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Biomedical subjects

J L Martin

Publications and source records attributed to J L Martin.

At least 217 records · Page 12Linked to original sources

Dimensions and form of dental arches in subjects with normal occlusions.

To determine the main mandibular dental arch forms, 278 dental casts of untreated French adults with normal occlusions were examined. Six measurements of the mandibular dental arches were performed, and five independent ratios were determined. By following the k-means clustering method on the basis of these ratios and the use of polynomial functions of the sixth degree, five mandibular dental arch forms were defined, and an arch guide was developed. The proposed forms are relatively narrow in comparison with previous studies. No significant differences in their distributions were seen between male and female subjects. However, the dental arches of the women have smaller dimensions.

Adolescent↗

Effects of AIDS-related bereavement and HIV-related illness on psychological distress among gay men: a 7-year longitudinal study, 1985-1991.

In this study we examined the influence of acquired immunodeficiency syndrome (AIDS)-related bereavement on psychological distress from 1985 through 1991. We predicted that this relation would be influenced by personal knowledge of human immunodeficiency virus (HIV) infection and symptoms consistent with HIV-related illness. Interview data collected each year on a cohort of 746 gay men included information on the deaths and illnesses of network members caused by AIDS, as well as on psychological distress, sedative use, HIV-related symptoms, and HIV infection status. Significant main effects of bereavement were found in each year after controlling for both losses occurring from 1 to 2 years previously and for AIDS and HIV health status. The intensity and duration of these bereavement effects diminished over time. Groups of men who were both bereaved and classified as having AIDS or were HIV positive reported the highest level of distress in every year compared with the 3 other groups.

Acquired Immunodeficiency Syndrome↗

The 5'-triphosphates of the (-) and (+) enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolane-5-yl]cytosine equally inhibit human immunodeficiency virus type 1 reverse transcriptase.

The (-) enantiomer of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolane-5-yl]cytosine is a potent inhibitor of human immunodeficiency virus type 1 in vitro. The 5'-triphosphates of the (-) and (+) enantiomers equally inhibited the production of full-length minus-strand DNA in an endogenous reverse transcriptase reaction, each competitively inhibited DNA synthesis, and each was used as a chain-terminating substrate.

Antiviral Agents↗

Neurotransmitters regulate energy metabolism in astrocytes: implications for the metabolic trafficking between neural cells.

In recent years a vast array of experimental evidence has indicated the presence of functional receptors for neurotransmitters on nonneuronal cells, in particular astrocytes. The two neurotransmitters vasoactive intestinal peptide (VIP) and noradrenaline (NA) exert profound, receptor-mediated, metabolic actions on astrocytes. Thus both neurotransmitters stimulate glycogenolysis in primary astrocyte cultures, with EC50s of 3 and 20 nM respectively. Astrocytes display basal glucose utilization rates ranging between 3 and 9 nmol/mg prot/min, a value that is remarkably close to glucose utilization of cerebral cortical grey matter as determined by the 2-deoxyglucose autoradiographic technique. NA markedly enhances glucose uptake and phosphorylation by astrocytes, with an EC50 of 1 microM. The metabolic substrate that is released by astrocytes is predominantly lactate and not glucose. Since lactate can support neuronal activity and synaptic function in vitro, the possibility should be considered that glucose uptake by the brain parenchyma occurs predominantly into astrocytes which subsequently release lactate for the use of neurons.

Animals↗

Immunohistochemical localization of carboxylesterase in the nasal mucosa of rats.

The enzymatic esterase activity of carboxylesterases is integral to the nasal toxicity of many esters used as industrial solvents or in polymer manufacture, including propylene glycol monomethyl ether acetate, dimethyl glutarate, dimethyl succinate, dimethyl adipate, and ethyl acrylate. Inhalation of these chemicals specifically damages the olfactory mucosa of rodents. We report the localization and differential distribution of a 59 KD carboxylesterase in nasal tissues of the rat by immunohistochemistry. Rabbit antiserum against the 59 KD rat liver microsomal carboxylesterase bound most prominently to the olfactory mucosa when applied to decalcified, paraffin-embedded sections of rat nasal turbinates. Within the olfactory mucosa, anti-carboxylesterase did not bind to sensory neurons, the target cell for ester-initiated toxicity; these cells apparently lack carboxylesterase. Instead, the antibody was preferentially bound by cells of Bowman's glands and sustentacular epithelial cells which are immediately adjacent to the olfactory nerve cells. In contrast, non-olfactory tissues (respiratory mucosa and squamous epithelium), which are more resistant to the toxicity of esters, had less carboxylesterase content. The distribution of immunoreactivity correlated well with the distribution of carboxylesterase catalytic activity described elsewhere. These findings help to link the metabolic fate of inhaled esters to the site-specific pathological findings that follow exposure to such chemicals.

Animals↗

Childhood sexual abuse and mental health in adult life.

The relationship between childhood sexual abuse and mental health in adult life was investigated in a random community sample of women. There was a positive correlation between reporting abuse and greater levels of psychopathology on a range of measures. Substance abuse and suicidal behaviour were also more commonly reported by the abused group. Childhood sexual abuse was more frequent in women from disrupted homes as well as in those who had been exposed to inadequate parenting or physical abuse. While elements in the individual's childhood which increased the risks of sexual abuse were also directly associated to higher rates of adult psychopathology, abuse emerged from logistic regression as a direct contributor to adult psychopathology. Severity of abuse reported was related to the degree of adult psychopathology. The overlap between the possible effects of sexual abuse and the effects of the matrix of disadvantage from which it so often emerges were, however, so considerable as to raise doubts about how often, in practice, it operates as an independent causal element. Further, many of those reporting childhood sexual abuse did not show a measurable long-term impairment of their mental health. Abuse correlated with an increased risk for a range of mental health problems, but in most cases its effects could only be understood in relationship to the context from which it emerged.

Adolescent↗

Estimated condom failure and frequency of condom use among gay men.

OBJECTIVES: Condoms are designed to bar transmission of the human immunodeficiency virus (HIV), but they sometimes fail. This paper explores the effect of experience with condoms on condom failure among gay men. METHODS: Risk of condom failure (breakage or slippage) on a single occasion is estimated for four sexual acts reported over 12 months by a sample of gay New York City men (n = 741). The estimation procedure assumes that each episode in which a condom is used is an independent event. Evidence is offered to support this assumption. RESULTS: Risk of condom failure in a single episode was fairly high, particularly in anal intercourse, for men who had engaged in each act only a few times in the previous year. It declined rapidly with experience (e.g., to below 1% for receptive anal intercourse after about 10 episodes in the previous year). Condoms failed less often in oral than anal sex, but estimated risk of failure also decreased with experience. CONCLUSIONS: Gay men should be especially cautious the first few times they use a condom; after moderate experience, however, they may expect a low risk of condom failure.

Adolescent↗

The topography of trifluoroacetylated protein antigens in liver microsomal fractions from halothane treated rats.

Sera from patients with halothane hepatitis contain immunoglobulin G (IgG) antibodies to trifluoroacetylated liver microsomal proteins of 100, 76, 59, 57 and 54 kDa, which are produced as a consequence of metabolism of halothane to trifluoroacetyl halide by cytochrome(s) P450. In the present study, the membrane topographies of the various antigens in rat liver microsomal fractions were investigated. Liver microsomal fractions from rats treated with halothane in vivo, and rat liver microsomal fractions which had been incubated with halothane in vitro, were used as the source of trifluoroacetyl antigens. The antigens were detected by immunoblotting. Whereas the 100, 76, 59 and 57 kDa antigens were solubilized from the microsomal membrane by either 0.1 M sodium carbonate or 0.1% (w/v) sodium deoxycholate, the 54 kDa antigen was not solubilized by 0.1% (w/v) sodium deoxycholate. In intact microsomal fractions, the 100, 76, 59 and 57 kDa antigens were not degraded appreciably by trypsin unless detergent was added to permeabilize the microsomal membrane. These results indicate that the 54 kDa antigen is an integral membrane protein, whereas the 100, 76, 59 and 57 kDa antigens are peripheral membrane proteins situated within the lumen of microsomal vesicles, and hence presumably located within the lumen of the endoplasmic reticulum in vivo.

Animals↗

VIP receptor subtypes in mouse cerebral cortex: evidence for a differential localization in astrocytes, microvessels and synaptosomal membranes.

The binding characteristics of a monoiodinated form of vasoactive intestinal peptide (M-[125I]VIP) to the membranes of astrocytes, intraparenchymal microvessels and synaptosomes were analyzed in mouse cerebral cortex. Binding to astrocytes, studied in primary cultures, indicates the presence of a single class of high affinity binding sites with a Kd of 3.3 nM and a Bmax of 565 fmol/mg protein. The structurally related peptide secretin does not compete for sites labeled by M-[125I]VIP. In cultured astrocytes, VIP has been previously shown to promote glycogenolysis. Secretin, despite its lack of interaction with sites labeled by M-[125I]VIP, stimulates glycogenolysis with an EC50 of 0.5 nM, thus demonstrating the presence in astrocytes of functional secretin receptors independent from those for VIP. Trypsinization of the primary astrocyte cultures followed by replating as secondary cultures, reveals a second class of low affinity binding sites, with a Kd of 41.3 nM and a Bmax of 881 fmol/mg protein. Secretin does not compete for this class of low affinity binding sites either. Binding of M-[125I]VIP to intraparenchymal microvessels reveals the presence of two classes of binding sites with Kd of 1.4 and 30.3 nM, and Bmax of 7.1 and 73.8 pmol/mg protein, respectively. Similar to what is observed in primary or secondary astrocyte cultures, secretin does not interact with these sites. In this cell type VIP stimulates cAMP formation with an EC50 of 18 nM, while secretin is ineffective. Finally, in agreement with previous reports in rat and guinea pig cerebral cortex, two classes of binding sites are observed in synaptosomal membranes: a high affinity class with a Kd of 4.9 nM and a Bmax of 316 fmol/mg protein, and a low affinity class with a Kd of 42.8 nM and a Bmax of 1578 fmol/mg protein. In contrast to what is observed in non-neuronal membranes, in synaptosomal membranes, secretin effectively competes for sites labeled by M-[125I]VIP with an EC50 of approximately 150 nM. These results indicate that secretin may represent a useful tool to discriminate between neuronal and non-neuronal VIP binding sites, since it competes with M-[125I]VIP exclusively for the neuronal class of binding sites.

Animals↗

Femtosecond spectral evolution of the excited state of bacterial reaction centers at 10 K.

The femtosecond spectral evolution of reaction centers of Rhodobacter sphaeroides R-26 was studied at 10 K. Transient spectra in the near infrared region, obtained with 45-fs pulses (pump pulses centered at 870 nm and continuum probe pulses), were analyzed with associated kinetics at specific wavelengths. The t = 0-fs transient spectrum is very rich in structure; it contains separate induced bands at 807 and 796 nm and a bleaching near 760 nm, reflecting strong changes in interaction between all pigments upon formation of the excited state. A complex spectral evolution in the 800-nm region, most notably the bleaching of the 796-nm band, takes place within a few hundred femtosecond--i.e., on a time scale much faster than electron transfer from the primary donor P to the bacteriopheophytin acceptor HL. The remarkable initial spectral features and their evolution are presumably related to the presence of HL, as they were not observed in the DLL mutant of Rhodobacter capsulatus, which lacks this pigment. A simple linear reaction scheme with an intermediate state cannot account for our data; the initial spectral evolution must reflect relaxation processes within the excited state. The importance for primary photochemistry of long distance interactions in the reaction center is discussed.

Cold Temperature↗

Alterations in tumor angiogenesis associated with stable expression of the HIV tat gene.

Recent evidence suggests that the human immunodeficiency virus type 1 (HIV) trans-activator gene (tat) has transforming properties and may be a causative factor in the development of certain types of cancers, in particular Kaposi's sarcoma (i.e., Vogel J. et al. Nature 335:606-611, 1988). To help elucidate the potential role or roles of the HIV tat gene in neoplastic transformation, cell lines were constructed that constitutively express a functional tat gene product. HeLa cells were coelectroporated with two plasmids, one containing the HIV tat gene in an expression cassette and another containing the dominant selectable marker gene xanthine guanine phosphoribosyltransferase (XGPRT). After XGPRT selection, single-cell clones that expressed a functional tat protein were identified by measuring chloramphenicol acetyltransferase (CAT) activity after electroporating a plasmid containing the CAT gene transcriptionally controlled by HIV trans-activation-responsive region (tar). Phenotypic alterations resulting from the expression of tat were then determined. Control cells and tat-expressing cells grew at similar rates in culture. However, when grown as tumors in nude mice, tat-expressing cells produced a lower percentage of tumors, and the tumors that were produced either regressed, stopped growing, or grew at a very reduced rate compared with cells not expressing tat. These differences may have resulted from a tat-associated reduction in neovascularization in the tumors. A comparison of total cellular proteins by two-dimensional polyacrylamide gel electrophoresis indicated only one reproducible alteration in a polypeptide of approximately 44 kDa and pl of approximately 6.2 associated with tat expression. These cells may be very useful in future in vitro and in vivo studies designed to examine the effects of HIV tat on endothelial and vascular smooth-muscle cells and the role of tat in the etiology of Kaposi's sarcoma.

Animals↗

Inhibition of human fibroblast insulin-like growth factors binding protein (IGFBP) production by IGFBP-3.

Human neonatal fibroblasts in monolayer culture secrete a number of insulin-like growth factor binding proteins (IGFBPs), including IGFBP-3, which may alter paracrine or autocrine IGF activity. Studies in vitro have demonstrated that exogenous IGFBP-3 can both inhibit and potentiate IGF action in these cells; however, it is not known to what extent there is regulatory interaction between the IGFBPs. In this study we report that exogenous and endogenous IGFBP-3 inhibit production of an IGF inducible IGFBP. When analyzed by SDS-PAGE and [125I]IGF-II ligand blotting, human neonatal fibroblasts secrete IGFBP-3, an IGFBP of 29-31 kDa, and a 22-24 kDa IGFBP after treatment with 50 ng/ml IGF-I. When IGF-I treatment was carried out in the presence of increasing concentrations (50-1000 ng/ml) of pure human serum-derived IGFBP-3, there was a dose-dependent decrease in the 29-31 kDa protein. In the presence of excess (250 ng/ml) IGF-I, IGFBP-3 had approximately 20-fold reduced potency in inhibiting 29-31 kDa IGFBP. When endogenous production of IGFBP-3 was increased by treatment with transforming growth factor-beta 1 (TGF beta 1), there was complete inhibition of 29-31 kDa IGFBP, while at high IGF-I concentrations TGF beta 1 had 2 to 3-fold reduced potency. These results demonstrate that fibroblast IGFBP production can be altered by exogenous and endogenous IGFBP-3, and suggest the existence of regulatory interactions between fibroblast IGFBPs.

Carrier Proteins↗

Insulin-like growth factor-I (IGF-I) and transforming growth factor-beta 1 release IGF-binding protein-3 from human fibroblasts by different mechanisms.

Human neonatal fibroblasts in monolayer culture secrete insulin-like growth factor-binding proteins (IGFBPs), which may modulate IGF action. To examine whether an increase in extracellular concentrations of IGFBPs in response to IGF-I is due to the release of cell-associated IGFBPs, we measured secreted and cell-associated IGFBP-3 immunologically in fibroblast monolayers treated with IGF-I and IGF analogs with altered affinities for the IGF receptors and IGFBPs. IGFBP-3 in medium conditioned by fibroblasts treated with IGF-I was significantly increased (P < 0.05) compared with that in medium from untreated cultures; concomitantly, cell-associated IGFBP-3 was significantly decreased (P < 0.05). [Ser24]IGF-I (reduced affinity for IGF receptors) also increased secreted IGFBP-3 and decreased cell-associated IGFBP-3. In contrast, IGFBP-3 concentrations in medium conditioned by fibroblasts treated with B-chain IGF-I (reduced affinity for IGFBPs) were not significantly increased, and cell-associated IGFBP-3 was unchanged. Heparin, which releases proteins attached to cell surface proteoglycans, increased medium concentrations of IGFBP-3 and decreased IGFBP-3 binding to fibroblasts. An IGFBP of 29-31 kilodaltons (kDa) showed a pattern of regulation similar to that of IGFBP-3, while a third IGFBP, of 24 kDa, was decreased in IGF-I- and [Ser24]IGF-I-conditioned medium and unchanged by B-chain IGF-I and heparin. Preincubation with transforming growth factor-beta 1 (TGF beta 1), which stimulates fibroblast IGFBP-3 production, or human serum-derived IGFBP-3 did not increase cell-associated IGFBP-3. Analysis of total RNA isolated from fibroblasts revealed that IGFBP-3 mRNA was increased by TGF beta 1, but not by IGF-I. These data suggest that IGFs and TGF beta 1 release fibroblast IGFBPs by distinct mechanisms: IGFs by binding and subsequent release of cell-associated IGFBP-3 and 29- to 31-kDa IGFBP, and TGF beta 1 by increased de novo synthesis of IGFBP-3.

Carrier Proteins↗

Experimental aspects of cerebrospinal hemodynamics: the relationship between blood flow velocity waveform and cerebral autoregulation.

The dynamic relationships among mean flow velocity, its pulsatile amplitude (FVa), cortical cerebral blood flow (CBF), and cerebral perfusion pressure (CPP) were studied in normal rabbits and rabbits with subarachnoid hemorrhage using 8-MHz pulsed transcranial Doppler ultrasound and hydrogen clearance under conditions of systemic hypotension and intracranial hypertension. A two-slope relationship was observed between FVa and CPP with a break point that correlated closely with the lower limit of CBF autoregulation in each animal. Below this CPP break point, FVa varied directly with CPP, and above the break point FVa varied inversely with CPP. In this experimental model, an inverse correlation between FVa and CPP indicates intact CBF autoregulation, whereas loss of that correlation implies exhaustion of autoregulatory reserve. Simultaneous recording and computation of FVa, CPP, and the correlation coefficient between FVa and CPP may be a means of monitoring CBF autoregulation in clinical practice.

Animals↗

Comparison of extraction methods for insulin-like growth factor-I in rat serum.

This study was undertaken to compare various extraction methods for insulin-like growth factor-binding proteins (IGFBPs) from insulin-like growth factor-I (IGF-I) in rat serum systematically, before measurement of IGF-I by radioimmunoassay (RIA). The values obtained in the IGF-I RIA following acid-ethanol (AE), acid-ethanol cryoprecipitation (AEC) and formic acid-acetone (FA) extraction methods were compared with the IGF-I values obtained following high-performance liquid chromatography (HPLC), which was the reference method. Radioligand blots were used to determine the pattern and degree of IGFBP removal by these methods. Over a wide range of circulating IGF-I levels, AE and AEC extraction gave IGF-I levels comparable with those obtained following HPLC. FA extraction resulted in IGF-I levels that were consistently higher (P < 0.01) than those obtained following HPLC and gave non-parallel displacement curves in comparison with recombinant IGF-I standards (P <0.01). Ligand blots demonstrated a similar pattern of IGFBP removal among the three methods with almost complete removal of IGFBP-3 but only 30-40% removal of the lower molecular weight IGFBPs. These lower molecular weight IGFBPs did not interfere with the RIA measurements of IGF-I from AE and AEC extracts. Therefore the AE extraction method of Daughaday, originally validated for use in human serum, is also satisfactory for use in rat serum. The complete removal of IGF-binding activity does not appear essential for accurate measurement of IGF-I by RIA, although this may depend on the specific binding characteristics of the IGF-I antiserum.

Animals↗