The ultrastructure of the accessory sex organs of the male rat. 9. The effect of an antiandrogenic compound, SKF 22,340. The coagulating gland and the dorsal lobe of the rat prostate were studied after administration of the antiandrogenic compound SKF 22,340. There was a general involution of the organs, with macroscopic atrophy and a reduced amount of secretory material. Ultrastructurally the cells contained fewer organelles as compared with the controls. There were also loss of cytoplasm and reduction both of cell height and width. Within the dorsal lobe, prominent nuclear and nucleolar changes were found. The alterations observed in the present study are similar to changes which were found in animals treated with another antiandrogenic compound, cyproterone acetate. The results are discussed in relation to the available biochemical data.


Spontaneous arteritis and glomerulitis in mice. A comparison of light and electron microscopic renal changes in PN/n, NZB/BL, 101/MAC, and CBA/MAC mice. Four PN/n mice between 12 and 17 months of age had fibrinoid necrosis of the renal arteries, but 32 mice up to the age of 17 months showed no consistent change in the media or intima of the renal arteries although perivascular cuffing with round cells was prominent from 9 months of age. Glomerulitis, indicated by increase in the mesangium on light microscopy, affected most mice over 7 months of age, and dense deposits on electron microscopy were present in most mice from 7 months of age. These changes occurred significantly more frequently than in CBA/MAC mice; the 101/MAC showed an intermediate frequency, and the pattern in a small sample of NZB/BL mice resembled that of the PN/n mice. Basement membrane thickening increased with age from 3 weeks in all of the strains but more often included dense deposits in PN/n mice. Splitting of the glomerular basement membrane in very young mice in all strains was not considered relevant and may have been developmental. Failure consistently to detect glomerulitis earlier by electron microscopy than by light microscopy was attributed to the greater sampling error of the former. Unidentified dense bodies in glomerular epithelial cells occurred at all ages in all strains, so the suggestion that they were virus particles relevant to the disease was not sustained. Intraobserver variation studies showed satisfactory repeatability for light microscopy and for dense deposits and basement membrane thickening, but the dense bodies were not detected with acceptable reproducibility, a difficulty partly due to technical variation.


Liver disease of the alcoholic.

Liver disease of the alcoholic. Significant liver disease including fatty metamorphosis, alcoholic hepatitis, cirrhosis, and hepatoma occur in two thirds of subjects who consume alcoholic beverages in sufficient quantities to interfere with work and social responsibilities; this is of major importance in the rapidly escalating morbidity and mortality from alcoholism. Chronic alcoholics should be routinely evaluated for the presence of altered liver function and structure. Clearance of indocyanine green using dichromatic ear densitometry and computer and analysis provides a simple and sensitive method for mass screening of such patients. Clinical studies of lymphocyte reactivity to purified alcoholic hyaline may be valuable in recognizing alcoholic hepatitis, the precursor of cirrhosis. Ethanol toxicity, malnutrition and constitutional factors contribute to the development of hepatic fibrosis and cirrhosis in alcoholics. Ethanol and/or acetaldehyde and the supernatant from lymphocytes stimulated by alcoholic hyaline cause a significant increase in the incorporation of proline into collagen of the damaged liver. Abstinence and correction of nutrient deficits are the cornerstones of treatment for alcoholic liver disease; a daily meal and dietary supplements should be provided for those with liver injury who continue to imbibe. Alcoholics with progressive liver disease despite supportive therapy may be aided by pharmacologic agents which suppress immunologic response and reduce fibrogenesis.


Adrenergic beta-receptor activity and cyclic AMP metabolism in vascular smooth muscle; variations with age. The relaxing effect of isoproterenol on aortic strips from rats decreases and disappears with increasing age of the animal. In aortas from young rats (1 month) the cAMP level increases after stimulation with isoproterenol (3.6 muM), whereas in old aortas (6 months) the cAMP level was unchanged. Basal and NaF stimulated adenyl cyclase activities are increased in aortas from rats 6 months of age compared with those one month old. The phosphodiesterase activities decrease with increasing age both low (10-7M) and high (10-4M) substrate concentration.


Nasopharyngeal angiofibroma in the elderly: report of a case. Although nasopharyngeal angiofibromas usually occur during puberty and adolescence, thus being considered as juvenile, very rare documented reports describe this condition in old persons.  The case of a 62-year-old man with a nasopharyngeal angiofibroma successfully resected is presented.  It was the only lesion found in an old individual among 283 cases seen during a 20-year period in a large city hospital.


IV. Multiple glomus tumors in the head and neck. Eight of 76 glomus tumors in the head and neck region are multiple.  The most common association is with carotid body tumors; the most common pattern is an ipsilateral glomus tympanicum and carotid body tumor.  The approach to clinical evaluation is based on a complete otolaryngologic, neurologic, and neuroradiologic evaluation of all patients with glomus tumors.  The rationale for priorities in management is the resection of the most dangerous lesions first.  This study confirms the previous observations that glomus tumors have a definite proclivity for multicentricity (10 percent) and a high incidence for other associated malignancies (8 percent).


Lipd profiles of plasma lipoproteins of fasted and fed normal and choline-deficient rats. Three major density classes of lipoproteins and a residual protein (d greater than 1.21) were isolated by ultracentrifugation from plasma of fasted, fed normal, and choline-deficient rats.  Lipid extracts were obtained from total plasma and the various density classes of lipoproteins, and each extract was examined in detail by thin layer and gas chromatographies.  The results indicated essentially identical compositions of molecular species of phosphatidyl choline, which suggested their rapid equilibration among the different plasma lipoprotein classes.  In contrast, the molecular species of the triacylglycerols and cholesteryl esters showed significant differences among the chylomicrons, very low and low, and high density lipoproteins, which excluded the possibility of their ready equilibration in vivo.  Omission of choline from diet resulted in a sharp and statistically significant decrease in all lipid components of the very low and low density lipoproteins with 2 days.  After 10 days of choline deficiency, the lipid levels of chylomicrons and very low and low density lipoproteins were ca. one-half the levels found in the choline supplemented animals, and there were discernible distortions in their lipid composition.  Reintroduction of choline led to a prompt return to normal levels and lipid composition of both chylomicron and very low and low density lipoprotein fractions.  The lack of equilibration of the triacylglycerols among the lipoprotein classes under normal conditions and in choline deficiency demonstrates an as yet unrecgnized source of compartmentation of plasma lipids.


Phospholipase C catalyzed formation of sphinogomyelin--14C from lecithin and N-(-14C)-oleoyl-sphingosine. Commercial preparations of Clostreidium perfringens were incubated with phosphatidyl choline and N-1-(-14C) oleoylsphingosine.  A radioactive product was formed which cochromatogramed with spingomyelin standard in three different solvent systems.  Several other phospholipases and phosphatases were unable to catalyze this reaction.  Neither choline, phosphoryl choline, cytidine diphosphate choline nor p-nitrophenyl phosphoryl choline were acitve donors.  Sphingomyelin was only slightly active as a phosphoryl choline donor.


Sterospecific analysis of hepatoma, host liver, and normal rat liver triglycerides from animals on chow and fat free diets. Triglycerides from normal liver, host liver, and heptoma of rats maintained on chow and fat-free diets were subjected to sterospecific analysis.  Normal and host liver triglycerides from animals on the same diet did not exhibit significant differences.  Fat-free diet reduced polyunsaturated fatty acids in normal and in host liver triglycerides.  Each position of hepatoma and liver triglyceride glycerol exhibited a characteristic fatty acid composition.  Palmitate concentrations were reduced dramatically and stearate levels were increased significantly at the 1 position of hepatoma triglycerides, relative to the corresponding position of liver triglycerides which were affected little by diet ot tumor. Except for higher percentages of C-20 and higher fatty acids, common to all three positions, the composition of hepatoma triglycerides at the 2 position appeared normal.  The 3 position of hepatoma triglycerides contained significantly higher percentages of stearate than liver.  Data obtained previously for Ehrlich ascites cell triglycerides were in good agreement with this hepatoma. Data from these two neoplasms suggest that the metabolic system that regulates or controls the fatty acid composition at the 1 and 3 positions of normal tissue triglycerides does not function normally in neoplasms.


Biosynthesis and structure of glycosyl diglycerides, steryl glucosides, and acylated steryl glucosides. A particulate enzyme fraction from Mycobacterim smegmatis catalyzed the transfer of -14C-glucose from the UDP--14C-glucose into neutral glycolipids.  The two major radioactive components were purified by column chromatography on O-diethylamino ethyl cellulose (acetate) and thin layer chromatography on silica gel in several solvents.  The first product yielded a water-soluble component upon saponification, which had a hexoseglycerol ratio of 1:1 with all of the hexose being identified as glucose.  The second product yielded a water-soluble component upon saponification which contained hexose and glycerol in a 2:1 ratio and, in addition to glucose, contained lesser amounts of mannose and galactose.  Palmitate and oleate were the predominant fatty acids and were present in equimolar amounts.  The products thus have been identified as monoglycosyldiglyceride and diglycosyldiglyceride.  The diglycosyldiglyceride could also be labeled with -14C-galactose when UDP--14C-galactose served as the donor, but the monoglycosyldiglyceride was only slightly labeled with -14C-galactose.  Membrane fractions from mung bean seedlings catalyzed the transfer of -14C-glucose from UDP--14C-glucose into a neutral glycolipid which has been purified by thin layer chromatography and analyzed by combined gas liquid chromatography-mass spectrometry.  It was determined to be a steryl glucoside with the two major sterol components being betasitosterol and stigmasterol linked to beta-D-glucose.  Particulate fractions from developing cotton fibers also catalyzed the formation of steryl glucosides and, in addition, they catalyzed the esterification of steryl glucosides at the 6 position of glucose with fatty acids (primarily palmitate and oleate) from an andogenous acyl donor.  Both the glucosyl transferase and the acyltransferase have been solubilized with Triton X-100 and partially purified by chromatography on Sephadex G-200.  The acyltransferase activity was reconstituted by the addition of the steryl glucoside and a phospholipid acyl donor.


Inhibtion of diplopterol synthesis in Tetrahymena pyriformis by a hypocholesteremic compound. The hypocholesteremic compound, 3beta-(beta-dimethylaminoethoxy)-androst-5-en-17-one was earlier shown to inhibit the synthesis of tetrahymanol and two undentified lipids.  It now has been demonstrated that one of the unidentified compounds is diplopterol.


Effects of repeated endurance exercise on serum enzyme activities in well-conditioned males. Daily fluctuations in serum enzyme activities during distance running in 3 well-conditioned males were measured for 8 consecutive days. During the study the exercise regimen comprised 8 mile runs on days 1, 2 and 5; a 10.5 mile run on day 3; a 15 mile run on day 4 and resting on days 6-8. Heart rate, rectal temperature, hematocrit, plasma hemoglobin, creatine phosphokinase (CPK, glutamic-oxaloacetic and glutamic-pyruvic transaminases, lactate dehydrogenase (LDH), adenylate kinase (AK), and lactate and pyruvate were measured before and after exercise and during the resting days. Significant increases occurred in heart rate and rectal temperature with each run but were unrelated to enzyme levels. Pre-exercise CPK levels, 49 plus or minus 1 mIU/ml on day 1, rose progressively to 123 plus or minus 25 mIU/ml on day 5, and returned to initial control levels by day 8. Post-exercise CPK levels were significantly greater than pre-exercise levels on each running day but were unrelated to the severity of the exercise. LDH and AK levels did not significantly change with the exercise stress, but pre-exercise AK levels in these trained males were higher than values in non-trained males (10-20 vs. 0-5 mIU/ml) (3). Post-exercise enzyme levels appeared unrelated to final heart rate, rectal temperature or plasma hemoglobin. These results suggest that (1) CPK, unlike the other enzymes studied, is a sensitive index of exercise stress in well-conditioned runners and (2) elevated CPK and AK levels in such runners represent physiologic responses. Appropriate caution should be used in making clinical judgements from these enzyme assays in trained individuals.


The bone marrow in multiple myeloma: correlation of plasma cell ultrastructure and clinical state. The bone marrow plasma cells of 52 patients with various kinds of monoclonal gammopathies were studied by electron microscopy, and compared to the bone marrow plasma cells of 22 patients with reactive plasmacytosis. Virtually every marrow from patients with myeloma and macroglobulinemia contained plasma cells with disparity between the nuclear maturation and cytoplasmic differentiation. This asynchronous development was not present in plasma cells of reactive marrows nor in plasma cells from patients with megaloblastic anemias. The degree of asynchrony observed in myeloma and macroglobulinemia was proportional to the extent of disease as judged by clinical criteria. For the most part plasma cells of patients with non-myelomatous monoclonal gammopathy failed to exhibit significant asynchrony. These observations are consistent with the view that multiple myeloma is a neoplastic disorder with a definably malignant-appearing cellular proliferation.


Effects of insulin, tolbutamide, and glucagon on activities of jejunal carbohydrate-metabolizing enzymes in humans. The activities of jejunal carbohydrate-metabolizing enzymes show adaptive drugs, and sex hormones. To learn whether insulin, tolbutamide, and glucagon had effects on these enzymes, we performed serial peroral jejunal biopsies in normal young men and in obese patients, before and after treatment with these agents. Jejunal mucosa was assayed for glycolytic enzyme activities, pyruvate kinase (PK), hexokinase (HK), and fructose-1,6-diphosphate aldolase (FDPA), and the nonglycolytic enzyme activity, fructose diphosphatase (FDPase). Insulin significantly increased the activity of jejunal PK (+48% change from control) and HK (+6%), decreased the activity of FDPase (-36%),and had no effect on FDPA. Glucagon had opposite effects; the activity of PK was decreased (-33%) and FDPase was increased (+50%). Tolbutamide significantly increased the activities of PK (+47%), HK (+14%), and FDPA (+7%), and decreased the activities of FDPase (-36%). The results of tolbutamide on glycolytic enzyme activities were independent of endogenous insulin. The data support the concept that jejunal carbohydrate-metabolizing enzymes in man respond to hormones and drugs similar to responses observed in rat liver. This is important because it now gives us a means of studying the actions of these hormones directly in human tissue.


Apolipoproteins in human pregnancy.

Apolipoproteins in human pregnancy. Apolipoproteins are important in the structure and metabolism of lipoproteins, and alterations in levels of apoproteins or in their interrelations occur in some forms of hyperlipemia. Pregnancy is regularly accompanied by hyperlipoproteinemia, but while data on lipoprotein lipids is available, the apopipoproteins have not been studied. To characterize the lipemia of pregnancy more completely, we studied some of the apolipoproteins in plasmas of pregnancy women. Thirty-eight normal fasting women were studied between the 18th and 39th weeks of gestation and again 23 plus or minus 17 weeks after delivery. Eight additional women were sampled every 4-6 wk during the second and third trimesters of gestation. Plasma and lipoprotein lipids were assayed by standard procedures and Apolipoprotein B (ApoB) was measured by radioimmunoassay. The interrelations of Apolipoprotein A (ApoA) in high-density lipoprotein (HDL) and of Apolipoprotein C (ApoC) in very-low-density lipoprotein (VLDL) were assessed by disc gel electrophoresis in four women during the last trimester of gestation and again 6-8 mo post partum and in four nongravid controls. Gestational triglycerides (TG) and cholesterol (Chol) were elevated in 95% of the pregnant women. TG in lipoproteins rose progressively during gestation, with VLDL-TG rising the most. Low-density lipoprotein (LDL) and HDL became enriched by TG relative to other components. Total-and VLDL-ApoB increased, while LDL-ApoB remained unchanged, resulting in a change in the density distribution of ApoB. (VLDL-ApoB X 100/total ApoB rose from 3.6% to 6.7%, P less than 0.02.) The accumulation of TG-rich LDL and the increases of VLDL-ApoB may be the result of changes in the rates of secretion or intravascular catabolism of VLDL. Which process is altered remains to be determined. The relative amounts of ApoC-II and ApoC-III in VLDL and the ApoA-I/ApoA-II ratios in HDL were unchanged in pregnancy. These results differ from those seen following high-carbohydrate diets.


Intestinal amoebiasis and amoebic liver abscess in Brisbane, 1956 to 1973. Clinical syndromes and the results of medical and surgical management. Nineteen patients presented to teaching hospitals in Brisbane with symptomatic amoebiasis from 1965 to 1973. The majority of patients gave a history of overseas travel or residence. Intestinal amoebiasis most frequently occurred in its non-dysenteric form, so that there were some problems in differentiating it from more commonly occurring forms of colitis. The potential for amoeboma to be mistaken for a neoplasm was evident. Amoebic liver abscess was confirmed in 10 cases and, in nine of these, the abscess was localized to the right lobe of the liver. A total colectomy had been performed in one case and an abdominoperineal resection of the rectum in another before hospital admission in Brisbane and confirmation of the diagnosis of amoebiasis. Five of the patients with amoebic liver abscess underwent laparotomy soon after admission because of upper abdominal symptoms and signs which resembled those of other surgical conditions. Although the indirect haemagglutination test was of considerable assistance in diagnosing amoebiasis, it was apparent that attention to detail in the collection and examination of faecal specimens remained of major importance. A trial of metronidazole, which is both effective and relatively safe, is advocated in cases of diagnostic difficulty, when amoebiasis is suspected but unproven, and when the adoption of an alternative diagnosis would lead to the initiation of less satisfactory drug therapy or involve otherwise unnecessary surgery.


Virus isolation and titration at 33 degrees and 37 degrees C. Various prototype viruses and original specimens were comparatively titrated in cell cultures at 33 degrees and 37 degrees C. Higher titers at 37 degrees were consistently obtained with adenoviruses; for other viruses (enteroviruses, herpesvirus hominis, vaccinia virus, parainfluenza viruses) the titers were mostly identical at either temperature. Original specimens and prototye strains showed the same behavior. The habit to cultivate viruses from throat swabs at 33 degrees C is unsatisfactory for adenoviruses.


False positive rubella virus haemagglutination inhibition reactions: occurrence and disclosure. A floatation centrifugation procedure is described by which antibodies and non-specific rubella virus haemagglutination inhibitors can be completely separated. Using this method it was shown that false positive reactions occur with the conventional pretreatments of sera for removing inhibitors, especially with the heparin-McCl2 procedure. Other methods for removal of inhibitors were examined in view of recent knowledge about the chemical nature of the inhibitors. Treatment with phospholipase C proved useful for disclosure of false positive reactions, while floatation centrifugation was the most sensitive method for demonstration of low antibody concentrations.


The effect of azide on the spectral and catalytic properties of ascorbate oxidase. (1) 45% of the total copper of green zucchini ascorbate oxidase is EPR-detectable. At least two species of copper are present, one with a small A parallel (Type 1) and one with a large A parallel (Type 2). Computer simulated spectra indicated 50% contribution by each type of copper. (2) Azide inhibited ascorbate oxidase activity by an uncompetitive mechanism. EPR and optical spectra performed on titration of ascorbate oxidase with azide indicated the formation of a copper-azide complex. The Type 2 copper appears to be the binding site of azide. The involvement of the EPR non-detectable copper as an anion binding site with high affinity toward azide can not be excluded.


Pleiotropic effects of a DNA adenine methylation mutation (dam-3) in Escherichia coli K12. The dam-3 mutation results in a five-fold reduction in the number of 6-methyl-adenine (6-meA) residues in the DNA of E. coli K12 or phage lambda. The DNA of phage fd appears to be devoid of 6-meA when propagated on dam-3 bacteria. The phenotypic differences between dam-3 and dam+ bacteria include: (i) increased free phage in lysogenic dam-3 cultures, (2) increased sensitivity to methyl methanesulfonate (MMS), (3) inviability of dam-3 lex-I strains, (4) lower molecular weight of DNA in dam-3 bacteria in the absence of DNA ligase and (5) increased rate of DNA degradation in dam-3 recA strains.


Mutagenicity testing with Salmonella typhimurium strains. II. The effect of unusual phenotypes on the mutagenic response. The enhanced sensitivity of some Salmonella typhimurium strains to the mutagenic action of a number of chemicals appears to be due to the defect in the uvrB gene product and not to an inability to produce H-2-S or to the absence of formic acid hydrogenlyase which also characterizes these strains.


Comparative studies on the biological activities of cardiotoxin, melittin and prymnesin. The actions of cardiotoxin (CTX), melittin and prymnesin were compared on dog erythrocytes, chicken biventer cervicis muscle, rabbit conjunctiva, acetylcholinesterase, succinate-cytochrome c reductase and turbidity of the rat liver mitochondrial suspension. 1. CTX and melittin were approximately equipotent in the various biological activities, while prymnesin was not. 2. The rate of direct ehmolysis induced by CTX was slow, while that induced by either melittin or prymnesin was fast. 3. Phosphate ions, 10mM Ca++, as well as 1 mM reduced glutathione, considerably inhibited the CTX-induced hemolysis, but only slightly inhibited that induced by melittin or prymnesin. 4. CTX, melittin and prymnesin caused contracture of the chicken biventer cervicis muscle. Prymnesin was much less active in this preparation as compared with its hemolytic potency. The CTX contracture was completely inhibited by high Ca++ (10mM) medium, while the melittin contracture was not. 5. The rate of CTX contracture to reach the peak tension was increased when the concentration of CTX was increased, while the rate of melittin contracture did not change very much as the concentrations varied. 6. All three toxins caused a local irritation of the conjunctival sac of the rabbit eye. 7. Both CTX and melittin inhibited acetylcholinesterase and succinate-cytochrome c reductase activities, and also increased the turbidity of the rat liver mitochondrial suspension, while prymnesin was totally inactive in these respects. It is concluded that the mechanism of actions of these toxins may be different at the molecular level. The role of the detergent properties of these toxins in their biological activities is discussed.


The in vitro effects of vinblastine and vincristine on the responses of the guinea-pig vas deferens to nerve stimulation. 1. Neither vinblastine nor vincristine (1x10-4M) appeared to cause a specific blockade of transmission through the guinea-pig hypogastric ganglion, since responses to preganglionic nerve trunk stimulation were lost no sooner than responses to postganglionic nerve trunk stimulation. 2. The responses to postganglionic nerve trunk stimulation were blocked by vinblastine or vincristine at a time when responses to stimulation of intramural nerve fibres were little affected. 3. The results do not support the suggestion that inhibition of the exocytotic release of transmitter is responsible for the early in vitro effects of these drugs.


Ultrastructural changes accompanying the induced differentiation of clonal rat nerve and glia. Dibutyryladenosine 3'-5' monophosphate (DBcAMP) induces ultrastructural transformations in clonal rat nerve and glia. Cells cultured in the presence of DBcAMP contain large numbers of aligned microtubules and microfilaments in their elongated processes, while control cultures without DBcAMP are relatively devoid of these structures. In addition, the cells exposed to DBcAMP contain 2000 A to 6000 A vesicles which are not observed in control cells.


Neurochemical aspects of post-tetanic potentiation of monosynaptic reflexes in the cat spinal cord. I. Analysis of amino acids at maximum of potentiation. In order to determine the chemical changes which might occur during post-tetanic potentiation, amino acids from the motor regions of the ventral horn of the spinal cord (potentiated and unpotentiated sides) of 10 different cats were analyzed. The intermittent tetanic stimulation of the Nn. gastroc. (only on the potentiated side) was carried out until a maximum of potentiation was reached (3--4 min). The monosynaptic reflexes were obtained from the ventral roots (L7 or S1) of both sides. The amino acids of the potentiated side were compared to those of the unpotentiated side (control) using a 14-C-dansyl chloride procedure. The two main amino acids considered to be excitatory neurotransmitters, glutamic acid and aspartic acid, showed a more than 20 per cent increase on the potentiated side as compared to the control side. Glycine, which plays an inhibitory role, especially in the spinal cord, reacted with 6 per cent decrease, whereas GABA which is also considered as an inhibitory neurotransmitter showed a change of + 11 per cent on the potentiated side as compared to the unpotentiated side. The importance of the potentiation time for those changes is pointed out.


The effect of pentobarbital on basal and ether-stimulated ACTH secretion in intact and adrenalectomized rats. Pentobarbital in a dose of 3.5 mg/100 g b.w. did not suppress the high  basal a.m. levels of plasma ACTH in adrenalectomized male rats. In both intact and adrenalectomized rats prior administration of the drug slightly depressed the rise in plasma ACTH induced by 2.5 min of ether inhalation, but this depression is of questionable statistical significance.


Growth hormone effects on sleep and wakefulness in the rat. The sleep-wakefulness pattern and brain protein levels were determined in rats for 3 h following these conditions: administration of an inhibitor of protein synthesis (anisomycin), administration of several doses of rat growth hormone (GH) or thyrotropin, and administration of a combination of anisomycin + GH or thyrotropin. Anisomycin inhibited sleep and increased wakefulness, GH increased REM sleep, and thyrotropin produced no change. The combined administration of GH and anisomycin returned sleep to control levels. Anisomycin produced a time-dependent decrease in brain protein levels, GH produced changes in brain protein levels as compared to controls in the second hour only, and thyrotropin had no effect upon brain protein levels. The results are discussed in terms of the possible relationship between sleep and proteins.


[Bilateral carcinoma of the breast].

[Bilateral carcinoma of the breast]. Bilateral breast cancer is examined in the light of the literature data and a personal series. Lobular, asynchronous forms, either in situ or infiltrating, are usually involved. The fact that in situ changes are often found in the second neoplasia, with metastases solely in its tributary lymph nodes, suggests that such carcinoma was already present at the time of the first operation, though not clinically detectable. Since bilateral forms are commonly hormone-dependent, multiple biopsies should be routine on the contralateral breast. Preventive mastectomy associated with ovariectomy shold be performed on the slightest sign of carcinomatous or even precancerous alterations.


Odontodysplasia. Report of two cases and review of the literature. Odontodysplasia is a rare developmental anomaly affecting the tooth structures in both deciduous and permanent dentitions. The enamel is thin and uneven in thickness, and the detinal tissue surrounds very large pulp chambers. Denticles are present in the pulp organ. The maxilla is involved twice as frequently as the mandible. Most of the affected teeth are in the anterior segments; however, all other teeth can be affected. The cause is unknown. Because of the tendency of the affected teeth to develop abscesses, the most common treatment is extraction. Two additional cases are reported, and the literature is reviewed.


[Changes in the muscle fiber induced by p-phenylenediamine in the rat]. P-phenylenediamine (PPD) induces skeletal muscle lesions in rats which have been chosen as a model for investigation of the inflammatory and degenerative pattern of the muscle fibers. With the use of histochemical and ultrastructural criteria, the morphology of the lesions have been analysed in the diaphragm. Fifteen minutes after the induction by PPD, a subsarclemmal oedema can be shown by electron microscopy. Enzymatic changes appear during the first hour. The pathologic features are more prominent after twenty-four hours. The lesions are characterized by a segmental necrosis adjacent to unaltered fibers and by particular types of fibers such as target, snake coils, core fiber. A comparison between the lesions induced by PPD and those occurring during other types of myopathies has been made.


[Gram negative bacillus septicemias. Results of treatment of 31 gram negative bacillus septicemias using intravenous nalidixic acid]. Enterobacteria multiresistant to usual antibiotics, often remain sensitive to nalidixic acid, sometimes as a result of synergy with polymixins. Use of the intravenous route makes it possible to obtain more than adequate serum levels. Pharmacological study has indicated appropriate doses in terms of renal function. Intravenous nalidixic acid has been used in the treatment of 31 cases of Gram negative septicaemia, with success in 22. These results are all the more significant given that the patients were all seriously ill, cultures having grown multiresistant organisms and that nalidixic acid was used only after other antibiotics had failed.


Enzymatic synthesis of oligonucleotides of defined sequence. Addition of short blocks of nucleotide residues to oligonucleotide primers. Polynucleotide phosphorylase from Escherichia coli can be used to catalyse the addition of short tracts of deoxyadenylate residues to the 3'-termini of deoxyribooligonucleotides of the type pdAn-dN (where dN = dC, dT or dG) using dADP as donor. Similarly, the enzyme can also be used to catalyse the addition of short tracts of adenylate residues to the 3'-termini of ribooligonucleotides of the type An-N (where N = C, U or G) using ADP as donor. In the ribooligonucleotide series, phosphorolytic cleavage of the primer oligonucleotides is significant and results in the concommitant production of oligoadenylates lacking the N residue. Oligomers of the same length, with and without the residue N, were readily separated by thermal elution from cellulose-pdT9 columns. This latter procedure therefore provides a simple method for purification of the oligoadenylates containing an internal base substitution and it also provides a convenient assay for oligonucleotide phosphorolysis.


Solid support synthesis of oligothymidylates using phosphorochloridates and 1-alkylimidazoles. A study of the synthesis of oligothymidylates via phosphotriester intermediates on a polystyrene support is described. The sequence involves condensation of a phenyl nucleoside-3' -phosphorochloridate with the 5'-hydroxyl group of the carrier bound oligonucleotide derivative in the presence of 1-methylimidazole. Conditions for preparation of the phenyl nucleo-side phosphorochloridate as well as for the condensation on the support are discussed. d-TpTpTpT was obtained in 31% overall yield from carrier bound thymidine in one series of experiments, and d-TpTpTpTpT was obtained in 9% yield in another. The cycle for addition of one nucleotide unit can be completed in about six hours.


The 3' terminal oligonucleotide of E. coli 16S ribosomal RNA: the sequence in both wild-type and RNase iii- cells is complementary to the polypurine tracts common to mRNA initiator regions. Application of Sanger techniques to the analysis of the 3' terminal oligonucleotide from E. coli 32-P-labelled 16 S rRNA yields the sequence AUCACCUCCUUAOH. This sequence is identical in RNA isolated from two wild-type strains (MRE600 and E. coli B, SY106) and from a mutant strain (AB301/105) defective in RNase III. Data presented here explains the previous derivation of an incorrect sequence (AUCCUCACUUCAOH) by others. The functional significance of complementarity between the 3' terminus of 16S rRNA and poly-purine tracts commonly found in mRNA initiator regions is discussed.


Specifity of DNA-basic polypeptide interactions. Influence of neutral residues incorporated into polylysine and polyarginine. An approach is described for evaluation of the specificity of basic polypeptides concerning the base pair composition of DNA. The polypeptides were covalently bound to CNBr activated agarose and two DNAs strongly different in base composition but of equal molecular weight were loaded and detached by a NaCl gradient. The difference in the NaCl concerntrations between the elution maxima of the two DNAs was taken as a measure for the recognition specificity. The results obtained confirmed the known AT- und GC-specificity of polylysine and polyarginine, respectively. Neutral residues incorporated into polylysine generally reduce the interaction affinity and also the AT-specificity of their host. This behavior is very pronounced with three homogeneous fractions of clupeine containing about one third of neutral aliphatic amino acids within clusters of arginine; the base pair specificity of these arginine copolymers was found to be practically nil.


Repair methylation of parental DNA in synchronized cultures of Novikoff hepatoma cells. Parental and filial DNA strands were isolated from a Novikoff rat hepatoma cell line, synchronized by S-phase arrest with excess thymidine, that had completed up to one round of DNA replication in the presence of (14-C-methyl)methionine and (6-3-H) bromodeoxyuridine. Both strands were methylated, the proportion of total methyl label in parental DNA increasing slightly with time in S-phase. The studies were repeated with (14-C-methyl)methionine and (3-H)deoxycytidine to determine if parental methylation occurred on extant or repair-inserted cytosine residues. Both (14-C) and (3-H) were found in parental DNA. The (14-C)/(3-H) ration of parental DNA-5-methylcytosine was about twice that in filial DNA while the (3-H) data showed twice the concentration of 5-methylcytosine in parental compared to filial DNA. Thus parental methylation occurred on repair-inserted cytosine residues and resulted in overmethylation. That the DNA damage and repair was due to 5-phase arrest was shown by repeating the studies using a sequential mitotic-G1 arrest method. With this method little (14-C) or (3-H) was found in parental DNA. We conclude that S-phase arrest leads to DNA damage and repair with subsequent overmethylation of repair-inserted cytosines; that sequential mitotic-G1 arrest minimizes DNA damage; and, that the latter technique, suitable for synchronization of large quantities of cells, may prove useful in relatively artifact-free studies of eukaryotic DNA replication.


Determination of the sequences of 18 nucleotides from the 5'-end of the 1-strand and 15 nucleotides from the 5'-end of the r-strand of T7 DNA. The sequences of 18 nucleotides from the 5'-end of the 1-strand and 15 nucleotides from the 5'-end of the r-strand of T7 bacteriophage DNA have been determined to be pT-C-T-C-A-C-A-G-T-G-T-A-C-G-T-C-C-C (1-strand) and pA-G-G-G-A-C-A-C-A-G-C-G-C-T-C (r-strand). The 5'-termini of whole DNA or separated strands were kinased using polynucleotide kinase and (gamma-32-P) rATP. The DNA was partially digested with pancreatic DNase and the fragments were separated by two dimensional electrophoresis and homochromatography. To complete the sequence, snake venom phosphodiesterase digestions of these fragments were carried out. The relationship of these sequences to the proposed cleavage of concatemeric DNA during DNA replication is discussed.


The determination of secondary structure in the poly(C) tract of encephalomyocarditis virus RNA with sodium bisulphite. The degree of secondary structure in the poly(C) tract of encephalomyocarditis virus (EMCV) RNA has been investigated using sodium bisulphite, which brings about the hydrolysis of non-base-paired cytidylic acid to uridylic acid in RNA. The percentage conversion of C to U in the poly(C) region of native EMCV RNA was similar to that found in a synthetic polynucleotide lacking secondary structure [poly(C)]. When poly(I) was annealed to either native or denatured EMCV RNA, it protected the poly(C) tract from the action of bisulphite. It is concluded that the poly(C) tract of EMCV RNA in solution is very largely single-stranded.


Differentiation between exonucleases and endonucleases and between haplotomic and diplotomic endonucleases using 3-h-dna-coated wells of plastic depression plates as substrate. Using our new method for assaying DNases with radioactively labeled DNA bound to wells of plastic depression plates as substrate, we could distinguish between endonucleases and exonucleases and between haplotomic and diplotomic endonucleases. Oligonucleotides smaller than 30 detach from the DNA binding sites of the well into the reaction mixture. Thus, a lag period was evident before endonucleases produced small soluble oligonucleotides, while exonucleases released mononucleotides or short oligonucleotides without any lag period. Haplotomic and diplotomic endonucleases were detected because of the different rates in which they produce small soluble oligonucleotides which were expressed in different lag periods. Under conditions in which the haplotomic DNase 1 changes its mode of action to become a diplotomic enzyme, the shift was clearly detected by a change in the lag period in the well assay.


The modified nucleosides of tRNAs. II. Synthesis of 2'-O-methylcytidylyl (3'-5') cytidine. The synthesis of 2'-O-methylcytidylyl (3'-5')cytidine by the triester method using as protecting groups, 2,2,2-trichloroethyl for phosphate hydroxyl group, p-chlorophenyoxyacetyl for 5-hydroxyl group, methoxymethylidene for 2',3'-cis-diol system, and benzoyl for the exo-amino group of cytidine is presented. The obtained product was characterised by UV, electrophoresis, chromatography and an enzymatic digestion.


Structural and compositional changes attending the ultracentrifugation of very low density lipoproteins. The effects of repetitive ultracentrifugation on the physical and chemical properties of very low density lipoproteins (VLDL) were investigated. VLDL recentrifuged one to seven times were characterized by chemical analyses, analytical ultracentrifugation and electron microscopy. The VLDL content of triglyceride was increased and the proportion of phospholipid decreased by ultracentrifugation. Recentrifugation of VLDL decreased the number of Sf-o 20-100 particles and generated particles of Sf-o greater than 400. The bulk of the material removed from VLDL by ultracentrifugation was lipoprotein having pre-beta mobility on paper electrophoresis, flotation rates of Sf-o 10-100 and a particle size of 300-400 A-O. Two ultracentrifugations separated an average of 14% of the starting VLDL protein. Characterization of the apoproteins in this material by polyacrylamide gel electrophoresis, gel chromatography, immunoprecipitation and amino acid analysis demonstrated a relatively high proportion of beta-apoprotein and relatively little C-apoproteins.


[Carcinoma of the breast in the male. Clinicopathological study of 10 cases]. The carcinoma of the male breast is a rare lesion, being aproximatelly 100 times less frequent than in women. Of 1930 cases of mammary cancer seen at the Hospital of Oncology of the National Medical Center, I.M.S.S. during a period of 10 years we found 10 histologically proved cases of carcinoma of the male breast. Their microscopic appearence was that of an invasive ductal carcinoma. The surgical treatment consisted in radical mastectomy on six patients, supermastectomy is one case and simple mastectomy in other. Two patients received radio and chemotherapy. In three patients bilateral orchiectomy was done and in other two cases a bilateral adrenalectomy was performed. The results of the review of these cases are compared with other previously reported.


[Experience in the use of competitive binding of hormones with proteins for the determination of non-metabolized glucocorticoids in the blood and urine in some pituitary-adrenal diseases]. A method of competitive protein-binding analysis was applied to the study of nonmetabolized glucocorticoids (NMG) in the plasma and urine of healthy persons and those suffering from hyper- and hypocorticism.  NMG determination by this method reflected adequately the funcitonal condition of the adrenal cortex under normal conditions and in hypophyseo-adrenal diseases, including tests with ACTH and dexametazan, and coordinated with the results obtained by standard chemical methods.


Serum prolactin levels and prolactin binding activity in adrenals and kidneys of male rats after dehydration, salt loading, and unilateral nephrectomy. Serum prolactin (PRL) levels and PRL binding activity in microsomal membranes from kidneys and adrenals were measured in control, water-deprived, unilaterally nephrectomized, and salt-loaded male rats. Unilateral nephrectomy and water deprivation increased serum prolactin levels significantly. Unilateral nephrectomy did not alter PRL binding activity in the kidneys, but significantly increased it in the adrenal glands. Salt loading had no effect on serum prolactin levels or PRL binding in the kidneys; but significantly increased PRL binding in the adrenal glands. Inhibition curves and tests of cross reactivity with LH, FSH, TSH, and GH showed that binding of PRL to its receptors in the kidneys and adrenals was specific. These observations suggest that PRL has a role in salt and water metabolism and that PRL receptors in the kidney and adrenals participate in this regulatory system.


Inhibition by levamisole of metastases by cells transformed by herpes simplex virus type I. Levamisole was tested to determine whether the drug could reduce metastases by HSV-1-transformed cells in a model hamster system. The results presented reveal an inhibition of metastases to the lungs even when the drug is inoculated after development of subcutaneous tumors at the site of inoculation of the cells.


[Estradiol receptors in the sex organs and some other organs of male rats]. A study was made of specific binding of estradiol (E2) by cytosol and the extracts of the nuclei of the testes, the prostate, the kidneys and the liver of the sexually-mature male rats. In the cytosol of all the mentioned organs there were found macromolecules with a high affinity (Kac similar 1--4-10(9)M(-1)). Low capacity ti the hormone (Nc similar to (1--2)--minus 14 mol per 1 mg of protein) and a marked hormonal sterospecificity--only the preparations with an estrogenic activity, but not testosterone, 5alpha-dihydrotestosterone, progesterone and corticosterone competed for H-3--E2 binding. The capacity of cytosol of these organs to bind E2 apecifically was eliminated by pronase, but not by RNA-ase and DNA-ase. The mentioned properties of the E2-binding macromolecules of cytosol of the testes, the prostate, the kidneys and the liver permitted to refer them to the estrogenic protein-receptors. Specific E2-binding was also revealed in the extracts of the nuclei of these organs, but its level was extremely low.


Follicle stimulating hormone stimulation of 125-I-human chorionic gonadotropin binding in porcine granulosa cell cultures. In order to see if FSH acts directly upon the granulosa cell to stimulate hCG binding, granulosa cells harvested from small 1-2 mm porcine follicles were grown in 250 ml flasks in chemically defined media containing 0.05 mug/ml highly purified human FSH for 2, 4, and 6 days. The defined medium consisted of culture medium 199 plus 0.4% bovine serum albumin, 0.2% lactalbumin hydrolysate and 10 munit/ml insulin. The cultures were harvested by scraping with a rubber policeman and incubated with 0.1 mug/ml 131-I- or 125-I-hCG. Binding expressed as cpm/culture or per mg protein yielded similar results. In five separate experiments addition of FSH stimulated hCG binding two- to fourfold above control cultures. In a typical experiment after 2 days of culture, the specific binding of control cultures to hCG was 962 plus or minus 45 cpm/culture (-x plus or minus SE; n = 3) and the binding in cultures grown in the presence of 0.05 mug/ml FSH was 3933 plus or minus 1787 (n = 3; P less than 0.01). Granulosa cells harvested from large (8-12 mm) follicles grown under similar conditions bound 29,669 plus or minus 948 cpm/culture (n = 4). These data demonstrate that FSH may have a direct stimulatory role upon induction of granulosa cell LH-hCG receptors in vitro.


[Reactivity of the adrenals to ACTH in rats with alloxan diabetes]. Experiments were conducted on rats. A study was made of the adrenal gland ACTH reactivity under conditions of alloxan diabetes. The function of the adrenal gland increased one month after the administration of alloxan; this was indicated by an increase of their absolute and relative weight, by an elevation of the corticosterone content in the peripheral blood and the glands proper. ACTH stimulated the adrenal gland function in rats with an intact pancreas, increasing the weight of the adrenal glands, the level of corticosterones in the blood and the adrenal glands. ACTH reactivity proved to be lowered in rats with alloxan diabetes. The blood corticosterone level increased in them less and changes in the weight of the glands and of the hormone concentration in them proved to be statistically insignificant.


[Effect of ACTH, TTH, and STH on respiration and oxidative phosphorylation in the liver of hypophysectomized rats]. An experimental study was make of the changes in respiration and of the oxidative phosphorylation in the hepatic mitochondria of the hypophysectomized albino rats, with consideration to the regulatory effects of the ACTH, TTH, and STH.  There was an intensification of the conjugation of the oxidative and of the phosphorylation processes in the mitochondria of the liver of hypophysectomized albino rats as a result of ACTH replacement therapy in a dose of 3 Units per 100 g of weight.  TTH given in a dose of 0.03 IU per 100 g of weight under conditions of hypophysectomy stimulated oxidation of alpha-ketoglutaric acid in the mitochondria of the liver of albino rats; phosphorylation remained reduced, i.e. there was seen a dissociation of the process of oxidative phosphorylation.  As a result of replacement therapy with the STH given in a dose of 10 gamma per 100 g of weight the energy metabolism in the liver of hypophysectomized albino rats changed in the direction of an increase in the P/O coefficient of the hepatic mitochondria.  ACTH, TTH, and STH were given from the 15th to the 21st days after hypophysectomy, twice a day, subcutaneously.


Specific immune adherence assay for human hepatitis A antibody application to diagnostic and epidemiologic investigations. A specific immune adherence (IA) test for hepatitis A antibody in human serum was described employing liver extract of marmosets infected with CR326 strain human hepatitis A virus. Persons with hepatitis A, but not hepatitis B, developed hepatitis A IA antibody soon after onset of the acute illness and this persisted thereafter. There was very close agreement in the tests for human hepatitis A immune adherence, complement fixing (CF) and neutralizing antibodies. IA antibodies appeared to develop somewhat later than CF or neutralizing antibody. A limited epidemiologic study of a family outbreak of hepatitis A and B in Costa Rica showed simultaneous occurrence of the two diseases and was supportive of the concept that susceptible persons in a country with high hepatitis A prevalence generally acquire their infections at an early age and are immune thereafter. Most persons of high socioeconomic level in an area of low hepatitis A incidence may proceed to adulthood without experience with hepatitis A. Person of low socioeconomic level, however, such as commercial blood bank donors and prisoners, show high incidence of hepatitis A antibody. Hepatitis IA and CF antibodies persisted in human subjects for at least 7 hr after hepatitis A virus infection. Captive chimpanzees and grivet and rhesus monkeys, not given hepatitis A virus, showed evidence of previous experience with human hepatitis A or an antigenically related virus based on tests for hepatitis A antibody. Other subhuman primates, rodents, and swine, not given hepatitis A virus, were without hepatitis A antibody. The IA test provides an excellent tool for diagnostic and epidemiologic investigations of hepatitis A and should be of considerable value to detect hepatitis A virus in attempts to propagate the virus in cell culture. There was considerable difference in hepatitis A IA antibody content of different lots of commercial human immune globulin, though the majority titered 1:4000 or 1:8000.


Inhibitory effect of prolactin on the development of fatty liver induced by ACTH in thrat. The action and interaction of ACTH and prolactin in the development of fatty liver were investigated in intact rats treated with exogenous hormones. Administration of ACTH or of combinations of ACTH and GH to intact female rats was found to elicit significantly greater increase in liver total lipids content and concentration than administration of combinations of ACTH, or ACTH and GH, with prolactin. In addition, the results support the data reported by Bates et al. (6) that simultaneous application of GH, prolactin and ACTH reduces the effct of ACTH, upon adrenal gland weight.


Protection of A/He mice by a Friend virus pseudotype against challenge with Friend virus. Prior inoculation of 7-wk-old A/He mice with the Graffi pseudotype of Friend virus protected the animals against subsequent challenge with Friend virus. Graffi leukemia virus itself did not induce protection, probably because it failed to replicate in these mice.


Rubella and rheumatoid arthritis: hyaluronic acid and susceptibility of cultured rheumatoid synovial cells to viruses. Synovial cell lines were established from patients with rheumatoid arthritis (RA) and from normal human embryos. High levels of hyaluronic acid (HA) were produced by some RA cell lines, some of which were partially or completely resistant to infection with Newcastle disease virus (NDV), vesicular stomatitis virus (VSV), and rubella virus (RV). Normal fetal synovial cells lines were susceptible to NDV, VSV, and RV. Infection with virus became possible after treatment of RA cells with hyaluronidase to depolymerize HA, and HA prevented infection of normal synovial cells with VSV. These results provide evidence that HA and not chronic or latent viral infection is responsible for the lack of susceptibility of RA synovial cells to certain viruses.


Specific adenosine binding proteins from rat liver. Specific adenosine-binding proteins from homogenates of rat liver have been fractionated on a DEAE-cellulose column. Three major peaks have been identified with respect to histone phosphokinase and cAMP and adenosine-binding activities. Peak I contains only histone phosphokinase activity not stimulated by cAMP. Peak II contains histone phosphokinase slightly stimulated by cAMP. Both cAMP- and adenosine-binding activities are found in this fraction. The major adenosine-binding protein is associated with Peak III. Histone phosphokinase in Peak III which also binds cAMP is stimulated 2-fold by 2.5 muM cAMP whereas adenosine at 2.5 X 10(-4)M inhibits these enzymes equally well in each of three peaks. The specificity of adenosine binding is discussed.


Differences and similarities between guanosine 3',5'-cyclic monophosphate phosphodiesterase and adenosine 3',5'-cyclic monophosphate phosphodiesterase activities in neuroblastoma cells in culture. There are phosphodiesterase activities in both particulate and supernatant fractions which hydrolyze guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP) with an apparent Km of 2-8 muM and with an apparent Km of 44-222 muM. 4-(3-Butoxy-4-methoxybenzyl-2-imidazolidinone (RO20-1724) did not inhibit cGMP phosphodiesterase activity in homogenates of mouse neuroblastoma cells, but markedly inhibited cAMP phosphodiesterase activity. Papaverine and theophylline inhibited both cGMP and cAMP phosphodiesterase activities to about the same extent. The former was more potent than the latter. The specific activity of cGMP phosphodiesterase as a function of protein concentrations first increased and then decreased. The specific activity of cAMP phosphodiesterase decreased under a similar experimental condition.


Quantitative histochemical study of a vitamin E analog on rat gastric cyclic AMP. The vitamin E analog, 2,2,7,8-tetramethyl-5,6-orthoquinonechroman, unlike vitamin E itself, had been reported to be a potent inhibitor of beef liver cyclic AMP-PDE in vitro (about 3.5 times more inhibitory than theophylline under the same conditions). In this in vivo study, single intraperitoneal injections were given to fasted rats, 15 min before killing, of a solution of 20, and of a suspension of 130, mg analog/kg in 4% ethanol. No significant increases over the 4% ethanol control values in cyclic AMP levels were produced in any of the histological regions of the glandular stomach. However, injection of the 4% ethanol itself produced a rise of about 50% (peak value 4.1 pmoles/mg wet wt, 0.16 pmoles/mug protein-nitrogen) in the cyclic AMP concentrations in the parietal cell region and had no significant effect in any of the other histological zones where the concentrations were much lower.


Concerning the relationship between protein synthesis and adenosine-3',5'-cyclic phosphate-stimulated steroidogenesis in isolated rat adrenal cells. Inhibitors of protein synthesis decrease protein synthesis in isolated rat adrenal cells to a greater extent than they decrease adenosine-3',5'-cyclic phosphate (cyclic AMP)-stimulated steroidogenesis. At low concentrations of the inhibitors, varying degrees of recovery of the rate of steroidogenesis occurs with increasing time of incubation. As the concentration is increased, the time required to achieve any recovery of the rate of steroidogenesis increases and the extent of recovery decreases. The recovery also depends on the amount of cyclic AMP present. During the process of recovery the inhibition of protein synthesis continues in a linear manner. An explanation consistent with these data involves a rapidly turningover protein, the concentration of which is independent of the level of cyclic AMP present. However, the extent of transformation of this protein to an active form depends on the concentration of cyclic AMP.


Effects of steroid hormones on replication of murine sarcoma virus in mouse embryo cultures. The androgenic steroid hormone, testosterone, inhibited focus formation by the murine Moloney sarcoma virus in mouse embryo cells. The inhibition of focus formation was enhanced by cyclic AMP. Although focus formation was inhibited, there was no inhibition of viral replication. The glucogenic adrenal corticosteroids, cortisol and dexamethasone, and 17-beta-estradiol and progesterone did not affect focus formation by MuSV(M).


The development of superficial infraslow potential oscillations of the brain in chick embryos. The development of superficial infraslow potential oscillations (ISPO) of brain hemispheres, cerebellum and optic lobes was studied in chick embryos between day 9 and 21 of incubation. The ISPO were firstly registered in brain hemispheres at day 10 of incubation, i.e. 5 days before the onset of spontaneous EEG activity. The ISPO in 10-day-old embryos had an average frequency of 9.9 c/min and an amplitude of 0.14 mV. During further development till hatching the frequency decreased to 7.5 c/min and the amplitude increased to 1.39 mV. Similar ISPO with the same developmental trend were also registered from the surface of the cerebellum and optic lobes. Superficial ISPO were not synchronized either between both hemispheres or between different fields of the same hemisphere.


Functional differentiation of splanchnic A delta fibres in relation to viscerosomatic reflexes. The splanchnic afferent signal in the myelinated fibre spectrum was analysed in cats and its relationship to viscerosomatic reflex activity was studied. In addition to Abeta and Adelta components, a further elevation was observed in the sympathetic chain neurogram. According to the conduction rate (15 plus or minus 4 m/sec), it was caused by myelinated fibres 2-3 mu in diameter. The presence of this component at thoracic dorsal root level, or in the sympathetic chain in stimulation of the postganglionic part of the nerve trunk, confirmed the afferent nature of the observed activity. The threshold stimulus for these fibres, which were termed group Adelta2, was four times higher than for Abeta fibres. Correlation of the neurogram with evoked activity in the intercostal nerves confirmed the different functional role of group Adelta2 fibres. Adelta2 fibre activity evokes the early component of the two-component viscerosomatic discharge and Adelta2 fibre activity its later component. The authors discuss the functional significance of Adelta2 fibres, which probably mediate nociceptive information from the viscera.


Relationship between the activity of postsynaptic spinal cord elements and propriospinal and spino-bulbo-spinal reflexes. The relationship between the activity of the lumbar spinal interneurones and propriospinal (PS) and spino-bulbo-spinal (SBS) efferent reflex responses evoked by somatic (muscle, skin) and splanchnic nerve stimulation was studied in chloralose-anaestetized adult cats. During stimulation of one somatic nerve, the postsynaptic cord elements could be divided into three groups, according to whether their activity was was synchronous with the PS component of the efferent discharge (PS group), with the SBS component (SBS group) or with both (PS-SBS-group). Group SBS and PS-SBS interneurones were localized in the ventral quadrant of the grey matter. On stimulation of different nerves, the same interneurone could in one case respond synchronously with the PS component of the efferent discharge and in another with the SBS component. The membrane of units which did not generate propagated spike potentials during PS or SBS reflex activity was hyperpolarized in this period, or failed to display changes characteristic for postsynaptic inhibition. Convergence of somatic and visceral afferentation was observed in all three groups of postsynaptic elements. In type PS-SBS and SBS units it was massive (occurring in 85% and 100% of the cases respectively). The results confirmed the intimacy of functional contact of PS and SBS systems activated by somatic and visceral afferents.


Nonspecific collagenolytic activity of the femoral bone in immobilized rat extremities. Nonspecific collagenolytic activity was studied in rat bones after immobilization. The left hind limb was immobilized by sectioning the sciatic nerve. Enzyme activity was determined by using synthetic pentapeptide substrate (Pz-Pro-Leu-Gly-Pro-D-Arg). After immobilization the activity of nonspecific collagenase increased and reached its maximum on the third day after the operation. The activity was decreased after one week and attained levels of control  bones three weeks after sciatic nerve section.


Kaposi's varicelliform eruption complicating local facial trauma. Case report. A patient who had facial lacerations and then developed Kaposi's varicelliform eruption is reported. Presently, there is no specific therapy for this disease.


L-Histidine: failure to affect the sleep-waking cycle in man. L-Histidine was administered to three patients with intractable narcolepsy (20 g/day for 2 weeks), to 4 normal volunteers (32.4 g/day for 5 days), and to a patient with progressive systemic sclerosis (48.6 g/day for 16 days). No effect was observed on noctural EEG sleep patterns in any of the subjects or on the symptoms of the patients with narcolepsy. These results fail to support the hypothesis that histamine is a waking factor.


Molecur mechanism of action of the radioprotective substance WR 2721. The radioprotective effect of WR 2721 on catalase and the type and loci of its interaction with the enzyme have been investigated by means of spectrophotometric and electron spin resonance, (ESR) methods. The radiation damage, indicated by a change in enzymatic activity and in the Soret absorption  band, has been the less the larger the WR 2721 concentration. In the case of ESR investigations, addition of WR 2721 has resulted in a reduction of the spin concentration of Cu-2+. Since cysteamine has exhibited similar results, however, to a lesser extent, it can be assumed that the RS-ions are responsible for the protective effect. From the results obtained it can be concluded that (the dephosphorilized) WR 2721 forms a complex with the enzyme and acts as an electron donor.


Roentgen features of the superficial depressed type of early gastric carcinoma. The superficial depressed type of early gastric carcinoma is described. The macroscopic appearance is characterized by an irregular erosion, often associated with a deeper central ulceration. The surrounding mucosal folds exhibit abrupt termination, narrowing, and clubbing. The roentgen diagnosis requires good demonstrations of detail. The double-contrast technique is most important and informative and can be used to study almost any part of the stomach.


Intracranial tumors: correlation of angiography with dynamic radionuclide studies. In a group of 100 supratentorial brain tumors, 23% demonstrated increased activity during the dynamic portion of the brain scan. Increased activity correlates best with the following angiographic characteristics: (a) increased size of supplying vessels, and (b) vascular supply simultaneously from both parenchymal and meningeal arteries. Increased activity has no correlation with the presence of early venous drainage, peritumoral edema, or degree of tumor vascularity and/or stain.


The effect of phlebotomy on canine erythrocyte metabolism. Enzyme activity declines with erythrocyte age in most mammals. To test this concept in the dog, we decreased the PCV to less than 20 by phlebotomy. The erythrocytes were restored rapidly (1.57 per cent per day). The resulting decline in the mean erythrocyte age was accompanied by increased activity by most of the erythrocyte enzymes studied. Enzymes with lower initial enzymatic activity (hexokinase, pyruvate kinase, 6-phosphogluconate dehydrogenase and glutathione reductase) increased proportionally more than those with higher initial activity (lactate dehydrogenase, 3-phosphoglycerate kinase, glyceraldehyde-3-dehydrogenase and glucose-6-dehydrogenase). Among species, increases in enzyme activity after phlebotomy appear to be related to each species' life span. Most of the metabolites increased concomitantly with the highest reticulocyte period. Diphosphoglycerate concentrations did not change significantly during the experiment.


The demonstration by interference tests of an infective agent in fetuses from ewes inoculated with Border disease tissue. Fetuses and placental tissues were taken from pregnant ewes at intervals varying between eight and 21 days after inoculation with tissue suspensions from cases of Border disease. Virus isolation procedures involving the detection of a cytopathic effect in tissue cultures with or without interference tests produced universally negative results but interference tests, using a plaque technique with the NADL strain of bovine virus diarrhoea virus as a challenge virus, detected the presence of an agent in tissues from six out of 10 fetuses. Inoculated ewes allowed to proceed to term showed a serological response characteristic of Border disease infection, as measured by four different tests. Although hairy shaker lambs were not seen, the occurence of abortion and stillbirth due to causes other than bacterial agents, was an indication that the Border disease agent was present. Electron microscopy of fetal fluids failed to detect viral particles.


Changes in enterocyte mitochondria associated with deficiency of copper in cattle. Comparisons were made between specimens of intestinal mucosa from three young Friesian steers, killed when showing clinical signs associated with copper deficiency, and three controls that had received supplementary copper. Copper deficiency was associated with marked depletion of cytochrome oxidase in the epithelium of the duodenum, jejunum and ileum, and with partial villus atrophy in the duodenum and jejunum. Enterocytes from the duodenum, jejunum and ileum showed mitochondrial abnormalities ranging from slight swelling to marked localised dilation. Many of the mitochondria not affected by swelling had a distinctly condensed appearance. These changes are discussed in relation to the copper-responsive diarrhoea that affects a proportion of cattle suffering from copper deficiency.


Experimental infection of calves with respiratory syncytial virus. Three bovine isolates and one human isolate of RS virus were given intranasally to gnotobiotic, colostrum-deprived and conventional calves. All isolates produced a biphasic pyrexia associated with a serous nasal discharge. Virus was recovered from nasal secretions 4-10 days after inoculation from nasal, tracheal and bronchial mucosae and lung of animals killed 7-13 days after inoculation. Infection did not produce any macroscopic lesions, but histologically there was a focal degenerative rhinitis and a catarrhal bronchiolitis with the occasional formation of syncytia in bronchioles and alveoli.


[Spinal chrodoma - III. Review of the literature since 1960]. Vertebral chordomas develop from the intrarachidial -- and more often the intrasomatic --vestiges of the embryonic notochord, and are rare caancers that are more likely to become manifest, usually between 30 and 40 years of age, with a painful radiculo-medullary syndrome than with the clear signs of a tumour. The insidious evolution of this type of cancer, which gives rise to few metastases, and its ambiguous radiological appearance explain why it is usually diagnosed late after an anatomo-pathological examination. The fundamental histological element is the physaliphorous cell, ultrastructural studies of which have demonstrated that the large "mucous" inclusions of interstitial material. The discovery, by Murad and Murthy, of particles enclosed in a membrane in the chordomatous cells indicates possible viral involvement. Radio-surgical treatment results in more comfortable survival (very variable) although it involves repeated high-dose cobalto-therapy and repeated surgical excisions.


[Determination of urinary cyclic AMP in phosphorus and calcium pathology]. Quantitative analysis of urinary cyclic AMP in phospho-calcic pathology. The authors describe a method measuring amounts of cyclic AMP. Normal daily elimination in urine was measured in a group of normal subjects. Elimination was found to be raised in two-thirds of the patients with primary hyperparathryroidism, normal in those with idiopathic hypercalcaemia and neoplastic hypercalcaemia, and subnormal in patients with hypoparathyroidism. The urinary excretion of cyclic AMP after perfusion of parathyroid hormone was very low in cases of pseudo-hypoparathyroidism compared with that in surgical hypoparathroid controls. The results are compared with data from the literature. The theoretical and diagnostic value of these quantitative analyses is discussed.


Turnover of plasma total and very low density lipoprotein triglyceride in man. Basal plasma total triglyceride and very low density lipoprotein (VLDL) triglyceride turnover rates were determined in 110 subjects whose triglyceride concentrations ranged from low normal to markedly elevated values. The mean total triglyceride turnover rate was 13.7 mg - kg-1- hr-1, whereas the mean VLDL triglyceride turnover rate was 13.2 mg - kg-1 - hr-1. A highly significant correlation was present between the two turnover rates (r equal + 0.75). The endogenous serum triglyceride transported in the other lipoproteins (LDL and HDL) may account for more than half of the circulating triglyceride mass, but its significance in the total triglyceride transport is small. In a selected subgroup of 31 healthy subjects the plasma VLDL triglyceride concentration did not exceed 160 mg/100 ml. The range of this group's triglyceride turnover rate was completely comparable with most data reported in the literature for total serum or VLDL triglyceride transport in normal human subjects. When the turnover rate was plotted against the VLDL triglyceride concentration, three kinetic subgroups could be separated in accordance with the earlier experience on total serum triglyceride transport kinetics.


The esterification of cholesterol in plasma after acute myocardial infarction. The rate of plasma cholesterol esterification (LCAT activity) and the concentration of eight proteins in the plasma have been studied in the ten male patients during the course of acute myocardial infarction. Samples were drawn 22 hr, 3 days, 8 days, 2 weeks, and 7 weeks after the onset of the acute myocardial infarction. The changes of the plasma proteins were typical for the acute-phase reaction. LCAT activity decreased initially during the illness. The lowest values were found after 8 days. Concomitantly, a reducation in the plasma concentration of total and free cholesterol and cholesteryl esters was demonstrated. The rate of cholesterol esterification correlated significantly with the concentration of prealbumin, alpha-lipoprotein, and albumin. Seven weeks after onset of the infarction, the LCAT values were equal to those in a reference group. The results suggest that the synthesis of LCAT was decreased during the acute-phase reaction.


Herpesvirus hominis infections in renal transplant recipients. A longitudinal, prospective study of herpesvirus hominis (HVH, herpes simplex virus) was carried out in immunosuppressed renal allograft recipients using serologic, virologic and clinical techniques. The final study group consisted of 37 patients of which 31 were followed for at least 2 months and 26 for more than 1 year. A 4-fold rise or more in HVH complement-fixing antibody in relation to titers measured at the time of transplantation was found in 11 patients. Eight of these 11 patients had clinically recognizable herpetic lesions. An additional 9 patients had lesions without titer rise being demonstrable. The 20 of the 37 patients studied (54%) had evidence of active infection with HVH. Because of pain and discomfort herpetic sores were of clinical importance in 11 patients and lasted for 1 month or more in 9. Herpetic keratitis was seen in 3 and left permanent damage to sight in 2. Multiple, extensive, prolonged and sometimes destructive herpetic lesions affected 5 (16%) of all patients studied.


Antibiotic susceptibility testing of anaerobic bacteria by the standardized disc diffusion method with special reference to bacteroides fragilis. The susceptibility of 90 strains of Bacteroides fragilis to 16 antibacterial drugs was determined by the agar plate dilution test and the disc diffusion test. Good correlation of results was obtained with the two methods, and regression line analysis could be performed for beta-lactam antibiotics, erythromycin, tetracyclines, lincomycin and clindamycin. Thus the standardized disc diffusion method can be used for susceptibility testing, but only a clear distinction between sensitive and resistant strains can be seen.


[Complications in primary tumors of the small intestine]. Of 112 000 patients undergoing surgery between 1952 and 1973, 67 had a primary tumor of the small intestine. 22 patients had a benign tumor, 8 a carcinoid, 21 carcinoma and 15 sarcoma. Benign tumors were more frequent in the duodenum and ileum, carcinoids in the terminal ileum and carcinomas in the duodenum and jejunum. Sarcomas were found equally in all parts of the small intestine. The most common symptom for all types of the tumor was variable pain in the abdomen. Loss of weight occurred only in patients with carcinomas and sarcomas; heavy intestinal blood loss was most common in patients with benign tumors. Benign tumors often show invagination, while sarcomas cause occlusive ileus or perforation. All duodenal tumors show heavy intestinal bleeding but hematemesis is rare. Emergency surgery was necessary in 42% of patients with benign tumors or sarcoma and in 30% of patients with carcinoma. Five-year survival in patients with benign tumors is excellent (100%). Compared to this, five-year survival in patients with carcinoma, sarcoma or carcinoids is only 15%.


Adenosine inhibition of lymphocyte-mediated cytolysis: possible role of cyclic adenosine monophosphate. The in vitro destruction of tumor cells by specifically sensitized mouse lymphocytes was inhibited by adenosine; this inhibition was markedly potentiated by the presence of an inhibitor of adenosine deaminase. The inhibition of cytolysis by adenosine was accompanied by a rapid elevation in lymphocytic adenosine 3',5'-monophosphate (cyclic AMP) concentrations. Both the inhibition of cytolysis and the elevation of cyclic AMP were reversed by prolonged incubation of the lymphocytes in the presence of adenosine or, more rapidly, by removal of the adenosine. Low concentrations of adenosine also caused an elevation of cyclic AMP in human lymphocytes, and this effect of adenosine may contribute to the lack of immune response associated with adenosine deaminase deficiency.


Cell-mediated immunity to antigens associated with endogenous murine C-type leukemia viruses. Splenic lymphocytes from (BALB/c times A/J) F 1 mice are cytotoxic for BALB/c fibroblasts infected with an endogenous C-type leukemia virus, but are not cytotoxic for uninfected BALB/c fibroblasts. These results indicate that mice do not exhibit cell-mediated immune tolerance to antigens associated with endogenous C-type viruses.


Changes in protein levels in perfusates of freely moving cats: relation to behavioral state. Perfusates from the brains of freely moving cats, obtained by means of a push-pull cannula, contain high concentrations of proteins. The levels vary in a cyclic fashion and are higher during rapid eye movement sleep than during the waking state. The proteins represent a distinctive class of tissue protein and their changing levels appear to reflect an alteration in the protein content of the extracellular space of brain related to behavioral state.


Immunofluorescent localization of cyclic AMP in toad urinary bladder: possible intercellular transfer. By use of an immunofluorescent cytochemical staining technique, adenosine 3',5'-monophosphate (cyclic AMP) has been localized in toad bladder epithelial cells. Within 2 minutes after addition of vasopressin, staining intensity increases in both mitochondria-rich and granular cells. This finding, taken together with the precise anatomical relation between these two epithelial cell types and the observation that after separation of the two cell types vasopressin stimulates cyclic AMP accumulation in only mitochondria-rich cells, suggests that cyclic AMP may be transferred from mitochrondria-rich to granular cells as part of the response of the toad urinary bladder to vasopressin.


Analogs of cyclic adenosine monophosphate: correlation of inhibition of Purkinje Neurons with Protein Kinase Activation. Cyclic adenosine monophosphate (cyclic AMP) and 11 derivatives were applied to rat cerebellar Purkinje cells by iontophoresis. Cyclic AMP inhibited 63 percent of the cells, while the 8-parachlorophenylthio- and 8-benzylthio- analogs of cyclin AMP inhibited the spontaneous firing of 92 and 89 percent of cells, respectively. The ability of the 11 analogs to inhibit neuronal firing correlated (  r= + .78) with their reported potency in activating cyclic AMP-dependent protein kinase. These results extend previous studies, pointing to the mediation by cyclic AMP of the noradrenergic inhibition of Purkinje neurons, and provide new physiological evidence that protein phosphorylation is a major step in the action of cyclic AMP.


[Transcobalamins in megaloblastic anemias]. Transcobalamins are proteins which carry vitamin B12 and which are normally partly unsaturated. This study of transcobalamins was carried out in 17 subjects with megaloblastic anemia (12 true cases of pernicious anemia and 5 cases of folate deficiency). Among the latter, the transcobalamins were studied in 4 cases of pernicious anemia, before and after treatment with vitamin B12. The distribution of endogenous B12 was determined in four normal controls and two cases of pernicious anemia. This vitamin is normally distributed roughly equally between the three transcobalamins, whereas in B12 deficiency, T.C.2 is very unsaturated together with T.C.1 to a lesser degree. The latent fixation capacity of the serum is increased together with the latent fixation capacity of T.C. I and, above all, T.C. II but that of T.C. III is reduced in patients with pernicious anemia. In folate deficiency, only the latent fixation capacity of T.C. II is increased. When vitamin B12 is administered in physiological dosage, T.C. I becomes gradually saturated. In pharmacological dosage, total fixation capacity together with that of T.C. I and T.C. II become gradually reduced, but in spite of high levels of circulating B12, these proteins remain partially unsaturated. Various theories are suggested to explain the variations of these three transcobalamins in megaloblastic anemia but the problem is still unclear.


[Search for anti-intrinsic factor antibodies in the diagnosis of Biermer's anemia]. The diagnostic interest of a search for anti-intrinsic factor antibodies is emphasized from the authors research on more than 200 patients or controls. Antibodies of type I, so-called blocking antibodies, were detected in 66% of cases where the diagnosis of pernicious anemia was made. Type II, so-called precipitating antibodies, were found in 47% of patients with antibodies of type I and only in the latter. Certain etiological factors, already noted in the world literature, were found, in particular the link with the female sex and with blood group A. The specificity of these antibodies is very great and false positives are exceptional. We did not find them in any of the 104 controls. They were observed, however, in 5 of the 56 patients where the diagnosis of pernicious anemia was not definite, but it is likely that, in these 5 cases, pernicious anemia existed with some other disease. Our study also showed the limits of other methods of investigation of this disease; hypovitaminimia B12 is often corrected by treatment without proper inductions and B12 malabsorption on the Schilling test may not be corrected by the addition of intrinsic factor.


[Biermer's anemia with chronic lymphoid leukemia and hemolysis with autoantibodies]. The authors report a case of chronic lymphatic leukemia occurring four years after the onset of pernicious anemia. Multiple immunological abnormalities were detected. Hemolytic anemia with auto-antibodies and anti-thyroglobulin antibodies. Anti-intrinsic factor antibodies of type 1 were found but disappeared later. This case, the 9 th in the world literature, emphasizes the links between pernicious anemia, an auto-immune disease, and malignant disorders of the lymphatic and immune systems.


[Folate deficiency and neurologic disorders]. Estimation of serum folate was carried out in 74 patients with various neurological disorders. Levels less than normal were detected in 63 of them, with mainly peripheral neuritis, cerebellar syndromes and/or psychological disorders. The role of certain etiological factors was demonstrated, e.g. alcoholism, malnutrition, diarrhea, anti-epileptic treatment. Links between these neurological disorders and the folate deficiency remain to be demonstrated. In at least 8 cases, treatment with folic acid seems to have had a favourable influence on the course of these disorders.


[Macrocytic animia due to the combination trimethoprim-sulfamethoxazole]. The authors report a case of macrocytic anemia due to folate deficiency occurring suddenly after the administration of trimethoprime-sulfamethoxazole and completely cured by folic acid. This type of complication occurs particularly often in patients who already have a relative folate deficiency. In our case only moderate alcoholism was found. Thus individual predisposition due to enzyme abnormality must be considered. Prophylactic administration of folic acid in patients receiving this drug association is thus advisable.


[Lysozyme in hematologic diseases].

[Lysozyme in hematologic diseases]. Blood lysozyme estimation seems to be important in hematological practice. Serum levels are roughly proportional to the size of the pool and, above all, granulocytic renewal. Thus levels are increased compared with levels of circulating polynuclear cells. In bone marrow disorders, and particularly in myelofibrosis, owing to the infective granulopoiesis and/or increased destruction of the neutrophil polymorphs. It is lowered in neutropenia with a scanty bone marrow. It provides an important contribution to diagnosis of the type of acute leukemia, the fall in the lymphoblastic forms contrast with normal or increased levels in myeloblastic forms. Finally, there is a marked increase in lysosome urea in acute monocytic or myelomonocytic leukemia.


Surveillance of enterovirus infections in Bangkok. I. Isolation of enterovirus from faecal specimens of healthy children. During the period August 1970 through July 1973, about 50 faecal specimens collected each month from healthy pre-school children of lower economic status in Bangkok were studied for virus isolation using primary monkey kidney cells and new born mice. From a total of 1,823 samples, 557 (30.5%) were positive: 86 (4.8%) polioviruses, 77 (4.2%) coxsackieviruses B, 223 (12.2%) echoviruses, and 127 strains (7.0%) of unidentified viruses. Altogether, 45 serotypes of enteric viruses were identified. More than 30 serotypes, including the 3 types of poliovirus, were present each year. Infection rates were higher in males than in females and highest at one year of age, the rates decreasing with progressing age. There was no marked seasonal variation of enterovirus infections in Bangkok. The poliovirus infection index was low from September to January, and the index of polio and non-polio enterovirus infections was highest in April.


Parasitology survey and seroepidemiology of amoebiasis in South Kalimantan (Borneo), Indonesia. A parasitology surevy was conducted among inhabitants of 7 villages in 3 regencies in South Kalimantan Province, Indonesia. A total of 2,169 stool specimens, 2,756 blood smears and 1,027 serum specimens were obtained, representing samples from approximately 10%, 12% and 5% of the population, respectively. One to 8 different intestinal parasitic infections were detected in 97% of the people. Those parasites most frequently found were Trichuris trichiura (83%), Ascaris lumbricoides (79%), and hookworm (65%), followed by Entamoeba coli (37%), Endolimaxnana (12%), Entamoeba histolytica (12%), Iodamoeba bütschlii (11%), Giardia lamblia (5%), Entamoeba hartmanni (2%), Chilomastix mesnili (2%). Other parasites found were Enterobius vermicularis, Strongyloides stercoralis, Capillaria sp., Echinostoma sp., Hymenolepis diminuta, and Trichomonas hominis. Giardia lamblia was found more often in younger people and Entamoeba coli, Iodamoeba bütschlii and hookworm in the older age group. Ascaris lumbricoides occurred more frequently in females, and hookworm in males. Plasmodium vivax and Plasmodium falciparum were found in the blood smears of 4.4% of the people, mostly in the younger age groups. Seroepidemiological studies on amoebiasis were done by use of the indirect hemagglutination test with antigens prepared from the HK9 strain of Entamoeba histolytica maintained in axenic cultures. The frequency distribution of the reciprocal antibody titers showed a bimodal distribution with 34% of the population demonstrating positive reactions at titers of 1:128 or greater.


Unusual malignant tumours of the maxilary sinuses. Six rare tumours of the maxillary sinus occuring in South African Blacks are described. The incidence of sarcomas and tumours of glandular epithelium in the nasal sinus region is discussed and the literature is reviewed.


Plasma fatty acids and the control of lipolysis by cathecholamines. The role of lipolysis in adipose tissue is described in relation to the maintentance of plasma levels of fatty acids. The molecular details of the hormonal control of lipolysis in the human adipocyte are discussed.


Errors in metabolic regulation. A regulatory defect in the human adipocyte. Some of the control elements required for the fine regulation of metabolic processes in the adipocyte are described. These include substrate carriers, hormone receptors, allosteric enzymes and template surfaces. A possible example of an acquired defect of a rate-determining enzyme of glycolysis in the lipoma adipocyte is described. This is manifest as an impaired sensitivity of phosphofructokinase to feedback inhibtion by citrate. The orgin and consequences of this lesion are discussed.


Epipodophyllotoxin (VP 16-213) in the treatmetn of diffuse histiocytic lymphoma. Twenty-seven patients with diffuse histiocytic lymphoma, of whom 20 had failed to respond to all other forms of chemotherapy and radiotherapy, were treated with intravenous VP 16-213. Initial dramatic response was obtained in 5 (19%), good objective response in 12 (4%), and the remaining 10 (37%) either failed to respond or thad only minimal objective change in theri disease status. The response characteristically occured within two courses of therapy, but 8 of the 17 (47relapsed at this stage resulted in remission again begin achieved in these patients. It is concluded that VP 16-213 is an effective agent in diffuse histiocytic lymphoma, but it is of limited value when used as a single agent. This drug has surprisingly little myelotoxicity, and prospective studies are now in progress to evaluate its role in combination therapy.


[Clinical characteristics and genetic identity of the basal cell nevus syndrome (Gorlin-Goltz syndrome)]. The clinical, genetic, radiological, dental and dermatological aspects of 3 patients with the autosomal dominant basal cell naevus syndrome are reported. An analysis of the phenotypic features of 72 cases described in the literature is presented and compared with a previous analysis. Ash leaf hypopigmentation similar to that found in tuberous sclerosis represents a unique finding in this syndrome. Other similarities to the phacomatoses are discussed. We were able to support a previous report that patients with the basal cell naevus syndrome have a normal end-organ response to parathormone stimulation, and that it is most probably not related to pseudohypoparathyroidism, as earlier reports suggested.


Current management of hepatic tumors.

Current management of hepatic tumors. Today, the presence of a hepatic tumor can be diagnosed with considerable accuracy by means of isotope scans, arteriogram and ultrasonic imaging. Its localization to one lobe or other lobes is also generally achievable but with less accuracy because it is not yet possible to visualize the interlobar fissure by a noninvasive technique. Exploratory laparotomy with a view to resection is the preferred approach if the patient is in good general condition. Percutaneous biopsy of a hepatic lesion should be avoided unless laparotomy is not contemplated. Resection is the mainstay of therapy for all forms of hepatic malignant tumors and is the only modality that gives some prospect of cure. The prohibitively high operative mortality rate of former years, mostly due  to hemorrhage, has gradually decreased with improved understanding of hepatic anatomy and innovations in surgical technique. By means of adequate vascular control and, if necessary, parenchymal cold perfusion, major resections of difficult and bulky lesions can now be accomplished with safety. Systemic chemotherapy with single agents, intra-arterial infusion chemotherapy and hepatic dearterialization have each been found to be of modest therapeutic value in a variable proportion of patients with diffuse unresectable cancer of the liver. The results of current experience indicate that the response rate is not high and long term control of tumor is rare. Multiple drug combinations with or without infusion therapy or dearterialization are being tried in many centers. Therapeutic strategy and end results for the different forms of benign and malignant neoplasms of the liver are discussed.


Gliobastoma multiforme of the cerebellum. Glioblastoma multiforme of the cerebellum is rare. Approximately 33 case of cerebellar glioblastoma have been reported. Two-thirds of the cases occurred in adults and the male to female ratio was 2:1. The mean age was 46.7 years in adults and 10.4 years in children. Most of the tumors were lateral in location. Two of the patients (6%) had multiple glioblastomas. The time from onset of symptoms to death was approximately one year.


A survey of asthma mortality in patients between ages 35 and 64 in the Greater London hospitals in 1971. We have examined the death certificates from all patients aged 35-64 years who were recorded as dying from asthma in Greater London Council hospitals in 1971. Of the 47 death certificates studied, nine suggested that the primary cause of death was not asthma. From the remaining 38 deaths we have obtained 36 case records and found that 15 deaths occurred outside hospital and another two patients died in hospital having been admitted in a stable state. We have examined the remaining 19 case records to find out the circumstances of death in patients with asthma who die in hospital. We have been unable to exclude the possibility that many of the deaths in hospital were avoidable. Assessment of severity in most patients was incomplete, as judged by a retrospective analysis of case records, and many of the patients would be regarded as having had insufficient treatment. Four patients did not receive corticosteroids and in a further three the dose given was small. No physiological assessment of airflow obstruction was made in over half the patients. A comparison with 19 survivors of an admission to hospital with asthma did not provide enough information to account for the deaths. The survivors were in hospital for a shorter period of time, were slightly less ill, and were given comparable treatment regimens. Both groups of patients were inadequately assessed, and sedatives were given to approximately 70% of all subjects studied. The deaths in hospital usually occurred suddenly in the early morning in general medical wards.


Ultrastructural pathology of leaf cells of ryegrass (Lolium multiflorum) infected with ryegrass mosaic virus. Ryegrass mosaic virus particles and virus induced lamellar inclusions were found in mesophyll and epidermal cells of virus infected ryegrass leaves. The lamellar inclusions were occasionally found in phloem cells also. Virus particles occurred in cytoplasm, inside plasmodesmata and often in membrane bound sacs embedded in a matrix between plasmalemma and cell wall at or near plasmodesmata. Electron dense plugs protruding from plasmodesmata, finger-like cell wall outgrowths and cell wall deposits usually at plasmodesmata were also observed. Cytopathological changes in organelles in infected cells included dense deposits in the cisternae of endosplasmic reticulum and Golgi apparatus, mitochondria with electron-dense or opaque matrix, proliferating cristae and deteriorating unit membrane; and disintegrating chloroplasts.


Structure and development of P-protein in phloem parenchyma and companion cells of legumes. Phloem parenchyma and companion cells from four species of legumes, Phaseolus vulgaris L., Melilotus alba Desr., Desmodium canadense, L. and Dolichos lablab L., were examined electron microscopically to estabish the presence, structure and development of P-protein. P-protein components consisting of granular, fibrillar, tubular or crystalline structures were found in parenchyma cells of all species and in companion cells of M. alba. The earliest stages of P-protein formation were closely associated with dictyosome cisternae, dictyosome vesicles and/or spiny vesicles. After their formation, the P-protein bodies were frequently transformed into one or more structurally different components. Although these components appeared to be develop-mentally related, their specific associations and transformations differed in each species examined.


Structural and functional dynamics of oogenesis in Glossina austeni: general features, previtellogenesis and nurse cells. Glossina austeni oogenesis throughout its nine-day pregnancy cycle is described with the focus on previtellogenic stages. The ultrastructural details of the oocyte-nurse cell relationship and cyst formation is presented. The oocyte develops in a syncytial association with 15 nurse cells with the entire unit surrounded by a follicular epithelium. The nurse cells have large elaborate nucleoli. Evidence of nuclear emissions and the presence of an unusual cytoplasmic membrane association were found. A variety of nuclear inclusions are seen in the oocyte. Glycogen, lipid, ribosomes and membrane organelles accumulate in the oocyte during previtellogenesis.


The histology and fine structure of the olfactory organ of the squid Lolliguncula brevis Blainville. The olfactory organ of the squid has a thick, pseudostratified epithelium containing five morphological types of ciliated receptors. In the simplest receptors the cilia originate separately in the distal pole of the cell. All other receptors have some type of cilia filled cavity, varying from a simple pocket of cilia at the surface to a completely closed vesicle filled with cilia in cells deep in the epithelium. The receptors are compared to cells in the rhinophore of Nautilus and the olfactory organs of coleoid cephalopods. Possible functions of the olfactory organ, based on its morphology, are discussed.


Morphological variations in gap junctions of ovarian granulosa cells. Granulosa cells in ovarian follicles of rat, mouse, rabbit and hamster were studied by lanthanum tracer and freeze-fracture techniques. Abundant gap junctions exhibited striking intraspecific variation in size and pattern of particle aggregation. The smaller gap junctions showed close packing of the intramembranous A face particles. In large gap junctions, ranging up to 6 mu in diameter, particles were packed in rectilinear arrays separated by a labyrinthine network of particle-free 'aisles'. Small clusters of particles in a particle-poor circumferential zone suggested enlargement of junctions by peripheral accretion. Linear intramembranous structures, resembling those of occluding junctions, occasionally bounded large gap junctions. Spherical intracytoplasmic structures limited by gap junctional membranes were shown by tracer studies to arise by invagination of the cell surface. These were intrepreted as a means of disposal of junctions by interiorization.