[Erythrocyte magnesium and HLA groups].

Red blood cell Magnesium levels were determined in 351 unrelated male subjects with known HLA groups. Significantly lower values are observed among subjects carrying BW 35 allele. Furthermore, significant variations are also noted according to the constitution of HLA-B groups with respect to BW 4 and BW 6 public specificities. This observation brings to light other variations among the subjects carrying B 8 allele.


Clinical correlations between long-term (IgE) and short-term (IgG S-TS) anaphylactic antibodies in atopic and 'non-atopic' subjects with respiratory allergic disease.

The sera of atopic and non-atopic persons with allergic pulmonary disorders were examined for long-term sensitizing, IgE and short-term sensitizing heat-stable (S-TS) antibodies which were present separately or together in the sera of some patients sensitive to antigens such as budgerigar serum proteins and Aspergillus funigatus. In fourteen atopic patients with extrinsic asthma, six had both types of antibody to common allergens, and of nine non-atopic patients with crytogenic (intrinsic) asthma, four had only heat-stable short-term sensitizing antibodies. The sera of atopic subjects with type I prick test reactions and positive RAST's, showed specific IgE antibody by baboon PCA tests to budgerigar serum proteins, A. funigatus, Timothy grass pollen extract and hen egg extract, and not to Dermatophagoides farinae, possibly because of naturally occurring mite antibodies in the baboon. The sera of non-atopic asthmatics, who had given negative prick test but positive immediate, dual or late intracutaneous tests, and only late asthmatic reactions, contained precipitins in most cases and gave little or no RAST reaction. On baboon PCA these sera contained either, S-TS antibody alone, or S-TS plus long-term sensitizing antibody, or long-term sensitizing antibody alone. Some of the sera with long-term sensitizing antibody contained blocking antibody which could diffuse away in the 24 hr delay for the baboon PCA test and could also be responsible for the negative RAST. Tests with insoluble anti-IgE immuno-adsorbents on two sera from persons sensitive to aspergillus confirmed that the S-TS activity was not due to IgE, and on two sera with negative RAST and negative prick tests to budgerigar serum antigens confirmed that the 24 hr monkey PCA responses were due to IgE.


The effect of lisuride hydrogen maleate, an ergot derivative on anterior pituitary hormone secretion in man.

The effects of single oral doses of 0.2 mg of lisuride hydrogen maleate, a semisynthetic ergot derivative, on serum levels of prolactin (PRL), growth hormone (GH), thyroid stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), cortisol and blood glucose were studied in six normal males. Lisuride effectively inhibited basal PRL secretion as well as the PRL response to TRH given 3 h later. In addition, the drug raised basal GH levels and decreased basal and TRH stimulated TSH secretion. No significant differences between lisuride and control were observed in basal LH and FSH, LHRH stimulated gonadotrophins or in cortisol. Drowsiness was noted by all subjects, one became nauseated and another vomited, 60 and 90 min respectively after administration of lisuride. No changes were seen in pulse rate and blood pressure. The endocrine effects of lisuride were attenuated by the prior administration of the dopamine antagonist metoclopramide. These results suggest that lisuride acts as a long-acting dopamine agonist and that therefore this drug could be of therapeutic use in hyperprolactinaemic states and acromegaly.


Metoclopramide stimulation: a test of growth hormone reserve in adolescent males.

A comparison was made between the growth hormone (GH) response to metoclopramide ('Maxolon'--Beecham Laboratories) and insulin induced hypoglycaemia in thirty-five short adolescent males. Both tests initially caused adequate release of GH from the pituitary gland in 86% of those subjects who had normal GH reserve. The peak growth hormone responses of the two tests were similar in magnitude and were strongly correlated (r = 0.80, P less than 0.001). Both tests raised serum GH to a similar degree in twenty-nine out of the thirty-five boys (83%), but four boys who responded satisfactorily to hypoglycaemia failed to respond to metoclopramide (MCP) stimulation, and two boys who failed to respond to hypoglycaemia responded satisfactorily to MCP stimulation. MCP stimulation does not require prior preparation of the patient and is relatively free of side effects. Consequently, it is suggested that MCP stimulation may be a useful 1 hour out-patient test for growth hormone deficiency in this relatively common group of patients.


Chronic dopamine receptor stimulation using bromocriptine: failure to modify thyroid function.

Administration of 2.5 mg bromocriptine (Parlodel), a dopamine agonist, on two occasions to six normal volunteers did not alter the plasma TSH response to an i.v. injection of 100 micrograms TRH, but significantly (P less than 0.01) blunted it after 200 micrograms. Chronic bromocriptine treatment (7.5--50 mg/day) of fifteen acromegalic subjects failed to influence basal plasma TSH or the response pattern to 200 micrograms TRH. The thyroxine Binding Index (TBI) and the levels of T3 and T4 were not modified by treatment. These results indicate that chronic dopaminergic therapy with bromocriptine does not alter thyroid function.


Free thyroxine (FT4) and free triiodothyronine (FT3) in autonomous thyroid nodules.

Total and free thyroid hormones (T3, T4, FT3 and FT4), TSH and its response to TRH were determined in sixty-three patients affected by autonomous thyroid nodules: mean concentrations of free T3 (FT3) were significantly higher in hot nodules (suppressing extranodular tissue on the scan) as compared to warm ones, even in those cases where total T3 and T4 were within normal ranges (hot nodules, group as a whole: 8.8 +/- 3.5 pg/ml; warm nodules: 5.3 +/- 1.2; hot nodules with normal total T3 and T4 concentrations: 7.5 +/- 3). Also the clinical condition of thyrotoxicosis appeared to be correlated with FT3 concentrations (toxic patients, group as a whole: 9.6 +/- 4.0 pg/ml; euthyroid patients: 6.8 +/- 3.1; toxic patients with normal values of T3 and T4; 8.3 +/- 2.8). On the contrary the correlation of total and free thyroid hormone concentrations with the response of TSH to TRH was not significant.


Function of the hypothalamo-hypophysial-thyroid axis in chronic renal failure.

Hypothalamo-hypophysial-thyroid function has been studied in twenty-five patients with chronic renal failure. Eight were receiving conservative treatment, nine peritoneal dialysis and eight haemodialysis. All were clinically euthyroid. Total thyroxine (T4) and triiodothyronine (T3) levels were reduced but free T4 levels were normal, while free T3 was reduced in patients with the most severe renal failure. It is suggested that the binding of thyroid hormones by the transport proteins is reduced and that peripheral conversion of T4 to T3 is impaired in renal failure. The thyrotrophin response to thyrotrophin-releasing hormone (TRH) is reduced in renal failure but this reduction is probably independent of alterations in thyroid hormone metabolism. Growth hormone was released by TRH in seven of the patients studied, possibly as a result of protein malnutrition.


Lumbar kyphosis in Hunter's disease (MPS ii).

Although radiological involvement of the lower dorsal and upper lumbar vertebrae is common in the severe form of Hunter's disease (MPS II), there are reports in the literature that clinical kyphosis does not occur. We report a boy with marked clinical kyphosis in whom the diagnosis of MPS II was proved by demonstrating a severe deficiency of serum and leucocyte iduronate-sulphate sulphatase and an accelerated incorporation of radiosulphate into his cultured fibroblast glycosaminoglycans, which could not be corrected by the product of other typed reference MPS II cells. The existence of several other genetic diseases, sometimes complicated by kyphosis, was excluded by assay of fibroblast lysosomal enzymes.


Interaction of amino acids with glycl-L-leucine hydrolysis and transport in monkey small intestine.

1. There are two saturable transport processes in the monkey small intestine for glycyl-L-leucine, one with Vmax. 1 mumol min-1 g-1 wet weight of tissue and an affinity constant (kt) of 5 mmol/l, and the other with Vmax 3.9 mumol min-1 g-1 wet weight of tissue and kt 33 mmol/l. 2. Glycyl-L-leucine uptake is inhibited by a wide variety of amino acids, although to a variable extent. The inhibition was shown to be competitive with leucine used as the representative amino acid. Phenylalanine, methionine, alanine and leucine are the most potent in their inhibitory action. 3. The effect of various amino acids on the hydrolysis of glycyl-L-leucine by particulate and cytosol fractions of monkey small intestine was studied. All the amino acids, except glycine, proline, alanine and glutamic acid, inhibit both the particulate and cytosol glycyl-L-leucine hydrolase activities. In general, the cytosol enzyme is more susceptible to amino acid inhibition than the particulate enzyme. 4. There is no correlation between the effects of amino acids on glycyl-L-leucine uptake and hydrolysis of glycyl-L-leucine by either particulate or cytosol fraction.


Muscle protein degradation in premature human infants.

1. Myofibrillar protein degradation has been measured by the rate of 3-methylhistidine excretion in premature infants weighing between 635 g and 1295 g. Analyses were made in conjunction with 1--3 day nitrogen balance studies. 2. In 56 balance studies in 36 infants, total muscle protein breakdown varied between 0.70 and 2.58 (mean 1.05) g day-1 kg-1 body weight while the percentage of total muscle protein degraded each day was between 3.3 and 8.3 (mean 4.8). 3. Both total and fractional rates of protein breakdown showed highly significant negative correlations with nitrogen retention but no relationship to total energy input. 4. Protein degradation was higher than average in infants who were losing weight at the time of the balance study, lower in infants who were gaining weight and higher in those who died within 2 weeks of the analysis. 5. Myofibrillar protein breakdown was not different between infants fed orally and those receiving total parenteral nutrition. 6. Generally the effects of nitrogen and evergy status on muscle protein degradation in the premature infants are different from changes reported in adult human beings or adult rats. We suggest that this difference may be a consequence of the very limited energy reserves of the premature infant.


The skin, the eye, and systemic disease.

Both the skin and the eye are easily accessible structures which may reflect systemic disorders. Certain systemic conditions frequently involve the oculocutaneous structures and will be discussed herein. The practitioner must be aware of these disorders, and the interrelationship of the skin and the eye.


Disseminated gonococcal infections (DGI).

Neisseria gonorrhoeae infects superficial membranes of the eyes, oropharynx, genital tract, and rectum prior to dissemination. Gonococcal isolates cultured from patients with disseminated gonococcal infections (DGI) show resistance to serum bacteriolysis, are very sensitive to penicillin, and have characteristic growth requirements for certain amino acids. DGI is characterized by recurrent chills and fever, polyarthralgias and/or polyarthritis (with effusions), and skin lesions. The skin manifestations of DGI include vesicopustules, hemorrhagic bullae, and petechiae. These lesions are found over the juxta-articular areas of the hands (extensor surfaces) or the feet (dorsal aspects). Focal and disseminated gonococcal infections are now treated with several types of penicillin regimens, tetracycline, or spectinomycin.


Simultaneous scabies and gonococcal infection.

A case is presented of an unusual complication arising in a man with scabies and gonococcal urethritis: the secondary infection of excoriated genital lesions by Neisseria gonorrhoeae. This occurred after he had occluded his genitals with a plastic wrap.


A simplified technique to prepare fungal specimens for scanning electron microscopy.

A simplified technique to prepare fungal specimens for scanning electron microscopy is described and discussed. Fixation in either 6% glutaraldehyde or 2% Os04 (both unbuffered aqueous solutions), yielded good results. The minimum fixation time in OSO4 was 2 h, in glutaraldehyde 4 to 5 h. Chemical dehydration with 2-methoxyethanol or 2,2-dimethoxypropane proved to be useful since it considerably reduced the preparation time. Because of the relatively few changes of reagent solutions during the whole process, the fungal specimens were less disturbed without much loss of material. The preparation technique described has been applied to specimens of various fungal groups with good results.


Antibiotic compatibility and stability in a parenteral nutrition solution.

Eight antibiotics, alone and in selected combinations, were evaluated for stability and compatibility in a protein hydrolysate parenteral nutrition solution. Samples were stored under varying conditions and evaluated at 12-hour intervals over a period of 24--48 h. Compatibility and stability were assessed by quantitative bacteriologic assay, pH determinations and visual inspection. In most cases, antibiotics were compatible and stable over the entire study period. Carbenicillin, methicillin in combination with gentamicin, and tobramycin in combination with cephalothin or methicillin, exhibited a gradual loss of antibacterial activity after 24 h. These results indicate that the antibiotics studied may be administered in protein hydrolysate parenteral nutrition solutions. This mode of therapy offers a means of combating infection, while maintaining a nutritional source for host defences, tissue repair, and growth.


Induction of prematurely condensed chromosomes from testicular cells of the mouse.

Mitotic CHO cells and mouse testicular cells were fused with polyethylene glycol. Several types of prematurely condensed chromosomes were observed. From chromosome morphology it was possible to determine that most of the PCC represented mouse cells. Labeling of either the CHO cells in vitro or the testicular cells in vivo with 3H-TdR prior to fusion also demonstrated that the PCC were derived from the mouse cells. In some PCC, 20 chromosomes could be counted, the haploid number for mouse. It is assumed that these PCC were induced in mouse spermatid nuclei.


Additional metabolic correlates of 1-alpha-acetylmethadol (LAAM)-induced cellular tolerance and physical dependence: the role of the hepatic microsomal electron transport system.

The microsomal cytochromes P-450 and b5 and the enzymes of the hepatic microsomal electron transport system (HMETS) including NADPH-cytochrome c reductase and NADPH oxidase activities were monitored in male ICR mice (25-30 g) over a six-day period following the repeated oral administration of 7, 14 and 28 mg/kg per day of l-alpha-acetylmethadol hydrochloride (LAAM) or an equivalent volume of water. Cytochrome P-450 and the microsomal enzyme activity of NADPH oxidase were maximally elevated (three- to four-fold above control values) by the third day of LAAM administration (28 mg/kg per day). These elevations not only correlated on a dose and a temporal basis with previously reported microsomal activities including LAAM N-demethylase, but also with the reported development of cellular tolerance and physical dependence following an identical regimen of LAAM. In addition, NADPH-cytochrome c reductase and cytochrome b5 increased in activity and content, respectively, after the repeated administration of this narcotic. However, the enzyme activity was first significantly elevated after only a single dose of LAAM. Thereafter, it showed a pattern of induction similar to that of NADPH oxidase. In contrast, cytochrome b5 was only elevated after the last repeated dose. The significance of these findings is discussed in some detail relative to the generation of the two analgesically active metabolites of LAAM.


[The psychotropic action of TRH].

During a double-blind trial about using TRH perfusions, the authors didn't established any antidepressive effect. On the other hand they observed an anxiety reaction under a 1,200 microgram in perfusion. The study of the basic level of T3, T4, T.S.H. and Prolactin corroborated the normality of the biological evaluation among the depressed. No difference of the hormonal response under T.R.H. was established depending on different types of depression. The authors reported that the Prolactin respons is higher among the subjects for whom the T.R.H. was the more distressing.


Episodic and TRH induced growth hormone release in primary hypothyroidism of man and rat.

In 27 hypothyroid subjects studied over 20 to 120 minutes, the concentration of serum growth hormone (GH) was variable with the amplitude and frequency of the secretory patterns similar to those reported by others for normal individuals. Serum GH, after the administration of thyrotropin releasing hormone (TRH) did not differ from values observed as spontaneous surges, in contrast to a consistent increase in thyrotropin and prolactin. Episodic secretion of GH persisted in thyroidectomized rats and did not differ significantly from that present in intact controls. It is concluded that episodic GH secretion is not abolished in primary hypothyroidism and that TRH is not a constant GH secretagogue in human subjects with hypothyroidism.


5'-Methylthioadenosine phosphorylase from Caldariella acidophila. Purification and properties.

The occurrence of 5'-methylthioadenosine phosphorylase in Caldariella acidophila, a thermophilic bacterium growing optimally at 87 degrees C, is reported. It represents the first example in prokaryotes of a phosphoryolytic cleavage of the thioether. The reaction products, purified by ion-exchange chromatography, have been identified as 5-methylthioribose-1-phosphate and adenine by several analytical procedures. The enzyme has been purified to homogeneity in 32% yield by using DEAE-cellulose and hydroxyapatite chromatography, gel filtration and isoelectric focusing. The enzyme shows a high degree of thermophilicity, its temperature optimum being at 93 degrees C; furthermore no loss of activity is observable after exposure for 1 h at 100 degrees C. The kinetic data indicate a sequential mechanism of the reaction. The apparent Km values are 0.095 mM for 5'-methylthioadenosine and 6.1 mM for phosphate. The specificity of the reaction is rather strict. Experiments performed with analogues of the substrate, i.e. 5'-methylthioinosine, 5'-dimethylthioadenosine sulfonium salt, 5'-n-butylthioadenosine, 5'-isobutylthioadenosine, 5'-isobutylthioinosine, adenosylhomocysteine, 5'-thioethanoladenosine, adenosine, indicate the relevance of the adenine amino group and the sulfur in thioether form in the binding to the enzyme protein.


Isolation, characterization and localization of the proteinase B inhibitor IB3 from Saccharomyces carlsbergensis.

A heat-stable polypeptide has been detected in Saccharomyces carlsbergensis which inhibits specifically proteinase B from yeast. This proteinase B inhibitor IB3 differs substantially in chemical, physical and antigenic properties from the earlier described proteinase B inhibitors IB1 and IB2 from yeast. The inhibitor IB3 has been purified from S. carlsbergensis and appears to be homogeneous by disc gel electrophoresis and sodium dodecyl sulfate gel electrophoresis. The molecular weight has been estimated at 11 500, with no evidence for the existence of subunits. The amino acid analysis shows the absence of tryptophan. No compounds other than amino acids could be detected. The isoelectric point is 4.6. The inhibitor is not affected by incubation with proteinase B but is inactivated by proteinase A and carboxypeptidase Y from yeast and by trypsin from bovine pancreas. The proteinase B inhibitor association constant was calculated to be 3.3 x 10(9) M-1 and the enzyme inhibitor complex is stable at 25 degrees C in the pH range 5--10. The inhibitor does not exhibit immunological cross-reactivity with IB1 and IB2. After centrifugal fractionation at 40 000 x g of a metabolic lysate from spheroplasts the inhibitor was found to be localized in the supernatant, i.e. the extravacuolar soluble fraction.


Purification and properties of alcohol oxidase from Poria contigua.

1. Alcohol oxidase (alcohol:oxygen oxidoreductase) was purified 22-fold from the brown rot fungus Poria contigua. The final enzyme preparation was homogeneous as judged by polyacrylamide gel electrophoresis, and by sedimentation in an ultracentrifuge. The molecular weight was calculated to be 610000 +/- 5000 from sedimentation equilibrium experiments. Electrophoresis in sodium dodecylsulfate gels and electron microscopic analysis indicate that the enzyme is an octamer composed of eight probably identical subunits, each having a molecular weight of 79 000. The enzyme contains eight mol FAD/mol as the prosthetic group. 2. This alcohol oxidase oxidizes not only methanol but also lower primary alcohols (C2-C4), 2-propin-1-ol and formaldehyde. The apparent Km value for methanol is 0.2 mM, and that for formaldehyde 6.1 mM. Sodium azide was found to be a competitive inhibitor with respect to methanol. 3. The enzyme from the fungus Poria contigua is immunologically different from the alcohol oxidase isolated from the methanol-utilizing yeast Candida boidinii. Furthermore antiserum raised against this enzyme did not cross-react with the alcohol oxidase from the white rot fungus Polyporus obtusus.


Requirement for ribosomal protein BM-L11 in stringent control of RNA synthesis in Bacillus megaterium.

A spontaneously occurring thiostrepton-resistant mutant of Bacillus megaterium has been shown to yield ribosomes lacking protein BM-L11, a protein immunologically related to Escherichia coli ribosomal protein L11. Here we have demonstrated that the mutant strain has acquired the relaxed phenotype and is unable to synthesise guanosine tetraphosphate and pentaphosphate in vivo. Ribosomes from the mutant strain are unable to support the synthesis of these two compounds in vitro, but this deficiency can be overcome by re-addition of purified protein BM-L11 to the ribosomes. Thus protein BM-L11 appears to be indispensable for the synthesis of guanosine tetraphosphate and pentaphosphate; the implications of this observation are discussed.


Kinetic study of a phosphoryl exchange reaction between fructose and fructose 1-phosphate catalyzed by the membrane-bound enzyme II of the phosphoenolpyruvate-fructose 1-phosphotransferase system of Bacillus subtilis.

A phosphoryl exchange reaction between fructose 1-phosphate and fructose was found to be catalyzed by a membrane preparation isolated from Bacillus subtilis. The regulation of the biosynthesis of the activity in the wild type as well as in the regulation mutants fruB closely correlates with that of the membrane-bound enzyme II of the phosphoenolpyruvate fructose 1-phosphotransferase system which is known to mediate the transmembrane vectorial phosphorylation of fructose. The computed analysis of the kinetic data shows that the mechanism of the enzyme II is ping-pong, i.e. that a phosphoryl-enzyme intermediate occurs in the reaction. The apparent dissociation constants of the enzyme II/fructose 1-phosphate complex and of the phosphoryl enzyme II/fructose complex are estimated. The value of the standard free energy of the hydrolysis of the bond between the phosphoryl moiety and the enzyme suggests a covalent bonding. This intermediate is assumed to occur in the physiological functioning of the enzyme which utilizes the phosphocarrier protein HPr as phosphoryl donor. The exchange reaction is competitively inhibited by high fructose concentrations: this indicates that the same site of the enzyme binds fructose and fructose 1-phosphate, this site being accessible to fructose on the external side of the membrane when the enzyme is phosphorylated.


Hydrolysis of aryl beta-D-glucopyranosides and beta-D-xylopyranosides by an induced beta-D-glucosidase from Stachybotrys atra.

The induced beta-D-glucosidase from Stachybotrys atra hydrolyzes aryl beta-D-glucopyranosides and aryl beta-D-xylopyranosides by the same basic two-step mechanism. In the first step the aglycon group is split of with simultaneous formation of an enzyme-glycosyl complex. In the second step this intermediate complex reacts with water yeilding beta-D-glucose or beta-D-xylose. For beta-D-xyloside hydrolysis each of the two steps is partially rate-controlling, whereas for beta-D-glucoside hydrolysis the second step is rate-limiting. The enzyme is inhibited by high concentrations of substrate and the exact rate-concentration equation is a second-order equation. 1-Thio-beta-D-glycopyranosides with an aromatic aglycon inhibit the reaction in both a competitive and non-competitive way. A tentative mechanism is proposed to explain all types of inhibition. In this mechanism substrates and inhibitors with an aromatic aglycon group bind through hydrophobic forces to the 'aglycon subsite' of the intermediate enzyme-glycosyl complex. Binding of the second substrate molecule or of the inhibitor to this complex does not prevent the reaction of the glycosyl moiety with water, it only decreases the rate of the second step.


Sensitization of bleached Stentor to far UV.

Stentors are more sensitive to far UV-induced delay of oral regeneration following bleaching of their UV-absorbant cortical pigment granules. This finding supports a subcortical location of UV-sensitive sites.


Structure, synthesis and orientation of microfibrils. VI. The role of ions in microfibril deposition in Oocystis solitaria.

The action of a series of chelators, cryptates and ionophores on microfibril deposition and the presence of cortical microtubules in Oocystis solitaria has been investigated. Having a potent inhibitory effect on cellulose synthesis were the calcium ionophores A 23187 and X-537A, the flourescent calcium chelator chlorotetracycline and the cryptates 211 and 221. Only at unphysiological concentrations, e.g. 100 mM or more, were the chelators EDTA and EGTA effective in completely inhibitory cellulose synthesis. A reduction in the rate of cellulose synthesis was observed with the sodium-selectiv ionophore dianemycin. This partial inhibition was independent of the ionophore concentration. Without effect on microfibril deposition were the potassium-selective ionophore valinomycin and cryptate 222. In all cases, whether cellulose synthesis is blocked or not, none of the above agents prevented the reassembly of cortical microtubules when applied during the recovery from colchicine treatment. Destruction of cortical microtubules through the calcium ionophore may be achieved, but only when additional (2 mM) calcium is added to the culture medium.


Insensitivity of ciliary outgrowth in situ by Stentor to far UV.

Outgrowth of membranellar cilia in situ by the ciliate protozoan Stentor coeruleus is not affected by either far UV or by postirradiation exposure to cycloheximide, while UV does affect the outgrowth of membranellar cilia during the more elaborate process of oral regeneration in this ciliate, and cycloheximide prolongs the UV effect. These results suggest that direct damage to outgrowing ciliary shafts cannot explain the UV sensitivity of oral regeneration.


Recent memory in aged non-human primates: hypersensitivity to visual interference during retention.

The effect of irrelevant visual information presented during retention of recent memory was investigated in young and aged monkeys. The monkeys were required to remember the location of a visual stimulus over short durations, during which time, on certain trials, irrelevant visual stimulation was presented. It was found that although the young monkeys performed as well with or without the irrelevant stimulation, the aged monkeys were significantly impaired when irrelevant stimulation was presented. Thus, these data provide direct support for the notions that aged subjects suffer a decreased ability to suppress visual stimuli from interfering with accurate behavior, and that this disability contributes to the memory impairments reported with old age. When considered with previous research in humans and non-human primates, these results suggest that this disability to suppress sensory interference may reflect a general effect of aging which may contribute to many other age-related behavioral impairments. Finally, it was suggested that the striking similarities of the behavioral profile now established for the aged monkey to that of younger monkeys suffering destruction of the frontal cortex (and anatomically related subcortical sites) offers the heuristic possibility that these two syndromes share a common neurological etiology.


Anticlotting properties of fragments D from human fibrinogen and fibrin.

It appeared from our previous studies that Ca2+ concentrations comparable to those occurring in blood protect the C-terminal part of the gamma-chain remnants of fibrin(ogen) fragments D against further plasmin attack. This study shows that purified fibrin(ogen) fragments D formed in the presence of Ca2+ ions have anticlotting activity in vitro, whereas shortening of the gamma-chain remnants leads to loss of such activity.


Effects of gastrointestinal hormones on fasting gallbladder storage patterns in man.

Gallbladder storage and emptying patterns were studied in fasting normal subjects by a duodenal perfusion technique using indocyanine green as a biliary marker. Fasting gallbladder storage patterns were very variable but a more uniform biliary output with net storage of about 40% of the biliary marker was observed during a simulated interprandial state (2--4 h after meals) produced by a low dose intravenous infusion of secretin and caerulein. With this background hormonal stimulation, infusion of bovine pancreatic polypeptide to achieve physiological interprandial levels promoted further gallbladder storage of bile. Bovine pancreatic polypeptide produced storage by a major effect on the gallbladder rather than on the liver, common bile duct or sphincter of Oddi since a reduction of biliary output was not observed during bovine pancreatic polypeptide infusion in cholecystectomized subjects. Bovine pancreatic polypeptide had a separate effect on the pancreas, reducing trypsin output in both normal and cholecystectomized subjects.


Sulphr containing amino acids in chronic renal failure with particular reference to homocystine and cysteine-homocysteine mixed disulphide.

We measured plasma sulphur amino acids in twenty-two patients with chronic renal failure and compared the findings with those obtained in twenty-two normal subjects. In fasting blood (08.00 hours) cysteine-homocysteine mixed disulphide was significantly increased in the renal patients, mean values (+/- SD) being 8.2 +/- 3.4 and 3.1 +/- 1.0 mumol/l respectively (P less than 0.001). The increase was positively correlated with reduced renal function, as assessed by serum creatinine (r = 0.62; P less than 0.01). Homocystine was detected in nineteen patients, the mean concentration (+/- SD) being 1.7 +/- 0.6 mumol/l; it was not found in any normal subject. Methionine levels were not different but there were significant increases in cystine (P less than 0.001) and taurine (P less than 0.05) in the patients. Similar values for these amino acids were found in a second blood sample drawn at 16.00 hours. Changes in the other neutral and acidic amino acids measured were in agreement with those reported in chronic azotaemia. We concluded that plasma levels of all the principal sulphur amino acids except methionine are elevated in chronic renal failure emphasizing the importance of the kidney in sulphur excretion. Prolonged accumulation of homocysteine and cysteine-homocysteine mixed disulphide may be relevant to the development of accelerated vascular disease in patients with chronic renal failure by producing endothelial damage.


Beneficial effect of practolol in preventing adrenaline-induced systemic and myocardial metabolic changes.

The aim of the study was to investigate whether the beta blocking agent, practolol, is able to modify some of the metabolic and hormonal responses and the local myocardial changes evoked by an excess of adrenaline similar to that seen after acute coronary occlusion. Adrenaline (1.2 micrograms/kg/min) and practolol (1 mg/kg) were infused concurrently to anaesthetized intact dogs for 5 h. Blood free fatty acid and triiodothyronine levels were measured initially and after 2, 4 and 5 h of infusion. At the end of the infusion the myocardium was subjected to biochemical, histoenzymatic and electron microscopic examination. The results were compared with those obtained in dogs infused with adrenaline alone and with saline alone. Practolol reduced the adrenaline-induced increase in free fatty acids and a fall in triiodothyronine in the blood. Myocardial acetate accumulation and ATP decrease were both reduced by practolol. Histoenzymatic and electron microscopic changes were less. These effects of practolol upon systemic and myocardial disturbances induced by the excess of adrenaline indicate that it might be effective in modifying any excessive adrenergic response which may occur in acute myocardial infarction.


Acute dietary effects on plasma lipids, lipoproteins and lipolytic enzymes in healthy normal males.

Diurnal plasma lipids and lipoproteins were studied in twelve healthy young males on corn oil and palm oil diets, respectively. The major triglyceridy. Lecithin-cholesterol acyl transferase, lipoprotein lipase and hepatic triglyceride lipase were also measured. diurnal changes of triglycerides and cholesterol were confined to lipoproteins of d less than 1.006 kg/l. There was a diurnal rise of lecithin-cholesterol acyl transferase activity with corn oil but not with palm oil. Fasting and postprandial postheparin lipoprotein lipase and hepatic triglyceride lipase were similar but there was a significant correlation of postprandial hepatic lipase with postprandial plasma triglycerides on palm oil. Marked diurnal changes of triglyceride fatty acids were observed not only in 'very low density lipoprotein' but also in high-density lipoprotein amounting to approximately one third of total high density lipoprotein triglyceride fatty acids.


Inhibition of fracture healing by indomethacin in rats.

The effect of indomethacin (2 mg/kg/day) on the healing of closed unimmobilized femoral fractures was examined in rats. A standard femoral fracture was produced in 205 male adolescent rats, and three different experiments were done. In a long-term experiment, the rats were treated with either indomethacin or placebo for 29 days and fracture healing followed for a maximum of 91 days. In two short-term experiments, the rats were treated with either indomethacin or placebo for a week and followed for a maximum of 122 days. The effect of age was studied in one experiment. Indomethacin plasma levels were about 1 microgram/ml in the indomethacin-treated animals. In the long-term experiment, indomethacin inhibited fracture healing (P less than 0.006) and increased the angulation between the femur fragments. In the short-term experiments indomethacin inhibited fracture healding (P less than 0.033) and increased the interfragmentary angle as well as fracture instability. All untreated fractures healed within 10 weeks in younger rats (210 g), whereas only 44% healed in older rats (295 g).


Synthesis of fatty acids and cholesterol by liver, adipose tissue and intestinal mucosa from obese and control patients.

Biopsies of adipose tissue, liver and small bowel mucosa obtained from grossly obese and control subjects were used to study absolute rates of fatty acid, cholesterol, and other nonsaponifiable lipid synthesis using glucose as substrate and 3H2O as the isotopic marker. Fatty acid synthesis in subcutaneous adipose tissue expressed on a cell basis was greater in obese than control subjects and was stimulated by a high concentration of insulin (1000 micro U/ml), but not by a lower amount (100 micro U/ml). Fatty acid synthesis in omental adipose tissue exceeded by 3-fold that of subcutaneous fat. Fatty acid synthesis in obese liver was twice that of control liver and 20 times greater than obese adipose tissue. In terms of total organ activity fatty acid synthesis in fat tissue equalled or exceeded that of liver in both obese and control subjects. The cholesterol content of obese adipose tissue 1.86 +/- 0.11 mg/g exceeded that of controls 1.47 +/- 0.07 mg/g. All tissues examined synthesized cholesterol and nonsaponifiable lipids, liver greater than adipose tissue greater than small bowel mucosa. Nonsaponifiable lipid synthesis per gram of adipose tissue or liver was similar in obese and control tissue. The synthesis of total nonsaponifiable lipids including sterols, hydrocarbons and squalene was appreciable in adipose tissue and was approximately 15% of that of liver. However, cholesterol synthesis in the liver exporessed in terms of total organ activity was 50 times that in adipose tissue. The study demonstrates by direct comparison that liver is the dominant cholesterogenic organ in man and also shows that adipose tissue is a significant site of formation of fatty acids and nonsaponifiable lipids.


Capillary permeability in healthy males with different insulin response to glucose.

The capillary permeability in human skeletal muscle, expressed as capillary diffusion capacity (CDC) for 51Cr-EDTA, was determined during exercise with a local clearance method in two groups of healthy male subjects: a younger group with a mean age of 30 years and an older one with a mean age of 58 years. The main finding was that, in both age groups, CDC was significantly negatively correlated to the early phase of insulin response to an intravenous glucose load. No correlation was found between CDC and peripheral insulin sensitivity. CDC was significantly higher in the older age group (P less than 0.01) independent of insulin response, blood flow and body weight. These data indicate that subjects with low insulin response to glucose have a higher capillary permeability than high responders, and that muscle capillary permeability increases with age.


Abnormal cation composition and transport in erythrocytes from hypertensive patients.

Red cell sodium and potassium were determined in 100 untreated subjects with uncomplicated essential hypertension and compared with the values from 908 healthy normotensive control subjects. Red cell sodium concentration (expressed as mmol/l of erythrocytes) was significantly higher in hypertensive than in normotensive subjects. Red cell potassium concentration (in mmol/l of erythrocytes) was not significantly different in the two groups. Passive efflux of red cell potassium into buffered isotonic sucrose solution determined in eight hypertensive and nine normotensive subjects showed a lower potassium efflux rate in the hypertensive subjects. Comparison of active sodium efflux in sixteen hypertensive and fourteen normotensive subjects showed that ouabain-sensitive active sodium efflux was higher in red cells of normotensive than in those of hypertensive subjects.


Distribution of beta-endorphin in normal and schizophrenic human brains.

beta-Endorphin was measured by radioimmunoassay in post-mortem human brains. Samples of brain were taken from five discrete areas, both from control brains and brains of schizophrenic patients. No difference in beta-endorphin levels was found in these two groups of brains. beta-Endorphin was confirmed to be widely distributed in the brain, but there were considerable differences in the concentrations in different areas.


On the contribution of prostaglandin-like substances to the action of bradykinin on intestinal motility and blood flow in canine jejunal loop in situ.

Blood flow and motility were studied in a canine jejunal loop in situ with intact innervation. Bradykinin was administered into a side branch of the supplying artery and indomethacin was infused intravenously 1 h before experiments. In the control group without indomethacin infusion, bradykinin 1-10 nmol/l gradually increased blood flow without significantly altering motility. Higher concentrations of bradykinin (20-100 nmol/l) augmented rhythmic contractions of the intestine. Phasic blood flow decreased during contraction and increased after relaxation, and mean blood flow increased. Bradykinin (0.2-1.0 mumol/l) caused tonic intestinal contractions. Blood flow initially increased but was soon impeded in proportion to the amplitude and duration of the tonic contractions. With intestinal muscle relaxation, blood flow increased to values markedly higher than control. In the group pretreated with indomethacin, blood flow did not increase after bradykinin administration. However, administration of PGE2 produced significant increase in flow, similar to that observed after bradykinin. Acetylcholine or isoprenaline also markedly increased blood flow. Increased intestinal motility caused by bradykinin mechanically impeded blood flow through the intestine, thus masking its direct vasodilating action. The action of bradykinin on the intestinal vascular bed is probably mediated or modulated by endogenous prostaglandin-like substances.


Lactate elimination in man: effects of lactate concentration and hepatic dysfunction.

Lactate elimination was studied in twenty-six healthy volunteers during primed constant lactate infusion or multiple lactate injection tests, at blood lactate concentrations of 1-8 mmol-1. Although lactate elimination fitted a single exponential curve over a 30 min period, a significant correlation between the rate removal constant (KL) and the peak blood lactate concentration (Lphi) was demonstrated: loge KL = -2.43-0.132 Lphi (P = 0.003, r = 0.63, n = 20) This suggests that lactate removal does not follow first order kinetics over a wide concentration range but becomes saturated at relatively low blood lactate concentrations. Estimates of the lactate distribution volume did not differ significantly at different dosage levels, but remained in the range 270-300 ml kg-1. Skeletal muscle uptake accounted for about 26% of the infused lactate load. Seven patients with well-compensated hepatic cirrhosis were compared with a group of six control subjects during primed constant infusion tests. Fasting and steady state blood lactate concentrations achieved were similar in both groups. A significant prolongation in lactate half-life was demonstrated in the cirrhotics (18.8 +/- 1.4 min (mean +/- SEM) compared to 14.7 +/- 2.2 min; P less than 0.02). Since peripheral uptake of lactate in the forearm was similar in the two groups, this suggests that hepatic lactate uptake was impaired, due either to hepatocyte dysfunction or portal diversion.


A rosette assay for the determination of C 1 q receptor-bearing cells.

A rosette assay for the identification of cells with receptors for C 1 q is described. Glutaraldehyde-treated bovine erythrocytes bound C 1 q specifically, and the reagent thus prepared provided a valid indicator for rosette formation mediated by C 1 q receptors. The presence of these receptors on the membrane of a subset of human peripheral lymphocytes (mainly non-G cells) and on B-derived lymphoblastoid cells was confirmed. Rosette formation was dependent on the number of C 1 q molecules bound per indicator cell and was specifically inhibited by soluble native C 1 q and pepsin-resistant C 1 q fragments. These data, together with the reduced binding activity of C 1 r-C 1 s-associated C 1 q, indicated that the C 1 q binding sites for lymphoid membranes are expressed on the collagen-like moiety, C 1 q rosette formation provided a simple new procedure for fractionation of human lymphocyte populations and separation from phagocytes that do not express receptors for C 1 q.


The detection of membrane-associated complement components (C 3 and C 4) on circulating human normal and leukemic leukocytes and on cultured cells with monkey erythrocytes.

Monkey erythrocyte (Mk) rosette formation is described as an exquisitely sensitive method for the detection of complement (C) components on the membrane of human leukocytes. Blocking of the immune adherence receptor on Mk blocked subsequent rosette formation as did pretreatment of leukocytes with antiserum to the C components C 3 and C 4. In vitro C deposition by immune complex formation with normal human lymphocytes enhanced Mk rosette formation, and this could be inhibited with antiserum to C 3. The use of Mk rosette formation revealed that cells from a wide variety of human lymphoid and myeloid leukemias carry membrane-bound C. It was also shown that several lymphoblastoid cell lines, including a T cell line, probably synthesize both C 3 and C 4. Mk rosette formation is not dependent on metabolic activity of the rosetting leukocyte, and it is suggested that this technique will be of value in detecting C deposition in a variety of situations.


MK-771-induced electromyographic (EMG) activity in the rat: comparison with thyrotropin releasing hormone (TRH) and antagonism by neurotensin.

Administered by either intravenous (i.v.) or intracisternal (i.cis.) injections, MK-771 and TRH induced a dose-related increase in EMG activity recorded from the flexor ulnaris muscle in pentobarbital-anesthetized rats. By the i.v. route, MK-771 was 6 times more potent than TRH and with i.cis. administration MK-771 was some 30 times more active than TRH. At equieffective doses of the two peptides, MK-771 exhibited a greater (approximately 3 fold) duration of action than TRH. In unanesthetized, spinally transected rats MK-771 was also more potent than TRH in eliciting EMG activity recorded from the biceps femoris muscle. Substance P, administered by the i.cis route failed to induce EMG activity. Intracisternally administered neurotensin, which did not affect EMG activity by itself, antagonized the actions of MK-771 while somatostatin was inactive in this regard. Neurotensin did not affect the EMG activity induced by physostigmine. While these studies do not delineate the mechanism whereby TRH and MK-771 induce EMG activity, it appears reasonable to suggest that TRH and related peptides, such as MK-771, may have some influence in functional disorders of human muscle.


Motor unit responses in muscles stretched by imposed displacements of the monkey wrist.

Imposed angular displacements of monkey's wrist produce three major peaks of activity (terms M1, M2, and M3 peaks) in the averaged gross EMG activity ot the stretched muscles. The displacements were imposed on monkey's wrist by computer controlled step loads (range 60--540 g). Gross EMG was recorded simultaneously with the activity of single motor units (SMUs) in the stretched muscles. SMUs were identified and separated using a computer "shape-fitting" program. Average response histograms (ARHs) were constructed for each SMU's responses to randomly presented repetitions of up to five different step loads. Eighty-three percent of the SMUs showed a single excitatory response peak that was limited to a time interval corresponding to that of only one of the gross EMG peaks. Despite marked differences in the time courses of the imposed displacements, the time courses of the SMU excitatory responses were maintained. By increasing the background load and hence the tonic firing of the individual SMUs, the histograms show that the long latency of the M2 peak is not due to an inhibitory-excitatory sequence. The SMUs responding at longer latencies (M2 and M3 SMUs) show firing characteristics in keeping with those reported for fast twitch motor units while those of M1 SMUs correlate with those found for slow twitch units. These results establish that the M1, M2, and M3 peaks do not merely represent synchronized oscillatory activity of the motoneurons but largely result from the reflex excitation of separately responding motoneuron "subpopulations", each of which contributes to the generation of only one of the gross EMG peaks.


Disturbance of delayed match-to-sample in macaques by tetanization of anterior commissure versus limbic system or basal ganglia.

Three pig-tailed macaques were trained to select ("match") from a pair of colored images that which they had seen ("sample") and responded to 5--15 s previously. The anterior commissure (AC) and/or its radiation, various loci in basal ganglia, hippocampal formation and "control" areas, (splenium of corpus callosum, precentral gyrus, insular cortex), totalling 40 loci, were each tetanized for 4 s during presentation of the "sample" image, during the delay period, or when the monkey was required to select the "matching" image. For several loci in the hippocampal formation tetanization at any phase of the task reduced "matching" to chance levels and gave evidence of electrical after-discharge; but other comparable hippocampal loci had little or no effect. Response to "sample" or "match" stimuli were absent during tetanization of basal ganglia or anterior commissure. When finally made, upon cessation of tetanization, responses were equally correct for basal ganglia and "control" sites, but for AC were at chance levels.


Compensation of postural reactions to fall in the vestibular neurectomized monkey. Role of the reamining labyrinthine afferences.

The electromyographic (EMG) responses from soleus and tibialis anterior muscles and the monosynaptic H- and T-reflex responses from soleus muscles were recorded bilaterally from conscious baboon while unexpectedly dropping it with unrestricted vision. These responses were recorded either after unilateral vestibular neurectomy (U.N. Baboons) or after bilateral neurectomy performed in one stage (B.N. 1 baboons) and in two stages (B.N. 2 baboons). A positive correlation was found between modifications and development of EMG responses and reflex data. In the U.N. baboons, some differences were observed when comparing data from the H- and T-reflex methods, suggesting that recovery of normal responses to fall is achieved both by means of direct influences on alpha-motoneurons and via the gamma-loop. In the U.N. baboons postural reactions to fall developed in three distinct periods. The first or critical stage showed asymmetrical EMG and reflex responses with increased responses from contralateral soleus muscle and decreased responses from ipsilateral soleus. Opposite effects were recorded from tibialis anterior flexor muscles. The second or acute stage which began around 4 to 7 days after surgery exhibited symmetrical, but very reduced, responses when compared to the control in soleus muscles, and symmetrical, but increased, responses from tibialis anterior muscles. This stage lasted until about the end of the second postoperative week and was followed by the third or compensatory stage during which EMG as well as reflex responses developed towards the control pattern in all tested muscles. Almost normal responses were recorded on both sides 3 weeks after surgery. Only a partial recovery was found in the B.N. 1 baboons, indicating that the contralateral remaining labyrinthine afferences constitute a necessary condition for the full compensation of postural reactions to fall in the case of unilateral vestibular neurectomy. The Bechterew's compensation was obtained in the B.N. 2 baboons. These results are discussed in relation with the general organization of the vestibulospinal pathways and with those concerning development of the postoperative activity at the vestibular nuclei level. A model of vestibular compensation achieved by means of a multisensory substitution process is suggested.


Vestibular nuclei activity in the alert monkey during suppression of vestibular and optokinetic nystagmus.

Single neurons were recorded in the vestibular nuclei of monkeys trained to suppress nystagmus by visual fixation during vestibular or optokinetic stimulation. During optokinetic nystagmus vestibular nuclei neurons exhibit frequency changes. With the suppression of optokinetic nystagmus this neuronal activity on average is attenuated by 40% at stimulus velocities of 40 degrees/s. At a stimulus velocity of 5 degrees/s responses are, under both conditions, close to threshold. For steps in velocity, suppression of vestibular nystagmus shortens the time constants of the decay of neuronal activity from 15--35 s to 5--9 s, while the amplitude of the response remains unchanged. The results are discussed in relation to current models of visual-vestibular interaction. These models use a feedback mechanism which normally operates during vestibular and optokinetic nystagmus. Nystagmus suppression interrupts this feedback loop.


Silymarin, an inhibitor of lipoxygenase.

Silybin (I), silydianin (II) and silychristin (III), the constituents of silymarin, non-competitively inhibit the lipoxygenase from soybeans (EC 1.13.11.12) in vitro.


Silymarin, an inhibitor of prostaglandin synthetase.

Silybin (I), silydianin (II) and silychristin (III), the main constituents of silymarin, inhibit the formation of prostaglandins in vitro. The inhibition is log-linearly dependent on the concentration of the effectors.


Isolation and partial characterization of ovine lactoferrin.

Ovine lactoferrin was isolated by ammonium sulfate precipitation and ion exchange chromatography. Comparative analyses were performed with the bovine protein. Differences in the amino acid compositions and the tertiary structure of the proteins were observed.


Genetic polymorphisms and intrauterine development. Evidence of decreased heterozygosity in light-for-dates human newborn babies.

In 2 independent samples of low-birth-weight infants the proportion of females and homozygotes for a series of polymorphic systems was higher in light-for-dates than in preterm babies. The observation seems to give support to the hypothesis that homozygosity for 'normal' polymorphisms may decrease in general intrauterine growth rate. Since it is known that survival rate is strongly related to birth weight, a correlation between growth retardation and homozygosity may have a major role in the maintenance of such polimorphisms.


A species comparison of 2,4-dinitrotoluene metabolism in vitro.

Postmitochondrial supernatants prepared from livers of mice, rats, rabbits, dogs, and monkeys metabolized 2,4-dinitrotulene. The pattern of metabolites was characterized in both sexes of the species examined. In addition, the pattern of metabolites was altered by varying incubation conditions and pretreating male rats with phenobarbital or SKF 525-A.


Use of fats and oils in child feeding.

The nutritional status of mal- or undernourished children can be improved by increasing their dietary intake of calories. Where this is liable to be restricted by the sheer bulk of the diet, alternative feeding programmes may be called for. A more fundamental solution is to increase the calorie density of the diet by the addition of fat. Cost may, however, be an overriding factor.


Time dependency of a critical effect of EGTA on DNA synthesis in cultures of Swiss 3T3 cells.

In a temporal analysis of the mitogenic response to serum, a critical period has been demonstrated just prior to the onset of replicative DNA synthesis during which transient calcium depletion blocks the subsequent entry of the cells into the S phase of the mitotic cycle. Transient washington of monolayer cultures of 3T3 cells with 2.5 mM EGTA between 6 and 8 h after serum-stimulated initiation of DNA synthesis was found to reduce cell-associated calcium levels and to inhibit thymidine incorporation, whereas similar treatment before (1-5 h) and after (8-9 h) had no detectable effect on either of these parameters when estimated after 21 h incubation. The effects during the chelation-sensitive period were reversed by the subsequent addition of fresh serum.


Calcium and pancreatic beta-cell function. 6. Glucose and intracellular 45Ca distribution.

Glucose stimulates the uptake of 45Ca into beta-cell-rich pancreatic islets isolated from ob/ob-mice. The distribution of the incorporated radioactivity was analysed by labelling the organelles with 45Ca in their cellular environment. The radioactive content of the organelles was measured after homogenization and fractionation of the islets under conditions preventing 45Ca redistribution. The 45Ca taken up in response to glucose appeared essentially in the secretory granule fraction and in that enriched in mitochondria. Modification of the 45Ca loading procedure, involving reduction of the oxygen tension and incubation volume, resulted in the disappearance of the glucose effect on the mitochondrial fraction whereas part of the stimulatory effect on the secretory granules persisted. Buffering of calcium by the secretory granules and mitochondria may be important for regulating the cytoplasmic Ca2+ involved in stimulus-secretion coupling.


Cost-benefit analysis of BCG-vaccination in Austria.

BCG-vaccination in Austria is performed generally in newborn, but only partially in school children. A cost-benefit analysis was performed considering age-dependent immunizations, tuberculosis morbidity, protection rate and duration of protection, costs of vaccination, costs of tuberculosis therapy, frequency of complications due to vaccination and costs for treatment of these complications. This analysis shows an economic balance between costs and benefits with regard to immunication of newborn, i. e., costs of vaccination are approximately compensated by the saved costs of prevented diseases. In contrary vaccination of school children reveals a considerable economic gain. General revaccination of schoolchildren would make BCG-vaccination much more effective in an economic respect.


Cost-benefit calculations of vaccinations against measles and mumps in Austria.

The analysis of combined measles-mumps vaccination in Austria showed that this measure is highly profitable in economical respect. The benefit-cost ratio Qc amounts to 2.65 without and 4.48 with consideration of the so-called "nursing vacation", a one week's vacation which is being granted in Austria to employed mothers for the nursing of a sick child once a year. The benefit-cost difference Dc amounts to AS 672.85 OF 1,681.90 respectively, per child. Twelve years after the beginning of vaccination of 100,000 one year old children per year which corresponds roughly to the birth rate in Austria an amount of 63 mill. AS can be saved, if "nursing vacations" are not considered. This amount will be even 528 mill. AS, if "nursing vacations" are taken in account.


Benefit-cost and cost-effectiveness analysis: theory and application.

Benefit-cost analysis and cost-effectivensss analysis are terms used with increasing frequency by health planners and those concerned with review and evaluation of specific programs. The economic bases for these formal techniques are however often obscured by adaptations of convenience or misapplications of the concepts by biological scientists (and others). This paper reviews briefly the theory of benefit-cost analysis and its potential as a tool in choosing programs of optimum size, of maximum economic efficiency as a given size, and in choosing amongst worthwhile alternative projects. Because of the difficulties of quantification of necessary data and the political nature of many policy decisions, the technique of benefit-cost analysis seldom finds application but cost-effectiveness emerges as a calculus of more practical use and acceptability. Examples are drawn from WHO papers and the medical literature to illustrate the "benefits and risks" of these techniques.


Cost-benefit studies of vaccinations in Finland.

The benefits of vaccination are, in general, recognized. For some diseases these benefits are obvious. When starting or evaluating new vaccination programmes, a more critical approach is needed. Before starting vaccination against measles and rubella in Finland a cost-benefit study was performed. According to those studies the net benefits of each vaccination would be ca. 100 million Finnish marks in 25-30 years. Those benefits not measurable in money value of human life, decrease of suffering, etc., were not included. For the purpose of formulating the national influenza vaccination policy a similar study was performed on influenza. The method used before seemed to be less suitable, however, with certain assumptions the vaccinations against influenza proved to be profitable.


Methods for risk-benefit and cost-benefit analysis of vaccinations.

The basic aim of vaccination is to prevent more severe complications of the respective disease than might be caused by the vaccine itself. Following this idea formulae were developed for calculation of the risk ratio Q and the risk difference D. The following parameters are considered in this formulae: risk of the disease (R), risk of vaccination (r), protection rate (p) and duration of protection (t). Besides, for calculations with partially vaccinated populations the immunization rate "I" has to be considered. A vaccination is beneficial if Q greater than 1.0 and D greater than 0. If vaccinations have proved to be valuable from the medical point of view, additional cost-benefit calculations may be of great importance for socio-economic considerations. Consequently, the above mentioned formulae were modified for calculation of the benefit cost ratio (Qc) and the benefit cost difference (Dc) for monovalent as well as for bivalent vaccines.


Pseudomonas aeruginosa: prevention better than cure?

Pseudomonas aeruginosa is a common pathogen in certain groups of patients. The use of antibiotics in these patients may be associated with toxic side effects, drug resistance and therapeutic failure. Pseudomonas vaccines have been prepared by many workers and one vaccine has been widely used in clinical trials. Administration of this vaccine was associated with a high incidence of toxic reactions. A new polyvalent pseudomonas vaccine has recently been prepared. We report the reactivity of this polyvalent vaccine in healthy volunteers and compare this with the reactivity of the earlier pseudomonas vaccine reported in the literature. The vaccine is at present being used in burned patients and has been associated with a significant reduction in mortality. We suggest that this new polyvalent vaccine has a low incidence of toxic effects and promises a considerable advance upon earlier vaccines.


Carbamazepine serum levels in children with epilepsy: a micro immuno-assay technique.

In part 1 of this study, 26 children with seizures were given 20 mg/kg/day carbamazepine and five developed side-effects. With this initial dose, equilibrium was reached in the serum within four to six days in 25 of the 26 children. The sudden withdrawal of other anticonvulsants did not usually affect the rise of carbamazepine in serum, unless given in high doses. In Part 2 of the study it was shown that satisfactory levels were obtained in the serum of 38 children given carbamazepine either twice or three times daily, but higher levels were obtained with the latter. The lowest carbamazepine serum level associated with complete control of seizures was 6mg/1. Seizure control was comparable whether carbamazepine was given twice or three times daily. Complete control of temporal-lobe seizures was obtained in nine of 20 children, and of grand mal in 10 of 18 children. Serum levels of carbamazepine remained remarkable constant during the follow-up period of between 10 and 30 months.


Phenytoin serum levels in children with epilepsy: a micro immuno-assay technique.

The enzyme multiple immuno-assay technique (EMIT) was used to study phenytoin serum levels in 50 children with seizures. It was found that: (1) a single dose of phenytoin suspension or capsules (5mg/kg/day) produced inadequate serum levels 16 and 24 hours after ingestion, and for this reason single dosage is not recommended; (2) twice-daily dosage of phenytoin suspension or capsules (5mg/kg/day) produced adequate serum levels in most children throughout the 24 hours, and this dosage is recommended; (3) 12 children continued to have seizures but when the dose was increased to 10mg/kg/day six of the 12 obtained control of seizures; (4) phenytoin reached equilibrium in the serum in five days provided the child had not previously been taking phenobarbitone; (5) of 13 children who had been taking phenobarbitone, 10 did not achieve equilibrium of phenytoin in serum for one to four weeks; (6) phenytoin suspension given twice-daily produced satisfactory serum levels provided the bottle was shaken well before dispensing; (7) apart from minor variations, phenytoin maintained its level in serum during the 14 to 30 months follow-up period, whether 5mg or 10mg/kg/day of phenytoin was given.


Mutagenic and DNA-damaging effects of N-alkyl-N-(alpha-acetoxyalkyl)nitrosamines, models for metabolically activated N,N-dialkylnitrosamines.

Mutagenic and DNA-damaging effects of a series of N,N-dialkylnitrosamines monosubstituted at the alpha-carbon with an acetoxyl group were tested in Salmonella typhimurium, Escherichia coli, and Bacilus subtilis in the absence of metabolic activation system. The compounds comprised 8 N-alkyl-N-(acetoxymethyl)nitrosamines (alkyl=methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, or tert-butyl) and N-butyl-N-(1-acetoxybutyl)nitrosamine. All the compounds, except one with a tert-butyl group, gave positive results in these mutagenicity and repair tests. Presumed release of alkyl cations from the corresponding alpha-acetoxy derivatives by hydrolysis and heterolysis caused mutagenic and DNA-damaging effects in the bacteria. Structure-activity correlation of the compounds was noted in these tests and discussed in regard to the mutagenicity with metabolic activation and carcinogenicity of N,N-dialkylnitrosamines. The results support the hypothesis that alpha-carbon hydroxylation is one probable mechanism involved in the metabolic activation of N,N-dialkylnitrosamines.


[Cost benefit analysis of the program for the improvement of perinatal mortality and morbidity in Austria (author's transl)].

A retrospective cost benefit analysis is initiated for the program to improve the perinatal mortality and morbidity in Austria which was started by the Federal Ministry for Health and Environment in 1974. Based on the official registry of birth in Austria the expenses for the intensive maternity care and delivery are calculated. From 1974-1978 the perinatal mortality of 2,514 children was prevented. It is assumed that for each prevented case of perinatal mortality two cases of cerebral damage were prevented. The benefit is calculated as alternative cost. The comparison of cost and benefit showed an approximate balance.


Genetic determination of the developmental program for mouse liver beta-galactosidase: involvement of sites proximate to and distant from the structural gene.

The identification and mode of action of genetic loci that program gene expression during development are important for understanding differentiation in higher organisms. Previous work from this laboratory has identified two patterns for the postnatal development of liver beta-galactosidase among inbred mouse strains: type I, where activity levels remain constant after about 30 days of age, is found in strains DBA/2J, CBA/J, and BALB/cJ, among others; type II, where activity levels increase between 25 and 50 days of age to reach a new adult level, is found in strain C57BL/6J and related strains. It has been shown that the type I vs. type II developmental difference between strains C57BL/6J and DBA/2J is due to variation at a locus, Bgl-t, that maps with the beta-galactosidase complex, [Bgl], on chromosome 9. In the present study, we have confirmed the existence of Bgl-t as a temporal locus within [Bgl] by analysis of both a congenic strain carrying the beta-galactosidase complex of strain CBA/J in the C57BL/6J genetic background and a cross of strains CBA/J and C57BL/6J. The existence of additional temporal loci for beta-galactosidase that segregate independently of the structural gene and participate in determination of the type I vs. type II difference was revealed by analysis of: (1) a congenic strain containing the beta-galactosidase complex of strain BALB/cJ in the C57BL/10Sn background; (2) recombinant inbred lines derived from progenitor strains C57BL/6ByJ and BALB/cByJ; and (3) a genetic cross between strains C57BL/6ByJ and BALB/cByJ. Thus, for these pairs of strains, the type I vs. type II developmental difference is due to variation at a temporal locus (or loci) unlinked to the enzyme structural gene, and not at Bgl-t. These facts, together with information gathered from an examination of the distribution of beta-galactosidase phenotypes among over 100 inbred strains (Breen, Lusis and Paigen 1977), have led us to conclude that the postnatal developmental pattern for liver beta-galactosidase is determined by a set of interacting temporal genes. One of these, Bgl-t, is located within [Bgl], and one or more are separable from [Bgl] by recombination. A possible mode of interaction among the temporal and instructural loci is suggested.


[Combined effect of alkylating compounds on human chromosomes].

A combined effect of thiophosphamide and dipin on chromosomes of unstimulated human lymphocytes was studied in experiments carried out thrice according to the scheme of a complete two-factor experiment. The exposure to the mutagens lasted for an hour, the concentrations being from 3.17 to 22.19 . 10-5 M. After washing a fresh medium with PHA was added to lymphocytes and then they were cultivated during 60 hrs. Both at separate and combined action of tested chemicals the effect observed in all the cytogenetic tests was not subjected to a linear dependence on the concentration of mutagens. With the change in the proportion between thiophosphamide and dipin, given that the summed number of their molecules was constant, the cytogenetic effect was directly proportional to the part of each mutagen in a combined treatment. The analysis of variance and regression analysis of the results obtained as well as the analysis of types of appearing chromosome aberrations and the analysis of distribution of breaks in cells at the combined action showed that, taking into account that the concentration dependences were not linear. the combined effect of thiophosphamide and dipin was additive, without any interaction of individual effects.


[Modelling modification of chemical mutagenesis in human cells. III. Linear index of protection as the standardized criterion of modification].

The effect of substances with radioprotective activity, APAETP 2,3 (aminopropylaminoethylthiophosphoric acid 2,3), APAETP 3,3 and cystaphos, on chromosome aberrations, induced by thioTEPA in the culture of human lymphocytes was investigated. It is shown that the obtained curves "concentration -- effect" for thioTEPA can be described by equations rho = 1 -- e-(KC + alpha)2 and X = E -(KC + alpha)2 --1 for aberrant cells and for chromosome breaks in the presence of the investigated substances. On the basis of comparison of angle coefficients of regression the unificated characteristic of the efficiency of chemical mutagenesis is proposed: the linear protection index (LPI), with generalizes the effect of modificators in chemical mutagenesis.


[Production and study of Bacillus subtilis mutants for genes involved in nucleoside catabolism].

By means of selection for a low thymine requirement the mutants fo thymine auxotrophs for deoxyriboaldolase (dra) and phosphodeoxyribomutase (drm) genes were obtained. Besides the mutants for pyrimidinenucleoside phosphorylase gene (pdp) were olso isolated using selection on the fluorodeoxyuridine resistance. The latter enzyme provides for pyrimidine nucleosides catabolism (thymidine, uridine) in Bacilli, as well as the conversion of exogenous thymine to thymidine in thymine auxotrophs. The data obtained when studying the deo-enzymes activities in various types of the mutants and also under the condition of induction by thymidine and acetoaldehyde are in accordance with the assumption that deoxyriboso-5-phosphate is an inductor of the deo-enzymes in Bacillus subtilis. The genes dra and pdp were tightly linked as it had been shown by the transformation experiments; in contrast, no linkage was revealed between dra and drm or pdp and drm. A secondary mutation (adn), not linked with dra and blocking the ability of bacteria to catabolise adenosine (purine nucleoside phosphorylase activity remains constant) was found in some dra-mutants.


[Radiosensitivity of somatic cells and imaginal disks of male and female Drosohila].

Primary chromosome damages as well as the frequency of spontaneous and X-rays induced chromosome aberrations in Drosophila melanogaster males and females are studied. It is found using cytofluorimetric method that primary chromosome damages in ganglia cells of females and males are the same. In these cells as well as in cells of imaginal discs the frequency of induced chromosome aberrations, except gaps, is considerably higher for females. Ganglia cells of females and males of Drosophila are found not to differ from each other in their proliferation activity. The frequency of morphoses for both sexes is also the same. The assumption is made concerning the role of the non-identical repair in the increased mutability of female somatic cells, which is more intensive in this sex, as well as concerning more intensive identical repair in imaginal discs of females.


Isolation and characterization of recombinant DNA plasmids carrying Drosophila tRNA genes.

Recombinant plasmids carrying Drosophila melanogaster tRNA genes were constructed by ligation of HindIII-cleaved Drosophila DNA to HindIII cut pBR322 DNA. 90 clones were isolated that contained genes for one or more of eleven tRNAs. 43 of the plasmids were characterized by a number of methods: restriction nuclease digestion; agarose gel electrophoresis; hybridization with individual, purified, 125I-labelled Drosophila tRNA molecules and in situ hybridization to Drosophila chromosomes. The results show that several different tRNA genes have been isolated which code for single, specific isoacceptors. The DNAs from 8 plasmids each hybridize to single sites on Drosophila polytene chromosomes. In addition, the data show examples of two different plasmids hybridizing to different loci coding for the same tRNA; this means that we have isolated representatives of tRNA genes which map at widely separated points on the Drosophila genome.


Construction and characterization of E. coli promoter-probe plasmid vectors. I. Cloning of promoter-containing DNA fragments.

Derivatives of the Escherichia coli drug-resistance plasmid pBR316 have been constructed which act as molecular probes for promoter-containing DNA restriction fragments from various prokaryotic genomes. The plasmids, designated pBRH1 and pBRH3B, contain a unique EcoRI restriction site located within the promoter for the tetracycline resistance (Tcr) gene. This site was created by the insertion of a chemically synthesized octanucleotide, containing the EcoRI cleavage sequence, into the HindIII site of pBR316. Base-pair alterations within the Tc promoter produced by this insertion resulted in a substantial reduction (pBRH3B) or elimination (pBRH1) in ability of these plasmids to confer Tc resistance to the host strain. Cloning of EcoRI-cleaved foreign DNA fragments into the EcoRI site of these plasmids allows for the isolation of recombinant transformants with Tcr levels greater than that of the plasmid vector. Further characterization of these recombinant plasmids demonstrates that the Tcr phenotype is dependent upon the orientation of the inserted fragment, but not on the molecular weight. We have concluded that these fragments carry promoters which, in the proper orientation, allow for the transcription of the Tcr gene. The utility of these "promoter-probe" plasmids lies in the ability to select for promoter-containing DNA fragments by insertional activation of the Tcr gene.


Evaluation of the teratogenicity of anticonvulsants.

Evaluation and comparison of the reports on teratogenicity of drugs are very difficult because many fundamental, clinical and social problems exist in the research of congenital anomalies and detection of human teratogens. Since the etiological significance of anti-convulsants has not been established in humans, the following efforts should be made extensively: 1) systematic collection and detailed analysis of more human cases, 2) study on the role of epilepsy and treatment with multiple drugs, 3) investigation on the mechanism of teratogenesis including comparative pharmacokinetic studies in animals and humans.


Effect of triiodothyronine administration on the plasma TSH and prolactin responses to TRH in patients with hypothalamic-pituitary insufficiency.

A study was carried out in 10 patients with multiple pituitary hormone deficiencies to determine the response of thyroid-stimulating hormone (TSH) and prolactin (PRL) to thyrotropin-releasing hormone (TRH) and their suppressibility by treatment with triiodothyronine (T3) given at a dose of 60 microgram/day for 1 week. In 3 patients the basal tsh values were normal and in 7 patients, 2 of whom had not received regular thyroid replacement therapy, they were elevated. The response of TSH to TRH was normal in 6 patients and exaggerated in 4 (of these, 1 patient had not received previous substitution therapy and 2 had received only irregular treatment). The basal and stimulated levels of TSH were markedly suppressed by the treatment with T3. The basal PRL levels were normal in 7 and slightly elevated in 3 patients. The response of PRL to TRH stimulation was exaggerated in 2, normal in 6 and absent in 2 patients. The basal PRL levels were not suppressible by T3 treatment but in 4 patients this treatment reduced the PRL response to TRH stimulation. From these findings the following conclusions are drawn: (1) T3 suppresses TSH at the pituitary level, and (2) the hyperreactivity of TSH to TRH and the low set point of suppressibility are probably due to a lack of TRH in the type of patients studied.


Effect of 5-bromo-2'-deoxyuridine on growth and differentiation of cultured embryonic retinal pigment cells.

Chicken embryo retinal pigment cells cultured for 2 weeks in 1 or 10 microns BrdU accumulate only 25% of the amount of melanin found in controls. Growth is inhibited by 10 microns BrdU but not by 1 micron BrdU. Cells cultured with BrdU had decreased tyrosinase activity and lost the typical epithelial appearance of controls. Equimolar concentrations of deoxythymidine did not prevent the inhibition of melanogenesis due to BrdU but did prevent the growth inhibition of the higher concentration of BrdU (10 microns). Tenfold higher concentrations of deoxythymidine prevented inhibition of epithelial differentiation and melanogenesis. Ultrastructurally, BrdU produced an absence of melanosomes and disruption of the lamellar array of rough endoplasmic reticulum. The perinuclear arrangement of microfilaments became irregular. The cell surface was radically affected as membranes were no longer ruffled and cell junctions disappeared. Melanogenesis is a complex form of differentiated function, involving synthesis of tyrosinase and control of its activity, macromolecular synthesis of the melanosome, and the subsequent synthesis of melanin within the melanosome. BrdU appears to inhibit melanogenesis through a coordinated and simultaneous interference with these processes, suggesting that there may be a "program" of gene activity for melanogenesis that is regulated as a unit.


Primary cultures of hepatocytes on human fibroblasts.

Parenchymal hepatocytes isolated from adult rats were cultured on three types of collagen-containing substrata: collagen-coated plates, collagen membranes and confluent diploid human fibroblasts. Hepatocytes on the latter two substrata maintained characteristic morphology for at least 10 days in culture, whereas degenerative changes (cell death and formation of multinucleated hepatocytes) and growth of nonparenchymal elements were seen after 5 days in cultures on collagen-coated plates. Parallel findings were seen on basal and induced levels of cytochrome P-450 and NADPH-cytochrome C reductase. The basal levels of cytochrome P-450 were not measurable after day 3 in hepatocytes cultured on collagen-coated plates, whereas measurable levels were maintained in the hepatocytes cultured on the other two substrata. Addition of phenobarbital or methylcholanthrene at day 5 in culture caused an increase in cytochromes P-450 and P-448, respectively, only in hepatocytes cultured on collagen membranes and confluent fibroblasts. Analogous results were seen for the enzyme NADPH-cytochrome C reductase. The similarities in performance between hepatocytes on collagen membranes and on human fibroblasts show that a continuous collagen-containing substratum is important for optimal performance of hepatocytes in primary culture. The possible importance of cultures of hepatocytes on human fibroblasts for carcinogenesis studies is discussed.


Immune mechanisms against canine distemper. II. Role of antibody in antigen modulation and prevention of intercellular and extracellular spread of canine distemper virus.

Specific antibody was shown to be highly effective in neutralizing extracellular canine distemper virus (CDV) as well as preventing the intercellular spread of this virus. Thus, relatively low levels of antibody neutralized 1 x 10(5) TCID50 of extracellular CDV and the development of plaques or CPE in Hep-2 and Vero cells respectively could be prevented even when up to 5% of the cells were infected. This inhibition of CPE and virus spread was most pronounced when antibody was added early but could still limit the degree of CPE if added as late as 48 h post-infection. This anti-viral activity was observed in different cell types including canine macrophages, cells normally infected with CDV in vivo. Prolonged exposure of infected target cells to high concentrations of antibody led to redistribution of surface viral antigens and their subsequent disappearance. The possible role of antibody in the defence against, and/or recovery from CDV and the mechanism(s) by which antibody may aid in recovery are discussed.


[Balanced parenteral and oral feeding of underweight newborn infants].

The oral feeding of 50 newborns with low birth weight was combined with infusions of two different amino acid solutions (mother milk-adapted and requirement-adapted), parenteral lipids and glucose. All infants showed a rapid weight gain, the N-balance became positive, hypoglycemic or hyperosmotic reactions were missing. Amino acid imbalances could not be seen, values of glutamic acid, aspartic acid and asparagine differed in both groups just as proline. In management of infants with low birth weight the supplemental application of these amino acid solutions, lipids and glucose has advantages.


[Total and partial parenteral feeding of premature and newborn infants: nitrogen balances and serum amino acid chromatograms].

We report upon 30 critically ill premature and newborn infants (mean birth weight: 2,350 g). In all cases we applied initially total parenteral nutrition with increasing supplies, subsequently partial parenteral nutrition. Donors of nutritive substance and calories were a 6% mother-milk adapted amino-acid solution, a glucose solution 10% and 20% and a 20% lipid emulsion. Serum electrolytes, urea, glucose, serum aminograms and nitrogen balances were determined at regular intervals. Serum aminograms were found altogether acceptable in relation to those of breast-fed newborns and small infants and to normal values, which we evaluated among 45 premature and newborn infants before supplying protein.


[Effect of peripheral venous parenteral feeding on the postoperative protein status].

Following limited abdominal surgery peripheral-venous parenteral feeding was performed in 30 patients: 15 patients (group II) received 0.8 g amino acids and 4 g carbohydrates/kg BW; and 15 patients (group III) 1 g amino acids and 5 g carbohydrates/kg BW. As a control group (I) 10 patients were infused only with water, electrolytes and vitamins. A significant improvement of nitrogen balances was noticed in both groups of patients with parenteral nutrition, and about 90% of the infused amino acids was retained as nitrogen. However, the serum levels of various proteins--albumin, transferrin, pre-albumin and retinol-binding protein--presented no significant changes. There was no evidence that peripheral parenteral nutrition improved postoperative metabolism of plasma proteins. It is assumed that the administered amino acids are probably utilised in peripheral tissues (e.g. muscle, wound-repair) and are, therefore, not or only in low measures available for synthesis of plasma proteins in liver.


[Use of different parenterally administered amino acid solutions with healthy test subjects].

We studied the alterations in the pattern of free serum amino acids during continuous parenteral infusion of 4 different standardised L-amino acid solutions. Nearly for all amino acids, a dose-dependent steady state could be established, usually as early as 30 or 60 minutes after starting the infusion. Amino acid solutions that caused the smallest changes of the amino acid pattern in plasma during infusion produced always the smallest increase of total amino acid nitrogen and the greatest rate of amino acid transfer. So we conclude that these solutions are utilised most effectively.


Periapical surgery.

A retrospective study of 572 teeth treated with periapical surgery was undertaken in order to evaluate the influence of preoperative, operative and postoperative factors in the healing process as well as the operation method used. It was also the aim to assess whether the histophatological diagnosis of biopsies taken at the operation could be correlated to healing. Statistical analyses by the AID method and conventional cross-classification methods were performed. Factors of importance were found to be the extent of the destrucion, the operation method used, the bone surrounding the destruction, the quality of the orthograde root filling, the age of the patient, and the marginal bone buccally. The operation method was of importance in large destructions where root fillings were considered as not having properly sealed the canals, and when treating inflamed cysts. The histopathological diagnosis could not be ascribed any definite prognostic value.


Primary reconstruction of defects in the upper and lower lips following tumor excision.

Three cases of basal cell carcinoma and epithelioma in the upper and lower lips are reported. The defects in the upper lip following tumor excision were repaired with an application of Burow's technique. Martin's method, after modification of Bernard cheiloplasty, was used for the repair of the lower lip defect. The methods proved to be quite effective in providing excellent aesthetic results. No disturbance was noted in the activity of the repaired upper lips. The labial function, however, associated with the orbicularis oris was left impaired in the newly formed lower lip.


Cervico-facial actinomycosis. A retrospective study.

A retrospective investigation of 25 cases of verified cervico-facial actinomycosis recorded in the period 1971--76 is presented. The results have been compared with the findings from a previous examination carried out by one of the authors during 1955--64. A marked increase of cervico-facial actinomycosis was noted. The clinical picture seems to be changing to a more alarming appearance, in agreement with the classical description of this entity. According to this agreement with the classical description of this entity. According to  this a prolongation of the period of treatment was found. Other aspects of the disease are discussed based on the present results. The recommended treatment is still a combination of antibiotic medication and surgical removal of infectious foci.


Attenuated mumps virus therapy of carcinoma of the maxillary sinus.

This paper presents treatment of carcinoma of the maxillary sinus with an attenuated mumps virus. The mumps virus was inoculated into two cases of very advanced carcinoma of the maxillary sinus by local and general injection. Shortly after injection, relief from severe cancer pain and growth inhibition or necrosis of tumor were observed in both cases. In this communication, we discuss a possible mechanism of antitumor effect of mumps virus by utilizing immunologic tests and interferon assay.


Aspiration using prefilled dental anesthetic cartridges.

The purpose of this study was to make clear if aspiration was possible by the non-aspirating technique using non-aspirating cartridges. Four prefilled anesthetic cartridges used in Scandinavia generally were selected for study. The pressure required for aspiration varied between 130--320 mm Hg. In the majority of cases, aspiration did not occur in the pressure of 320 mm Hg. Thus, if the patient has normal blood pressure- the aspiration occurs very seldom by using non-aspirating cartridges.


Treatment of a persistent oro-antral fistula with a posteriorly based lateral tongue flap.

Occasionally an oro-antral communication persists after vigorous standard therapy. This case report demonstrates the successful use of a posteriorly based lateral tongue flap in such a situation.


Changes in bone mass in rat mandibles after tooth extraction.

An experimental study concerning changes in bone mass in trabecular bone of mandibles on rats after extractions of upper molars has been carried out. The material consisted of 32 SPF Wistar rats, fed on Nafag-184 only. Experimental and control groups consisted of eight females and eight males, each group having same average weight with respect to sex at the age of 16 weeks. At this age the upper right molars were extracted on all rats in the experimental group. The rats were sacrificed after 16 weeks. Identical increase in weight within each sex group was found. Microradiograms of two buccal-lingual 100-mu-thick ground sections at a distance of 0.5 mm through the first molar in each side of the mandible were used. Quantitation of bone mass (bone area in percent) of a trabecular bone was done by electronic point counting. No significant difference in bone mass was found between left and right sides in the control group (P greater than 0.50), whereas a significant difference was found between left and right sides in the experimental group (P approximately 0.0001) with lowest mean value in right sides. Conclusively the analysis shows that local reduction in bite force causes osteoporotic changes in trabecular bone of the jaw.


Cultivation of fibroblasts on human teeth. Ultrastructural observations of cells cultivated in multilayers.

The periodontal ligament in a traumatically lost tooth is often destroyed due to drying. In attempts to restore the periodontal ligament, a technique has been worked out for using gingival biopsies as an alternative cell source. A biopsy from the attached gingiva was set up for tissue cultivation. After the establishment of a pure fibroblast culture, cells were repeatedly added to the root surfaces of 12 human teeth from which the cells and the original periodontal ligament had been removed. The teeth were examined in the transmission electron microscope. The root surface of specimens from all 12 teeth was covered with a pelliclelike material arranged in a layered pattern. The cells frequently appeared in multilayers on top of the pellicle. The cells were flattened and appeared elongated in sections. Areas of close proximity between cells and the pellicular material were seen and were interpreted as adherence junctions. The possibility that these multicellular arrangements can replace the periodontal ligament in transplantation has to be further investigated.


Ameloblastic fibro-odontoma.

An ameloblastic fibro-odontoma in a 14-year-old girl is reported. The case has clinical interest because of the location and the size of the tumor which was surgically enucleated. The different views about clinical, radiographical and histopathological characteristics and the classification of this benign tumor are discussed. The postoperative course was uneventful and the case has been controlled for 3 years without recurrence.


Prognosis of teeth involved in the line of mandibular fractures.

The management of teeth positioned in the line of mandibular jaw fractures was studied by a follow-up examination of 132 patients with mandibular fractures involving 185 teeth. The observation period varied from 1 to 3 years. The clinical and radiographic findings revealed complete recovery in 59% of the involved teeth. The degree of periodontal and pulpal complications were closely related to the displacement between the fragments and to the type of fracture. Six different fracture types were classified with regard to the extent of involvement of the tooth supporting tissue; 23% of the teeth which initially responded negatively to electric stimulation showed positive sensibility at the time of reexamination. Thus, a long time observation period is advisable with regard to the final outcome of the pulp damage. Conservative treatment of teeth involved in the line of mandibular fractures has a favorable prognosis especially if optimal reduction of the jaw fragments is achieved.


Synthesis of a series of residue 1 (pyroglutamic acid) analogs of thyrotrophin releasing hormone.

This report describes the synthesis of 23 analogs of thyrotrophin releasing hormone, L-pyroglutamic acid-L-histidyl-L-prolineamide, where only the pyroglutamic acid moiety is modified. Twelve of the analogs contain different heterocyclic rings or are derivatized pyrrolidone rings. The syntheses of these pyroglutamic acid analogs are also described. Peptide bond formation was generally achieved by catalyzing carbodiimide coupling with 1-hydroxybenzotriazole. The histidine side chain was protected with the 2,4-dinitrophenyl group during di- and tripeptide synthesis and was removed with benzenethiol Final purification of tripeptides involved passage of synthetic material over a Dowex 1--X4 (bicarbonate) column. The route for synthesis of thyrotrophin releasing hormone and its analogs is highly efficient, since the native hormone may be obtained with 90% efficiency.


I.R.-Stimulated catalysis (a potential spectral tool).

Catalytic rate is proposed as an infrared spectrographic index. Initial investigations of catalytic activity, on beta-galactosidase show a 1-2 fold increase in rate for a mutant enzyme when exposed to 10.6 micrometer irradiation at 2%. No increase was obtained for the wild-type enzyme.


Molecular weight of B. subtilis alpha-amylase derived from chemical studies.

Bacillus subtilis alpha-amylase was cleaved with cyanogen bromide and the amino terminal sequences of the purified products were determined. The molecular weights of the cyanogen bromide fragments were ascertained on an agarose column equilibrated with 6 M guanidine hydrochloride. The molecular wieghts of these fragments were also calculated from their amino acid compositions. The data obtained bzyme monomer as 48,000.


[Histology and clinical aspects of cutaneous neurinomas].

27 year old male patient suffered for four years from multiple cutaneous and subcutaneous neurilemmomas of the right lower leg. The patient showed no symptoms of neurofibromatosis von Recklinghausen. The small tumors attained a size not greater than 1.5--2 cm in diameter. On pressure and sometimes spontaneously they proved to be painful. Histologically, the tumors are composed of two parts, the more solid portion (Antoni A tissue) and the loose, cystic portion (Antoni B tissue).


Effect of varying CO2 equilibria on rates of HCO3- formation in cerebrospinal fluid.

The effects of elevated plasma CO2 partial pressure (PCO2) and [HCO3-] on cerebrospinal fluid (CSF) HCO3- accession have been reviewed in the context of the basal route of CSF HCO3- formation. The basal rate of 53 mM/h appears to be a consequence entirely of formation, via the reaction CO2 + OH- leads to HCO3-. Two-thirds of this rate is catalyzed by carbonic anhydrase, and the remainder uncatalyzed. The HCO3- accession matches 37% that of sodium, so that the HCO3- rate is involved with CSF turnover. When PCO2 is elevated twofold, the rate of HCO3- formation increase 10%, and results in elevation of CSF [HCO3-] by 5 mM in 1 h. Also, when plasma [HCO3-] is elevated 15 mM, CSF [HCO3-] rises about 5 mM/h; this is transfer of HCO3- "as such" by diffusion from plasma. The effects of hypercapnia and metabolic alkalosis on CSF HCO3- accumulation are additive, but they occur by separate processes. The effect of hypercapnia is an exaltation of the normal process due to increased substrate (CO2), but that of increased plasma HCO3- is due to imposition of an abnormal diffusion gradient for this ion between plasma and CSF. The effect of hypercapnia in elevating brain HCO3- operates to maintain brain pH and is also based on the formation of HCO3- from CO2. Brain HCO3- may also be a source of CSF HCO3-. Relations have been sought between the chemically calculated rates of HCO3- formation in CSF and those observed. The chemically calculated catalytic rate is 1,600 times greater than that observed, agreeing with the fact that more than 99.9% of choroid plexus carbonic anhydrase must be inhibited to yield a decrease in fluid formation or ion transport from plasma to CSF. The calculated uncatalyzed rate agrees closely with what is observed after complete inhibition of the enzyme. These considerations support the idea that all the HCO3- reaching the CSF is formed from CO2, rather than by transfer of the ion from plasma to CSF.