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Biomedical subjects

D Schultz

Publications and source records attributed to D Schultz.

At least 109 records · Page 6Linked to original sources

Monokines regulate glycosylation of acute-phase proteins.

The acute-phase response to inflammatory stimuli, characterized by increased synthesis of acute-phase proteins (APP), is often accompanied by changes in the glycosylation patterns of some of these proteins. While expression of APP genes in hepatocytes is regulated by monokines, mechanisms governing changes in glycosylation are not known. Exposure of human hepatoma cell line Hep 3B to conditioned medium from LPS-activated human monocytes and to medium from the keratocarcinoma cell line COLO-16 led to increased synthesis of alpha 1 proteinase-inhibitor and ceruloplasmin and to alterations of their glycosylation patterns similar to those seen in human serum in various inflammatory states. IL-1, tumor necrosis factor, and hepatocyte stimulating factor I increased synthesis of ceruloplasmin without alterations in the pattern of its glycosylation. These findings demonstrate that altered glycosylation seen in plasma in some inflammatory states can be explained by the effects of monokines on glycosylation in hepatocytes and that gene expression and glycosylation of some APP during the acute-phase response may be regulated by different mechanisms.

Acute-Phase Proteins↗

Complement activation and corticosteroid therapy in the development of the adult respiratory distress syndrome.

Fifty-nine patients in septic shock were observed for the development of the adult respiratory distress syndrome (ARDS) prior to and after receiving either 30 mg/kg methylprednisolone sodium succinate, 6 mg/kg dexamethasone sodium phosphate or no steroid. Serum levels of C3, C4 and Factor B allowed classification of 42 patients by activation of complement pathways. Despite a trend toward patients with severe septic shock who activate the alternative pathway being protected from the development of ARDS, complement pathway determination did not allow prediction of the development of ARDS and steroid pretreatment did not influence complement levels or prevent ARDS.

Complement Activation↗

Diet, blood pressure, and hematologic variables of nulliparous women attending a prenatal clinic.

Diet, hematology, and blood pressures of 1800 black and white nulliparous women were surveyed at a prenatal clinic. Although black women had higher blood pressure and lower hemoglobin and hematocrit means that white women, no racial differences were found for prevalence of anemia or hypertension. White women reported less adequate intakes of protein/iron and vitamins B and C compared with black women. No associations between dietary intake and anemia or hypertension were found in univariate analysis. Failure to find racial differences in prevalence of hypertension and anemia may reflect improvements in the dietary supplementation and health care available to lower socioeconomic, black women in the last decade.

Adolescent↗

Anticonvulsant effect of primidone in the gerbil. Time course and significance of the active metabolites.

The anticonvulsant effect of primidone was determined in gerbils, in which seizures were elicited by a blast of compressed air, over the time range of 30 min to 18 h after oral administration. ED50s remained fairly constant from 1 to 12 h after administration: 46-73 mumol/kg with the minimal value at 6 h. Of the metabolites, phenobarbital was maximally effective at 2 h after administration (ED50 35 mumol/kg), whereas phenylethylmalondiamide (PEMA) only had a weak anticonvulsant effect (ED50 1.55 mmol/kg at 2 h). By determination of primidone and its active metabolites in plasma and brain at 1, 4 and 12 h after administration of the respective ED50s, it could be shown that unchanged primidone is mostly responsible for the anticonvulsant effect of the first hours, but, at 12 h, only phenobarbital could be detected in both tissues. PEMA could not be detected in brain. From the effective brain concentrations at different times it could be calculated that primidone and phenobarbital have the same anticonvulsant potency on a molar base in the gerbil. The concentrations necessary to control seizures in this model were considerably lower than those needed to suppress convulsions in maximal seizure models in mice and rats.

Administration, Oral↗

Synthesis and secretion of C-reactive protein by rabbit primary hepatocyte cultures.

The synthesis and secretion of the acute-phase protein C-reactive protein by rabbit primary hepatocyte cultures was investigated. Hepatocytes prepared from animals that had received inflammatory stimuli 18-24 h before cell isolation were found to incorporate radiolabelled amino acids into C-reactive protein throughout the 48 h culture period. Intracellular C-reactive protein was found to be in steady state and there was no significant degradation of extracellular C-reactive protein, permitting direct estimation of rate of synthesis from rate of extracellular accumulation. Both C-reactive protein and total secreted protein were synthesized at constant rates for at least 24 h in culture. Mean rate of accumulation of newly synthesized total proteins in medium of cultures from six stimulated animals was 40% greater than was found in cultures from nine control (unstimulated) animals; this difference did not achieve statistical significance (0.05 less than P less than 0.10). Mean rate of C-reactive-protein synthesis represented 3.9% of total secreted-protein synthesis in cultures prepared from stimulated animals compared with 0.3% in cultures from control animals (P less than 0.001). Further, there was a correlation between C-reactive-protein synthesis by cultured hepatocytes and serum C-reactive-protein concentration at time of hepatocyte isolation (P less than 0.001). Rates of C-reactive-protein synthesis by hepatocyte cultures from stimulated animals were in good agreement with those previously measured in isolated perfused livers and those calculated from results of studies in vivo.

Animals↗

Anticonvulsant potency of common antiepileptic drugs in the gerbil.

In gerbils, 'minor' (myoclonic) and 'major' (clonic-tonic) seizures were induced by blowing at the animals with compressed air. The anticonvulsant ED50 of the following drugs was determined after oral administration against both types of seizures: phenytoin, phenobarbital, carbamazepine, sodium valproate, ethosuximide, and diazepam. Valproate, ethosuximide, and diazepam were most potent against 'minor' seizures which could not or only partially be suppressed by phenytoin or carbamazepine, respectively. The 'grand mal' drugs phenytoin, phenobarbital, and carbamazepine were, on the other hand, more potent against 'major' than against 'minor' seizures. When phenobarbital was administered for several days, a strong induction of hepatic microsomal enzymes occurred.

Animals↗

High anticonvulsant potency of gamma-aminobutyric acid (GABA)mimetic drugs in gerbils with genetically determined epilepsy.

Seven GABAmimetic drugs, namely cetyl gamma-aminobutyric acid (cetyl GABA), 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridine-3-ol, progabide, aminooxyacetic acid, alpha-acetylenic GABA, (-)-nipecotic acid ethyl ester and (+/-)-cis-4-hydroxynipecotic acid methyl ester, were tested for their potency to block "major" (generalized clonic-tonic) seizures in gerbils, induced by blowing at the animals with compressed air. Valproic acid was included as a reference standard. All drugs proved able to protect gerbils from induced seizures. Most effective were 4,5,6,7-tetrahydroisoxazolo [5,4-c] pyridine-3-ol (ED50, 1.3 mg/kg i.p.), aminooxyacetic acid (0.9), cetyl GABA (4.5) and gamma-acetylenic GABA (2.1). A comparison with anticonvulsant ED50 values of common antiepileptics in the gerbil showed that these four GABAmimetics were clearly more potent than phenobarbital, phenytoin, carbamazepine, ethosuximide and valproic acid and were only surpassed in potency by diazepam. Furthermore, most GABAmimetics proved strikingly more active in the gerbil compared with the classical electroshock and pentylenetetrazol seizure models in mice. After administration of gamma-acetylenic GABA, GABA increases in the brain of only about 40% were found sufficient to reach almost complete seizure protection in gerbils. The present data are compatible with the possibility that the GABA system is critically involved in the seizure-prone state in the gerbil.

Alkynes↗

Aortic input impedance in man: acute response to vasodilator drugs.

In 18 patients who underwent coronary arteriography, aortic velocity and pressure data were obtained during a control state and during either isoproterenol infusion at 1, 2 and 3 micrograms/min or graded nitroprusside infusion (average peak dose 60 micrograms/min). Impedance moduli and phase angles were derived to 10 Hz for controls states, isoproterenol at 2 micrograms/min, and at peak nitroprusside effect. Averaged control data included a mean resistance of 1460 dyn-sec-cm-5 and a characteristic impedance of 88 dyn-sec-cm-5 The characteristic impedance did not correlate with age (r = 0.21), coronary artery disease score (r = 0.17) or mean aortic pressure (r = -0.01). In 11 patients, isoproterenol induced a 38% reduction in mean resistance and a 10% reduction in mean aortic pressure. There was slight reduction in characteristic impedance and phase angles became less negative, to 2 Hz. In seven patients, nitroprusside induced a 38% reduction in mean resistance and a 22% reduction in mean aortic pressure. Impedance moduli decreased to 1.8 Hz and phase angles became less negative, to 3 Hz. Based on the different cardiovascular actions of these two drugs, the data suggest that vasodilators do not induce significant changes in the aortic impedance spectrum when not associated with a decrease in mean aortic pressure.

Adult↗

[Diagnostic value of muscle biopsy findings in myotonic dystrophy (Curschmann-Steinert) (author's transl)].

By histological, enzyme histochemical, histometrical and ultrastructural studies of 15 muscle biopsies from patients with myotonic dystrophy the typical morphological picture of a myopathy with multiple internal nuclei, sarcoplasmic masses and ring fibers can be shown only in 7 cases with very severe or prolonged clinical course. There is fiber degeneration under the sarcolemma which corresponds to findings in myopathies caused by hypothyroidism. Type-I-fiber-atrophy, which is thought to be an early morphological sign of the disease. can be demonstrated in our material only in proximal muscle groups, especially biceps muscle, whereas tibialis anterior muscle shows a slight focal atrophy of both mean fiber types, which is not helpful for differential diagnosis. Therefore in early cases of myotonic dystrophy which are not clarified by clinical and electromyographic investigation, a biopsy of biceps muscle should be done. Advanced cases as a rule can be confirmed by EMG without muscle biopsy. The morphological differential diagnosis of type-I-fiber-atrophy and the similarities of fiber degeneration under the sarcolemma in myotonic dystrophy as well as in myopathy caused by hypothyroidism are discussed.

Biopsy↗

[Sequential hepato-splenic scintigraphy for measurement of hepatic blood flow (author's transl)].

The arterial and portal components of total liver blood flow were determined quantitatively in 31 patients by means of a new, non-invasive method. Sequential hepato-splenic scintigraphy has been employed, using a scintillation camera linked to a computer system. In normals, the proportion of portal flow was 71%, whereas in patients with portal hypertension it averaged 21%. Our experience indicates that the procedure can be of considerable value in the pre-operative diagnosis and postoperative follow-up of portal hypertension.

Adolescent↗

Effect of guanidine, germine, and steroids in a case of botulism.

A patient with severe type A botulism demonstrated several interesting features. Characteristic electrophysiologic findings are not necessary for the diagnosis. Guanidine hydrochloride provided mild improvement. High doses of steroids and low dose of germine-monoacetate had no effect.

Action Potentials↗