Restitution of infectivity to spikeless vesicular stomatitis virus by solubilized viral components. Noninfectious spikeless particles have been obtained from vesicular stomatitis virus (VSV, Indiana serotype) by bromelain or Pronase treatment. They lack the viral glycoprotein (G) but contain all the other viral components (RNA, lipid, and other structural proteins). Triton-solubilized VSV-Indiana glycoprotein preparations, containing the viral G protein as well as lipids (including phospholipids), have been extracted from whole virus preparations, freed from the majority of the detergent, and used to restore infectivity to spikeless VSV. The infectivity of such particles has been found to be enhanced by poly-L-ornithine but inhibited by Trition or homologous antiserum pretreatment. Heat-denatured glycoprotein preparations were not effective in restoring the infectivity to spikeless VSV. Heterologous glycoprotein preparations from the serologically distinct VSV-New Jersey serotype were equally capable of making infectious entities with VSV-Indiana spikeless particles, and the infectivity of these structures was inhibited by VSV-New Jersey antiserum but not by VSV-Indiana antiserum. Purified, detergent-free glycoprotein selectively solubilized from VSV-Indiana by the dialyzable detergent, octylglucoside, also restored infectivity of spikeless virions of VSV-Indiana and VSV-New Jersey.


Brain scans, dexamethasone therapy, and brain tumors. Eight men with primary or metastatic brain tumors were examined with brain scans before and after the administration of dexamethasone. All patients demonstrated some improvement in their clinical neurologic status during therapy, and two patients had a dramatic response. Seven of the eight patients examined showed a decrease in the apparent size of the original lesion on recent brain scan while receiving dexamethasone. Comparison of immediate scans obtained 15 to 20 minutes following the administration of sodium pertechnetate Tc 99m with those obtained two or three hours later suggests that the change in apparent size of the original lesion results from decrease in peritumor edema.


Control of aldosterone responsiveness in terminal renal failure. Control of aldosterone responsiveness in terminal renal failure. Plasma aldosterone concentration in 30 hemodialysis patients correlated closely with renin concentration, renin activity or renin and potassium concentrations combined (r is greater than or equal to 0.62; P is less than 0.01), and increased consistently in response to upright posture or corticotropin administration. Aldosterone response to hemodialysis was variable. Significant correlations (r is greater than or equal to 0.65; P is less than 0.01) were demonstrated between postural plasma aldosterone and renin responses, between aldosterone responses to corticotropin and basal plasma aldosterone or renin and potassium values, between hemodialysis-induced changes in plasma aldosterone and those in potassium or renin; but not between various indexes of heparin treatment and aldosterone activity. Bilateral nephrectomy reduced basal plasma renin and aldosterone concentrations and aldosterone responsiveness in five preoperatively normoreninemic or hyperreninemic patients, but not in a hyporeninemic patient. These results demonstrate the complementary roles of circulating renin and potassium in the control of aldosterone release under basal and stimulatory conditions in patients with terminal renal failure. Administration of heparin in dosages used during long-term hemodialysis does not appear to significantly interfere with aldosterone control.


Spontaneous diabetes mellitus in Macaca cyclopis and Mandrillus leucophaeus: case reports. Spontaneous diabetes mellitus was reported in a Mandrillus leucophaeus (drill baboon) and a Mpacaca cyclopis (Formosan rock macaque). Each had hyperglycemia, impaired clearance of glucose during tolerance test, and reduced concentrations of immunoreactive insulin; the M cyclopis also had increased triglyceride and prebetalipoprotein concentrations. Both monkeys had extensive amyloid infiltration into the islets of Langerhans and loss of beta cells. Beta cell obliteration can account for the appearance of the diabetic syndrome in these and other nonhuman primate species.


Control of arrhythmias following ligation of the circumflex artery. In experimental work, three groups of 10 dogs each were subjected to ligation of the circumflex coronary artery. One group was given prophylactic medication with procainamide and another group was allowed a 2 hour interval between thoracotomy and ligation. The effects of these measures on the incidence of ventricular arrhythmias during the 30 minutes immediately after coronary artery occlusion were then compared. The two groups of animals on which these preventive measures were tested both showed a significant reduction in incidence of arrhythmias as compared to the control group. The therapeutic use of procainamide was also assessed by administering the drug intravenously to all animals developing postligation arrhythmias in the two groups which were not prophylactically medicated. In 46 per cent of these cases, the arrhythmias were suppressed and threatened ventricular fibrillation was obviated.


Effect of acute dietary alteration upon intestinal lipid synthesis. The specific activities of three enzymes engaged in complex lipid synthesis, diglyceride acyltransferase, cholinephosphotransferase, and lysolecithin acyltransferase were studied in intestinal mucosa of hamsters fed either saline, hydrolyzed casein, or corn oil for 9 1/2 hr. In the most proximal intestine, saline feeding was associated with a reduced specific activity in villous tips with all three enzymes studied when compared with the two caloric supplemented groups. In the most distal intestine, oil feeding increased the activity of lysolecithin acyltransferase and choline phosphotransferase twofold as compared to casein fed hamsters; diglyceride acyltransferase was increased one- and one-half-fold. The response of lysolecithin acyltransferase and diglyceride acyltransferase to fat feeding was incomplete when compared to hamsters fed a fat supplemented diet for 7 days, suggesting that their pattern of response to dietary substrate was similar to the disaccharidases. By contrast, the response of cholinephosphotransferase to fat feeding was complete at 24 hr, suggesting that it responds in a manner similar to the glycolytic enzymes.


Broad-beta disease versus endogenous hypertriglyceridemia: levels and lipid composition of chylomicrons and very low density lipoproteins during fat-free feeding and alimentary lipemia. To assess the roles of endogenous and exogenous lipid in the production of the abnormal lipoprotein patterns characteristic of broad-beta desease (with a type IVIII lipoprotein pattern) and endogenous hypertriglyceridemia (with a type IV pattern), oral fat loads (50 g/M-2) were administered to six subjects with broad-beta disease and to eight with endogenous hypertriglyceridemia following at leat 72 hr of 0% fat, 85% carbohydrate isocaloric formula feeding. Total plasma and Sf greater than 400, 100-400, 60-100, 30-60, and 20-30 lipoprotein cholesterol, triglyceride, and phospholipid levels were measured at 0 hr, 6 hr (at or before the peak of alimentary lipemia), and 24 hr following the fat load. Following fat-free feeding the levels and composition of the endogenous Sf greater than 400 lipoproteins were similar in both disorders; whereas total Sf20-400, and most notably, Sf 30-60 and 20-30 levels were increased and enriched in cholesterol in the subjects with broad-beta disease.


Stimulation of human purine synthesis de novo by fructose infusion. In order to clarify the mechanism of hyperuricemia and hyperuricosuria resulting from rapid infusion of fructose in man, the effects of an intravenous infusion of 125-200 g of fructose given over 3-4 hr on the rate of purine synthesis de novo was measured in one individual with osteoarthritis and four patients with gout. The incorporation of 1-minus 14C glycine into urinary uric acid was measured, and the pool size and turnover of urate were assessed by renal excretion of simultaneously administered 15-N urate. Fructose caused an expansion of body urate pool in all subjects, while urate turnover was increased in four. The rate of incorporation of 14-C glycine into urinary uric acid corrected for extrarenal disposal was increased in all cases (21%-430%). In two patients, rates of incorporation of 14-C glycine into urinary creatinine were increased by 10% and 11%, while rates of incorporation into uric acid were increased 84% and 159%, respectively, as a result of fructose infusion. Specific enhancement of the rate of purine synthesis de novo was suggested by these findings. The rate of infusion appeared more important than total dose in determining the magnitude of this effect. Whether the increased rate of purine synthesis was a result of direct stimulation by a fructose metabolite or was secondary to fructose-induced purine nucleotide depletion is uncertain, since the kinetics of glycine incorporation were consistent with either mechanism. Erythrocyte PP-ribose-P concentrations, however, were diminished during infusion rather than increased as might be expected if fructose infusion stimulated purine synthesis by increasing availability of this regulatory substrate.


Pathogenesis and management of hypoparathyroidism and other hypocalcemic disorders. Hypocalcemia frequently presents as an acute medical emergency or a chronic disorder which is difficult to control. Occasionally, it is found in routine blood screening tests when it is not anticipated. Recent developments in basic endocrine science have contributed greatly to our understanding and treatment of hypocalcemic disorders. The maintanance of a normal serum calcium concentration depends on the balanced actions of parathyroid hormone (PTH), vitamin D, and, to a lesser extent, calcitonin, Recent work on PTH secretion has defined the factors controlling its secretion in normal and abnormal states. In primary hypoparathyroidism, hormone secretion is decreased or absent, while in most other forms of hypocalcemia, secretion is stimulated secondarily by the hypocalcemia. However, acute or chronci disorders associated with hypomagnesemia may also decrease effective PTH secretion. Patients with the rare disorder, pseudohypoparathyroidism, have defects of hormone action and usually have elevated levels of PTH prior to therapy. Several forms of pseudohypoparathyroidism have been recognized, each representing a defect as a different site of PTH action. Calcitonin excess, as noted in medullary carcinoma of the thyroid, could theorectically cause hypocalcemia, but rarely does so. Vitamin D undergoes a series of two carefully controlled hydroxylation reactions leading to the final active metabolite, 1,25-hihyroxycholecalciferol. Chronic ingestion of certain drugs can lead to osteomalacia and hypocalcemia by potentiating the metabolism of vitamin D to inactive compounds. At least one form of rickets has been shown to result from a specific enzyme defect in the vitamin D pathway. Severe renal damage limits the conversion of vitamin D to its active form and contributes to vitamin D resistance. Current progress in the area depends on the development of procedures for the measurement of the metabolites in plasma and assessing the role of the vitamin (hormone) in normal and abnormal physiology. Although the therapy of acute hypocalcemia is usually readily accomplished, chronic hypocalcemia remains a very difficult therapeutic problem. Vitamin D, the hallmark of therapy, is a long-acting drug with a narrow therapeutic range. The complications of the disease and therapy are sometimes irreversible. The unraveling of vitamin D metabolism has led to the development of new therapeutic agents which might provide better relief of chronic hypocalcemic states. This review related new information about calcium homeostasis to the clinical situation encountered in the patient with hypocalcemia.


[Studies to the in-vitro-effectiveness of Spectacillin (author's transl)]. In this study the sensibility of important disease germs of a clinical and an ambulatory test material has been investigated to the substances "Epicillin" and "Ampicillin". Thereby could be found that 67% (43%) of the E. coli and 55% (36%) of the proteus type, as well as 96% (96%) of the enterococcus type of the ambulatory (clinical) test material were sensitive to Epicillin and Ampicillin. Staphylococcus not producing penicillinase, were well-sensitive, while staphylococcus producing penicillinase, contrarily showed to be insensitive. Salmonellae proved to be well-sensitive up to 97%, and the rest left was limited sensitive. The minimal inhibitory concentration (MIC) resulted in favourable findings for enterococcus, staphylococcus aureus and salmonellae; at a corresponding sensibility the same is valid for E. coli and the proteus. The investigations carried out in-vitro, reveal an equal effectiveness of Epicillin and Ampicillin.


[Experimental investigations concerning spectrum, serum concentration, and excretion of Spectacillin (author's transl)]. By means of the diffusion test, the range of action of the ampicillin successive preparation spectacillin was determined using 12 000 pathological germs freshly isolated from in-patients. The result was a range of action similar to that of ampicillin. A comparison, however, is only possible in case the test platelets (without over-dosage) are each charged with exactly, e.g., 25 gamma. The analyses of serum concentrations have shown that spectacillin is satisfactorily absorbed after oral as well as after parenteral application. Thus, the calculation of the accumulated area of infinity beneath the serum concentration curve had the following results: After single intravenous injection of 1 g spectacillin (n equals 12) 51.46 gamma/ml - h; after single intravenous injection of 2 g spectacillin 86.20 gamma/ml - h; after intramuscular injection (twice) - interval of 12 hours - 29.94 gamma/ml - h after 12 hours; same values as before, but after 24 hours, 29.37 gamma/ml - h. After a single oral application of one capsule of spectacillin (capsule equals 500 mg), the value of the accumulated area was 8.46 gamma/ml - h. In analogy of the good absorption, excretion in urine/24 hrs (after application of 1 g spectacillin intravenously) was 61.74 p.c., after 2 g i.v. 54.30 p.c., and after applying twice 1 g spectacillin intramuscularly 61.40 p.c.; after oral application of 500 mg, the percentage was 28.42. Tolerance of spectacillin was good after oral as well as after parenteral application. No side effects were observed.


The regulation of glycerol 3-phosphate oxidase of rate brownadipose tissue mitochondria by long-chain free fatty acids. Added free fatty acids inhibit oxidation of glycerol 3-phosphate, succinate and NADH in brown-adipose tissue mitochondria from 10-day-old rats. The most pronounced is the inhibitory effect of glycerol 3-phosphate cytochrome c reductase (GP-cyto. c reductase). Contrary to other reductases, GP-cyto. c reductase activity of freshly isolated mitochondria is already inhibited by the fraction of endogenous free fatty acids. Both added and endogenous free fatty acids inhibition of GP-cyto. c reductase is fully reversible by the removal of free fatty acids by bovine serum albumine treatment. The inhibition of GP-cyto. c reductase is of strictly non-competitive type. The most inhibitory are unsaturated long-chain free fatty acids-oleic and linoleic acid. Results are discussed with regards to the regulatory importance of free fatty acids in brown-adiposetissue during intensive non-shivering thermogenesis.


[The value of pyrophosphate scintigraphy for the assessment of the activity of spondylarthritis ankylopoietica (author's transl)]. Seriological and scintigraphic activity was compared in 29 patients with spondylarthritis ankylopoietica (Bechterew's disease). Among our cases, 11 serologically active patients also had positive scans. the details being: cervical vertebral column in 5, thoracic vertebral column in 7 cases and the lumbar vertebral column and iliosacral joint in all 11 patients. In the group of 16 serologically inactive patients, 12 cases could be confirmed radiologically, in the remaining 4 early detection of ankylosing spondylarthritis was possible from the scintigraphic findings in combination with the clinical symptoms. The clinically suspected diagnosis of an incipient Bechterew's disease could not be justified in the remaining 2 patients who had no positive scintigraphic or serological results.


Complementing xeroderma pigmentosum fibroblasts restore biological activity to UV-damaged DNA. UV survival curves of adenovirus 2 using fused, complementing xeroderma pigmentosum (XP) fibroblast strains as virus hosts showed a component with an inactivation slope identical to that given by normal cells. This component was not observed when the fibroblasts were not fused or when fusion involved strains in the same complementation group. Extrapolation of this component indicated that at zero dose 3% of the viral plaque-forming units had infected cells capable of normal repair. These results suggest that 3% of the cells were complementing heterokaryons, a value similar to that actually observed by autoradiographic analysis of UV-induced unscheduled DNA synthesis. Thus, heterokaryons formed from XP fibroblasts belonging to different complementation groups are as capable of restoring biological activity to UV-damaged adenovirus 2 as are normal cells.


Involvement of separate pathways in the repair of mutational and lethal lesions induced by a monofunctional sulfur mustard. The mutagenic and lethal effects of a monofunctional sulfur mustard, 2-chloro-ethylethylsulfide (CEES), have been studied in a number of repair deficient variants of Escherichia coli K12, B/r and B. The results indicate that CEES induces a (pre)mutational lesion which is subject to Uvr+-excision-repair. Extensive CEES-induced mutagenesis can occur in exrA- uvrA- and recA- uvrB- variants suggesting that the majority of the mutations in Uvr-bacteria do not arise from error-prone repair. These findings are similar to results previously reported with a volatile degradation product of captan and with ethyl methanesulfonate (EMS) but differ from those reported with methyl methanesulfonate (MMS). It is hypothesized that CEES alkylates guanine at the O-6 position (R-O-6-G) and that this R-O-6-G which is Uvr+-excisable is directly mutagenic by producing G-C to A-T transitions during replication. Reduced levels of induced mutation frequencies observed in an endonuclease II-deficient variant lead us to postulate that, in constrast to Uvr- bacteria, CEES-induced mutation in wild-type cells arise from error-prone repair of apurinic sites. Analysis of the lethal actions of CEES indicates that the lesion produced is largely unexcisable by the Uvr+ system. Host-cell reactivation of CEES-treated TI bacteriophage shows that the production of the (pre)ethal lesion is dependent on both the initial dose and post-treatment incubation. The efficient repair of the (pre)ethal lesion requires both endonuclease II and polymerase I. Moreover, deficiencies of these two enzymes rendered bacteria more sensitive to the cytotoxic action of CEES. It is postulated that the lethal mechanism of CEES involves: (I) alkylation at the N-3 position of adenine and the N-7 position of guanine; (2) spontaneous depurination of these alkylated bases; and (3) production of apurinic sites which are lethal unless repaired by the endonuclease II-polymerase I excision-repair system.


Reversions of the two missense and one nonsense trp-mutations induced by UV-light or methyl methanesulfonate in E. coli wild type and its polAi and uvrE502 mutants. Two missense mutations, trpA58 and trpA78, and one nonsense mutation-trp-ochre, were used to determine the types of base-pair substitution caused by ultra, violet irradiation and methyl methanesulfonate (MMS) in Escherichia coli. UV irradiation of the wild-type bacteria led to the formation of revertants mainly arising as a result of GC yields AT transitions (suppressor revertants of the trpA58 mutant). True revertants of the trp- mutant (arising via transitions of AT pairs) and 5-methyl tryptophan-sensitive (MT-s) Trp+ of the trpA78 mutant (arising via unidentified transversions) occurred at a lower frequency. The polAI mutation did not change the frequency of the UV-induced transitions GC yields AT or that of the substitutions of the AT pairs. The uvrE502 mutation significantly increased the frequency of the UV-induced revertants arising via the transition GC yields AT. Treatment of the wild-type bacteria with MMS resulted in the formation of revertants mainly due to the GC yields AT substitution, and with a lower frequency to the AT yields GC transitions. MMS also induced, with a low frequency, some transversions. The frequency of the MMS-induced GC yields AT transitions was enhanced in the uvrE502 mutant. On the other hand, the uvrE502 mutation eliminated or significantly lowered MMS-induced revertants arising as a result of AT yields GC transitions or transversions.


Mutagenesis by nitrosoguanidine, ethyl methanesulfonate, and mutator gene mutH in continuous cultures of Escherichia coli. Induction of T5-R mutations by alkylating agents N-methyl-N'-nitro-N-nitrosoguanidine (NTG) and ethyl methanesulfonate (EMS) was examined in glucose limited chemostat cultures of non-mutator and mutator (mutH) bacteria. In agreement with the proposal that NTG mutagenizes DNA at the replication fork, this mutagen (6.8 X 10-minus 6 M) showed replication-dependent mutagenesis in continuous culture. EMS (5-10-minus M)) induced mutagenesis could not be correlated with growth rate, which probably means that induction of mutagenic lesions (promutations) by this mutagen does not involve replicating genes. A large synergic response was found for the mutH gene in combination with NTG, supporting the hypothesis that the mutH gene product acts during DNA replication.


Association of an isomeric species of carcinoembryonic antigen with neoplasia of the gastrointestinal tract. We studied the association between serum levels of an isomeric species of carcinoembryonic antigen and neoplasia of the gastrointestinal tract in 993 patients. With use of an empirically determined threshold, the antigen was found to be elevated in 80.4 per cent of 138 patients with neof other tumors, predominantly lung and breast tumors. Serum levels were elevated in 0.23 per cent of random patients and 0.41 per cent of 725 patients without neoplasia, including those with liver diseases, inflammatory bowel disease and chronic renal disease. The results of this study suggest that this species of carcinoembryonic antigen, and that assay for it offers an improved approach to the diagnosis and management of neoplasia of the gastroinetestinal tract.


Elevated plasma and tissue levels of vasoactive intestinal polypeptide in the watery-diarrhea syndrome due to pancreatic, bronchogenic and other tumors. The actions of the vasoactive intestinal polypeptide make it a potential candidate for mediating certain manifestations of the watery-diarrhea syndrome. Peptide levels were measured by radioimmunoassay in 25 controls and 30 patients with chronic watery diarrhea. Plasma levels were too low to measure (smaller 200 pg per milliliter) in 22 of the controls, averaging 79 plus or minus 64 pg per milliliter (S.D.). Levels were elevated in 26 of 28 plasma samples (5.1 plus or minus 2.5 ng per milliliter), and in each of 13 tissue extracts (5.1 plus or minus 10.9 mug per gram); in all, 28 patients had elevated levels in plasma or tissue or both. Thirteen patients had pancreatic islet-cell adenoma, four islet-cell hyperplasia, five bronchogenic carcinoma, and one each pheochromocytoma and ganglioneuroblastoma. The findings indicate that the peptide is a probable mediator of the watery-diarrhea syndrome, that the syndrome may result from a variety of non-pancreatic tumors, and that this or a related peptide may also be secreted by these tumors.


A correlated study of kidney function and ultrastructure in potassium-depleted rats. In order to provide an ultrastructural description of kaliopenic nephropathy in rats, potassium deficiency uncomplicated by chloride depletion or extracellular fluid volume expansion was induced by dietary means alone. After 12 days, serum and muscle analyses demonstrated severe potassium depletion, while urine concentrating ability was markedly impaired. Although micropuncture techniques demonstrated that net fluid transport in proximal tubules was normal, the epithelial cells showed the following morphological alterations: electron-lucent vacuoles and lysosome-like dense bodies were numerous, focal cytoplasmic degradation was present, and intercellular spaces were dilated in many proximal tubules. Medullary cell droplets were characterized by fusion, massive enlargement with sequestration of cytoplasmic components such as ribosomes, and occasional extrusion through ruptured plasma membranes--features not previously reported.


Cytoplasmic inclusion bodies in superior rectus muscle of the eye. Cytoplasmic inclusion bodies are found in fibers of superior rectus muscle of the eye. They occur in middle-aged and old individuals dying with various unrelated diseases not affecting muscle and in patients with myotonic dystrophy. With light microscopy they can be observed in fibers with pathologic changes, and with electron microscopy they appear to be associated with crystals of probable viral origin. It is suggested that cytoplasmic inclusion bodies in superior rectus muscle are the result of viral activity and may represent an incidental viral infection of the senescent period.


A menstruation-linked periodic hypersomnia. Kleine-Levin syndrome or new clinical entity? A 13-year-old girl showed periodic episodes of somnolence without megaphagia recurring in association with each menstruation. During somnolent episodes total sleep time averaged 14 hours and 19 minutes per 24 hours. The level of performance evaluated by means of the Wilkinson Addition Test was significantly impaired. There was an abnormal increase of 5-hydroxyindolacetic acid in the cerebrospinal fluid after probenecid test, suggesting an increase of the turnover of 5-hydroxytryptamine during periodic hypersomnia. Investigation of the menstrual cycle failed to document any striking hormonal abnormality. Nevertheless, the close relationship between the episodes of hypersomnia and the end of the menstrual cycle led us to hypothesize a role of progesterone and to try a hormonal type of treatment that is thus far successful.


Studies on the antiparkinsonism efficacy of lergotrile. The antiparkinsonian activity of lergotrile mesylate, a presumed dopaminergic receptor stimulating agent, was investigating in monkeys with surgically induced tremor and in parkinsonian patients. The administration of lergotrile resulted in a dose-dependent reduction in the intensity of tremor in the monkeys. In 13 patients with Parkinson's disease treated with lergotrile (up to 12 mg a day), overall improvement was observed in five. Tremor was the main clinical feature to benefit, and the improvement reached statistical significance. In a subgroup of four patients treated with a higher dose of lergotrile (up to 20 mg a day), further improvement in rigidity and bradykinesia was noted, but again, only improvement in tremor was statistically significant. Adverse effects included orthostatic hypotension, behavioral alterations, and nausea and vomiting. These were severe enough to result in drug withdrawal in three patients.


Radiologic features of benign pleomorphic adenoma of the hard palate. The clinical and radiographic features of two cases of pleomorphic adenoma are discussed. With the use of hypocycloidal tomography, definitive radiographic signs of benignity are demonstrated. They include (1) a radiolucent defect with well-defined cortical margins; (2) beveled margins which describe an intraoral origin of the neoplasm; (3) confinement of the neoplasm within the actual osseous defect, or within the projected circumferential diameter of the defect, if complete erosion has occurred; and (4) lack of periosteal reaction or osseous involvement of the hard palate adjacent to the radiolucent defect.


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.


The chronically reserpinized rat as a possible model for cystic fibrosis. I. Submaxillary gland morphology and ultrastructure. Rats treated for 7 days with reserpine develop structural changes in the submaxillary gland that resemble those that have been reported in cystic fibrosis. The salivary exocrinopathy is characterized by increased amounts of PAS-reactive mucoprotein in the acinar cells and by obstruction and dilatation of ducts by precipitated material with the same staining characteristics as those found in the acinar elements.


Hyperornithinemia, hyperammonemia, and homocitrullinuria associated with decreased carbamyl phosphate synthetase I activity. Six subjects from three sibships with hyperornithinemia, homocitrullinuria, and hyperammonemia are described. Assays of liver biopsy in one showed decreased CPS I and leukocyte assays indicate a similar defect in all six. Loading studies with ornithine and citrulline are consistent with a block early in the urea cycle between ornithine and citrulline. They thus support the results of the enzymatic assays. Similar studies with lysine and homocitrulline indicate there is excessive homocitrulline biosynthesis that is related to lysine intake, but there is no evidence of a block in the main lysine catabolic pathway. The younger more severely affected patients require protein restriction to 1.2 and 1.5 g/kg/24 hr to control hyperammonemia; hyperornithinemia remains unaffected. Adult subjects avoid large protein meals but tolerate a diet that is almost normal. The mode of inheritance of this disorder appears to be autosomal recessive. The fine structure of liver shows the presence of large and abnormally configurated mitochondria. There is a peculiar periodic structure situated closely to the inner mitochondrial membrane, and it is possible that the presence of this may be related to the impairment of transport of ornithine into the mitochondria; this in turn may give rise to hyperornithinemia. This disorder adds to the metabolic errors that suggest that there are close links of lysine metabolism to the urea cycle but the details are yet to be defined.


The effect of exogenous 3':5'-adenosine monophosphate on urinary output in children with vasopressin-resistant diabetes insipidus. The administration of c-AMP and DB c-AMP to six children with NDI has failed to yield an antidiuretic effect. From the present study it may be concluded that, at the doses used, neither c-AMP nor its dibutyryl derivative can mimic the action of ADH in NDI as they do in normal subjects. On the contrary, DB c-AMP increased urine volume and Cosm in a very marked way, without changing the creatinine excretion.


[Acute bovine mastitis caused by clostridium perfringens type A (Author's transl.)]. An acute case of bovine mastitis caused by clostridium perfringens type A is described. The condition appeared before delivery and was characterised by gas formation in the udder and severe general signs. In spite of parenteral treatment with large doses of penicillin and streptomycin combined with frequent stripping of the udder the animal died two days after the onset of symptoms. The strain isolated proved sensitive to penicillin, chloramphenicol and tetracyclin, but resistant to streptomycin and sulphonamides.


Horizontal transmission of turkey herpesvirus to chickens.  3. Transmission in three different lines of chickens. Horizontal transmission of turkey herpesvirus (HVT) was studied in three separate trials using three different lines of chickens in each trial.  There was no horizontal spread of HVT to contact cagemates through 8 weeks regardless of the line of donor chickens, when inoculated subcutaneously with 9.2 times 10-3 plaque-forming units (PFU) of HVT at 1 week of age.  The virus spread poorly to a few cagemates from an experimental line of White Leghorns (W.S.U.-V.S.), but not from a commercial line of White Leghorns (C.-W.L.) or meat-type (C.-M.T.) chickens, when inoculated with 9.4 times 10-4 PFU of HVT at 1 week of age.  The virus spread readily to contact cagemates from W.S.U.-V.S. but not at all from C.-W.L. or C.-M.T. chickens when inoculated with 2 times 10-4 PFU of HVT at 8 weeks of age.  The incidence among cagemates of contact infection by HVT appeared similar regardless of genetic lines.  This observation indicated a difference among different genetic lines of chickens in the development and/or shedding of infectious HVT following virus inoculation.


Distribution studies of glycine and serine enzymes in chicks. Day-old broiler type chicks were fed a practical starter ration for three weeks, sacrificed and the D-3-phosphoglycerate dehydrogenase (E.C.1.1.1.s), phosphoserine phosphatase (E.C.3.1.3.3.), glycerate dehydrogenase (E.C.1.1.1.29), hydroxypyruvate-P: glutamate transaminase, serine transhydroxymethylase (E.C.2.1.2.1), and serine dehydratase (E.C.4.2.1.13) enzyme activities were determined in liver, kidney, heart, spleen and brain tissue in evaluating glycine and serine metabolism. The distribution of the various glycine and serine biosynthetic enzymes in the chick tissues studied show that the major portion of glycine and serine synthesis occurs in hepatic tissue via the "phosphorylated pathway".


Effect of regression of Rous sarcoma tumors upon egg production in an inbred line of White Leghorns. Reserach was conducted to determine whether development and subsequent regression of a Rous sarcoma virus (RSV) induced wing-web tumor influenced egg production.  Fifty-seven six-week old pullet chicks of inbred line 6 of the United States Department of Agriculture, Regional Poultry Research Laboratory, East Lansing, Michigan, were inoculated subcutaneously in the left wing-web with 0.1 ml. of a 10-minus 3 dilution of a pseudotype of Bryan high titer RSV designated BH-RSV (RAV-1).  Thirty chicks were left uninoculated.  Each chick was examined for tumor growth at regular intervals to 10 weeks post-inoculation.  A tumor was considered regressed if it disappeared completely.  Ninteen regressor and 22 uninoculated females were placed in laying cages at 4.5 months of age and egg production data obtained over seven 28-day periods.  The difference in hen-day egg production between regressors and uninoculated controls favored regressors by 2.7 eggs/bird and was statistically significant.  Physiological stimulus from cellular immunity, linkage and pleiotropy are discussed as possible caused of the higher egg production in regressors.


A comparative study of iodine and potassium perchlorate metabolism in the laying hen.  1. incorporation of I-131 in chicken ova. The uptake of 131-I in chicken ova was studied for 3 hours after a single intramuscular dose.  There was uptake as early as 10 minutes and it continued throughout the 3 hours in spite of a rapid decrease in blood activity.  The fast growing ova, weightin 0.5 to 2.0 grams, were the most efficient in the uptake of 131-I per unit weight.  Autoradiograms of the topographic distribution of 131-I showed a peripheral deposition.  When multiple doses were given, concentric rings in the growing ovocytes were seen.


The effect of diet on the severity of losses from infectious bursal disease (Gumboro) in a commercial broiler genetype. A natural outbreak of infectious bursal disease occurred in an experimental broiler flock being reared on 3 starter diets having 18.8, 21.6 and 24.0 per cent protein.  Groups fed the highest protein starter exhibited significantly higher mortality and had larger numbers of stunted birds.


Antibody response of genetically susceptible and resistant chickens to cell-free and attenuated JM-V leukosis strain and its influence on early type II (Marek's) leukosis infection. Experiments were carried out to: 1) determine the antibody response of chickens to cell-free and attenuated preparations of JMV leukosis strain, 2) determine the differences in antibody response to these antigens between susceptible (P-line) and resistant (N-line) chickens by means of serum neutralization and indirect fluorescent antibody tests, 3) investigate the influence of maternal (passive) antibody on early (day-old) JMV vaccination and 4) investigate the influence of maternal antibody in chicks naturally exposed continuously to JM virus from day-old to 8 weeks of age on the pathogenesis of Type II leudosis (Marek's) infections and oncogenesis.


[The functional state of the adrenal cortex in patients with gonadal dysgenesis and a female phenotype]. Excretion of 17-KS and 17-OCS was studied in the urine of 86 patients with various cytogenetic variants of gonad dysgenesis of a female phenotype under basic conditions and after ACTH stimulation; in 10 patients endogenous hypophyseal ACTH reserve after block of the adrenal cortex by metopyrone was investigated as well.  A conclusion was drawn on the presence in these patients of differnet types of deviations of the adrenal gland function.  In some of the cases there is a primary "global" or dissociated injury of the adrenal cortex, apparently directly associated with gonosome anomaly; in other cases--with disturbed regulation of ACTH secretion.


[The clinical value of contrast-less mammography in endocrine diseases]. The authors analyze the X-ray picture of the changes occurring in the mammary glands in women with various endocrine diseases and in men with gynecomastia.  Contrastless mammagraphy was carried out in 189 persons.  In studying the mammagrams in patients with endocrine diseases assessment was made of the state of the subcutaneous-adipose cellular tissue, total dimensions of the organ.  The majority of the endocrine diseases were accompanied at the initial stages of their development by changes in the endocrine gland, this serving as a direct indication for the use of contrastless roentgenography for the purpose of earlier and proper choice of the therapeutic method.


Methylated simian virus 40-specific RNA from nuclei and cytoplasm of infected BSC-1 cells. Host cell and virus-specific poly(A)-containing RNAs isolated from nuclei and cytoplasm of monkey kidney cells infected with simian virus 40 contain different methylated nucleotides. In the cytoplasmic simian virus 40-specific RNA, about 75% of the radioactivity derived from (methyl-3-H)methionine was in N-6-methyladenosine (N-6mA) after digestion with Penicillium nuclease and bacterial alkaline phosphatase. The remainder was in a negatively charge component with properties of 5'-terminal structures, i.e., digestion with nucleotide pyrophosphatase and bacterial alkaline phosphatase released 2'-O-methyladenosine (A-m), 2'-O-methylguanosine (G-m), and 7-methylguanosine (m-7-G), consistent with a 5'-terminal structure of the type, m7-GpppNm. The nuclear virus-specific RNA contained N6mA, GM, 2'-O-methyluridine (U-m), and a smaller proportion (10%) of nuclease-, phosphatase-resistant presumptive 5' termini that also yielded A-m, G-m, and m7-G upon further hydrolysis. The infected cell nuclear and cytoplasmic RNAs that did not hybridize to DNA of simian virus 40 contained all four 2'-O-methylnucleosides. The possible role of methylation in the processing and translation of simian virus 40-specific mRNA is discussed.


[Participation of cerebral dopamine receptors in activating the endocrine function of the male sex glands]. One hour after the administration of 10 gamma of dopamine into the third ventricle of the brain to male albino rate the level of testosterone in the peripheral blood plasma (determined fluorimetrically) proved to double.  Such effect was absent against the background of complete postero-lateral or posterior deafferentation of the meidal-basal area of the hypothalamus (MBAH).  Section of the anterior nervous connections of the MBAH with the preoptic region failed to prevent the stimulating action of dopamine administered into the ventricle: blood testosterone level doubled as in the rats with an intact hypothalamus.  A conclusion was made that dopamine receptors associated with the endocrine function of the male gonad were located outside the MBAH.  Nervous tracts conducting this excitation reached the hypophyseotrophic zone of the hypothalamus through its posterior connections.


[The state of the peripheral endocrine glands 14 months following hypophysectomy and their sensitivity to the tropic hormones of the hypophysis]. Rats hypophysectomized at the age of four weeks continued to grow at a delayed rate during the whole fourteen month's observation period.  A spontaneous development of the sexual apparatus was noted in some of the hypophysectomized animals: an increase in the weight of the testes, of the ventral prostate and of the seminal vesicles.  In fourteen months the peripheral endocrine glands retained their sensitivity to the tropic hormones of the hypophysis; a ten-day adminstration of a corresponding tropic hormone led to a double increase in weight of the dependent endocrine gland and a sharp elevation of its functional activity.


Immunohistochemical localization of 3': 5'-cyclic AMP and 3': 5'-cyclic GMP in rat liver, intestine, and testis. Cyclic GMP and cyclic AMP have been localized in rat liver, small intestine, and testis by a fluorescent immunocytochemical procedure. In liver, cyclic AMP is distributed along sinusoids predominantly, and increased fluorescence is seen sinusoidal areas after glucagon administration. Cyclic GMP is located in nuclear elements and on the plasma membranes of hepatocytes. In jejunum, cyclic AMP is found predominantly at the basal and lateral sides of brush border cells and in the lamina propria, while cyclic GMP is located to the brush border membrane, smooth muscle, and nuclear elements. In testis, cyclic AMP is found in cytoplasm of cells at the perimeter of the seminiferrous tubules and in interstitial cells, while cyclic AMP is visualized on the plasma membrane of the cells lining the tubules. Cyclic GMP is also seen on chromosomes of premeiotic spermatocytes and in sperm. These data provide histological evidence implicating diverse roles for the nucleotides in these tissues. The nuclear localization of cyclic GMP in all of these tissues suggests a role for the nucleotide in nucleus-directed events.


Properties of cytoplasmic mutants of Saccharomyces cerevisiae with specific lesions in cytochrome oxidase. Two mutants with specific defects in cytochrome c oxidase (ferrocytochrome c:oxygen oxidoreductase; EC 1.9.3.1) have been isolated from cultures of Saccharomyces cerevisiae exposed to the mutagens ethyl-methane sulfonate and Mn++. The mutations have been shown to be extranuclear by two criteria. The phenotype persists in diploids formed by a cross with a p-o strain of yeast of the opposite mating type. Tetrad analysis indicates a non-Mendelian segregation (4:0 and 0:4) of the mutations. Both mutants show a total absence of cytochrome oxidase activity and of spectral cytochromes a and as. One of the mutants has been shown to be missing a polypeptide synthesized by mitochondria. The migration of this protein on polyacrylamide gels corresponds to the highest-molecular-weight subunit of cytochrome oxidase.


[The effect of STH, TTH and ACTH on several aspects of copper, sodium and potassium metabolism in the livers of hypophysectomized white rats]. It was found in experiments on male albino rats that hypophysectomy was accompanied by an increase of potassium (on account of its accumulation in the mitochondria, nuclei and the microsomes) and copper in the liver.  At the same time there was an increase in this organ of tha activity of Mg-2+-Na-+-K-+-ATPase and Mg-+-ATPase, and also a rise of ceruloplasmin activity in the blood serum.  STH and TTH restored the sodium content to the normal and increased potassium level in the liver of hypophysectomized rats.  ACTH and STH increased copper content in the hepatic tissue and normalized the activity of ceruloplasmin in the blood.  All the hormones used promoted normalization of ATP-ase activity.


Involvement of nicotinamide adenine dinucleotide in the action of cholera toxin in vitro. NAD is a necessary cofactor for the activation of adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1) by cholera toxin. Lysates of certain types of cell that hydrolyze their endogenous store of NAD after cell disruption respond poorly or not at all to cholera toxin. Lysates of pigeon erythrocytes, which lack enzymes that degrade NAD, provide a convenient and reproducible system for assaying the activity of cholera toxin in vitro and allow investigation of the mechanism of action of the toxin upon broken cells.


Beta-adrenergic stimulation of pineal N-acetyltransferase: adenosine 3':5'-cyclic monophosphate stimulates both RNA and protein synthesis. The lag period in the induction of rat pineal N-acetyltransferase (arylamine acetyltransferase or acetyl-CoA:arylamine N-acetyltransferase EC 2.3.1.5) by catecholamines via the beta-adrenergic receptor varies with the length of exposure of the rat to light or darkness. If rats have been exposed to light and reduced sympathetic nerve activity for more than 12 hr, this lag period is 1-2 hr long. Under these conditions, actinomycin D completely blocks the induction of N-acetyltransferase by isoproterenol and by dibutyryl adenosine 3':5'-cyclic monophosphate (cyclic AMP). In contrast, if enzyme activity is caused to fall by brief exposure to light at night when N-acetyltransferase activity is high, reinduction by catecholamines occurs almost immediately. In this case, actinomycin D does not block the reinduction of N-acetyltransferase by isoproterenol or by dibutyryl cyclic AMP. Cycloheximide blocks N-acetyltransferase induction under all conditions tested. Thus, new protein synthesis is always required for N-acetyltransferase induction; however, the requirement for RNA synthesis is variable, and contributes to the length of the lag period for induction. It is postulated that both beta-adrenergic stimulation and dibutyryl cyclic AMP act intracellularly at two separate sites in the induction of pineal N-acetyltransferase. One site is in the stimulation of transcription, and the other is in the stimulation of post-transcriptional events.


Isolation of a glycogen synthase I kinase that is independent of adenosine 3':5'-monophosphate. Three protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) were detected when the soluble fraction of rabbit kidney medulla was chromatographed on DEAE-cellulose with a linear NaC1 gradient. The first two kinases eluted (Peak 1 and Peak II) were cyclic-AMP-dependent, wheras Peak III was cyclic-AMP-independent. A procedure was developed to separate the catalytic subunit of Peak II cyclic-AMP-dependent protein kinase (representing the bulk of the histone kinase activity) from Peak III protein kinase. In contrast to the catalytic subunit, Peak III protein kinase phosphorylated casein more rapidly than histone. Peak III was insensitive to the heat-stable protein inhibitor of cyclic-AMP-dependent protein kinases and appeared to have a higher requirement for ATP than did the catalytic subunit. Peak III catalyzed the conversion of glycogen synthase (UDPglucose:glycogen alpha-4-glucosyltransferase, EC 2.4.1.11) from the I (glucose-6-phosphate-independent) to the D (glucose-6-phosphate-dependent) form. This conversion was dependent on Mg-2+ and ATP and was unaffected by cyclic AMP, cyclic GMP, or the protein inhibitor. Glycogen synthase I in the soluble fraction of kidney medulla could be converted to the D form by endogenous glycogen synthase I kinase if Mg-2+ and ATP were added. Most of this glycogen synthase I kinase activity was unaffected by cyclic AMP or by the protein inhibitor, suggesting that Peak III may be of major importance in the regulation of glycogen synthase in vivo.


Changes in relative levels of guanosine-3':5'-monophosphate-dependent and adenosine-3':5'-monophosphate-dependent protein kinases in lung, heart, and brain of developing guinea pigs. Canges in relative levels of protein kinases (ATP:protein phosphotransferase, EC 2.7.1.37) stimulated by either guanosine 3':5'-monophosphate (cyclic-GMP) or adenosine 3':5'-monophosphate (cyclic-AMP) were examined in extracts of the lung, heart, brain, and liver from guinea pigs at various stages of development. The level of cyclic-GMP-dependent protein kinase in the fetal lung, which was found to be the highest of any mammalian tissue samples examined, declined during development. On the other hand, the level of cyclic-AMP-dependent protein kinase in the same extracts, which was initially lower than that of the cyclic-GMP-dependent enzyme, increased during development and reached a level higher than that of the cyclic-GMP-dependent enzyme when the animals reached maturity. This reciprocal change in level of the two classes of protein kinases in developing lung was demonstrated further by chromatographing the extracts on Sephadex G-200 and quantitating the activity of the isolated enzymes. A decrease in the ratio of the two classes of protein kinases qualitatively similar to that seen in the lung was also noted in the developing heart. An increase in the ratio of the enzymes, however, was seen in the developing brain. Unlike in the lung, heart, and brain, no change in relative level and ratio of the enzymes was noted in liver during development. These results suggest that a balance between the effects of cyclic-GMP-dependent and cyclic-AMP-dependent protein kinases may be important in normal development of certain tissues.


Neutron scattering study of human serum low density lipoprotein. Regions of different proton density in the low density lipoprotein (LDL) particle from human serum have been determined by neutron scattering. From measurements in various H2O/D2O mixtures, the LDL particle appears to be quasi-spherical, with the centers of gravity of the hydrocarbon and polar regions coinciding. The average volume occupied by a particle was found to be 3.2 X 10-6 A-3, with the volume fraction occupied by the hydrocarbons being 60%. The ratius of gyration of the hydrocarbon region was 64 A, while that of the polar region was 100 A. consequently, the core of LDL is predominantly occupied by the hydrocarbon chains, while the outer shell is sparsely occupied by protein emerging from the lipid core.


NAD-dependent inhibition of protein synthesis by Pseudomonas aeruginosa toxin,. Pseudomonas aeruginosa toxin (PA toxin) inhibits protein synthesis in a reticulocyte cell-free system. The inhibition requires NAD and results in a block at an elongation step of polypeptide assembly. PA toxin was found to act like diphtheria toxin fragment A. Both toxins catalyze the transfer of radioactivity from nicotinamide(U-14-C)adenine dinucleotide ((14-C)NAD) into covalent linkage with the 100,000 dalton elongation (EF-2) protein. Furthermore, in the presence of a limiting amount of EF-2, excess toxin, and (14-C)NAD, the two toxins were non-additive in the amount of label transferred to EF-3. Unlike free fragment A of diphtheria toxin, the enzymatic activity of PA toxin is heat labile and neutralizable with antibody to PA toxin but not with antibody to fragment A. Although PA and diphtheria toxins have different cellular specificities and molecular properties and produce different clinical symptoms, their intracellular mechanisms of action appear to be identical.


Adenosine 3':5'-cyclic monophosphate as mediator of catabolite repression in Escherichia coli. Measurements of intracellular adenosine 3':5'-cyclic monophosphate (cAMP) concentrations in E. coli under a variety of conditions show that levels of this nucleotide are well correlated with the rate of synthesis of beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23) in both catabolite repression and transient repression. These results, combined with extensive genetic and in vitro studies from a number of laboratories on the role of cAMP in E. coli, provide strong support for the concept that intracellular cAMP levels mediate the effects of catabolite and transient repression on rates on enzyme synthesis. Under all conditions studied, excretion can be described by a single rate constant, 2.1 min-1 at 37 degrees, indicating that intracellular levels cannot be regulated by alterations in the rate of cAMP excretion. Our data are fully consistent with the idea that carbon sources control intracellular cAMP levels by effects on its synthesis.


Antigen-stimulated changes in cyclic nucleotide levels in the mouse. Mice injected intravenously with sheep erythrocytes (sRBC) demonstrate a transient increase in splenic cAMP levels (4-fold), which peak at 2 min after injection and return to basal levels by 20 min. In addition to the change in cAMP, an increase in splenic cGMP levels (1.5-fold) occurs beginning 5-10 min after sRBC injection, and persists for up to 7 days. During this period cAMP levels remain at or below control levels in the spleen. There is no change in 3':5' cyclic nucleotide levels in the liver and a small increase (1.2- to 1.3-fold) in the thymus at the time when splenic cyclic nucleotide levels are elevated. The changes in splenic cyclic nucleotide levels appear to be dependent on the presence of thymus-derived (T) lymphocytes, since little change occurs in cAMP and changes in cGMP are absent in athymic nude mice. In addition, cAMP levels were increased by pretreatment of normal mice with cortisone acetate, which selects for mature T lymphocytes. Agents that block autonomic nervous system functions have no effect on the early sRBC-induced changes in cyclic nucleotide levels.Indomethacin, an inhibitor of prostaglandin synthesis, reduces the change in cAMP level by 50% and blocks the change in cGMP levels completely. Secondary stimulation with sRBC results in a larger increase in cAMP levels than that seen with a primary injection of sRBC, indicating the presence of specific antigen-sensitive memory cells. Changes in splenic cyclic nucleotide levels cannot be detected at early times after the injection of soluble protein antigens such as bovine serum albumin and keyhole limpet hemocyanin. Salmonella H antigen stimulates a 2-fold increase in cAMP levels, the increase occurring more slowly than with sRBC. The in vivo changes incyclic nucleotide levels are correlated with known changes in cyclic nucleotide levels which have been documented in vitro in both T-cells and T-cell-dependent-B-cell (bone-marrow derived) antibody responses.


A genetic determinant of the phenotypic variance of the molecular weight of low density lipoprotein. The molecular weight of monodisperse human plasma low densitylipoprotein has been measured in 69 individuals and found to vary over the range of 2.4 to 3.9 X 10-6. By contrast, the molecular weight of low density lipoprotein measured on two separate occasions for specific individuals shows a mean difference of 0.07 X 10-6 and a standard deviation of 0.08 X 10-6; hence low density lipoprotein differing in molecular weight by greater than 0.2 X 10-6 may be considered different macomolecules. The distribution of the molecular weight of low density lipoprotein does not differ as a function of age or sex. Hyperlipemic subjects having monodisperse low density lipoprotein show similar molecular weight distribution to normal subjects, as do subjects with premature coronary artery disease. Family studies reveal a correlation coefficient of 0.82 between average molecular weights of parents and offspring, with significance at 0.01. In order to assess the influence of environment on molecular weight of low density lipoprotein, the correlation coefficient between the fathers' and mothers' low density lipoprotein was measured and no statistically significant correlation was found. These data are interpreted as strong evidence for a genetic determination of molecular weight of low density lipoprotein. A study of individuals in five families yields molecular weight data consistent with a single gene locus genetic mode of inheritance without dominance. The regression coefficient of the mean low denisty lipoprotein parental molecular weight on the offspring molecular weight is 0.30. If the variability of molecular weight is considered as an expression of phenotypic variance, then the regression analysis identified 30% of this phenotypic variance as arising from additive gene action presumably at a single locus. Segregation in the family data is consistent. Since the differences in molecular weight of low density lipoprotein arise from differences in the amount of lipid bound to the apoprotein, it is likely that an additional portion of the phenotypic variance of the molecular weight results from individual variations in the metabolism of low density lipoprotein, which yield differences in lipid content. The individual variation in molecular weight is only approximately 5%; hence those metabolic sequences that influence molecular weight of low density lipoproteins must be precisely controlled.


Viral and cellular DNA synthesis in nuclei from human lymphocytes transformed by Epstein-Barr virus. A DNA-synthesizing system in vitro, using nuclei prepared by treatment of human lymphocytes with the detergent Brij 58, was developed. Nuclei from cultured lymphocytes synthesized DNA for as long as 5 hr, and required ATP, deoxynucleoside triphosphates, magnesium, and a calcium chelator. In nuclei from a partially synchronized line of cultured lymphocytes carrying several hundred copies of the Epstein-Barr viral genome, synthesis in vitro was predominately viral in early S phase and cellular in late S phase. These and other data suggested that the DNA synthesis observed in vitro was predominately replicative.


Coenzyme A requirement of malaria parasites: enzymes of coenzyme A biosynthesis in normal duck erythrocytes and erythrocytes infected with Plasmodium lophurae. Normal duck erythrocytes and erythrocytes infected with Plasmodium lopharae have all of the enzymes for coenzyme A biosynthesis, whereas parasites freed from their host cells have non. Since erythrocytefree cultivation of P. lophurae requires an exogenous source of coenzyme A, this parasite must obtain its coenzyme A entirely from the host cell during infection.


The relationship of small limb movements during REM sleep to dreamed limb action. Ten adult subjects, selected for good dream recall and ability to produce spontaneously fine limb movements in the laboratory, reported their last dream experience after awakenings from REM sleep during various limb movement and no movement conditions. The reports were rated for amount and girdle location of dreamed actions by judges blind to the awakening condition. There was a significant correlation between the number of girdles moving before awakening and the amount of dreamed action. Also, when dreams from single girdle movement awakening conditions were examined, the girdle active before awakening was dreamed as moving to a significant degree.


The air bronchogram in interstitial disease of the lungs. A radiological-pathological correlation. The air bronchogram classically signals an end-air-space or "alveolar" filling process such as alveolar proteinosis and bronchioloalveolar-cell carcinoma. However, it can also occur in interstitial diseases, possibly leading to compressive atelectasis and causing crowding of tissue around open airways. In addition, such disease processes may encroach on distal airways, producing obstructive pneumonia which may then surround open proximal airways, as in sarcoidosis and lymphoma. In mixed "alveolar" and interstitial processes such as Pneumocystis carinii pneumonia and the late stages of hemosiderosis, "alveolar" filling may mask the interstitial disease.


A new method of diagnosing myocardial contusion in man by radionuclide imaging. A new method of diagnosing myocardial contusion was studied in 8 patients in whom the injured mycardium was visualized as an abnormal area of increased activity in the region of the heart one hour after intravenous injection of 10 mCi of 99m-Tc-Sn-polyphosphate or pyrophosphate. Serum enzymes in these patients were elevated, but electrocardiograms were nonspecific for myocardial injury. It is hoped that this new technique of imaging the injured myocardium will provide specific and confirmatory diagnosis of myocardial contusion associated with closed chest injuries.


Total-lung irradiation in the treatment of pulmonary metastases. Sixty-two patients with pulmonary metastases from a variety of primary malignant neoplasms were treated with total-lung irradiation. The incidence of radiation pneumonitis was 21%(13/62) overall, rising to 23% (9/39) in those receiving a tumor dose of 1,500 rads or more. Nine patients with radiation pneumonitis were given chemotherapy (actinomycin D) together with irradiation, and in this group the incidence of radiation pneumonitis was 25%. Five survivors, including 4 treated for metastatic Wilms' tumor, were treated more than 13 months prior to analysis without evidence of disease thus far. Total-lung irradiation for primary malignant neoplasms other than Wilms' tumor does not presently appear to be indicated. A dose of 1,500 rads in 2 weeks in conjunction with actinomycin D is recommended for metastatic Wilms' tumor.


Ultrastructural changes accompanying mitosporogenesis in Ectocarpus parvus. The plurilocular zoosporangium of Ectocarpus parvus Saunders in initiated as a uniseriate branch from a vegetative cell. Subsequent anticlinal and periclinal divisions of the cells leads to enlargement of the sporangium and the formation of multiple locules. Each locule containes a single biflagellate zoospore. Ultrastructural changes accompanying these events include a reduction in the size of chromatophores, a reduction in the number of dictyosomes and the appearance of plasmalemmasomes in later stages. Enlargement of the mitochondria and a decrease in size of the nucleus occur in the final stages of zoospore formation. Comparison with the vegetative and sporogenous cells of other brown algae are made.


Evidence for a possible prostaglandin link in ACTH-induced steroidogenesis. The steroidogenic response to ACTH prostaglandin E2 (PGE2) was studied in cat adrenocortical cells dispersed with trypsin. The dose-response curves of both agents were qualitatively and quantitatively similar. Exposure to PGE2 or ACTH in the presence of labeled steroid precursor (acetate) resulted in the accumulation of comparable levels of steroid intermediates and end-product. Submaximal or maximal concentrations of ACTH and PGE-2 given simultaneously elicited a response which was no greater than that obtained with either stimulant alone. Although calcium was required for optimal PGE-2 stimulation of steroid production, this requirement with ACTH as the stimulant, but greater than with butyryl cyclic AMP. PGE-2-induced increase in the adrenal cyclic AMP was not statistically significant and was small in relation to that found with equipotent steroidogenic ACTH concentrations. The possible relationship between prostaglandins, cyclic AMP, and calcium in the action of ACTH is discussed.


Action of luteinizing hormone-releasing hormone and synthesis of prostaglandin in the pituitary gland. The possibility that prostaglandin E2 (PGE2) may play a role in luteinizing hormone (LH) release was examined using an in vitro model. Addition of luteinizing hormone-releasing hormone (LH-RH) to the culture medium stimulated cyclic AMP accumulation and LH-release by incubated hemipituitaries, but did not affect the level of PGE2 or prostaglandin synthetase activity in the gland. Aspirin and indomethacin reduced both prostaglandin synthetase activity and PGE2 or prostaglandin synthetase activity in the gland. Aspirin and indomethacin reduced both prostaglandin synthetase activity and PGE2 content in the pituitary, but did not impair the stimulatory action of LH-RH on either cyclic AMP accumulation or LH-release. Flufenamic acid on its own caused LH-release, but the drug abolished the effect of LH-RH on cyclic AMP accumulation. The mechanism of this action of flufenamic acid is not understood. It is concluded that the stimulatory action of LH-RH on pituitary cyclic AMP production and LH release is not mediated by prostaglandins.


Inhibition of RNA-dependent DNA polymerase reaction by 6-(p-hydroxyphenylazo)-uracil: A result of drug induced dithiothreitol oxidation. 6-(P-hydroxyphenylazo)-uracil (HPUra) reduced by dithiothreitol inhibited AMV or RLV virion associated exogenous RNA-dependent DNA polymerase reactions. However, the inhibition was variable from experiment to experiment and was not consistent with the base specificity of HPUra seen for inhibition of gram positive DNA-dependent DNA polymerases. Increasing the concentration of dithiothreitol reversed the inhibition. Furthermore, at non-toxic concentrations, HPUra did not influence the plating efficiency of RLV in tissue culture, as measured by the ability to induce foci on sarcoma virus positive-leukemia virus negative cells. Oxidation of dithiothreitol in the presence or absence of HPUra was followed spectrophotometrically under enzyme conditions. HPUra catalyzed the oxidation of dithiothreitol under these conditions. Since dithiothreitol is required for optimum reaction rates, as well as complete disruption of virus in some polymerase assay systems, the oxidation of dithiothreitol in the presence of HPUra is sufficient to explain the inhibition seen.


Pseudorabies virus - induced neural hyperreactivity following occular and skin infections in the rat. The types of functional disturbances caused by a neurotropic virus was investigated by means of neurophysiological techniques. Two types of neurophysiologic lesions were produced in the superior cervical sympathetic ganglia and sural nerve in rats infected with two distinct strains of pseudorabies virus. The pruritus-producing strain following intraocular inoculation displayed spontaneous activity in the ganglia both in vivo and in vitro. This activity was susceptible to the actions of ATP, AMP, pyridoxine, pyridoxamine, serotonin and gamma-aminobutyric acid (GABA). Following intradermal inoculation, spontaneous activity and pruritus were seen along the sural nerve. The non- pruritus producing strain caused meningoencephalitis with impaired sympathetic synaptic conduction. The relationship of these pathopharmacologic findings to pathogenesis of syndromes naturally or experimentally occurring in viral infection was assessed.


Epstein-Barr virus: comparison of different strains for their biological activities in vitro. Several sources of Epstein-Barr virus (EBV) were tested for the ability to superinfect Raji cells or to transform human cord blood leukocytes. EBV prepared from P3HR-1 cells showed only the ability to superinfect Raji cells whereas EBV from QIMR-WIL cells from a cell line (CRU-L1) derived from an infectious mononucleosis (IM) patient or virus from throat washings from IM patients transformed human cord blood leukocytes, but did not superinfect Raji cells.


Cellular cooperation in transformation by EB virus. Human lymphoid cells transformed by Epstein-Barr (EB) virus are thought to be B-lymphocytes. Transformation of human mononuclear leukocytes by Epstein-Barr virus was decreased or lost by removing adhering or nonadhering mononuclear cells from the mixtures of peripheral blood leukocytes but was not decreased by removing T-lymphocytes. Recombining adherent and nonadherent mononuclear cells without T-lymphocytes restored transformability, but conditioned medium from cultures of adherent cells did not. Cooperation between non-adherent (B-cells) and adherent cells (monocytes) is necessary for EB virus transformation.


Latent infection of sensory ganglia with herpes simplex virus: efficacy of immunization. Mice were used to test the efficacy of active immunization in preventing latent infection of local sensory ganglia that follows inoculation of superficial epithelial surfaces with herpes simplex virus. Substantial but not complete protection was observed in animals immunized and challenged with herpes simplex virus type 1, but no protection was noted in animals immunized and challenged with herpes simplex virus type 2. Latent ganglionic infection can develop in immunized animals despite the presence of high titers of neutralizing antibody.


Cell surface differences in ducts from cancerous and noncancerous human breasts. The scanning electron microscope reveals structural differences between the apical microvilli of duct cells from cancerous and noncancerous human breasts. The alterations in the microvilli from carcinomatous breasts appear to be highly specific, to extend throughout the affected breast, and may be pathognomonic for this condition.


Cell rigidity: Effect on concanavalin A-mediated agglutinability of fibroblasts after fixation. A quantitative hemadsorption assay distinguishes the effects of membrane fixation on concanavalin A-mediated agglutinability of fixed cells with unfixed cells. We observed undiminished adherence of unfixed erythrocytes to glutaraldehyde-fixed normal and virus-transformed hamster fibroblasts coated with concanavalin A. Fixation of the erythrocytes abolished agglutination with fixed fibroblasts. The agglutinability of fixed cells is more likely related to increased cell rigidity than to decreased membrane fluidity.


Induced adhesion in Crassostrea virginica larvae. Normal motile veliger larvae of the oyster, Crassostrea virginica, were observed swimming in pairs or trios. Adhesion between animals is firm and has a specific orientation. This adhesion can be induced in low frequencies by culturing larvae at high densities, and in much higher frequencies by inclusion of an antibiotic mix in the seawater culture medium.


[Anterior antehypaphyseal insufficiecency in the elderly]. The authors report 4 personal cases, and analyse 18 cases of anterior pituitary insufficiency in the elderly found in the world literature. The initial symptoms are not specific and are difficult to interpret. They are frequently attributed to physiological ageing. In the absence of early diagnois, the patient may become comatose, this coma is often irreversible in spite of hormone treatment. In 60% of cases, the cause of the pituitary failure was not found. In the onset of the latter, the role of ageing on pituitary function, the responsibility of circulatory failure between the hypothalamus and the pituitary and, finally, the existence of auto-immune mechanisms are then discussed.


[Does rheumatic pleuresy exist?].

[Does rheumatic pleuresy exist?]. The authors report the case of a 20 year-old young man with old rheumatic heart disease in whom suddenly occurred sero-fibrinous pleurisy with fever. The usual cause of pleurisy, e.g. tuberculosis, were eliminated. On the other hadn, there was considerable evidence, including lengthening of the P-R interval, and raised anti-streptolysin titer at 1920 units, which suggested recurrence of rheumatic fever. The relationship between this disease and sero-fibrinous pleurisy is then discussed.


[2 cases of hepatorenal polycystosis].

[2 cases of hepatorenal polycystosis]. The authors report two cases of polycystic liver andkidney in two women. They were unusual in that the liver first gave risr to symptoms and the renal lesions were completely latent. Both hepatic and renal lesions were well tolerated in spite of hepatomegally. They emphasize the interest of laparoscopy and biopsy of the liver under direct vision, and selective aortography, in the diagnosis. They discuss the basic differences between polycystic liver and kidney in adults, from that in children ornewborn, and caroli's disease. Finally, they emphasize the usually poor prognosis dominated by progressive renal failure which should guide treatment. The latter depends on periodic supervision of the patient for the disease usually evolves slowly. Treatment should therefore be conservative. Tn some cases, however, renal transplantaton should be considered before irreversible renal failure in young subjects, at an age when it is still possible. On the other hand, the liver lesions do not require any radical treatment, unless there is intercurrent infection or pressure on neighbouringorgans.


[Acute non-tuberculous military lung].

[Acute non-tuberculous military lung]. The authors report the case of a young woman with acute miliary appearance of the lung with asphyxia, from which she rapidly recovered.  No cause was demonstrated; this illustrates the difficulty in diagnosis of this disease.  Contact with a bird, led the authors to consider exogenous, allergic granulomatosis, but immunological examinations did not confirm this.  Apart from tuberculosis, almost 50 different pathogenic organisms may cause acute respiratory failure associated with a miliary or reticulo-nodular appearance of the lung.  The main methods of diagnosis are discussed in relation to the most commonly observed causes in France.


[Neurologic complications of pagetic basilar impressions and their surgical treatment]. Paget's disease of the skull is the main cause of basilar artery syndromes in the adult. They may cause various neurological symptoms, including signs of ischemia of the spinal cord or medulla, or involvement of the cranial nerves and brain stem and, also, distant symptoms due to hydrocephalus, with various mental disorders including transient, recurrent, coma. The authors discuss 30 cases found in the world literature and 6 unreported personal cases, study the clinical symptoms of these cases of basilar artery compression due to Paget's disease, and the methods of neuro-radiological investigation, and emphasize the interest, in severe forms, of early surgical decompression before the stage of severe neurological complications. Regular supervision of patients with Pagets disease is thus essential to detect at an early stage, decompensation of basilar artery insufficiency in Paget's disease. In late forms, calcitonin may be indicated.


[Myeloma and osteocondensation (apropos of 2 cases)]. The authors report two cases of multiple myeloma which were typical both clinically and in the laboratory but XRay examination, on the other hand, showed appearances of osteocondensation. In the first case, XRay showed both lesions of osteolysis in the cranial vault and homogeneous condensation of D11 and L1, together with the left iliac crest. In the other case, there was osteolysis of the acetabulum together with areas of osteocondensation distributed throughout the pelvis and upper ends of the femurs, with two areas of annular fibrosis circumscribing the area of osteolysis, finally, homogeneous condensation of the skull. In both cases, bone biopsy confirmed the diagnosis of multiple myeloma showing both osteofibrosis and plasma cell infiltration of the bone marrow. This also permitted the authors to note the absence of any myelofibrosis or metamorphic neo-osteogenesis. Illustrated by these two cases, condensing multiple myeloma is a rare entity, the special clinical characteristics of which reside in its fairly frequent coexistence with peripheral neuritis which is probably similar to a para-neoplastic syndrome. The radiological appearances are mainly of four types: 1) Focal areas of bony condensation. 2) Areas of annular fibrosis circumscribing osteolysis. 3) Appearances of radial spicules, or 4) Osteocondensation extending to a fairly large part of the skeleton. The laboratory signs are identical with those in other types of multiple myeloma with a few exceptions, such as, rareness of hypercalcemia, more frequent tendency to hypocalcemia, rise in alkaline phosphatase, in a few cases. Bone biopsy confirms the diagnosis. The osteofibrosis resulted here from thickening of the osteoid seams by laying down of successive layers of bony substance, irregularly calcified and, also secondarily, metamorphic neo-osteogenesis in a few rare cases which also included myelofibrosis.


[Results of 79 hepatic biopsies in untreated bacillary pleurs pulmonary tuberculosis patients]. The authors report 79 needle biopsies of the liver, using a Menghini needle, carried out as routine in untreated cases of pulmonary tuberculosis with positive sputum. Apart from the histological study, the authors carried out, in 30 cases, a bacteriological study of the liver fragment. The bacteriological and histological results are reported here in detail, then compared with those in the world literature. No significant correlation was found between the histological type of the suggestive hepatic lesions, e.g. follicular appearances or appearances of nodular küpferian hyperplasia and the radioclinical variety of pulmonary tuberculosis, e.g. parenchymatous, pleural or miliary. The authors emphasize the significance of each type of pathological lesion encountered, in particular, the appearance of nodular küpferian hyperplasia or intralobular, lymphohistiocytic islets, which seem to them remarkable by their relative frequency and their chararacter fairly suggestive of tuberculosis. In spite of the low number of pathological appearances obtained in these liver biopsies, the present study nevertheless permitted a few interesting conclusions on the blood spread of the tubercle bacillus and the significance of changes in the Küpfer system during common pulmonary tuberculosis.


[Diagnostic and therapeutic problems posed by 2 cases of exudative enteropathy]. The authors report two cases of exsudative enteropathy characterised by the existence of oedema of the lower limbs associated with hypoproteinemia and marked lymphopenia with disturbances of the P.V.P. test. In both cases lymphography demonstrated major abnormalities with obvious obstruction in one case, and signs of slowing of lymph flow with appearances of dysplasia in the other. Surgery permitted us in one case, to discover a calcified lymph node probably due to tuberculosis. The etiology of these cases is discussed and seems to be mainly related to abnormalities of the lymphatic system. A low fat diet and administration of medium-chain triglycerides, gave an undoubted improvement when the treatment was followed by the patient. These two cases illustrate well the difficult diagnostic and therapeutic problems sometimes raised by syndromes of exsudative enteropathy, in particular owing to the many possible causes.


[Supravermian subdural triangle limited by the veins of the posterior fossa. Normal radio-anatomical study. Vermis herniation in the supravermian subdural space or superior vermis herniation]. The author describes a conical sub-dural space above the vermis limited in front by Galien's ampulla, behind by the right venous sinuses and, below by the superior cerebellar vein. This space, which is not filled with air injected by the cisternal route, is only shown in lateral views thanks to its venous outlines. In cases of raised intracranial pressure, the superior cerebellar vermis may occupy this space so that a sort of impaction occurs at this level, which the author proposes calling smaller than superior vermial impaction greater than. Among forms of cerebral herniation, vermial impaction may not occur when the CSF obstruction occurs at another level.


[Malignant lymphoma with pulmonary localization. Attempt at an anatomo-pathological classification]. The authors reported 33 cases of malignant lymphoma in the lung observed over a period of 6 years on the Pathological Department of the Beaujon Hospital. Whatever their cytological, lymphocytic, lymphoblastic or reticular type (Hodgkin's disease was excluded from this study), they may be grouped in two main pathological categories: 1) Malignant lymphoma involving the lung and mediastinum without extra-thoracic lesions detected at the time of diagnosis (4 cases). In 3 cases, the disease had been present for 2 to 6 months. In 1 case the course was favourable for 5 years then the patient developed acute lymphoblastic leukemia. 2) The pulmonary lesions observed during general infections, whether as presenting symptoms in 9 cases, or simply discovered on autopsy as in 20 cases. Histological examination, essential for the diagnosis of malignant lymphoma, provides no evidence in favour of the primary pulmonary origin of the disease; this diagnosis can only be made after full blood investigations. The prognosis is also difficult to determine for survival for many years may be followed by sudden general malignant blood disease.


Predictability of response to endocrine ablation in breast cancer. Carcinoma of the breast remains the most common and most frequently lethal form of cancer in women. In far-advanced disease, endocrine manipulation remains the major modality of treatment. Recent advances have shown that approximately 40% of breast cancers contain estradiol receptors in their cytoplasm. The presence or absence of these receptors is a good indicator of whether or not the patient will respond to endocrine ablation.


Friedreich's ataxia.

Friedreich's ataxia. The clinical and pathologic findings in Friedreich's ataxia were discussed and recent literature was reviewed with respect to associated heart disease, diabetes mellitus, peripheral nerve involvement, and EEG changes. Recent research aimed toward discovering an enzyme defect or defects was reviewed and, when available, our conclusions were stated. Friedreich's ataxia remains an unexplained spinocerebellar degeneration occurring in early life, inherited in a predominantly autosomal recessive fashion, and associated with cardiac dysfunction, diabetes mellitus, and peripheral sensory nerve involvement.


Cytomegalic virus infection of bowel in adults. Cytomegalic virus infection of the bowel in 2 adult patients is reported. The controversies related to this rare pathology are evaluated, particularly the role of cytomegalic inclusion virus (CMV) as a primary or secondary pathogen in bowel.


Paediatric renal masses. Some experiences with ultrasound and arteriography. Renal masses in children are common, their pathology varying in different age groups. Using ultrasound to establish a diagnosis, the supine position should first be attempted. For black-and-white echography a medium frequency of 2,5 megahertz is suitable, but careful technique and interpretation are essential. Arteriography using a 70-mm camera is not suitable for selective evaluation of avascular masses. Four illustrative cases to show diagnostic points and pitfalls are recorded.


The radiological diagnosis of hepatoma with special emphasis on angiography. The radiological findings of 69 out of a total of 81 cases of proven primary hepatocellular carcinoma are reviewed retrospectively. Selective angiography was performed on 42 patients and the results are analysed according to specific angiographic findings and distribution of the neoplasm, Because of the more aggressive approach to surgical treatment of hepatomas, angiography is of utmost importance in the pre-operative evaluation of the extent of the lesion and the vascular supply to the liver. Apart from the conventional angiogram, the technique of slow-infusion hepatic angiography is discussed as well as the value of enhancement techniques such as photographic subtraction and the use of vasoconstrictor drugs. Response to chemotherapy can be assessed by an infusion hepatic angiogram if a catheter has been surgically placed in the hepatic artery. The majority of tumours were easily disgnosed on the angiogram but special problems were encountered in distinguishing multicentric forms of hepatoma from hepatic metastases and avascular lesions from primary cholangiocarcinoma. The wide variety of clinical and angiographic findings that may be found, are emphasised in 4 brief case repots.


Klippel-Trenaunay syndrome. A case report and review of the literature. Clinical and radiological assessment of a female patient suffering from varicose veins revealed many of the features first described by Klippel and Trenaunay. The findings are presented in detail and the lymphographic features are illustrated. The previous literature is briefly reviewed.


Liver pathology in alpha1-antitrypsin deficiency. A review. Alpha1-antitrypsin deficiency (AATD), in addition to its association with chronic pulmonary disease, is reported with liver disease. Twenty per cent of Pi-type ZZ AATD infants present with a cholestatic type of neonatal hepatitis and develop a slowly progressive cirrhosis, and most die before adult life. Ten per cent of Pi-type ZZ adults develop cirrhosis. They have an increased frequency of primary liver carcinoma. In Z homozygotes and heterozygotes specific globules, due to accumulation of a type of alpha1-antitrypsin, are seen in liver cells. They are thought not to be hepatotoxic but to render the liver cell more susceptible to damage by an additional factor.


Some aspects of corticosteroid-induced cleft palate: a review. Since the discovery 25 years ago that cortisone can produce cleft palate in mouse embryos investigations into possible mechanisms of this corticosteroid-induced defect have been many and varied. However, the teratogenic mode of action remains not fully clarified. It is with this thought in mind that we have reflected upon what is known concerning corticosteroids and cleft palate. The major metabolic pathways upon which glucocorticoids act as well as their intracellular mode of action are well known. Differential sensitivity of various mouse strains to cortisone treatment as well as recent results from interstrain blastocyst transfer experiments demonstrate that corticosteroid action is influenced by both the fetal and maternal genomes. Labeling experiments indicate that corticosteroid-induced cleft palate is the result of direct action of the steroid molecule on the fetus, whose own sensitivity to insult, perhaps owing to differences in binding of corticosteroids to tissue proteins, determines the final effect. Possible mechanisms that have been proposed by which corticoids may produce cleft palate include: disruption of glycosaminoglycan or collagen synthesis or both, intracellular lysosomal membrane stabilization, myopathy, weakened midline fusion, and loss of amniotic fluid. Also discussed is the role of stress and stress-induced corticosteroids and their possible role in the production of cleft palate.


Tissue phosphatase changes following triamcinolone associated with cleft palate in rats. One theory of the development of cleft palate in rats involves the action of lysosomal enzymes secreted by epithelial cells at the time of fusion of the palatal shelves. To test this theory we studied the biochemistry of the palates of fetal rats daily between days 14 and 19 (from 3 days before to 3 days after palate closure). Triamcinolone was administered once im on gestation day 14 to Wistar rats; 0.5 mg/kg body weight produced approximately 50% cleft palates. Pooled control palatal tissue was compared with pooled experimental tissue; that from fetuses with clefts being pooled separately from those not affected. Acid phosphatase and beta-glucuronidase were assayed. Concentration vs. time curves for both enzymes were very similar. Prior to the time of palate closure both enzymes were present in low concentration. Between days 16 and 17, the normal time of closure, there was an abrupt increased in enzyme concentration, with experimental tissue showing a significant elevation over control tissue on days 17 and 18. Alkaline phosphatase was also present in small amounts before closure and significantly higher in control tissue on day 17. Protein was depressed in palates having clefts on day 17; thus the ratio of enzyme activities to protein synthesis was significantly elevated at a critical time. Unaffected experimental palates had a normal ratio. These results suggest imbalanced acid phosphatase, beta-glucuronidase, and alkaline phosphatase activity compared with protein synthesis at the time of palate closure following triamcinolone in rats.


[Results of combined Wilms tumor therapy with special reference to therapy-induced skeletal changes]. Prognosis of Wilms' tumors has remarkably improved by combination of surgery, radiation and chemotherapy.  Incidence and extent of skeletal changes after standardized treatment (1967-1973) of 24 children were analysed in dependence on time of therapy and age.


Radioactive ruthenium red accumulation by tumors: a potential scanning agent. The distribution of 103-Ru-Ruthenium red in tumour bearing animals indicates that Ruthenium red labelled with radioruthenium shows the characteristics of a tumour scanning agent. Its accumulation seems to be related to its specific binding to mucopolysaccharides. In addition, this radiocompound shows a potential value in the study of other pathological states involving the metabolism of mucopolysaccharides and glycoproteins.


The human mixed lymphocyte-endothelium culture interaction. Cells separated from the wall of the umbilical cord vein by collagenase digestion could be identified as endothelial by their characteristic ultrastructure, their growth pattern in culture, and their microscopical morphology. These cells, both freshly explanted and after long-term culturing, were capable of stimulating allogeneic lymphocytes in vitro. Control experiments indicated that this stimulation was not attributable to contamination of the endothelial cell suspensions by foetal fibroblasts or passenger lymphocytes. The dose response characteristics and kinetics of the lymphoproliferative response using endothelial stimulating cells was similar to mixed lymphocyte cultures. Sera which were capable of inhibiting the mixed lymphocyte culture response were relatively ineffective in inhibiting the stimulation caused by endothelial cells.


Prevalence of cardiac tumours at autopsy in Ibadan. The post mortem specimens, protocols, slides and hospital case notes of 6064 necropsies carried out in the University College Hospital, Ibadan over a seven year period were reviewed. Cardiac tumours were found in 64 subjects (1.06%) of all autopsies and in 8.5% of all 752 malignancies that came to autopsy during the same period. Only two of these tumours arose primarily in the heart whilst the remaining were metastatic tumours. The right side of the heart was more often involved than any other part (31.38%). The tumour with the highest cardiac involvement was Burkitt's lymphoma with an incidence of 30 cases i.e. 8.24% of all malignancies; 0.48% of all necropsies studied; 53.6% of all Burkitt's lymphoma autopsied. The risk of associating the rate of cardiac involvement of any tumour with its index of higher frequency was emphasized in the light of the paucity of involvement in a more frequent malignancy (hepatocellular) carcinoma in this environment. Routine medical examination coupled with an awareness of the possible susceptibility of the heart to secondary involvement by Burkitt's lymphoma would aid ante-mortem diagnosis of intracardiac malignancy particularly in patients of Burkitt's lymphoma age group.


Ultrastructural-morphometric analysis of the rat prostate (ventral lobe). A morphometric model, which provides information on the structure of the normal gland (ventral lobe) has been developed for the rat prostate. The model consists of morphologically defined space and membrane compartments, which are used to describe the specific components of the protein and enzyme synthesizing and secreting glandular cells. The results presented are relative to a cubic centimeter of prostatic tissue, a cubic centimeter of acinar parenchyma and glandular cell cytoplasm. Special interest was given to the cell compartments which are involved in protein and enzyme synthesis.


Retroperitoneal renal transplantation in young children. Children with urologic causes of renal failure constitute an increasing percentage of patients requiring transplantation. Two children weighing less than 20 Kg. underwent successful transplantation despite multiple previous intra-abdominal procedures. The retroperitoneal technique employed for these patients is described and its advantages emphasized.


Beneficial effects of adriamycin on Wistar-Furth Wilms' tumor. The Wilms' tumor (Wistar-Furth, Columbia University) animal model kills the host in a predictable period of time, associated with widespread metastases (lungs, liver, spleen) regardless of the route of tumor transplantation. Actinomycin D in single or multiple doses has previously been shown to increase survival, reduce the primary tumor weight, as well as the number of metastases in this experimental model. The model thus has close similarity to man. The present report describes a remarkable effect of adriamycin in this animal system. The beneficial results are, however, limited by severe dose-related toxicity. Nevertheless, faced with recurrent or metastatic lesions following prior current conventional clinical therapy, based on the present experimental results, we believe adriamycin treatment should be given serious clinical consideration.


Ectopic ACTH production in disseminated prostatic adenocarcinoma. The second fully documented case of ACTH-producing prostatic adenocarcinoma with elevated plasma and tissue levels of ACTH is presented. The distinguishing characteristics of ACTH-producing extrapituitary neoplasms and the various modes of therapy are discussed.


Asymmetric hindquarter syndrome (AHQS) in the pig. Outbreaks of the asymmetric hindquarter syndrome (AHQS) in two pig herds are reported together with the results of test matings and dissection studies on affected pigs. The condition (apparently identical with that described in Germany in 1967), is characterised by a variable asymmetry of the hindquarters and particularly of individual muscles of the posterior, lateral and medial aspects of the thigh. It does not noticeably interfere with locomotion but can adversely affect carcase conformation and may detract from the usefulness of carcase dissection studies as a basis for genetic selection. AHQS has a familial incidence and is usually first detected clinically after weaning. A variety of degenerative and dystrophic changes have been seen in the muscles of AHQS pigs but these are not constantly present in nor confined to 'undersized' muscles. The precise aetiology of AHQS is still unresolved but it is concluded that it probably occurs post-natally and that some pigs have a genetic liability to develop the condition.


Glomerular deposition of immune complexes in dogs following natural infection with canine adenovirus. The renal lesions were studied in eight dogs which had either died as a result of acute canine adenovirus infection (Rubarth's disease) or were in various stages of recovery from the clinical disease. Using immunofluorescence techniques granular deposits of IgG were detected in the glomeruli of six dogs; four of these animals had similar glomerular deposits of canine adenovirus antigen. Eluates obtained from kidney tissue of four dogs were found to contain antiviral antibody. Histologically those animals in which glomerular deposits of IgG and viral antigen were detected showed segmental glomerular hypercellularity. These findings were attributed to the deposition of circulating virus antigen-antibody complexes in the glomeruli.


Effect of citrate and aminotriazole on matrical plates induced in hepatic microbodies. Feeding of acetylsalicylic acid (ASA), clofibrate and dimethrin induces formation of matrical plates in heptaic microbodies. Administration of sodium citrate prevents formation of matrical plates in rats fed ASA, but not in rats treated with clofibrate or dimethrin. Propionate has a similar effect on rats fed ASA but not those fed clofibrate. Feeding of aminotriazole prevents formation of matrical plates in rats fed ASA without inhibiting the proliferation of microbodies. Sodium citrate and aminotriazole and feeding decrease also the activity of hepatic catalase in rats fed ASA.


[Study of glycogen metabolism in the liver in type III glycogenosis (limit dextrinosis)]. Data on biochemical study of a patient with glycogenosis of the III type (limit dextrinosis) are presented. In a punctate of liver tissue absence of amylo-1,6-glucosidase activity and significant accumulation of glycogen, which was anomalous in structure, were noted. Loading with galactose and adrenaline caused alterations typical for the III type of glycogenosis. Content of glucose and lactate in blood were also studied in response to the peroral administration of glucose and protein. In erythrocytes of the patient the polysaccharide structure was shown to be anomalous; it resembled the structure of a polysaccharide from liver tissue of the patient.


[Action of deoxyadenosine on nucleic acid synthesis by tumor cells in the presence of a deaminase inhibitor]. Deoxyadenosine, which was phosphorylated to dATP, inhibited DNA synthesis in malignant cells. However, on incubation of the substance in vitro with Zaidela ascites hepatoma cells the inhibitory effect was gradually decreased due to dephosphorylation of dATP and to deamination of deoxyadenosine to deoxyinosine. In order to prolong the inhibition of nucleic acids synthesis, N-6-methyl adenosine, which was recognized as an inhibitor of adenosine deaminase, was added to the cells. Optimal inhibition of DNA synthesis was observed in presence of deoxyadenosine and N-6-methyl adenosine at 1 with 10-minus 3 M concentration. Addition of N-6-methyl adenosine, after incubation with deoxyadenosine within 2 hrs, caused more prolonged inhibition of DNA and RNA synthesis than it was observed in presence of deoxyadenosine.


[Liver hexokinase isoenzymes in carcinogenesis]. Four isoenzymes of hexokinase were isolated by means of chromatography on DEAE-cellulose from soluble fraction of Vistar rat liver tissue. One of the isoenzymes (IV) was a glucokinase. Four fractions were also found in starch gel electrophoresis. These fractions catalyzed phosphorylation of glucose. Besides alterations in the total activity of hexokinase the changes in isoenzyme spectra were observed in carcinogenesis, caused by diethyl nitrosoamine. In the course of development of the blastomatose process in liver tissue content of isoenzymes I, II and, especially, of III was increased, and content of isoenzyme IV was decreased. In tissue of primary hepatomas, induced by diethyl nitrosoamine, the isoenzyme spectra of hexokinase did not significantly differ from the spectra of the enzyme in liver tissue at later stages of carcinogenesis.