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Biomedical subjects

G Holz

Publications and source records attributed to G Holz.

9 recordsLinked to original sources

Comparison of several lizard Leishmania species and strains in terms of kinetoplast minicircle and maxicircle DNA sequences, nuclear chromosomes, and membrane lipids.

Eight strains of a lizard Leishmania species, L. tarentolae, were compared with four other saurian species [L. hoogstrali, L. adleri, L. agamae and Leishmania sp. LizS], with L. major from man and with Trypanosoma platydactyli, a putative lizard trypanosome, in terms of kinetoplast DNA minicircle and maxicircle sequences and in terms of nuclear chromosome patterns on orthogonal gel electrophoresis. The L. tarentolae strains fell into two major groups, one (group A) consisting of the L. tarentolae strains, UC, Krassner and Trager, derived from an Algerian gecko isolate and the other (group B) consisting of five L. tarentolae LEM strains isolated from geckos in southern France. T. platydactyli TPCL2, which was postulated by Wallbanks et al. to represent the lizard form of a French L. tarentolae strain, was closely related to the UC strain and not to the LEM strains, in all respects analyzed. Leishmania sp. LizS from a Mongolian gecko and L. hoogstrali from a Sudanese gecko showed some sequence similarities to the L. tarentolae strains, but the leishmanias said to be L. adleri from a Kenyan lacertid and L. agamae from an Israeli agamid showed no minicircle sequence similarities with lizard Leishmania and in fact were probably the same species. The maxicircle divergent region was larger in the group B strains than in the group A strains, but there were sequences in common with both groups, and not with L. hoogstrali and L. major. Four strains of L. tarentolae, the four other supposed saurian Leishmania species, three mammalian leishmanias, T. platydactyli and four other trypanosomes, T. cyclops (Malaysian macaque), T. conorrhini (Hawaiian reduviid bug), T. cruzi (man) and T. lewisi (feral rat) were analyzed for their contents of sterols and phosphoglyceride fatty acyl groups. T. platydactyli TPCL2 contained a sterol (5-dehydroepisterol), a phosphatidylcholine fatty acyl group (alpha-linolenic acid) and a phosphatidylethanolamine fatty acyl group (dihydrosterculic acid) characteristic of members of the genus Leishmania and not the genus Trypanosoma. The proportions of those lipids in the free sterol and phosphoglyceride fractions of T. platydactyli TPCL2 most closely resembled those seen in the Leishmania strains from Algerian, French, Mongolian and Sudanese geckos.

Animals↗

The status of Leishmania tarentolae/Trypanosoma platydactyli.

Taxonomic studies and classification of Leishmania species have developed rapidly in recent years, but controversy still surrounds the relationships between those species infecting lizards and those infecting mammals. Some authorities maintain that the leishmanias o f lizards form a sufficiently distinct group to be ranked as a separate genus - Sauroleishmania(1,2) - while Wallbanks et al. have gone further to suggest that such species might be classified within the genus Trypanosoma(3). This suggestion followed from work showing that promostigote forms of Trypanosoma platydactyli from a gecko, had similar isoenzyme profiles to Leishmania tarentolae, a well-known species from lizards. In this article however, Larry Simpson and George Holz Jr discuss conflicting evidence, concluding from recent studies of DNA and lipid composition that the lizard leishmanias are more closely related to mammalian leishmanias than to trypanosomes.0.

Journal Article↗

Paget's disease of bone in West Germany. Prevalence and distribution.

In the region of Baden-Württemberg, 6751 doctors (general practitioners, internists, surgeons, and orthopedists) were asked to report on patients in their practice with Paget's disease of bone. Two hundred forty-nine doctors reported on 325 cases of Paget's disease, half of which were regarded as needing treatment. Since the authors' unit received 47 Paget patients in Baden-Württemberg and about half of them were registered during the investigation, it can be concluded that around 300 patients with clinically significant disease needing treatment are known. They represented only 0.25% of an estimated 120,000 cases of Paget's disease in people older than 40 years of age expected among the 4.03 million people of this age group. Analysis of the epidemiologic data from 103 cases of Paget's disease of bone revealed an equal sex distribution (51 men and 52 women), but age at diagnosis was about one decade earlier in men. The anatomic distribution showed most often involvement of pelvic bones, followed by femora, calvarium, tibiae, and lumbar vertebrae. Right-sided preference was not evident, but the distribution favors the suggestion that physical stress may be a factor or cofactor in the clinical manifestations of the disease.

Adult↗

[Etidronic acid therapy in Paget's disease of bone].

Treatment of Paget's disease of bone was done in 32 patients using monotherapy with disodium etidronate (Diphos). A further 19 patients underwent combined treatment with etidronate and human calcitonin. Both monotherapy and combined treatment led to marked regression of disease activity in most patients as measured be decreased activity of alkaline phosphatase. In most cases this coincided with improvement of complaints. In two cases with initial monotherapy and in six with combined treatment success of treatment remained unsatisfactory. The latter group comprised patients with very serious illness. Our experience suggests that etidronic acid is an effective and well tolerated drug relatively free of side-effects for the treatment of Paget's disease of bone.

Alkaline Phosphatase↗

Glycoproteins containing peanut-agglutinin receptors from human-peripheral-blood T-lymphocyte plasma membranes.

A glycoprotein fraction possessing peanut agglutinin receptors has been isolated from detergent extracts of neuraminidase-treated human peripheral blood T-lymphocyte plasma membranes with affinity matrices comprising the peanut agglutinin co-valently immobilised on Sepharose 4B. This fraction could be specifically eluted from affinity columns using buffer solutions supplemented with 0.2 M D-galactose and was shown, by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate (0.1%), to contain four major glycoprotein components with apparent molecular weights of 200000, 190000, 110000 and 95000. It is suggested, from the observed reactivity of these glycoproteins with various lectins in double-diffusion experiments, that they possess both O-glycosidically and N-glycosidically linked carbohydrates.

Cell Membrane↗

Comparison of isolated peanut agglutinin receptor glycoproteins from human, bovine and porcine erythrocyte membranes.

Affinity chromtography has been used to isolate and compare the peanut agglutinin receptors from neuraminidase-treated human, bovine and porcine erythrocyte membranes. Passage of Triton X-100-solubilised membrane material through either Sepharose- or acrylamide-based affinity columns resulted in the reversible binding of receptor molecules to the immobilised lectin. Elution with 0.2 M galactose released specifically bound glycoprotein fractions, the composition and molecular weights of which were determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. Carbohydrate analysis by gas chromatography identified these bound glycoprotein fractions as the major sources of the O-glycosidic-linked disaccharide galactosyl-beta-(1 leads to 3)-N-acetylgalactosamine in these membranes. It is suggested that these isolated fractions represent a discrete population of glycoproteins within the membranes studied, which possess both O-glycosidic- and N-glycosidic-linked carbohydrates.

Animals↗

New insights concerning the glucose-dependent insulin secretagogue action of glucagon-like peptide-1 in pancreatic beta-cells.

The GLP-1 receptor is a Class B heptahelical G-protein-coupled receptor that stimulates cAMP production in pancreatic beta-cells. GLP-1 utilizes this receptor to activate two distinct classes of cAMP-binding proteins: protein kinase A (PKA) and the Epac family of cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs). Actions of GLP-1 mediated by PKA and Epac include the recruitment and priming of secretory granules, thereby increasing the number of granules available for Ca(2+)-dependent exocytosis. Simultaneously, GLP-1 promotes Ca(2+) influx and mobilizes an intracellular source of Ca(2+). GLP-1 sensitizes intracellular Ca(2+) release channels (ryanodine and IP (3) receptors) to stimulatory effects of Ca(2+), thereby promoting Ca(2+)-induced Ca(2+) release (CICR). In the model presented here, CICR activates mitochondrial dehydrogenases, thereby upregulating glucose-dependent production of ATP. The resultant increase in cytosolic [ATP]/[ADP] concentration ratio leads to closure of ATP-sensitive K(+) channels (K-ATP), membrane depolarization, and influx of Ca(2+) through voltage-dependent Ca(2+) channels (VDCCs). Ca(2+) influx stimulates exocytosis of secretory granules by promoting their fusion with the plasma membrane. Under conditions where Ca(2+) release channels are sensitized by GLP-1, Ca(2+) influx also stimulates CICR, generating an additional round of ATP production and K-ATP channel closure. In the absence of glucose, no "fuel" is available to support ATP production, and GLP-1 fails to stimulate insulin secretion. This new "feed-forward" hypothesis of beta-cell stimulus-secretion coupling may provide a mechanistic explanation as to how GLP-1 exerts a beneficial blood glucose-lowering effect in type 2 diabetic subjects.

Animals↗