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At least 1,729 records · Page 96Linked to original sources
PubMed2000

Clomethiazole protects against hemineglect in a primate model of stroke.

Permanent occlusion of the M1 segment of the middle cerebral artery (pMCAO) in the marmoset, a New World species of monkey, produces unilateral functional deficits, including motor neglect with the contralesional arm and contralesional spatial hemineglect. In this study we examined whether clomethiazole, a drug which modulates the gamma-aminobutyric acid(A) receptor, reduced the severity of the hemineglect and other deficits in this primate model of stroke. Nine monkeys received pMCAO; 1 h later four of the nine were administered clomethiazole by intraperitoneal injection and subcutaneous implantation of osmotic mini-pumps, which released clomethiazole for 48 h. The monkeys had been trained and tested on a number of behavioral tasks prior to surgery and were re-tested 3 and 10 weeks later. Three weeks after pMCAO, monkeys treated with clomethiazole had a significantly reduced degree of spatial neglect compared to untreated controls. Clomethiazole was not effective against the severe contralesional motor impairment in the current study, although it ameliorated a somewhat less severe motor deficit in a previous study in which the more distal, M2 segment of the middle cerebral artery had been occluded. Postmortem analysis of the brains showed that clomethiazole treatment had significantly reduced the area of damage in part of the parietal cortex. These data suggest that clomethiazole may reduce the neglect that can be a debilitating consequence of right-sided stroke in man.

Animals↗
PubMed2000

Progressive inactivation of the haploid expressed gene for the sperm-specific endozepine-like peptide (ELP) through primate evolution.

The endozepine-like peptide (ELP) is a novel intracellular molecule which is expressed in high amounts at both mRNA and protein levels very specifically in late haploid male germ cells. It is closely related to the ubiquitous acyl-CoA binding protein, is highly conserved, shares a similar ability to bind mid-long chain acyl-CoA, and is thus likely to be involved in mature sperm metabolism. While it has been characterized from diverse mammals, it has so far not been possible to identify an equivalent molecule in the primate testis. Using a PCR approach, combined with cDNA cloning and Northern hybridization, testicular transcripts and/or genomic DNA were analysed for different primate species, including human. In the marmoset and cynomolgus macaque normally structured transcripts appear to be expressed, though at a low level. In the human testis, two rare transcripts were characterized, hELP1 and hELP2, the products of independent duplicated genes. Both transcripts were longer than in non-mammalian species, included frame-shift mutations and substantial sequence insertions, preventing the translation of a sensible protein. Genomic PCR analysis of three anthropoid species, chimpanzee, gorilla and orangutan, showed the presence of a similarly mutated hELP1 gene. Only in the gorilla was a hELP2 gene identified, apparently lacking the frame-shift mutation, and thus potentially able to give rise to a functional ELP protein. Taken together, these results show that during primate evolution there has been a progressive inactivation of the ELP gene, initially with a down-regulation in lower primates, and subsequently with inactivating mutations in the open reading frame. At some time during simian evolution prior to these mutations there has been a gene duplication, though this second gene has also become inactivated in humans. In its pattern of evolution the ELP gene shows similarities with the MDC/fertilin family, whose members are also considered essential components of haploid sperm in non-primates, but which are progressively inactivated in anthropoids and humans. We should like to speculate that the established subfertility of the human male may not be a recent event, but the consequence of a longer evolutionary process whereby primates have traded off absolute fertility against social or sexual advantages.

Amino Acid Sequence↗
PubMed1997

Four-week repeated inhalation study of HCFC 225ca and HCFC 225cb in the common marmoset.

Four male and three female marmosets in each group were exposed to air only, 1000 ppm of HCFC 225ca or 5000 ppm of HCFC 225cb, for 6 h per day for 28 consecutive days. HCFC 225ca caused a slight reduction in body weight. HCFC 225cb occasionally caused somnolence during exposure and vomiting on the first day of exposure. Clinical chemistry findings included a mild reduction of triglyceride, cholesterol and phospholipid levels and increased GOT level in the HCFC 225ca exposure group. HCFC 225cb also caused a reduction of triglyceride levels in some animals. HCFC 225ca caused a slight increase of hepatic carnitine palmitoyltransferase (CPT) activity while HCFC 225cb slightly increased cyanide-insensitive palmitoyl CoA beta-oxidation (FAOS) activity. In the HCFC 225cb exposure group, an increase in cytochrome P-450 content was also observed. HCFC 225ca caused a fatty change in the hepatic cells. Increased incidence of lipid droplets in the hepatic cells and myelin-like bodies in hepatic cells, Kupffer's cells and hepatic blood vessels were observed electron microscopically in the HCFC 225ca exposure group. A proliferation of smooth endoplasmic reticulum was observed in the HCFC 225cb exposure group. Decreased peroxisome volume density in the HCFC 225ca group, and increased volume density in the HCFC 225cb exposed females were seen. However, organ weight measurement and histopathological examination did not reveal hepatomegaly or hypertrophy with either substance. Although slight changes were noticed in peroxisome volume density and in some of the peroxisomal enzyme activities, the changes related to peroxisome proliferation with HCFC 225ca and 225cb were minimal in marmosets compared to those seen in rats. Histopathological examination and hormonal analysis did not reveal any abnormalities in the pancreas or testes.

Administration, Inhalation↗
PubMed2000

Automated quantitative determination of the new renin inhibitor CGP 60536 by high-performance liquid chromatography.

A fully automated high-performance liquid chromatography method with fluorescence detection for the determination of the renin inhibitor CGP 60536 in animal and human plasma and urine has been developed and validated. After addition of an internal standard, the compounds were automatically extracted from 400 microl of plasma or urine with methyl alcohol-acetic acid (99:1, v/v) on 100-mg Bond-Elut CN cartridges using the Gilson ASPEC system. The on-line chromatographic separation was performed on a LiChrospher 100 RP8 5-microm particle size packed analytical column (25x0.4 cm I.D.). The mobile phase consisted of acetonitrile-0.01 M potassium dihydrogenphosphate (65:35, v/v) at a flow-rate of 0.8 ml/min. The analytes were detected using a fluorescence detector at excitation and emission wavelengths of 280 and 330 nm, respectively. The limit of quantitation was established at 4.5 ng/ml in plasma (accuracy 106% and precision 1%), and 9.0 ng/ml in urine (accuracy 101% and precision 13%). The method was applied to the investigation of the pharmacokinetics of CGP 60536.

Animals↗
PubMed1997

Differences between guinea pig and rat in the dorsal cochlear nucleus: expression of calcium-binding proteins by cartwheel and Purkinje-like cells.

This study describes differences between guinea pig and rat in the immunoreactivities for calbindin (CB-IR) and parvalbumin (PV-IR) in cartwheel (CWC) and Purkinje-like (PLC) cells of the dorsal cochlear nucleus (DCN). CWCs are the most important inhibitory interneurons of the DCN. Their soma and dendrites stain intensely for CB-IR in guinea pigs but only weakly and incompletely in rats. In both species, the CWCs do not show PV-IR. PLCs, a rare type of DCN cells often interpreted as displaced cerebellar Purkinje cells misrouted during migration, are known from rat and mouse and are here described for guinea pig DCN. PLCs are intensely and completely stained for CB-IR and PV-IR in guinea pigs. In rats, they stain with similar completeness only for CB-IR, PV-IR being weak and restricted to the cell's soma. Similar staining differences between the two species are seen with the cerebellar Purkinje cells, i.e., PLCs resemble the cerebellar Purkinje cells more than do the CWCs. Based on the present material (and preliminary findings in a primate (marmoset), we speculate that the PLCs have their place in the circuitry of the DCN receiving input via parallel fibers, like the CWCs, and possibly projecting their axon onto the cerebellum.

Animals↗
PubMed1995

Molecular identification of two distinct hemagglutinin types of measles virus by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).

Contemporary isolates of measles virus, characterized by their inability to hemagglutinate, have been shown to possess a hemagglutinin type distinct from that of classical strains such as the Edmonston strain in that there is a new glycosylation site at amino acid residue 416. This change abolishes a Sau3Al site that is found in the corresponding position of the hemagglutination-positive classical strains. This molecular information prompted us to develop a restriction fragment length polymorphism (RFLP) assay that is capable of distinguishing these two distinct hemagglutinin types. The assay consists of the amplification of a 349-bp segment of the hemagglutinin gene by reverse transcription followed by the polymerase chain reaction and Sau3Al digestion of this amplification product. The resulting two distinct RFLP patterns identified the hemagglutinin types with regard to the presence or absence of the potential new glycosylation site. This assay was applied to determine the relative frequencies over a 28-year period of these two hemagglutinin types present in the archival acute serum specimens taken from patients with measles. This study revealed that strains carrying the classical hemagglutinin type predominated until the early 1980s when it became completely replaced with strains possessing the contemporary hemagglutinin type. Because of its direct applicability to the clinical specimens avoiding selection bias during cell-culture adaptation, this assay provides a valuable asset in both clinical laboratory and epidemiological settings.

Animals↗
PubMed1999

Positive correlation between mammalian life span and cellular resistance to stress.

Identifying the mechanisms determining species-specific life spans is a central challenge in understanding the biology of aging. Cellular stresses produce damage, that may accumulate and cause aging. Evolution theory predicts that long-lived species secure their longevity through investment in a more durable soma, including enhanced cellular resistance to stress. To investigate whether cells from long-lived species have better mechanisms to cope with oxidative and non-oxidative stress, we compared cellular resistance of primary skin fibroblasts from eight mammalian species with a range of life spans. Cell survival was measured by the thymidine incorporation assay following stresses induced by paraquat, hydrogen peroxide, tert-butyl hydroperoxide, sodium arsenite and alkaline pH (sodium hydroxide). Significant positive correlations between cell LD90 and maximum life span were found for all these stresses. Similar results were obtained when cell survival was measured by the MTT assay, and when lymphocytes from different species were compared. Cellular resistance to a variety of oxidative and non-oxidative stresses was positively correlated with mammalian longevity. Our results support the concept that the gene network regulating the cellular response to stress is functionally important in aging and longevity.

Animals↗
PubMed2002

Predicting functional properties of visual cortex from an evolutionary scaling law.

The number of neurons in the primary visual cortex (V1) is, across primate species, related to the number of neurons in the visual thalamus (the lateral geniculate nucleus [LGN]) by a power law with an exponent of 3/2. This evolutionary scaling law is explained by a simple relation according to which the fineness of resolution in cortex is related to the number of neurons in the area of cortex used to process the information from a single point of light (the point-spread area). The same theory provides a link between two functional properties of the visual cortex, the areal cortical magnification factor (ACMF) and the receptive field (RF) area.

Animals↗
PubMed1993

The behaviour of mandibular condylar cartilage in cell culture.

This investigation aimed to identify the behaviour of primate mandibular condylar cartilage cells in an in vitro model. Cells were harvested from the mandibular condyles of 1-year-old marmosets and maintained in primary culture for up to 30 d. Cell proliferation, structure, and phenotype were assessed at regular intervals by phase-contrast microscopy, cytologic staining, and immunocytochemistry. Cell growth increased progressively, and cultures reached confluence after 22 d. Cells were initially small and round but later became enlarged and heterogeneous in shape. Polygonal and hypertrophic chondroblast-like cells dominated the mature cultures. Glycosaminoglycan synthesis increased as cultures aged. Type I collagen was produced by early cultures, whereas type II collagen predominated in mature confluent monolayers. It is suggested that this mixed population of cells underwent phenotypic changes in primary cell culture that closely resemble the normal in vivo maturation process.

Animals↗
PubMedDate not supplied

Bacteriocin production by Actinobacillus actinomycetemcomitans isolated from the oral cavity of humans with periodontal disease, periodontally healthy subjects and marmosets.

The ability of Actinobacillus actinomycetemcomitans to produce bacteriocin has rarely been reported. Antagonistic substance production may confer an important ecological advantage for the producer microorganisms, especially in a competitive ecosystem such as the oral cavity. In the present study, 75 A. actinomycetemcomitans strains isolated from the oral cavity of human patients with periodontal disease, periodontally healthy subjects and marmosets, as well as two reference strains (A. actinomycetemcomitans ATCC 29523 and FDC Y4) were evaluated for auto-, iso-, and heteroantagonistic activity. Fifty-one (68.00%) strains exhibited antagonistic activity; heteroantagonism was observed more often than isoantagonism. Isolated strains antagonized 17 different species of gram-positive and gram-negative bacteria from the oral and nonoral microbiota. Sensitivity to heat and to proteolytic enzymes constituted strong evidence that the antagonistic substance has a proteic nature. Taken together, our data enabled us to confirm that the antagonistic substance detected was a bacteriocin. The wide spectrum of activity indicates the possibility that more than one antagonistic substance is produced and that these substances play an important role in the ecological balance of the oral ecosystem.

Actinobacillus Infections↗
PubMedDate not supplied

A human B-lymphoblastoid cell line constitutively producing Epstein-Barr herpesvirus and JHK retrovirus.

The human B-lymphoblastoid cell line, designated JHK-3, with pre-B-cell characteristics, chronically produces two viruses, Epstein-Barr virus (EBV) and JHK virus, an apparently novel retrovirus. The JHK-3 cells are much more productive of extracellular EBV than the high-producer marmoset line B95-8. The extracellular virus of the JHK-3 EBV strain is relatively fragile, more broadly dispersed in an ultracentrifuged sucrose gradient than the B95-8 EBV and more susceptible to disruption by combined treatment with urea and dithiothreitol. By restriction fragment length polymorphism analysis, the JHK-3 EBV strain resembles the EBV strain FF-41. The JHK-3 cells also produce an incompletely characterized, relatively fragile, enveloped, icosahedral RNA virus that contains Mn(++)-dependent reverse transcriptase. JHK virions measure 85 nm in ultrathin sections, much smaller than other Retroviridae. The JHK virus exhibits a distinctive morphogenesis, most nearly resembling C-type retroviruses. The JHK-3 cell line provides a human cell model for investigating virus/virus interactions and their pathogenetic affects on host cells which chronically and simultaneously produce DNA and RNA viruses.

Animals↗
PubMed1992

In vitro characteristics of Yersinia pseudotuberculosis of nonhuman primate origin.

Six strains of serotypes 1 or 2 of Y. pseudotuberculosis were isolated from dead squirrel monkeys, a cotton-top tamarin and a marmoset hybrid. All strains harboured a 71.6 kb plasmid, all were totally oxacillin-resistant and partially resistant to cephalosporins. Biochemically, serotypes 1 and 2 differed from each other in their beta-galactosidase production in a nonfermenter system, whereas the lack of rhamnose, maltose, salicin and trehalose fermentation seemed to be attributable to technical causes.

Animals↗
PubMed1995

Visualization of hydrogen peroxide (H2O2)-production from histamine.

The cellular and intracellular metabolization sites of the tissue hormone and paracrine compound histamine as a source for the indirect and potentially toxic or physiological mediator molecule H2O2 are not yet known. Therefore, in the present study, histamine was used as the substrate in a cerium-diaminobenzidine-H2O2-Co procedure to visualize for the first time the oxidative deamination and H2O2-production sites of this amine in various laboratory animals. Diamine oxidase (DAOX) was shown to be the responsible enzyme. With the exception of marmosets, all species could deaminate histamine oxidatively and form H2O2. In most species, H2O2 was produced by DAOX from histamine in small intestinal enterocytes; in rats H2O2 was generated in all vascular and non-vascular smooth muscle cells; in guinea-pigs only smooth muscle cells in the digestive tract and uterus and in addition the cardiac and gastric capillary endothelium and hepatic sinusoidal endothelium produced H2O2. Furthermore, in some species H2O2 was generated by DAOX with histamine as the substrate in certain renal, adrenal and splenic cell types. While H2O2-production in enterocytes may derive from luminal-borne histamine, i.e., from histamine of foreign origin, the formation of H2O2 in the other cells suggests endogenous (mast cell, basophilborne) histamine as the substrate and H2O2 source.

Amine Oxidase (Copper-Containing)↗
PubMed1998

The synthesis of novel matrix metalloproteinase inhibitors employing the Ireland-Claisen rearrangement.

Matrix metalloproteinase inhibitors of general formula (1) were synthesised by a route involving an Ireland-Claisen rearrangement which enables systematic modification of the substituent alpha to the hydroxamic acid. An analogue (12c) possessing an alpha-cyclopentyl group is a potent broad spectrum inhibitor that displays high and sustained blood levels following oral dosing in both the rat and marmoset ex-vivo bioassays. This compound and analogues are also potent inhibitors of TNF alpha release.

Administration, Oral↗
PubMed1999

Piperidine-renin inhibitors compounds with improved physicochemical properties.

Piperidine renin inhibitors with heterocyclic core modifications or hydrophilic attachments show improved physical properties (lower lipophilicity, improved solubility). Tetrahydroquinoline derivative rac-30 with a molecular weight of 517 and a log D(pH 7.4) of 1.9 displays potent and long lasting blood pressure lowering effects after oral administration to sodium depleted conscious marmosets.

Animals↗
PubMed2002

Novel 4,1-benzoxazepine derivatives with potent squalene synthase inhibitory activities.

A series of (3,5-trans)-2-oxo-5-phenyl-1,2,3,5-tetrahydro-4,1-benzoxazepine derivatives were synthesized and evaluated for squalene synthase inhibitory and cholesterol biosynthesis inhibitory activities. Through modification of substituents of the lead compounds 1a and 1b, it was found that 4,1-benzoxazepine-3-acetic acid derivatives with isobutyl and neopentyl groups at the 1-position, the chloro atom at the 7-position, and the chloro and methoxy groups at the 2'-position on the 5-phenyl ring, had potent squalene synthase inhibitory activity. Among such compounds, the 5-(2,3-dimethoxyphenyl) derivative 2t exhibited potent inhibition of cholesterol biosynthesis in HepG2 cells. As a result of optical resolution study of 2t, the absolute stereochemistry required for inhibitory activity was determined to be 3R,5S. In vivo study showed that the sodium salt of (3R,5S)-7-chloro-5-(2,3-dimethoxyphenyl)-1-neopentyl-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepine-3-acetic acid 20 effectively reduced plasma cholesterol in marmosets.

Administration, Oral↗
PubMed1998

A comparison of rectal and subcutaneous body temperature measurement in the common marmoset.

Two methods of measuring body temperature were compared in common marmosets. Subcutaneous temperatures were measured remotely via previously implanted subcutaneous microchips (Plexx BV, IPTT-100) prior to measurement of rectal temperature using a conventional rectal probe. Marmosets were treated with saline or the brain penetrant, 5-HT1A/B/D receptor agonist SKF-99101H (3-(2-dimethylaminoethyl)-4-chloro-5-propoxyindole hemifumarate) (0.3-3 mg/kg SC), which has previously been shown to induce hypothermia in guinea pigs. Body temperature was sampled immediately before drug administration and at 30-min intervals thereafter for a period of 2.5 h. SKF-99101H dose-dependently induced hypothermia in the common marmoset and there was close agreement between rectal and subcutaneous body temperatures, with an average difference in absolute body temperature of 0.26+/-0.02 degrees C. The data show that subcutaneously implanted microchips provide a simple, reliable measure of body temperature in common marmosets which is sensitive to pharmacological intervention, minimizes handling induced stress, and is minimally invasive.

Animals↗