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Biomedical subjects

M Schultz

Publications and source records attributed to M Schultz.

At least 91 records · Page 5Linked to original sources

Site-specific mutagenesis of PRD1 DNA polymerase: mutations in highly conserved regions of the family B DNA polymerase.

The PRD1 DNA polymerase is a small multifunctional enzyme containing three major conserved amino acid sequences shared by family B DNA polymerases. Thus, the PRD1 DNA polymerase provides an useful model system with which to study structure-function relationships of DNA polymerase molecules. In order to investigate the functional and structural roles of the highly conserved amino acid sequences, we have introduced mutations into each of the 3 conserved regions of the PRD1 DNA polymerase. Genetic complementation study as well as DNA polymerase assay indicated that each mutation inactivated DNA polymerase catalytic activity, but not the 3' to 5' exonuclease activity.

Amino Acid Sequence↗

Giant axonal neuropathy (GAN): an immunohistochemical and ultrastructural study report of a Latin American case.

Giant axonal neuropathy (GAN), a progressive childhood disorder of intermediate filaments (IF), is characterized by a peripheral neuropathy and central nervous system involvement. Twenty-eight cases have been reported while several pathogenic hypotheses have been proposed. Sural nerve biopsy of a 10-year-old Argentinian girl showed a reduced number of myelinated fibers as well as several enlarged axons up to 30 microns in diameter, thinly myelinated or devoid of myelin sheath, displaying accumulation of neurofilaments (NF), but few microtubules (MT) beneath the axolemmal membrane. There was IF accumulation in Schwann and perineural cells as well as in melanocytes, fibroblasts, pericytes, endothelial and epithelial cells in both nerve and skin biopsy. Our findings strongly support GAN as a generalized IF disorder with MT segregation from NF in giant axons. Abnormal NF phosphorylation is suggested by heavy immunostaining of enlarged axons by a monoclonal antibody to NF phosphorylated determinants (SMI 31-Sternberger's) and lack of reaction with a monoclonal antibody with different phosphoepitopes affinity (SMI 34-Sternberger's).

Axons↗

Phenomenological kinetics of pharmacological response.

The evaluation and quantitative analysis of the time course of drug response are difficult tasks even in uncomplicated fields of pharmacology. In an attempt to assist the analysis of the pharmacological effect, a procedure is presented which incorporates widely used intuitive-experimental practices of evaluation, and descriptive kinetic functions. The aim is to find a simple function which can approximate the time course of the response curves at different doses. Having estimated the values of parameters for each curve, valuable information can be drawn by examining the dose-parameter relationships. The method is illustrated by one possible evaluation and interpretation of the blood pressure-time curves of a drug.

Animals↗

Induction of heterotypic virus resistance in adult inbred mice immunized with a variant of Coxsackievirus B3.

Infection of adult male C3H/HeJ mice with a host range variant of Coxsackievirus B3 (CB3W-RD) induced resistance in these mice to an otherwise lethal dose of Coxsackievirus B1 (CB1). The protective effect induced by CB3W-RD was detectable as early as 1 day post-vaccination and was still present 10 weeks later. While untreated mice infected with CB1 died within 5 days because of massive hepatic necrosis, the liver was spared in mice immunized with CB3W-RD and then challenged with CB1. In general, CB1 titers in heart, liver, and pancreas of CB3W-RD-vaccinated animals were lower than that found in unvaccinated animals. Virus neutralizing antibody was not a mediator of this heterotypic, virus-induced protective effect. In addition, the outcome of CB1 infection could be modified if superinfection with CB3W-RD took place within 1-4 days following CB1 infection. In this regard, maximum therapeutic efficacy was observed when CB1 infected mice were superinfected 2 days after CB1 infection. CB1-infected mice that survived as a result of treatment with CB3W-RD exhibited liver regeneration but did develop myocardial necrosis.

Animals↗

[Results of osteologic studies of medieval pediatric skeletons with special reference to the population of Anatolia].

Causes and frequency of diseases during childhood in populations of the Middle Ages were studied. The infant skeletons of ten populations from Central Europe and Anatolia were examined by macroscopical, radiological, endoscopical, histological, and scanning-electron microscopical techniques. Because only little is known about Anatolian populations, more attention was paid to the Byzantine populations. The infant skeletons are very well preserved. Therefore, the morbidity and the mortality could be studied in detail. The following disorders were diagnosed: anemia, C-avitaminosis, D-avitaminosis, osteomyelitis, meningitis-meningoencephalitis, otitis media and mastoiditis, perisinusitis, inflammation of the cavum nasi, inflammation of the paranasal sinuses, stomatitis, periodontal diseases, caries, pleuritis, trauma, and malformations. The frequency of diseases and the mortality depended on the type and the intensity of particular external life conditions. These may have been quite different in several social groups of the same population. In summary, these studies provide new information on the etiology and the epidemiology of diseases during childhood in the Middle Ages.

Age Determination by Skeleton↗

Pathogenesis of acute myocardial necrosis in inbred mice infected with coxsackievirus B3.

The pathogenesis of myocardial necrosis due to CB3W infection was studied in BALB/c and C3H/HeJ mice. BALB/c mice infected with 5 x 10(4) pfu were found to die of massive hepatic coagulative necrosis before myocardial changes occurred. Reducing the inoculum size to 5 x 10(2) pfu resulted in sublethal hepatic involvement and multifocal myocardial coagulative necrosis by day 7 p.i. In contrast, C3H/HeJ mice survived infection and developed multifocal myocardial coagulative necrosis, but not liver disease following inoculation with as much as 5 x 10(6) pfu of CB3W. As with BALB/c mice infected with 5 x 10(2) pfu, myocardial lesions became apparent in C3H/HeJ mice a few days after peak cardiac virus titer was attained. Minimal inflammatory infiltrate was seen following development of cellular necrosis and was restricted to the areas of virus-induced pathologic change. However, no evidence was found for virus-specific cytotoxic T cell activity or for delayed type hypersensitivity responses. Furthermore, myocardial necrosis in CB3W-infected, T cell-depleted C3H/HeJ mice was as severe as in CB3W-infected, immunocompetent mice. These data have led us to conclude that cardiac lesions were due to virus-induced cytopathology rather than immunopathogenic mechanisms.

Animals↗

Relation between renal and hepatic excretion of drugs: X. Excretion of nalorphine in young and adult rats pretreated with hormones or xenobiotics.

Different processes are involved in renal and hepatic excretion of organic anions and cations. In contrast to our knowledge of anion excretion, information about cation transport in kidney and liver is relatively scarce. In this study, the elimination of nalorphine was investigated to characterize the relation between renal and hepatic excretion of organic cations. Nalorphine is excreted effectively both via kidney and liver. However, its hepatic excretion dominates in adult rats. In young, 20-day-old animals biliary nalorphine elimination is immature and the excreted amounts are significantly lower. Renal excretion of nalorphine is quite similar in rats of both ages. After bile duct ligation renal excretion of nalorphine increases significantly in adult rats whereas it remains unchanged in young ones. Remarkably, after bilateral nephrectomy hepatic elimination of nalorphine is even diminished in both age groups. In further experiments renal excretion of nalorphine could be stimulated in adult rats after repeated administration of trometamol, triiodothyronine, or dexamethasone; these treatments had no consequences on biliary secretion of nalorphine.

Aging↗

Problems of experimental tumourigenesis by fibrous dusts, especially by asbestos (with regard to stanton's hypothesis).

Asbestos dust has got a very great importance because cancerogenicity is imputed into it in occupational and, perhaps, in common environmental conditions too. The short review deals with general problems in experimenting with fibrous dusts, especially the modes of its application, the transferability of results to human pathology and the cause and pathway of cancerisation by fibres and crystals.

Animals↗

[Asbestos-induced malignant tumors].

Asbestos had been increasingly used in many applications across numerous industries on account of its particular material properties, including resistance to heat and fire as well as to aggressive chemicals, high mechanical strength, insulation capacity, other physical parameters, and for its low price. World wide asbestos production and processing thus went up from 50 tons to 5.5 million tons per annum, in about 100 years. Widespread application of asbestos as well as of asbestos-containing materials and workpieces together with the understanding that asbestos for its fibrogenicity is capable of causing pulmonary and pleural asbestoses constitute a major challenge for thorough elucidation of related occupational diseases and their relationship with asbestos. This demand is additionally supported in urgency by the cancerogenicity of asbestos potentially leading to malignant diffuse mesotheliomas, bronchial carcinomas, and, obviously, other tumors. In the context of malignant mesotheliomas, emphasis has to be laid on characteristic morphological features, biological behaviours, and asbestos-related aetiology. As bronchial carcinomas have several aetiological backgrounds, answers will have to be found to the questions for which of them may have been fully or partially caused by asbestos and which have not. No differentiation has so far been feasible, in this context, by tumour morphology, including histological typing. After all, when it comes to malignant tumours of other organs, additional epidemiological as well as pathologico-anatomic efforts will have to be made to find out, if and where a given case of tumour growth has coincided with exposure to asbestos.

Asbestos↗

[Interstitial lung diseases of the interstitial-proliferative type].

The term of "chronic interstitial pneumonia" had been more accurately redefined by Liebow and, subsequently, by Otto and had been subdivided by different pathomorphological phenomena. The interstitial-proliferative type is of particular interest, in this context. Reported in this paper is the bioptic histopathological pattern of 15 patients with interstitial lung disease of the interstitial-proliferative type, with these findings being correlated to clinical symptoms. A distinction is made between an independent form in its own right and a histologically identical interstitial phenomenon accompanying other pulmonary diseases, primarily in concomitance with lung cancer, and recordable also from postmortem investigations. Interstitial-proliferative inflammations are adequately controllable by antibiotics.

Adult↗

Cobra venom factor and human C3 share carbohydrate antigenic determinants.

As tools to study structural relationships of cobra venom factor (CVF) and human complement component C3, murine monoclonal antibodies to CVF were produced. In this paper we describe two of these monoclonal anti-CVF antibodies designated GV1.8 and GV1.10, both of which bind to carbohydrate epitopes. On immunoblotting, antibody GV1.8 binds to both the alpha- and beta-chains of CVF, whereas antibody GV1.10 binds only to the alpha-chain of CVF. After enzymatic deglycosylation of CVF with N-glycanase (peptide-N4-(N-acetyl-beta-glucosaminyl) asparagine amidase), both antibodies lose their ability to bind to the deglycosylated protein. Additionally, the free oligosaccharide chains of CVF are able to inhibit the binding of antibodies GV1.8 and GV1.10 to CVF on enzyme-linked immunosorbent assay, further demonstrating their carbohydrate specificity. Both monoclonal antibodies to CVF cross-react with human C3. Antibody GV1.8 binds to both chains of human C3 indicating that the shared antigenic epitope present on the two glycosylated chains of CVF is also present on the two chains of human C3. Antibody GV1.10 cross-reacts only with the beta-chain of human C3 which is the homologous chain to the alpha-chain of CVF. After enzymatic deglycosylation of human C3 by N-glycanase, both antibodies lose their ability to bind to the deglycosylated protein consistent with the carbohydrate nature of the recognized epitopes. These results indicate that CVF and human C3 share carbohydrate epitopes on their homologous and nonhomologous chains.

Carbohydrates↗

[Pharmacodynamics of vecuronium in infants during intravenous induction of anesthesia with ketamine].

The pharmacodynamic effects of vecuronium in children aged 1 to 6 years were investigated after intravenous induction of anaesthesia with ketamine, using an initial dose of vecuronium of 0.08 mg/kg body wt. 0.1 mg/kg body wt. The degree of neuromuscular blockade was determined by measuring the contraction force of the m. adductor pollicis after supramaximal stimulation of the ulnar nerve using an electromechanical device. The results (median, chi min and chi max) were as follows. For the initial dose 0.08 mg/kg body wt., the onset time was 150 s (110-360 s); total blockade: 5 of 9 children, D25 (duration of 25% recovery) 13 min (10-31); RI (recovery index): 8.5 min (6.0-14.5); D90 (duration of 90% recovery): 27 min (20-44). For the initial dose of 0.1 mg/kg body wt., the onset time was 135 s (80-300); total blockade: all children, D25: 19.5 min (12-32.5); RI: 8.75 min (6.5-13.5); D90 35 min (22-45). Only the D25 was significantly shorter using an initial dose of 0.08 mg/kg body wt. For a total blockade, a higher dose of vecuronium is necessary using intravenous induction of anaesthesia compared with previously described inhalation techniques. Even with the high dosage, recovery from neuromuscular blockade is so rapid in this age group that it can be used even for short operations without reversal.

Anesthesia, Intravenous↗