Proline hydroxylase activity and collagen content of pigeon aortas with naturally-occurring and cholesterol-aggravated atherosclerosis. Proline hydroxylase activity and collagen content were determined in atherosclerotic plaque, fatty streak, and normal tissue from aortas of White Carneau pigeons with naturally-occurring of cholesterol-aggravated atherosclerosis. Little increase in collagen content or proline hydroxylase activity occurred in fatty streaks or plaques from birds with cholesterol-aggravated atherosclerosis. This is consistent with the morphologic observation of the presence of little or no "fibromuscular cap" in these cholesterol-aggravated lesions. Both normal and plaque tissue from arotas of birds with naturally-occurring atherosclerosis contained more collagen than did similar tissues from control birds or birds with cholesterol-aggravated lesions. The largest proportion of this increase in collagen content probably represented an age effect since it occurred in normal as well as atherosclerotic tissue. Plaques from aortas of birds with naturally-occurring atherosclerosis did contain, however, significantly more collagen than normal tissue from the same aortas. This is consistent with the presence of a prominent "fibromuscular cap" in these naturally-occurring lesions. Proline hydroxylase activity was less in these lesions than in normal tissue from the same aortas. Consequently increased proline hydroxylase activity and collagen content are not greatly altered in association with development of cholesterol-aggravated atherosclerotic lesions in pigeons. On the other hand, well-developed naturally-occurring lesions contained increased concentrations of collagen but showed no increase proline hydroxylase activity. This is not to say though, that active collagen synthesis and presukably increased proline hydroxylase activity did not take place at some point in the development of these naturally-occurring lesions.


The effect of nicotinic acid on the metabolism of the plasma lipoproteins of rhesus monkeys. The effect of nicotinic acid was investigated in Rhesus monkeys. Subcutaneous injections of nicotinic acid lower the plasma very low density lipoprotein (VVLDL) and low density lipoprotein (HDL) concentration. The fall in LDL concentration is not accompained by any change in the lipid or protein composition of either lipoprotein. Analysis by Sephadex gel chromatography and polyacrylamide-gel electrophoresis showed that the proteins of monkey VLDL and LDL are qualitatively similar to those of human VLDL and LDL, although there are differences in the proportions of the various proteins present in the two species. Subcutaneous injections of nicotinic acid diminish the maximum incorporation of 14C from [14C]threonine into VLDL and LDL apoproteins, but have no effect on incorporation into albumin or HDL apoprotein. Peak incorporations into the apo-B and apo-C of VLDL are diminished to about equal extents by nicotinic acid. Comparison of the amount of 14C lost from apo-B of VLDL after  the peak of incorporation, with that gained by apo-B of LDL during the same period, suggests that some of the circulating apo-B of LDL IS DERIVED FROM SOURCES OTHER THAN CIRCULATING VLDL.


An examination of octanol and octanal metabolism to octanoic acid by horse liver alcohol dehydrogenase. The kinetics of the horse liver alcohol dehydrogenase (alcohol: NAD+ oxidoreductase EC 1.1.1.1) catalyzed metabolism of octanol and octanal to octanoic acid have been examined. On incubation of octanol with horse liver alcohol dehydrogenase in the presence of NAD+, NADH as well as octanal and octanoic acid were seen as the initial products. However, on continued incubation, the octanal concentration progressively decreased to where only negligible quantities were present in the incubation after 10 min. The production of NADH was biphasic. An initial phase was followed in about 2 min with a slower but linear rate of NADH production. The production of octanoic acid was approximately linear throughout the 10 min incubation period. Since octanal is an intermediate in the oxidation of octanol to octanoic acid, the ability of semicarbazide to inhibit the metabolism of octanol to octanoic acid was examined. At a concentration of semicarbazide which was 63 times the concentration of octanol in the incubation media, the rate of formation of octanoic acid was inhibited by only 30%. The results of these experiments suggest that in the oxidation of octanol to octanoic acid a portion of the octanal formed from octanol is not released from the enzyme but, in the presence of NAD+, is oxidized to octanoic acid.


The separation, properties and possible subunit composition of adenosine 3',5'-monophosphate-dependent protein kinases in brown adipose tissue. Two 8.5-S protein kinases (ATP : protein phosphotransferase EC 2.7.1.37) and one 6.6-S protein kinase were purified 500--1000-fold from the acid-soluble fraction of brown adipose tissue. The catalytic properties of the kinases were similar. Each kinase was activated by cyclic AMP and had two components of cyclic AMP binding. In the presence of 200 nM cyclic AMP, undissociated kinase activity sedimented at 7.7 or 5.5 S. Free catalytic activity (3.2 S) could be detected but was unstable. Free regulatory units could not be detected. The 8.5-S protein kinase was dissociated by freezing and thawing to a 7.7-S variety with loss of the higher affinity component of binding. The 7.7-S kinase was sedimented through linear gradients of sucrose containing different concentrations of cyclic AMP. At each concentration, kinase activity lost from the holoenzyme peak (% of original) was identical with the amount of cyclic AMP bound at equilibrium (% oof maximum). Similar experiments on the 8.5-S kinase showed that the binding component with higher affinity was not associated with the release of catalytic activity. The results were consistent with the propostal that the kinases isolated contained one more cyclic AMP binding subunit than catalytic subunit (3 : 2 for 8.5 S and 2 : 1 for 6.6 S) and that this extra subunit was released to give an equal number of subunits of each type before catalytic activity was liberated.


The effect of ADP, calcium and some inhibitors of platelet aggregation on protein phosphokinases from human blood platelets. A protein phosphokinase (ATP: protein phosphotransferase EC 2.7.1.37) which is stimulated by 3',5'-cyclic adenosine monophosphate (cyclic AMP) has been partially purified from both the cytoplasmic and membrane fractions of human platelets. The kinetics of both enzymes preparations are similar in respect to cyclic AMP, ATP, ADP and AMP. 5-10-minus 7 M cyclic AMP stimulated both preparations by approximately 100%. Both ADP and AMP at a concentration of 5-10-minus 5 M inhibited protein phosphokinase activity of the soluble and membrane preparation by between 50% and 70%. The response of the two enzyme preparations to calcium differed. 10 mM Ca-2+ inhibited soluble protein phosphokinase activity approximately 80% both in the presence and absence of 5-10 minus 7 M cyclic AMP whereas the same concentrations of Ca-2+ inhibited the membrane-bound enzyme by approximately 60% in the presence of 5-10-minus 7 M cyclic AMP and 40% in the absence of cyclic AMP. This observation may be of importance in understanding the mechanism of platelet aggregation.


The porcine endothelial cell in tissue culture. Endothelial cells from porcine aorta and inferior vena cava have been harvested, using trypsin, EDTA or collagenase, and grown in tissue culture. Growth-behaviour, cytology, scanning and electronmicroscopy findings are reported. It is hoped that this technique will prove useful in the investigation of atherosclerosis.


Hydrolysis of guanosine and adenosine 3',5'-monophosphates by rat blood. Cyclic nucleotide phosphodiesterase activity was measured in whole blood, plasma, and suspensions of platelets and erythrocytes from rats. In fresh whole blood, apparent phosphodiesterase activity was low, but it rose strikingly during the hour after blood withdrawal. The apparent phosphodiesterase activity in platelet-free plasma showed no such increase, but that in platelet-enriched plasma increased in parallel with that in whole blood. The apparent phosphodiesterase activity of blood or of platelet-enriched plasma also was increased markedly by sonication. The increase in rat blood phosphodiesterase activity with aging thus appeared to be due to damage of platelets. Most of the phosphodiesterase activity in rat erythrocytes and platelets was located in the soluble fraction of sonicated preparations, but the total enzyme activities from the two sources exhibited marked differences in substrate specificity. With erythrocyte preparations, the rate of hydrolysis of muM concentrations of cyclic AMP was approx. 50 times that of cyclic GMP, while with platelet preparations, cyclic GMP was hydrolyzed about 20 times faster than cyclic AMP at muM levels. The activity of phosphodiesterase in platelets was much greater than that in erythrocytes at all concentrations of both substrates.


Purification and properties of a peptidase acting on a synthetic substrate for collagenase from monkey kidney. A peptidase cleaving a synthetic substrate for collagenase, 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg (designated as PZ-peptide) has been purified extensively (about 5200-fold) from a soluble extract of monkey kidney with a view of carrying out studies on its possible physiological role. The purified PZ-peptidase appeared essentially free of collagenase, nonspecific protease and di- and tri-peptidase activities. The properties of the purified PZ-peptidase resemble very much the granuloma enzyme. It is optimally active around pH 7.0. Its apparent Km value for PZ-peptide is 0.72 mM and V is 10.1 mumol/mg protein/min. It is reversibly inhibited by p-hydroxymercuribenzoate and HgCl2, whereas iodoactetamide does not affect the enzyme activity. N-Ethylmaleimide inhibited the enzyme partially (50%). Heavy metals like Cu-2+, Cd-2+, Ag+, Pb-2+, Ni-2+, and Zn-2+ completely inhibited the enzyme activity, while the inhibition by Co-2+ was only partial. Fe-2+ did not exert any effect on the activity. The enzyme activity was completely inhibited by EDTA and was restored almost to the original value by metal ions like Mn-2+, Mg-2+, Ca-2+ and Ba-2+. The approximate molecular weight of the purified enzyme was estimated to be 56 000.


Collagenase production by Achromobacter iophagus. Achromobacter iophagus produced collagenase (EC 3.4.24.3) when cultured aerobically in buffer containing 5% peptone. The bacterium is non-pathogenic and tests on rabbits indicated that the culture medium was atoxic. The collagenase, which hydrolyzed insoluble and soluble native collagen, was purified by (NH4)2 SO4 precipitation, starch block electrophoresis, and gel filtration. It was shown to be serologically distinct from Clostridium histolyticum collagenase and to have molecular weight and sedimentation coefficient values of approx. 112 000 and 5.3 S, respectively.


Separation of lipoamide dehydrogenase isoenzymes by affinity chromatography. 1. Lipoamide dehydrogenase NADH: lipoamide oxidoreductase, (EC 1.6.4.3) from pig heart has been separated into two sets of isoenzymes by chromatography on lipoyl- and NAD+-derivatized Sepharose-4B matrices. The first fraction is eluted at 30 mM sodium phosphate buffer (pH 7.2), the other requires a higher ionic strength. The two groups originate from the alpha-ketoglutarate and the pyruvate dehydrogenase complex respectively. 2, Hydrophobic chromatography on a homologous series of alkyl-Sepharoses lead to similar results. The first fraction is eluted with 30 mM phosphate buffer in the case of propyl- and butyl-Sepharose but a high ionic strength is required in the case of an increased chain length (C5--C6). The second fraction is reversibly bound on Sepharose-NC3 and -NC4 but binding becomes irreversible at higher chain lengths. 3. Aminoalkyl-Sepharose behave qualitatively as the alkyl derivatives although elution, particularly in the case of the second fraction, can be realized at lower ionic strength. 4. Matrices which  are negatively charged (Sepharose-NCnCOOH, n equal 3--7) have no affinity at pH 7.2. 5. The influence of a neutral polar substituent has been studied by comparing the following matrices: Sepharose-NC6OH, Sepharose-NC6NH2 and Sepharose NC6. Binding of the various isoenzymes is completely reversible in the case of a Sepharose-NC6OH matrix and the elution behaviour is identical to that on propyl- and butyl matrices.


Influence of glucocorticoids on some morphological and biochemical aspects of rat small intestinal mucosa. Glucocorticoid administration (5 mg/day per 100 g of body weight) to month-old rats elicited a reduction of maltase and alkaline phosphatase. Corticotrophic stimulation on month-old rats elicited a specific rise in maltase and alkaline phosphatase activities, total protein content remaining unchanged. Immunological, histological, radioautographical and biochemical studies have shown that these two opposing phenomena do not depend on enzyme activation, on membrane stabilisation, or on modifications of proliferative parameters of the intestinal epithelium. They appear rather to derive from the same origin, i.e. the action of glucocorticoids on the enterocyte differentiation.


Spectroscopic properties of ferrous heme complexes of sterically hindered ligands. Mesoheme IX complexes of sterically hindered ligands 2-methylimidazole, tert-butylamine and 2-methylpyridine in aqueous glycerol solutions are characterized by broad visible absorption spectra at ambient temperature exhibiting close similarities to high-spin ferrous hemeproteins. Spectrophotometric titrations of mesoheme IX with these ligands indicate well-defined equilibria for 2-methylimidazole and tert-butylamine corresponding to the formation of penta-coordinate strong-field ligand complexes. Variable temperature spectra of these complexes from ambient to 77 degrees K exhibit a change to hemochrome spectra characteristic of the low-spin unhindered ligand complexes. Corresponding changes in the visible spectra are not observed for the high-spin hemeproteins deoxymyoglobin, horse-radish peroxidase and cytochrome ć. The appropriate utilization of these hindered ligand heme complexes as model systems for high-spin ferrous hemeproteins has been discussed.


Binding of progesterone to the proteins of the uterine luminal fluid. Identification of uteroglobin as the binding protein. 1. The uterine luminal fluid of rabbits treated with estradiol and progesterone contains a protein factor with high affinity for [3-H] progesterone which is not present in the uterine secretion of control rabbits treated with estradiol. 2. This progesterone dependent factor is shown by gel filtration and polyacrylamide gel electrophoresis to be identical with the uterus specific protein uteroglobin, which seems to be required during the preimplantation phase. Uteroglobin specific antiserum, prepared in guinea pigs, completely inhibits the progesterone binding activity of the proteins of the uterine fluid. 3. Progesterone binding to uteroglobin is dependent upon millimolar concentrations of dithioerythritol. At saturation, one molecule of progesterone binds per uteroglobin molecule and the apparent association constant is 2 x 10-6 M-1 at 0 degrees C. 4. The progesterone binding species of uteroglobin exhibits a molecular weight of around 12 000 on polyacrylamide gels containing dodecylsulfate, and of 15 000 upon gel filtration, indicating a non-globular shape. This molecule is compased of two subunits of similar molecular size which are held together by a disulfide bridge among other forces.


Effect of decapitation and ACTH on somatic development of the rabbit fetus. Rabbit fetuses were decapitated, injected with ACTH or decapitated and injected with ACTH on day 24 of gestation. On day 29 the body weight and weight of the interscapular fat pad were compared with those of littermates. The weight, total DNA and weight/DNA ratio of the liver, heart and kidney were measured in experimental and control fetuses. A comparison was made between decapitated and control fetuses of the length of the hind limb bones and number of ossified vertebrae. The body weight of the decapitated or ACTH-injected fetus ranked significantly below the mean for the litter, but decapitated fetuses injected with ACTH ranked close to the litter mean. The growth retardation of the decapitated fetus was not manifest in the kidneys which were heavier and had a greater number of cells than normal, nor in the cell size of the heart, liver or kidneys which were equal to those of the heaviest fetus in the litter. Decapitation had no specific effect on ossification. Growth retardation of the ACTH-injected fetus was mirrored by different patterns of DNA and weight/DNA reduction in the three organs studied. Decapitation retards growth in body weight of the fetal rabbit which may be corrected by ACTH. It is concluded that the hypophyseal-adrenal axis plays a role in the control of normal fetal growth but that excess secretion of glucocorticoids results in stunting.


The factors controlling stem cell recirculation. II. ACTH-induced inhibition of migration of hemopoietic stem cells. Injections of ACTH of prolonged action (twice 1.5 units per mouse) given to lethally (800 R) irradiated mice with a hind limb shielded to the middle of the tibia brought about a twofold decrease in the number of spleen colonies. ACTH injections after sublethal whole-body irradiation (600 R) did not affect the number of endogenous spleen colonies. ACTH injection of normal mice brought about a substantial decrease in the CFU content in the circulating blood at the time of increased 11-hydroxycorticosteroid concentrations in the plasma. The results obtained are interpreted as inhibition of CFU migration from a shielded area of bone marrow induced by a high 11-hydroxycorticosteroid content in the plasma that followed ACTH injections which had no mitostatic effect on CFU proliferation.


Noradrenaline and motor transmission in the vas deferens of the mouse. 1. A comprehensive investigation of the innervation of the vas deferens of the mouse was made using pharmacological, histochemical and electronmicroscopical techniques. 2. Guanethidine inhibited the response of the vas to transmural stimulation and potentiated the response to noradrenaline (NA). Phentolamine abolished responses to NA and to transmural stimulation. 3. After chemical sympathectomy degenerative changes were seen in presumptive noradrenergic axons; histochemical fluorescence due to catecholamines was absent. The vas failed to respond to transmural stimulation, and a 10-fold increase in sensitivity of the vas to exogenous NA was observed. 4. NA is shown to diffuse slowly through this tissue whose muscle cells are densely packed. This is disscussed in relation to the apparent "insensitivity" of the vas to exogenous NA. 5. A cholinergic component was identified histochemically which did not contribute significantly to the motor response of the vas as chemical sympathectomy abolished completely the motor response elicited by transmural stimulation. 6. It is concluded that NA is the motor trnasmitter for the smooth muscle of the vas deferens of the mouse.


Nicotine-induced stimulation of steroidogenesis in adrenocortical cells of the cat. 1. The effect of nicotine on steroid production and release from trypsin-dispersed cat adrenocortical cells was investigated. 2. Nicotine, like adrenocorticotrophin (ACTH), elicited a dose-dependent increase in steroidogenesis, which depended upon the presence of calcium in the medium. 3. Augmented steroid production evoked by submaximal concentrations of ACTH monobutyryl cyclic adenosine 3',5'-monophosphate (AMP), or prostaglandin E2 was further enhanced by steroidogenic concentrations of nicotine. 4. These results are discussed in relation to the possible mode of action of nicotine on cortical cells and to the potential consequences of smoking during stress.


Role of cyclic adenosine 3',5'-monophosphate in the isoprenaline-induced relaxation of the oestrogen dominated rabbit uterus. 1. The role of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the relaxation produced by isoprenaline in muscle strips from the oestrogen dominated rabbit uterus has been investigated. 2. Isoprenaline 2 times 10- minus 8 M produced an inhibition of the mechanical activity but no increase in cyclic AMP. Isoprenaline 2 times 10- minus 6 M produced both inhibition of mechanical activity and increase in cyclic AMP. 3. The increase in cyclic AMP, but not the inhibition of mechanical activity, was blocked by propranolol 3.4 X 10-MINUS 6 M. 4. Dibutyryl-ccylic AMP produced a relaxation which mimicked that produced by isoprenaline, in that the longitudinal strips were more sensitive than the circular ones. 5. It is concluded that cyclic AMP may be a mediator of the beta-adrenergic effect in the oestrogen dominated rabbit myometrium. However, it seems not to be an obligatory link between stimulation of beta-adrenoceptors and relaxation. Other mechanisms may also exist.


Tetramethylenedisulphotetramine: an inhibitor of gamma-aminobutyric acid induced depolarization of the isolated superior cervical ganglion of the rat. Tetramethylenedisulphotetramine (TETS), a potent convulsant, antagonized the depolarizing action gamma-aminobutyric acid (GABA) in the isolated superior cervical ganglion of the rat. No antagonism of responses to the cholinomimetic agent carbachol was observed. TETS appeared to act in a non-competitive manner and was reversible. Its activity profile was comparable to that of bicuculline in the same tissue except that the latter appears to act in a competitive manner.


Colours experienced in dreams.

Colours experienced in dreams. Colours seen in dreams by six observers were recorded from memory and plotted on a CIE u, v, chromaticity diagram. Only about half the dreams recorded contained colour, and in those in which colour appeared the more saturated purples, blues and blue greens were absent. It is suggested that during achromatic dreams the areas of the visual cortex which seem to respond only to colour may be inoperative. The paucity of blue in dreams could be anatomically related to the small population of blue units in the colour areas of the cortex.


Carcinoma of the large bowel in the Sudan. Large bowel cancer is not common but is showing increased frequency in the northern part of the Sudan. It is relatively uncommon among southerners, which may be due to the socio-economic factors prevailing in the Sudan. The disease affected our population at a younger age than has been generally reported in the literature, and the lesions in nearly 30 per cent were of the mucoid and undifferentiated types. The incidence in young adults is difficult to explain in the absence of precancerous lesions, and there is not enough evidence to incriminate parasitic infestation.


Possible parathyroid origin of gastrin in a patient with multiple endocrine adenopathy type I. After removal of two large pancreactic insulinomas, although the presenting spontaneous hypoglycaemia was eliminated, severe and persisting haematemesis and melaena supervened with a rise in serum gastrin. The patient had multiple endocrine adenopathy (pituitary, parathyroids and islet cells), but no evidence of a pancreatic gastrin-producing tumour. After emergency gastric operation for the bleeding, the serum gastrin remained high until the hypercalcaemia and hyperparathyroidism had been corrected by subtotal parathyroidectomy. Immunofluorescence studies showed gastrin in the parathyroid tissue.


Neuropathy in latent hereditary hepatic porphyria. Peripheral nerve conduction velocoties were measured in 20 patients with acute intermittent porphyria and five with variegate porphyria and in 25 controls matched for age and sex. None of the porphyric patients had acute symptoms on examination, and nine had never had symptoms. Compared with the controls, patients had a significantly slower conduction velocity of the slower motor fibres of the ulnar nerve (P less than 0-001) and a slower sensory conduction velocity of the ulnar and median nerves (P less than 0-05). There was no significant difference between the patients and controls in the maximum motor conductionvelocity of the median, ulnar, deep peroneal, or posterior tibial nerves. Slight peripheral neuropathy seems to be associated with latent hereditary hepatic porphyria, even in patients who have never had symptoms.


Methodichlorophen as anti-tumor drug.

Methodichlorophen as anti-tumor drug. Methodichlorophen was given to 26 patients with terminal malignant disease. Eight patients received adequate doses, and five of them showed objective evidence of tumour regression while three failed to respond. Those who responded included four out of five patients with lung cancer (three with squamous-cell carcinoma and one with oat-cell carcinoma) and a patient with hypernephroma. Two patients with testicular teratomas and one with acute myeloid leukemia failed to respond. The drug may be given safely by mouth to outpatients if certain precautions are taken.


Peripheral neuropathy and indomethacin.

Peripheral neuropathy and indomethacin. A patient with seronegative inflammatory polyarthritis developed a predominantly motorperipheral neuropathy associated with the use of indomethacin. Three other cases of peripheral neuropathy associated with indomethacin treatment have been reported to the Committee on Safety of Medicines. In all cases the neuropathy regressed when indomethacinwas stopped. Peripheral neuropathy should be recognized as a rare complication of indomethacin therapy and considered in the differential diagnosis of a neuropathy accompanyingrheumatoid arthritis.


Actions of vitamins D2 and D3 and 25-OHD3 in anticonvulsant osteomalacia. In 54 epileptic outpatients treated for at least one year with anticonvulsants the bone mineral content (B.M.C.), an estimate of total body calcium, and serum calcium were measured before and during treatment with three doses of cholecalciferol (vitamin D3; 200, 100, and 50 mu-g daily) and 25-hydroxycholecalciferol (25-OHD3; 40, 20, and 10 mu-g daily) for 12 weeks. The results, when compared with the effects of calciferol (vitamin D2; 200, 100, and 50 mu-g daily) in 40 epileptic outpatients, showed different actions in anticonvulsant osteomalacia of vitamin D2 on the one hand and vitamin D3 and 25-OHD3 on the other. In the patients who received vitamin D2 an increase in B.M.C. was found whereas serum calcium was unchanged. The patients who received vitamin D3 or 25-OHD3 showed an increase in serum calcium but unchanged values of B.M.C. The results suggest that liver enzyme induction cannot alone explain anticonvulsant osteomalacia.


Value of Papanicolaou-stained smears in the diagnosis of trichomoniasis, candidiasis, and cervical herpes simplex virus infection in women. In the diagnosis of trichomoniasis Papanicolaou-stained cervical smears gave marginally better results than cultures of vaginal secretion; stained cervical smears and wet films of vaginal material gave similar results. Culture of vaginal secretion on Sabouraud's medium gave the best results in the diagnosis of candidiasis; Papanicolaou-stained smears gave significantly fewer positive results than either cultures or Gram-stained vaginal smears. Papanicolaou-stained smears were reported as positive in only two of five patients with cervical herpes simplex virus infection. It is concluded that Papanicolaou smears are as good as wet films or cultures in the diagnosis of trichomoniasis but cannot be relied on for the diagnosis of candidiasis, or for detecting herpes simplex virus infection.


Genital yeasts in female patients attending a VD clinic. A study of 552 female patients was undertaken to determine the frequency of yeast infections in women attending a V.D. clinic. The findings were as follows: (1) 207 of the 552 (37.5 per cent.) were found to have yeasts. (2) C. albicans accounted for 86 per cent. of these yeasts. (3) There was no difference in incidence related to age or seasonal variation. (4) Oral contraceptives increased the incidence of yeasts (43.2 per cent. on "the pill"; 33.2 per cent. not on the pill"), but the incidence of Trichomonas was decreased (6.8 per cent. on "the pill", 19.3 per cent. not on "the pill"). (5) Previous antibiotics also contributed to the incidence; 23.2 per cent. of patients with yeasts had had antibiotics previously compared with 13.6 per cent. of those without yeasts. (6) Other infections were associated in seventy cases (33.8 per cent.). (7) Culture is essential for the detection of yeasts; 64 per cent. were positive only on culture. (8) Symptoms were present in 70 per cent. of patients with yeasts. (9) 93 male consorts were seen and in 31 (33 per cent.) yeasts were detected by smear, or culture. Of the 47 in whom cultures were examined, 23 (49 per cent.) were positive. The general factors affecting the incidence of yeasts are discussed as well as the differentiation of the saprophytic from the pathogenic role of yeasts. It is suggested that asymptomatic yeast infections are often best treated, but that each case should be considered individually. Male consorts should also be treated to prevent re-infection.


Neutral red with photoinactivation in the treatment of herpes genitalis. A clinical trial was undertaken to compare the efficacy of neutral red photodynamic inactivation treatment of genital herpes infections with that of a non-photoactive dye, phenol red, as a control. In a series of nineteen patients with virologically proven herpes genitalis who were adequately followed, eleven were treated with neutral red, and eight with phenol red; no difference in response to therapy was found between the two groups, and it is concluded that under the conditions of this trial neutral red with photoinactivation was not effective in the treatment of acute genital herpes infections. Approximately 75 per cent. of those with vulval lesions also had concurrent cervical infection, so that an effective topical treatment would need to be applicable to both anatomical sites.


Donovanosis (granuloma inguinale) of the oral cavity. A female patient suffering from donovanosis of the oral cavity without associated lesions elsewhere is reported. The importance of remembering donovanosis in the differential diagnosis of chronic granulomatous ulceration of the mouth is emphasized.


Effect of withdrawal from chronic ethanol ingestion on the cAMP response of cerebral cortical slices using the agonists histamine, serotonin, and other neurotransmitters. The effect of ethanol withdrawal on the cAMP response of cerebral cortical brain slices was studied. The cAMP response was evoked in vitro by various neurotransmitters including norepinephrine (NE), histamine, serotonin, dopamine, acetylcholine, and gamma-aminobutyric acid (GABA). The cAMP response to NE and histamine was enhanced by ethanol withdrawal. Serotonin evoked a cAMP response in the brain slices from ethanol-withdrawal rats but not in pair-fed controls. The histamine and serotonin evoked responses were blocked by chlortripolon and methysergide, respectively. The responses to histamine and serotonin were also blocked by alpha- and beta-adrenergic antagonists, possibly because of the nonspecific membrane stablizing effect of these antagonists. GABA inhibited the NE stimulated cAMP response possibly through the hyperpolarizing action of GABA. The results support the hypothesis that ethanol withdrawal induces a nonspecific postjunctional supersensitivity. It is postulated that the supersensitivity involves a partial depolarization of the receptor membrane. Alternative hypotheses are reviewed.


Presynaptic effect of the aziridinium ion of acetylcholine mustard (methyl-2-acetoxyethyl-2'-chloroethylamine) on the phrenic nerve--rat diaphragm preparation. The rat diaphragm has been used to investigate the neuromuscular blocking action of acetylcholine mustard which yields a potent nicotinic agonist, an aziridinium ion, in aqueous medium. Evidence was obtained that the acetylcholine mustard aziridinium ion impaired neuromuscular activity when the phrenic nerve was stimulated and that the ion did not directly inhibit muscle contraction. Impairment of neuromuscular activity was characterized by a latent period and depended both on the concentration of aziridinium ion and the frequency of stimulation of the phrenic nerve. Elevated concentrations of Ca-2+ and choline changed the response of the rat diaphragm to the aziridinium ion, the former increasing the rate of development of neuromuscular block and the latter protecting against neuromuscular block. These results indicated that the aziridinium ion may act either at the site of choline uptake or have an effect on acetylcholine synthesis in the nerve ending and that impairment of neuromuscular transmission in the rat diaphragm involved the availability of acetylcholine. Similar results were obtained with acetylcholine mustard aziridinium ion subjected to alkaline hydrolysis. This substance is thought to be choline mustard aziridinium ion. Although difficult to prove with the rat diaphragm it is possible that acetylcholinesterase of this preparation could hydrolyze acetylcholine mustard aziridinium ion at the neurotransmitter site and the resultant choline mustard aziridinium ion would interfere with the uptake of choline and eventually prevent neuromuscular transmission. This hemicholinium-like hypothesis for the mechanism of action of choline mustard aziridinium ion is compatible with reported date for toxicity of acetylcholine mustard aziridinium ion in the mouse.


Cellular hypersensitivity to basic myelin (P2) protein in the Guillain-Barré syndrome. Lymphocytes of 29 subjects were assayed for MIF production in response to P2 peripheral nerve protein, crude human peripheral nerve and human central nervous system Al basic myelin protein. Seven were performed in normal control subjects, 12 in Guillain-Barre patients (GB), 5 with other polyneuropathies and 5 in patients with multiple sclerosis (MS). Only GB patients with acute illness produced MIF in response to neuritogenic P2 protein and crude human nerve. Two MS patients in the acute phase of an exacerbation and one GB patient produced MIF in Response to Al protein. The results of this study demonstrate cellular hypersensitivity to a neuritogenic consituent in peripheral nervous tissue and support the concept that this may be important in the pathogenesis of GB.


Neurophysiological changes following spinal cord lesions in man. A study has been made of the neurophysiological changes that follow spinal cord lesions in man. The Achilles tendon reflex (ATR) is used to estimate transmission in the Ia monosynaptic pathway, and the tonic vibration reflex (TVR) to estimate transmission in the Ia polysynaptic pathway to motoneurons. The inhibition of the H reflex by vibration is used as an estimate of presynaptic inhibition of the Ia monosynaptic pathway. Immediately following a complete lesion of the spinal cord presynaptic inhibition of the Ia monosynaptic pathway appears to be greatly increased. This enhanced inihibition may last several months but it eventually declines and in some instances becomes less than normal. Transmission in the Ia polysynaptic pathway is permanently abolished by a complete spinal lesion. A hypothesis is developed from these findings to explain the evolution of some of the clinical features that follow complete spinal lesions in man. Distinct differences are observed when the spinal lesion is incomplete. Transmission in the Ia polysynaptic pathway may be preserved and there may be no increase in presynaptic inhibition. These differences may depend upon the integrity of certain spinal long tracts which cannot be tested clinically.


Nucleolar phosphoproteins of normal rat liver and Novikoff hepatoma ascites cells. The nucleolar acid-soluble proteins from normal rat liver and Novikoff hepatoma ascites cells were labeled in vivo for 2 hr after the injection of [32P]orthophosphate and in vitro with [gamma-32P]adenosine triphosphate in systems containing 0.25 M sucrose, 5 mM MgCl2, 12.5 mM NaCl, and 0.05 M Tris-HCl buffer, pH 7.3, AT 37 DEGREES. Two-dimensional polyacrylamide gel electrophoresis and autoradiography showed that approximately 40 and 20 protein spots were labeled in vivo and in vitro, respectively. There were some marked differences in labeling in vivo between normal rat liver and Novikoff hepatoma acid-soluble nucleolar proteins. By 32P analysis of gel slices, the proportion of the total 32P incorporated into protein Spot A1-4 was greater in normal liver, and the proportion of 32P incorporated into some high-molecular-weight protein spots, such C23-24 and C26-27, was greater in the Novikoff hepatoma ascites cells. With the in vitro incubation system, the 32P uptake per mg protein was about twice as high in Novikoff hepatoma nucleolar proteins as in normal rat liver nucleolar proteins but, generally, the same proteins were labeled in both tissues.


Sulfhydryl group quantitation of hepatoma and liver microsomal fractions. The relationship of sulfhydryl and disulfide groups to protein synthesis in normal and rapidly growing tissues was investigated by quantitation of sulfhydryl groups in endoplasmic reticulum and polyribosomes of normal liver and hepatomas. Stripping by ethylenediaminetetraacetate and potassium chloride of normal liver smooth and rough endoplasmic reticulum reduced by 15 percent and increased 30 percent, respectively, the sulfhydryl groups available for carboxamidemethylation by iodoacetamide. This could reflect the removal of ribosomes from rough endoplasmic reticulum with the subsequent exposure of sulfhydryl groups. Exposed sulfhydryl groups of normal mature female rat liver smooth endoplasmic reticulum were decreased to a similar degree by the stripping procedure with ethylenediaminetetra-acetate and potassium chloride when quantitated by either iodoacetamide or 4,4'-dithiodipyridine. This was not the case in young male and female rats, where the stripping procedure failed to decrease the exposed sulfhydryl groups of smooth endoplasmic reticulum. An increase in the quantity of exposed sulfhydryl groups of normal young and mature rat liver rough endoplasmic reticulum after stripping by ethylenediaminetetraacetate and potassium chloride was observed with iodoacetamide. However, when 4,4'-dithiodipyridine was used, no change could be detected. The hypothesis that smooth endoplasmic reticulum arises by degranulation of the rough endoplasmic reticulum in vivo is not supported by our sulfhydryl group quantitation of smooth endoplasmic reticulum and in vitro degranulated rough endoplasmic reticulum. A negative correlation between exposed sulfhydryl groups on the polyribosomes and the rate of growth of normal liver and of Morris hepatomas 6 and 38B suggests that the conformation of the free polyribosomal proteins could be a control factor for the rate of protein synthesis. Faster growing hepatomas also have greater quantities of sulfhydryls and disulfides.


Regulation of growth of mouse mastocytoma cells. N6,O2'-Dibutyryladenosine cyclic 3',5'-phosphate plus theophylline inhibited the growth of the mouse mast cell tumor line PY 815 both in vivo and in vitro. The inhibitory effect on growth in vitro was rapidly reversed following removal of the drugs. Growth inhibition was accompanied by reduced cell surface activity and increased cell-cell adhesion. The drug-treated cells accumulated distinct membrane-bound granules, which are characteristic of more mature mast cells. Treated cells also developed increased amounts of surface-associated acidic mucopolysaccharides. These results suggest that increased intracellular cyclic adenosine 3':5'-monophosphate causes mouse mastocytoma cells to decrease growth and elicits the expression of a more differentiated mast cell phenotype. The effect of the antileukemia drug, 4'-(9-acridinylamino)methanesulfon-m-anisidine, on cyclic adenosine 3':5'-monophosphate and adenosine 5'-triphosphate in mastocytoma cells is also reported.


Independence of sialic acid levels in normal and malignant growth. Sialic acid content in breast or tumor tissue and serum of mouse strains that are either susceptible or resistant to breast cancer was measured at various age periods. Sialic acid content was also studied in normal lung tissue and in lung adenoma and hepatoma. Sialic acid levels during nonmalignant growth of a tissue were measured in breast tissue during pregnancy and lactation, and in regenerating liver, as well as in newborn and postnatal liver. The sialic acid content, when expressed per mg of protein, increased in mammary tumor, lung adenoma, and hepatoma. It also increased in nonmalignant growth of breast tissue during pregnancy and lactation and of regenerating liver and postnatal liver. Increase in sialic acid per mg DNA was observed only in lung tumors, regenerating liver, and postnatal liver. It appears that the changes in sialic acid level are independent of the normal or malignant growth of a tissue and that these changes might be the function of the parameter used to express the sialic acid values, i.e., either the DNA content or protein content of a given tissue.


Transcription of the repetitive DNA sequences in polyoma-transformed and nontransformed mouse cells in culture. RNA-DNA saturation hybridization experiments were used to estimate the extent of transcription of repetitive DNA sequences in polyoma-transformed and nontransformed mouse cells in culture. Measurements were made with RNA from nontransformed cells in both the subconfluent and confluent stages of growth, transformed cells in normal growth medium, and transformed cells grown in medium containing 5-bromodeoxyuridine, 3 mu-g/ml, a treatment which reduces their tumorigenic potential. No differences were observed in the amount of repetitive  DNA transcribed or in the families of sequences expressed, except in transformed cells grown in the presence of 5-bromodeoxyuridine, in which case the extent of transcription was reduced.


Neoplastic response of the avian liver to host infection with strain Mc29 leukosis verus. Studies were made on the oncogenic response of 3086 young chicks to i.v. inoculation of MC29 avian leukosis virus from blood plasma of previous-passage birds or the supernatant fluid of cultures of chick embryo cells infected with strain MC29. Among the large variety of neoplasms of other tissues previously described, there occurred a high incidence of primary growths of the liver. Pathomorphology of the growths frequently differed greatly in both different hosts and the same bird, but some uniformity of the types of neoplasms was evident in many animals. Despite much variation in histopathology, the large proportion of growths could be grouped in several distinctive categories. Examinations by light and electron microscopy provided evidence of derivation of the tumors by alteration of hepatocytes originating principally in the portal regions as indicated by forms transitional from the parenchymal cells to the cells of the different types of growths. Neoplastic aspects of the growths were evident by infiltration and invasion of adjacent tissues, penetration of blood vessels, transplantability to other avian hosts (described in another report), and metastasis to distant organs including the lung, kidney, and spleen. There was no evidence of tumors arising from the biliary system, and growths of cells resembling the biliary type could be traced to altered hepatocytes. None of the findings suggested conversion of biliary-type cells to hepatocytes. Continued growth resulted in anaplastic and metaplastic changes in cell morphology and structural organization and in the formation of cartilage, osteoid, and sarcoma-like spindle-cell tumors of probable epithelial origin. Development of the growths wasnot associated with cirrhosis, and necrosis was limited to infrequent disseminated, essentially unicellular changes or necrobiosis of small groups of cells. The marked variations in the type of virus-induced growths demonstrated the remarkable capacity of cells morphologically inidistinguishable from the hepatocytes for the most diverse alterations in cell structure and tissue organization. This neoplastic response of hepatocytes to the MC29 strain constitutes the only demonstration thus far of the specific hepatocarcinogenic activity of an avian tumor virus.


Alteration of hepatocytes by subcarcinogenic exposure to n-2-fluorenylacetamide. These experiments examined the effects of a single, subcarcinogenic dose of dimethylnitrosamine or N-hydroxyfluorenylacetamide when administered after a subcarcinogenic dietary regimen of N-2-fluorenylacetamide. Control rats that received either carcinogen diet alone or a single dose of carcinogen demonstrated neither hepatic nodules nor hepatocellular carcinomas. Those animals that received dimethylnitrosamine subsequent to carcinogen diet demonstrated many persistent hepatic nodules and 100% hepato-cellular carcinomas. These data support the concept that the nodules produced by subcarcinogenic ingestion of N-2-fluorenylacetamide are not composed simply of normal hepatocytes undergoing compensatory regeneration but consist of cells that have been altered by the carcinogen. One manifestation of this alteration is an increased susceptibility to further carcinogenic evolution.


The steroid alcohol and estrogen sulfotransferases in rodent and human mammary tumors. Rodent and human mammary tumor systems were investigated to relate the steroid alcohol and estrogen sulfotransferase activities to the hormoanl dependency of the tumor as determined by estrogen receptor content. Unlike the normal mammary gland or the hyperplastic alveolar nodule, rodent mammary neoplasms displayed significant levels of these two sulfotransferases. In the hormone-independent mouse tumors produced from out-growth lines D1, D2, and D8, high dehydroepiandrosterone sulfotransferase activity was characteristic of the rapidity with which hyperplastic alveolar nodules developed into a neoplasms (V-max = 52.8 versus 1.8 fmoles/min/mg protein) while estrone sulfotransferase activity was either not detectable or low (V-max = 5.5 fmoles). After oophorectomy of mice bearing slowly developing tumors, both sulfotransferases in the nonregressing neoplasms showed marked increases in activity (V-max dehydroepiandrosterone = 30.0 fmoles; V-max estrone = 18.5 fmoles). Strain differences not the estrogen receptor content of hormone-dependent rat mammary tumors. In Wistar-Lewis rats the steroid alcohol sulfotransferase activity was at least 35 times higher than in the Sprague-Dawley strain. As was observed in the mouse mammary tumor, Sprague-Dawley rat neoplasms that grew in the absence of ovarian hormones contained significantly greater levels of the steroid alcohol sulfotransferase. Possible correlaion between presence of the steroid alcohol sulfotransferase and the estrogen receptor protein was observed in a limited number of human breast carcinomas.


Kinase and deaminase activity in a variety of subcutaneous mouse tumors. Extracts of solid mouse tumors were examined for deoxycytidine kinase and deaminase activities. 1beta-D-Arabinofuranosylcytosine nucleotide was formed at a rate of 45 nmoles/hr by Glioma 26/57 and only 14 nmoles/hr by Ridgway osteogenic sarcoma. Deaminase activity was highest in Lewis lung (114 nmoles of 1-Beta-D-arabinofurano-syluridine formed per hr) and in CaD2 (104 nmoles of u-beta-D-arabinofuranosyluridine formed per hr). Deaminase activity in tumor extracts is sensitive to freezing, while deaminase activity in monkey serum is not. It was observed that kinase activity varies by as much as 50% in different cell lines of the same tumor. In the presence of tetrahydrouridine, kinase activity was significantly increased in most of the tumors studied.


Development of a 3T3-like line from an embryo culture of an inbred strain of Syrian golden hamster. An embryo culture of an inbred strain of Syrian hamster developed into a permanent cell line under the "3T3" 3 X 10-5 cells/60-mm dish. The resulting cell line had properties very similar to those of the mouse 3T3 series and was named HAMS 3T3. The cell showed density-dependent inhibition of division with a saturation density of 1.0 to 1.2 x 10-6 cells/60-mm dish or 4.5 to 5.5 x 10-4 cells/sq cm. Addition of fresh medium containing 5 or 10% fetal calf serum to a confluent culture induced DNA synthesis in 18 hr with subsequent cell division. Cells were hyperdiploid with a mode of 45 chromosomes (80% of the cells). When cells at the 60th passage were injected into the skin or cheek pouch of an inbred hamster of the same strain as that from which they were derived, they produced a benign tumor that regressed after 3 weeks. Morphological transformation was obtained by infection with the Moloney strain of murine sarcoma virus.


Amino acid and sugar transport incells permissively infected with simian virus 40. Transport of alpha-aminoisobutyric acid and 2-deoxy-D-glucose in African green monkey kidney cells was measured 8 to 100 hr following permissive simian virus 40 infection. No differences in transport were detected during the time-period studies, and no significant differences were seen between the apparent Michaelis-Menten constants of normal and virally infected cells. The absence of transport enhancement in permissive simian virus 40 infection suggests that the augmented transport of viral-transformed cell lines devolves upon altered host genome function.


5alpha-dihydrotestosterone-binding proteins and androgen sensitivity in prostatic cancers of Copenhangen rats. A line (R-3327-A) of androgen-insensitive squamous cell carcinomas of the prostate of Copenhagen rats has been derived from an established line (R-3327) of androgen-responsive tumors R-3327 A tummors have a growth rate of approximately 10 times that of R-3327. The response of R=3327 A to hormonal environment has been determined by measuring the growth rate of the tumor transplanted to males, females, and castrated males. No great differences were observed. The metabolism of testosterone by tumore samples was studied following s.c. injections of the labeled steroid. The results show very little 5alpha-reduction of testosterone compared with that obtained in the prostate gland itself, as well as in the androgen-sensitive R-3327 tumors. A comparison of the presence of 17beta-hydroxy-5alpha-androstan-3-one-binding proteins in cytoplasmic extracts from both lines of tumors shows that the receptor proteins are present only in the androgen-sensitive R-3327 and not in the androgen-insensitive R-3327 A. The levels of the receptor proteins in R-3327 tumors are higher in tumors borne by male than by female animals, and castration of males decreases the amount of 17beta-hydroxy-5alpha-androstan-3-one binding.


Virion-associated and cellular RNA methylase activity in normal and neoplastic mammary tissue from mammary tumor virus-infected and -uninfected mice. A comparison of cellular RNA methylase activities and patterns between normal and neoplastic mouse mammary tissue indicated the following. The rna methylases of mammary tumor tissue extracts are qualitatively different from those of normal lactating mammary tissue, based on differences in extent of methylation; the normal lactating tissue extracts have a greater capacity of methylate RNA than do the tumor extracts studied to date. There is no correlation between capacity and either the malignant state or the etiological agent. There is a qualitative effect on methylation patterns attributable to the presence of virus. Finally, both the etiological agent, mouse mammary tumor virus, and its putative nucleoprotein core, intracytoplasmic A particles, have a N-2-guanine RNA methyltransferase integrally associated with them. These conclusions are consistent with the aberrant nucleic acid methylation hypothesis, with the reservation that aberrant does not imply hypermethylation.


In vitro transformation of hamster cells by herpes simplex virus type 2 from human prostatic cancer cells. A cell-associated herpes simplex virus type 2 found in a human prostatic carcinoma induced in vitro transformation of hamster embryo cells. The transformed cells (YW-74) have been shown to be hamster cells by karyotype analysis. Their epithelial morphology and growth pattern, which are different from the parental cell, have remained stable through cell passages. The presence of herpesvirus antigens in the transformed cells was determined by specific immunofluorescence and colony inhibition tests. Immunofluorescence staining with specific anti-herpes simplex virus type 2 serum showed an intense and distinctive nuclear and perinuclear fluorescence in about 95% of the transformed cells. In addition, exposure of these transformed cells to herpes simplex virus type 2-sensitized lymphocytes resulted in inhibition of growth and colony formation, while no effect was seen with nonsensitized lymphocytes. Both observations are consistent with the involvement of herpesvirus type 2 in the transformation event. This virus, which does not produce a lytic infection and is not found either in extracellular spaces or supernatant fluid of the transformed cell cultures, is unique in the fact that it is cell associated, noncytopathogenic, and capable of transforming cells in vitro, and its antigens are clearly demonstrated in the transformed cells.


Uncertainties in the use of periodate oxidation for determination of dextran structure. A glucan of high molecular weight isolated from stale sugar-cane, and previously shown to have a marked effect on sucrose crystallisation processes-1, is a relatively linear dextran. Approximately 96-97% of its D-glucose residues are involved in (1 yields 6)-alpha-D linkages and constitute the linear backbone of the polymer. The remaining 3-4% of D-glucose residues form branch-points by (1 yields 3)-alpha-D linkages. The periodate-oxidation technique, which has been extensively used by other workers to determine dextran structure, gave erroneous results when applied to the dextran from stale sugar-cane.


The fine structure of the oocyte of bankia australis (teredinidae, bivalvia) before and after fertilization. The fine structure of the oocyte of Bankia australis is compared with that of other bivalve oocytes. It was observed that following fertilization, the microvilli changed their spatial organisation and behaviour towards sperm, the cortical granules disappeared in regions of high concentrations of supernumerary sperm, and the mitochondria apparently stated to divide.


The fine structure of the epidermis of two species of salmonid fish, the Atlantic salmon (Salmo salar l.) and the brown trout (Salmo trutta L.). I. General organization and filament-containing cells. The fine structure of the epidermis or two species of salmonid fish has been described. Gross characteristics have been noted along with many apparent differences in the epidermis of different body regions of the fish. The major cell type is the filament-containing cell and this has been described in detail. The major inclusions of the cell are the tonofilaments. Differences in basal, mid-epidermal and periphal filament-c0ntaingcells have been characterized. Comparisons of fish epidermis with that of other vertebrates has been made.


Morphological changes in cultured mammalian cells: prevention by the calcium ionophore A23187. The morphological changes induced by butyrate in HeLa cells and by monobutyryl or dibutyryl cAMP in CHO cells are prevented by micromolar concentrations of the divalent cation ionophore A23187. The ionophore is unable to prevent such changes in medium from which calcium is omitted. At slightly higher (but nontoxic) concentrations, the ionophore inhibits the butyrate-mediated induction of the ganglioside biosynthetic enzyme, sialyltransferase, in HeLa. In CHO, sialyltransferase activity is normally high and not altered by any of the compounds tested.


An established preadipose cell line and its differentiation in culture. II. Factors affecting the adipose conversion. When cells of the established preadipose line 3T3-L1 enter a resting state, they accumulate triglyceride and convert to adipose cells. The adipose conversion is brought about by a large increase in the rate of triglyceride synthesis, as measured by the incorporation rate of labeled palmitate, acetate, and glucose. In a resting 3T3 subline which dose not undergo the adipose conversion, the rate of triglyceride synthesis from these precursors is very low, and similar to that of growing 3T3-L1 cells, before their adipose conversion begins. If 3T3-L1 cells incorporate bromodeoxyuridine during growth, triglyceride synthesis does not increase when the cells reach a stationary state, and triglycerides do not accumulate. As would be expected from their known actions on tissue adipose cells, lipogenic and lipolytic hormones and drugs affect the rate of synthesis and accumulation of triglyceride by 3T3-L1 cells, but in contrast to bromodeoxyuridine, these modulating agents do not seem to affect the proportion of cells which undergoes the adipose conversion. Insulin markedly increases the rate of synthesis and accumulation of triglyceride by fatty 3T3-L1 cells, and produces a related increase in cell protein content. Of 20 randomly selected clones isolated from the original 3T3 stock, 19 are able to convert to adipose cells. The probability of such a conversion varies greatly among the different clones, in most cases being much lower than for 3T3-L1; but once the conversion takes place, the adipose cells produced from all of the 19 clones appear similar. The adipose conversion would seem to depend on an on-off switch, which is on with a different probability in different clones. This probability is quasistably inherited by the clonal progeny.


The 5' terminal structure of the methylated mRNA synthesized in vitro by vesicular stomatitis virus. The 5' terminal structure of the mRNA synthesized in vitro by the virion-associated RNA polymerase of vesicular stomatitis virus in the presence of S-adenosyl-L-methione consists of 7-methyl guanosine linked to 2'-O-methyl adenosine through a 5'-5' pyrophosphate bond as m7G(5')ppp(5')A-m-p ... The alpha and beta phosphated of GTP and alpha phosphate of ATP are incorporated into the blocked 5' terminal structure.


Methylated and blocked 5' termini in vesicular stomatitis virus in vivo mRNAs. Methyl groups derived from 3H-methyl methionine were incorporated into vesicular stomatitis virus (VSV) MRNAs isolated from infected cells. Sequential degradation of the 12-18S viral mRNA species with ribonuclease T2, penicillium nuclease, and alkaline phosphatase yielded a single 3H-labeled dinucleotide. A similar resistant 32P-labeled fragment was obtained by digesting VSV mRNA uniformly labeled with 32P. This methylated and blocked oligomer was further cleaved with nucleotide pyrophosphatase, yielding two methylated 5' nucleotides. We postulate that the 5' terminal structure of the vivo 12-18S VSV mRNA contains 7-methylguanosine linked by a 5'-5' pyrophosphate bond to a methylated derivative of adenosine. In contrast to the mRNAs (+ strand), the VSV genome RNA ( MINUS STRAND) IS NOT BLOCKED.


Differential cytotoxic acitivity of anticollagen serum on rat osteoblasts and fibroblasts in tissue culture. Rat skin fibroblasts grown in tissue culture were lysed by anti-rat-tail collagen serum and antibodies to the ordered collagen-like synthetic polymer (Pro-Gly-Pro)-n. This cytotoxic effect is complement-dependent and occurs only if the fibroblasts were pretreated with trypsin. These anti-sera have very little cytotoxicity on cultured rat osteoblasts. This differential cytotoxicity is not due to differential binding of anticollagen serum to the cells. Both osteoblasts and skin fibroblasts bind the anticollagen serum as was demonstrated by fluorescent immunoglobulin.


Effect of prolonged low-dose angiotensin II infusion on the sensitivity of adrenal cortex in man. The effect of incremental infusions of isoleucine-5-angiotensin II on blood pressure and plasma aldosterone concentrations was studied in normal man before and after 66 hours of intravenous infusion of angiotensin II at 2 ng kg-1 min-1, sodium and potassium balance being kept roughly constant throughout. Plasma sodium and ACTH concentrations were unaltered, but plasma potassium and magnesium levels and basal plasma cortisol fell slightly after prolonged angiotensin administration. During the prolonged angiotensin infusion plasma renin activity was suppressed, and there was a sustained elevation of arterial pressure and plasma aldosterone concentration. Aldosterone excretion, while clearly increased, showed a regular circadian rhythm, with peak values in the early morning. The angiotensin II-pressor relationship was not significantly changed after the prolonged infusion of angiotensin II, while the angiotensin II-aldosterone dose-response curve was steeper than in the basal state but not identical with that of sodium depletion. No differences were observed in the pressor or aldosterone-stimulant effects of the isoleucine-5 and valine-5 forms of angiotensin II. A trophic effect of angiotensin II on the adrenal cortex may provide a partial explanation for the enhanced response of aldosterone to angiotensin II in sodium depleted man.


Technetium stannous pyrophosphate myocardial scintigrams in patients with chest pain of varying etiology. Technetium-99m stannous pyrophosphate was utilized for myocardial imaging in 202 patients admitted to the hospital with chest pain of uncertain etiology. One hundred and one patients had clinical and evolved electrocardiographic and enzymatic evidence of acute myocardial infarction. Ninety-six of these 101 patients had increased myocardial uptake of the technetium stannous pyrophosphate and positive myocardial scintigrams; there was nearly precise correlation between the ECG and myocardial imaging localization of the area of infarction for acute transmural myocardial infarctions. In the five patients with negative myocardial images the scintigrams were obtained after seven or more days had elapsed following the myocardial infarction. In the remaining 101 patients no clinical, ECG, or enzymatic evidence of infarction developed; 92 of these patients had negative myocardial scintigrams. Seven of the remaining nine patients were admitted with "unstable angina pectoris", and despite the absence of diagnostic ECG and enzyme evolution each of these patients had faintly and diffusely positive myocardial scintigrams. The remaining two patients had positive myocardial scintigrams but no definite ECG or enzymatic evidence of acute myocardial infarction. Thus the technetium pyrophosphate imaging technique appears safe, inexpensive and to correlate well with ECG and enzyme identification of the presence of infarction and with ECG localization of myocardial infarction. In addition the positive myocardial scintigrams in some patients with "unstable angina" suggest that there may be limited myocardial necrosis that is ordinarily undetected by ECG and enzymes in these patients. The incidence of false positive and false negative scintigrams appears to be small.


Molar absorptivities of beta-NADH and beta-NAD at 260 nm. To determine the molar absorptivities of beta-NADH and beta-NAD at 260 nm, we purified the reduced form of the coenzyme by repeated anion-exchange chromatography. A NADH preparation was so obtained for which the 260 nm/340 nm absorbance ratio was 2.265. When calculated with epsilon 340 beta-NADH = 6.22 times 10-3 for beta-NADH at 260 nm and 25 degrees C, a molar absorptivity of 14.1 times 10-3 liter - mol minus 1 - cm minus 1 resulted from this quotient. By use of the lactate dehydrogenase or glycerol-3-phosphate dehydrogenase assay, respectively, and referring to the new absorption coefficient for NADH at 260 nm, the molar absorptivity of beta-NAD at 260 nm and 25 degrees C was established to be 17.4 times 10-3 liter - mol minus 1 - cm minus 1. The values observed are lower than those reported thus far.


Peripheral resistance to thyroxine: a cause of short stature in a boy without goitre. A euthyroid pubertal boy was investigated for short stature and was found to have an elevated serum thyroxine and delayed bone age. In spite of high thyroxine levels, there were no clinical signs of hyperthyroidism and kinetic studies revealed a normal rate of thyroxine metabolism. Plasma TSH levels were elevated but there was no goitre. Administration of up to 900 mug of thyroxine or 225 mug of triiodothyronine led to minimal changes in urinary hydroxyproline excretion, pulse rate and body weight. These observations indicate that this boy has a target organ insensitivity to thyroid hormones. When compared with other patients with this disorder, the studies further emphasize that this condition may have a variable clinical presentation. In addition, the extent of the target organ defect may not be evident from routine clinical and laboratory observations. The possible molecular basis of the defect is discussed.


Effect of oral thyrotrophin-releasing hormone on serum thyroxine in growth hormone deficient and normal children. Oral administration of synthetic TRH in a dose of 80 mg/1-73 m-2 at 0 and 12 h to normal and constitutionally small children caused a significant increase of total serum thyroxine (T4) within 6-24 h. The mean maximal T4 increment was +3-7 plus or minus 1-1 and +3-8 plus or minus 1-2 mug/dl (mean plus or minus 1 SD) respectively in the two groups. Of seventeen euthyroid GH deficient children, fifteen showed a normal and two patients a slightly subnormal response. Of fifteen hypothyroid GH deficient children nine had a prompt and normal increase of serum T4 indicating primary TRH deficiency. Two had a delayed T4 response and four had no response, even after prolonged stimulation. The localization of the primary defect in these latter subjects with severe hypothyroidism can not be made by measuring T4 only, since the thyroid gland may become unresponsive to TSH after longstanding TSH deficiency. TSH measurements are necessary in these circumstances for a clear localization of the primary defect. One GH deficient patient with hypothalamic TRH deficiency was treated with high oral TRH doses for 7 months and showed no side effects.


Comparison of the effects of ethinyl oestradiol and conjugated equine oestrogens in oophorectomized women. Seventeen oophorectomized women were treated for 3 month periods, in random sequence, with ethinyl oestradiol 20 and 50 mug daily and conjugated equine oestrogens (Premarin)0-625 and 1-25 mg daily. The serum cholesterol, clot lysis time, plasma fibrinogen, platelet adhesiveness and activated partial thromboplastin time remained unchanged throughout the different oestrogen regimes. There was a significant rise of serum triglyceride levels on both doses of ethinyl oestradiol but no significant change with Premarin. Serum luteinizing hormone levels were depressed most by ethinyl oestradiol 50 mug daily, although no down to the levels in premenopausal women.


The effect of yttrium-90 implantation on endocrine function and visual fields in patients with "functionless" pituitary tumors, with biopsy and radiological findings. Thirty patients with symptoms from "functionless" pituitary tumours were treated by yttrium-90 implants, and we report here the effects on symptoms, pituitary function and visual fields. On biopsy, about a third of the tumours showed some hormone granules. In the sixteen fully assessed at 1 year, pituitary function was improved in 25%, unchanged in 62-5%, and reduced in 12-5%. Improvement was confined to those in whom gonadotrophin secretion was the only function impaired pre-implant. Visual field defects were present pre-implant in ten patients (twenty eyes); at 1 year post-implant these defects had lessened in 80% and deteriorated in only 5% of eyes. Subsequently, within 5 years of the implant the field defects had worsened or recurred in four patients, all with initially extensive suprasellar projection; further treatment was then given. Remineralization of the sella was seen after implantation in seven cases, with reduction in fossa size in five. Thus pituitary implantation appears to be a practicable and reasonably simple procedure suitable for the treatment of most cases of "functionless" pituitary tumour. The "supressive" doses of irradiation used are adequate to shrink most tumours without loss of pituitary function.


Circulating levels of corticotrophin and cortisol after infusions of L-DOPA, dopamine and noradrenaline, in man. Intravenous infusions of noradrenaline and dopamine in normal saline, and L-dopa in sodium lactate, were given to seven patients with Parkinsonism, and to five healthy volunteers. Infusions of saline and lactate were given, in a similar manner, to six additional healthy volunteers, who formed a control group. Dopamine and noradrenaline were each given in gradually increasing doses, for periods of 4 min, until a 30% increase in systolic blood pressure had occurred. L-Dopa (320 mg) was given a constant rate of infusion over 80 min. Plasma fluorogenic corticosteroids (cortisol) increased with dopamine , and decreased with noradrenaline. These changes were significantly different from the control group in the case of noradrenaline only. ACTH values changed in a similar manner. L-Dopa produced a consistent rise in both ACTH and cortisol that was significantly different from control subjects. The implications of these observations are discussed.


Hemihypertrophy of lower extremity associated with multifocal intraosseous hemangioma. This is a case report of a child with hemangioma of the bones of the lower extremities. The evolution of the disease in several bones, during the period between infancy and maturity, and serial growth studies of the extremities and differences in length of bones reveals that in some cases the involved bone grew longer than its fellow, whereas in others it grew shorter. Histological examination of an epiphyseal plate demonstrates that hemangioma grew on either side of the plate.


Lesions of the atlas and axis.

Lesions of the atlas and axis. The atlas and axis support the head on the lower cervical spine while providing for considerable mobility in flexion, extension, rotation and lateral bending.  The first two vertebrae also function as conduits for the cervical cord and vertebral arteries.  Lesions of the atlas and axis, therefore, can cause instability with loss of support and encroachment on the upper cord and vertebral arteries, or less often stiffness with restricted motion.  Congenital lesions of the occipito-cervical spine such as occipitalization of the atlas or accessory occipital vertebrae can constrict the upper cord with osseous, dural, or fibrous compression.  Such encroachment on the cord at this level produces a varying array of clinical complaints and findings frequently difficult to interpret.  Instability of the upper cervical spine can result from congenital, traumatic, inflammatory or neoplastic disruptions of the interlocking mechanism of the atlas and axis.  Such factors as the loss of structural integrity of the dens or stretching or tearing of the transverse ligament can permit instability with cord involvement.  Because of the serious potential of these lesions, patients with abnormalities of the atlas and axis require prompt recognition and treatment.


The GP as a psychiatric community resource. One hundred pyschiatric inpatients were interviewed to determine their normal use of a family doctor and opinion about his value in aftercare. The ward team made a similar decision and when appropriate, a family doctor was approached about his willingness to undertake the aftercare. There were 54 patients who had a family doctor, 38 felt he could assist in aftercare. By contrast, the ward team seldom considered referral appropriate and family doctors were initially hostile to the concept. The demographic variables and attitudes underlying the views of patients, staff, and family doctors are discussed together with their implications for community care.


Fluorimetric determination of dipeptidyl carboxypeptidase. (angiotensin-I-converting enzyme). A fluorimetric assay of dipeptidyl carboxypeptidase is described. It involves incubation at 37 degrees C with the substrate, Z-Phe-His-Leu, and reaction of the dipeptide His-Leu which is released upon enzymatic hydrolysis, with o-phthalaldehyde to yield a fluorescent compound. The method is simple, precise and sensitive. The assay in serum is conveniently performed on 20 mul samples. Normal values in human serum range from 0.04 to 0.22 U/l.


Leucocyte energy metabolism. V. Glycolytic and hexose monophosphate shunt enzymes in leucocytes from adults and newborn infants. The activities of ATP-consuming and ATP-producing steps of the Embden-Meyerhof pathway, as well as other glycolytic enzymes (phosphoglucomutase and enolase) and glucose-6-phosphate dehydrogenase are lower in leucocytes from cord blood than in white cells from adults. These results are related to previous observations (reduced anaerobic glycolysis and nitroblue tetrazolium-test in leucocytes from newborn infants) and discussed in connection with the fact that newborn infants are more susceptible to infections than normal adults.


Enzymes of fructose metabolism in human kidney. Activities of enzymes involved in fructose metabolism were measured in samples of human kidney cortex and medulla. The enzymes are ketohexokinase, aldolase, NAD- and NADP-dependent alcohol dehydrogenase, aldehyde dehydrogenase, triokinase and glycerate kinase; hexose biphosphatase and sorbitol dehydrogenase were also investigated. With the exception of glycerate kinase, all enzymes involved in fructose metabolism were found in the human cortex and medulla. The enzyme levels in the medulla were low in comparison with the cortex.


Enzymes of fructose metabolism in human small intestine mucosa. The enzyme activities involved in fructose metabolism were measured in human intestine mucosa. Mucosa of the following gut sections were used: duodenum, jejunum, jejunum in the region of the flexura duodenojejunalis, jejunum distal region, ileum middle region and ileum in the region of the valvula ileo coecalis. Ketohexokinase, aldolase, alcohol dehydrogenases NAD- and NADP- dependent were found in all gut sections. The activity of aldehyde dehydrogenase was low in all sections tested. Triokinase could be found only in the duodenum and jejunum region and was absent in the ileum. Glycerate kinase was not present in the human intestine mucosa.


A 3'-deoxymononucleotide-producing nuclease from the marine sponge Verongia aerophoba. I. Purification. A four-step procedure for purification of a nuclease from the keratinous sponge Verongia aerophoba is described. The extracted material is lyophilized, acidified, and subjected to chromatography on Sephadex, hydroxyapatite, and phosphocellulose. The nuclease is purified about 1,000-fold from the crude extract and approximately 1,600-fold from concomitant acid RNase. Phosphodiesterase is lost after chromatography on Sephadex. The purified enzyme solution contains one single activity as determined by polyacrylamide gel electrophoresis.


Insulin: interaction with membrane receprots and relationship to cyclic purine nucleotides and cell growth. Insulin action is discussed with emphasis on events that occur at the plasma membrane. A summary is presented of previous studies which indicate that the insulin receptor of fat and liver cells is a large glycoprotein, partially buried in the outer surface of the plasma membrane, with a high (K-D approximately 10-10 M) and specific affinity for insulin. The participation of membrane phospholipids in the binding of insulin and the role of sialic acid residues in the transmission of the insulin binding signal are discussed. The relation of insulin action to its effects on cyclic nucleotide levels is explored. On the one hand, insulin action (glucose transport) is inhibited by compounds (cholera toxin, ACTH, glucagon and L-norepinephrine) that stimulate adenylate cyclase; conversely, insulin both inhibits the lipolytic action of these compounds, and raises cellular levels of cyclic GMP. An hypothesis is presented whereby a single cyclase species may be responsible for the formation of either cyclic AMP or cyclic GMP, depending on the nature of the hormone stimulus. The role of membrane phosphorylation in the action of insulin is discussed in the context of experiments demonstrating a specific inhibition by ATP of insulin-mediated glucose transport, in association with the phosphorylation of two specific membrane proteins. The ability of insulin to modulate cyclic nucleotide levels in cultured cells and to act as a growth factor is discussed. Insulin stimulates DNA synthesis and the uptake of alpha-aminoisobutyric acid in human fibroblasts, which effects are also mediated by epidermal growth factor. Insulin acts at concentrations much higher than those obtained in vivo, whereas epidermal growth factor acts at concentrations thought to be physiological. The insulin binding sites (K-D is approximately equal to 10-9 M) related to growth, and observed both in human fibroblasts and in lectin-stimulated and leukemic human lymphocytes would not be appreciably occupied at physiological insulin concentrations. The implications of such 'low affinity' binding sites for insulin are discussed in relation to the action of other growth factors.


Relation of insulin receptors to insulin resistance. The status of insulin-receptor interactions in a variety of insulin-resistant states is reviewed. Utilizing large adipocytes from adult rats and small fat cells from young rats, we have conducted a series of in vitro experiments in an attempt to determine the cellular alteration(s) responsible for the insulin resistance associated with obesity. Stimulation of glucose oxidation by insulin is reduced in large cells. Studies using a mimicker of insulin action, spermine, as well as measurements of 125I-insulin binding to large and small cells indicate that receptor number and affinity are not responsible for hormone resistance. Furthermore, when rapid and direct measurements of sugar uptake were made, insulin stimulation was virtually identical in both cell types. These findings indicate that large adipocytes have an efficient insulin-responsive D-glucose transport system and suggest that the apparent hormone resistance may be due to alterations in intracellular glucose metabolism. It has been proposed that altered insulin-receptor interaction underlies the insulin resistance of human obesity. We have investigated this particular aspect of insulin action by 125I-insulin binding studies. Similar numbers of insulin receptors per cell and affinity for insulin were observed in adipocytes obtained from normal weight subjects and morbidly obese patients. Thus, the initial step in insulin action is unaltered in human obesity.


[Classical and current aspects of the formation of motor dominance in man]. In the paper, significance of driving phenomenon for formation of motor dominant is considered and experimentally corroborated with the aid of autocorrelation and spectral analysis of the working man's EEG.  The A.A. Ukhtomsky classical postulate has been complemented by contemporary ideas of the role of phasic relationships between the cortical activity for extablishing intercentral interconnections and the functional differentiation of working and irrelevant cortical structures.  Data of correlation, crosscorrelation, and coherent EEG analysis enable to ascertain stages of formation of motor dominants at the cortical level and to judge of possible mechanisms of concentration of the dominant consstellations, as well as to show significance of the coadjustment for a common rhythm and of coincidence in phase of oscillations for improvement of the effectiveness of motor activity in man.


[Work dominance and its age-related development]. When studying working industrial processes, peculiar displays of the dominant corresponding to common signs of the Ukhtomsky dominant, were revealed. Some physiological processes characteristic of the dominant were studied in their developing in children of different age and in adolescents.


[Polygraphic study of sleep in dogs].

[Polygraphic study of sleep in dogs]. Phenomenology and structure of the dog sleep were studied in chronic experiments.  Three stages of NREM and REM phases were revealed.  Sleeep in the dog was shown to differ from sleep in the rat, rabbit, and cat by appearance of alpha-like regular rhythm 8--9/sec during the onset of drowsiness, and by the sigma-rhythm first appearing against the background of clear slow waves.  The exact estimation of REM sleep was shown to need a combined consideration of the EEG data with one of the two other signs (EMG or EOG).


Gastric acid secretion and sleep stages during natural night sleep. Gastric acid secretion during natural sleep was studied in 4 healthy female volunteers for 11 nights. Acid output was measured by means of intragastric titration and a telemetering capsule, and sleep was monitored continuously by recording EEG and eye movements. Compared to the waking state, sleep was found to be associated with significantly lower levels of acid secretion. Although there were no significant differences between acid secretion during sleep stages 1 to 4 and rapid eye movement (REM), acid secretion decreased with deeper stages of sleep. During all REM phases only small amounts of acid were produced. Arousal or periods of waking in the course of the night, as well as waking in the morning, were associated with an increase in acid output.


[The atypical vessels of the feminine breast in the plate-thermography (author's transl)]. In 215 atypical--including 109 carcinomas and 8 carcinomata in situ--as well as 294 verified benign histological evidences of the breast the value of the main clinical, mammographical and plate-thermographical symptoms is examined. The clinical palpable tumors, the mammographical irregular connective tissue and/or the homogenous opacity, as well as plate-thermographical atypical vessels proved to be a relatively insecure sign of a carcinoma. The individual characteristics of the atypical vessels in the plate-thermography according to Tricoire were worked out. The sudden and blunt breaking-off of a atypical vessel has to be considered the most suspicious sign for a carcinoma. The plate-thermography according to Tricoire is also usable as additive method for diagnosis of benign breast-tumors that don't have to be exstirpated.


Genetic control of radiation sensitivity in Schizosaccharomyces pombe. Genetic analysis of a large number of radiation-sensitive mutants of S. pombe, isolated in different laboratories, showed that these isolates represent 22 non-allelic loci. The mutants were shown to fall into three distinct classes concerning response to UV and ionizing radiation, including two mutants which are primarily sensitive to ionizing radiation but not to UV. Single-gene mutants were crossed to obtain supersensitive double mutants. Such double mutants showed a marked increase in sensitivty to a variety of inactivating agents as compared to the parental strains. The isolation of three classes of radiation-sensitive mutants and the construction of double mutants implies the presence of multiple pathways in S. pombe for repair of radiation-induced damage. The bearing of these data on cellular repair mechanisms in eukaryotes is discussed.


Complementation analysis of methyl methane-sulfonate-induced recessive lethal mutations in the zeste-white region of the X chromosome of Drosophila melanogaster. Recessive lethan mutations in the 3A1 to 3C2 region of the X-chromosome of Drosophila melanogaster were detected in 113 of 33,544 sperm treated by feeding 5 mM methyl methanesulfonate in 1% sucrose for 22 hours. Seven of the 113 lethans were sterile, leaving 106 for analysis by complementation tests. With only one exception, these mutants were found to have lesions restricted to single loci. One of these single-site mutations was in qt, 2 in tko, 18 in zw-1, 12 in zw-8, 6 in zw-4, 3 in zw-10, 3 in zw-13, 21 in zw-2, 7 in zw-3, 5 in zw-6, 6 in zw-12, 1 in zw-7, 12 in zw-5, 5 in zw-11, and 3 in zw-9. One of the lethals, m69, was non-complementary to two adjacent loci, zw-2 and zw-3, possible indicating a deletion encompassing two loci. The results confirm that there are at least 15 recessive lethal loci in the region and are consistent with the hypothesis of LIM and SYNDER (1968 and 1974) that inability of monofunctional alkylating chemicals to induce deletion associated mutations is a characteristic of the compounds.


The determination of paraquat using thin-layer chromatography. A thin-layer chromatographic method for the detection and determination of Paraquat in biological materials is presented. Paraquat was concentrated efficiently with the ion-exchange resin Dowex 50W-4 using a batch operation. Of the 16 solvent systems used the best results were obtained on silica gel G plates with methanol : 6N hydrochloric acid (20 : 30) or methanol : 6N sulfuric acid (20 : 30); and on cellulose plates with methanol : 6N hydrochloric acid (35 : 15) or methanol : 6N sulfuric acid (40 : 10). Also described is a microplate method for the thin-layer chromatography of Paraquat.


Multiple hormone producing islet cell carcinomas of the pancreas. A morphological and biochemical investigation. Biochemical, light, and electron microscopic studies of two multiple hormone producing metastic islet cell carcinomas of the pancreas are presented. Both tumors initially produced symptoms referable to a single hormone and over a period of years produced two other endocrine active polypeptides. The tumor in case 1 had been studied electron microscopically six years previously and had demonstrated no significant ultrastructural changes since then. The tumor in case 2 contained secretory granules of markedly varying size and density, suggesting a formation of packaged precursor molecules of possibly all three hormones. The pathogenesis of these tumors is discussed in light of recent evidence concerning the origin of endocrine cells.


Histologic variants of infiltrating lobular carcinoma of the breast. Thirty-eight breasts with lobular carcinoma in situ and an additional intraductal or infiltrating cancer were studied. Twenty-six of the additional cancers were diagnosed as infiltrating lobular cancer on the basis of a single population of small uniform cells cytologically identical to those in lobular carcinoma in situ. In 20 of these cases the conventional pattern of infiltrating lobular cancer was evident with an individual cell infiltrate with foci of single filing. In the other six there was a confluent arrangement of cells in solid sheets. This pattern has not been previously reported as a pattern of infiltrating lobular cancer. Because of the identical cytologic appearance, we believe it is a variant of infiltraing lobular cancer and should be diagnosed as such.


Studies on the immune response and pathogenesis of Sendai virus infection of mice. III. The effects of cyclophosphamide. Studies of the effects of cyclophosphamide on a non-lethal primary Sendai virus infection of mice are reported. Treatment with cyclophosphamide resulted in failure to limit or eradicate virus, diminished and delayed the appearance of immunoglobulin-secreting cells in the lungs and the production of local and serum antibody, reduced and delayed the appearance of bronchial basement membrane damage and the desquamation of infected mucosal cells, and reduced the incidence of immune complex deposition in the kidneys. Evidence is presented which indicated that some escape from immunosuppression occured by day 6, resulting in local antibody production. The appearance of the local antibody response was associated with increased tissue damage in the lungs and the deposition of immune complexes of viral antigen and antibody in the kidney. Nine further experiments were performed in mice to investigate this renal manifestation and preliminary results are presented. In four of seven Sendai and one of two avirulent influenza A (Kunz) virus infections glomerular immune complexes were found. Studies in C3H and C57 B1 mice and their F1 hybrid suggested that genetic factors play some part in the renal findings. The results are discussed with respect to the possible beneficial and harmful effects of the immune response to trivial respiratory virus infections.


Immunodeficiency in the chicken. I. Disparity in suppression of antibody responses to various antigens following surgical bursectomy. The extent of suppression of antibody response by bursectomy (Bx) was examined as a measure of the seeding sequence of different clones from the bursa to peripheral lymphoid tissues. Chickens were bursectomized surgically 1, 4 or 7 days after hatching and immunized later with four antigens: sheep red blood cells (SRBC); Bordetella pertussis (Bp); human serum albumin (HSA); influenza virus (IV). The kinetics of the antibody responses were delayed in bursectomized birds when compared with the control groups. The following order in the degree of immunosuppression was established: Bp greater than HSA greater than SRBC greater than IV. This is discussed in relation to the 'sequential maturation' theory of ontogenesis of immunocyte differentiation. The data also stress the limitation of non-specific markers for assessing partial immunodeficiency states.


Immunodeficiency in the chicken. II. Production of monomeric IgM following testosterone treatment or infection with Gumboro disease. Chickens were treated at an early embryonal age with testosterone propionate or infected neonatally with the virus producing Gumboro disease. Their sera were subsequently fractionated by Sephadex G-200 chromatography, and showed a complete deficiency of IgG and the presence of IgM which was eluted with the 7S protein fraction. Purified and 125-I-labelled monomeric IgM was examined by SDS-acrylamide gel electrophoresis and found to contain both mu and light chains, together with a chain of intermediary size, which was absent from the patterns of 19S IgM or IgG.


Interaction of collagen with serum complement: inhibition of complement-mediated hemolysis. Collagens from various vertebrate tissues were tested for their ability to consume complement (C) activity upon incubation in human serum or with isolated components of complement. 10 of 12 collagens tested had anticomplementary activity. The heat-denatured form of collagen, gelatin, was found weakly anticomplementary, but elastin was found inactive in the interaction with C. Inactivation of C is a reaction which is dependent on the time of incubation and the collagen concentration and partially dependent on the temperature of incubation. Most collagens depleted C from human serum in presence of cation chelators, EDTA and EGTA, whereas the large part of anticomplementary activity of soluble collagens obtained from rat skin was abolished in presence of EDTA. Evidence is presented that two different principles in collagens play a role in inactivation of C. A factor, contained in insoluble collagens and inhibitable by mild oxidation with periodate, inactivates C1 directly even in presence of chelating agents. Another principle, contained in soluble and insoluble collagen and resistant to periodate treatment, depletes C in serum by utilization of C via the alternate pathway (the C3 shunt).


Dreams and dementia: a laboratory exploration of dream recall and dream content in chronic brain syndrome patients. Seventeen (seven mild and ten severe) chronic brain syndrome patients were testes in the sleep laboratory for dream recall and content. The mildly organic patients had 57 per cent recall while the severely organic patients had 35 per cent recall. We also studied four aged severely organic patients. These patients showed a recall rate of 8 per cent. The difference between the recall rates in mildly and severely organic middle-aged patients was not statistically significant. The difference between the recall rates of the aged severely organic patients and either or both of the middle-aged groups was statistically significant (p smaller than .001). In addition, we found dream content differences between the mildly and severely organic middle-aged groups and between the combined group and normal young men.


Effects of ionizing radiation on dried spores of Osmunda regalis III. 35 GHz e.s.r. study. The use of 35 GHz microwave frequency has greatly simplified the separation of overlapping signals in dried irradiated fern spores. While in general confirming the conclusions previously drawn from X-band spectra, the use of Q-band has clarified several assignments of radical groups and allowed the recognition of additional radical groups or sub-groups.


Comparison of radiolysis products of thymine and thymidine with e.s.r. results. Radicals determined by e.s.r. spectrometry of irradiated thymine or thymidine and radiolytic products generated under tha ction of gamma rays in aerated aqueous solutions have been compared. This comparison lies mainly in the fact that a radical R gives rapidly the corresponding peroxide ROOH. The authors have isolated and characterized twenty peroxides, i.e., the four isomers cis (-), cis (+), trans (-), trans(+) of 6-hydroperoxy-5-hydroxy-5,6-dihydrothymidine; the four isomers cis (-), cis (+), trans (-), trans (+) of 5-hydroperoxy-6-hydroxy-5,6-dihydrothymidine; 5-hydroperoxy-2-deoxyuridin;cis and trans 6-hydroperoxy-5-hydroxy-5,6-dihydrothymine; cis and trans 5-hydroperoxy-6-hydroxy-5,6-dihydrothymine; 5-hydroperoxymethyl-uracil; 5-hydroperoxy-5,6-dihydrothymine;cis and trans 6-hydroperoxy-5,6-dihydrothymine; 5-hydroperoxy-5-methyl barbituric acid; 5-hydroperoxy-5-methyl hydantoin; trans 5,6-dihydroperoxy-5,6-dihydrothymine. Most of thethymine and thymidine radicals hypothesized or described in the literature were correlated to these peroxides. However, the presence of certain peroxides could not be explained by recognized radicals. Taking advantage of this fact, the existence of new thymine or thymidine radicals so far unknown can be predicted.


Muscle fiber and motor end plate involvement in the extraocular muscles of the myotonic mouse. The extraocular muscles of the C57BL/6Jdy-2j myotonic mouse were studied by phase and electron microscopy. The most susceptible ocular muscle was the levator palpebrae; the other muscles manifested scattered abnormalities to varying degrees. Central nucleation and fiber splitting were prominent. Junctional abnormalities consisted of a reduction in post-junctional folding, excessive numbers of axonal terminals on hypertrophic fibers, and the presence of dense granules between axon and muscle. This study demonstrates the affection of both muscle fiber and motor end plate in mouse myotonic dystrophy.


Mucolipidosis IV: ocular, systemic, and ultrastructural findings. The ocular and systemic findings in four children with mucolipidosis IV (ML IV), a new variant of mucolipidosis, are described. Corneal clouding from birth or early infancy is a prominent feature in all of the patients and in two of them, this was the presenting symptom. Psychomotor retardation usually does not become apparent until the end of the first year of life. Conjunctival biopsies revealed two types of abnormal inclusion bodies: (1) single-membrane-limited cytoplasmic vacuoles containing both fibrillogranular material and membranous lamellae, and (2) lamellar and concentric bodies similar to those found in Tay-Sachs disease. The abnormal cytoplasmic organelles were present in both the stromal fibroblasts and the epithelial cells. The electroretrinogram performed in one patient was subnormal.


Cytologic changes of the retina and pigment epithelium during hibernation. The pigment epithelium and the retina of hibernating frogs, bats, and ground squirrels are studied electron microscopically and the findings are compared with those of the same animals obtained in normal condition. The smooth endoplasmic reticulum of the pigment epithelial cell becomes sparse and transforms into large tubular structures during the hibernation. No appreciable changes are noted in the rod outer segments of hibernating bats and frogs. However, the cone outer segments of the ground squirrel show striking disappearance during experimental hibernation. Regeneration of the cone outer segments of the squirrel retina is found to be fast when the animals are placed in a normal environment.


The effect of nonspecific immune stimulation on the recurrence rate of herpetic keratitis in rabbits. Cellular immunity is of primary importance in resistance to virus infection. In this study, 75 rabbits were immunized with live BCG, 75 rabbits were immunized with Staphylococcus aureus, and 75 rabbits were injected with saline. Two weeks after immunization the corneal epithelium of both eyes was infected with McKrae strain herpes virus, and five weeks after immunization the rabbits were skin tested with old tuberculin or staphylococcus to ascertain their immune status. The corneas were observed under the slit lamp for recurrent epithelial herpes from day 52 through day 84 after immunization. During the second week of observation the group immunized with BCG had statistically significantly fewer recurrences than the saline-injected control group. The data for the BCG group during the remainder of the observation period, and for the SPL immunized group, were not statistically distinguishable from the control group. These experiments indicate that nonspecific immune stimulation provides little protection against recurrent herpetic infection. It is possible that manipulation of dosage and timing could enhance this effect.


Experimental cerebral vasospasm and cyclic adenosine monophosphate (c-AMP). Blood induced acute and chronic cerebral vasospasm were studied in Rhesus monkeys by serial angiography.  Two vasoactive agents were evaluated.  In acute spasm, phosphodiesterase inhibition by Aminophylline consistently reversed the vasospasm.  This agent alone was ineffective in chronic spasm and required the addition of Isoproterenol to produce reversal of vasospasm.  It is proposed that cerebral vasospasm may be associated with a decrease of intracellular c-AMP in vascular smooth muscle which can be reversed by manipulation of the enzyme pathway involved.  It is further proposed that c-AMP is a basic common pathway through which adrenergic vascular reactivities are mediated.