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Biomedical subjects

M Strauss

Publications and source records attributed to M Strauss.

At least 271 records · Page 15Linked to original sources
PubMed1979

Tumor sterilization following high-dose pre-operative irradiation for advanced cancer of the larynx or pyriform sinus.

Twenty-two patients with advanced laryngeal cancer and 5 with advanced pyriform sinus cancer were given 51 Gy (5,100 rad) followed by surgical resection. In 10 (45%) of patients with laryngeal cancer, no tumor was found at the primary site pathologically; 15 (68%) had negative neck specimens. All of those with pyriform sinus cancer had positive specimens. Eighteen patients with laryngeal cancer are free of disease. In contrast, only 1 with pyriform sinus cancer is free of disease; 1 has had a local recurrence and 3 have had metastases. The data suggest that 51 Gy (5,100 rad) are insufficient to sterilize pyriform sinus cancer; higher doses together with adjuvant chemotherapy are needed.

Adult↗
PubMed1978

Evidence against the existence of real isozymes of hypoxanthine phosphoribosyltransferase.

A method for reducing the degree of heterogeneity in the electrophoretic enzyme activity pattern of hypoxanthine phosphoribosyltransferase preparations by incubation with a (magnesium) phosphoribosyl diphosphate substrate is described. Hypoxanthine phosphoribosyltransferase was isolated from human erythrocytes and Chinese hamster livers. A subunit molecular weight of 26000--27000 as reported by other authors was obtained for both enzymes by gel electrophoresis in the presence of dodecylsulfate. Gradient gel electrophoresis revealed that the native enzymes mainly have a molecular weight of 105000--110000 and are thus apparently tetrameric, when held in the active state by the presence of phosphoribosyl diphosphate. The dimeric enzyme with a molecular weight of 52000--55000, was also found under other conditions. The trimer occurred only in the absence of phosphoribosyl diphosphate, for instance by glycerol gradient centrifugation. The enzyme from human erythrocytes was partly degraded during purification in the absence of a protease inhibitor. The purified enzyme has a very low protease contamination level. Proteolysis is an additional cause of heterogeneity and might therefore explain earlier conflicting results. Since the heterogeneous nature of hypoxanthine phosphoribosyltransferase is caused only by the secondary processes of dissociation/association and, in the case of the human erythrocyte enzyme, degradation, we suggest that the use of the term 'isozyme' to describe the different forms should be avoided.

Erythrocytes↗
PubMed1978

The incorporation of homologous and heterologous hypoxanthine-guanine phosphoriboxyltransferase into mutant cells.

Experiments are described leading to partial compensation of a deficiency in the enzyme hypoxanthine-guanine phosphoribosyltransferase in mutant cells by supplying the cells with exogenous purified enzymes. DEAE-dextran is an effective helper agent, whereas poly (L-lysine), lysolecithin and amphotericin B seem to inhibit the entry of the enzymes of their activity. Enzyme preparation from Chinese hamster was found to have different effects in different mutant cell lines. In mutant Chinese hamster cells, the electrophoretic activity pattern remains unchanged for the Chinese hamster enzyme, but changes progressively to faster-moving activity peaks for the human enzyme after several hours. The metabolic effect of the incorporated enzyme is in the range between 3 and 4% of the normal cellular enzyme activity which corresponds to a 10--20 fold increase of hypoxanthine-guanine phosphoribosyltransferase activity in the mutant cells.

Amphotericin B↗
PubMed1978

Fetal respiratory distress causing CNS and inner ear hemorrhage.

Fifty-two consecutive temporal bones of infants who died neonatally, or in utero of natural causes, were studied. Complete autopsies were performed. Twenty-eight infants had a variety of pulmonary disorders which resulted in severe respiratory distress prior to their death. Of these, the majority had bleeding intracranially and into the inner ear. There were five major pathways of central nervous system and subarachnoid hemorrhage involvement of the inner ear: 1) the modiolus, 2) cochlear aqueduct, 3) retrograde via the cochlear vein, 4) episodes of spontaneous bleeding into various compartments of the inner ear, and 4) hemorrhage via the otic capsule. The remaining 24 infants died of other natural causes. Two had CNS bleeding with no extension to the inner ear. We propose that there is a syndrome which consists of 1) neonatal respiratory distress, 2) intracranial hemorrhage, and 3) bleeding into the inner ear--an extension of a subarachnoid or subependymal matrix bleeding diathesis.

Cerebral Hemorrhage↗
PubMed1977

Mutagenesis by simian virus 40. II. Changes in substrate affinities in mutant hypoxanthine-guanine phosphoribosyl transferase enzymes at different pH values.

A number of 8-azaguanine-resistant clones selected from Chinese hamster cells infected with SV 40, and supposed to originate by virus infection was investigated to demonstrate and analyze genetic alterations occurring in the cells after infection. All resistant clones tested showed reduced but detectable activity levels of the enzyme hypoxanthine-guanine phosphoribosyltransferase. The extent of reduction in the activity was not identical for different substrates. In all the clones tested, spontaneous mutants included, the pH optimum for the enzymic reaction with guanine was shifted to lower values. The reduced enzymic activities of resistant clones correlated with their colony-forming ability in corresponding selective media. The results support the suggestion that SV 40 is able to induce gene mutations.

Azaguanine↗
PubMed1977

Cytomegalovirus endolabyrinthitis.

A premature male infant, who died 22 days after birth with hyaline membrane disease, was found to have had cytomegalic inclusion disease at autopsy. Histopathologic examination of the temporal bones showed cytomegalovirus (CMV) infection of the entire endolabyrinth without involvement of the neural and sensory structures. These findings support the thesis that late gestational or perinatal fetal CMV infection results in an endolymphatic labyrinthitis. We hypothesize that blood-borne virus passes from the stria vascularis into the endolymphatic spaces and infects the nonneurosensory epithelium. This pattern of infection differs from the perilabyrinthitis of human varicellazoster and experimentally produced mouse CMV.

Cytomegalovirus↗
PubMed1976

Synthesis and biological activity of 3,5-dinitro-4- and -2-(1H-purin-6-ylthio)benzoates, prodrugs of 6-mercaptopurine.

A series fo prodrug modifications of 6-mercaptopurine (6-MP) containing dinitrobenzoate ester moieties with varying chain length has been prepared. These compounds were shown to be cytotoxic in several cell culture screens and also exhibited significant activity against L1210 lymphoid leukemia in vivo. The possibility exists that the transport and distribution of these compounds in vivo will be determined, in part, by increased lipophilic character, with a consequent selective localization in lymphatic and CNS tissue.

Animals↗
PubMed1975

Determination of the subunit molecular weight of hypoxanthine-guanine phosphoribosyltransferase from human erythrocytes by recovery of enzyme activity from sodium dodecyl sulphate gels.

The molecular weights of the subunits of the enzyme hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) from human erythrocytes were determined with a simple novel method, including electrophoresis in sodium dodecyl sulphate gels, gel slicing, elution of protein from the gel slices and enzyme reactivation in the presence of the substrate 5-phosphorylribose-1-pyrophosphate. As molecular weight standards glutaraldehyde-polymerized polypeptides of human haemoglobin were used. The experiments clearly showed the existence of molecular weight differences in human erythrocyte hypoxanthine-quanine phosphoribosyltransferase.

Chromatography, Gel↗
PubMedDate not supplied

Intravenous administration of recombinant adenoviruses causes thrombocytopenia, anemia and erythroblastosis in rabbits.

BACKGROUND: Recombinant adenoviruses are highly efficient gene transfer vehicles but their administration to mammals is accompanied by a strong inflammatory response. The present study reports additional side effects observed during adenoviral gene transfer studies in rabbits. METHODS: Hematological and serological parameters, the course of viremia and the organ distribution were analyzed after in vivo administration of E1-deleted adenoviruses in rabbits. RESULTS: The systemic administration of a therapeutic dose of 5 x 10(11) infectious particles/kg (infusion time 20 min) led to an average reduction of 80-90% in the platelet count within 48 h. Full recovery took 10-14 days. Virus administration induced a strong but transient erythroblastosis (peaking 24 h after administration) which settled 48 h later. Normochromic anemia occurred over the next 10 days with hemoglobin levels dropping by about 40% to reach the lowest level 10 days after administration and taking two months for full recovery. Dose-dependent thrombocytopenia was also found in mice, but neither erythroblastosis nor anemia was observed (in equivalent doses). The hematological findings did not improve after local injection via the portal vein. Local and systemic administration led to a comparable course of viremia. Only minor differences were found in the biodistribution of viruses between local and systemic administration. Large amounts of viral DNA and transgene expression were found in the lungs, the kidneys and the ovaries, even after local administration via the portal vein. CONCLUSIONS: Local intravenous injection via the portal vein does not prevent systemic spread of viral vectors and the occurrence of vector-related side effects. The hematological changes observed in rabbits suggest the need for careful monitoring of hematological and rheological parameters in clinical trials.

Adenoviridae↗
PubMedDate not supplied

Occult distant metastases of well-differentiated thyroid carcinoma.

BACKGROUND: The tendency of well-differentiated thyroid carcinoma to remain localized and its slow progression have supported the belief that this disease behaves as a low-grade malignancy. Consequently, a conservative approach in the management of the well-differentiated thyroid carcinoma has existed during the years. Occult distant metastases of thyroid cancer is an occasional finding considered of ominous significance. METHODS: In a retrospective study, we reviewed the records of 187 adult patients with well-differentiated thyroid carcinoma treated by total thyroidectomy. These cases were found among 1,240 thyroidectomies performed in our department between 1982 and 1993. Occult distant skeletal and lung metastases disclosed by total body 131I scans, after total thyroidectomy, were present at the time of initial treatment in 11 patients (11/187). This group included 9 women and 2 men ranging in age from 36 to 70 years, with a mean age of 47 years. Seven patients had papillary carcinoma, whereas follicular malignancy was found in four. Review of the surgical specimens showed total involvement of the gland in 5 cases, with extracapsular tumoral spread in 3 patients. Multicentric disease was present in 6 specimens. Patient follow-up revealed a mortality rate of 64% (7/11) during the first 3 post-operative years. CONCLUSIONS: Analysis of this population confirms that well-differentiated thyroid carcinoma with distant metastases is an aggressive disease with lethal consequence. Early detection and therapy of occult distant metastases present at the time of initial treatment is possible only after total thyroid ablation, because otherwise the radioactive iodine is trapped by the gland's remnants.

Adenocarcinoma, Follicular↗