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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 235 records · Page 13Linked to original sources
PubMed1999

Prognostic factors in invasive lobular carcinoma of the breast: a multivariate analysis. A multicentre study after seventeen years of follow-up.

BACKGROUND AND GOALS: The purpose of this study was to characterize the biologic determinants that affect the behavior of invasive lobular carcinoma of the breast. MATERIAL AND METHODS: A prospectively accrued data base containing 9,619 breast cancer cases was queried for specific pathological features. From this data base, 390 patients with invasive lobular carcinoma of the breast treated and followed at any of these three centers: San Carlos Hospital, Doce de Octubre Hospital or The Jimenez Diaz Foundation in Madrid (Spain) were reviewed and results, in terms of overall survival and disease-free survival were recorded for a long-term follow-up of 206 months (17 years). RESULTS: The parameters that showed an important statistical influence on survival were the stage at diagnosis, the tumor size and nodal status, as well as the tumor grade. Age showed a limited influence, and multicentricity, or the type of surgical procedure had no statistical impact on survival. CONCLUSIONS: Our analysis specifies the clinico-pathological features that influence the prognosis of invasive lobular carcinoma of the breast, and confirms that conservative therapy may be an appropriate treatment for this type of cancer.

Adult↗
PubMed1998

Bcl-2-mediated inhibition of apoptosis prevents immunogenicity and restores tumorigenicity of spontaneously regressive tumors.

Tumor cell clones from a rat colon carcinoma differ in their tumorigenicity and immunogenicity. The PRO clones give rise to progressive tumors, whereas the REG clones yield tumors that regress in a few weeks through a specific immune response. REG cells were more sensitive than PRO cells to apoptosis triggered by serum withdrawal in vitro. Furthermore, a fraction of REG cells, but no PRO cells, underwent apoptosis in the hours following injection into syngeneic rats. To further analyze the role of apoptosis, we overexpressed the antiapoptotic protein Bcl-2 in REG cells. Unlike parental or fake-transfected REG cells, Bcl-2-overexpressing REG cells resisted serum withdrawal-induced apoptosis, did not undergo apoptosis at 48 h postinjection into naive syngeneic rats, and gave rise to progressive, metastatic, and lethal tumors. Interestingly, REG-bcl2 cells were rejected by syngeneic hosts that had been preimmunized by an injection of parental REG cells, indicating that Bcl-2 overexpression did not alter tumor cell sensitivity to the effector cells of the immune response. Taken together, these observations indicate that tumor cell apoptosis may contribute to immunogenicity.

Adenocarcinoma↗
PubMed1998

Effect of radial gradient of temperature on the performance of large-diameter high-performance liquid chromatography columns. I. Analytical conditions.

The performance of a large-diameter chromatographic column can be drastically reduced when the solvent enters the column at a temperature different from that of the wall of the column. A radial temperature gradient inside the column will affect the physical properties of the solvent and the chromatographic behaviour of the solute resulting in a deformation of the band profile. A mathematical model is proposed to take into account the effect of a radial gradient of temperature in a large-diameter column on the chromatographic peak shape under linear conditions. The model is then compared with experimental results in preparative columns of different sizes. A good agreement between experiment and theory has been found showing a serious effect of thermal conditions on separation quality, depending on the column size. It is also demonstrated that a small difference of temperature can be helpful to compensate practical effect of frits and distribution of the sample at the extremities of the packed bed. Finally, it demonstrates the necessity to perform efficiency measurement under different thermal conditions to have a good comparison between columns.

Chromatography, High Pressure Liquid↗
PubMed1998

Vitamin D3 inhibits proliferation and increases c-myc expression in fibroblasts from psoriatic patients.

Fibroblast cultures were established from the skin of normal and psoriatic subjects. The response to 1 alpha,25-dihydroxyvitamin D3 [1,25-(OH)2D3] of each kind of cells was assessed by measuring tritiated thymidine incorporation into DNA as an index of cell proliferation. We found that both types of cells responded with a similar dose- and time-dependent inhibition of thymidine incorporation. We also studied the response of the mRNA encoding the proto-oncogene c-myc, since its level is associated to the proliferative state in many cell types. Psoriatic fibroblasts contained higher basal amounts of c-myc RNA than control fibroblasts. Addition of 1,25-(OH)2D3 to the culture medium induced a time-dependent increase of c-myc RNA in psoriatic fibroblasts but not in controls. As a control, retinoic acid had no effect in any of the two cell types. It is concluded that in primary normal human fibroblasts, c-myc RNA levels are not correlated with the proliferative state, and that there is an altered expression of this proto-oncogene in psoriasis.

Adult↗
PubMed1998

[Modular memory training for elderly adults: concept and evaluation].

We present a modular concept of a cognitive training relevant to the demands of everyday life of community dwelling older adults. The concept has three major advantages. First, it takes into account the current performance levels and needs of the trainees. Second, the training is economical in aiming at selecting the most effective training elements. Third, the concept allows the evaluation of single elements of the training. The application of this concept points at the importance of training content being relevant to trainees' everyday lives. Results indicate that training effectiveness depends on the starting level of performance and the cognitive domain being trained. Overall, the results demonstrate the possibility to maximize training gains of older adults by designing adequate trainings for well-defined subgroups of normal older adults.

Activities of Daily Living↗
PubMed1998

Alternating radiotherapy and chemotherapy in limited disease small cell lung cancer.

In a pilot study of 29 patients treated for localized small cell lung cancer, three new approaches were introduced, i.e. an increased initial drug dose, an early alternation of chemotherapy and thoracic radiotherapy and initial accelerated and hyperfractionated irradiation. The results were interesting. However, a high rate of fatal toxicity (21%) was observed.

Adult↗
PubMed1998

Abnormal phenotype of cultured fibroblasts in human skin with chronic radiotherapy damage.

PURPOSE: The pathophysiological aspects of radiation-induced fibrosis (RIF) have not been well characterized. We therefore cultured human fibroblasts from samples of skin with RIF to investigate the long-term effects of therapeutic irradiation. MATERIALS AND METHODS: Biopsies of normal and RIF skin were obtained from patients previously irradiated for cancer, without recurrence. Cells were extracted from dermis samples by the outgrowth technique, seeded as monolayers and cultured at confluence. Enzyme activities and proteins were assayed, RNA was isolated and Northern blot analysis was performed on surviving cells between passages 2 and 5. RESULTS: RIF cell cultures displayed heterogeneous fibroblasts populations. The initial outgrowth consisted of one-third small cells that floated rapidly, one-third spindle-shaped cells migrating far from the explant to form islets and one-third large pleiomorphic cells. In subsequent subcultures, surviving cells exhibited either myofibroblastic characteristics with a normal proliferative capacity or senescent morphology with a reduced proliferative capacity. These RIF cells had a brief finite lifespan, with dramatically reduced growth rate during their initial outgrowth and the following passages. Study of the antioxidant metabolism showed that Mn superoxide dismutase and catalase activities were significantly weaker in surviving RIF cells than healthy fibroblasts. These exhausted RIF cells exhibited no overexpression of transforming growth factor beta or tissue inhibitor of metalloproteinase. CONCLUSION: Irradiation may lead to apparently contradictory effects such as fibrosis and necrosis in clinical practice. In cell culture, we observed two main cellular phenotypes which may be related to both processes, i.e. myofibroblast-like cells and fibrocyte-like cells. These two phenotypes may represent two steps in the differentiation induced as a long-term effect of therapeutic irradiation of the skin. Cell culture probably accelerates the induction of the terminal differentiation in RIF fibroblasts.

Adult↗
PubMed1998

Synthesis, electrophysiological properties and analysis of structural requirements of a novel class of antiarrhythmic agents with potassium and calcium channel blocking properties.

Class III antiarrhythmic agents have been shown to prevent reentrant arrhythmias but also to be responsible for initiating arrhythmias characterised by afterdepolarizations and triggered activities. By combining potassium and calcium channel antagonistic actions, as with BRL-32872 (1), it might be possible to reduce the incidence of proarrhythmias albeit retaining antiarrhythmic efficacy. In the present study we synthesised and tested for their electrophysiological activity in guinea pig papillary muscle a wide panel of analogues of BRL-32872. Some qualitative relationships between compound structure and the inhibitory effect on the rapidly activating component of the delayed rectifier potassium current and/or the L-type calcium current will be presented. New derivatives depicting bell-shaped dose-response curves on action potential duration may therefore represent novel agents for improved antiarrhythmic therapy.

Action Potentials↗
PubMed1998

Energetic and morphological plasticity of C6 glioma cells grown on 3-D support; effect of transient glutamine deprivation.

The energetic metabolism of rat C6 glioma cells has been investigated as a function of the proliferative and differentiation states under three-dimensional (3-D) growing conditions on microcarrier beads. First, the transient deprivation of glutamine from the culture medium induced a marked decrease in the growth rate and a differentiation of C6 cells through the oligodendrocytic phenotype. Second, the respiratory capacity of the C6 cells during short-term subcultures with or without glutamine continuously declined as a function of the cell density, in part due to the mitochondrial content decrease. During the transition from the early exponential to the plateau growth phase in glutamine-containing medium, the oxygen consumption rate per single cell decreased concomitantly with a decrease in the glucose consumption and lactate production rates. This phenomenon led to a sixfold decrease in the total ATP production flux, without significantly affecting the cellular ATP/ADP ratio, thus indicating that some ATP-consuming processes were simultaneously suppressed during C6 proliferation. In glutamine-free medium, the cellular ATP/ADP ratio transiently increased due to growth arrest and to a reduced ATP turnover. Moreover, the results indicated that glutamine is not an essential respiratory substrate for rat C6 glioma under short-term glutamine deprivation. Worth noting was the high contribution of the mitochondrial oxidative phosphorylation toward the total ATP synthesis (about 80%), regardless of the proliferation or the differentiation status of the C6 cells.

Animals↗
PubMed1998

Immunophenotypic and clinical features of T-cell receptor gammadelta+ T-lineage acute lymphoblastic leukaemia.

The immunophenotypic and clinical features of TCR-gammadelta+ T-lineage acute lymphoblastic leukaemia (T-ALL) were prospectively analysed in 52 children with membrane CD3+ T-ALL. We observed a relatively high incidence of TCR-gammadelta+ T-ALL (26/52 patients). Leukaemic blasts from 22 children demonstrated TCR-alphabeta positivity, and simultaneous expression of the TCR-beta and -delta chain was found in four children. Clinical and haematological features of TCR-alphabeta and gammadelta+ T-ALL did not differ significantly, except that haemoglobin levels were significantly lower in TCR-gammadelta+ cases. Event-free survival at 4 years was significantly better in TCR-gammadelta+ compared with TCR-alphabeta+ T-ALL, but expression of TCR molecules did not emerge as an independent prognostic factor in multivariate analysis.

Acute Disease↗
PubMed1998

Correlation of testicular pathology and sperm extraction in azoospermic men with ejaculated spermatids detected by immunofluorescent localization.

Limiting testicular biopsy for intracytoplasmic sperm injection (ICSI) to those with a high chance of having testicular spermatozoa has not been possible because of the poor predictive value of current clinical and laboratory methods. In order to predict testicular pathology and sperm extraction, we characterised the semen of 28 men with azoospermia due to gonadal failure in terms of the presence of spermatids using an immunological method. The results were compared with the assessment of testicular biopsies by histology and the extraction of spermatozoa into culture medium. Washed cellular elements in the ejaculate were smeared on microscope slides and fixed in 100% methanol, before incubation with acrosome-specific monoclonal antibody (18.6), fluorescein isothiocyanate-labelled anti-mouse goat IgG, and examination by epifluorescent microscopy. Semen from men with oligozoospermia and obstructive azoospermia served as positive and negative controls, respectively. Twelve patients who had positive immunofluorescence (one or more spermatids present) had spermatozoa retrieved from their testes (five hypospermatogenesis, seven focal spermatogenesis), and 16 patients with negative immunofluorescence (spermatids absent) had apparent Sertoli cell-only syndrome (12) or maturation arrest histological pattern (four). However, four patients with apparent Sertoli cell-only syndrome had testicular spermatozoa present after extraction from the biopsy. Plasma follicle stimulating hormone concentration and testicular volume did not predict retrieval of seminal spermatids or testicular spermatozoa. We conclude that the immunofluorescent localization of one or more spermatids in the ejaculate can be used to predict the likelihood of obtaining testicular spermatozoa for ICSI. However, in some patients with Sertoli cell-only syndrome, spermatozoa could still be recovered in the absence of apparent seminal spermatids.

Acrosome↗
PubMed1998

Tyrosine phosphorylation of a 95 kDa protein and induction of the acrosome reaction in human spermatozoa by recombinant human zona pellucida glycoprotein 3.

Protein tyrosine phosphorylation and induction of the acrosome reaction (AR) in non-capacitated and capacitated human spermatozoa was investigated in response to recombinant human zona pellucida glycoprotein (rhZP3) produced by Chinese hamster ovary cells transfected with a plasmid containing human ZP3 cDNA. rhZP3-containing medium promoted the AR in a high proportion of capacitated spermatozoa (48.6 +/- 3.2%; P < 0.01) compared with control (no rhZP3) samples (14.8 +/- 2.1%). However, rhZP3-containing medium did not cause increased acrosomal exocytosis in non-capacitated spermatozoa (16.8 +/- 3.0%). Induction of the AR was associated with increased tyrosine phosphorylation of a 95 +/- 5 kDa epitope only in capacitated spermatozoa. A dose-dependent increase in the protein phosphorylation of a 95 kDa epitope in response to rhZP3 was detected by [gamma-32P]-ATP labelling of detergent-solubilized sperm proteins. When spermatozoa were co-incubated with monoclonal antibody 97.25 (mAb 97.25) recognizing a 95 kDa tyrosine kinase epitope, there was no rhZP3 induction of tyrosine phosphorylation of the 95 kDa protein. Such co-incubation also markedly inhibited the AR (23.9 +/- 3.1%). These results support the model that initial interaction of the fertilizing spermatozoon with ZP3 involves the tyrosine phosphorylation of a 95 kDa tyrosine kinase protein and that this requires capacitation.

Acrosome Reaction↗
PubMed1998

Long-term results of pediatric liver transplantation: an analysis of 569 transplants.

OBJECTIVE: To analyze a single center's 13-year experience with 569 pediatric orthotopic liver transplants for end-stage liver disease. SUMMARY BACKGROUND DATA: Despite advances in medical therapy, liver replacement continues to be the only definitive mode of therapy for children with end-stage liver disease. Innovative surgical techniques and improved immunosuppression have broadened the application of liver replacement for affected children. However, liver transplantation in the child remains challenging because of the scarcity of donor organs, complex surgical technical demands, and the necessity to prevent long-term complications. METHODS: The medical records of 440 consecutive patients younger than 18 years of age undergoing orthotopic liver transplantation for end-stage liver disease from March 20, 1984, to November 15, 1997, were reviewed. Results were analyzed using Cox multivariate regression analysis to determine the statistical strength of independent associations between pretransplant covariates and patient and graft survival. Actuarial patient and graft survival rates were determined at 1, 3, 5, and 10 years. The type and incidence of posttransplant complications were determined, as was the quality of long-term allograft function. The median follow-up period was 4.1 years. RESULTS: Biliary atresia was the most common cause (50.4%) of endstage liver disease in this patient population. The median recipient age was 2.4 years; 239 patients (54%) were younger than 3 years of age and 1 11 patients (25%) were younger than 1 year of age. There were 471 whole organs, 29 were ex vivo reduced size, 33 were living-related donor, and 36 were in situ split-liver allografts. Three hundred forty-three (78%) patients underwent a single allograft, whereas 97 patients required retransplantation; hepatic artery thrombosis was the most common indication for retransplantation (55 patients). The 1-, 3-, 5-, and 10-year actuarial patient survival rates were 82%, 80%, 78%, and 76%, respectively; allograft survival rates were 68%, 63%, 60%, and 54%. Long-term liver function remains excellent: current median follow-up values for total bilirubin and aspartate aminotransferase were 0.5 mg/dl and 54 IU/L, respectively. Cox multivariate regression analysis demonstrated that pretransplant patient age, the era of transplantation, and the number of allografts performed significantly and independently predicted patient survival rates, whereas allograft type and pretransplant diagnosis did not. CONCLUSIONS: Liver transplantation in the pediatric patient is a durable procedure that provides excellent long-term survival. Although there have been overall improvements in patient outcome with increased experience, the effect is most pronounced for patients younger than 1 year of age. Retransplantation, although effective in a meaningful number of patients, continues to carry a progressive decrement in survival with the number of allografts performed. Use of living-related and in situ split-liver allografts has dramatically reduced waiting times for small children and has improved patient survival.

Actuarial Analysis↗
PubMed1998

Cytokines and adhesion molecules in elective and accidental trauma-related ischemia/reperfusion.

BACKGROUND: The major pathophysiologic role of cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6, as well as of the (soluble) adhesion molecules ICAM-1 and E-selectin, has been identified using different experimental models of ischemia/reperfusion injury. Moreover, in intensive care management, evaluation of these agents as diagnostic or prognostic tools is of great interest in ischemia/reperfusion injury caused by surgical or accidental trauma. For this reason, inflammatory mediators including those mentioned above were investigated in three different groups of surgical patients. METHODS: The first group (A, n = 13) comprised patients undergoing elective limb surgery without a tourniquet. The second group (B, n = 36) included patients subjected to limb surgery with a tourniquet. The third group (C, n = 30) was composed of accidental trauma patients who were retrospectively divided into those with and without multiple organ dysfunction (+MOD and -MOD, respectively) as defined by the Denver Score. Serial blood samples were taken during a 5-day (elective surgery) or 14-day (accidental trauma) observation period for monitoring of cytokines and soluble adhesion molecules. The clinical course and the degree of MOD were recorded daily. RESULTS: Only when a tourniquet was applied for a mean time of 105 minutes did elective limb surgery result in significantly increased serum levels of IL-6, IL,-1ra, and IL-10 but not TNF-RII. Yet, the increase in cytokine levels was not sufficient to cause an enhanced shedding of adhesion molecules, and both soluble ICAM-1 and soluble E-selectin remained unchanged in groups A and B throughout the 5-day observation period. In patients with multiple injuries (group C), all parameters increased early after trauma up to 10- to 20-fold in comparison with the elective limb surgery patients in groups A and B. When the accidental trauma patients were divided according to the Denver Score for +MOD (n = 8, mean Injury Severity Score = 33.8) and -MOD (n = 22, mean Injury Severity Score = 31.2), a clear difference became evident in serum IL-6 and IL-1ra levels within the first 4 days and in serum IL-10 levels for the first 2 days after trauma, with cytokine levels being significantly higher in the +MOD patients 3 to 4 days before the onset of MOD. Although highly elevated, TNF-RII levels did not differentiate between +MOD and -MOD at any time. The increase in serum cytokine levels was associated with a remarkable expression and shedding of ICAM-1 and E-selectin made obvious by significantly increased soluble serum ICAM-1 levels in +MOD patients compared with the -MOD group between days 3 and 5 after trauma and increased soluble serum E-selectin levels between days 2 and 4 after trauma. CONCLUSION: The release of cytokines and soluble adhesion molecules into the circulation correlates well with the degree of trauma (elective surgery vs. accidental multiple trauma), depending on the extent of the associated ischemia/reperfusion injury. Both groups of mediators are also clearly related to the development of MOD in patients with multiple injuries with generalized ischemia/reperfusion injury caused by hemorrhagic shock. They may be predictive of patients at risk for MOD when measured early in the posttraumatic period.

Adult↗
PubMed1998

Telomere dynamics in HIV-1 infected and uninfected chimpanzees measured by an improved method based on high-resolution two-dimensional calibration of DNA sizes.

We developed an improved method for accurately measuring telomere lengths based on two-dimensional calibration of DNA sizes combined with pulsed field electrophoresis and quantitative analysis of high-resolution gel images. This method was used to quantify the length of telomeres in longitudinal samples of peripheral blood mononuclear cells (PBMCs) from five chimpanzees infected with human immunodeficiency virus type 1 (HIV-1) and three uninfected animals, 14 to 27 years of age. The average length of the telomere restriction fragments (TRF) of infected and uninfected chimpanzees were 11.7 +/- 0.25 kbp, and 11.6 +/- 0.61 kbp, respectively, and were about 1 kbp and 3 kbp longer than those of human infants and 30 year old adults, respectively. There was a trend of a slight decrease (30-60 bp per year) in the TRF of two HIV infected chimpanzees over 30-35 months, while the TRF of one naive chimpanzee slightly increased over 20 months. Although the number of chimpanzees in this study is small and no statistically significant linear dependencies on time were observed, it appears that in chimpanzees, rates of shortening of the TRF are comparable or smaller than in adult humans and are not significantly affected by HIV-1 infection, which may be related to the inability of HIV-1 to cause disease in these animals.

Age Factors↗
PubMed1998

Phenotypic and genotypic characterization of nosocomial Staphylococcus aureus isolates from trauma patients.

Staphylococcus aureus is a major cause of nosocomial infections. During the period from March 1992 to March 1994, the patients admitted to the intensive care unit of the University of Maryland Shock Trauma Center were monitored for the development of S. aureus infections. Among the 776 patients eligible for the study, 60 (7.7%) patients developed 65 incidents of nosocomial S. aureus infections. Of the clinical isolates, 43.1% possessed a polysaccharide type 5 capsule, 44.6% possessed a type 8 capsule, and the remaining 12.3% had capsules that were not typed by the type 5 or type 8 antibodies. Six antibiogram types were noted among the infection-related isolates, with the majority of the types being resistant only to penicillin and ampicillin. It was noted that the majority of cases of pneumonia were caused by relatively susceptible strains, while resistant strains were isolated from patients with bacteremia and other infections. Only 16 (6.3%) of the isolates were found to be methicillin-resistant S. aureus (MRSA). DNA fingerprinting by pulsed-field gel electrophoresis showed 36 different patterns, with characteristic patterns being found for MRSA strains and the strains with different capsular types. Clonal relationships were established, and the origins of the infection-related isolates in each patient were determined. We conclude that (i) nosocomial infection-related isolates from the shock trauma patients did not belong to a single clone, although the predominance of a methicillin-resistant genotype was noted, (ii) most infection-related S. aureus isolates were relatively susceptible to antibiotics, but a MRSA strain was endemic, and (iii) for practical purposes, the combination of the results of capsular and antibiogram typing can be used as a useful epidemiological marker.

Adolescent↗