immunofluorescence, they do not reveal hypophyseal cellular elements distinctly enough. Good results have been obtained with 0.3% water solution of toluidine blue, 0.5% solution of methylene light blue, methylene blue, as well as with Gram--Weigert's staining and with gallocyanin after Einarson. For special staining of corticotropocytes, the authors recommend 0.1% solution of bromphenol blue in barate buffer, pH 8.2.


Drusen in the optic nerve head. Verification by computerized tomography. Five patients with a clinical diagnosis of buried or exposed drusen of the optic nerve head were examined by computerized tomography (CT). The relative x-ray absorption within their nerve heads was significantly larger than in controls, reflecting the high calcium content of drusen. Computerized tomography, and particularly high-definition CT, therefore merits consideration in the investigation of disc swelling.


The distribution of Feulgen stained nuclei in the periphery of human head and neck tumours--cytophotometric investigations. With single cell cytophotometry we investigated the distribution of Feulgen stained cell nuclei of ENT tumours. In the periphery of exophytically growing tumours these cells seem to be distributed homogeneously. Because of the difficulties in determination of the DNA synthesizing cells Feulgen cytophotometry should be completed by other cell kinetic methods e.g. pulse cytophotometry and autoradiography.


Physical and chemical properties of human plasma alpha2-macroglobulin. Alpha2-M (alpha2-macroglobulin) was purified from human plasma by two different procedures. As well as having no detectable impurities by the usual criteria for testing the homogeneity of protein preparations, these alpha2M preparations showed a single component, after reduction in urea, of 185000 daltons by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. The molecular weight of the alpha2M was found to be 718000 by sedimentation equilibrium experiments using the gravimetrically determined -v of 0.731 ml/g. The interaction of several proteinases with alpha2M was studied by using a novel discontinuous polyacrylamide-gel system, which showed clear separation of the enzyme-complexed alpha2M from the free alpha2M. These studies indicated that urokinase, as well as trypsin, chymotrypsin, plasmin and thrombin forms complexes with alphaM. The cleavage of the 185000-dalton subunit to a 85000-dalton species on interaction of trypsin with alpha2M was demonstrated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis after reduction of the alpha2M-trypsin complex in urea. The amino acid composition, carbohydrate content, absorption coefficient at 280 nm, the specific refractive increment and the sedimentation coefficient for these alpha2M preparations were measured. The stability of the trypsin-binding activity of the alpha2M preparations was also studied under several storage situations.


Supression of ventricular extrasystoles by perhexiline. The antiarrhythmic effects of perhexiline were investigated in 13 of 20 patients with frequent and long standing ventricular extrasystoles in a double blind crossover trial using 24-hour electrocardiograph tape recordings, routine electrocardiograms, and treadmill exercise testing. With a dose of 300 to 400 mg per day, there was a significant decrease (mean 41%) in the number of ventricular extrasystoles per 24 hours. There were large differences in the individual responses to perhexiline, which were significantly related to the diurnal variations of ventricular extrasystoles: those patients whose ventricular extrasystoles disappeared spontaneously during sleep were less likely to respond to perhexiline than those whose ventricular extrasystoles persisted throughout the night. Suppression of ventricular extrasystoles was also apparent from the routine electrocardiogram and the exercise tests. Side effects (dizziness and unsteadiness) were troublesome in 5 of 20 patients. It is concluded that in selected patients perhexiline is an effective antiarrhythmic drug, and is likely to be most useful in patients with coexisting angina and ventricular extrasystoles. Because of its potential toxicity, it should not be used as a drug of first choice.


Vectorcardiographic features of ventricular extrasystoles correlated with conventional scalar electrocardiographic interpretation. Horizontal and frontal plane QRS loops of patients in sinus rhythm with uniform ventricular extrasystoles were constructed from digitised Frank orthogonal electrocardiograms. In 4 patients ventricular extrasystoles were indistinguishable from right bundle-branch complexes, and in another they were indistinguishable from left bundle-branch complexes. In 25 patients ventricular extrasystoles showed an initial delay (greater than or equal to 20 ms) of the QRS, followed by an R loop, which in 13 patients resembled left bundle-branch block complexes, and in 12 patients resembled right bundle-branch block complexes, with an anterior clockwise loop in the horizontal plane. However, the frontal plane loop often did not resemble that of either right or left bundle-branch block. In 51 patients ventricular extrasystoles had an initial delay which was prolonged into the efferent limb of the QRS loop with acceleration of the afferent limb, and/or the QRS loop was directed anteriorly, inferiorly, and to the left. Conventional recordings of these extrasystoles usually showed an initial slow upstroke (or downstroke) of the QRS resembling a delta wave. Apparently uniform ventricular extrasystoles on scalar recordings were shown to be multiform vectorcardiographically though in all such cases the direction of the initial 40 ms forces was constant. It is suggested that the slow initial inscription of ventricular extrasystoles is the result of excitation of ventricular muscle directly and not through specialised His-Purkinje fibres, and that the direction of such initial forces may indicate the ventricular origin of ventricular extrasystoles.


Mahaim conduction producing left axis deviation and normal QRS. An unusual patient is described in whom electrophysiological studies strongly suggest the occurrence of Mahaim conduction. The patient whose electrocardiogram previously showed a left anterior hemiblock pattern then developed advanced atrioventricular (AV) block (AH block). Beats conducted through the atrioventricular node always had a short HV interval (20 ms) and QRS complexes of left anterior hemiblock pattern. Junctional escape beats always had a normal HV interval (50 ms) with normal intraventricular conduction. His bundle pacing showed the StV interval and QRS contour of escape beats. These findings suggest the existence of an accessory pathway (Mahaim fibres) passing from the area of block, presumably the uppermost portion of the His bundle, to the posteroinferior division of the left bundle-branch. The surface electrocardiogram did not show the characteristic delta wave of the Wolff-Parkinson-White syndrome. Our observations suggest that patients in whom there is conduction along Mahaim fibres may show only the pattern of intraventricular conduction defect without a delta wave.


Carcinoembryonic antigen in hepatocellular cancer. Serum carcinoembryonic antigen (CEA) concentrations were found to be raised in 28 of 72 black patients (39%) with hepatocellular cancer (HCC). The degree of elevation was slight or moderate, except in 3 patients in whom values greater than 20 ng/ml were recorded. No significant correlation could be demonstrated in individual patients between the serum CEA concentration and various tests of liver function. The mean CEA value in the patients with cirrhosis in the non-tumorous liver was slightly higher than that in those without cirrhosis, but the difference did not reach statistical significance. There was no correlation between serum CEA and alpha-foetoprotein (AFP) levels.


Maternal plasma alpha-fetoprotein screening for fetal neural tube defects. Maternal plasma alpha-fetoprotein (AFP) screening for fetal neural tube defects (NTD) was used as a part of routine antenatal care in three hospitals over a 26 month period. Blood samples were obtained for plasma AFP measurement at 15 to 20 weeks gestation from 6377 women, representing 79 per cent of antenatal bookings. The outcome of pregnancy was ascertained in 96 per cent of patients: 13 cases of anencephaly and 7 of open spina bifida were detected by plasma screening and a further 3 cases of open NTD through the mother's previous medical history and amniotic fluid determination. Four fetuses with open NTDs and four with closed NTDS were not detected by plasma AFP measurement and the detection efficiency for open NTDs was thus 83 per cent. Integration of screening into the existing pattern of antenatal care required only minor alterations in clinic schedules. Some extra time was needed for explanation of the objectives of the study, for ultrasound examination and for amniocentesis. Eight patients declined the offer of a plasma test, while only one refused an amniocentesis.


Maternal serum alpha-fetoprotein and birth weight in twin pregnancies. In 102 twin pregnancies the mean birth weight of each pair showed a statistically significant negative association with maternal serum alpha-fetoprotein (AFP) levels early in pregnancy. Women with AFP levels of four or more times the median value for singleton pregnancies gave birth to infants with a median birth weight 660 g less than that of infants born to women with AFP levels between 1.0 and 1.5 times the median for singleton pregnancies. Maternal serum AFP has been shown to be an early predictor of low birth weight delivery in singleton pregnancies. Our results indicate that this is also true in twin pregnancies.


Effect of chelating agents and metal ions on the degradation of DNA by bleomycin. The degradation of DNA by bleomycin was studied in the absence and in the presence of added reducing agents, including 2-mercaptoethanol, dithiothreitol, reduced nicotinamide adenine dinucleotide phosphate, H2O2, and ascorbate, and in the presence of a superoxide anion generating system consisting of xanthine oxidase and hypoxanthine. In all cases, breakage of DNA was inhibited by low concentrations of chelators; where examined in detail, deferoxamine mesylate was considerably more potent than (ethylenedinitrilo)tetraacetic acid. Iron was found to be present in significant quantities in all reaction mixtures. Thus, the pattern of inhibition observed is attributed to the involvement of contaminating iron in the degradation of DNA by bleomycin. Cu(II), Zn(II), and Co(II) inhibit degradation of DNA by bleomycin and Fe(II) in the absence of added reducing agents. A model is proposed in which the degradation of DNA in these systems is dependent on the oxidation of an Fe(II)-bleomycin-DNA complex.


Unique human glycoprotein, alpha1-microglycoprotein: isolation from the urine of a cancer patient and its characterization. A human glycoprotein was isolated from the urine of a patient with plasma cell leukemia. It appears pure and homogeneous when examined by immunoelectrophoresis, sodium dodecyl sulfate (NaDodSO4)-polyacrylamide gel electrophoresis, gel filtration in 6 M guanidine hydrochloride (Gdn.HCl), and NH2-terminal amino acid sequence analysis. It has a brown color due to a tightly (most likely covalently) bound chromophore group(s) and migrates to the alpha1 region in immunoelectrophoresis. A molecular weight (mol wt) of 27 000 was obtained for the glycoprotein by gel filtration in 6 M Gdn.HCl. Its approximate mol wt determined by Na-DodSO4-polyacrylamide gel electrophoresis is 29 000 on 5% and 7.5% and 10% gels. Amino acid and hexosamine analyses showed that it is a glycoprotein and indicated that it contains four half-cystine residues per molecule. Based on the above observations we designated it "alpha1-microglycoprotein" (alpha1-MGP). Isoelectric focusing of alpha1-MGP showed a significant charge heterogeneity, although only a single NH2-terminal amino acid sequence was obtained for alpha1-MGP, i.e., Gly-Pro-Val-Pro-( )-Pro-Pro-Asx-Asx-Ile-Glx-Val-Glx-Glx-Asx-Phe-Phe-Ile-(Ser or Ala)-Arg. The alpha1-MGP was found in significant concentrations in the urine of many patients with neoplastic diseases.


Inhibitor of trypsin and chymotrypsin in cultures of HeLa cells. An inhibitor of trypsin and chymotrypsin with apparent molecular weight of 68 000 and a mobility similar to alpha1-globulin on polyacrylamide gel electrophoresis, was isolated from serum-free supernatant preparations from HeLa cells. Immunoelectrophoresis assays indicated that the inhibitor differed serologically from known inhibitors of serine proteinases in plasma and urine but shared antigenic determinants with an unidentified protein in these body fluids and with an inhibitor recently isolated from cultures of lung.


Clostridiopeptidase B inhibition by plasma marcroglobulins and microbial antiproteases. Clostridiopeptidase B (EC 3.4.22.8) was not inhibited by stoichiometric amounts of lima bean trypsin inhibitor, ovomucoid trypsin inhibitor, Kuntiz bovine trypsin inhibotor, Kunitz soybean trypsin inhibitor or ovoinhibitor. Activity was diminished at relatively high concentrations of the three latter inhibitors. Human plasma alpha 2-macroglobulin inhibited both the amidase and protease activity of the enzyme. Rat and dog plasmas contained high molecular weight inhibitors, presumably macroglobulins as well. Inhibition by this component was greater in rat plasma than in dog plasma, which may be related to the observation that clostridiopeptidase B-induced generation of kinin activity is indirect in the former plasma, but direct in the later. Leupeptin (N-acetyl-L-leucyl-L-leucyl-L-argininal) and antipain ([S)-1-carboxy-2-phenylethyl] carbamoyl-L-arginyl-L-valyl-L-argininal) inhibited clostridiopeptidase B (Ki of 2 . 10(-8) and 3 . 10(-8) M, respectively). They were potent inhibitors of clostridiopeptidase B-induced kinin release in dog plasma.


Isolation of tau-phosphohistidine from a phosphoryl-enzyme intermediate of human prostatic acid phosphatase. The carbethoxylation of prostatic acid phosphatase (orthophosphoric-monoester phosphohydrolase (acid optimum), EC 3.1.3.2) was accompanied by modification of histidine residues and the inactivation of the enzyme. These findings are consistent with photoinactivation experiments described earlier (Rybarska, J. and Ostrowski, W (1974) Acta Biochim, Polon. 21, 377--390). Prostatic acid phosphatase was phosphorylated at alkaline pH using p-nitrophenyl [32P]phosphate as substrate. Phosphoryl enzyme is stable in alkaline solutions and undergoes dephosphorylation at acidic pH. After hydrolysis of phosphoryl enzyme in strong alkaline solution, a single phosphoryl amino acid was isolated from hydrolyzate and identified as the tau-phosphohistidine.


The in vitro interactions of rat pancreatic elastase and normal and inflammatory ray serum. The partition of labelled rat pancreatic elastase (EC 3.4.21.11) between the different protease inhibitors of rat plasma was studied at different levels of saturation of the inhibitors of rat plasma was studied at different levels of saturation of the inhibitor capacity of plasma with the enzyme. The reaction mixtures were analysed by immunoelectrophoretic methods utilizing specific antisera against the different inhibitors and by gel filtration on Sephadex G-200. Rat serum was shown to contain four elastase binding  proteins. alpha 1-antitrypsin, alpha 1-macroglobulin and alpha 2-acute phase protein and alpha 1-inhibitor 3 which exhibits immunologic cross-reaction with human inter-alpha-trypsin inhibitor and is of similar molecular weight. With minute amounts of labelled elastase the partition among the binding protein was alpha 1-macroglobulin 60%, alpha 1-antitrypsin 24% and alpha 1-I3 16%. The 60% value of alpha 1-M bound radioactivity in normal serum corresponds to the sum of alpha 1-M and alpha 2-AP labelling in inflammatory serum.


Effect of isonicotinic acid hydrazide-copper complex on Rous sarcoma virus and its genome RNA. The copper complex of the antituberculous drug, insonicotinic acid hydrazide (INH), inhibits the RNA-dependent DNA polymerase of Rous sarcoma virus and inactivates its ability to malignantly transform chick embryo cells. The INH-copper complex binds to the 70S genome RNA of Rous sarcoma virus (RSV), which may account for its ability to inhibit the RNA-dependent DNA polymerase. The complex binds RNA more effectively than DNA in contrast to M-IBT-copper complexes, which bind both types of nucleic acids equally. The homopolymers, poly rA and poly rU, are bound by the INH-copper complex to a greater extent than poly rC. Isonicotinic acid hydrazide alone and CuSO4 alone bind neither DNA, RNA, poly (rA), poly (rU), nor poly (rC). However, CuSO4 alone binds poly (rI); INH alone does not. In addition to viral DNA synthesis, chick-embryo cell DNA synthesis is inhibited by the INH-copper complex. The extent of inhibition of cellular DNA synthesis is greater than that of cellular RNA and protein synthesis. No selective inhibition of transformation in cells previously infected with Rous sarcoma virus is observed.


Serum protein changes associated with alpha1-antitrypsin deficiency. Using a radial immunodiffusion technique, the concentrations of eight serum proteins have been measured in sera from 60 chest clinic patients previously shown to have abnormally low alpha1-antitrypsin levels, and in 60 age and sex matched control sera. Of the proteins, only alpha2-macroglobulin showed a highly significant increase in the alpha1-antitrypsin deficient group. The findings confirm a previously reported association between alpha1-antitrypsin deficiency and increased alpha2-macroglobulin, and lend support to the suggestion that the rise in alpha2-macroglobulin is a specific compensatory response.


Search for endogenous C-type viruses in cultures of non leukemic human cells. Cultures of cells derived from non-leukemic human tissues were submitted to treatments known to induce endogenous C-type viruses of a number of animal species. Virus expression was evaluated by reverse transcriptase (RT) assays in the growth medium. Of 20 cultures treated or untreated with bromodeoxyuridine, 18 were totally negative in RT assays. Of the 2 positive cultures, one was a human-mouse hybrid in which the induction of RT activity coincided with the expression of murine antigens. The other culture, a diploid strain which exhibited borderline enzymatic activity, was subjected to more detailed analysis after treatment with several chemical inducers and/or irradiation, but none of these procedures gave clearly positive results. The apparent lack of an endogenous virus synthesis in these human cells is discussed.


[Tissue specific antigen of the caudal lobe of the chicken adenohypophysis]. The tissue-specific water-soluble antigen of the chick pituitary gland was revealed by immunochemical analysis. The content of this antigen was found to be predominant in the caudal lobe of the adenohypophysis. The antigen was found from the 13th day of embryogenesis by immunoelectrophoresis and immunofluorescence. Two kinds of the antigen (with high and low relative electrophoretic mobility) were discovered in the chick adenohypophysis. A conclusion was drawn that the adenohypophysis cells differed by the differentiation level.


5-Hydroxytryptamine: the effects of impaired synthesis on its metabolism and release in rat. 1 Control rats given L-tryptophan (100 mg/kg) showed a smaller increase of brain 5-hydroxytryptamine (5-HT) than its metabolite 5-hydroxyindoleacetic acid (5-HIAA). However, when brain 5-HT concentrations were depleted by 40-50% after treatment with the synthesis inhibitor p-chlorophenylalanine (PCPA) (150 mg/kg) L-tryptophan caused a considerable increase in 5-HT but no change in 5-HIAA. Similar results were obtained following depletion of brain 5-HT by pretreatment with p-chloroamphetamine (10 mg/kg).2 Electrical stimulation of the median raphe nucleus of control rats significantly increased 5-HIAA in the hypothalamus, hippocampus and striatum. However, stimulation of PCPA (200 mg/kg) pretreated animals did not significantly increase 5-H1AA either 24 or 72 h after administration of the drug.3 Pretreatment of rats with PCPA (200 mg/kg) increased striatal synaptosomal uptake of [(3)H]-5HT by 30% and reduced 5-HT concentration in the rest of the brain by 62%.4 PCPA (150 mg/kg) markedly reduced the acute behavioural response (-76%) to p-chloroamphetamine (10 mg/kg) although brain 5-HT was only moderately reduced (-36%). L-Tryptophan (100 mg/kg) given 15 min before p-chloroamphetamine restored both brain 5-HT and the behavioural effects of p-chloroamphetamine in PCPA pretreated rats and enhanced the behavioural response to p-chloroamphetamine in control rats.5 The results suggest that newly synthesized 5-HT is less rapidly metabolized in rats with low brain 5-HT. The possible reasons for this and the relevance of the results to the use of L-tryptophan in the treatment of depressive illness are discussed.


Mechanism of histamine release from rat mast cells induced by the ionophore A23187: effects of calcium and temperature. 1 The mechanism of histamine release from a pure population of rat mast cells induced by the lipid soluble antibiotic, A23187, has been studied and compared with data for anaphylactic histamine release reported in the literature. 2 Histamine release induced by A23187 in the presence of calcium 10(-3) mol/l was completed in 10 minutes. By preincubation of the mast cells with A23187 for 10 min in the absence of calcium the histamine release induced by calcium, 10(-3) mol/l or 5 x 10(-3) mol/l, was completed in 90 s and 45 s, respectively. 3 A23187-induced histamine release was maximal with calcium 10(-3) mol/l when the cells were incubated at 33 to 39 degrees C for 10 minutes. 4 The cellular mechanism, which was stimulated by A23187 and calcium for the release of histamine, was irreversibly inactivated by incubation at 45 degrees C. 5 An inhibition of energy metabolism was excluded as the cause of the heat inactivation. 6 The dependence of A23187-induced histamine release on calcium and temperature, the time course of histamine release and the heat inactivation are consistent with the view that the same mechanism is involved in A23187-induced and anaphylactic histamine release.


Cells of origin of propriospinal fibers and of fibers ascending to supraspinal levels. A HRP study in cat and rhesus monkey. In the spinal cord of cat and rhesus monkey the cells of origin of long and short propriospinal fibers and those of the spinal fibers ascending to supraspinal levels were identified by means of retrograde HRP labeling after large unilateral HRP-injections, i.e. in the spinal white and grey matter at different levels, in the pons and in the dorsal column nuclei. The findings indicate the existence of the following arrangement. Long ascending supraspinal fibers arise mainly from neurons in the dorsal grey (laminae I-IV and the medial parts of laminae V and VI) as well as from neurons in the medial part of the ventral grey (lamina VIII), in Clarke's column and in the spinal border cell area. Some neurons in the dorsal grey projects to the dorsal column nuclei, which in turn distribute fibers back to the spinal cord. Long propriospinal fibers mainly derived from neurons in the medial part of the ventral grey (lamina VIII), while short propriospinal fibers are characteristically derived from neurons in the intermediate zone (lateral halves of laminae V and VI and lamina VII). The neurons located laterally in laminae V-VII distribute fibers mainly ipsilaterally, while those located medially in lamina VII distribute them to some degree bilaterally. The findings in cats with transections of either the dorsal or the ventral halves of the spinal white matter (both above and below the injected segment), show that the fibers from the dorsal grey and the lateral parts of laminae V-VII travel mainly through the dorsal half of the white matter, while those from the medial part of lamina VII and from lamina VIII travel mainly through the ventral half.


Brain stem nuclei giving fibers to lobules VI and VII of the cerebellar vermis. The HRP method has been used to identify all the brain stem nuclei, which may project to lobule VI and/or VII of the posterior cerebellar vermis. Three tentative degrees of labeling of the different structures have been assigned: 'massive', 'clear' and 'discrete'. (1) Massive projections have been found to reach lobule VI and VII from the inferior olive and lobule VII only from the nucleus reticularis tegmenti pontis. (2) Clear projections have been found to reach lobule VI only from the pontine nuclei, the nucleus reticularis tegmenti pontis, the nucleus reticularis lateralis and the reticularis paramedianus; lobule VII only from the raphe nuclei, and both VI and VII from the perihypoglossal and vestibular nuclei. (3) Discrete projections have been found to reach lobule VI and VII from the deep cerebellar nuclei; lobule VI only from the nucleus tracti solitarii and nucleus cuneatus externus; lobule VII only from the nucleus lemnisci lateralis pars ventralis, the nuclei parabrachiales and the nucleus subcoeruleus.


[Evidence for polypeptide synthesis during cytotoxic reactions in sipunculid worms]. The occurence of a polypeptidic synthesis during the in vitro cytotoxic reaction of sipunculid worns is demonstrated. Some drugs such as actinomycin D, cycloheximide, cytochalasin B, Colchicine, vinblastine and iodoacetate have been tested. Hypothesis are expressed on the use of the products synthetized by leukocytes.


Direct-acting mutagens in automobile exhaust. Particulate matter in city air contains chemicals which are mutagenic in the Ames Salmonella typhimurium assay. In residential urban areas, the principal mutagens in air do not require liver enzymes to be activated. The source of these liver independent (direct-acting) mutagens may be automobile exhaust because (1) the mutagenic activities were correlated to the lead content or air, (2) the mutagens were found exhaust samples from automobiles and from an experimental CFR single-cylinder gasoline engine, and (3) these mutagens were not found in fuel or unused motor oil, but were found in used motor oil. The strain specificity and the fact that liver enzymes were not required for activation indicated that the exhaust and airborne mutagens were not unsubstituted polycyclic aromatic hydrocarbons (PAH), aromatic amines, alkylnitrosamines or aliphatic epoxides, peroxides and hydroepoxides. A number of nitro-substituted aromatic compounds are direct-acting mutagens in the Ames test, and it is possible that nitration of PAH in exhaust may form the compounds observed here. We synthesized 6-nitrobenzo [a] pyrene and found it to be a potent, direct-acting mutagen with activity comparable to that of benzo-[a] pyrene.


Type D primate retroviruses: a review.

Type D primate retroviruses: a review. The prototype virus of the type D retroviruses is the Mason-Pfizer monkey virus (MPMV). MPMV was originally isolated from a breast carcinoma of a female rhesus monkey (an Old World monkey). MPMV is of obvious importance in that it is the only retrovirus thus far isolated from a mammary tumor of a primate and has been shown to have transforming potential for primate cells in vitro. Subsequent to the isolation of MPMV viruses morphologically and immunologically indistinguishable from MPMV have been isolated from normal placenta and lactating mammary glands of other rhesus monkeys in captivity. Recently, viruses morphologically resembling MPMV have been isolated from a langur monkey (another Old World monkey) and from squirrel monkeys (a New World monkey). Based on nucleic acid hybridization studies, the latter 2 viruses represent endogenous viruses in their species of origin, whereas MPMV appears to be a horizontally related to the langur monkey isolate. Studies on the immunological relatedness of the type D retroviruses have demonstrated interspecies cross-reactivities between the major internal and external proteins of the viruses. Furthermore, these viruses also share cross-reactivity of their major external glycoproteins with those of the type C baboon endogenous virus. These interspecies reactivities can also be demonstrated in natural sera from both imported and laboratory-bred monkeys. The demonstration of these interspecies cross-reactivities shared by distantly related primate retroviruses provides a means for detecting determinants that are representative of all primate retroviruses presently known and yet to be isolated and may provide new assays for detection of a human retrovirus.


Accelerated growth of mammary tumor cells in normal and athymic mice after treatment in vitro with dexamethasone. The tumorigenicity of dexamethasone-treated tissue-cultured mammary tumor cells was compared to that of untreated mammary tumor cells. The dexamethasone-induced cells progressed faster in normal syngeneic animals than did untreated mammary tumor cells. The fact that the growth rate differential was also observed in athymic mice suggests that T-lymphocyte-mediated  immunity was not a factor in the accelerated progression in vivo of the tumor cells that had been cultured in the presence of dexamethasone.


Copper(II)-binding ability of human alpha-fetoprotein. The copper(II)-binding ability of human alpha-fetoproteins, which were purified from umbilical cord serum and from ascites fluid of a hepatoma-bearing patient, was examined by equilibrium dialysis and gel filtration methods. The pH dependence of the copper(II)-binding ability of alpha-fetoprotein was quite similar to that of albumin. Alpha-fetoprotein bound 1 mol of copper(II) ion per mol of protein above pH 6.0 and 0.5 mol of copper(II) ion at pH 5.4, which is close to the pK value of the imidazole group of histidine. Photooxidation of alpha-fetoprotein in the presence of methylene blue resulted in the loss of the copper(II)-binding ability of the protein in parallel with the destruction of the histidyl residues. A synthetic amino-terminal undecapeptide of alpha-fetoprotein also bound copper(II) ion. These results indicate that the histidyl residue at the amino-terminal region of alpha-fetoprotein plays an important role in the copper(II)-binding ability of the protein.


Pharmacokinetic considerations in evaluating the effects of tetrahydrouridine on 5-azacytidine chemotherapy in L1210 leukemic mice. The pharmacokinetics of 5-azacytidine (5-azaCR) and tetrahydrouridine (THU) were considered in evaluating the effect of THU on chemotherapy with 5-azaCR in L1210 leukemia mice. The administration of three different dose levels of THU and 5-azaCR ip in either a 6- or 72-hour infusion gave minimal increases in therapeutic effect. At the high-dose combinations (except in the 72-hour infusion), THU appeared to enhance toxicity. Toxicity, however, occurred only after exceeding a theoretic plasma concentration for 5-azaCR of 61 microgram/ml. THU was effective in increasing the excretion of 5-azaCR by sixfold and in altering its urinary metabolites when given simultaneously with or up to 1 hour prior to 5-azaCR.


cis-Dichlorodiammineplatinum(II) and bleomycin in the treatment of esophageal carcinomas. Forty-seven patients with squamous cell carcinoma of the esophagus were treated with a combination of cis-dichlorodiammineplatinum (II) (cis-DDP) and bleomycin by infusion. cis-DDP at a dose of 3 mg/kg with mannitol and prehydration was given on Day 1. On Day 3, bleomycin was started as a 10--15-unit/m2 loading dose followed by a 10--15-unit/m2 24-hour infusion for 4--7 days. Three groups of patients were treated: group 1 (no clinical evidence of metastatic disease) included 25 patients, all with no prior therapy; group 2 (measurable metastatic disease) included 13 patients, eight previously treated with surgery and/or radiation; group 3 (known nonmeasurable metastatic disease) included nine patients, all previously treated with surgery and/or radiation and/or chemotherapy. A second course of therapy was given on Day 28 to groups 2 and 3, and as soon after surgery as possible in group 1. Nineteen percent of patients had complete or partial responses with another 44% having minor regressions. Toxic effects were mainly renal effects, alopecia, nausea and vomiting, and stomatitis. There were two drug-related deaths. The combination of cis-DDP and bleomycin is useful in the treatment of patients with squamous cell carcinoma of the esophagus.


Phase II study of the failure of vincristine and bleomycin for previously treated children with metastatic neuroblastoma: a report from the Childrens Cancer Study Group. Twenty-two patients with previously treated but progressive stage IV neuroblastoma received combination therapy with vincristine (1.0 mg/m2) followed in 6 hours by bleomycin (15 mg/m2). Therapy was administered twice weekly. No responses were seen in the 19 patients who received four or more doses of the bleomycin-vincristine combination.


Phase II study of adriamycin and bleomycin in patients with multiple myeloma. Twenty-seven patients with far-advanced multiple myeloma, resistant to standard agents, were treated with either adriamycin (eight patients) or bleomycin (19 patients). Adriamycin was given iv at a dose of 60 mg/m2 every 3 weeks and bleomycin was administered im at a dose of 15 mg/m2 weekly. Drug toxicity was modest. One partial response was seen with each agent, both occurring in "good-risk" patients.


Pigment architecture of the human telencephalic cortex. III. Regio praesubicularis. Cortical lamination and parcellation of the human presubicular region is described with the aid of stereomicroscopical analysis of pigment preparations up to 1000 micrometers thick. The region can be subdivided into three major territories each of which is strongly influenced by the adjoining cortical tissue. The three subregions are: 1) the presubiculum sensu stricto. It lies near the subiculum at its medial margin and can be subdivided into 6 areas. 2) the parasubiculum. It borders on the entorhinal region and is composed of 5 areas. 3) the transsubiculum. It forms a transitional zone between allocortical and isocortical fields and consists of 3 areas. The presubicular region is characterized by a conspicuous layer of small and densely packed cells which--except the marginal parts of the subiculum--does not appear outside this region. Besides this autochthonous parvopyramidal layer, the presubicular cortex is composed of "foreign" cell layers which penetrate in varying number and to a varying extent into the region from the surrounding fields. The presubicular cortex shows extensive and incessant local variations, in so far as each one of its layers is very variable in breadth. In spite of this, a reliable parcellation can be achieved when only those layers are taken into consideration whose marginal parts are clearly recognizable. Hence, the proposed parcellation is based on the changing pattern of lamination which is depicted in diagrams for easy recognition of the various areas.


The ultrastructure of the accessory sex organs of the male rat. XII. Nuclear alterations of prostatic epithelial cells induced by anti-androgens. The fine structure of the nuclei of epithelial cells of the dorsal lobe of the rat prostate were studied after administration of three different anit-androgenic compounds. The nucleolus appears to undergo a progressive disorganisation with partial fragmentation and dispersion of its normal components. Different types of intranuclear inclusions were found. The various alterations observed were often encountered within the same section. This may indicate that the nuclear alterations occur in the same compartment of the cell, and represent a dysfunction of integrated biochemical events occurring within this compartment. The findings support a view that the stimulatory secretory effect of androgens is mediated via a "secretory center", located within the nucleolus-associated chromatin. Within this "secretory center", the initial steps of the secretory process, the binding of the DHT receptor complex to DNA is assumed to occur.


The reversible effect of colchicine on the taste bud cells of the central circumvallate papilla in the rat. It is believed that differentiation and maintenance of taste buds in vertebrates is dependent on the trophic function of their sensory nerve supply. In the present work, colchicine was injected into the circumvallate papilla of the rat. This produced a reversible blockade of neuroplasmic transport and disappearance of taste buds. Colchicine inhibited the further differentiation of bud cells, but apparently did not change the life cycle of the cells present already at the time of injection. It is speculated that the neurotrophic factors in this particular cell system are effective to induce cell differentiation only.


High frequency of aberrant expression of Moloney murine leukemia virus in clonal infections. Clones of cells were isolated from single virus-single cell infections of NIH/3T3 cells with Moloney murine leukemia virus. Approximately one third of such clones aberrantly expressed viral gene functions. One clone produced virus with altered plaque morphology, while others failed to produce particles able to make plaques on XC cells. In addition, clones that made particles lacking reverse transcriptase were found, and these did not synthesize the reverse transcriptase precursor Pr180 gag-pol. One clone (M23) lacked any detectable glycoprotein or reverse transcriptase. Despite these defects, each clone released particles of type C morphology, suggesting that gag gene function alone may be sufficient for particle production. All the particles contained viral RNA of 60-70S that was composed of the normal 35S size subunits except for M23, which had a deletion in the viral genome of approximately 1000-1500 nucleotides. A variety of defective clones were also isolated following infection of rat cells with Moloney virus. It is apparent that the murine leukemia virus genome is ofter mutated by spontaneous processes generating a wide range of phenotypes.