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Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 109 records · Page 6Linked to original sources
PubMed1990

Correlation between phospholipid breakdown, intracellular calcium mobilization and enzyme secretion in rat pancreatic acini treated with Boc-[Nle28, Nle31]-CCK-7 and JMV180, two cholecystokinin analogues.

In this work in vitro pharmacological profiles of two analogues of the C-terminal heptapeptide of cholecystokinin (CCK) were evaluated. The analogue Boc-[Nle28, Nle31]-CCK-7, a stable analogue of CCK-8, has the same activity profile as CCK-8, and was found to be very potent in stimulating amylase secretion, phospholipid breakdown and [Ca2+]i mobilization from rat pancreatic acini. It can be used as a probe for studying CCK-actions. The CCK-analogue Boc-Tyr(SO3H)-Nle-Gly-Trp-Nle-Asp-2-phenylethylester, (JMV180), which stimulates amylase secretion without inhibition at supramaximal concentrations, has different effects on phospholipid hydrolysis and [Ca2+]i mobilization, compared to CCK-8 and Boc-[Nle28, Nle31]-CCK-7. Compound JMV180 was unable to significantly promote phospholipid breakdown, and was only 50%-60% as efficacious as Boc-[Nle28, Nle31]-CCK-7 in promoting [Ca2+]i mobilization. These findings suggest that low affinity CCK-receptors might be responsible for the supra-maximal inhibition of amylase secretion, and are correlated with phospholipid breakdown and maximal [Ca2+]i mobilization.

Amylases↗
PubMed1990

Insulin in the acute renal adaptation to dietary phosphate restriction in the rat.

Dietary phosphate restriction produces a rapid increase in tubular reabsorption of phosphate. To evaluate whether insulin is important in the acute renal adaptation following a low phosphate meal, four groups of conscious rats were studied by renal clearance methods, following a single meal by gavage. Group A received a normal (0.8%) phosphate meal, followed by saline infusion; Group B, a low (0.03%) phosphate meal, followed by saline infusion; Group C, a low phosphate meal, followed by infusion of somatostatin to suppress endogenous insulin secretion; and Group D, a low phosphate meal, followed by infusion of somatostatin plus insulin. Baseline plasma phosphate, insulin, glomerular filtration rate, and fractional excretion of phosphate were similar in all four groups. Following a low phosphate meal in Groups B, C, and D, there was a decrease in plasma phosphate, as compared with Group A. Whereas fractional excretion of phosphate decreased when plasma phosphate fell in Group B, administration of somatostatin (Group C) prevented the drop in fractional excretion of phosphate, despite a lower plasma phosphate. The addition of exogenous insulin (Group D) restored the antiphosphaturic effect of the low phosphate meal. These results suggest that insulin contributes to the acute decrease in phosphate excretion following a low phosphate meal.

Adaptation, Physiological↗
PubMed1990

Sodium and water excretion in nephrotic patients: effects of changes in renal haemodynamics.

1. Eight nephrotic patients were studied in order to evaluate the effects of acute changes in renal plasma flow and glomerular filtration rate on renal solute and water handling, in the absence of plasma volume expansion. 2. The subjects were studied first after the administration of captopril, a manoeuvre that increased renal plasma flow without a significant change in glomerular filtration rate, and a second time after receiving combined therapy with captopril and ibuprofen, a manoeuvre that decreased glomerular filtration rate without a significant change in renal plasma flow. 3. After captopril therapy, despite the increase in renal plasma flow, there was no significant change in proximal sodium reabsorption (as estimated from fractional lithium reabsorption), urine volume or urine osmolality. 4. The decrease in glomerular filtration rate observed after the administration of captopril plus ibuprofen was associated with decreases in fractional excretion of sodium and urine volume, and an increase in urine osmolality. The changes in these parameters of tubular function were proportionate to the changes in glomerular filtration rate. Fractional proximal sodium reabsorption increased substantially. 5. These observations suggest that, in the absence of plasma volume expansion, an increase in renal plasma flow does not increase sodium or water excretion by the nephrotic kidney. Moreover, during acute decreases in glomerular filtration rate, glomerulotubular balance appears to be disrupted, resulting in disproportionately high rates of proximal tubule sodium reabsorption.

Adult↗
PubMed1990

Inhibition of Theiler's virus-induced demyelination in vivo by tumor necrosis factor alpha.

Employing a murine model of multiple sclerosis which utilizes intracranial injection of Theiler's virus murine encephalomyelitis (TMEV) into SJL/J mice, we tested the potential role of tumor necrosis factor alpha (TNF-alpha) in ameliorating CNS demyelination. Infection with TMEV caused early grey matter inflammation (7 days post-infection) in the brain and spinal cord followed by chronic demyelination (35 days post-infection) in the spinal cord. Administration of recombinant human or mouse TNF-alpha starting 12 h prior to infection and then three times weekly had minimal effect on development of grey matter inflammation in the spinal cord. In contrast, TNF-alpha dramatically reduced demyelination present in spinal cord on days 14 and 35 after TMEV infection (P less than 0.01) when compared to controls. CNS virus titers of TMEV were not modified by TNF-alpha administration as measured on days 7, 14, and 35 following infection. In vivo administration of TNF-alpha inhibits TMEV-induced demyelination in susceptible SJL/J mice without affecting virus replication in the CNS.

Animals↗
PubMed1990

Persistent infection of a glioma cell line generates a Theiler's virus variant which fails to induce demyelinating disease in SJL/J mice.

Theiler's murine encephalomyelitis virus (TMEV) induces demyelinating disease which is associated with persistent virus infection of the central nervous system. To study the interaction between TMEV and host cells, we infected the G26-20 glioma cell line in vitro, and this resulted in a lytic infection in which most, but not all, cells were killed. Surviving cells divided and formed a viable monolayer in which a small proportion of cells displayed viral cytopathic effects. Levels of virus produced by these cultures over a 6 month period fluctuated between 6 and 8 log10 p.f.u./ml as measured by viral plaque assay. Similarly, the percentage of cells producing both viral antigen and viral RNA, as measured by a simultaneous immunoperoxidase/in situ hybridization technique, varied between 5 and 30%. Although persistently infected cultures were susceptible to challenge by both vesicular stomatitis virus and herpes simplex virus, they were resistant to infection by homologous viruses. Interferon activity was not identified. TMEV isolated from passage 12 produced smaller plaques than wild-type Daniels strain virus (wt-DAV) on L-2 cell monolayers. In contrast to demyelination induced in SJL/J mice after intracerebral inoculation with wt-DAV, mice infected with the small plaque variant virus failed to develop viral persistence or chronic demyelination. However, following immunosuppression by total body irradiation, SJL/J mice infected with the small plaque variant developed viral persistence but no demyelination. Characterization of the biochemical and molecular determinants of the variant will lead to a better understanding of determinants important in viral persistence.

Animals↗
PubMed1990

Synthesis of cyclic analogues of cholecystokinin highly selective for central receptors.

Cyclic CCK analogues in which positions 28 and 31 have been replaced by lysine residues and whose side chains are bridged by a succinic moiety, were synthesized. They were tested for their ability to inhibit the binding of 125I-BH-CCK-8 to isolated rat pancreatic acini and to guinea pig brain membranes. These cyclic CCK-analogues were compared to the potent CCK analogue Boc-[Nle28,31]-CCK-7 and to Boc-Trp-Leu-Asp-Phe-NH2, analogue of CCK-4. These cyclic compounds appeared to be highly selective for central CCK receptors.

Amino Acid Sequence↗
PubMed1990

Neuroblastoma differentiation involves the expression of two isoforms of the alpha-subunit of Go.

The regulation of GTP-binding proteins (G proteins) was examined during the course of differentiation of neuroblastoma N1E-115 cells. N1E-115 cell membranes possess three Bordetella pertussis toxin (PTX) substrates assigned to alpha-subunits (G alpha) of Go (a G protein of unknown function) and "Gi (a G protein inhibitory to adenylate cyclase)-like" proteins and one substrate of Vibrio cholerae toxin corresponding to an alpha-subunit of Gs (a G protein stimulatory to adenylate cyclase). In undifferentiated cells, only one form of Go alpha was found, having a pI of 5.8 Go alpha content increased by approximately twofold from the undifferentiated state to 96 h of cell differentiation. This is mainly due to the appearance of another Go alpha form having a pI of 5.55. Both Go alpha isoforms have similar sizes on sodium dodecyl sulfate-polyacrylamide gels, are recognized by polyclonal antibodies to bovine brain Go alpha, are ADP-ribosylated by PTX, and are covalently myristylated in whole N1E-115 cells. In addition, immunofluorescent staining of N1E-115 cells with Go alpha antibodies revealed that association of Go alpha with the plasma membrane appears to coincide with the expression of the most acidic isoform and morphological cell differentiation. In contrast, the levels of both Gi alpha and Gs alpha did not significantly change, whereas that of the common beta-subunit increased by approximately 30% over the same period. These results demonstrate specific regulation of the expression of Go alpha during neuronal differentiation.

Adenylate Cyclase Toxin↗
PubMed1990

Major histocompatibility complex-conferred resistance to Theiler's virus-induced demyelinating disease is inherited as a dominant trait in B10 congenic mice.

Intracerebral inoculation of Theiler's murine encephalomyelitis virus into susceptible strains of mice produces chronic demyelinating disease in the central nervous system characterized by persistent viral infection. Immunogenetic data suggest that genes from both major histocompatibility complex (MHC) and non-MHC loci are important in determining susceptibility or resistance to demyelination. The role of the MHC in determining resistance or susceptibility to disease can be interpreted either as the presence of antigen-presenting molecules that confer resistance to viral infection or as the ability of MHC products to contribute to pathogenesis by acting as viral receptors or by mediating immune attack against virally infected cells. These alternatives can be distinguished by determining whether the contribution of the MHC to resistance is inherited as a recessive or dominant trait. Congenic mice with different MHC haplotypes on identical B10 backgrounds were crossed and quantitatively analyzed for demyelination, infectious virus, and local virus antigen production. F1 hybrid progeny derived from resistant B10 (H-2b), B10.D2 (H-2d), or B10.K (H-2k) and susceptible B10.R111 (H-2r), B10.M (H-2f), or B10.BR (H-2k) parental mice exhibited no or minimal demyelination, indicating that on a B10 background, resistance is inherited as a dominant trait. Although infectious virus, as measured by viral plaque assay, was cleared inefficiently from the central nervous systems of resistant F1 hybrid progeny mice, we found a direct correlation between local viral antigen production and demyelination. These data are consistent with our hypothesis that the immunological basis for resistance is determined by efficient presentation of the viral antigen to the immune system, resulting in local virus clearance and absence of subsequent demyelination.

Animals↗
PubMed1990

Strains from both Theiler's virus subgroups encode a determinant for demyelination.

The GDVII strain and other members of the GDVII subgroup of Theiler's murine encephalomyelitis viruses (TMEV) cause an acute lethal neuronal infection in mice, whereas the DA strain and other members of the TO subgroup of TMEV cause a chronic demyelinating disease associated with a persistent virus infection. We used GDVII/DA chimeric infectious cDNAs to produce intratypic recombinant viruses in order to clarify reasons for the TMEV subgroup-specific difference in demyelinating activity. We found that both the GDVII and DA strains contain a genetic determinant(s) for demyelinating activity. No demyelination occurs following GDVII strain inoculation because this strain produces an early neuronal disease that kills mice before white matter disease and persistent infection can occur.

Animals↗
PubMed1990

Differential action of restriction endonucleases on chromosomes prepared for light and electron microscopy.

Whole mounted chromosomes from the L929 mouse cell line were digested on grids with HinfI and AluI restriction endonucleases and studied by electron microscopy. Results show differences in the pattern of bands obtained in a marker chromosome when compared with those previously reported by light microscopy with the same restriction endonucleases. These differences suggest that the accessibility of restriction sites on chromosomes may be modulated by preparatory methods for chromosome analysis.

Animals↗
PubMed1990

Interaction of captopril and ibuprofen on glomerular and tubular function in humans.

Renal hemodynamics and tubular solute and water handling were evaluated in normal subjects during water diuresis, before and after the acute administration of captopril, ibuprofen, or the combination of both drugs. The glomerular filtration increased after captopril administration but did not change after ibuprofen alone or in combination with captopril. Renal plasma flow increased with captopril alone and captopril plus ibuprofen but did not change after ibuprofen alone. Urine volume and Na excretion increased with captopril and decreased after ibuprofen; coadministration of ibuprofen attenuated the tubular effects produced by captopril alone. FELi, fractional delivery of solute to the distal nephron, and FELi-FENa, fractional distal reabsorption of solute, both significantly increased after captopril and decreased after ibuprofen but did not change with the combined regimen. (FELi-FENa)/FELi, fractional reabsorption of distally delivered Na, significantly decreased after captopril and increased after ibuprofen but remained unchanged after captopril plus ibuprofen. Thus captopril and ibuprofen have opposing effects on tubular Na and water handling, which are attenuated by the addition of the other drug. This interaction may have clinical relevance in patients with heart failure or hypertension, in whom captopril is used to enhance Na and water diuresis.

Absorption↗
PubMed1990

A reappraisal of the epidemiology of multiple sclerosis in Olmsted County, Minnesota.

A review of multiple sclerosis (MS) case reports, using the unified record system at the Mayo Clinic for the Olmsted County population, revealed age- and sex-adjusted prevalence rates per 100,000 persons of 160 for Olmsted County and 173 for Rochester, Minnesota, on January 1, 1985. The annual age- and sex-adjusted incidence rate per 100,000 person-years from 1975 to 1984 for Olmsted County was 6.2 and for Rochester, 6.3. This incidence rate is significantly higher than what had been reported previously in Rochester (3.6/100,000) or in other communities. The estimated 25-year survival of the MS population was 76.2% +/- 4.5% compared with 87.7% for the general US white population of a similar age and sex. Survival for men was less than for women. There was no increase in survival for patients diagnosed with MS in more recent decades. No significant increase was found in cancer or autoimmune disease rates in the MS patients.

Adolescent↗
PubMed1990

Renal sodium and water handling in hypothyroid patients: the role of renal insufficiency.

The mechanism responsible for renal tubular abnormalities in sodium and water excretion in hypothyroid patients is poorly understood. To evaluate the possible contribution of the reduced glomerular filtration rate of hypothyroidism to these abnormalities, tubular function in hypothyroid patients was compared with that in patients with chronic renal failure and in normal subjects. The lithium clearance method and oral water loading were used to evaluate parameters of tubular sodium and water handling, respectively. The hypothyroid and the chronic renal failure patients were selected to have similar reductions in glomerular filtration rate. As compared to the normal subjects, the hypothyroid and chronic renal failure patients had a decrease in proximal sodium reabsorption and an increase in distal sodium reabsorption. The changes in tubular handling of sodium were not different in the hypothyroid and the chronic renal failure patients. Maximal urinary flow rate and free water clearances were similarly reduced in the hypothyroid patients and the chronic renal failure patients. For all subjects studied, proximal sodium reabsorption and maximal urinary volume were directly correlated with the glomerular filtration rate, and distal nephron sodium reabsorption was proportionate to delivery of sodium from the proximal tubule. The results suggest that the abnormalities in tubular sodium and water handling in hypothyroid patients are comparable to those present in other patients with a similar degree of renal insufficiency. Thus, the tubular abnormalities in hypothyroidism may be a consequence of the associated decrease in glomerular filtration rate.

Adult↗
PubMed1990

Correlation between EEG spectral parameters and an educational evaluation.

EEG spectral parameters were computed in a group of children with different degrees of difficulty in learning to read and write. For statistical analyses, Z-transformed values according to normative age-regression equations were used to control the age effects. Canonical Correlation Analysis between absolute power in different bands and the categories of the educational evaluation (good, regular, poor and very poor) showed that more delta was probably related to a poor evaluation and more alpha in occipital areas to a good one. MONOVA also showed highly significant differences in the absolute power in many leads between children with different evaluations. As children with a poor evaluation very frequently had antecedents of risk factors related to brain damage and were from a low socioeconomic status, and both factors have been shown to affect absolute power, it may be that the differences observed were due to these causes. However, relative power correlated more with the learning problems. Children with minor difficulties, with no antecedents and with good socioeconomic status had more theta in almost all leads than children with a good evaluation and with the same characteristics. Children with a poor, or very poor, evaluation had more delta in left frontal and temporal areas (F3, F7 and T3) which may reflect underlying cerebral dysfunction of these regions directly involved in reading and writing processes.

Child↗
PubMed1990

Cyclic cholecystokinin analogues that are highly selective for rat and guinea pig central cholecystokinin receptors.

Cholecystokinin (CCK) analogues (JMV310, JMV320, JMV328, and JMV332), obtained by side chain to side chain cyclization of a lysine residue in position 28 with a lysine residue in position 31, were found to be highly selective for the brain CCK receptor (CCK-B receptor), both in guinea pig and rat. In these analogues, the C-terminal tetrapeptide region of the molecule, which is the crucial determinant for binding to CCK-B receptors, has been constrained by cyclization. These analogues were highly potent in inhibiting binding of labeled CCK-8 to rat and guinea pig brain membranes (apparent affinity in the nanomolar range) but were poorly efficacious in inhibiting binding of labeled CCK-8 to rat or guinea pig pancreatic acini. In agreement with their low affinity for the pancreatic receptor, these CCK analogues were not very potent in stimulating amylase secretion. These cyclic CCK analogues were demonstrated to be highly selective for the brain CCK receptors.

Amylases↗
PubMed1990

Acute effects of captopril and ibuprofen on proteinuria in patients with nephrosis.

Captopril decreases protein excretion in patients with nephrosis. To evaluate whether captopril has an acute antiproteinuric effect and to evaluate the role of changes in renal hemodynamics or glomerular permselectivity on this effect, renal clearance studies were performed in patients without diabetes but with nephrosis. Protein excretion and renal hemodynamics were measured at baseline and after the administration of captopril. To measure the contribution of renal prostaglandins, patients were restudied on a separate day, after the combined administration of captopril and the prostaglandin synthetase inhibitor ibuprofen. Both treatments significantly reduced mean protein excretion, but the change was greater with combined therapy than with captopril alone (40.6% vs 20.0%). Mean glomerular filtration rate (GFR) decreased by 4.8% (not significant) and 16.5% (p less than 0.001), and filtration fraction (FF) decreased by 13.6% (p less than 0.001) and 14.9% (p less than 0.001) after captopril alone and combined therapy, respectively. No significant correlation was found between changes in proteinuria and changes in GFR or FF after treatment with captopril alone. In contrast, the decrease in proteinuria correlated with the change in GFR after combined drug administration (r = 0.68, p = 0.06). The ratio of immunoglobulin G to albumin clearance, an index of glomerular permselectivity, was unaffected by captopril but decreased significantly (by 43%) after combined drug administration. The results suggest that the acute antiproteinuric effect of captopril is not due to changes in FF, GFR, or glomerular perselectivity. The addition of ibuprofen enhances the antiproteinuric effect of captopril by decreasing the GFR as well as by enhancing the permselectivity of the glomerular capillary membrane.

Captopril↗
PubMed1989

Novel activity of angiotensin-converting enzyme. Hydrolysis of cholecystokinin and gastrin analogues with release of the amidated C-terminal dipeptide.

ACE (angiotensin-converting enzyme; peptidyl dipeptidase A; EC 3.4.15.1), cleaves C-terminal dipeptides from active peptides containing a free C-terminus. We investigated the hydrolysis of cholecystokinin-8 [CCK-8; Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2] and of various gastrin analogues by purified rabbit lung ACE. Although these peptides are amidated at their C-terminal end, they were metabolized by ACE to several peptide fragments. These fragments were analysed by h.p.l.c., isolated and identified by comparison with synthetic fragments, and by amino acid analysis. The initial and major site of hydrolysis was the penultimate peptide bond, which generated a major product, the C-terminal amidated dipeptide Asp-Phe-NH2. As a secondary cleavage, ACE subsequently released di- or tri-peptides from the C-terminal end of the remaining N-terminal fragments. The cleavage of CCK-8 and gastrin analogues was inhibited by ACE inhibitors (Captopril and EDTA), but not by other enzyme inhibitors (phosphoramidon, thiorphan, bestatin etc.). Hydrolysis of [Leu15]gastrin-(14-17)-peptide [Boc (t-butoxycarbonyl)-Trp-Leu-Asp-Phe-NH2] in the presence of ACE was found to be dependent on the chloride-ion concentration. Km values for the hydrolysis of CCK-8, [Leu15]gastrin-(11-17)-peptide and Boc-[Leu15]gastrin-(14-17)-peptide at an NaCl concentration of 300 mM were respectively 115, 420 and 3280 microM, and the catalytic constants were about 33, 115 and 885 min-1. The kcat/Km for the reactions at 37 degrees C was approx. 0.28 microM-1.min-1, which is approx. 35 times less than that reported for the cleavage of angiotensin I. These results suggest that ACE might be involved in the metabolism in vivo of CCK and gastrin short fragments.

Amino Acid Sequence↗