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Biomedical subjects

D Martinez

Publications and source records attributed to D Martinez.

At least 145 records · Page 8Linked to original sources
PubMed1987

Tumors secreting human TNF/cachectin induce cachexia in mice.

Anorexia and weight loss are serious complications that adversely effect the prognosis of cancer patients. It has been suggested that TNF/cachectin may cause cachexia. To determine if TNF/cachectin can induce progressive weight loss in tumor-bearing animals, a clone of the human TNF/cachectin gene was isolated and inserted into a mammalian expression vector. This construct was transfected into CHO cells, and a cell line (CHO/TNF-20) that secretes TNF/cachectin was isolated. A cell line (CHO/CMV-Neo) that contains the same expression vector without the TNF/cachectin gene was also isolated. Nude mice injected intraperitoneally with CHO/TNF-20 cells died more quickly than mice injected with CHO/CMV-Neo cells. Eighty-seven percent of mice inoculated intramuscularly with CHO/TNF-20 cells developed severe cachexia and weight loss. All mice bearing CHO/CMV-Neo tumors maintained or increased their body weight. We conclude that mice bearing tumors that secrete TNF/cachectin develop progressive wasting and die more quickly than mice bearing control tumors.

Animals↗
PubMed1987

Novel regulatory actions of 1 alpha,25-dihydroxyvitamin D3 on the metabolism of polyphosphoinositides in murine epidermal keratinocytes.

The in vitro incubation of murine keratinocytes in the presence of 1 alpha,25-dihydroxyvitamin D3 enhanced the rapid hydrolysis of the prelabeled keratinocyte polyphosphoinositides (polyPtdIns) when compared to untreated cells. The rapid hydrolysis of the polyPtdIns and the release of the inositol phosphates (particularly InsP3 and InsP2) precede the onset of differentiation of these cells. These data therefore suggest that 1 alpha,25-dihydroxyvitamin D3 functions in vitro to initiate the rapid generation of InsP3 from cellular polyPtdIns; this in turn may mobilize intracellular Ca2+, thus providing the signal which program the murine keratinocytes from a proliferating mode into a differentiating mode.

Animals↗
PubMed1987

Antibodies against amino acids 1-15 of tumor necrosis factor block its binding to cell-surface receptor.

Human tumor necrosis factor (hTNF) mediates a variety of biologic activities, which are dependent on the attachment of hTNF to cell-surface receptors. To identify regions of the hTNF protein involved in binding hTNF to its receptor, we prepared five synthetic peptides [hTNF-(1-15), hTNF-(1-31), hTNF-(65-79), hTNF-(98-111), and hTNF-(124-141)] and two hydroxylamine cleavage fragments [hTNF-(1-39) and hTNF-(40-157)] of hTNF. The hTNF-synthetic peptides and hTNF fragments were tested in hTNF receptor binding assays and in two biologic assays: cytolysis of tumor cells and suppression of lipoprotein lipase in adipocytes. Neither the synthetic peptides nor hTNF fragments were active agonists or antagonists in these assays. The synthetic peptides were also conjugated to thyroglobulin, and peptide-specific antisera were raised. All five peptide-thyroglobulin conjugates induced antibody responses to the immunizing peptide and to hTNF. Each antiserum was tested for antagonist activity in hTNF binding assays. Only antisera raised against hTNF-(1-15) or hTNF-(1-31) and antisera against whole hTNF blocked binding. IgGs purified from these three antisera also block hTNF-induced cytolysis and lipoprotein lipase suppression. We conclude that antibodies that recognize the N-terminus of hTNF block the attachment of hTNF to its cellular receptor and inhibit the biologic effects of hTNF.

Antigen-Antibody Reactions↗
PubMed1986

Pharyngeal size in snorers, nonsnorers, and patients with obstructive sleep apnea.

We measured pharyngeal cross-sectional area and its change with alterations in lung volume in 10 subjects who snored and had obstructive sleep apnea, 6 subjects who snored and did not have obstructive sleep apnea, and 9 subjects who did not snore. Pharyngeal area was measured with use of an acoustic-reflection technique. We found that snorers with and without sleep apnea had a significantly smaller mean (+/- SE) pharyngeal cross-sectional area (4.1 +/- 0.2 and 3.7 +/- 0.9 cm2, respectively) at functional residual capacity than nonsnorers (5.4 +/- 0.5 cm2, P less than 0.025). When lung volume decreased from functional residual capacity to residual volume, both nonsnorers and snorers with sleep apnea had a decrease in pharyngeal area (from 5.4 +/- 0.5 to 4.5 +/- 0.4 cm2 and 4.1 +/- 0.2 to 3.4 +/- 0.2 cm2, respectively), whereas snorers without sleep apnea had no such decrease, suggesting that their pharynxes were less collapsible at low lung volumes. We conclude that snorers with and without sleep apnea have smaller pharyngeal cross-sectional areas than nonsnorers and that snorers with sleep apnea have a further decrease as lung volume falls.

Adult↗
PubMed1985

Prophylaxis of Pseudomonas aeruginosa infections in leukopenic mice by a combination of active and passive immunization.

Mice rendered leukopenic with cyclophosphamide and then challenged with viable Pseudomonas aeruginosa were used to determine the protective efficacy of active immunization against exotoxin A and of passive immunization with human antiserum to Escherichia coli J5, a rough mutant of Escherichia coli O111:B4. Neither treatment alone provided a greater degree of protection than its respective control. However, the combination of these treatments produced a moderate, yet consistent, increase in the survival of infected immunosuppressed mice.

ADP Ribose Transferases↗
PubMed1985

Physiological determinants of nocturnal arterial oxygenation in patients with obstructive sleep apnea.

Among patients with similar degrees of obstructive sleep apnea (OSA) there is considerable variability in the degree of associated nocturnal hypoxemia. The factors responsible for this variability have not been clearly defined. Therefore we studied 44 patients with OSA to identify the physiological determinants of nocturnal arterial O2 saturation (SaO2). All patients underwent pulmonary function testing, arterial blood gas analysis, and overnight polysomnography. Mean nocturnal SaO2 ranged from 96 to 66% and apnea-hypopnea index from 11 to 128 per hour of sleep. Several anthropometric, respiratory physiological, and polysomnographic variables that could be expected to influence nocturnal SaO2 were entered into a stepwise multiple linear regression analysis, with mean nocturnal SaO2 as the dependent variable. Three variables [awake supine arterial PO2 (PaO2), expiratory reserve volume, and percentage of sleep time spent in apnea] were found to correlate strongly with mean nocturnal SaO2 (multiple R, 0.854; P less than 0.0001) and accounted for 73% of its variability among patients. Body weight, other lung volumes, and airflow rates influenced awake PaO2 and expiratory reserve volume but had no independent influence on nocturnal SaO2. In a further group of 15 patients with OSA a high correlation was obtained between measured nocturnal SaO2 and that predicted by the model (r = 0.87; P less than 0.001). We conclude that derangements of pulmonary mechanics and awake PaO2 (generally attributable to obesity and diffuse airway obstruction) are of major importance in establishing the severity of nocturnal hypoxemia in patients with OSA.

Adult↗
PubMed1984

Toxoids of Pseudomonas aeruginosa exotoxin-A: photoaffinity inactivation of purified toxin and purified toxin derivatives.

For the preparation of greatly detoxified but highly immunogenic toxoids, two enzymatically active, low-toxicity derivatives of Pseudomonas aeruginosa exotoxin-A were further inactivated by photoaffinity labeling. These derivatives were formed during toxin purification, when a relatively crude toxin preparation was concentrated by ammonium sulfate precipitation and subsequently dialyzed. These derivatives, designated peak-1 protein (PK-1) and peak-2 protein (PK-2) were antigenically indistinguishable from native toxin, but had isoelectric points (5.00 and 4.90, respectively) that were different from that of the native toxin (4.95). Although the enzymatic activities and molecular weights of PK-1 and PK-2 were similar to those of native toxin, their toxicities were greatly reduced (ca. 500-fold). Photoaffinity labeling of fully active toxin-A, purified by a process which limits the formation of these derivatives, decreased its enzymatic activity (ca. 30-fold) and toxicity (ca. 100-fold). Likewise, photoaffinity labeling of purified PK-1 and PK-2 decreased their enzymatic activities and toxicities (ca. 30-fold and 100-fold, respectively) and, thus, yielded toxoids that were ca. 50,000-fold less toxic than unpurified native toxin. These toxoids were irreversibly detoxified and highly immunogenic during 9 months of storage at 4 degrees C.

ADP Ribose Transferases↗
PubMed1984

Observations on local heat treatment for cutaneous leishmaniasis.

Local heat treatment was tested and found effective in three patients with diffuse cutaneous leishmaniasis (DCL), a form of disease poorly responsive to the usual chemotherapy. A water bath that circulated water through a pad wrapped around the lesion provided a temperature of 39 degrees C to 41 degrees C for a cumulative time of at least 20 hours, over a period of several days. In the DCL patients beneficial effect of heat treatment was documented by pre- and post-treatment biopsies and cultures. Several other patients with ordinary cutaneous leishmaniasis did not respond to the same form of treatment. It was concluded that different strains and/or species of leishmanial parasites vary in their sensitivity to elevated temperature. While local heat treatment may be curative in certain cases of cutaneous leishmaniasis, such therapy is still experimental and should be monitored by quantitative parasitological studies to document its usefulness.

Adolescent↗
PubMed1984

Monocyte suppression of antigen-specific lymphocyte responses in diffuse cutaneous leishmaniasis patients from the Dominican Republic.

Patients from the Dominican Republic with diffuse cutaneous leishmaniasis showed in vivo and in vitro anergy to leishmanial antigen. Relatives of these DCL patients living in the same endemic area frequently showed skin test and lymphocyte reactivity to leishmanial antigens. This further supports the concept of specific anergy in patients with diffuse cutaneous leishmaniasis. Adherent suppressor cells modulate the antigen-specific lymphocyte proliferative response. Suppressor cells could also be isolated by Percoll gradient centrifugation. Co-culturing of lymphocytes and monocytes from HLA-identical leishmanin responders and nonresponders also identified the suppressor cell as a monocyte. In one patient, this suppression disappeared when clinical cure had been accomplished.

Adolescent↗
PubMed1984

[Cytologic demonstration of immunoreactivity characteristic of adenopituitary peptides in the digestive epithelium of the rat and man].

Using immunoperoxidase techniques, the possible localization of pituitary regulatory peptides in fundic, antral and duodenal mucosae was investigated in both rat and man. All results obtained were similar in the two species. No glycopeptide (FSH, LH, TSH) was detected in the digestive tract. With different antisera directed against beta-lipotropin, alpha-MSH, beta-MSH, endorphins, ACTH 1-24, ACTH 17-39, a positive reaction was only obtained in the antral mucosae with an antiserum specific for the synthetic fragment 17-39 of ACTH. However neither the common precursor, proopiomelanocortin, nor the complete sequence of ACTH seem to be present in endocrine cells of the digestive tract. On the other hand, three antisera, directed against human growth hormone (GH), visualized numerous endocrine cells scattered in the glandular epithelium of the fundic and antral mucosae. Most cells were identified as ECL type in the gastric mucosae. Others are probably of the gastrin cell type in the antral mucosa, since these cells could be visualized on adjacent sections either with the antiserum against GH, or with a specific antiserum for gastrin.

Adrenocorticotropic Hormone↗
PubMed1983

Determination of amphetamine and methylamphetamine by gas-liquid chromatography (head space).

1 A method for determining amphetamine and methylamphetamine in urine by gas-liquid chromatography is described. 2 Chromatography is performed on a 10% Apiezon L, 10% KOH column with alkali-flame detection (NPD). This method avoids the losses of these volatile substances which are known to occur when solvent extraction is used. An alkalinized urine sample (1 ml) is introduced into a sealed vial which is heated in a water bath at 70 degrees C for 20 min. A 1 ml portion of the gas phase in equilibrium with the liquid phase is chromatographed. 3 Amphetamine and methylamphetamine can be detected and measured in urine samples after single therapeutic doses of the drugs.

Amphetamine↗
PubMed1982

Heterogeneous pituitary adenomas. A light microscopic, immunohistochemical and electron microscopic study.

The combined use of several histological procedures (i.e. conventional light microscopy, immunohistochemistry and electron microscopy) among 45 unselected pituitary adenomas demonstrated the existence of 9 tumors (20%) containing several identifiable adenohypophyseal cell types. The cellular associations were between 2 or 3 identifiable cell types. Mammosomatotrophic tumors were the most frequent but not the only mixed type (somatomammocorticotrophic, somatocorticotrophic tumors were also found). The cellular components varied in size but the cells appeared randomly distributed in the tumours. In all the adenomas there was an unidentified cell component (no reactivity with antisera used) varying from sparse to numerous elements. On adjacent sections the adenomatous cells reacted with a single specific antiserum, but in two cases the immunohistochemistry on contiguous paraffin embedded sections did not confirm this with certainty. These results confirm those of others and a new term is proposed to designate these tumors: heterogeneous pituitary adenomas. According to the nature and the proportions of the cell components the heterogeneous adenomas were subdivided into two groups: a group A which comprised adenomas formed by a major identifiable cellular type associated with one or two other less frequent cell types, and a group B formed by a predominant unidentifiable (no reactivity with immunochemical stainings) cell type associated with one or two other identified cell types. The present morphofunctional classifications of pituitary adenomas should be modified to include homogeneous adenomas with a single cell type and heterogeneous adenomas with several cell types.

Adenoma↗
PubMed1982

Objective and subjective evaluations of a TV-program versus small group instruction for the Iowa Drug Information Service.

The purpose of this study was to determine if the TV approach for instructing drug information systems is more efficient in terms of cost and learning effectiveness vs. traditional educational programming. The Iowa Drug Information Service system was selected as a typical representative for a study model. Second professional year pharmacy students (N = 66) were evaluated in a random selection, pre-test post-test, controlled experimental procedure. A 19 minute UTCHS in-house production served as the experimental variable. The control group received equivalent training (time and content) via lecture notes, and on-site practice coaching. Outcomes were assessed according to objective test score criteria and 10 subjective self-rating opinion scales. The data revealed that students subjected to the TV variable achieved significantly better post-exposure test scores (P = 0.002). A one-time cost of +500 was expended for complete TV production and three tapes, resulting in unlimited teaching capacity and recoverable within two years relative to instructor time expenditures for this system. Five of 10 opinion scales were significantly different in comparison, and students clearly preferred traditional teaching over our TV production. This investigation substantiates previous reports from medical disciplines wherein TV was an effective teaching approach but only mildly popular. The repetitive nature of didactic drug information systems training, superior TV outcomes, and cost-effectiveness warrants a mix of TV and limited personalized instruction as a policy approach.

Cost-Benefit Analysis↗