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Biomedical subjects

J Martinez

Publications and source records attributed to J Martinez.

At least 397 records · Page 22Linked to original sources
PubMed1988

A pseudopeptide that is a potent cholecystokinin agonist in the peripheral system is able to inhibit the dopamine-like effects of cholecystokinin in the striatum.

There are no known specific effective cholecystokinin (CCK) receptor antagonists of both peripheral and central nervous systems. Here, we describe experiments which demonstrate that a synthetic pseudopeptide analogue of CCK-7 is a potent agonist in the peripheral system and behaves as a selective and highly potent inhibitor of the dopamine-like effects of CCK in the striatum. This compound, t-butyloxycarbonyl-Tyr (SO3H)-Nle psi (COCH2)Gly-Trp-Nle-Asp-Phe-NH2, is able to stimulate enzyme secretion from rat pancreatic acini, with high efficacy and potency. It is also very potent in inhibiting the binding of labeled CCK-8 to rat pancreatic acini (IC50 = 5 nM) and to guinea pig and mouse brain membranes (IC50 = 0.7 nM). However, this compound is able to antagonize the effects of intrastriatally injected t-butyloxycarbonyl-[Nle28,31] CCK-8 in mice, with high potency.

Animals↗
PubMed1988

Binding and cross-linking of rabbit fibronectin by rabbit hepatocytes in suspension.

Fibronectin purified from rabbit plasma was radioiodinated, and its interaction with rabbit hepatocytes in suspension was studied. Iodinated fibronectin interacted in a time-dependent fashion reaching plateau at 3 h. The interaction was greater in the presence of calcium than in the presence of magnesium or EDTA. Saturation occurred at about 140 nM fibronectin with about 1,400,000 molecules bound per cell. The interaction could be inhibited by unlabeled fibronectin or fibrinogen but not by the tetrapeptide Arg-Gly-Asp-Ser or by albumin, transferrin, or fetuin. About 50% of the bound iodinated fibronectin was incorporated, in a calcium-dependent fashion, into cross-linked high molecular weight complexes at the cell surface through a mechanism consistent with a cellular transglutaminase-mediated reaction. Iodinated fibronectin which could be displaced from the cell was monomeric in nature, while the cell-associated material remained in high molecular weight complexes. The role of the interaction is currently under investigation, but it is possible that the binding may promote cellular adhesion or facilitate intercellular interaction.

Animals↗
PubMed1988

Asymptomatic form of left pulmonary artery sling.

Eight patients with left pulmonary artery sling, which were asymptomatic at the time of the last consultation, are described: 2 adults and 1 child with no history of symptoms, 3 children with mild forms of airways obstruction and 2 patients with typical severe symptoms of airways obstruction in infancy. The mean follow-up of these 8 patients was 10 years (range 4 to 23), and in 1986, all were in good health and free of respiratory symptoms. The long-term prognosis is usually good.

Airway Obstruction↗
PubMed1988

Correlation of phosphorus-31 magnetic resonance spectroscopy and morphologic findings in Alzheimer's disease.

Senile plaques (SPs), especially, and neurofibrillary tangles are important pathologic markers for the diagnosis of Alzheimer's disease (AD), but neither is pathognomonic for AD. We hypothesize that elevations in levels of phosphomonoesters, precursors of membrane phospholipids, occur early in the pathogenesis of AD and precede the appearance of SPs. In contrast, elevations in levels of phosphodiesters, breakdown products of phospholipids, reflect degeneration of neural membranes and will correlate with the appearance of SPs. Correlative phosphorus-31 magnetic resonance spectroscopy and morphologic studies conducted to test this hypothesis disclosed that elevations in levels of phosphomonoesters had a negative correlation with the numbers of SPs, and elevations in levels of phosphodiesters had a positive correlation with the numbers of SPs. No correlations were observed for either membrane parameter and neurofibrillary tangles. These findings support our hypothesis and suggest that aberrations in the synthesis of membrane phospholipids are early metabolic events in the pathogenesis of AD.

Aged↗
PubMed1988

Cholecystokinin suppresses food intake in cats: structure-activity characterization.

Our experimental models in this study were cats fitted with gastric fistulae. Intravenous infusion of sulfated CCK 8 and nonsulfated Boc CCK 7 inhibited both sham-feeding and feeding in fasted cats. The threshold dose (1.2 pmol/kg.hr) required for inhibition of sham-feeding was identical to that required to inhibit feeding in the same animals. However, the gastric secretory studies indicated that this dose was 90 times lower than the threshold dose stimulating gastric acid secretion (109 pmol/kg.hr). In nonfasted animals, sulfated CCK 8 and nonsulfated Boc CCK 7 (219 and 875 pmol/kg.hr) are both capable of decreasing the food intake at different intervals following the infusion with no significant effect on daily food intake. Our findings clearly show that there is no difference in the sensitivity of CCK's ability to inhibit sham-feeding and feeding, suggesting that CCK's suppressive effect on food intake does not solely involve gastric distension mechanisms. In contrast to gastric acid secretion, the sulfate group is not a "restrictive" factor for peripherally-induced CCK satiety.

Animals↗
PubMed1988

Flow cytometry shows recurrent aneuploid clone after remission in megakaryocytic leukemia.

Flow cytometry using a DNA label can quantitate aneuploid clones in malignant tissue. We illustrated the clinical value of this technique in a 71-year-old woman with acute megakaryocytic leukemia, which was diagnosed by staining of the blasts with factor VIII antigen and their morphologic resemblance to megakaryoblasts. Marrow cells were removed from needle biopsies by vortexing in RPMI medium, centrifuged in Ficoll-Hypaque, stained with a propidium-iodide/NP-40 mixture, and analyzed at 488 nm using an argon laser. During 3 weeks of low-dose cytosine arabinoside (ara-c) infusion therapy, hyperdiploid peak A dropped from 35% (day 0) to 2.3% (day 14) to 0% (day 21), with development of marrow hypoplasia. Similarly, hyperdiploid peak B, went from 7.6% to 9.1% to 3.5%. Subsequently, her marrow recovered normal morphology and lost the aneuploid peaks. Her blood counts recovered to near normal. Four months later, she relapsed and had a return of the day-21, incompletely eradicated peak B. There was no evidence of peak A. Repeated treatment with ara-c resulted in temporary suppression of the disease, but she died 3 months later with progressive hepatosplenomegaly. Analysis of cells from her enlarged liver, heavily infiltrated with blasts, showed a large hyperdiploid peak B. In this patient, ara-c therapy induced a remission with permanent eradication of one clone, but incomplete eradication of a second clone, which ultimately led to her relapse and death.

Aged↗
PubMed1988

2-Phenylethyl ester and 2-phenylethyl amide derivative analogues of the C-terminal hepta- and octapeptide of cholecystokinin.

Syntheses of analogues of the C-terminal octa- and heptapeptide of cholecystokinin are described. These analogues were obtained by replacing the C-terminal phenylalanine residue by 2-phenylethyl alcohol or by 2-phenylethylamine derivatives and by replacing the tryptophan residue by a D-tryptophan. The CCK-derivatives were tested for their ability to inhibit binding of labeled CCK-8 to rat pancreatic acini and to guinea pig brain membranes, and for their action on stimulation of amylase release from rat pancreatic acini. Some of these derivatives appeared to exhibit only part of the CCK-activity on amylase release, the D-Trp analogues behaving as CCK-antagonists.

Amino Acid Sequence↗
PubMed1988

Structure-activity relationship studies on cholecystokinin: analogues with partial agonist activity.

In the present study, hepta- and octapeptide analogues of the C-terminal part of cholecystokinin, modified on the C-terminal phenylalanine residue, were synthesized. CCK analogues were prepared in which the peptide bond between aspartic acid and phenylalanine had or had not been modified and were lacking the C-terminal primary amide function. These CCK derivatives were able to cause full stimulation of amylase release from rat pancreatic acini but without a decrease in amylase release at supramaximal concentrations. There was a close relationship between the abilities of these derivatives to stimulate amylase release and their abilities to inhibit binding of 125I-BH-CCK-9 to CCK receptors on rat and guinea pig pancreatic acini. These CCK analogues were also able to recognize the guinea pig brain CCK receptors, some of them being particularly potent. The findings indicate that the aromatic ring of phenylalanine is important for the binding to brain and pancreatic CCK receptors, whereas the C-terminal primary amide function is not essential for the binding to pancreatic CCK receptors but is crucial for biological activity of rat pancreatic acini.

Amylases↗
PubMed1988

Ganglioglioma, a malignant tumor? Correlation with flow deoxyribonucleic acid cytometric analysis.

This study describes the flow cytometric deoxyribonucleic acid (DNA) analysis of a resected ganglioglioma. The initial histopathological analysis revealed a benign tumor characterized by a predominance of mature ganglion cells. The flow cytometric DNA analysis of the necrotic areas, however, demonstrated an aneuploid population of cells. Further examination by histological analysis of the tumor revealed both benign and atypical foci. The retrospective DNA analysis performed from paraffin sections of tissue with benign-histological findings demonstrated euploid populations of cells consistent with a benign, slow-growing lesion. In contrast, DNA analysis performed from tissue with atypical histological findings revealed aneuploid populations of cells consistent with a malignant phenotype. Our analysis provides additional data supporting the existence of tumor progression in some gangliogliomas. Results support the concept of tumor cell heterogeneity and the importance of adequate tumor sampling. The finding of aneuploid populations with unfavorable histology further supports the use of flow cytometry as an adjunct method in assessing tumor biology.

Adolescent↗
PubMed1988

High prevalence of genital tract papillomavirus infection in female adolescents.

To investigate clinical condyloma, abnormal cervical cytologic findings, and evidence of human papillomavirus infections, 89 adolescent girls were examined. Cellular DNAs extracted from exfoliated cervical cells were examined for human papillomavirus genomic sequences by Southern transfer hybridization using 32P-labeled human papillomavirus DNA probes. Human papillomavirus sequences were detected in 12 (13%) young women, abnormal cytologic specimens in 21 (24%), and vulvar condylomas in 12 (13%). The human papillomavirus types identified included HPV-6/11 (four instances), which is known to be associated with benign lesions, and HPV-16, -18, and -31 (eight instances) which are considered to have oncogenic potential. Two young women were infected with both HPV-16 and -31. Human papillomavirus sequences were found in 48% of the young women with abnormal cytologic findings and in 3% of patients with normal cytologic findings (P less than .0001). Condylomatous changes in the cervical smear were associated with the presence of HPV-6/11 and mild dysplasia with the presence of HPV-16, -18, and -31. The presence of vulvar condylomas correlated with condylomatous changes in the cervical smear and with the recovery of HPV-6/11 from the cervical epithelium. The results indicate that the prevalence of human papillomavirus infections in this population is high and that a majority of the infections are with viruses associated with lower genital tract malignancies.

Adolescent↗
PubMed1987

A synthetic peptide derivative that is a cholecystokinin receptor antagonist.

So far, there are no known peptidic effective receptor antagonists of both peripheral and central effects of cholecystokinin (CCK). Here, we describe a synthetic peptide derivative of CCK, t-butyloxycarbonyl-Tyr(SO3-)-Met-Gly-D-Trp-Nle-Asp 2-phenylethyl ester 1 (where Nle is norleucine), which is a potent CCK receptor antagonist. In rat and guinea pig dispersed pancreatic acini, this peptide derivative did not alter amylase secretion, but was able to antagonize the stimulation caused by cholecystokinin-related agonists. It caused a parallel rightward shift in the dose-response curve for the stimulation of amylase secretion with half-maximal inhibition of CCK-8-stimulated amylase release at a concentration of about 0.1 microM. Compound 1 was able to inhibit the binding of labeled CCK-9 (the C-terminal nonapeptide of CCK) to rat and guinea pig pancreatic acini (IC50 = 5 X 10(-8) M) as well as to guinea pig cerebral cortical membranes (IC50 = 5 X 10(-7) M). These results indicate that Compound 1 is a potent competitive CCK receptor antagonist.

Amylases↗
PubMed1987

Binding and processing of fibrinogen by rabbit hepatocytes.

We describe a specific fibrinogen-hepatocyte interaction. Rabbit 125I-labeled fibrinogen (125I-FGN) was incubated at 4 degrees C with suspensions of rabbit hepatocytes (approximately 1 X 10(6) cells/ml). Bound ligand was separated from free by centrifugation of cells through oil and quantitated by gamma-scintillation counting. Specific binding, determined by subtraction of nonspecific binding in the presence of 8 mM EDTA from total binding in the presence of 2 mM CaCl2, required 3 h to plateau and represented approximately 70% of total binding. Specific binding was calcium-dependent and was negligible in buffer containing 2 mM MgCl2. Half-maximal saturation occurred at approximately 30 nM 125I-FGN with approximately 480,000 molecules/cell at saturation. Dilution experiments revealed comparable affinities for labeled and unlabeled fibrinogen. Total binding was irreversible as determined by addition of excess unlabeled fibrinogen or EDTA. Specific binding of 25 nM 125I-FGN was inhibited, in a concentration-dependent fashion, by unlabeled fibrinogen or fibrinogen fragment D95 (Mr = 95,000), but not by fibrinogen fragment E or Arg-Gly-Asp-containing peptides. Unlabeled fibrinogen (3.1 microM) completely abolished specific binding, whereas greater than 80% inhibition was achieved with 10 microM fragment D95. Sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography of 125I-FGN bound in the presence of calcium demonstrated disappearance of A alpha chains with formation of products of Mr greater than 200,000; EDTA or unlabeled fibrinogen prevented fibrinogen processing. These data describe a unique fibrinogen-hepatocyte interaction which differs considerably from the platelet-fibrinogen interaction, especially with regard to the processing of the fibrinogen molecule.

Animals↗
PubMed1987

Prophylaxis for deep vein thrombosis and pulmonary embolism in the surgical patient.

This article reviews the pathophysiology for the development of deep vein thrombosis and pulmonary embolism in the surgical patient. Patients are stratified into risk groups based on predisposing criteria for the development of thrombosis. Seven modalities of prophylaxis are reviewed with respect to appropriate application. Five major types of surgery are described assessing incidence and prophylaxis of choice. The final section deals with the special consideration of patients with thrombotic disease undergoing surgery.

Humans↗
PubMed1987

Synthesis and biological activity of partially modified retro-inverso pseudopeptide derivatives of the C-terminal tetrapeptide of gastrin.

The effects of partial retro-inverso modifications of selected peptide bonds of the N-terminal tetrapeptide of gastrin have been studied. In some of the synthesized compounds, the phenylalanyl residue has been replaced by the (R,S)-2-benzylmalonyl, 3-phenylpropionyl, benzylcarbamoyl, or benzyloxycarbonyl moieties. All pseudopeptides showed affinity for the gastrin receptor, in vitro, with potencies varying from IC50 = 10(-7) to IC50 = 10(-4) M. These compounds exhibited little or no activity on acid secretion in the anesthetized rat but were able to antagonize the action of gastrin. Among the most potent were Boc-Trp-Leu-gAsp-CO-CH2CH2C6H5 (20) (ED50 = 0.15 microM/kg), Boc-Trp-Leu-gAsp-m(R,S)Phe-NH2 (3) (ED50 = 0.15 microM/kg), and Boc-Trp-gLeu-D-Asp-m(R,S)Phe-NH2 (7) (ED50 = 0.3 microM/kg).

Animals↗
PubMed1987

Synthesis and biological activities of pseudopeptide analogues of the C-terminal heptapeptide of cholecystokinin. On the importance of the peptide bonds.

A series of pseudopeptide analogues of the C-terminal heptapeptide of cholecystokinin in which each peptide bond, one at a time, has been replaced by a CH2NH bond were synthesized: Z-Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp psi-(CH2NH)Phe-NH2 (1), Z-Tyr(SO3-)-Nle-Gly-Trp-Nle psi (CH2NH)Asp-Phe-NH2 (2), Z-Tyr(SO3-)-Nle-Gly-Trp psi-(CH2NH)Nle-Asp-Phe-NH2 (3), Z-Tyr(SO3-)-Nle-Gly psi(CH2NH)Trp-Nle-Asp-Phe-NH2 (4), Z-Tyr(SO3-)-Nle psi-(CH2NH)Gly-Trp-Nle-Asp-Phe-NH2 (5), Z-Tyr(SO3-)-Met-Gly-Trp-Nle-Asp psi (CH2NH)Phe-NH2 (6), Z-Tyr-(SO3-)-Met-Gly-Trp-Nle psi (CH2NH)Asp-Phe-NH2 (7), Z-Tyr(SO3-)-Met-Gly-Trp psi (CH2NH)Nle-Asp-Phe-NH2 (8). These derivatives were studied for their ability to stimulate amylase release from rat pancreatic acini and to inhibit the binding of labeled CCK-9 to rat pancreatic acini and to guinea pig brain membrane CCK receptors. They were compared to the potent CCK-8 analogue Boc-Asp-Tyr(SO3-)-Nle-Gly-Trp-Nle-Asp-Phe-NH2. All of these pseudopeptides were able to stimulate amylase secretion with the same efficacy as CCK-8 but with varying potencies. These compounds were also potent in inhibiting the binding of labeled CCK-9 to CCK receptors from rat pancreatic acini and from guinea pig brain membranes.

Amylases↗
PubMed1987

Inhibition of Adenosine Triphosphatase Activity from a Plasma Membrane Fraction of Acer pseudoplatanus Cells by Carbanilate Derivatives.

Thirty-one carbanilate derivatives were assayed for their capabilities to inhibit the ATPase activity of a plasma membrane fraction from Acer pseudoplatanus cells. At a concentration of 100 micromolar, nine compounds strongly inhibited the ATPase activity, with I(50) ranging from 14.5 micromolar to 35 micromolar. These molecules were also inhibitory to plasma membrane ATPases of other origins: plant (maize shoot), yeast (Schizosaccharomyces pombe), and animal (dog kidney). The most efficient molecule appeared to be 2,2,2-trichloroethyl 3,4-dichlorocarbanilate.

Journal Article↗