Differential effects of 4-hydroxyaminoquinoline-1-oxide on pancreatic and liver DNA synthesis in rats.

The effect of 4-hydroxyaminoquinoline-1-oxide (4-HAQO) on DNA synthesis in the pancreas and liver, target and non-target organs for 4-HAQO carcinogenesis, respectively, were compared. Pancreatic and liver DNA synthesis were simultaneously induced in rats fed a protein deficient diet containing 0.5% DL-ethionine for 18 days, and DNA synthesis in both tissues was inhibited by hydroxyurea. A single i.v. injection of 4-HAQO at a dose of 7 mg/kg body weight also inhibited DNA synthesis in both tissues within 4 h. In the pancreas the inhibition was maximum at a dose of 7 mg/kg, and DNA synthesis was less than in the pancreas of rats fed a control grain diet. This inhibition continued for the subsequent 5 days which were tested. In the liver, the degree of inhibition was less than in pancreas but the value remained higher than in rats fed control diet. The inhibition of liver DNA synthesis at a dose of 7 mg/kg completely recovered within 1 day. These results suggest that the lesions of DNA induced by 4-HAQO and its repair might be different between the pancreas and the liver. A pancreatic chemical carcinogen, 4-HAQO, might thus have the same cytotoxic effect that liver carcinogens have toward the liver resulting in failure to respond to mitotic stimuli. This might be causally related to the organotropism of 4-HAQO toward the pancreas.


Hypothesis on the mechanism of erythrocyte invasion by malaria merozoites.

Plasmodium knowlesi merozoites invade erythrocytes by a sequence of events: attachment, widespread deformation of the erythrocyte membrane, endocytosis, and resealing of the membrane and vesicle. The possible mechanisms by which these events occur are discussed. In particular, there is a detailed discussion of the role of the Duffy blood group system in invasion.


A freeze-fracture study on the parasite-erythrocyte interrelationship in Plasmodium knowlesi infections.

Freeze-fracture studies were made on the parasite and the erythrocyte in P. knowlesi infections. There is a loss of transmembrane integral proteins from the plasma membrane of the schizont-infected erythrocyte and the intraerythrocytic parasite synthesizes new transmembrane proteins as development proceeds. Formation of the parasitophorous vacuole includes changes in the number of integral proteins present in the vacuolar membrane, indicating that this membrane may be modified by and in part derived from the parasite.


Labelling of membrane glycoprotein in erythrocytes infected with Plasmodium knowlesi.

Normal rhesus monkey erythrocytes and erythrocytes infected by P. knowlesi were labelled with galactose oxidase (EC 1.1.3.9) and tritiated sodium borohydride. The glycoproteins of normal erythrocytes were not labelled unless the cells were pretreated with neuraminidase, when peaks of activity with apparent molecular weights of 170 000, 126 000, 90 000, 50 000, and 35 000 were observed. Schizont-infected erythrocytes showed an absence of glycoprotein labelling even after neuraminidase treatment. The results indicate that there is an alteration in the glycoproteins of schizont-infected erythrocytes, which may contribute to the increased permeability and the immunological alterations on the surface of these cells.


Lipids and the malarial parasite.

Merozoite endocytosis initiates Plasmodium development in a vacuole bounded by an erythrocyte-derived membrane, whose asymmetrical distribution of lipids and proteins is reversed in its orientation with respect to the parasite plasma membrane. Reorientation may accompany the proliferation of the membrane associated with the parasite's growth and phagocytic and pinocytic feeding. Increases in the membrane surface area of the parasite, and in some cases of the erythrocyte, parallel parasite growth and segmentation. Augmentation of all the membrane systems of the infected erythrocyte causes the lipid content to rise rapidly, but the parasite lipid composition differs from that of the erythrocyte in many respects: it is higher in diacyl phosphatidylethanolamine, phosphatidylinositol, polyglycerol phosphatides, diacylglycerols, unesterified fatty acids, triacylglycerols, and hexadecanoic and octadecenoic fatty acids and lower in sphingomyelin, phosphatidylserine, alkoxy phosphatidylethanolamine, cholesterol, and polyunsaturated fatty acids. Active lipid metabolism accompanies the membrane proliferation associated with feeding, growth, and reproduction. Plasmodium is incapable of de novo biosynthesis of fatty acids and cholesterol; however, it can fabricate its glycerides and phosphoglycerides with host-supplied fatty acids, nitrogenous bases, alcohols, ATP, and coenzyme A, and can generate the glyceryl moiety during glycolysis. Cholesterol is obtained from the host but nothing is known of sphingolipid origins. Lipid metabolism of the parasite may be associated with alterations in the amounts of octadecenoic fatty acids and cholesterol in the erythrocyte plasma membrane, which in turn are responsible for changes in permeability and fragility.


Release of protein by erythrocytic stages of Plasmodium knowlesi during cultivation in vitro.

Erythrocytes infected with schizonts of P. knowlesi and labelled in vitro with (3)H-isoleucine were shown to release radioactivity when placed in unlabelled culture medium containing uninfected erythrocytes. Release of radiolabel probably occurred during schizont rupture and invasion of new erythrocytes and was not observed to any great extent at earlier stages in the erythrocytic life cycle. Approximately 55% of the released radioactivity was soluble in 10% trichloroacetic acid, the remainder being acid insoluble and therefore presumably protein in nature. Particulate or aggregated material appeared to comprise 40-50% of the acid-insoluble radiolabelled fraction. Two major labelled polypeptide species were observed on sodium dodecyl sulfate polyacrylamide gel electrophoresis of samples of concentrated culture medium. These proteins had apparent molecular weights of 45 000 and 49 000, which correspond closely with the sizes of two main protein species previously identified in P. knowlesi-infected cells.


Cofactors and vitamins in the metabolism of malarial parasites. Factors other than folates.

Relatively few cofactors have so far been demonstrated to be essential for the intracellular development of erythrocytic stages of malarial parasites. Besides 4-aminobenzoic acid, presumably required for the synthesis of folates, these are biotin and pantothenate. The pantothenate is not used directly by the parasites but rather as coenzyme A synthesized by the host erythrocyte. Parasites maintained extracellularly in vitro also have a requirement for exogenous adenosine triphosphate. No information is available concerning cofactor requirements of the sporogonic or pre-erythrocytic stages.


Preservation of intraerythrocytic forms of malarial parasites by one-step and two-step cooling procedures.

Ring, trophozoite, and schizont stages of Plasmodium knowlesi were cooled in dimethyl sulfoxide either by direct immersion in liquid nitrogen or by a two-step method in which the cells were held at temperatures slightly below 0 degrees C for different lengths of time before they were cooled to -196 degrees C. After the direct plunge treatment, thawed trophozoites and schizonts were found to be extensively damaged. Their survival was markedly increased by holding them at -31 degrees C for 30 min before plunging them into liquid nitrogen. Freeze-substitution showed that cells cooled by the two-step procedure were grossly shrunken and had relatively few intracellular ice cavities. Large amounts of ice formed in trophozoites and schizonts preserved by direct immersion in liquid nitrogen. The two-step protocols investigated did not improve the survival of ring-stage parasites, 25-50% of which survived rapid cooling to -196 degrees C. Infected cell agglutination tests were carried out with frozen and thawed schizonts. Variant specificity was demonstrated with cells that had been plunged directly to -196 degrees C, but cells cooled by the two-step method tended to agglutinate spontaneously.


Effect of nitroglycerin on exercise-induced abnormalities of left ventricular regional function and ejection fraction in coronary artery disease. Assessment by radionuclide clineagiography in symptomatic and asymptomatic patients.

The effects of nitroglycerin (TNG) on exercise-induced abnormalities of left ventricular wall motion and ejection fraction are unknown in symptomatic and asymptomatic patients with coronary artery disease (CAD). In the present investigation radionuclide cineangiographic studies were performed in 47 patients with CAD (14 without angina during exercise) and in 25 normal subjects. All CAD patients, including those without symptoms, demonstrated regional wall motion abnormalities during exercise. In all patients, ejection fraction (EF) also responded abnormally to exercise: EF decreased from 48% at rest to 36% during exercise (P less than 0.001). EF increased in all normal subjects from an average of 58% at rest to 71% during exercise (P less than 0.001). In all CAD patients TNG reduced exercise-induced regional wall abnormalities and increased EF attained during exercise from an average of 36 to 48% (P less than 0.001). EF in normal subjects was unchanged by TNG. Thus, exercise can cause abnormalities in left ventricular regional function and ejection fraction in patients with or without symptoms; these abnormalities can be mitigated by prophylactic TNG.


The treatment of seasonal allergic rhinitis with a 2% aqueous solution of sodium cromoglycate delivered by a metered dose nasal spray.

A double-blind, group comparative trial of 2% aqueous solution of sodium cromoglycate in seasonal allergic rhinitis (hay fever) is reported. All twenty-five patients in the active group found the treatment a success whereas fourteen out of nineteen in the placebo group regarded this as a failure. The method of application (metered dose spray) was acceptable to all patients.


Asthma induced by sulphur dioxide, benzoate and tartrazine contained in orange drinks.

Of 272 patients with asthma, thirty (11%) gave a history of exacerbations occurring after ingestion, solutions of orange orange drinks. Fourteen of these were given provocation tests by drinking, on separate occasions of sulphur dioxide, sodium benzoate and tartrazine, which are present in all orange drinks. Eight reacted to sulphur dioxide with a fall in FEV1, four to sodium benzoate and one to tartrazine, and four did not react to any of these agents. Three of the benzoate patients were also sensitive to sulphur dioxide. The sulphur dioxide sensitive patients were predominantly young, with extrinsic asthma. The benzoate sensitive patients were predominantly middle-aged and the proportion with intrinsic asthma was higher. Prior inhalation of sodium cromoglycate by four patients inhibited the reaction to these substances. Sulphur dioxide has not previously been reported to cause exacerbations of asthma when ingested as a food preservative. It is used as a preservative in a wide range of acidic beverages and foods, and should be considered as possibly causal in patients suffering from apparently cryptogenic asthma, and asthma seemingly due to food allergy.


Analysis of immunological features of intrinsic and extrinsic asthma and clinical response to DSCG.

A large range of immunological investigations in patients with extrinsic or intrinsic asthma showed higher leucocyte counts in intrinsic asthma. Blood sputum eosinophilia were almost equally frequent. Immediate skin responses to inhalant antigens are seldom present in intrinsic asthma, but delayed responses to bacterial antigens, endotoxins, Candida albicans ans aspiryl-PPL are frequently positive. This correlates with the frequent presence of precipitins and in vitro stimulation of lymphocytes, and the production of macrophage migration inhibition factor by most of these substances. These results suggest that bacterial factors may play a prominent role as aetiological agents in at least some cases of intrinsic asthma. In intrinsic asthma there was a high incidence of tissue autoantibodies, whereas the incidence was negligible in patients with atopic asthma. The level of serum immunoglobulins was not statistically different between the two groups of patients except for IgE. The patients with intrinsic asthma showed a favorable response to sodium cromoglycate.


Precipitating antibody to antigens of Pseudomonas aeruginosa in chronic obstructive lung disease.

Two antigens designated Pseudomonas aeruginosa cytoplasmic antigen (P(1-5)) and P. aeruginosa cell wal antigen (PCW) were prepared by ultrasonic disintegration and hot phenol extraction of a smooth polyagglutinable strain of P. aeruginosa isolated from the respiratory tract. It was shown that P(1-5) and PCW are immunologically distinct, that P(1-5) is heat-labile while PCW contains a heat-stable component which stains positively for polysaccharide, is positive for endotoxin and cross-reacts with a cell wall antigen of Haemophilus influenzae prepared by hot phenol extraction. Both antigens were able to activate the alternate pathway for complement. A statistically significant number of patients with cystic fibrosis and bronchiectasis have precipitating antibody to that fraction of cytoplasmic antigen specific for P. aeruginosa (P(1-2)) and PCW compared to controls, whereas patients with asthma and chronic bronchitis do not. The use of both antigens increases the number of patients with antibody to P. aeruginosa. Radioactive immunodiffusion studies indicate that 80.8% of controls have precipitating antibody to PCW antigen and that antibody to it is IgG, IgA and IgM. These studies indicate that consideration should be given to PCW as well as P(1-5) in any consideration of the pathogenesis of P. aeruginosa in these conditions.


Treatment of ragweed hay fever with intranasally administered disodium cromoglycate.

In a double-blind study the therapeutic effect of a 4% disodium cromoglycate (DSCG) nasal solution was evaluated in thirty-nine patients with acute symptoms of ragweed hay fever. Patients were randomly assigned to the DSCG or placebo group as they presented with allergic rhinitis. Overall, the DSCG was not more effective than placebo in controlling the symptoms of rhinitis or in decreasing the need for concomitant antihistamines or corticosteroids. Among patients with the highest pretreatment serum ragweed-specific IgE (RW IgE) levels, drug-treated patients had some reduction in symptoms as compared to their placebo controls during the peak of the ragweed pollen season. DSCG treatment did not influence the usual seasonal rise in RW IgE. Side effects from both the active and placebo aerosols were frequent but mild. We conclude that DSCG nasal solution used for the treatment of seasonal ragweed allergic rhinitis is relatively ineffective.


Results for serum and plasma compared in 15 selected radioassays.

We evaluated the results for serum vs. plasma samples for 15 selected radioassay procedures, using 19 manufacturers' kits. Blood samples were collected with heparin, oxalate-fluoride, or ethylenediaminetetraacetate anticoagulants and compared with serum samples. Differences were demonstrated between serum and plasma which may be of sufficient magnitude to alter clinical interpretation of the results. Assays also demonstrated significant differences based on the kit manufacturer and procedure used.


Selective staining of alpha1-antitrypsin (alpha1-protease inhibitor) with Schiff's reagent after separation from serum by analytical isoelectrofocusing in polyacrylamide gel.

After electrofocusing serum from human and various animals in the pH range 4.0-6.0, only the isoproteins of antitrypsin stain with Schiff's reagent. As an additional advantage, this staining provides information about the relative contents of the Schiff-positive carbohydrates of various antitrypsins.


The effect of Mycoplasma contamination on the in vitro assay of pyruvate dehydrogenase activity in cultured fibroblasts.

Cultured fibroblasts contaminated with mycoplasma were shown to have increased in levels of apparent pyruvate dehydrogenase and pyruvate dehydrogenase complex enzyme activity. The apparent pyruvate dehydrogenase specific activity was about 1000-fold greater in cultured Mycoplasma pneumoniae than in cultured fibroblasts. Several acid hydrolytic enzyme activities were also shown to be present in M. pneumoniae though a lower apparent specific activity than in cultured fibroblasts.


A micromethod for determining adenosine deaminase and purine nucleoside phosphorylase activity in cells from human peripheral blood.

A radiochromatographic method is described for measuring adenosine deaminase and purine nucleoside phosphorylase activity in cells from human peripheral blood. The respective substrates, [8-14C]adenosine or [8-14C]inosine, are converted either to inosine and hypoxanthine or hypoxanthine, respectively. A single simple and rapid chromatographic procedure is used to isolate the products of both reactions. The mean normal activity (nmol h-1mg-1) of ADA for erythrocytes is 63 +/- 24 (+/- 1 S.D.) for leukocytes, 750 +/- 280 and for lymphocytes, 2105 +/- 1170. Corresponding activities for purine nucleoside phosphorylase are 1850 +/- 490, 3665 +/- 1170 and 5890 +/- 2030. With the described methods a further patient with severe combined immuno-deficiency and adenosine deaminase deficiency has been identified.


Interrelationship of tryptophan pyrrolase with tyrosinase in melanogenesis of Bufo melanostictus.

Tryptophan pyrrolase, a microsomal enzyme responsible for the break-down of tryptophan, has been detected in Bufo melanostictus. The enzyme has been found to be deactivated under influence of antivitiligo drug psoralene and activated by hydroquinone, an inhibitor of tyrosinase. Tryptophan pyrrolase has been found to have an antagonistic relationship with tyrosinase in Bufo melanostictus. The implication of the results has been discussed in relation to melanogenesis in vitiligo.


Studies on excretion of renal antigens in normal and pathological urine.

The report deals with attempts to identify and quantitate renal antigens excreted into the urine of normal subjects and patients with renal disease. Although no useful information was obtained on the possible excretion of glomerular basement membrane antigens, renal tubular epithelial antigen (RTE) proved to be interesting. Curiously, massive excretion of RTE occurred most prominently in cases of 'minimal change' disease. In addition, a correlation between the selectivity of the proteinuria and excretion of RTE was noted. In general there did not seem to be any relation between RTE excretion and tubular/interstitial lesions.


Pericellular glycosaminoglycans in cultured human cells. A possible source of error in prenatal diagnosis of mucopolysaccharidoses.

Normal fibroblasts and amniotic fluid cells, and cells from patients with Mucopolysaccharidosis type I and II, were cultured in the presence of 35SO4. After harvesting by trypsinization, the radioactivity was recovered from the intracellular and pericellular pool of glycosaminoglycans. The amount of incorporated radioactivity in these respective pools was 1 : 2.3 in normal fibroblasts and 1 : 7.2 in control amniotic fluid cells. Incorporation in the pericellular pool was not elevated in cells from patients with Mucopolysaccharidosis type I and II, in contrast to incorporation in the intracellular pool. Studies on different methods of harvesting showed that reliable prenatal analysis can be performed only if the pericellular pool is removed by trypsinization. Amniotic fluid cells from a pregnancy carrying a fetus affected with Hurler's disease revealed the expected increased level of 35SO4 incorporation if the cells were trypsinized, but the intracellular accumulation of glycosaminoglycans was obscured by the pericellular pool if the cells were harvested by scraping.


Increases in serum concentrations of follicle-stimulating hormone (FSH) during thyrotrophin-releasing hormone (TRH) infusions in normal men.

Increases in serum FSH values to approximately 50% above basal concentrations were found during TRH infusions of 2.0 microgram/min into normal men (n = 10). These increases could not be explained by cross-reactivity of thyrotrophin (TSH) in the FSH assay. No significant change was found in serum concentrations of FSH during saline infusions (n = 4) nor in LH concentrations during either TRH or saline infusions. Many previous studies using single injections of TRH have failed to demonstrate changes in serum FSH concentrations. It is possible that prolonged infusions of TRH, as used in this study, are more likely to lead to non-specificity of the effects of this tripeptide on pituitary hormone secretion.


Response to thyrotrophin-releasing hormone and triiodothyronine suppressibility in euthyroid multinodular goitre.

In twenty-two female patients with euthyroid multinodular goitre of varying size, thyroid suppression of 131I thyroid uptake by triiodothyronine (T3) and thyrotrophin (TSH) release after thyrotrophin-releasing hormone (TRH) administration were compared with thyroid weight, estimated by a planimetric method, and with serum thyroxine (T4) and T3 concentrations. Maximal increment of TSH (deltaTSH) after TRH and per cent T3-suppressibility were inversely related to thyroid weight and not related to basal serum T4 or T3 concentrations. deltaTSH and per cent suppression correlated positively, but deltaTSH was more often subnormal than T3-suppressibility. A practical consequence of our study is that nonconformity of the two tests may occur. This should be kept in mind in the evaluation of patients with thyroid disorders.


Partial deletion of long arm of chromosome 11: del (11) (q23).

The cytogenetic analysis of an infant with multiple congenital anomalies revealed a small deletion of the long arm of one No. 11 chromosome: 46,XX,del(11)(q23). The main clinical manifestations included: ocular colobomata, absent philtrum, severe congenital heart disease, contractures of the large joints and skin pigmentation. Both parents showed a normal chromosome constitution. In comparison to the previously reported cases of 11q-, the patient presented here had more severe congenital anomalies. The correlation of the size of the deletion, and the location of the break, with the physical findings is discussed.


Inhibition of bovine cerebral cortex prostaglandin synthetase by phenoxybenzamine and cyproheptadine in vitro.

1. Bovine cerebral cortex (BCC) microsomes were isolated from fresh brain using standard techniques. 2. Two a-adrenoceptor antagonists (phenoxybenzamine and phentolamine) and two anti-serotonin compounds (cyproheptadine and cinanserine) were compared with the anti-inflammatory drugs indomethacin and keptoprofene for inhibition in vitro of prostaglandin (PC) synthetase. 3. Henoxybenzanine and cyproheptadine inhibited BCC PG synthetase in vitro, but their potency was 1% that of indomethacin and keptoprofene. Phentolamine and cinanserine did not inhibit PG synthetase in concentrations up to ten times the effective concentrations of the other test drugs. 4. It is suggested that the antipyrogenic effect of phenoxybenzamine and cyproheptadine may be due to their inhibitory effect on prostaglandin synthesis.


Continuous intragastric infusion of elemental diet: experiences with 10 infants having small-intestinal diseases.

Five infants with gastrointestinal disease requiring neonatal surgery and two infants with nonsurgical disorders were nourished successfully using a constant intragastric infusion of an elemental diet. Two additional patients who developed persistent distension and gastric retention on IED had mechanical obstruction requiring surgery and another died of NEC during treatment. Use of IED avoided the risks of TPN and was followed by successful introduction of standard feeding techniques. IED provides a valuable alternative to TPN in selected infants and newborns. Caution with any enteral feeding method is required in infants at risk for NEC.


Expenditures for health care of children and youth in the United States.

This paper describes the expenditures for health care in the United States in fiscal year 1975. Proportionately, health expenditures for children and youth are lower than for other age groups. The average per capita expenditure for children and youth was $212.00. For children and youth public health care expenditures represented 24 per cent of the total; from public funds, Medicaid and the Department of Defense were the largest two programs; from the public sector, the federal government provided two thirds of the total health expenditures. For children and youth, two thirds of all health expenditures were for hospital care and physicians' services.


Hand-washing degerming: a comparison of povidone-iodine and chlorhexidine.

Two antiseptic preparations for hand washing were compared by the glove-juice method in a crossover study on 10 volunteers. The reference preparation was 7.5% povidone-iodine (Betadine Surgical Scrub); the test agent was 4% chlorhexidine gluconate combined with 4% isopropyl alcohol (Hibiclens). The experimental model included inoculation of the hands with a mixture of Serratia marcescens, Escherichia coli, Providentia stuartii, and Pseudomonas aeruginosa. The reference preparation achieved a reduction ratio in colony counts of 695 to 1 under the conditions of this study. The average postwash colony count after use of 7.5% povidone-iodine was significantly less than the preinoculation colony count. Logarithmic values, and the paired t test applied to them, showed a highly significant difference (p = less than 0.001) in favor of the degerming ability of the reference agent compared to the test agent. These data are of value in the selection of preparations for hand washing and may point the way to quantitative methods for other degerming studies.


Protein turnover, synthesis and breakdown before and after recovery from protein-energy malnutrition.

1. Rates of total protein turnover, synthesis and breakdown were measured in five children before and after recovery from severe protein-energy malnutrition and while receiving 0.6 g of protein and 397 kJ day-1 kg-1. 2. Thes rates were calculated after giving doses of [15N]glycine every 2 h along with the feeds and measuring the rate of excretion of [15N]urea in urine. 3. Malnourished children had significantly lower rates of protein turnover, synthesis and breakdown than after they had recovered. 4. During recovery from protein-energy malnutrition, two children on a daily intake of 1.2 g of protein and 605 J/kg body weight, had rates of protein turnover, synthesis and breakdown that were twice as great as those found on admission and higher than after recovery. 5. On the study diet the malnourished children maintained their weight while the recovered children lost weight; the apparent nitrogen balance was more positive in the malnourished children. 6. In recovered children, the rate of protein synthesis was unchanged over a wide range of protein intake, whereas the rate of protein breakdown appeared to rise with a reduction in protein intake.


Sheep experimentally infected with Sarcocystis from dogs. II. Abortion and disease in ewes.

This is the first study of Sarcocystis-induced abortion in sheep. Eleven pregnant ewes were experimentally inoculated with 50,000, 100,000, or 500,000 Sarcocystis ovicanis sporocytis from dogs. Eight ewes either aborted, died, or became moribund before term; they produced 15 fetuses, 11 of normal appearance and 4 necrotic. No evidence of intrauterine transmission was obtained. All infected ewes became anemic, inappetent, and lost weight. Ewes inoculated with the greatest numbers of sporocysts exhibited the most striking signs of acute illness. At necropsy of acutely ill ewes the heart was the most severely affected organ, appearing nearly black as a result of hemorrhagic pancarditis. Less hemorrhage was seen in the kidney, liver, spleen, and skeletal muscles. Microscopically, schizonts were found in capillary endothelial cells of most organs 24 to 33 days after inoculation. Ewes surviving the acute illness appeared generally unthrifty and exhibited the additional signs of wool breaking, and nervous disturbances. At postmortem, the heart and kidneys of these ewes were moderately hemorrhagic, and the adrenal glands and mesenteric lymph nodes were enlarged. Microscopically, sarcocysts were found in the heart, diaphragm esophagus, tongue, skeletal and eye muscles, cerebellum, and cerebrum.


Viability of Leptospira interrogans serotype grippotyphosa in swine urine and blood.

Normal swine urine, devoid of its microbial flora, diminished the viability and virulence of Leptospira interrogans serotype grippotyphosa. Bovine serum albumin diluent effectively offset the urine's deleterious effects. Membrane filtration (0.45 micrometer) rendered urine free of bacteria, but permitted passage of limited numbers of leptospires. Most of the commonly used anticoagulants did not alter viability of grippotyphosa in whole blood. However, EDTA significantly reduced the number of viable cells.


The effect of tablet formulation on the haemodynamic properties of glyceryl trinitrate.

A non-invasive haemodynamic study was carried out in 13 normal subjects to compare the pharmacodynamics of glyceryl trinitrate when formulated as a moulded tablet ('Nitrostat') rather than as a generic compressed tablet. The glyceryl trinitrate moulded tablet, with a much more rapid and predictable dissolution time, produced an earlier onset of systolic blood pressure fall (p less than 0.01) and a greater maximum percentage change in peripheral blood flow (p less than 0.02). No other significant differences in effect on pulse rate, blood pressure or peripheral blood flow were noted.


In vitro activity of netilmicin (SCH 20569) against bacterial isolates from ill children.

A new aminoglycoside antibiotic, netilmicin, was tested against 306 clinical isolates from ill children and compared with sisomicin and gentamicin. Activity against Enterobacteriaceae was similar to that of gentamicin but less than that of sisomicin. Two gentamicin-resistant strains of Enterobacteriaceae (Klebsiella, MIC 6.25 microgram/ml, Escherichia coli, MIC 12.5 microgram/ml) were susceptible to netilimicin (MIC 3.12 microgram/ml). Netilmicin was ineffective against almost all strains of Pseudomonas but active against the majority of strains of Staphylococcus, Neisseria meningitidis and Haemophilus influenzae tested. Disc diffusion sensitivity results correlated in general with the agar dilution test. Netilmicin had little activity against Pseudomonas but may be useful in the treatment of infections due to gentamicin-resistant Enterobacteriaceae.


Antimicrobial synergism in the therapy of gram-negative rod bacteremia.

To determine if antimicrobial synergism might affect the results of treatment of gram-negative rod infections, 444 bacteremias from 1972 through 1974 were studied. On these, 173 were treated with two antibiotics to which the infecting organisms were sensitive. Clinical responses were observed in 80% of 83 cases where antibiotic activity was synergistic, as defined by a minimum inhibitory concentration (MIC) of each antibiotic in combination being one-fourth or less than the MICs of individual drugs. This response rate was significantly better than the 64% response seen in patients treated with nonsynergistic combinations (p less than 0.05). Synergism correlated with significantly better clinical responses in those patients with "rapidly fatal" and "ultimately fatal" underlying disease (p less than 0.005), neutropenia (p less than 0.001), shock (p less than 0.01) and Pseudomonas aeruginosa infections (p less than 0.05). These results suggest that the use of antibiotic combinations to treat patients with gram-negative rod bacteremia who have the poorest prognosis is clinically justified and the improved results may be related to the synergistic activity of antimicrobial agents.


First annual Arnar-Stone lecture: The importance of the endocrine and metabolic responses to shock and trauma.

Trauma and shock result in activation of a wide variety of endocrine and metabolic systems. Based upon experimental work demonstrating metabolic deficits, a variety of metabolic therapies have been developed to assist in the treatment of patients with shock or trauma. Evidence to date is inconclusive as to whether this therapy will be of significant benefit to critically ill patients. Some of the senior author's previous research has been analyzed as it relates to important health policy issues. We suggest that a peer review mechanism be set up within organized professional groups to assess major research trends and develop informed opinions on key research subjects within their domain. These peer review assessments must be effectively communicated to Congress and the executive branch of the government, as well as to the general public, if support commensurate with the importance of the research is to be achieved.


[Folic acid levels in patients with compensated renal failure and during long-term haemodialysis (author's transl)].

Folic acid concentration in plasma and erythrocytes and vitamin B12 concentration in plasma were determined by radioassay in 56 patients with chronic renal failure. Compensated retention was present in 31, while 25 were haemodialysed at regular intervals, 14 at home, and 11 in hospital. One patient had megaloblastic anaemia. Mean folic acid concentration in plasma for the whole group was 4.60 microgram/l (normal 8.30 +/- 2.57  microgram/l), in RBC 385 microgram/l (normal 459 +/- 143 microgram/l. Vitamin B12 levels were normal. These was no significant difference in folic acid levels betwwen patients on home or on hospital dialysis. During dialysis there was a fall in folic acid concentration in plasma which was proportional to the intial levels. After a four-week replacement pause folic acid concentration in RBC had not decreased in those patients on long-term dialysis who had previously received folic acid. The decreased folic-acid concentration in plasma of patients in compensated chronic renal failure is not due to the renal failure. Folic acid concentration in RBC is decisive in the assessment of folic acid deficiency.


[Comparison of orthodromic and antidromic sensory nerve conduction. 1. Normals and patients with carpal tunnel syndrome (author's syndrome)].

In 32 healthy volunteers aged between 10 and 72 years the orthodromic and the antidromic sensory nerve conduction in the median nerve have been studied. Normal values for conduction velocities and for the configuration of the orthodromic nerve action potentials are described in detail. 26 patients suffering from a carpal tunnel syndrome have been examined both with the orthodromic and the antidromic method. It could be shown that the diagnostic yield of both methods is about the same for this special problem.


[Comparison of orthodromic and antidromic sensory nerve conduction. 2. Patients with polyneuropathies and polyradiculitis (author's transl)].

The results of the orthodromically and the antidromically recorded nerve action potentials from a median nerve in 30 patients with clinically slight or beginning polyneuropathies have been compared. Antidromic conduction velocity was slowed in 8 cases, in 8 patients it was normal and in 14 patients no definite antidromic nerve action potential could be recorded. This last finding is not considered as being definitely abnormal. In all but one patient orthodromic nerve action potentials could be elicited. In 28 out of 30 patients the orthodromic method gave pathological findings. Duration of the nerve action potentials and the number of their potential component were the most sensitive single parameters, which were abnormal in more cases than conduction velocity of the fastest fibres. For the detection of slight or beginning polyneuropathies the diagnostic yield of the orthodromic method turned out to be much greater than the antidromic. In contrast, in a group of 19 young patients, which previously had suffered from a polyradiculitis, no significant difference between the two methods was found.


[Early electroneurographic diagnosis of carpal tunnel syndrome (author's transl)].

A comparison of distal motor latencies after stimulation of the median and ulnar nerves proximal to the ligamentum carpi transversum and recording from the thenar muscles shows: a) in normal subjects (99 measurements) a 0,7 msec longer latency after stimulation of the ulnar nerve, b) in generalized polyneuropathies in 46% (n = 48) a reversal of the two motor latencies, i.e., a longer median than ulnar nerve latency. c) in manifest carpal tunnel syndromes with pathologically prolonged motor latencies this reversal in all cases; d) in carpal tunnel syndromes with only pathologically prolonged sensory latencies in 11 out of 13 patients a reversal of motor latencies; e) in patients with carpal tunnel syndromes a reversal of motor latencies in 65% (n = 46) on the clinically symptom-free side. It is concluded that a reversal of distal motor latencies may be the earliest sign of a carpal tunnel syndrome, if a generalized polyneuropathy is excluded and typical symptoms are reported.


[The staircase phenomenon in myasthenia gravis and other neuromuscular disorders (author's transl)].

The isometric contractions with repetitive stimulation of 2/sec during 90 sec have been recorded in 39 patients with neuromuscular disorders other than myasthenia gravis. Seven patients had falling amplitudes of the contractions, in 14 cases the increase was below 12 per cent and 21 patients had a normal staircase phenomenon. It is recommended to take only a falling of the contraction amplitudes as an important indication for myasthenia gravis. This finding, however, is not specific and in the indivisual case it has to be considered in combination with the other clinical, electro-physiological and histological findings.


[The relation of electroencephalographic foci to vasospasms in patients with subarachnoid haemorrhage (author's transl)].

During a period of five years 74 patients with acute subarachnoid haemorrhage were controlled by angiography and EEG. 19 patients demonstrated angiographically proved intracranial aneurysms, seven intracerebral haematomas, three arteriovenous abnormalities. 25 patients had vasospasms. 34 patients showed foci in the EEG. Focal neurological abnormalities were in 43 patients. A correlation was established between EEG focus and vasospasm, focus and intracerebral haematoma. Further a relationship between focus and focal neurological abnormalities was detected. There was no correlation between EEG focus and aneurysm. It was claimed, that some foci in the EEG could be the result of persistent vasospasms.


[The value of EEG after sleep deprivation (author's transl)].

Seventy seven adult epileptics and 30 patients with clinically non epileptic seizures were subject to a 24 hours sleep deprivation. The waking records of these patients were normal or unspecific abnormal. After sleep deprivation 29 (37%) of epileptics had abnormal EEG with epileptiform or focal activity, more often in cases with frequent (26 (60%) patients out of 43) epileptic seizures. Patients with sporadic attacks only exceptionally showed specific EEG changes (3 patients (8,8%) out of 34). Drug induced sleep emerged to be diagnostically less helpful. Twenty nine out of 30 patients with clinical nonepileptic seizures had no additional abnormalities in the EEG after sleep deprivation.


The endoscopic picture of the intramural oesophageal diverticulosis.

On the basis of the results in 3 own observations the endoscopic picture of the intramural oesophageal diverticulosis has been described in detail. It is characterized by an increased tonus of the oesophagus inlet musculature, a conspicuously non-irritant oesophageal mucosa, the absence or only a slightly indicated and irregular course of the expansion peristalsis, a poor distinction of the respiratory luman variations and the occurrence of circumscribed spasms and, above them, of segmental relaxation bulging. Pathogenitically the disease is probably caused by a disturbance of the muscular activity with bulging of the functioning mucosa at points of an oesophagus wall weakness.


How often does bacteraemia occur following endoscopic retrograde cholangiopancreatography (ERCP)?

In order to determine the risk of bacteraemia from ERCP, we cultured blood specimens from 83 patients before, during and 15 min, 1, 6, 12 and 24 hours after the examination as well as in the subsequent week whenever fever occurred. No bacteraemia was found in the 20 patients who had duodenoscopy only, i.e. in whom ERCP failed. Of the 20 patients with normal biliary and/or pancreatic ducts positive culture was obtained in one patient in whom inadvertent multiple injections of contrast material into the pancreatic duct had resulted in the occurrence of a pyelogram. Four positive cultures were found amongst the 43 patients in whom an obstructive pathology in the biliary or pancreatic system was present. These data support the need of on antibiotic prophylaxis for patients with valvular heart defects.


Prepapillary intradiverticular bezoar as cause of obstructive jaundice. Removed by endoscopy.

Obstructive jaundice was cured in a 70-years-old woman after endoscopic removal of a bezoar located in a prepapillary duodenal diverticulum.


Epileptic seizures precipitated by eating.

The case of a mentally retarded 18-year-old girl who for 2 years has experienced epileptic seizures exclusively during meals is discussed. Polygraphic recordings have defined the electrical and clinical features of these seizures. None of the possible precipitating factors considered in other cases in the literature (chewing, swallowing, conditioned reflex, etc.) seems to be involved in this case. We hypothesize that in our patient the precipitating factor is the complete act of eating a meal, which involves the satisfaction of a basic drive.


EEG operant conditioning in a monkey model: I. Seizure data.

EEG operant conditioning in an alumina-gel monkey model (N = 14) to decrease EMG, to increase 9 Hz or decrease 9 Hz, and to increase 23 Hz (18 Hz and 26 Hz in 2 pilot monkeys), respectively, was not consistently beneficial in reducing seizures. The data suggested: (1) that desynchronization of the EEG by reinforcing 18-26 Hz decreased in some animals the extent and severity of seizures while increasing seizure frequency; (2) that attending during conditioned EMG suppression reduced seizures somewhat; and (3) that the operant conditioning setting became stressful to the majority of monkeys under certain conditions, precipitating status epilepticus, gastrointestinal disturbances, and shock, which culminated in the death of 3 animals. Certain precautions are discussed in the therapeutic application of this technique to epileptic patients.


EEG operant conditioning in a monkey model: II. EEG spectral analysis.

EEG power spectral analysis was studied from 14 (alumina-gel) chronically epileptic, undrugged monkeys during an EEG operant conditioning experiment. The composite profile of the average epileptic monkey shows the majority of power to be below 10 Hz. Because of the large variance in the data, no significant changes in the EEG power spectra could be detected as a function of conditioning. The possible reasons for this large variance are discussed. Hypothesis from previous human "biofeedback" studies would allow the prediction that those frequencies corresponding to the mu and sensory-motor-rhythm should negatively covary with seizure frequency. Data from this study did not support such assertions. The method of using spectral analysis for quantifying changes in the EEG which covary with operant conditioning is evaluated.


Potassium clearance and reactive gliosis in the alumina gel lesion.

Potassium accumulation or impaired potassium clearance has been hypothesized to contribute to epileptogenesis in gliotic epileptogenic foci. To test this hypothesis, potassium clearance rates following direct cortical stimulation were measured in the cortex of monkeys rendered epileptic by the injection of alumina gel into the motor area. Reactive gliosis at the sites in which potassium clearance was measured was then quantitated histologically and compared with potassium clearance rates. Dense gliosis was associated with slowed potassium clearance, although the base-line potassium level appeared no different in actively epileptogenic areas or gliotic areas compared with normal areas. Possible mechanisms and significance of slowed potassium clearance in the alumina focus are discussed.


Profile of epilepsy in a developing country: a study of 1,000 patients based on the international classification.

The present prospective study undertaken in a specialized neurological center of a developing country deals with 1,000 epileptic patients classified in accordance with the International Classification. Eighty-one percent of the patients could be classified, with a lower incidence in the younger age group. Partial epilepsy was found to be far more common than generalized epilepsy (80% versus 20%). Primary generalized epilepsy was seen in 15% and secondary generalized in 5%. Partial epilepsy with elementary symptomatology was seen in 58% and complex symptomatology in 7%. Secondarily generalized seizures were seen in the remaining 15%. Primary generalized epilepsy and partial epilepsy with complex symptomatology were more common in adults. Secondary generalized epilepsy and partial epilepsy with secondarily generalized seizures were more common in children. Partial epilepsy with elementary symptomatology, however, did not vary significantly with age. The higher incidence of partial epilepsy in our patients, compared to the West, could be due to greater frequency of CNS infections and birth injuries, which are common childhood hazards in the developing countries.


Specificity of sialytransferase: structure of alpha1-acid glycoprotein sialylated in vitro. A new methodology for the determination of the structure of the linkage formed by glycosyltransferase action on galactosyl-oligosaccharide-protein acceptors.

The terminal galactosyl units of desialylated alpha1-acid glycoprotein were selectively labeled with tritium by a galactose oxidase/NaB3H4 procedure. The 3H-labeled glycoprotein was effective as an acceptor in sialytransferase reactions catalyzed by rat liver microsomes in vitro with unlabeled CMP-N-acetyl-neuramininic acid as sialic acid donor. Permethylation/hydrolysis of glycopeptides derived from the resialylated 3H-labeled glycoprotein yielded radioactive 2,3,4-trimethylgalactose indicating that rat liver microsomes are capable of transferring sialic acid to position C-6 of the terminal galactosyl units of desialylated alpha1-acid glycoprotein. No indication was obtained for transfer of sialic acid to other positions. This result is discussed in view of the multiplicity of positions of attachment of sialic acid to galactosyl residues in native alpha1-acid glycoprotein.


The hysteretic properties of glycogen synthase I.

Glycogen-free synthase I from human polymorphonuclear leukocytes is activated by its own substrate, glycogen, in a slow, time-dependent process (hysteretic activation). This lag in response to addition of glycogen depends on the concentration of glycogen, pH and temperature. At pH 7.4 and at a temperature of 30 degrees C, the half-time of activation t 1/2 decreases from 89 min at 0.004 mg/ml glycogen to 6 min at 25 mg/ml. The activation is accelerated by increasing temperature and pH, but is not influenced by enzyme concentration, glucose 6-phosphate, UDP, high ionic strength, EDTA, mercaptoethanol, glucose, sucrose or amylase limit dextrin. The Km for UDP-glucose (0.024 mM) and the activity ratio were unchanged during the activation process. The activation can be described by vt = vf + (vo - vf) e-kt where vt, vf and vo are velocities at times t, O and infinity and k is a complex rate constant. Evidence from ultracentrifugation and kinetic studies is presented to substantiate the hypothesis that the underlying mechanism is a simple biolecular process: enzyme + glycogen in equilibrium enzyme-glycogen complex, with the dissociation constant Ks = 0.003 mg/ml. The hysteretic activation may become rate-limiting during experiments in vitro with synthase. The possibility of a physiological role in glycogen metabolism, perhaps in the form of a concerted hysteresis with H+ is discussed.


Structure of seven oligosaccharides excreted in the urine of a patient with Sandhoff's disease (GM2 gangliosidosis-variant O).

The urine of a patient with Sandhoff's disease (GM2 gangliosidosis-variant O) contains 10--12 N-acetylglucosamine-rich oligosaccharides in high amounts. The structures of seven of these have been determined: beta-GlcNAc(1--2)-alpha-Man-(1--3)-beta-man-(1--4)-GlcNAc; beta-GlcNAc-(1--4)-alpha-Man-(1--3)-beta-Man-(1--4)-GlcNAc; beta-GlcNAc-(1--2)-alpha-Man-(1--6)-beta-Man-(1--4)-GlcNAc; beta-GlcNAc-(1--4)-alpha-Man-(1--6)-beta-Man-(1--4)-GlcNAc; beta-GlcNAc-(1--2)-alpha-Man-(1--3)-[beta-GlcNAc-(1--2)-alpha-Man-(1--6)]beta-Man-(1--4)-GlcNAc; beta-GlcNAc-(1--2)-alpha-Man-(1--3)[beta-GlcNAc-(1--2)-alpha-Man-(1--6)][beta-GlcNAc-(1--4)]beta-Man-(1--4)-GlcNAc; beta-GlcNAc-(1--2)-alpha-Man(1)-(1--3)[beta-GlcNAc-(1--2)-alpha-Man(2)-(1--6)]beta-Man-(1--4)-GlcNAc, with additional beta-GlcNAc, with additional beta-GlcNAc-(1--4) on mannose (1) or (2). An unusual oligosaccharide, with a tri-branched beta-mannose, has been characterized as the major component excreted in urine.


Initial stages of the thermal unfolding of yeast phenylalanine transfer RNA as studied by chemical modification: the effect of magnesium.

The early stages of thermal unfolding of the tertiary structure of yeast tRNAPhe have been followed, in the presence and absence of Mg2+, by measuring changes in the chemical accessibility of the bases uracil and guanine. The reagent used in these studies is 1-cyclohexyl 3-[2-morpholino(4)-ethyl]carbodiimide methotosylate. 32P-labelled tRNA was used so that the points of modification could be examined with ribonuclease digestion and established fingerprinting techniques. Two regions of protection of Mg2+ have been found. One is within the oligonucleotide U8-A-m2G10 and the other is in the vicinity of residue U-59. The tertiary interactions and the D stem are the most readily melted parts of the teritary structure. In the absence of Mg2+ the region of U-59 is the first part of the tertiary structure to become accessible to the reagent. This is closely followed by the opening up of the 'wobble' G-U base pair in the aminoacyl stem. Most of the triple interactions in the augmented D helix are also disrupted early in the melting. The region of intricate interactions between the invariant G-G part of the D loop and the T-psi-C-G loop contains the most stable set of tertitary structure interactions.


The effects of industrial lead poisoning on cytochrome P450 mediated phenazone (antipyrine) hydroxylation.

In a group of ten male adults admitted to hospital with clinical symptoms of lead exposure, phenazone, elimination rates, blood delta-amino-laevulinic acid dehydratase (ALA.D) activity, blood lead levels and haemoglobin were measured. Investigations were carried out before, immediately after and again at least 12 weeks after cessation of CaEDTA (sodium calcium edetate) chelation therapy. Following chelation, phenazone elimination rates were increased as assessed by a decrease in half life and increase in clearance. This was significant, both immediately after and 12 weeks after cessation of chelation therapy. The change in rate of phenazone metabolism was associated with improved clinical status, with lowered blood lead levels and raised haemoglobin and ALA.D activity. The results of the study suggest that the depression in phenazone elimination in lead intoxication is possibly due to depressed hepatic cytochrome P450 levels.


A dose ratio comparison of the interaction between morphine and cyclazocine with naloxone in rhesus monkeys on the shock titration task.

Dose-response curves for morphine (0.5-20 mg/kg) were obtained in 4 rhesus monkeys performing the discrete trials shock titration task. Naloxone (5-500 microgram/kg) uniformly produced a dose dependent, parallel shift of the morphine dose-response curves to right. Plots for the 4 animals of the Log (dose ratio--1) versus --Log (naloxone) revealed that the line had a slope of -0.96. The value of the pA2 was 7.2. Similar experiments were carried out in two rhesus monkeys using cyclazocine. Naloxone (50-1000 microgram) similarly produced a rightward dose dependent, parallel shift of the cyclazocine dose response curves. Unlike the results obtained with morphine, the pA2 for naloxone obtained with cyclazocine was 6.3 and the slope of the dose ratio line was -1.6.


A direct method for studying 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) production by brain in awake animals.

A direct method for measuring the rate of production of neurotransmitter metabolites by the brain of awake monkeys is described. The method utilizes a coupling of a measure of cerebral blood flow with the determination of the difference in concentration of the metabolite under study in arterial and internal jugular bulb blood. A consistent veno-arterial difference for 3-methoxy-4-hydroxyphenethylenglycol (MHPG) has been found. The concentration of MHPG in blood obtained from the right and left venous outflows from brain were not significantly different indicating that blood from either the right or left internal jugular bulb may be used with this method. The rate of production of MHPG by the brain of thw awake monkey is estimated to be 24.1 ng/100 g brain/min. The rate of MHPG production by brain is increased by the administration of piperoxan and decreased by clonidine. Using the experimentally determined rate of production of MHPG by brain and extrapolating to the human it is suggested that a substantial fraction of the total body production of MHPG in man occurs in brain.


Indirect sympathomimetic agents and cerebral blood flow and metabolism.

The effects upon cerebral blood flow (CBF) and oxygen consumption (CMRO2) of the infusion into the internal carotid artery of tyramine and amphetamine were investigated in 24 anaesthetized baboons. The infusion of tyramine was without effect upon CBF and CMRO2 at normocapnia, even at concentrations which significantly raised arterial blood pressure. However, marked reductions in cerebral blood flow were noted at hypercapnia during the infusion of tyramine (2.5 X 10(-7) moles/kg/min). The infusion of amphetamine (7.5 X 10(-10) moles/kg/min) resulted in significant increases in CBF (32%) and CMRO2 (37%). However, an increased concentration of amphetamine (2.5 X 10(-7) moles/kg/min) significantly reduced CBF (22%) and CMRO2 (20%). It is suggested that amphetamine, by virtue of being able to cross the blood--brain barrier and interact with the cerebral monoamine systems, is able to influence cerebral blood flow by inducing changes in cerebral metabolism, and that the minimal reactivity of the cerebral circulation to the infusion of tyramine is the result of the inability of tyramine to cross the blood--brain barrier.


Polymerization of phenolic intermediates of pesticides by a fungal enzyme.

The fungus Rhizoctonia praticola produces an extracellular phenol oxidase (laccase) which polymerizes phenolic intermediates of various pesticides. The enzyme catalyzes the formation of oligomeric products from halogenated phenolic intermediates of phenoxyalkanoate herbicides and from naphtholic products derived from carbamate insecticides. These findings permit further investigations into the mechanism and role of oxidative coupling leading to the incorporation of xenobiotic compounds into soil organic matter.


Uptake of ferritin from the medium by Tokophrya infusionum.

Tokophrya infusionum, a suctorian, is deprived of a mouth opening. The uptake of ferritin from the medium is accomplished through pits, invaginations of the plasma membrane which are permanent structures. From the pits containing ferritin, flat vesicles are pinched off transporting the ferritin to the cytoplasm.


The influence of anti-theta-globulin treatment on the growth of mastocytoma in mice.

DBA/2 mice were treated with four successive subcutaneous injections of rabbit anti-theta-gamma-globulin followed by the subcutaneous implantation of chemically induced mastocytoma (P-815-X2). Another series of animals received rabbit anti-thymus-gammaglobulin according to the same schedule and still another series of animals served as non-treated controls. A definite augmentation of the tumor growth, as evidenced by the dissemination of the tumor into the spleen, liver and kidney, was evident in the globulin-treated series. Such dissemination was not observed in the control animals, where the metastases were limited to the reginal lymph nodes. The studied gammaglobulins were different in two important respects; the death rate of animals and the frequency of thymic metastases were higher in the anti-theta-globulin series. These findings advocate the conclusion that anti-theta-globulin, prepared against the brain tissue, is the more specific and more potent T-lymphocyte suppressor of these two globulins studied. T-lymphocyte population seems to play an important role in host resistance against experimental neoplasia.


The behavioral toxicology of metals.

Many metals express their toxic actions through behavioral disturbances. Such disturbances most often reflect impairment of central nervous system function, but also may arise from deleterious effects in other systems. Numerous factors influence behavioral toxicity. Uptake into brain obviously is important; the chemical form of the metal (e.g., inorganic versus organic) and route of exposure are key determinants of brain penetration. Species differences in toxicity may arise from differences in kinetics (e.g., blood-brain ratio) and affinity to target brain structures. Developmental stage is still another crucial variable, but the young organism is not necessarily the most susceptible, and nutritional considerations confound the standard paradigms. Furthermore, parametric variations of behavioral functions can no more be ignored than dose-effect functions, a principle exemplified in research on methylmercury. Unwarranted loyalties to traditional psychological tests may be one source of the current dispute about safe levels of lead simply because parametric variations of clearly specified functions are beyond the scope of such instruments.


Foraging patterns of nonhuman primates and the nature of food preferences in man.

1) There are a variety of foraging and dietary patterns among primates; different species have generally obligate food habits. 2) There are a number of convergent dietary patterns among primates that are not taxonomically dependent; closely related species may have very different food habits, while the diets of unrelated forms may be quite similar. 3) At least at a general level, relationships exist between dietary patterns and alimentary tract adaptations. Further comparative studies of the histology of the gut tract of primates in conjunction with detailed and quantitative studies of the food habits of natural populations are needed to determine if more precise dietary/digestive tract relationships exist. Studies of this type should lead to a better understanding of digestive physiology. However, whether we can ever determine the "natural diet" of man by such comparisons, of course, still remains an unanswered question.


Regulation of lymphocyte proliferation and differentiation by macrophages.

In this paper, we consider the role of a macrophage secretory product in promoting thymocyte differentiation, as well as a macrophage-immune T cell interaction that results in augmented secretion of lymphostimulatory factors. When cultured with the thymocyte-differentiating factor (TDF), thymocytes show a physiological increase in H-2D and K, decreased sensitivity to lysis with anti-TL and complement, and acquisition of responsiveness in the mixed lymphocyte culture. Development of the mature phenotype requires 2 to 3 days of culture and, once attained, is stable. The induced antigenic changes do not require cell division. The activity demonstrated by TDF, which is not attributable to interferon and cannot be replaced by 2-mercaptoethanol, is also displayed by normal thymic macrophages themselves. Enhanced secretion of TDF and of a distinct mitogenic protein follows the interaction of macrophages and immune T cells. This interaction is shown to require physical contact of the two cell types and is regulated by products of the I-A region of the major histocompatibility complex.


The use, in diabetic rats and monkeys, of artificial capillary units containing cultured islets of Langerhans (artificial endocrine pancreas).

A unit was constructed that consisted of a core of hollow fibers through which low-molecular-weight substances, such as glucose and insulin, could pass freely but were impermeable to high-molecular-weight proteins, such as antibodies. Islets of Langerhans from normal rats were planted in the space surrounding the fibers, and either blood or nutrient medium was circulated through the fibers themselves. In experiments with animals, the units were attached to the vascular system of diabetic rats and monkeys. Blood glucose concentrations in the rats were reduced to nondiabetic levels within one hour and were maintained for the duration of the experiments. In monkeys the blood glucose level declined from 210 mg./100 ml. to 90 mg./100 ml. in four hours and insulin in the serum rose to 93 muU./ml. in one-half hour. Also, we have found that islets from monkeys cultivated in the artificial endocrine pancreas (AEP) continue to release insulin into circulating tissue culture medium for over eight months.


Comparison of mutagenicity and inducibility of DNA single-strand breaks and chromosome aberrations in cultured mouse cells by potent mutagens.

Induction of 8-azaguanine-resistant mutation, DNA single-strand breaks, and chromosome aberrations by treatment with ethyl methanesulfonate (EMS), N-methyl-N'nitro-N-nitrosoguanidine (MNNG), nitrogen mustard hydrochloride (HN2), or 4-nitroquinoline 1-oxide (4-NQO) was compared under similar experimental conditions using cultured FM3A cells from a C3H mouse mammary carcinoma. All the chemicals induced 8-azaguanine-resistant mutations and chromosome aberrations in a dose-dependent manner; a good correlation between the two activities was demonstrated. An alkaline sucrose gradient method demonstrated that DNA single-strand breaks were induced only in a high dose range by 1- and 24-hr treatment with the chemicals. One exception was that a 1-hr treatment with HN2 produced an anomalous sedimentation pattern. These data suggest that caution is necessary for the interpretation of results obtained by the alkaline sucrose gradient analysis, and that examination of mutagenicity and chromosome aberrations is more feasible as screening procedures for potential mutagens than analysis of DNA single-strand breaks.


Transformation of Bacillus subtilis and Escherichia coli by a hybrid plasmid pCD1.

The gene thyP3 from Bacillus subtilis bacteriophage phi 3T was cloned in the plasmid pMB9. The resulting chimeric plasmid, pCD1, is effective in transforming both Escherichia coli and Bacillus subtilis to thymine prototrophy. The activity of the thyP3 gene product, thymidylate synthetase, was assayed and found to be 9 times greater in a transformed strain of Escherichia coli than in a phi 3T lysogen of Bacillus subtilis. The physical location of restriction sites has been determined for two related plasmids pCD1 and pCD2. Hybridization studies clearly indicate that the plasmid gene responsible for Thy+ transformation is the gene from the bacteriophage phi 3T. The lack of restriction in this transformation process is consistent with our previous studies using bacterial DNA in heterospecific exchanges indicating that the nucleotide sequence surrounding the gene is the dominant factor in determining interspecific transformation.


Effect of site-specific endonuclease digestion on the thyP3 gene of bacteriophage phi 3T and the thyP11 gene of bacteriophage rho11.

phi 3T and rho11 are closely related bacteriophages of Bacillus subtilis which can "convent" thymine auxotrophs to thymine prototrophs upon infection or transfection. The effect of endonuclease digestion on the ability of both bacteriophage and prophage DNA from phi eT and rho11 to transform for thymine prototrophy was determined. All of the endonucleases tested: BamHI, Bg/II, BsuRI, EcoRI, HindII+ III, and HpaII reduced the efficiency of thyP transformation to an equal extent in prophage and bacteriophage DNA. Only HpaII completely abolished thyP transformation. The reduction in transformation with BamHI, Bg/II, BsuRI, EcoRI, and HpaII fragments is size related. The thyP transforming fragments generated by these endonucleases are potentially clonable.


Increased longevity of Drosophila melanogaster with diiodomethane.

Diiodomethane at a concentration of 10 microgram/ml increased the median life span of the fruit fly, Drosophila melanogaster, by 29.3%. Decreased flight activity was associated with increased longevity when the flies were reared and maintained on diiodomethane. Rearing only on diiodomethane increased life span by 13.6% and eliminated the decreased-flight-activity phenomenon. The effects of iodine, iodoform and hydriodic acid on longevity were also examined.


Incorporation, after single and repeated application of radioactive labelled DH-ergot alkaloids in different organs of the cat, with special reference to the brain.

1 h after intravenous administration, 3H-DH-ergot alkaloids showed maximal uptake in the range of 10(-5)M in various visceral organs, and of 10(-7)M in most parts of the CNS of the cat. The clearance function in both groups of tissues was logarithmical linear, the slope of the straight line for the parts of the CNS being considerably flatter. Repeated administration of these drugs demonstrated a higher retention in the CNS than in the other organs. The single-dose level in the CNS is reinforced and, in contrast to liver and lung, maintained for at least 24 h.


Changes in the rat electrocorticogram following administration of two dihydrogenated ergot derivatives.

Dihydroergotoxine mesylate (DHET; active substance of Hydergine) and dihydro-beta-ergosine altered the sleep-wakefulness cycle of the rat by increasing wakefulness and decreasing slow wave and rapid eye movement sleep. In addition, power spectrum analysis indicated that, in comparison with placebo, DHET increased total power. Dihydro-beta-ergosine increased relative power in the theta-(4--8 Hz) and in the fast beta-(30--40 Hz) bands of ther electrocorticogram. The alterations in the sleep-wakefulness cycle and in the distribution of power in the rat electrocorticogram are discussed as possible indices of changes in alertness and attention.


Biochemical and behavioural effects of hypoxic hypoxia in rats: study of the protection afforded by ergot alkaloids.

The conditioned avoidance response and the cerebral levels of dopamine and noradrenaline have been studied in control rats and in rats submitted to a hypobaric hypoxia. A protection against the effects of hypoxia was induced by both dihydroergocornine (20 microgram/kg) and dihydroergocryptine (100 microgram/kg), and the noradrenaline level did not decrease. This stabilization of cerebral noradrenaline level seems to be the main protection factor observed.


Setting priorities in health services.

A growing recognition that our resources are not limitless has made it necessary for us to abandon the concept of unlimited production and consumption and to set priorities among the goods and services that society is to provide. The author argues that determining priorities in the area of health services should be done on a rational basis, with increased emphasis on primary prevention.


Epilepsy and folic acid.

With 15 cases of epilepsy as the subject, studies were made of the therapeutic effects of folic acid on psychiatric symptoms and clinical seizures. Folic acid proved effective for a part of chronic and prolonged psychiatric symptoms shown by epileptic patients and brought on slight improvement in hyperexcitability, aggressiveness, bad humor and slowness of psychomotor activities. Improvement in mood was also observed. However, incidence of clinical fits increased in three cases. Electroencephalograms showed the desynchronizing phenomenon following oral administration of folic acid. Appearance or increase of spikes was noted in six cases. The epileptic group showed significantly low folic acid level in both serum and spinal fluid compared with the non-epileptic group. When folic acid was administered orally to the epileptic group, the serum folic acid level increased easily but the folic acid level in spinal fluid hardly increased.


Periodic EEG patterns observed in two cases with partial seizures.

Two cases with partial seizure and periodic EEG pattern were reported. Case 1. A 74-year-old woman reveal typical periodic lateralized epileptiform discharges (PLED's) on the right hemisphere. The patient was semicomatous with mild jaundice and epilepsia partialis continua in the left lower limb. Postmortem examination revealed a main metastatic carcinoma of pancreas head origin in the right parietooccipital region. In the right hemisphere, the cortical structures were relatively preserved, but the white matter including the frontal lobe was swollen and its demyelinating changes were observed diffusely. The PLED's might result from an anatomical or functional severance of the cerebral cortex from normal connections with deeper structures. Case 2. A 61-year-old woman, with idiopathic hypoparathyroidism showed partial complex seizure. The EEG revealed an anterior temporal spike focus and slowing in the right hemisphere, corresponding with repetitive seizures of about one minute duration and with several minutes interval. An interictal periodic EEG pattern appeared in the right anterior and mid-temporal region. No cerebral abnormalities were found with other neurological examinations including brain scanning, carotisangiogram, and echoencephalogram. The periodic pattern was assumed as subclinical focal seizure discharges from the right anterior temporal deep structures.


Polygraphic study on the clinical seizures induced during nocturnal sleep.

The subjects of this study consisted of 17 epileptic patients with clinical seizures during all-night sleep recording (the seizure group) and another 17 epileptic patients without clinical seizures (the control group). The results obtained were as follows: 1) The 50-90% out of total clinical seizures were induced in non-REM sleep, while a few clinical seizures were induced in REM sleep. The number of clinical seizures in sleep stage of higher activity level increased as the incidence of clinical seizure during all-night grew. 2) In the seizure group REM sleep could not be detectable during all-night in five cases out of 17 cases, while we could not find cases lacking REM sleep in the control group. This difference between two subject groups was statistically significant (P less than 0.025). 3) As to focal spike group, the spike discharge incidence of total sleeping time and of each sleep stage was higher respectively in the seizure group than that in the control group, and particularly in St.1, St.2 and REM sleep the figure of the discharge incidence was found significantly higher in the seizure group than that in the control group (P less than 0.05). We discussed on above-mentioned results, and we emphasized particularly that REM-sleep suppresses clinical seizures, although non-REM sleep induces clinical seizures.


Six and 14/sec positive spikes with widespread distribution over the scalp as a seizure pattern.

Five patients with either "diencephalic" or "brainstem" epilepsy or "diencephalosis" were examined EEGcally during the course of their hospitalization. The significant changes were detected, mainly by diphenhydramine activation as to the distribution of the 6-14/sec positive spike pattern on the scalp. When the patients were relatively free from their symptoms, the positive spikes were recorded partially on only one or very fre areas, and when they were experiencing clinical paroxysms, the spikes were detected diffusely in almost all areas of the scalp. Chronological EEG observations paralleling the clinical course of illness of a paroxysmal nature are unpopular. However, the necessity of efforts to record EEG's of patients during clinical paroxysms seems important and has been briefly discussed concerning the question as to whether the 6-14/sec positive spike pattern is an abnormal EEG change or perhaps a "seizure pattern".


Mental dullness associated with left frontal continuous focal discharge.

(1) The EEG in a patient of refractory epilepsy showed the unilateral continuous focal discharge in left frontal area repeatedly for 11 days (2) Stupor and/or mental dullness associated with the change of EEG was the clinical manifestation. (3) A brief discussion was made about the possible pathophysiological mechanisms.


[Therapy in bronchial asthma].

A division into two main groups is made: causal and symptomatic treatment. The first group includes elimination and avoidance of allergens and the specific hyposensitization according to own experiences. The second group is divided into medicamentous treatment (bronchodilatators, DNCG, corticosteroids, secretolytics, antibiotics, tranquilizers) and into a nonmedicamentous treatment like physiotherapy, climate therapy and psychotherapy.


The effects of TRH on prolactin, plasma renin activity, water and electrolyte excretion in normal males.

The effect of TRH induced secretion of TSH and prolactin (hPrl) on plasma renin activity (PRA), water and electrolyte excretion, was studied in 7 normal males before and after an intravenous injection of 2 ml normal saline or 200 microgram TRH. Plasma hPrl and TSH rose significantly (p less than 0.01) in all 7 subjects after TRH but not after saline injection. No significant differences in the hourly excretion of sodium, potassium and free water clearance were noted before and after either saline or TRH injection. Mean PRA values of the 7 subjects were similar after either the 2 ml saline of TRH injection. Our results indicate that despite a correlation between basal hPrl and sodium excretion as well as free water clearance, acute TRH induced elevation of hPrl is not associated with changes of urinary sodium and potassium excretion, free water clearance and PRA in normal males. These findings provide some evidence against a direct osmoregulatory role of hPrl in man.


[Direct immunological identification of proteins following electrophoretic separation in polyacrylamide micro-gradient gels and the effect of detergents on immunoprecipitation (author's transl)].

Methods for direct immunological identification of single protein components after fractionation of a protein mixture in microgels are described. Protein mixtures were separated with high resolution in polyacrylamide microgradient gels and transferred after electrophoresis into agarose layers containing suitable antisera. Monospecific as well as polyvalent antisera were used. The formation of immunoprecipitates could be observed within approx. 1 h. Immunoprecipitates are also formed in the presence of sodium dodecylsulfate or other detergents, thus allowing immunoreactions to be performed with water-insoluble proteins. Staining of the proteins in the gels did not completely inhibit the immunoreaction, while dansylation of proteins had no effect. The influence of different detergents e.g. sodium dodecylsulfate, Triton X-100, Brij 99, np-40 and urea, as well as different reducing agents e.g. mercaptoethanol, dithiothreitol, thioglycolic acid, on two-dimensional microdiffusion was also studied. When suitable concentrations of these compounds were used, the formation of immunocomplexes was observed within approx. 1 h. This technique can also be applied to immunoreactions with water-insoluble proteins dissolved in detergents.


[Bacteria and resistance patterns in bacteriuria of hospitalized patients (author's transl)].

During different periods in 1976 and 1977 the bacteria of hospitalized patients were selected at random in significant bacteriuria. The species determination was carried out exactly and the susceptibility to beta-lactam-and aminoglycoside antibiotics was investigated using the quantitative tube dilution test. The bacterial spectrum of 941 isolated strains is shown in Table I. E. coli was found in 50% only. The spectrum of bacteria is different in the various hospitals, caused by regional phenomenons of nosocomial infections (Table II). The sex distribution (Table III) shows that mostly E. coli and Strept. faecalis are isolated from women, and Klebsiella sp. from men. The difference is significant. May be there exists a sex specificity for some bacteria. The sensitivity tests include the antibiotics Ampicillin, Carbenicillin, Ticarcillin, Mezlocillin, Azlocillin, Cefalotin, Cefamandole, Cefazolin, Gentamicin, Tobramycin and Amikazin (Table IV). Different sensitivity patterns could be established because of the exact species determination.


Effects of autologous plasma on lymphocyte transformation in malaria and in acute protein-energy malnutrition. Comparison of purified lymphocyte and whole blood cultures.

Phytohaemagglutinin (PHA) induced lymphocyte transformation in whole blood and in purified lymphocyte cultures was investigated in Gambian children with acute Plasmodium falciparum malaria or with acute protein-energy malnutrition (PEM). Responses of purified lymphocytes cultured in the absence of autologous plasma were normal, with one exception. Autologous plasma depressed the response of purified lymphocytes to a low dose of PHA in several malaria and PEM patients. In whole blood cultures of 1 day and of 3 day duration, responses of several children with malaria or PEM were less than those of control children. Responses were not related to absolute lymphocyte counts. In 3 day, but not 1 day, cultures from control and malarious children, responses were inversely proportional to neutrophil counts. Cultures of whole blood and of purified lymphocytes in autologous plasma gave comparable results in 58 of 70 patients.


Enhanced resistance to Listeria monocytogenes in splenectomized mice.

Mice infected with live Listeria monocytogenes intravenously from 1 week to 3 months following splenectomy exhibit greatly enhanced antibacterial resistance to this micro-organism as compared to normal or sham-splenectomized mice. They survive a dose of Listeria 100 times higher than is the LD50 of this parasite for normal mice. Initially, the same number of viable micro-organisms lodge in the livers of splenectomized and normal hosts. However, within 24 h after infection, the number of viable Listeria which can be recovered from the livers of splenectomized animals is significantly reduced in comparison with control mice. This effect of splenectomy is transient and gradually disappears spontaneously within 3 months following splenectomy. Enhancement of anti-listerial resistance in splenectomized mice can be abrogated by the transfer of normal spleen cells. The presence of a normal splenic cell population that controls macrophage activation is postulated.


Lymphocyte surface IgD and IgM in Macaca monkeys: ontogeny, tissue distribution and occurrence on individual lymphocytes.

A proportion of lymphocytes in blood, spleen and lymph nodes of nonhuman primates had immunoglobulin on their surfaces detectable by fluorescent antibody to human IgM and IgD. The majority of the individual lymphocytes having either IgM or IgD on their surfaces possessed both classes of immunoglobulin. Lymphocyte surface IgD was capped independently of surface IgM on the same cell when incubated at 37 degrees with anti-IgD. Lymphocytes with surface IgM and/or IgD were present in blood at birth and the percentages over the first 6 months of life were increased compared to older monkeys. A corona of cells faintly positive for both IgM and IgD was observed around germinal centres of both lymph nodes and spleen.


[Glucose and fructose utilization and insulin requirement in postoperative parenteral feeding].

Clinical observations during postoperative feeding (observation period 10 to 30 days) are reported. We compared glucose and fructose intake at different intake rates to glucose and fructose urinary output. Insulin admixture per 100 g of glucose is not constant. It can be progressively reduced following operation.


[FGX 70% as an energy carrier in severe heart failure].

A case of decompensated heart failure due to a combined myocardial malformation is presented, in which intravenous nutrition with restricted fluid intake became necessary. Employing a 70% solution of FGX combined with an amino acid solution following the KE pattern the already catabolic metabolism was reversed and a loss of weight avoided. Over a long-term period of application (three weeks) no side effects due to this solution were noted. The necessity of continuous supervision of the FGX 70% infusion is stressed.


[Is ethanol suitable as an energy carrier in infusion therapy?].

Using experimental animals and human volunteers the suitability of ethanol for parenteral nutrition was investigated. The most evident disadvantage is the relatively low metabolic capacity for intravenous ethanol. A steady state was attained in the animal experiment with the low dose of 0.2 g/kg bodyweight per hour. No indications were found, however, that intravenous ethanol would contribute to the development of a lactate acidosis. Merely a short time before death because of hyperalcoholemia (5-7% blood concentration) an increase in lactate concentration is found which might be caused by circulatory collaps. Additionally, the effect of intravenous ethanol seems to be of minor importance. Small effects were found only in the experimental animal as well as in volunteers. A very strong inhibition of galactose metabolism was found to be a significant effect of ethanol application. Despite of similar metabolic reactions neither the application of xylitol nor of sorbitol causes an inhibition of galactose metabolism. These results might be interpreted as signs for compartmentalisation of the different metabolic reactions in the cytoplasma of the hepatocytes. According to the results of these investigations ethanol merely evokes small acute metabolic effects. The low metabolic capacity and the established hepatotoxicity are indications for a restrained use of ethanol in parenteral nutrition.


[The behavior of prealbumin, retinol binding protein and the immunoglobulins during 3 weeks of nutritional rehabilitation].

A significant improvement in the protein status of twelve malnourished geriatric patients was achieved during a three-week daily supplementation of the hospital diet by 9 g essential amino acids (eight classical essential amino acids plus histidine). This was especially evident in the doubled serum concentration of prealbumin and retinol-binding protein. The changes of total serum protein and hemoglobin were much less distinct. The immunoglobulins IgA, IgM and IgG remained unchanged for the entire observation period.


Passive protection by antitoxin in experimental Pseudomonas aeruginosa burn infections.

The protective effect of intravenously administered rabbit antitoxin serum was studied in lethal Pseudomonas aeruginosa burn infections in mice. Survival after infection with 2 median lethal doses of a toxigenic, low-protease-producing strain (PA103) was enhanced in antitoxin-treated mice, as compared with controls that had received anti-bovine serum albumin serum (P = 0.0004). Survival time was prolonged in other antitoxin-treated mice infected with toxigenic, high-protease-producing strains (PA86 and PA220, P = 0.0003 and P = 0.01, respectively). In contrast, antitoxin had no protective effect in mice challenged with a nontoxigenic strain (WR 5, P = 0.57). There were fewer viable bacteria in blood and liver of antitoxin-treated mice than in those of anti-bovine serum albumin-treated controls after infection with toxigenic organisms, whereas there were no significant differences between the two groups after challenge with the nontoxigenic strain. These data suggest that P. aeruginosa exotoxin A contributes to lethality in this burn infection model, and this effect is diminished by passive immunization with antitoxin.


Anomalous high native resistance to athymic mice to bacterial pathogens.

Congenitally athymic (nude) mice exhibited an anomalous high resistance against infections with the facultative intracellular parasite Listeria monocytogenes and other bacterial pathogens. Protection against lethal infection was demonstrated to result from the presence of naturally occurring activated macrophages in the reticuloendothelial organs of the nude mice. This was exemplified after intravenous challenge by enhanced bacterial clearance from the blood and augmented bacterial killing in the spleens and livers of nude mice as compared with immunologically competent control mice. Resident peritoneal macrophages of nude mice were not activated in terms of phagocytic, bactericidal, or tumoricidal potential. The development of activated fixed tissue macrophages appears to arise as a result of the T-lymphocyte deficiency since thymus implantation abrogated the enhanced resistance of nude mice. Antibiotic elimination of intestinal bacteria also modified resistance to bacterial infection, indicating a role of environmental factors on macrophage activation. Several possible mechanisms leading to macrophage activation and heightened resistance to infection in nude mice are offered.


Hyperthermia and human leukocyte functions: effects on response of lymphocytes to mitogen and antigen and bactericidal capacity of monocytes and neutrophils.

It has recently been demonstrated that fever, or hyperthermia, results in enhanced survival of lizards infected by Aeromonas hydrophila. In the present study, the effects of hyperthermia on certain immune functions were assayed in vitro with purified human leukocytes. Lymphocyte transformation responses to the mitogen phytohemagglutinin and the common antigen streptokinase-streptodornase were enhanced at 38.5 degrees C relative to 37 degrees C whether analyzed according to absolute counts per minute of incorporated tritiated thymidine or according to stimulation indexes. Enhancement of response was not accompanied by acceleration of response. Augmentation of transformation response was generally not seen at 40 degrees C; incubation at that temperature was associated with decreased cellular viability. Significant, though small, increases of the bactericidal capacity of polymorphonuclear leukocytes at 40 degrees C relative to 37 degrees C were shown at 1 h with Escherichia coli, Salmonella typhimurium, and Listeria monocytogenes, but not with Staphylococcus aureus. Mononuclear phagocytes did not show enhanced bactericidal capacity at the elevated temperature with any of these organisms in this in vitro system. Hyperthermia may enhance certain host defense mechanisms and warrants further study.


Cellular immunity to bacteria: impairment of in vitro lymphocyte responses to Pseudomonas aeruginosa in cystic fibrosis patients.

Lymphocyte responses to the mitogens phytohemagglutinin and concanavalin A and to Streptococcus pyogenes, Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa were evaluated in patients with cystic fibrosis and in normal individuals. Lymphocyte proliferation in vitro was stimulated by gentamicin-killed whole bacteria, and the proliferative response was measured by [3H]thymidine incorporation. The in vitro lymphocyte responses to antibiotic-killed bacterial reached maximum thymidine incorporation after 5 days in culture and followed a unimodal dose-response curve for each of the bacteria studied. A significant specific incapacity to respond to P. aeruginosa was detected in cystic fibrosis patients with advanced clinical disease.


Development of antitoxin with each of two complementary fragments of Clostridium botulinum type B derivative toxin.

Two fragments with molecular weights of 111,000 (fragment I) and 59,000 (fragment II) were separated from each other by gel filtration of dithiothreitol and urea-treated, trypsinized derivative toxin (molecular weight, 170,000) of the proteolytic Okra strain of Clostridium botulinum type B on a column of Sephadex G-200 (superfine) with a buffer containing dithiothreitol and urea. Upon removal of dithiothreitol and urea by dialysis, the two fragments reassembled to reconstruct the derivative toxin molecule. Both fragments were immunogenic, and both anti-fragments neutralized type B toxin. The neutralizing activities of both anti-fragment I and anti-fragment II were, however, lower than that of the anti-derivative toxin, suggesting that the molecular integrity of derivative toxin is essential for sufficient production of the neutralizing antibody. The immunological difference found between type B toxin from a proteolytic strain and that from a nonproteolytic strain was ascribed to the antigenic difference of fragment I.


Species specificity of attachment and damage to oviduct mucosa by Neisseria gonorrhoeae.

Neisseria gonorrhoeae colony type 1 were inoculated into organ cultures of oviducts obtained from various animal species. Gonococci rapidly attached to extensive areas of the mucosa of human oviducts (fallopian tubes), entered the mucous-secreting cells, and caused histological damage to the tissues. In addition, 2 to 4 days after infection there was complete loss of ciliary activity. In contrast, gonococci attached very scantily or not at all to the mucosa of rabbit, porcine, or bovine oviducts. However, the organisms multiplied in the medium of these organ cultures and were located sometimes in the base of mucosal cells and in large numbers in the submucosa. Despit this, there was no histological evidence of damage, and at least 7 days after infection ciliary activity was maintained equally as well as it was in uninfected control cultures. The host specificity of N. gonorrhoeae appears to be determined, at least in part, by a markedly diminished ability of the organisms to attach to and damage the genital mucosa of nonhuman species.


In vitro guinea pig leukocyte reactions to Rickettsia rickettsii.

The presence of cell-mediated immunity in Rocky Mountain spotted fever-infected guinea pigs was determined by two in vitro assays: whole blood lymphocyte transformation (LT) and macrophage migration inhibition. Increased LT was detected as early as 1 week in guinea pigs infected with Rickettsia rickettsii and treated with oxytetracycline and was detected by two weeks in infected but untreated guinea pigs. Elevated LT was still detectable at 10 weeks postinfection. Guinea pigs vaccinated with killed rickettsiae failed to develop lymphocyte responsiveness; however, there was a rapid lymphocyte response after challenge with live organisms, suggesting potentiation by the vaccine. Vaccinated guinea pigs that were challenged and then treated with antibiotic failed to develop LT, suggesting that infection is necessary for the observed response. Macrophage migration inhibition was detected in both infected and vaccinated guinea pigs by 1 week after infection, but this response was no longer detected 4 to 5 weeks later. Antibody appeared at 2 to 3 weeks postinfection and was present at low levels through week 10. Antibody-treated rickettsiae were phagocytized and destroyed by guinea pig peritoneal macrophages, whereas normal serum-treated rickettsiae replicated and eventually destroyed the phagocytes.


Biologic assessment of copper-containing amalgams.

In order to reduce creep and avoid marginal fractures in amalgam restorations, new alloys containing higher proportions of copper have been introduced. Fillings of these materials were placed in cavities prepared in the deciduous teeth of monkeys or placed in polyethylene tubes and implanted subcutaneously in rats. Conventional silver/tin alloys and zinc oxide eugenol cement were used as reference materials. Despite limitations due to the varying depths of cavities and the small number of animals involved it was concluded that the high copper alloys caused more severe pulp damage than the other materials studied. In the implantation studies many of the high copper specimens were exfoliated before the end of the experimental period. It is concluded that in deep cavities these materials require the use of a non-toxic base or lining material although as they are commonly used in young children's teeth the placement of linings and the isolation of the cavity pose problems.


The difference in effect of predosing with antiallergic compounds between the rat PCA model and the monkey asthma model. Comparison of the effects of PRD-92-Ea and disodium cromoglycate.

DSCG and PRD-92-Ea showed tachyphylaxis in the rat PCA test when a large intravenous dose (40 mg/kg of DSCG and 20 mg/kg of PRD-92-Ea) was given 30 min before administering intravenously the expected effective doses at the time of antigen challenge. This predosing led to a marked loss of effectiveness. Cross-reacting tachyphylaxis was also demonstrated in this model. Predosing rats with DSCG led to a great loss of effectiveness of a subsequent expected active dose of PRD-92-Ea and predosing with PRD-92-Ea had the same effect in preventing the antiallergic action of a subsequent dose of DSCG. The Rhesus monkey (Macaca mulatta) did not exhibit this phenomenon of tachyphylaxis. PRD-92-Ea and DSCG were given intravenously 30 min before and the same dose of 20 mg/kg repeated just before Ascaris suum challenge in the Rhesus monkey asthma model with no loss of their expected effectiveness.


Studies on corynebacterial precipitinogens common to Mycobacteria, Nocardiae and rhodochrous.

Ten strains of Corynebacterium were analyzed by means of the comparative immunodiffusion technique employing reference precipitation systems from strains of Mycobacterium, Nocardia and the rhodochrous taxon. The test strains had precipitinogens in common with the reference strains. Two of the intergenerical cross-reacting precipitinogens revealed were labelled x and y. Two other precipitinogens (alpha,beta), earlier found to be common for strains of mycobacteria, nocardiae, and rhodochrous, were not demonstrated in the corynebacterial strains, thus indicating a qualitative or quantitative serological difference between Corynebacterium and the other taxa. It was furthermore shown that the corynebacterial preparations reacted with antisera against ribosomal 30S fractions from mycobacteria. Common precipitinogens in ribosomal preparations from mycobacteria, nocardiae, rhodochrous, and corynebacteria are discussed.


A precipitate adsorption on surface technique: a combination of immunodiffusion and thin-layer immunoassay.

A new technique--precipitate adsorption on surface--is described. The technique implies a combination of immunoprecipitation in gel and diffusion-in-gel-thin-layer immunoassay. The principles of the technique are illustrated by a series of model experiments.


Rh antibodies produced by an isoimmunized chimpanzee; reciprocal relationship between chimpanzee simian-type isoimmune sera and human anti-Rho reagents.

An isoimmune chimpanzee serum was found to contain, in addition to expected antibodies of the simian-type specificity anti-Lc, a fraction of anti-Rho specificity, as proved by parallel tests with standard human anti-Rho sera as well as by absorption experiments using human and chimpanzee red cells. On the other hand, the two human anti-Rho sera tested in parallel were found to contain not only antibodies of specificity anti-Rho but also antibodies capable of detecting Lc specificity on the chimpanzee red cells. The reciprocal relationship between human and chimpanzee isoimmune sera constitutes the first example of symmetrical cross-reactivity between closely related species. The new source of anti-Rho reagents is expected to contribute additional information on the human Rh-Hr blood group system.


Scintigraphy in diagnosis of osteomyelitis of the jaws.

The symptoms of an acute osteomyelitis of the jaws are often uncharacteristic, and typical radiographic changes usually do not appear until after the first weeks of disease. Even when such changes are established it is difficult to distinguish an active infectious disease from lasting changes due to a sterilized osteomyelitis. Scintigraphy with bone-seeking radiopharmaceuticals appears to be a valuable diagnostic technique. A case of osteomyelitis of the mandible is reported.


Computer utilization in an oral biopsy service.

In order to improve our knowledge about the biological activity of oral lesions, a computer-based system of oral biopsy data recall has been established. The program is utilized in eight United States dental schools and is adaptable to almost any oral biopsy service with an available computer. This article deals with the implementation of the program at Washington University School of Dental Medicine.


Postoperative jaw pain--floctafenine versus dihydrocodeine.

A double-blind single dose trial was made of floctafenine 200 mg versus dihydrocodeine 30 mg in 100 patients complaining of jaw pain following oral surgery under general anaesthesia. There was no statistical difference between the two analgesics for the whole group, but dihydrocodeine was better for the relief of more severe pain.


Extraosseous calcifying epithelial odontogenic tumor (Pindborg tumor).

A 20-year-old man presented with a painless enlargement of the maxillary gingiva with no bone involvement. Microscopic examination with special stains confirmed the diagnosis of a clear cell variant of a calcifying epithelial odontogenic tumor (Pindborg tumor). This is the second reported case of such a variant in an extraosseous location.