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Biomedical subjects

J M Schmidt

Publications and source records attributed to J M Schmidt.

At least 19 recordsLinked to original sources
PubMed1992

Structural modifications of bryostatin 2.

Continuation of a structure/activity relationship study of the bryostatins was focused on bryostatin 2. Stepwise catalytic hydrogenation of bryostatin 2 gave the following results. Reduction of the side-chain diene system to saturated ester 2a (P388 cell line ED50 8.5 x 10(-3) micrograms/ml) did not significantly affect the murine P388 cell line inhibition by bryostatin 2. Further hydrogenation to hexahydro derivative 2b gave a reduced P388 ED50 of 5.1 x 10(-2) micrograms/ml. Conversion to the octahydrobryostatin 2c caused a further reduction of P388 cell line activity to ED50 2.9 x 10(-1) micrograms/ml. Other structural modifications of bryostatin 2 in respect to esterification at the C-7 position significantly affected the P388 lymphocytic leukemia cell line response. Each of the bryostatin 2 derivatives was also evaluated with respect to protein kinase C binding.

Animals↗
PubMed1991

Conformation of [8-arginine]vasopressin and V1 antagonists in dimethyl sulfoxide solution derived from two-dimensional NMR spectroscopy and molecular dynamics simulation.

Structural and dynamic properties of [8-arginine]vasopressin and a class of highly potent vasopressin V1 antagonists which contain 3-mercapto-3,3-cyclopentamethylene propionic acid (Mca) in position 1 of the vasopressin sequence have been determined. On the basis of two-dimensional NMR experiments in dimethyl sulfoxide solution, interproton distances were derived according to which model conformations were built and refined using molecular dynamics simulations. The conformation of vasopressin and the V1 antagonists differ mainly in the region of the mutated residue. The antagonistic property was found to be related to an inversed chirality of the disulfide bridge. In all investigated molecules, characteristic beta-turn structure elements were found for the backbone conformation of the endocyclic residues Tyr2-Asn5. For this portion of the peptide sequence, various conformational equilibria were detected which matched different time scales. For [Arg8]vasopressin, averaged NMR parameters were obtained which could be explained by rapid interconversion between different beta-turn geometries, whereas multiple slowly exchanging conformations were observed for the V1 antagonists. V1 antagonists containing sarcosine in position 7 exhibited multiple spectral patterns for the exocyclic part attributed to cis/trans isomerization. The X-ray structure of deamino-oxytocin [Wood, S. P., Tickle, I. J., Treharne, A. M., Pitts, J. E., Mascarenhas, Y., Li, J. Y., Husain, J., Cooper, S., Blundell, T. L., Hruby, V. J., Buku, A., Fischman, A. J. & Wyssbrod, H. R. (1986) Science 232, 633-636] was found to represent one sample of the conformational space covered by the multiple conformations found for [Mca1, Arg8]vasopressin.

Amino Acid Sequence↗
PubMed1991

Two-dimensional 1H, 15N-NMR investigation of uniformly 15N-labeled ribonuclease T1. Complete assignment of 15N resonances.

Uniformly 15N-enriched ribonuclease T1 (RNase T1) was obtained from Escherichia coli by recombinant techniques. Heteronuclear 1H, 15N-shift correlation spectra were recorded utilizing proton detection. Direct 1H, 15N connectivities were established applying the heteronuclear multiple-quantum coherence technique. Additional 1H, 1H-TOCSY or 1H, 1H-NOESY transfer steps allowed for sequential assignments. Nitrogen atoms without directly bonded protons were detected by means of the heteronuclear multiple-bond correlation experiment. Signals emerging from 15NH and 15NH2 groups were distinguished by heteronuclear triple-quantum filtering methods. 119 nitrogen resonances out of the expected 127 were assigned unambiguously; in addition, previously obtained proton assignments were extended. Preliminary 1H, 15N NMR investigation were performed on the RNase-T1-3'GMP inhibitor complex. Results were interpreted with respect to nucleotide binding.

Magnetic Resonance Spectroscopy↗
PubMed1991

Pasteuria nishizawae sp. nov., a mycelial and endospore-forming bacterium parasitic on cyst nematodes of genera Heterodera and Globodera.

This study describes Pasteuria nishizawae sp. nov., a fourth species of the genus Pasteuria. This mycelial and endospore-forming bacterium parasitizes the adult females of cyst-forming nematodes in the genera Heterodera and Globodera. The distinct ultrastructural features and unique host range found for this bacterium separate it from two closely related species, Pasteuria penetrans, which parasitizes several species of root-knot nematodes of the genus Meloidogyne, and Pasteuria thornei, which appears to parasitize only one species of the root-lesion nematode, Pratylenchus brachyurus. Because these obligate bacterial parasites of nematodes have not been cultured axenically, the taxonomic relationships described here for each species are based mainly on developmental morphology, fine structure of the respective sporangia and endospores, and their pathogenicity on nematode species.

Animals↗
PubMed1991

[The history of tuberculin therapy--its discovery by Robert Koch, its forerunners and further development].

Since tuberculosis had not been known either in its nature or in its proper therapeutics for thousands of years, Robert Koch (1843-1910) 1882 discovered its germs and 1890 recommended its treatment with tuberculin, i.e. an extract of its bacterial cultures. During the "Tuberkulin-sturm" which ensued from the publication of Koch, the substance was at once proved in numerous clinics in many countries. But in spite of sophisticated procedures of production it could not become standard therapy because of its considerable side-effects when not being applied accurately. In selected cases therapy with tuberculin is still applied even today. However, the effort of treating tuberculosis with tuberculin had already been made before its propagation by Robert Koch. Yet the forerunners of Koch's therapy with tuberculin had not been recognized by scientific medicine at the time because of lacking plausibility of its fundamental principles--not before Emil von Behring (1854-1917) within his scientific researches came to an explicit recognition of the homeo- and isopathetic principle of treatment.

Germany↗
PubMed1991

Aloe vera dermal wound gel is associated with a delay in wound healing.

We evaluated the time interval required for wound healing using a standard wound management protocol with and without aloe vera gel. Twenty-one women were studied who had wound complications requiring healing by second intention after cesarean delivery or laparotomy for gynecologic surgery. Wounds treated with standard management healed in a mean (+/- SD) time interval of 53 +/- 24 days, whereas those treated with aloe vera gel required 83 +/- 28 days (P = .003). The use of aloe vera dermal wound gel was associated with a significant delay in wound healing compared with treatment with an otherwise identical regimen that did not include aloe vera.

Adult↗
PubMed1988

Interactions of tubulin with potent natural and synthetic analogs of the antimitotic agent combretastatin: a structure-activity study.

Combretastatin, an antineoplastic and antimitotic agent, was isolated from the bark of Combretum caffrum [Can. J. Chem. 60: 1374-1376 (1982); Biochem. Pharmacol. 32:3864-3867 (1983)]. Structurally, combretastatin consists of two substituted benzene rings linked by a saturated, hydroxy-substituted two-carbon bridge. A large number of combretastatin analogs have now been synthesized or obtained from C. caffrum. These vary in substituents on the phenyl rings or bridge carbons, bridge length, unsaturation of the bridge (i.e., stilbene derivatives, with the two phenyl rings oriented either cis or trans), and in precise ring structure (two major variants, with the bridge incorporated into a third six-member ring to form a phenanthrene structure or a methyl group eliminated from vicinal methoxy substituents to form a benzodioxole ring). Available analogs (17 natural products and 22 synthetic agents) were examined for antimitotic and cytotoxic activity and for effects on tubulin polymerization and colchicine binding. Nineteen compounds inhibited cell growth by 50% or more at concentrations of 1 microM or less, and 14 inhibited tubulin polymerization by at least 50% at stoichiometric drug concentrations. The most potent cytotoxic agents generally strongly inhibited both tubulin polymerization and the binding of colchicine to tubulin. The most promising compound is the (cis)-stilbene derivative (cis)-1-(3,4,5-trimethoxyphenyl)-2-(3'-hydroxy-4'-methoxyphenyl)ethene, which has been named combretastatin A-4. This compound inhibited cell growth by 50% at 7 nM, inhibited tubulin polymerization by 50% at 2.5 microM (1/4 molar equivalent), and competitively inhibited colchicine binding with an apparent Ki of 0.14 microM.

Animals↗
PubMed1985

[Disseminated mycosis fungoides].

A case of mycosis fungoides (MF) that began with cutaneous eritemato-papular lesions leading to death with neurological symptoms is reported. Cutaneous histophatology was typical to MF and the liquoric citology showed Sézary cells. Necropsy evidenced extra-cutaneous dissemination of the tumor involving lymphnodes, heart, digestive system, bladder, liver, bone marrow and leptomeninges. The uncommon clinical manifestations and evolution are discussed.

Adult↗
PubMed1984

Unidirectional polar growth of cells of Seliberia stellata and aquatic seliberia-like bacteria revealed by immunoferritin labeling.

When grown in a complex peptone-yeast extract culture medium, Seliberia stellata and related morphologically similar aquatic bacterial strains typically divided asymmetrically, giving rise to a motile swarmer and a longer sessile rod. Indirect immunoferritin labeling of these bacteria, followed by incubation during which cell growth occurred, has provided evidence that antigenic cell-surface components are synthesized de novo in a sharply demarcated zone at one pole of the growing parent cells. Cell elongation occurred unidirectionally from the pole showing the de novo surface synthesis; it was this end of the elongating, helically sculptured (i.e., screw-like) rod that became the daughter swarmer cell. The daughter swarmers, produced after polar growth and division of the immunoferritin-labeled parent cells, were not labeled. The immunoferritin label remaining on the parent cell did not appear to be diluted or disturbed by the cell growth and division process. Under the cultural conditions used in this study, the growth and division events which led to production of swarmer cells in the seliberia strains examined met two major criteria of accepted definitions of budding (de novo cell surface synthesis and transverse asymmetry of division). However, the developing daughter cell was not initially narrower than the parent and thus did not increase in cell diameter during growth.

Bacteria↗
PubMed1984

Clinical trial of young red cell transfusions.

The lower mean cell age and prolonged 51Cr-labeled red cell survival of the top layer of centrifuged red blood cells suggest that this product may reduce blood requirements in patients with transfusion-dependent anemias. In a prospective clinical trial, we compared the effect of regular administration of young red cells with that associated with use of conventional frozen cells. Six patients with thalassemia major received 192 units of young red cells prepared from single donor units of whole blood using the IBM 2991 Cell Processor. The mean transfusion requirement to maintain the hemoglobin level greater than 9.0 gm/dl was 110 +/- 17 ml RBC/kg during the year of young cell transfusions, in comparison with 130 +/- 20 and 131 +/- 23 ml RBC/kg when conventional frozen cells were administered in the years before and after the young cell trial, respectively. Blood requirements in individual patients were reduced by 8% to 24% (mean 15.8%); the hemoglobin level remained constant. Although young cells of consistent quality can be prepared regularly in a clinical setting with little difficulty, the cost of the product is high and the effect on transfusion requirements is less than predicted from studies in vitro and from labeling experiments.

Blood Transfusion↗
PubMed1978

Presence of oncornavirus-like particles in the P388 murine leukemic cell line.

A culture of P388 murine lymphoblastoid cells has been shown to contain type C oncornavirus-like particles budding at the plasma membrane. Occasionally intracytoplasmic type A and immature type B particles were also observed by electron microscope techniques. The discovery of oncornavirus-like particles in the P388 cell line increases the utility of this neoplastic system for detecting potential antineoplastic agents.

Animals↗
PubMed1978

Life cycle of Mesocestoides corti in the dog (Canis familiaris).

Ten Beagle pups were each inoculated per os with 2,000 tetrathyridia of Mesocestoides corti from mice. The dogs were necropsied at 5-day intervals and the small intestine of each dog was divided into 3 equidistant sections. Adult cestodes were counted and characterized morphologically. The M corti reproduced asexually in the Beagles by longitudinal splitting of the parent scolex, separation of a new individual, and subsequent regrowth of 2 additional suckers on both the parent and newly formed scolices. Five days after the tetrathyridia were given, evidence of parent scolex division was present. The ability of M corti to reproduce asexually in the definitive host enabled rapid proliferation of new organisms, with approximately 53,000 present 45 days after inoculation.

Animals↗
PubMed1977

A review of exertional rhabdomyolysis in wild and domestic animals and man.

Exertional rhabdomyolysis is a condition arising in several species of newly captured wild animals after some form of physical exertion and stress. It is characterized by muscle necrosis and myoglobinuria. Death may result from secondary renal failure, acute or chronic heart failure and progressive emaciation.

Adrenal Cortex↗
PubMed1976

Fatty acid composition of selected prosthecate bacteria.

The cellular fatty acid composition of 14 strains of Caulobacter speices and types, two species of Prosthecomicrobium, and two species of Asticcacaulis was determined by gas-liquid chromatography. In most of these bacteria, the major fatty acids were octadecenoic acid (C18:1), hexadecenoic acid (C16:1) and hexadecanoic acid (C16:0). Some cyclopropane and branched chain fatty acids were detected in addition to the straight chained acids. Hydroxytetradecanoic acid was an important component of P.enhydrum but significant amounts of hydroxy acids were not detected in other prosthecate bacteria examined.

Bacteria↗