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Biomedical subjects

J Diaz

Publications and source records attributed to J Diaz.

At least 145 records · Page 8Linked to original sources
PubMed1994

[125I]iodoproxyfan, a new antagonist to label and visualize cerebral histamine H3 receptors.

Iodoproxyfan, i.e., 3-(1H-imidazol-4-yl)propyl-(4-iodophenyl)-methyl ether, is a novel potent and selective histamine H3 receptor antagonist. [125I]Iodoproxyfan binding to membranes of the rat striatum was reversible and saturable. Specific binding defined with 1 microM (R)-alpha-methylhistamine corresponded to 65% of the total at 30 pM. Scatchard analysis indicated a Kd of 65 pM and maximal binding capacity of 78 fmol/mg of protein. The specificity of [125I]Iodoproxyfan binding to H3 receptors was demonstrated by its pharmacological profile. A series of H3 receptor agonists inhibited [125I]iodoproxyfan binding with a similar maximal effect and with the expected order of potency and stereoselectivity ratio. H3 receptor antagonists inhibited the specific binding with the expected Ki values. In the presence of guanylnucleotides, 40% of sites exhibited a approximately 40-fold lower affinity for histamine, indicating that the H3 receptor belongs to the superfamily of G protein-coupled receptors and revealing the existence of two populations of sites. Well contrasted autoradiographic pictures of total [125I]iodoproxyfan binding to sections of the rat brain were obtained in a short time and over a low nonspecific binding. The heterogenous distribution of H3 receptors with high labeling of anterior cerebral cortex, ventral striatum and other limbic areas was confirmed. In addition, a clearly distinguishable laminated pattern of labeling was evidenced in the cerebral cortex and hippocampal formation. Hence, this new probe should be useful for sensitive assay and localization of the H3 receptor.

Animals↗
PubMed1993

Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation.

By using a strategy based on nucleotide sequence homology, we have cloned a cDNA encoding a functional serotonin (5-HT) receptor. The deduced amino acid sequence of the 5-HT7 receptor displays limited homology with that of other 5-HT receptors. In addition to the seven stretches of hydrophobic amino acids that characterize the superfamily of receptors interacting with guanine nucleotide-binding proteins, the 448-aa sequence of the 5-HT7 receptor contains a hydrophobic domain located at its N-terminal end. Genomic analysis indicated the presence of introns interrupting the coding sequence. The 5-HT7 receptor, stably expressed in transfected CHO cells, bound [3H]5-HT with high affinity (Kd = 1 nM), like receptors of the 5-HT1 subfamily from which, however, it was clearly distinguished by its pharmacology. 5-HT in nanomolar concentrations stimulated cAMP accumulation in these CHO cells by approximately 10-fold, whereas lysergic acid diethylamide displayed low intrinsic agonist activity. These various properties differentiate the 5-HT7 receptor from the four other subfamilies of mammalian 5-HT receptors (i.e., the 5-HT1-, 5-HT2-, 5-HT3-, and 5-HT4-like subfamilies) and, therefore, appear to define another receptor subfamily. Northern blot and in situ hybridization analyses showed the 5-HT7 transcripts to be expressed in discrete areas of the limbic brain (e.g., pyramidal hippocampus cells, tenia tecta, amygdaloid, or mammillary nuclei), suggesting that the receptor mediates serotoninergic controls in functions like mood, learning, or neuroendocrine and vegetative behaviors.

Amino Acid Sequence↗
PubMed1993

A novel rat serotonin (5-HT6) receptor: molecular cloning, localization and stimulation of cAMP accumulation.

Using a strategy based upon nucleotide sequence homology and starting from the sequence of the rat histamine H2 receptor (Ruat et al., Biochem. Biophys. Res. Commun. 1991, 179, 1470-1478), we have cloned a rat cDNA encoding a functional serotonin receptor (5-HT6). Its coding sequence corresponds to a glycoprotein of 436 amino acids displaying significant homology with other cloned monoaminergic receptors, e.g., various serotonin receptors. Genomic analysis of its gene indicated the presence of at least one intron. The major transcript of the 5-HT6 receptor gene has a size of approximately 4.1 kb but another minor 3.2 kb transcript was also evidenced. The highest expression, detected by Northern blot analysis as well as by in situ hybridization occurs in various serotoninergic areas of rat or guinea pig brain such as striatum, olfactory tubercle, nucleus accumbens and hippocampus, but a faint expression is also detectable in rat stomach. When transiently expressed in transfected COS-7 cells the 5-HT6 receptor appears to be positively coupled to cyclic AMP production.

Amino Acid Sequence↗
PubMed1993

Four-year experience in a randomized study of the Gyne T 380 Slimline and the Standard Gyne T 380 intrauterine copper devices.

Performance of the Slimline and Standard models of the Gyne T 380 were measured through four years in a comparative study initially involving 996 women, seventy percent of whom were randomized to the Slimline device. Cumulative pregnancy rates of Slimline users were 0.3 +/- 0.2 per 100 both at three and at four years, as compared with rates of 1.5 +/- 0.9 and 3.8 +/- 1.7 at the same intervals for users of the Standard model (P > .05). The four-year explusion rate of the Slimline, 8.6 +/- 1.3 per 100, was significantly higher than the comparable rate of the Standard model, 4.4 +/- 1.6 (P < .05). The two Gyne T* models did not differ in continuation rates. First time IUD users, however, had substantially lower continuation rates than did former users (P < .001), in consequence of their relative youth and desire to have additional children. Other performance measures did not differ importantly by device.

Adolescent↗
PubMed1993

Cardiac performance preserved despite thiopental loading.

BACKGROUND: Some cerebral artery aneurysms require cardiopulmonary bypass and deep hypothermic circulatory arrest to be clipped safely. During bypass these neurosurgical patients often are given large doses of thiopental in the hope that additional cerebral protection will be provided. However, thiopental loading during bypass has been associated with subsequent cardiac dysfunction in patients with heart disease. This study was undertaken to determine how patients without concomitant heart disease would respond to thiopental loading. METHODS: Twenty-four neurosurgical patients with giant cerebral aneurysms and little or no cardiac disease were anesthetized with fentanyl, nitrous oxide, and isoflurane. Thiopental was titrated to achieve electroencephalographic burst-suppression before bypass, and the infusion was continued until after separation. Prebypass hemodynamic and echocardiographic measurements were obtained during a stable baseline and 15 min after thiopental loading began. They were repeated after bypass. RESULTS: Prebypass thiopental loading increased heart rate from 61 +/- 11 to 72 +/- 13 beats/min and decreased stroke volume from 43 +/- 10 to 38 +/- 8 ml.beat-1.m-2, but arterial and filling pressures, vascular resistance, cardiac index, and ejection fraction remained the same. Before bypass, thiopental plasma concentration measured 28 +/- 8 micrograms/ml. Loading continued for 2-3 h until after bypass was terminated, and the overall infusion rate was 18 +/- 5 mg.kg-1.h-1. All patients were easily separated from bypass without inotropic support. Following bypass, vascular resistance was decreased; heart rate, filling pressures, and cardiac index were increased; stroke volume had returned to its baseline; and ejection fraction was unchanged. CONCLUSIONS: It was concluded that if preoperative ventricular function is good, thiopental loading to electroencephalographic burst-suppression causes negligible cardiac impairment and does not impede separation from cardiopulmonary bypass.

Adult↗
PubMed1993

Cytolytic (TIA-1+) tumor infiltrating lymphocytes in B cell non-Hodgkin's lymphomas. SWOG Central Repository Members.

TIA-1 is a monoclonal antibody (mAb) that identifies cytolytic cells. We studied eleven B cell non-Hodgkin's lymphomas (NHL) of low grade, eleven B cell NHL of intermediate-high grade, and 10 benign lymphoid hyperplasias (BLH) to investigate potential differences in the number of host cytolytic tumor infiltrating lymphocytes (TILs). Frozen sections were immunostained with TIA-1 mAb and the number of immunoreactive cells (TIA-1+) per mm2 of tissue was quantitated within reactive or neoplastic lymphoid follicles or random areas of diffuse NHL. The number of TIA-1+ cells/mm2 was significantly higher in intermediate and high grade B cell NHL than in low grade NHL or BLH with means +/- se of 1377.8 +/- 173, 866.2 +/- 92.3 and 774.1 +/- 76.2, respectively (p < 0.0183 and p < 0.0125). There was no significant difference between BLH and low grade NHL. The increased number of TIA-1+ TILs in B cell NHL of intermediate and high grade suggests the possibility of a host cytolytic immune response versus the tumor. Paradoxically, B cell tumors of worst biological outcome contained more cytolytic TILs. Functional defects of host cytolytic TILs in NHL patients should be investigated in future studies.

Antibodies, Monoclonal↗
PubMed1993

Simultaneous PAGE, immunoblotting, and immunohistochemical analysis of differentiation associated keratins in lesions of the oral mucosa.

The expression of differentiation associated high PM Keratin polypeptides of the oral mucosa lesions were studied by immunohistochemical and immunoblotting techniques applied to adjacent sections of each biopsy specimen. The material studied included specimens of leukoplakia, verrucous carcinoma, squamous cell carcinoma, adenocarcinoma and keratoacanthoma. Little or no expression of 65-67 Kd keratins was evident in squamous cell carcinoma and adenocarcinoma. Hyperkeratotic (both benign and dysplastic) lesions such as verrucous carcinoma, leukoplakia, and keratoacanthoma, showed great variations in the intensity of 65-67 bands and a very irregular immunohistochemical staining pattern. Increased amounts of horny substance was usually accompanied by absence of, or decreased expression of 65-67 Kd keratins, thus indicating a change in the polypeptide composition of the horny layer in pathological conditions of the oral epithelium.

Adenocarcinoma↗
PubMed1993

Combined histochemical stains in the differential diagnosis of Cryptococcus neoformans.

Three combinations of histochemical stains were used to study 69 routinely processed tissues containing various "yeast-like" fungal organisms (Cryptococcus neoformans, Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, Paracoccidioides brasiliensis, and Candida albicans). Fontana-Masson stain combined either with mucicarmine or Alcian blue produced distinctive staining of C. neoformans (Fontana-Masson-positive wall and mucin-positive capsule) that was not identified in other fungi. The Alcian blue stain combined with periodic acid-Schiff reaction also was useful for fungal classification, because the Alcian blue component reacted with only C. neoformans (capsule) and B. dermatitidis (wall) and the periodic acid-Schiff reaction reacted with the cell wall and body of each fungus. We concluded that the combined histochemical stains used in conjunction with morphologic study of hematoxylin and eosin- and Gomori methenamine silver-stained sections are helpful in the differential diagnosis of yeast-like fungal organisms.

Alcian Blue↗
PubMed1992

Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin.

We have identified 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin ([3H]7-OH-DPAT) as a selective probe for the recently cloned dopamine D3 receptor and used it to assess the presence of this receptor and establish its distribution and properties in brain. In transfected Chinese hamster ovary (CHO) cells, it binds to D3 receptors with subnanomolar affinity, whereas its affinity is approximately 100-, 1000-, and 10,000-fold lower at D2, D4, and D1 receptors, respectively. Specific [3H]7-OH-DPAT binding sites, with a Kd of 0.8 nM and a pharmacology similar to those at reference D3 receptors of CHO cells, were identified in rat brain. D3 receptors differ from D2 receptors in brain by their lower abundance (2 orders of magnitude) and distribution, restricted to a few mainly phylogenetically ancient areas--e.g., paleostriatum and archicerebellum--as evidenced by membrane binding are autoradiography studies. Native D3 receptors in brain are characterized by an unusually high nanomolar affinity for dopamine and a low modulatory influence of guanyl nucleotides on agonist binding. These various features suggest that D3 receptors are involved in a peculiar mode of neurotransmission in a restricted subpopulation of dopamine neurons.

Animals↗
PubMed1992

In vitro multiplication of Cryptosporidium parvum in mouse peritoneal macrophages.

Cryptosporidium parvum of bovine origin was developed in vitro in unsensitized mouse peritoneal macrophages. Macrophages growing in RPMI medium were infected with sporozoites or with oocysts, and after staining infections were studied by light microscopy. A high parasitic index was obtained with multiple infections occurring commonly. This is a simple method for the study of Cryptosporidium biology, and for in vitro assays of pharmacological activity.

Animals↗
PubMed1992

Pharmacokinetics and pharmacodynamics of vecuronium in the obese surgical patient.

The effect of obesity on the disposition and action of vecuronium was studied in 14 surgical patients. After induction of anesthesia with thiopental and maintenance of anesthesia by inhalation of nitrous oxide and halothane, seven obese patients (93.4 +/- 13.9 kg, 166% +/- 30% of ideal body weight, mean +/- SD) and seven control patients (60.9 +/- 12.3 kg, 93% +/- 6% of ideal body weight) received 0.1 mg/kg of vecuronium. Plasma arterial concentrations of muscle relaxant were determined at 1, 3, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, and 360 min by a spectrofluorometric method. Simultaneously, neuromuscular blockade was assessed by stimulation of the ulnar nerve and quantification of thumb adductor response. Times to 50% recovery of twitch were longer in the obese than in the control patients (75 +/- 8 versus 46 +/- 8 min) as were 5%-25% recovery times (14.9 +/- 4.0 versus 10.0 +/- 1.7 min) and 25%-75% recovery times (38.4 +/- 13.8 versus 16.7 +/- 10.3 min). However, vecuronium pharmacokinetics were similar for both groups. When the data were calculated on the basis of ideal body weight (IBW) for obese and control patients, total volume of distribution (791 +/- 303 versus 919 +/- 360 mL/kg IBW), plasma clearance (4.65 +/- 0.89 versus 5.02 +/- 1.13 mL.min-1.kg IBW-1), and elimination half-life (119 +/- 43 versus 133 +/- 57 min) were not different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Pharmacokinetics and pharmacodynamics of pipecuronium bromide (Arduan) in elderly surgical patients.

The neuromuscular response to pipecuronium bromide (Arduan), 70 micrograms/kg, was studied in 20 elderly (greater than 70 yr) and 10 younger patients (less than 60 yr) during nitrous oxide, fentanyl, and droperidol anesthesia. The adductor pollicis response to single 0.2-ms supramaximal pulses was recorded. Although all younger patients were completely paralyzed, 2 of 20 elderly patients did not attain 90% paralysis. Onset time in the elderly was prolonged (6.9 +/- 2.6 vs 4.3 +/- 1.5 min, P less than 0.02). Spontaneous recovery was similar in both groups, with 75% recovery occurring at 133 +/- 52 min in the elderly and 146 +/- 46 min in the younger patients. The pharmacokinetic variables were similar for the two groups, and pharmacodynamic analysis revealed a similar sensitivity at the neuromuscular junction. The pharmacologic actions of pipecuronium in otherwise healthy patients do not differ between young and elderly adults.

Aged↗
PubMed1992

Determination of T cell monoclonality in non-Hodgkin's lymphoma by frozen section immunohistology. The SWOG Central Repository Members.

Monoclonal antibodies (mAb) reactive with seven distinct T cell receptor (TcR) alpha/beta variable region (V) families have become available. We investigated the potential utility of these mAb to establish T cell clonality (restrictive expression of one single V region family type) by frozen section immunohistology. We studied 40 non-Hodgkin's lymphomas (NHL) previously classified, immunophenotypically and genotypically by the South Western Oncology Group (SWOG) as 20 B and 20 T cell NHL. Frozen sections of each neoplasm were immunostained with the following mAb: beta-V5a, beta-V5b, beta-V6a, beta-V8a, beta-V12a, alpha/beta-Va and alpha-V2a. The large atypical lymphocytes of 18 of 20 T cell NHL showed no reactivity with the seven V region family mAb and only two showed exclusive immunoreactivity (one with anti-alpha V2a and the other with anti-beta V6a). All large atypical B cells in the 20 B cell NHL were non-reactive with the V region family mAb and each of the 40 neoplasms disclosed no or a trace reactivity in small host T cells. The results show that clonality can be determined in only a small percentage of T cell NHL (Sensitivity 10%, specificity 100%). Therefore, until new mAb become available, genotypic analysis remains the most sensitive and reliable method to establish T cell clonality.

Antibodies, Monoclonal↗
PubMed1991

Two-year comparative trial of the Gyne T* 380 Slimline and Gyne T* 380 intrauterine copper devices.

In a randomized trial of the Gyne T* 380 Slimline, the-two year pregnancy rate was 0.3 per 100 and the continuation rate was 65 per 100. These rates did not differ statistically from those of the standard Gyne T* 380, nor did other performance parameters differ between devices by the log-rank test. Women under age 30 had lower continuation rates using either device than did women age 30 or older at admission because of removals for planned pregnancy. Conception rates among those who desired pregnancy were 35 per 100 at one month and 86 per 100 at one year.

Adult↗