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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 415 records · Page 23Linked to original sources
PubMed1994

HLA class II antigens and the HIV envelope glycoprotein gp120 bind to the same face of CD4.

Although the HIV gp120 binding site of CD4 is well characterized, its interaction site with HLA class II molecules is still controversial. Sixty-seven mutations within the four extracellular domains of CD4 were examined for their effects on cell surface expression and conformational changes and for adhesion of HLA class II-expressing B lymphocytes and HIV gp120 binding to CD4-transfected COS cells. Mutations within the gp120 binding site affected both assays similarly, indicating that the two sites fully overlap. A few additional substitutions of residues mapping on the same face of domains 1 and 2 induced decreased rosette formation. Molecular modeling studies indicated that this is likely to be the consequence of conformational changes induced by the mutations. Thus, CD4 appears to interact with HLA class II molecules mainly through the HIV gp120 binding site and possibly through a second minor interaction site mapping on the same face of the molecule.

Amino Acid Sequence↗
PubMed1994

Enhanced gene delivery and mechanism studies with a novel series of cationic lipid formulations.

The application of cationic liposome reagents has advanced DNA and mRNA transfection research in vitro, and data are accumulating which show their utility for in vivo gene transfer. However, chemical structure-activity data leading to a better mechanistic understanding of their biological activity is still limited. Most of the cationic lipid reagents in use today for this application are formulated as liposomes containing two lipid species, a cationic amphiphile and a neutral phospholipid, typically dioleoylphosphatidylethanolamine (DOPE). The studies reported here examine the effects of some systematic chemical structural changes in both of these lipid components. Cationic and neutral phospholipids were formulated together as large multilamellar vesicles (MLV) or small sonicated unilamellar vesicles (SUV) in water, and each formulation was assayed quantitatively in 96-well microtiter plates under 64 different assay conditions using COS.7 cells and an RSV-beta-galactosidase expression plasmid. The cationic lipid molecules used for these studies were derived from a novel series of 2,3-dialkyloxypropyl quaternary ammonium compounds containing a hydroxyalkyl moiety on the quaternary amine. A homologous series of dioleylalkyl (C18:1) compounds containing increasing hydroxyalkyl chain lengths on the quaternary amine were synthesized, formulated with 50 mol % DOPE, and assayed for transfection activity. The order of efficacy was ethyl > propyl > butyl > pentyl > 2,3-dioleyloxypropyl-1-trimethyl ammonium bromide (DOTMA). DOTMA, which is commercially available under the trademark Lipofectin Reagent, lacks a hydroxyalkyl moiety on the quaternary amine. A homologous series of hydroxyethyl quaternary ammonium derivatives with different alkyl chain substitutions were synthesized, formulated with 50 mol % DOPE, and assayed in the transfection assay. The order of transfection efficacy was dimyristyl (di-C14:0) > dioleyl (di-C18:1) > dipalmityl (di-C16:0) > disteryl (di-C18:0). The addition of 100 microM chloroquine in the transfection experiment enhanced the activity of the dioleyl compound by 4-fold and decreased the activity of the dimyristyl compound by 70%. For each of the compounds and formulations examined in this report, large multilamellar vesicles (MLV; diameter 300-700 nm) were more active than small unilamellar vesicles (SUV; diameter 50-100 nm). The neutral phospholipid requirements for transfection activity in COS.7 cells with these cationic lipid molecules were examined.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Interleukin-1-induced activation of a protein kinase co-precipitating with the type I interleukin-1 receptor in T cells.

We have investigated the possibility of a protein kinase participating in the signal transduction mechanisms of the interleukin-1 (IL-1) type I receptor (IL-1RI). Our data show that a protein kinase was co-precipitated with the IL-1RI from the two murine T helper cell lines D10N and EL-4. The kinase activity was detected in an in vitro kinase assay performed with the immuno beads in the presence of exogenous substrates. IL-1 treatment of the cells resulted in a rapid activation of this protein kinase in a concentration-dependent manner. Both forms of IL-1, IL-1 alpha and IL-1 beta, induced this kinase activity, whereas the IL-1 receptor antagonist (IL-1ra) was inactive. In excess IL-1ra competitively antagonized IL-1 stimulation. In the in vitro kinase assay the exogenous substrates myelin basic protein and histone H1 were phosphorylated, whereas casein or heat-shock protein HSP27 were not accepted, reflecting a certain selectivity of this protein kinase. The IL-1RI co-precipitable protein kinase showed a serine/threonine specificity and was inhibited by staurosporine, but not by inhibitors specific for protein tyrosine kinase or protein kinase C. These results show that a serine/threonine protein kinase directly interacts with the IL-1RI at the plasma membrane level of T helper cells forming a novel type of IL-1 inducible signaling complex. This protein kinase may resemble the link coupling the plasma membrane IL-1 receptor to cytosolic downstream elements in the IL-1 signaling pathway.

Animals↗
PubMed1994

Postnatal decrease of acetate concentration in rat cerebellum.

We examined the evolution of 1H-NMR detectable metabolites in rat cerebellum from the postnatal day 1-25, a period associated with intense metabolic changes as well as physiological and morphological modifications. The unexpected result reported here is the existence of a high concentration of acetate in neonatal rat cerebellum, progressively decreasing with age and maturation. In contrast, the cerebellum content of various metabolites such as N-acetyl-L-aspartate (NAA), glutamate, and aspartate increases from the first day onward.

Acetates↗
PubMed1994

The role of verbal ability in the processing of complex verbal information.

This study investigated the relation between psychometric mental-ability test scores and several reaction-time measures; a simple-reaction task, a choice-reaction task, the Posner and Mitchell (1967) letter-identification task, and a variation of the sentence-verification task. Scores on the Raven Advanced Progressive Matrices and the Verbal Subtest of the Scholastic Aptitude Test (SATV) were obtained. The less complex information-processing tasks replicate earlier studies in which general intelligence was only marginally related to reaction-time measures. The sentence-verification task systematically varied task complexity. Several direct and derived measures from the task were significantly correlated with psychometric mentalability measures. However, even though a number of precautions were taken to ensure that the sentence-verification task assessed purely verbal-processing efficiency, there was little evidence for an important task-specific relation between verification measures and verbal ability. Moreover, despite its relative verbal complexity, sentence verification did not reflect a greater relationship to verbal ability than other tasks did. Overall, the information-processing efficiency measures used in this study suggested a fairly general, rather than a task-specific, relationship to intellectual ability.

Adolescent↗
PubMed1994

Epidemiology of urinary stone disease in the Balearic Islands Community.

In a survey conducted on 1500 individuals, an overall prevalence of 14.3% for the year 1990 was found for urinary stone disease in the Balearic Islands. The prevalence showed higher figures for people living in rural areas than for those living in cities, and this could be correlated with traditional living habits such as traditional Balearic diet. Finally, a surprising fact is that only 54% had consulted a urologist as outpatients and the rare occasion at which the calculi were analyzed (15.1%).

Female↗
PubMed1994

Abnormal basement membrane in tumors induced by rat colon cancer cells.

BACKGROUND/AIMS: Colonic mucosa basement membrane results from a cooperation between epithelial cells and pericryptal fibroblasts characterized as myofibroblasts. This cooperation may be abnormal in colorectal carcinoma resulting in basement membrane alteration. METHODS: Basement membrane composition and myofibroblast distribution were studied in normal rat colon and two colon carcinoma models by immunohistochemistry. Colon cancer cells and tumor-associated myofibroblasts were also studied for their capacity to deposit three basement membrane components (laminin, heparan sulfate proteoglycan, and type IV collagen) in vitro. RESULTS: A continuous, type IV collagen-containing basement membrane, such as that observed in normal colon, was found only in the most differentiated tumor model and was restricted to the areas in which myofibroblasts were closely apposed to carcinoma cells. In other areas of this tumor and in the poorly differentiated tumor model, myofibroblasts dissociated from the epithelial cells and the basement membrane was devoid of type IV collagen. In vitro, carcinoma cells deposited laminin and heparan sulfate proteoglycan but not type IV collagen. Tumor-associated myofibroblasts deposited type IV collagen only in the presence of tumor cell extracellular matrix or laminin coating. CONCLUSIONS: The colon cancer basement membrane defect in type IV collagen may result from a physical disruption in the association between epithelial cancer cells and myofibroblasts.

Adenocarcinoma↗
PubMed1994

Radiotherapy alone versus combined chemotherapy and radiotherapy in unresectable non-small cell lung carcinoma.

We report the results observed in a large randomized study comparing radiotherapy alone to combined radiotherapy and chemotherapy in unresectable squamous cell and large cell lung carcinoma. Radiation dose was 65 Gy in both groups and chemotherapy included vindesine, cyclophosphamide, cisplatin and lomustine. One hundred seventy-seven patients received radiotherapy alone, and 176 received the combined treatment. The 2-year survival rate was 14% for patients receiving radiotherapy vs. 21% for patients receiving the combined treatment (P = 0.02). The distant metastasis rate was significantly lower in the group receiving the combined treatment (P < 0.001). Local control at 1 year was poor in both groups (17% and 15%, respectively) and remains a major problem in locally advanced non-small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Elevated serum progesterone levels on the day of human chorionic gonadotropin administration in in vitro fertilization cycles do not adversely affect embryo quality.

OBJECTIVE: To assess the effect of an elevated serum P level on the day of hCG administration in an IVF cycle on resulting embryos by evaluating their performance at subsequent frozen ET. DESIGN: A retrospective study. PARTICIPANTS: Ninety-six consecutive patients undergoing frozen ET cycles were studied in a tertiary care center. MAIN OUTCOME MEASURES: Serum obtained on the day of hCG administration in an IVF cycle was assayed for E2 and P by RIA. The main outcome measured was the development of a clinical pregnancy in a subsequent frozen ET cycle. RESULTS: Using a previously described breakpoint in serum P concentration of 0.9 ng/mL (2.86 nmol/L), 8 of 69 (11.6%) frozen ETs in which embryos from low P level IVF cycles were transferred and 7 of 27 (25.9%) frozen ETs of embryos from elevated P level IVF cycles were transferred resulted in the development of clinical pregnancies. Although this does not clearly demonstrate superiority of embryos obtained from elevated P cycles, employing a power calculation, the probability that the pregnancy rate in the elevated serum P group is at least equal to the observed rate in the low P group is 92.8%. CONCLUSION: These data suggest that an elevated serum P level on the day of hCG administration does not adversely affect the quality of oocytes or resulting embryos.

Chorionic Gonadotropin↗
PubMed1994

Parent-child relationships and the management of insulin-dependent diabetes mellitus.

Several dimensions of parent-child relationships were examined as predictors of adherence to treatment and metabolic control in a multi-informant study of 88 children and adolescents with insulin-dependent diabetes mellitus who were recruited from 2 endocrinology clinics. Ratings of parent-child discipline, warmth, and behavioral support were not significantly associated with diabetes outcome, but parent-child conflict was a consistent correlate of both adherence and metabolic control. Within a public hospital subsample, conflict was related to parent, child, and nurse ratings of adherence and to a physiological index of metabolic control. These results were partially replicated in a private practice sample where conflict was significantly related to parents' ratings of adherence and to metabolic control. Conflict accounted for unique variance in diabetes outcome beyond that associated with other measures of the parent-child relationship, but the relation between conflict and metabolic control was no longer significant when adherence ratings were entered into regression equations first.

Adolescent↗
PubMed1994

Interleukin-1-induced cyclooxygenase 2 expression is suppressed by cyclosporin A in rat mesangial cells.

The immunosuppressive drug cyclosporin A (CsA) has considerable nephrotoxic side effects which seem to be related to its interference with the synthesis of vasoactive prostanoids. Therefore, the molecular mechanism of the effect of CsA on the synthesis of prostaglandin E2 (PGE2) was investigated in rat renal mesangial cells (RMC). CsA effectively inhibited the PGE2 synthesis induced by inflammatory cytokines such as interleukin 1 (IL-1) or tumor necrosis alpha (TNF alpha). The induction by IL-1 and the inhibition by CsA were reflected in the enzyme activity of the cyclooxygenase. The changes in activity could be correlated with the expression of the inducible cyclooxygenase isoform (COX2), which is characterized by its 4.4 kb mRNA: the expression of this enzyme was enhanced by IL-1 and suppressed by CsA on the mRNA and protein level as determined by Northern and Western blot analyses. Suppression of COX2 mRNA was also observed when the message was induced by LPS or ionophore A23187. The expression of the basal cyclooxygenase isoform (COX1), which was constitutively expressed in proliferating mesangial cells, was not affected by IL-1 or CsA. Interferon gamma, which did not induce prostaglandin synthesis or influence COX mRNA expression, augmented the expression of MHC antigens in RMC. This induction was insensitive to CsA treatment. We could thus show that the inducible cyclooxygenase isoform in mesangial cells is a molecular target for CsA providing a possible mechanism for the interference of the drug with the balance of vasoactive prostanoids.

Animals↗
PubMed1994

Phase II trial of weekly IV vinorelbine in first-line advanced breast cancer chemotherapy.

PURPOSE: The study investigated the therapeutic effect of single-agent IV weekly vinorelbine (Navelbine, Pierre Fabre Oncologie, Boulogne, France) a semi-synthetic vinca-alkaloid, in women who had received no prior treatment for advanced or metastatic breast cancer. PATIENTS AND METHODS: Fifty-four patients with assessable advanced or metastatic breast cancer who had received no prior chemotherapy were entered into the study. Fifty patients were evaluable for toxicity and response by WHO criteria; 4 patients were not evaluated because they did not meet the eligibility criteria of the study. Vinorelbine was given as a weekly 30 mg/m2 short IV infusion; and treatment was continued until disease progression or the occurrence of unacceptable toxicity. RESULTS: The overall response rate was 50% (complete response 2%, partial response 48%). The response rate according to target was: lymph nodes 64%; liver 28%; lung 66%; local recurrence 60%. The median duration of response was 9 months, the median time to treatment failure was 5 months and the median survival was 15 months. TOXICITY: Six-hundred thirty cycles were given to 54 patients (53 assessable for tolerance). At least one episode of WHO grade 3/4 granulocytopenia was seen in each of 71% of the patients. Significant nausea/vomiting (WHO grade 3) was seen in less than 1% of cycles and other side effects were uncommon. CONCLUSION: This study confirms that vinorelbine has major single-agent anti-tumour activity as front-line therapy in advanced breast cancer. Given its excellent tolerance profile and low morbidity, it should be considered for inclusion in first-line combination chemotherapy regimens.

Adenocarcinoma↗
PubMed1994

Childhood-onset schizophrenia: history of the concept and recent studies.

Schizophrenic disorders in childhood are rare: 0.1-1 percent of all schizophrenic disorders manifest themselves before age 10, and 4 percent before age 15. There is, however, a remarkable increase in schizophrenia during adolescence. Age and developmental stage also influence symptoms, course, and outcome. The evidence for a male preponderance in the very early-onset group (< 14) does not apply for adolescents over age 14. The presence of positive and negative precursor symptoms can be demonstrated in child and adolescent schizophrenia before the first clinical manifestation leading to inpatient treatment. With regard to pharmacologic treatment, atypical neuroleptics such as clozapine can be used successfully. As to outcome, schizophrenic psychoses with early manifestation have a poor prognosis. The patients' premorbid personality also seems to be of great importance: A poor prognosis can be found in patients who were cognitively impaired, shy, introverted, and withdrawn before the beginning of their psychotic state.

Adolescent↗
PubMed1994

Effect of different doses of dietary calcium on murine colonic cell proliferation.

One-hundred and twenty 6-week-old 257BL/65 mice were fed for 2 or 7 weeks with diets supplemented with different combinations of bile acids and calcium. The effect of calcium, bile acids and the duration of these treatments on proliferative indices of the colonic mucosa was studied with a multiway analysis of variance. In mice not treated with bile acids, a low level (0.1%) of calcium in the diet was related to a significantly higher number of cells in each compartment of the crypt, compared with diets supplemented with 0.5 and 1% calcium (P < 0.01). There was no difference between the groups fed with normal and high calcium diets. Bile acids significantly increased proliferative indices in all animal groups whatever the duration of the treatment; however, this effect was significantly lower in the mice fed with 0.5% and 1% calcium than in those fed with 0.1% calcium (P < 0.01). There was a significant interaction between the effect of bile acids and the effect of calcium regarding the number of labeled cells and the labeling indices. Duration of the treatment had little effect on these indices. The effect of bile acids on colonic proliferative activity could be significantly reduced by calcium supplementation, and this effect was stable with time. Although there was no toxic effect of the highest calcium diet, there was no advantage in increasing the calcium dose beyond 0.5%.

Animals↗
PubMed1994

Expression of 72-kDa gelatinase (MMP-2), collagenase (MMP-1), and tissue metalloproteinase inhibitor (TIMP) in primary pig skin fibroblast cultures derived from radiation-induced skin fibrosis.

In addition to producing matrix degradation for normal tissue remodeling and repair, matrix metalloproteinases (MMPs) are also involved in various pathologic processes. MMPs and the tissue inhibitor of MMPs (TIMP) were investigated in primary cultures of pig fibroblasts from radiation-induced dermal fibrosis and compared to normal dermal fibroblasts. The free gelatinolytic, collagenolytic, and caseinolytic activities secreted into the culture medium were evaluated against specific 3H denatured collagen type I, native helical collagen, and casein alpha, respectively. The 72- and 68-kilodalton (kDa) forms of type IV collagenase were investigated by protease zymography and quantified by semi-automated image analysis. Transcription of the interstitial collagenase (MMP-1) and TIMP genes was studied by Northern hybridization analysis. Results revealed that in fibrotic fibroblasts, the amount of MMP-1 mRNA was greatly reduced to undetectable levels whereas the amount of TIMP mRNA was increased fourfold compared to controls. Functional assays using specific 3H substrates demonstrated an overall decrease in free MMP activities. Concomitantly, catheptic collagenolytic activity decreased in fibrotic fibroblast extracts compared to controls. These results indicate that in addition to accumulating large amounts of collagen, proteoglycans, and fibronectin, pig fibroblasts from radiation-induced dermal fibrosis also promote connective tissue matrix formation by repressing MMP-1 and stimulating TIMP expression at the transcriptional level, and by reducing overall free MMP and catheptic collagenolytic activities at the post-transcriptional level. In contrast, enzymography assays and automated image analysis demonstrated no significant change in the 72-kDa type IV collagenase activity of fibrotic pig skin fibroblasts. This opposite regulation of 72-kDa collagenase type IV to that of MMP-1 seems to indicate that it has a specific role in remodeling the extracellular matrix during wound healing, fibrogenesis, and angiogenesis.

Animals↗