Search PubMed⌕ Search

Biomedical subjects

A Martin

Publications and source records attributed to A Martin.

At least 343 records · Page 19Linked to original sources
PubMed1997

Measuring venous capacitance and blood flow in pregnancy.

Forearm or calf venous plethysmography has been used in pregnant women to examine the effects of pregnancy on the vascular system and more recently to measure blood flow changes in response to intra-arterial infusion of vasoactive substances. To examine the assumption that venous capacitance and blood flow measurements are the same in the forearm and calf, venous plethysmography was conducted simultaneously on the forearm and calf in normal (NP) and hypertensive pregnant women (HTP) in their third trimester and in normal nonpregnant women (N). All studies were made on the right forearm and calf with subjects in the left lateral recumbent position. There was no significant difference between venous capacitance in the forearm (median: 124 x 10(3)mL/100mL/mmHg for both NP and HTP) and leg (134 [NP] and 106 [HTP] x 10(3)mL/100mL/mmHg) for both pregnant groups but venous capacitance in the nonpregnant group was greater in the leg than arm (174 versus 112 x 10(3)mL/100mL/mmHg, p < 0.001). Blood flow was similar in the leg and forearm (median 4.9 versus 3.9mL/100mL/min respectively) in nonpregnant women. Forearm blood flow was also similar to calf flow in NP women (6.2 versus 4.3mL/100mL/min respectively) but greater than calf blood flow in HTP (9.7 versus 5.3mL/100mL/min, p < 0.01). Using left lateral recumbency, forearm and calf vein capacitances are similar in pregnant women, in contrast to nonpregnant women. Blood flow is higher in the forearm than the calf only in hypertensive pregnant women. These observations should be borne in mind when interpreting studies of regional blood flow in pregnancy.

Adult↗
PubMed1997

Karyotypic Variability in Ribosomal DNA Subchromosome Size among Colpodid Ciliates, a Possible Tool To Differentiate Colpodid Species.

Pulsed-field gel electrophoresis has been applied to analyze the karyotypic variability among colpodid ciliates. The 18S ribosomal gene was found at different locations in the electrophoretic pattern, and these size variations in the ribosomal DNA subchromosomal molecule seem to be species specific. This could potentially be a useful new tool with which to differentiate colpodid ciliates.

Journal Article↗
PubMed1997

Protein kinase C alpha and tumorigenesis of the endocrine gland.

A point mutation in the protein kinase C alpha (PKC alpha) gene has been discovered in a subpopulation of human pituitary tumors characterized by their invasive phenotype. Here we show that: (1) thyroid tumors can express the PKC alpha mutation detected in a subpopulation of follicular adenomas and carcinomas, and (2) mutated PKC alpha has modified enzymatic properties as compared to wild-type PKC alpha. It has lost its capacity to phosphorylate the S17R substrate and exhibits a higher sensitivity to degradation as compared to wild-type PKC alpha. In conclusion, the presence of the PKC alpha mutant in tumors other than pituitary tumors and the observation that the presence of the point mutation induces changes in PKC alpha properties suggest the involvement of this mutant in tumorigenesis.

Adenoma↗
PubMed1997

Vitamin E inhibits low-density lipoprotein-induced adhesion of monocytes to human aortic endothelial cells in vitro.

Monocyte adhesion to human aortic endothelial cells (ECs) is one of the early events in the development of atherogenesis. ECs were used to investigate the role of vitamin E in human monocyte adhesion to ECs in vitro. ECs incubated with 40 to 193 mg/dL of low-density lipoprotein cholesterol (LDL) for 22 hours exhibited increasing dose-dependent adherence for untreated, isolated human monocytes (P < .05). ECs exposed to the highest dose of LDL (193 mg/dL) but pretreated with 19 mumol/L alpha-tocopherol for 24 hours showed a trend to lower adherence for monocytes compared with non-treated ECs (4.4 +/- 1.2% versus 7.6 +/- 1.9%; P = .09). This effect of vitamin E became more significant (P < .05) when ECs were exposed to a lower level of LDL (40 mg/dL) or were pretreated with a higher level of alpha-tocopherol (42 mumol/L) and then exposed to 80 mg/dL LDL. Presupplementation of ECs with 15, 19, and 37 mumol/L alpha-tocopherol significantly (P < .05) reduced monocyte adhesion by 6 +/- 1%, 37 +/- 6%, and 69 +/- 17%, respectively. Levels of soluble intercellular adhesion molecule-1 (sICAM-1), one of the adhesion molecules for monocytes, increased after incubation of ECs with LDL 80 mg/dL (4.7 +/- 0.7 versus 6.4 +/- 1.2 ng/mL, respectively; P < .05). Treatment of ECs with alpha-tocopherol (42 mumol/L) significantly reduced induction of sICAM-1 by LDL to 2.2 +/- 2.3 ng/mL. After exposure to LDL, prostaglandin I2 production by ECs was diminished, whereas presupplementation of ECs with alpha-tocopherol partially reversed the LDL effect. Production of interleukin-1 beta was not detectable when ECs were treated with alpha-tocopherol, LDL, or alpha-tocopherol followed by LDL. Our findings indicate that vitamin E has an inhibitory effect on LDL-induced production of adhesion molecules and adhesion of monocytes to ECs via its antioxidant function and/or its direct regulatory effect on sICAM-1 expression.

Aorta↗
PubMed1997

Both intracellular and extracellular vitamin C inhibit atherogenic modification of LDL by human vascular endothelial cells.

Oxidative modification of LDL by vascular cells has been proposed as a mechanism by which LDL becomes atherogenic. Antioxidants that can prevent LDL oxidation may therefore act as antiatherogens. We used endothelial cells (ECs) from human aortas (HAECs), human saphenous veins (HSECs), and bovine aortas (BAECs) to investigate the role of intracellular and extracellular vitamin C (ascorbate) in EC-mediated LDL modification. Incubation of LDL (0.1 mg protein per milliliter) with confluent HAECs in Ham's F-10 medium led to time-dependent modification of the lipoprotein. In contrast, incubation of LDL with HAECs in medium 199, which does not contain redox-active transition metal ions, did not lead to LDL modification. Both HAEC-mediated and cell-free LDL modifications in Ham's F-10 medium were strongly inhibited in a time- and dose-dependent manner by physiological concentrations of ascorbate. Confluent HAECs cultured under conventional conditions contained very little intracellular ascorbate (< 0.5 nmol/mg protein) but could be loaded with up to 20 nmol ascorbate per milligram protein in a time- and concentration-dependent manner. Ascorbate-loaded HAECs exhibited a lower capacity to modify LDL than did non-ascorbate-loaded control cells. When LDL was incubated with HSECs instead of HAECs, similar time- and concentration-dependent inhibitory effects on LDL modification of intracellular and extracellular ascorbate were observed. In contrast to human ECs, BAECs did not take up vitamin C and therefore only coincubation but not preincubation with ascorbate inhibited BAEC-mediated LDL modification. Our data show that enrichment of human vascular ECs with vitamin C lowers their capacity to modify LDL. In addition, extracellular vitamin C strongly inhibits EC-mediated, metal ion-dependent atherogenic modification of LDL.

Animals↗
PubMed1997

Preservation of functioning human thyroid "organoids" in the scid mouse. IV. In vivo selection of an intrathyroidal T cell receptor repertoire.

To study the in vivo influence of thyroid cells on the T cell receptor repertoire in human autoimmune thyroid disease, we mixed lymphocyte-free thyrocytes (approximately 1.2 x 10[6]) from patients with Graves' disease with autologous peripheral blood mononuclear cells (PBMC; approximately 1.5 x 10[6]) and transplanted this mixture sc into scid mice while suspended in a basement membrane gel (approximately 0.4 ml). Controls included mice that received either thyrocytes only or PBMC only. The resulting artificial mixed cell thyroid organoids were explanted after 5 weeks, and their T cell receptor repertoire was examined. Of a total of 63 organoids constructed, 60 were recovered (95.2%). Total RNA was extracted and then analyzed by reverse transcription-PCR primarily for human T cell receptor (hTcR) Vbeta gene expression using 21 hTcR Vbeta amplimers. A restricted pattern of hTcR Vbeta gene expression was found, with 6 Vbeta genes (Vbeta5, 6, 7, 8, 13.1, and 18) predominantly expressed [P < 0.05, by ANOVA on ranks and Student-Newman-Keul's (SNK) test]. PBMC and control organoids showed no preferential selection of particular hTcR V gene-expressing T cells. This reductionist, mixed cell, thyroid model reflected earlier observations in human and murine autoimmune thyroid diseases in which a bias in hTcR V gene family expression had been observed. The model permitted in vivo T cell selection and/or enrichment of potentially disease relevant human T cells.

Animals↗
PubMed1997

Detection of major T cell epitopes on human thyroid stimulating hormone receptor by overriding immune heterogeneity in patients with Graves' disease.

To examine the major immunogenic regions of the human TSH receptor (hTSHR), we examined 14 patients with Graves' disease and 14 healthy control subjects for their peripheral blood T cell proliferative responses to 29 synthetic peptides representing the entire ectodomain of the hTSHR (TSHR-ecd). By combining an analytical approach encompassing the grading of peptide-induced responses and nonparametric testing, we obtained evidence for highly significant differences (P = < 0.000001) in the patient group compared with minor differences in the control group (P = 0.045). To account for this difference, we identified four major T cell epitopes (amino acid 247-266, 202-221, 142-161, and 52-71), by multiple comparison analysis, in the patient group. Furthermore, we demonstrated by radiolabeled PCR that the responding T cells were clonally expanding. These findings demonstrate that despite likely differences in human leukocyte antigen type among patients with Graves' disease, several distinct hTSHR epitopes elicited significant responses in the immune system of patients with Graves' disease, and that such patients are most often poorly tolerant to particular epitopes of the TSH receptor ectodomain, The data support the notion of TSHR peptide antigens overriding human immune heterogeneity in patients with Graves' disease, and raise the possibility of applying analog peptide blockade to suppress T cell responsivity.

Adult↗
PubMed1997

Development and validation of a discriminative quality of life questionnaire for osteoporosis (the OPTQoL).

We report the development and validation of an osteoporosis-targeted quality of life questionnaire to measure the impact of the disease in the general population. From multiple focus groups with women with osteoporosis, healthy women at risk for osteoporosis, spouses and relatives of women with osteoporosis, and health care providers, we identified over 300 potential items related to the disease. A lengthy questionnaire incorporated these items and was administered to a second large study cohort of 222 women with clinical osteoporosis (history of fracture, significant height loss, and/or kyphosis); 101 women with known low bone mineral density levels that would categorize them as osteoporotic but who had not yet shown obvious physical manifestations of the disease; and 142 women with other conditions (such as arthritis, cancer, depression) expected to also have an impact on quality of life. Final items from among the original 300 were chosen for their demonstrated relationship with osteoporosis as measured by clinical manifestations and low bone density and with quality of life measured by a standard generic questionnaire, the SF-36. The final questionnaire contains 26 scored items in three domains-physical activity, adaptations, and fears- and six nonscored questions relating to osteoporotic changes and diagnosis. This instrument is unique among osteoporosis-targeted questionnaires in that it attempts to measure the total impact of the disease on quality of life within a population at a single point in time.

Community-Institutional Relations↗
PubMed1997

Urinary chondroitin sulfates, heparan sulfate and total sulfated glycosaminoglycans in interstitial cystitis.

PURPOSE: We compared urinary glycosaminoglycan levels in patients with interstitial cystitis and healthy controls. MATERIALS AND METHODS: Total sulfated glycosaminoglycans assayed by dimethylmethylene blue binding and individual glycosaminoglycans analyzed by cellulose acetate electrophoresis were compared in patients with interstitial cystitis and healthy controls. Also, multiple urine samples were obtained from healthy female controls for 2 months to assess the relationship of urinary glycosaminoglycan and creatinine concentrations, and to determine whether glycosaminoglycan excretion changes during the menstrual cycle. RESULTS: Total sulfated glycosaminoglycan and creatinine concentrations correlated well in random voided samples. Menstrual cycle day did not affect total sulfated glycosaminoglycan levels. Cellulose acetate electrophoresis revealed 3 bands corresponding to chondroitin sulfates, heparan sulfate and acidic glycoprotein. Patients with interstitial cystitis had decreased urinary concentrations of each of these individual components and total sulfated glycosaminoglycans. However, glycosaminoglycan-to-creatinine ratios were similar in interstitial cystitis and control urine. CONCLUSIONS: Using these assays total and individual urinary glycosaminoglycan levels normalized to creatinine were not altered in interstitial cystitis.

Chondroitin Sulfates↗
PubMed1997

SPECT image analysis using statistical parametric mapping: comparison of technetium-99m-HMPAO and technetium-99m-ECD.

UNLABELLED: The goal of this study was to examine the apparent differences in regional cerebral blood flow (rCBF) between two groups of normal individuals who received either of the two tracers, 99mTc-D,L-hexamethylpropylene amine oxide (99mTc-HMPAO, or exametazime) or 99mTc-ethylene-dicysteine diethylester (99mTc-ECD, or bicisate). METHODS: Individuals were screened for drug use, head injury, medication status and other psychiatric and medical illnesses. The two groups were matched for age, sex and race. SPECT measurement of brain perfusion was performed in 35 individuals who received 99mTc-HMPAO and in 55 who received 99mTc-ECD. Subsequent analysis of these scans was done using computer software including Statistical Parametric Mapping and Analyze. Images were intensity-thresholded and spatially normalized to a standardized stereotactic (Talairach) space. This allowed for the objective, quantitative analysis of these data, demonstrating the extent and magnitude of rCBF changes. RESULTS: Our results showed significant changes between these two groups of normal individuals, presumably due to differences in pharmacokinetics between the two radiolabeled tracers. Specifically, large areas of the parietal, occipital and superior temporal cortices were significantly lower in the 99mTc-HMPAO group than in the 99mTc-ECD group. Increases were seen in the subcortical nuclei, parts of the brain stem, hippocampus and small areas of the cerebellum in the 99mTc-HMPAO group as compared to the 99mTc-ECD group. CONCLUSION: We present a method of image analysis to semiquantitatively measure rCBF in SPECT images and the changes seen due to differences between the two radiotracers.

Adult↗
PubMed1996

Functional relationships of the genetic locus encoding the glycosyltransferase enzymes involved in expression of the lacto-N-neotetraose terminal lipopolysaccharide structure in Neisseria meningitidis.

The biosynthetic function of the lgtABE genetic locus of Neisseria meningitidis was determined by structural analysis of lipopolysaccharide (LPS) derived from mutant strains and enzymic assay for glycosyltransferase activity. LPS was obtained from mutants generated by insertion of antibiotic resistance cassets in each of the three genes lgtA, lgtB, lgtE of the N. meningitidis immunotype L3 strain phi3 MC58. LPS from the parent strain expresses the terminal lacto-N-neotetraose structure, Galbeta1-->4GlcNAcbeta1-->3Galbeta1-->4Glc. Mild hydrazine treatment of the LPS afforded O-deacylated samples that were analyzed directly by electrospray ionization mass spectrometry (ESI-MS) in the negative ion mode. In conjunction with results from sugar analysis, ESI-MS revealed successive loss of the sugars Gal, GlcNAc, and Gal in lgt B, lgt A, and lgt E LPS, respectively. The structure of a sample of O- and N-deacylated LPS derived by aqueous KOH treatment of lgt B LPS was determined in detail by two-dimensional homo- and heteronuclear NMR methods. Using a synthetic beta-GlcNAc acceptor and a beta-lactose acceptor, the glycosyltransferase activities encoded by the lgtB and lgtA genes were unambiguously established. These data provide the first definitive evidence that the three genes encode the respective glycosyltransferases required for biosynthesis of the terminal trisaccharide moiety of the lacto-N-neotetraose structure in Neisseria LPS. From ESI-MS data, it was also determined that the Gal-deficient LPS expressed by the lgt E mutant is identical to that of the major component expressed by immunotype L3 galE-deficient strains. The galE gene which encodes for UDP-glucose-4-epimerase plays an essential role in the incorporation of Gal into meningococcal LPS.

Carbohydrate Conformation↗
PubMed1996

Activation of phospholipase D and phosphatidylinositol 4-phosphate 5-kinase in HL60 membranes is mediated by endogenous Arf but not Rho.

Membrane-associated phospholipase D (PLD) in HL60 cells can be activated by the small GTP-binding proteins Arf and RhoA, but polyphosphorylated inositol lipids were required for maximum activity. The intact lipid was required because neither inositol 1,4, 5-trisphosphate nor stearoyl-arachidonyl glycerol could substitute for phosphatidylinositol 4,5-bisphosphate (PIP2). Arf-stimulated but not Rho-stimulated PLD activity was increased by the inclusion of Mg2+ and ATP. ATP-dependent PLD activation occurred when phosphatidylinositol 4-phosphate (PIP), PIP2, or phosphatidylinositol 3,4,5-trisphosphate (PIP3) were included, but PIP2 formation was only detected with PIP; no PIP3 production was detected under any conditions. Therefore, the ATP-dependent increase in PLD activity cannot be explained by PIP2 or PIP3 formation. Association of endogenous Arf and RhoA with membranes was increased by incubation with GTPgammaS. This treatment increased membrane PLD and PIP kinase activities in the absence of exogenous p21 proteins. Reduction of Arf translocation suppressed the increase in PLD and PIP kinase activities, whereas complete removal of Rho but not Arf from membranes with RhoGDI was without effect on PLD activity but increased PIP kinase activity. Therefore, although recombinant Arf and Rho can activate PLD and PIP kinase in HL60 cells, it is the endogenous Arf but not Rho that regulates PLD, and thus a role for Rho in the physiological regulation of PLD in HL60 cells is unlikely.

ADP-Ribosylation Factors↗