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Biomedical subjects

P Martin

Publications and source records attributed to P Martin.

At least 181 records · Page 10Linked to original sources

Synthesis and amphiphilic properties of glycosyl-1,4-benzodiazepin-2,5-diones.

Glycosyl-1,4-benzodiazepin-2,5-diones were prepared by coupling polyhydroxylated groups at N-1 of the corresponding benzodiazepine. The groups include 1-deoxy-D,L-xylit-1-yl, 6-deoxy-D-glucopyranos-6-yl, and 6-deoxy-3-OR-D-glucopyranos-6-yl (R = n-CnH(2n +1); n = 8, 12, and 16). The structural variations of the sugar group allowed comparison of such amphiphilic data as water solubility (Sw), critical micelle concentration (CMC), and corresponding surface tension (gamma) values. At 25 degrees C, unsubstituted benzodiazepines have Sw values from 0.9 to 4.2 10(-3) mol L(-1), whereas xylit-1-yl and 6-deoxy-D-glucopyranos-6-yl derivatives are, respectively, 7.4-25 and 58-204 times more soluble. Also, compounds with R = n-C8H17 are more soluble than corresponding benzodiazepines (1.4-5.8 times) and give micelles with CMC from 2.7 to 5.6 10(-3) mol L(-1) and corresponding gamma from 29 to 37 mN m(-1). In contrast, compounds with R = n-C12H25 and n-C16H33 are not soluble enough to reach the critical micelle concentration.

Benzodiazepinones↗

NEAR at eros: imaging and spectral results

Eros is a very elongated (34 kilometers by 11 kilometers by 11 kilometers) asteroid, most of the surface of which is saturated with craters smaller than 1 kilometer in diameter. The largest crater is 5.5 kilometers across, but there is a 10-kilometer saddle-like depression with attributes of a large degraded crater. Surface lineations, both grooves and ridges, are prominent on Eros; some probably exploit planes of weakness produced by collisions on Eros and/or its parent body. Ejecta blocks (30 to 100 meters across) are abundant but not uniformly distributed over the surface. Albedo variations are restricted to the inner walls of certain craters and may be related to downslope movement of regolith. On scales of 200 meters to 1 kilometer, Eros is more bland in terms of color variations than Gaspra or Ida. Spectra (800 to 2500 nanometers) are consistent with an ordinary chondrite composition for which the measured mean density of 2.67 +/- 0.1 grams per cubic centimeter implies internal porosities ranging from about 10 to 30 percent.

Journal Article↗

Quasi-single-helicity reversed-field-pinch plasmas

The reversed field pinch (RFP) is a configuration for plasma magnetic confinement. It has been traditionally viewed as dominated by a bath of MHD instabilities producing magnetic chaos and high energy transport. We report experimental results which go beyond this view. They show a decrease of magnetic chaos and the formation of a coherent helical structure in the plasma, whose imaging and temperature profile are provided for the first time. These quasi-single-helicity states are observed both transiently and in stationary conditions. The last case is consistent with a theoretically predicted bifurcation. Our results set a new frame for improving confinement in high current nonchaotic RFP's.

Journal Article↗

Optimisation of procedures for the extraction of structural analogues of propranolol with molecular imprinted polymers for sample preparation.

A propranolol-derived molecular imprinted polymer (MIP) was prepared using methacrylic acid as monomer and ethylene glycol dimethacrylate as cross-linker. The extraction properties of five compounds structurally related to propranolol were assessed on the MIP and on a blank polymer made under the same conditions but in the absence of an imprint molecule. Using application from aqueous solution with methanol-water-triethylamine (TEA)-based solvents for elution (i.e. reversed-phase conditions) the MIP showed only marginal selectivity for the compounds on the MIP compared to the blank. Despite the limited selectivity there did appear to be a relationship between structure of the compound (relative to propranolol) and the extent of selective retention. Application of the compounds in toluene with elution using toluene-TEA or toluene-trifluoroacetic acid resulted in the MIP showing dramatically enhanced retention and selectivity of the compounds on the MIP compared to the blank. The enhanced selectivity for extraction on to the MIP relative to the blank, for all compounds using normal-phase solvents seem to be a class effect as there was no apparent relationship between compound structure and retention.

Adrenergic beta-Antagonists↗

Histopathological features of hepatitis C in renal transplant candidates [see comment].

BACKGROUND: Although hepatitis C virus (HCV) infection is common in renal transplant candidates, its clinical significance remains unclear in this population. Little detailed information is available about the histological severity of HCV infection in these patients. We evaluated the liver biopsy features of chronic HCV in a large population of renal transplant candidates and investigated associations between histopathological changes and host- and virus-related factors. METHODS: Thirty-seven patients seropositive for anti-HCV with chronic renal failure (CRF) referred to UCLA Medical Center for kidney or kidney/liver transplantation during the period 1992-1997 were included. HCV genotype and viral load were measured. A multivariate analysis by logistic regression model was performed: age, gender, race, HCV load and genotype, CRF level, aspartate and alanine aminotransferase activity, duration of HCV infection, underlying nephropathy, and alcohol abuse were independent variables; liver histology score was assumed a dependent variable. RESULTS: Liver disease was present in all HCV-infected patients. Logistic regression analysis revealed that histological damage was (P = 0.0017) independently associated with the CRF level; the severity of liver disease, as shown by univariate analysis, being significantly higher in CRF patients not requiring dialysis than among dialysis population. All patients on dialysis showed mild or moderate necroinflammatory activity; the majority (22/28 = 79%) of these individuals had fibrosis, three (3/28 = 11%) dialysis patients had established cirrhosis. Thirty-one (84%) of 37 patients were tested by polymerase chain reaction, 25 (81%) patients had detectable HCV RNA in serum, the mean HCV load among viremic patients was 10.9x10(5) copies/ ml. The most frequent HCV genotypes were la (8/24 = 33%) and 1b (7/24 = 29%), followed by genotype 2b (3/24 = 12%). CONCLUSIONS: Pathological changes on liver biopsy were observed in all HCV-infected patients awaiting renal transplantation. The severity of histologic damage observed on liver biopsy was less in dialysis than predialysis CRF patients. All dialysis patients had mild or moderate necroinflammatory activity; fibrosis was frequent with 11% of them having cirrhosis. The HCV viral load was rather low; no relationship between liver histology changes and virological features of HCV or aminotransferase activity was apparent. Further studies with repeat liver biopsies after kidney transplantation to observe the evolution of HCV-related liver disease after immunosuppressive therapy are indicated. We suggest including liver biopsy in the evaluation of the HCV-infected renal transplant candidate.

Adult↗

Salivary endothelin concentrations in the assessment of chronic heart failure.

We have shown that salivary endothelin concentrations are raised in patients with chronic heart failure and indicate progression of disease severity through each New York Heart Association Functional Class. Furthermore, endothelin concentrations in saliva seem to discriminate between controls and patients with mild symptoms of chronic heart failure.

Case-Control Studies↗

Validation of a model of colon cancer progression.

A unique feature of SW480 and SW620 colon carcinoma cell lines is that they are derived from primary and secondary tumours resected from a single patient. As such, they may represent a valuable resource for examining genetic changes late in colon cancer progression. In order to verify this, both cell lines have been characterized to determine whether phenotypic differences have been retained despite long-term cell culture in vitro. The primary tumour-derived SW480 cells have an epithelioid morphology in vitro, while metastasis-derived SW620 cells have a fibroblast-like appearance. Xenografts of SW480 cells form gland-like structures in vivo, while SW620 xenografts form solid sheets of tumour cells. SW620 cells have a higher BrdU labelling index than SW480 cells, and are more highly tumourigenic and metastatic. Furthermore, SW620 cells show less susceptibility to apoptosis induction by TNFalpha and anti-Fas monoclonal. Findings from these investigations therefore indicate that SW480 and SW620 cell lines do show appropriate phenotypic differences and represent an interesting model for studying the genetic events in the late stages of colon cancer progression.

Animals↗

Spectrum of COL4A5 mutations in Finnish Alport syndrome patients.

Alport syndrome (AS) is a hereditary kidney disorder, mainly caused by mutations in the X-chromosomal gene (COL4A5) encoding the type IV collagen a5 chain. In this study, detection of COL4A5 mutations was performed in 17 Finnish Alport syndrome families. Regions around the 51 previously known exons, as well as the two recently characterized exons 41A and 41B in COL4A5, were PCR-amplified from the patient DNA. Direct sequencing of the amplified products was performed and mutations were found in 12 families. None of the mutations involved exons 41A or 41B. Three of the mutations were potential splicing mutations, two of which were studied at the mRNA level. Seven of the mutations were single base substitutions, and two were deletions. In five families, no mutations were found.

Adolescent↗

Apoptosis in cultured midgut cells from heliothis virescens larvae exposed to various conditions.

We exposed midgut cells from primary cultures of Heliothis virescens larvae to cell-free previously used medium, the Vaughn X and HyQ SFtrade mark media used for serum-free culture of insect cell lines which do not support H. virescens midgut cells, and to toxin from Bacillus thuringiensis. A statistically significant increase in the percent of dying cells was counted in cell populations in Vaughn X medium. Use of the TUNEL method to detect apoptosis indicated a low rate (7.2%) of apoptosis in control cultures grown in Heliothis medium, an increase to approximately 20% in previously used and HyQ SFtrade mark media, and to approximately 45% of cells remaining after exposure to and initial destruction by B. thuringiensis toxin. Apoptotic nuclei were predominant (approximately 6%) in mature columnar cells in control cultures. Approximately 1% of goblet, stem, and differentiating cells were apoptotic. However, apoptosis rose to 12% in stem and differentiating cells exposed to used and unsuitable medium. B. thuringiensis exposure to toxin for 2-3 days resulted in visible membrane damage and necrosis, causing the death of 84% of the cells as measured by both the TUNEL and Annexin methods. Some of the columnar cells and stem and differentiating cells that remained also contained apoptotic nuclei. Stem and differentiating cells normally replace dying mature cells in the midgut. Thus, exposure of cultures of H. virescens midgut cells to adverse environments such as unsuitable or poisonous media appeared to induce down-regulation of the cell populations by apoptosis.

Animals↗

Conserved mechanisms of repair: from damaged single cells to wounds in multicellular tissues.

The capacities to repair minor membrane holes in damaged single cells, and the more major damage sustained when a multicellular tissue is wounded, both involve a series of ancient and highly conserved processes. In this review, we discuss what is known about how the plasma membrane of a single cell and its underlying cortical cytoplasm are repaired following cell damage, and how multicellular wounds to the embryonic and adult skin are also able to heal. Pivotal for all these processes is the actin cytoskeleton and we draw analogies between the actin machineries that drive repair and those that appear to underlie several genetically tractable morphogenetic processes that occur during Drosophila and Caenorhabditis elegans embryogenesis.

Actins↗

Rapidly evolving lineages impede the resolution of phylogenetic relationships among Clitellata (Annelida).

The phylogenetic relationships of the Clitellata were investigated using a data set with published and new complete or partial 18S rRNA and mtCOI gene sequences of 13 and 49 taxa representing 8 and 14 families, respectively. Three different alignments were considered for 18S, and the possible influence of departures from rate constancy among sites was evaluated by analyses using a Gamma model of rate heterogeneity. Maximum-likelihood estimates of the shape parameter alpha of the Gamma distribution were very low, whatever the alignment or the gene considered, suggesting that phylogenetic reconstructions taking into account the rate heterogeneity among sites are likely to be the most reliable. Analyzed separately, the two genes did not resolve the relationships among the Clitellata, but the consensus tree was congruent with the morphology-based relationships. Our data suggest the inclusion of the Euhirudinea, Acanthobdellida, and Branchiobdellida in the Oligochaeta and suggest the Lumbriculidae as the link between both assemblages. Although separate analyses of both genes, as well as different alignments for the 18S rRNA sequences, yielded conflicting results concerning the phylogenetic position of leeches and leech-like worms vis-à-vis the Oligochaeta, subsequent analyses using the Gamma model greatly reduced the observed inconsistencies. Our analyses show that among the Clitellata, the leeches and the leech-like and gutless worms represent significantly faster evolving lineages. It is suggested that the observed higher mutation rates may be explained by the fact that these lineages contain almost exclusively commensal and/or parasitic taxa.

Animals↗

[Success and variability of success of inpatient rehabilitation of the elderly: an empirical study based on medical-psychiatric and psychosocial indicators].

This study considers findings of psychological gerontology as particularly important for geriatric rehabilitation research. Its concrete aim was to describe the course and outcome of geriatric rehabilitation based on a wide range of success criteria, to explore the influencing role of age, sex, and diagnosis as well as to describe the variability pattern of success. The data were gathered from a sample of 100 older adults who underwent treatment in a German inpatient rehabilitation unit. Participants were assessed across five measurement occasions by use of a state-of-the-art geriatric assessment and a psychological data collection part. The results underline, for one, that significant improvements of functional as well as psychological capacity were obtained. Second, age and sex played practically no role concerning the course of the success criteria, whereas diagnosis revealed some statistically meaningful effects. Third, it was found that the variability of success was characterized by a relatively homogeneous pattern of gain with regard to functional criteria; with respect to psychological variables, heterogeneity was more pronounced and some participants show loss as well, a chance for further improvement of the geriatric rehabilitation.

Adult↗

[Personality, cognitive ability and health in East and West Germany: results of an interdisciplinary longitudinal study of aging].

The goal of the Interdisciplinary Longitudinal Study of Aging (ILSE) is to assess healthy and satisfying aging in middle adulthood and later life. In addition, this study compares adults from eastern and western Germany. The data for this study were collected between late 1993 and early 1996 as part of the first measurement point of the ILSE. Five-hundred and one participants from the Leipzig region were compared with 500 participants from the Heidelberg area on four specific dimensions: personality, cognitive functioning, subjective well-being, and health. Age differences were obtained for neuroticism, extraversion, openness, and agreeableness. Differences were also obtained in cognitive functioning and health. Regional differences between eastern and western Germany were obtained in the personality dimensions neuroticism, openness and conscientiousness, as well as in subjective well-being. Significant age by region interactions were obtained for openness and some of the cognitive measures, as well as for the physicians' health ratings of the participants, suggesting selective historical effects. The results are discussed with respect to functional abilities and levels of satisfaction in midlife, as well as with respect to regional differences that might be due to prior political system differences in the east and west.

Adult↗

[Aging, activity and longevity].

From its origin to its death the human organism is submitted to functional, material, and morphological changes that are perceptible. These changes permit classifying an individual as young, adult, old, active or infirm. But this estimation is not always correct. Some appear younger, some older than expected from their chronological age. But what is aging and how can it be measured? For this, so-called markers or biological markers of aging are used which are measurable indicators of aging in live organisms. A description of the complexity, the asynchronous course, and the biological variety and variability of biological age is less successful with a single indicator than with the inclusion of several markers in a multi-factorial measuring system, in a so-called test battery. Various test batteries have already been applied in numerous studies that consist of biochemical scans, mental and also social parameters in different combinations. A more precise description of such a test battery can be seen in the following example of a discussion of the ILSE study.

Activities of Daily Living↗

Patient reports of complications of bone marrow transplantation.

In recent years, significant improvements have been made in the management of neutropenia and thrombocytopenia and other potentially life-threatening complications of ablative chemotherapy. While these complications are of particular concern to physicians, patients receiving ablative therapy for bone marrow or blood stem cell transplants are often troubled by other side effects such as nausea, vomiting, diarrhea and mouth sores. The purpose of the study was to gain a better understanding of patients' experiences while undergoing a transplant. The same professional medical interviewer conducted in-depth interviews with 38 subjects (10 men, 28 women; mean age 46.9 years) who had received ablative therapy for bone marrow and/or peripheral blood stem cell transplants. Participants were consecutively identified through physician and patient referrals, cancer and BMT patient support groups, and newspaper advertisements. Twenty-eight patients (74%) received autologous stem cell transplants and 10 patients (26%) received allogeneic transplants. Participants reported mouth sores, nausea and vomiting, diarrhea, and fatigue as the most troubling side effects of their transplants. Mouth sores were selected as the single most debilitating side effect (42%), followed by nausea and vomiting (13%). Many patients mentioned that mouth sores made it difficult or impossible to eat (n = 23), swallow (n = 21), drink (n = 17), and/or talk (n = 8). Twenty patients reported pain in the mouth, throat, and/or esophagus. Two-thirds (66%) of patients reported receiving opioid analgesics, most frequently morphine, to relieve oral pain. For many, opioids caused incapacitating side effects, including hallucinations, a feeling of loss of control and a decrease in mental acuity. Patients receiving ablative chemotherapy identify oral mucositis as a significant cause of suffering and morbidity. Effective interventions to alleviate this complication are urgently needed.

Activities of Daily Living↗

A 'made in one piece' skeleton in a 22-year-old man suffering from sickle cell anaemia.

A 22-year-old African male with known sickle cell anaemia was referred by a Congolese medical centre with a request to improve his poor physical condition. He was unable to walk, stand or sit because his large joints and his spine were either ankylosed or very rigid. Radiographs showed joint fusion from the third to the fifth cervical vertebrae, of both hips, of the left knee, and a bilateral osteonecrosis of the humeral head. There was no scintigraphic evidence for an active osteomyelitis (99mTc-MDP (methyldiphosphonate) bone scan, Tc monoclonal antigranulocyte scan and 99mTc sulphur colloid scan). To improve his mobility the right femoral head was resected in June 1997; 14 days later the left femoral head was resected. Four months after the resection of the right hip, a right uncemented total hip prosthesis was implanted on this side. One month later the same type of hip arthroplasty was performed on the left side. During the postoperative rehabilitation period the patient regained autonomy. We have found no previous reports of such severe and multiple joint complications in a single patient suffering from sickle cell anaemia.

Adult↗