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Biomedical subjects

M F Gonzalez

Publications and source records attributed to M F Gonzalez.

At least 19 recordsLinked to original sources
PubMed2001

The association between physical activity, cardiorespiratory fitness, and lipoprotein(a) concentrations in a tri-ethnic sample of women: The Cross-Cultural Activity Participation Study.

The purpose of this cross-sectional study was threefold: (1) to examine ethnic differences in plasma lipoprotein(a) [Lp(a)] concentrations; (2) to examine the relationship between physical activity levels (moderate, moderate-vigorous, and total MET-min/day) and Lp(a) concentrations; and (3) to determine the relationship between maximal treadmill time and Lp(a) concentrations among African-American, Native American, and Caucasian women (n=140, ages 40-70 years: 54.5+/-10.7). Physical activity records were kept for two 4-day periods, scheduled 1 month apart, a total of 8 days, and each activity was assigned a code from the 'Compendium of physical activity'. Subjects completed a graded exercise test to determine maximal treadmill time, and a fasted blood sample was collected to quantify Lp(a) concentration. Lp(a) concentrations were negatively skewed with a geometric mean of 28.3 mg/dl (25-75%: 10.4-43.1 mg/dl) in African-Americans (n=47), 2.9 mg/dl (25-75%: 1.2-7.4 mg/dl) in Native Americans (n=45), and 9.4 mg/dl (25-75%: 2.6-22.4 mg/dl) in Caucasians (n=48). African-American women had significantly higher (p<0.05) Lp(a) concentrations than either Native Americans or Caucasians. No relationships were observed among moderate, moderate-vigorous, and total MET-min/day of physical activity, maximal treadmill time, and Lp(a) concentrations. Significant ethnic differences in Lp(a) concentrations were found, with African-American women having higher Lp(a) concentrations than Native American and Caucasian women. Lp(a) concentrations were not associated with any physical activity variables. Therefore, physical activity and maximal treadmill time did not influence Lp(a) concentrations in this tri-ethnic population of women.

Adult↗
PubMed1999

Contrasting effects of selective T- and L-type calcium channel blockade on glomerular damage in DOCA hypertensive rats.

Mibefradil and amlodipine are calcium antagonists with different channel selectivities. Mibefradil blocks both L- and T-type calcium channels; although in the usual pharmacological doses, it predominantly blocks the T-type channels. In contrast, amlodipine selectively blocks L-type channels. The goal of the present study was to assess whether this differential selectivity would result in different effects on end-organ damage in experimental hypertension. For this purpose, deoxycorticosterone acetate (DOCA)-salt hypertensive rats were treated either with equipotent doses of mibefradil or amlodipine (30 mg. kg(-1). d(-1) as food admix). Despite the fact that both drugs decreased systolic arterial pressure to the same extent (140+/-5 mm Hg in the mibefradil group and 144+/-3 mm Hg in the amlodipine group versus 225+/-5 mm Hg in the untreated-DOCA group), only mibefradil decreased proteinuria (35. 5+/-6.5 versus 103.3+/-14.1 mg/24 h in untreated DOCA-salt animals) and prevented glomerular lesions. Both drugs, however, prevented the occurrence of vascular renal lesions. To elucidate the mechanism responsible for this difference, we evaluated in an additional series of experiments the effects of mibefradil and amlodipine on plasma and renal renin concentrations, as well as the effects of the addition of enalapril, an ACE inhibitor, given on top of both drugs on proteinuria. Amlodipine, in contrast to mibefradil, markedly stimulated the plasma (17.8+/-2.6 ng Ang I. mL(-1). h(-1) in the amlodipine group versus 3.9+/-0.4 ng Ang I. mL(-1). h(-1) in the mibefradil group and 3.2+/-0.3 ng Ang I. mL(-1). h(-1) in the untreated-DOCA group) and renal (2.42+/-0.37 ng Ang I. mL(-1). h(-1) in the amlodipine group versus 0.36+/-0.04 ng Ang I. mL(-1). h(-1) in the mibefradil group and 0.26+/-0.08 ng Ang I. mL(-1). h(-1) in the untreated-DOCA group) renin concentrations. Stimulation of the renin-angiotensin system could explain the absence of a renal protective effect of amlodipine. This was also suggested by the fact that enalapril given in addition to amlodipine could decrease proteinuria. In conclusion, T-type channel blockade by mibefradil decreases blood pressure without stimulation of the renin-angiotensin system and therefore prevents most of the glomerular damage in DOCA hypertensive rats.

Amlodipine↗
PubMed1997

Functional development of the vibrissae somatosensory system of the rat: (14C) 2-deoxyglucose metabolic mapping study.

Functional development of the rat whisker somatosensory system was studied by using the (14C) 2-deoxyglucose (2DG) metabolic mapping technique. Restrained rat pups had their left mystacial vibrissae stroked for 30 minutes and their brains harvested, sectioned, and autoradiographed from the level of the lower medulla to the frontal cortex. Subjects were tested at postnatal days (PNDs) 0-9 and 21. At birth, all subjects exhibited a significant increase of 2DG uptake in the left spinal trigeminal nuclei, the principal trigeminal sensory nucleus, and a portion of the right ventral posteromedial thalamic nucleus. The primary somatosensory cortex exhibited significant 2DG uptake contralateral to stimulation by PND 6, followed by the secondary somatosensory cortex at PND 7. The pattern of 2DG uptake in the somatosensory cortices became more intense and well defined by PND 9. Given that the somatosensory system develops in an orderly fashion from the periphery to higher brain structures, the present results show that brain structures mediating whisker sensory input are not metabolically active until projections from lower somatosensory centers are established. Neurons become responsive to whisker stimulation in the subcortical structures at birth and in the somatosensory cortex a few days later. This cortical activity follows the organization of the upper tier of thalamocortical fibers into a "barrelfield." Moreover, there is a gradual enhancement in functional activity of the vibrissa neurons at different somatosensory nuclei as rats mature. The present study elucidates the time course of functional development in the rat somatosensory system.

Animals↗
PubMed1996

A prospective evaluation of atherosclerotic risk factors and hypercoagulability in young adults with premature lower extremity atherosclerosis.

PURPOSE: Fifty-one consecutive patients with premature lower extremity atherosclerosis were prospectively evaluated for atherogenic risk factors and primary or acquired hypercoagulability, which might contribute to early ischemia and revascularization failure. METHODS: Laboratory tests included plasma assays of (1) natural anticoagulants (NAC), lipoprotein (a) (Lp[a]), and anticardiolipin antibodies, and (2) fibrinolytic activators and inhibitors at baseline and stimulated after 20 minutes of upper extremity venous occlusion. RESULTS: Forty-six (90%) of these 51 patients had laboratory abnormalities. One or more NAC deficiencies were found in 15 (30%) patients and included antithrombin III (n = 5), protein C (n = 8), protein S (n = 4), and heparin cofactor II (n = 2). Hypofibrinolysis was identified as a deficiency of stimulated tissue plasminogen activator in 22 (45%) patients and elevated plasminogen activator inhibitor-1 (PAI-1) in 29 (59%). Elevated Lp(a) was found in 43 (86%) patients. Five (10%) patients had anticardiolipin antibodies. Ten patients had combined NAC deficiency and hypofibrinolysis. Five (10%) patients had no abnormality. NAC deficiencies, especially protein C deficiency, were associated with acute ischemia (p < 0.01), prior vascular intervention (p < 0.01), an increasing number of total vascular procedures (p < 0.01), and major amputation (p < 0.01). PAI-1 was associated with a history of heart disease (p < 0.05) and prior vascular procedures (p < 0.05). Elevated Lp(a) was associated with elevated PAI-1 (p < 0.05). Retesting in 20 patients suggested that 80% of NAC deficiencies were acquired, but abnormalities persisted in 66% of patients with elevated PAI-1 and in 93% of those with elevated Lp(a). CONCLUSIONS: These data strongly support the hypothesis that the convergence of atherogenic risk factors and hypercoagulability play an important role in early ischemia and poor results reported for lower extremity vascular procedures in young adults.

Adult↗
PubMed1995

Neonatal capsaicin treatment (NCT) alters the metabolic activity of the rat somatosensory cortex in response to mechanical deflection of the mystacial vibrissae.

Capsaicin, a selective neurotoxin of unmyelinated C-fibers, was administered to neonatal rat pups at birth. Following a recovery period of 10 days, pups were injected with 2-deoxy-glucose (2DG) and subjected to repetitive mechanical stimulation to the left whiskerpad. Their brains were then harvested for autoradiography. The observed changes in 2DG uptake in the somatosensory cortex of capsaicin-treated rats were compared to vehicle-treated rats. The cross-sectional area and density of 2DG uptake by the primary and the secondary somatosensory cortex (SSI and SSII, respectively) were measured. Capsaicin-treated rats significantly exhibited a reduction in area of activation and a decrease of 2DG uptake in both structures. The present data indicates that neonatal capsaicin affects the functional activity of the rat somatosensory cortex. It is suggested that unmyelinated sensory afferents play a role in the development of the rat somatosensory system.

Age Factors↗
PubMed1995

Massive lower extremity arterial thrombosis and acute hepatic insufficiency in a young adult with premature atherosclerosis associated with hyperlipoprotein(a)emia and antiphospholipid syndrome. A case report.

The authors describe a healthy young male smoker with familial history of recurrent thromboembolism who presented with severe, rapidly progressive lower limb ischemia and abnormal results from liver function tests. An arteriogram of the lower extremities showed bilateral infrainguinal atherosclerotic arterial occlusions. The laboratory findings, in addition to abnormal liver function findings, included moderately elevated antiphospholipid antibodies and hemostatic abnormalities involving elevated fibrinogen, lipoprotein (a) levels, and deficient fibrinolysis. He underwent bilateral femoral thrombectomy, which was followed by a meticulous anticoagulation, and had gradual improvement of ischemic symptoms and liver functions. This is, to their knowledge, the first reported case in the English literature of premature lower extremity atherosclerosis and antiphospholipid syndrome associated with elevated lipoprotein (a) levels and documented complex hemostatic abnormalities contributing to systemic thrombosis.

Acute Disease↗
PubMed1995

Plasma angiotensin in binephrectomised mice.

Plasma renin-angiotensin parameters were measured before and 24h after binephrectomy (BNx) in male Swiss (Ren-1, Ren-2) and BALB/c (Ren-1) female mice (representing the extremes of differences in tissue renin expression), together with in vivo inhibition of residual renin. Plasma Ang II increased from 18.9 +/- 7.3 to 48.1 +/- 16.9 pg/ml after BNx in conscious Swiss mice (+/- sd, p < 0.001, n = 11&12), renin activity (PRA) increased 2.76 times, angiotensinogen (aogen) increased 4.57 times and renin concentration (PRC) fell by 65%. In BALB/c, Ang II+Ang III decreased slightly (56.6 +/- 11 to 37.7 +/- 14.7, p < 0.05, n = 5&6), PRA was unchanged, aogen increased 12 times and PRC fell by 93%. Plasma ACE decreased by 26% and 28% respectively. Aogen did not increase further when post BNx plasma renin was inhibited with antirenin in vivo during 20h. Thus plasma angiotensin is maintained or considerably increased following BNx in mice and the change is consistent with first-order kinetics with respect to renin and aogen in the circulation. Whether the strain carries one or two renin genes, high renal and extrarenal renin production combined with a low plasma aogen phenotype yields resting angiotensin levels similar to other mammals. A kinetic regulation of aogen levels is proposed in mice wherein Ang II production is limited by low substrate concentration thereby ensuring normotension in the face of abundant extrarenal renin secretion.

Angiotensin II↗
PubMed1994

Whisker stimulation metabolically activates thalamus following cortical transplantation but not following cortical ablation.

Local cerebral glucose utilization was assessed during whisker stimulation by 2-deoxyglucose autoradiography. Whisker stimulation increased local cerebral glucose utilization in brainstem, thalamus and whisker sensory cortex in normal rats. Whereas whisker stimulation increased glucose metabolism in brainstem, whisker stimulation failed to increase glucose metabolism in thalamus of rats that had whisker sensory cortex ablated 5 h to five weeks previously. The failure of whisker stimulation to activate thalamus after cortical ablations was probably not due to decreased cortical input to thalamus because whisker stimulation activated thalamus after large cortical tetrodotoxin injections. Failure of whisker stimulation to activate thalamus at early times (5 h and one day) after cortical ablations was not due to thalamic neuronal death, since it takes days to weeks for axotomized thalamic neurons to die. The failure of whisker stimulation to activate thalamus at early times after cortical ablations was likely due to the failure of trigeminal brainstem neurons that project to thalamus to activate axotomized thalamic neurons. This might occur because of synaptic retraction, glial stripping or inhibition of trigeminal brainstem synapses onto thalamic neurons. The thalamic neuronal death that occurs over the days and weeks following cortical ablations was associated with thalamic hypometabolism. This is consistent with the idea that the thalamic neurons die because of the absence of a cortically derived trophic factor, since the excitotoxic thalamic cell death that occurs following cortical kainate injections is associated with thalamic hypermetabolism. The glucose metabolism of parts of the host thalamus was higher and the glucose metabolism in surrounding nuclei lower than the normal side of thalamus in rats that sat quietly and had fetal cortex transplants placed into cavities in whisker sensory cortex five to 16 weeks previously. Whisker stimulation in these subjects activated the contralateral host thalamus and fetal cortical transplants. This was accomplished using a double-label 2-deoxyglucose method to assess brain glucose metabolism in the same rat while it was resting and during whisker stimulation. The high glucose metabolism of parts of host thalamus ipsilateral to the fetal cortical transplants is consistent with prolonged survival of some axotomized thalamic neurons. The finding that whisker stimulation activates portions of host thalamus further suggests that the cortical transplants maintained survival of the host thalamic neurons and that synaptic connections between whisker brainstem and thalamic neurons were functional.

Animals↗
PubMed1994

Dealing with death and dying.

We instituted two thanatology seminars for medical students and residents which emphasized feelings more than objective data. The seminars began with students filling out a death certificate on themselves. Eighty-four per cent predicted that their own probable cause of death would be from an acute illness. Discussion and reflection on this experience helped them realize how difficult it would be to deal with a chronic illness. By answering a question about what they were most grateful for, they became aware that they valued family and friends most highly. We believe that this experience legitimized feelings which form the basis of empathy.

Attitude of Health Personnel↗
PubMed1994

Influence of sodium diet on L-NAME effects on renin release and renal vasoconstriction.

The intervention of the L-arginine-NO pathway in renal vasodilation and renin secretion was studied in an isolated perfused rat kidney model. NG-nitro-L-arginine methyl ester (L-NAME, 1-25 microM), an inhibitor of nitric oxide (NO) synthesis, caused a dose-dependent increase in perfusion pressure (PP) and a dose-dependent decrease in renal perfusate flow. Renin was inhibited independently of the rise in PP, since the effect of L-NAME on renin release was the same when PP was maintained constant. Exposure of rats to low [salt depleted (SD)] or high [salt repleted (SR)] salt intake for 1 mo influenced the renal vascular response to L-NAME (3 microM). Isolated SR rat kidney vasculature vasoconstricted to a greater extent after inhibition of NO synthase than did that of SD kidneys. A similar fall in renin release was observed after L-NAME in both groups, despite a higher renin secretion rate in SD than in SR rats. These results suggest that NO-dependent vasodilation counteracts the renal vasoconstrictor effect of sodium loading.

Analysis of Variance↗
PubMed1993

Expression of c-fos in brain subcortical structures in response to nauseant lithium chloride and osmotic pressure in rats.

Immunohistochemistry was used to map c-fos expression in rats to investigate the neural substrates that mediate the emetic action of lithium chloride and the effect of osmotic pressure. Solutions of 3% lithium chloride or 4.14% saline, isotonic to each other, as well as 0.65% lithium chloride or 0.9% saline, also isotonic to each other, were administered intraperitoneally (3 ml/kg) in rats. Both lithium chloride and osmotic pressure enhanced c-fos expression in the nuclei of the solitary tract, the paraventricular nuclei and supraoptic nuclei of the hypothalamus, and in the amygdala. This suggests that these brain structures might be the sites where the autonomic, neuroendocrine and behavioral responses elicited by lithium chloride and osmotic pressure are integrated.

Animals↗
PubMed1993

The induction and suppression of c-fos expression in the rat brain by cholecystokinin and its antagonist L364,718.

Immunohistochemical techniques were used to map c-fos expression in the rat brain after the i.p. administration of CCK-8 (8 micrograms/kg). C-fos expression was observed in the rostral and the caudal parts of the nuclei of the solitary tract (NTS), and the paraventricular nuclei (PVN) in the hypothalamus. The c-fos expression in these areas was suppressed by the administration of L364,718 (120 micrograms/kg). Since L364,718 is known to be a powerful selective antagonist to the peripheral CCK-A receptors, these data suggest that the effects produced by exogenous CCK are due to peripheral receptors that project to the NTS.

Animals↗
PubMed1993

Association of HLA-DR4-Dw15 (DRB1*0405) and DR10 with rheumatoid arthritis in a Spanish population.

OBJECTIVE: To analyze the associations of HLA class II antigens with rheumatoid arthritis (RA) in a Spanish population. METHODS: We used DNA oligotyping to determine DR types, DQA1 and DQB1 alleles, and DR4 variants in 70 unrelated seropositive RA patients and 189 healthy controls living in Spain. RESULTS: A significantly higher frequency of DR4 was seen in RA patients compared with controls (relative risk [RR] = 2.40). The DR10 specificity correlated most strongly with disease susceptibility (RR = 3.84). A significant decrease in the frequency of DR7 was observed in the RA patients (RR = 0.48). DR4-Dw15 (DRB1*0405) was found to be the unique DR4 allele associated with RA (RR = 4.27, P < 0.05), whereas Dw4 (DRB1*0401) and Dw14 (DRB1*0404/0408) showed no association, and both Dw10 (DRB1*0402) and Dw13 (DRB1*0403/0407) were negative risk factors for the disease. Approximately one-third of the cases of RA could not be explained by the "shared epitope" hypothesis. Investigation of the DQ alleles associated with DR4 showed that the haplotype Dw15-DQ8 (DRB1*0405-DQB1*0302) was a susceptibility factor for RA (RR = 6.36, P < 0.05). CONCLUSION: Our results suggest that HLA class II alleles involved in RA susceptibility can vary among different Caucasian populations.

Alleles↗
PubMed1993

Limited availability of medications for cancer patients.

We surveyed both chain and independent pharmacies within 10 counties of central South Carolina to determine the availability of certain medications that are often prescribed for patients during cancer treatment. One hundred twenty (59%) of the 202 surveys distributed were returned. Results indicate that many of the 65 products included in the survey are not stocked on a regular basis by the majority of the pharmacies that responded. Limited availability of these medications not only may prevent a patient from receiving timely drug therapy, but may exacerbate the anxieties and frustrations experienced by patients as they deal with their disease as well. This limited accessibility to medications could directly influence patient compliance. Therefore, patients need to be informed that availability is often limited, and that prescribed medications may require special ordering by their pharmacist. Awareness of this potential problem and increased communication among physicians, nurses, pharmacists, and patients could alleviate delays in drug therapy and improve the continuity of patient care.

Analgesics↗
PubMed1992

Decreased renin release and constant kallikrein secretion after injection of L-NAME in isolated perfused rat kidney.

A possible role of the endothelial L-arginine/NO pathway in the control of renal hemodynamics, renin release and kallikrein secretion was studied in an isolated rat kidney model perfused in a closed-circuit. NG-nitro-L-arginine methyl ester (L-NAME, 1-50 microM), an inhibitor of nitric oxide biosynthesis, caused a dose-dependent increase in perfusion pressure (PP) and a dose-dependent decrease in renal perfusate flow. Renin release was inhibited independently of a rise in PP. L-NAME did not change the urinary kallikrein secretion. These results confirm the intervention of the L-arginine/NO pathway in the vasodilation of this isolated perfused kidney model and demonstrate the inhibitory effect of L-NAME on renin release. They suggest that nitric oxide synthesis plays a role in stimulating renin release and is not involved in the regulation of urinary kallikrein secretion.

Analysis of Variance↗
PubMed1992

A human monoclonal autoantibody to a nucleolar structure.

Peripheral blood lymphocytes from a scleroderma patient (CDC) were isolated, transformed with Epstein-Barr virus and fused to the heteromyeloma SHM-D33. Supernatants from cultures were screened for autoantibody production against nucleoprotamine by ELISA. Positive wells were cloned by limiting dilution. After cloning, supernatants from two wells were positive for the nucleoprotamine assay. One named CDC-1 has been studied in our laboratory. CDC-1 recognized a nucleolar antigen by indirect immunofluorescence. By using an ELISA with purified recombinant antigens, CDC-1 reacted against Ro/SS-A, U1 (RNP) and Sm. By immunoblotting using a lysate of MOLT-4 cell line, CDC-1 was able to react against a structure of 60 kD. When the antigen recognized by CDC-1 was purified, SDS-PAGE under reducing conditions with purified antigen and subsequent silver staining of the gel allowed us to detect three bands at 60, 55 and 39 kD, respectively. A screening by ELISA with previously characterized antisera against our purified antigen demonstrated reactivity of the CDC-1 antigen with those antisera able to recognize Ro/SS-A.

Antibodies, Antinuclear↗
PubMed1992

Production of heterohybridomas secreting autoreactive and polyreactive human monoclonal antibodies.

Peripheral blood lymphocytes from two polytransfused renal dialysis patients were transformed by Epstein-Barr virus, fused to a heteromyeloma and cloned. Eight human monoclonal antibodies from the resulting clones were tested for their binding to a variety of antigens by ELISA, indirect immunofluorescence and immunoblotting. Antigens tested included B-cell lines, T and B lymphocytes, red blood cells, chronic lymphocytic leukaemic B cells, IgG, ssDNA, dsDNA, histones, nucleoprotamine, sperm nuclei, thymus and spleen extracts, MOLT4 cell lysates, affinity purified autoantigens, tetanus toxoid, bacterial lipopolysaccharide, insulin, and a tissue section screen. These human monoclonal antibodies reacted with more than one antigen to varying degrees and were autoreactive and polyreactive. One of these heterohybridoma cell lines exhibited cytoplasmic staining with an anti-CD5 monoclonal. Our findings support the concept that in adult individuals a subset of B cells produce heterogeneous IgM antibodies which can bind to a variety of different autoantigens and also to foreign antigens. These monoclonals were different from the autoantibodies usually seen in renal dialysis patients in the sense that they were not lymphocytotoxic.

Antibodies↗