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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 379 records · Page 21Linked to original sources
PubMed1995

Ezrin NH2-terminal domain inhibits the cell extension activity of the COOH-terminal domain.

Overexpression in insect cells of the full coding sequence of the human membrane cytoskeletal linker ezrin (1-586) was compared with that of a NH2-terminal domain (ezrin 1-233) and that of a COOH-terminal domain (ezrin 310-586). Ezrin (1-586), as well as ezrin (1-233) enhanced cell adhesion of infected Sf9 cells without inducing gross morphological changes in the cell structure. Ezrin (310-586) enhanced cell adhesion and elicited membrane spreading followed by microspike and lamellipodia extensions by mobilization of Sf9 cell actin. Moreover some microspikes elongated into thin processes, up to 200 microns in length, resembling neurite outgrowths by a mechanism requiring microtubule assembly. Kinetics of videomicroscopic and drug-interference studies demonstrated that mobilization of actin was required for tubulin assembly to proceed. A similar phenotype was observed in CHO cells when a comparable ezrin domain was transiently overexpressed. The shortest domain promoting cell extension was localized between residues 373-586. Removal of residues 566-586, involved in in vitro actin binding (Turunen, O., T. Wahlström, and A. Vaheri. 1994. J. Cell Biol. 126:1445-1453), suppressed the extension activity. Coexpression of ezrin (1-233) with ezrin (310-586) in the same insect cells blocked the constitutive activity of ezrin COOH-terminal domain. The inhibitory activity was mapped within ezrin 115 first NH2-terminal residues. We conclude that ezrin has properties to promote cell adhesion, and that ezrin NH2-terminal domain negatively regulates membrane spreading and elongation properties of ezrin COOH-terminal domain.

Actins↗
PubMed1995

High-dose chemotherapy for breast cancer: clinical advantages of autologous peripheral blood progenitor cells (PBPC) compared with autologous bone marrow transplantation (ABMT).

Peripheral blood progenitor cell (PBPC) autografts have a number of advantages over autologous bone marrow transplantation (ABMT) as haematopoietic support after high-dose chemotherapy in patients with breast cancer. These may include less contamination by tumour cells, reduced morbidity and mortality and additional dose escalation of chemotherapy. A dose-escalation study is described using recombinant granulocyte colony-stimulating factor (G-CSF; filgrastim) primed PBPC support and post-infusion filgrastim for patients with high-risk or metastatic breast cancer. The regimen involved the use of cyclophosphamide, thiotepa and carboplatin at five dose levels. The main problem to emerge was organ toxicity induced by chemotherapy or sepsis. Patients receiving higher levels of chemotherapy were therefore allocated or not to an additional regimen involving pentoxifylline, ciprofloxacin and dexamethasone in an attempt to inhibit tumour necrosis factor alpha (TNF-alpha) which is believed to be one of the principal mediators of chemotherapy-related organ toxicity. The incidence of bilirubin elevations, weight gain > 5% and veno-occlusive disease (VOD) was lower in patients receiving the 'anti-TNF' therapy. The simultaneous use of PBPC support and 'anti-TNF' therapy therefore allows a substantial increase in chemotherapy dosage. Further studies with larger patient numbers are required to show whether this decreased toxicity also produces increased patient survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Recombination rates across the HLA complex: use of microsatellites as a rapid screen for recombinant chromosomes.

Meiotic recombination does not appear to occur randomly across chromosomes, but rather seems to be restricted to specific regions. A striking example of this phenomenon is illustrated by the HLA class II region. No recombination within the 100 kb encompassing the DRB1-DQA1-DQB1 loci has been reported, whereas the random association of TAP1 with TAP2 alleles suggests the presence of a hotspot for recombination within the 15 kb separating the closest variant sites of these two loci. Recombination rates between loci may provide clues to the functional properties of haplotypes. Absence of recombination may suggest the necessity to keep alleles of certain genes in phase and, alternatively, high recombination rates may suggest selective pressure to diversify haplotypes within the population. To address this issue, recombination rates across the HLA complex were determined using the 59 Centre d'Etude Polymorphisme Humain (CEPH) pedigrees. The allele frequencies of four microsatellite markers which map at sites ranging from the telomeric to centromeric ends of the complex were determined and the markers were used as a rapid means for identification of recombinant chromosomes. Typing these as well as other polymorphic loci within the HLA class I, II and III regions allowed assignment of the segments where recombination occurred. Recombination rates within the class II region (defined here as DRB1 to DPB1) and class III region (defined here as HLA-B to DRB1) regions were 0.74% and 0.94%, respectively, both of which are within an expected range given the standard of 1% recombination rate per megabase of DNA per meiosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1995

Competition of HLA-DR and a beta 2 domain peptide for HIV envelope glycoprotein gp120 binding to CD4.

HLA class II molecules and the HIV envelope glycoprotein gp120 are ligands of CD4. Reciprocal interaction sites have been well characterized for gp120 and CD4, but require further definition for HLA class II and CD4. A major CD4 binding site encompassing amino acids 134-148 in the beta 2 domain of HLA-DR has been previously identified. Recently, we have shown, by extensive characterization of mutated CD4 molecules expressed in COS cells, that HLA class II antigens interact mainly through the HIV gp120 binding site and possibly through a second minor interaction site mapping on the same face of the molecule. Based on the direct binding in vitro of iodinated affinity-purified HLA-DR1 molecules to polystyrene immobilized human IgG3-CD4, we now report on reciprocal binding inhibition of gp120, HLA-DR1 and the DR beta 2 synthetic peptide to CD4. The results strongly suggest that gp120 and the beta 2 region (amino acids 134-148) of HLA-DR1 bind mainly to the same part of CD4 domain 1 and that the CD4 binding site of HLA-DR requires the existence of a class II homodimer. In that case, alpha 2 chain residues might interact with CD4 residues different from those involved in the binding of gp120 but located close to them in the first domain.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1995

Medical knowledge and medical practice: geriatric medicine in the 1950s.

This article examines the development of medical knowledge and practice with regard to sickness in old age in the early years of the National Health Service. It suggests that the creation of a speciality of geriatrics was inspired by the need to prevent hospital beds being blocked by long-stay patients. Thus, the efficient use of hospital provision required the diagnosis, treatment, and rehabilitation of elderly patients. The publication of medical texts on sickness in old age, provided the basis for a more interventionist approach to the care of sick, elderly people, but the development of geriatrics as a separate speciality was hindered by professional disputes over administrative responsibility, funding, private practice, and medical training. One key area of debate was whether sickness in old age was primarily a social rather than a medical problem. This needs to be considered with regard to the relationship between the hospital and the local community and the article examines the contribution of social and medical surveys of elderly people at home to the discourse on sickness and old age.

Geriatrics↗
PubMed1995

Tension pneumopericardium following blunt injury.

Pneumopericardium caused cardiac tamponade in a patient who was struck in the chest by a motor vehicle. Subxiphoid pericardial window and pericardial drainage successfully treated this condition. Diagnosis of this rare form of tamponade depends on clinical examination supported by chest radiographic findings.

Accidents, Traffic↗
PubMed1995

Predictors of skilled nursing placement in a multilevel long-term-care facility.

OBJECTIVE: To determine if cognitive and functional data gathered before admission to residential care (i.e., board and care) placement can predict nursing home placement. DESIGN: Retrospective study using Cox proportional hazards analysis and pairwise assessment of adjusted relative risk factors to determine which independent variables predicted skilled nursing placement. Subjects were followed for an average of 23.7 months (SD = 18.6 months). SETTING: Multilevel 1,735-bed long-term care facility, Jewish Home for the Aging, Reseda, California. PARTICIPANTS: Of the 248 consecutive residential care admissions studied, 80% were women. Subject's mean age was 84.8 years (SD = 5.0); 67% had no significant cognitive impairment. INDEPENDENT VARIABLES: Categorical variables were classifications with respect to dementia status, incontinence, hearing, and ambulation. Interval variables were number of medications, Katz ADL, and five neuropsychological tests. Demographic variables were gender, age, language of origin, and education. OUTCOME VARIABLE: Time between preadmission testing and the move up to skilled nursing placement. RESULTS: Pairwise assessment of adjusted potential risk factors indicated that cognitive dysfunction, less than perfect Katz ADL performance, and hearing loss were the most important independent risk factors for nursing placement. CONCLUSIONS: The findings remind us to pay careful attention to residents exhibiting even relatively mild cognitive deficits upon admission because these residents are likely to need increased environmental support.

Aged↗
PubMed1995

Integral bias in the cognitive processing of emotionally linked pictures.

It is well established that human cognitive processes are subject to systematic biases associated with particular emotional states. But how do these cognitive biases arise? This question was addressed by means of a pictorial Stroop task which allowed the development of such a bias to be assessed. In each of two experiments, spider-phobic participants were significantly impaired at naming the colours of phobia-related pictures relative to those of control pictures. Investigation of the magnitude of this effect for participants of different ages allowed two contrasting hypotheses concerning the development of such biases to be compared. The integral bias hypothesis asserts that the effects of emotion on cognition reflect integral links between emotional states and cognitive mechanisms, links that are not arbitrary but instead are fixed constituents of our mental architecture. In contrast, the inferred bias hypothesis asserts that these effects arise as a consequence of the gradual establishment of associations between particular emotional states and particular patterns of cognitive behaviour. It was found that the magnitude of the observed bias remained approximately constant irrespective either of the ages of participants or of the directly estimated durations of their phobias. This fixed relation provides strong support for the integral bias explanation of the cognitive effects of an emotional disturbance. Finally, the evolutionary context in which integral links between emotion and cognition may arise is discussed.

Adolescent↗
PubMed1995

Polymer production by Klebsiella pneumoniae 4-hydroxyphenylacetic acid hydroxylase genes cloned in Escherichia coli.

The expression of Klebsiella pneumoniae hpaA and hpaH genes, which code for 4-hydroxyphenylacetic acid hydroxylase in Escherichia coli K-12 derivative strains, is associated with the production of a dark brown pigment in the cultures. This pigment has been identified as a polymer which shows several of the characteristics reported for microbial melanins and results from the oxidative activity of 4-hydroxyphenylacetic acid hydroxylase on some dihydroxylated compounds to form o-quinones. A dibenzoquinone is formed from the oxidation of different mono- or dihydroxylated aromatic compounds by the enzyme prior to polymerization. We report a hydroxylase activity, other than tyrosinase, that is associated with the synthesis of a bacterial melanin.

Cloning, Molecular↗
PubMed1995

Serum lipoprotein (a) levels in patients with chronic renal failure--evolution after renal transplantation and relationship with other parameters of lipoprotein metabolism: a prospective study.

In order to analyze the relationship between lipoprotein (a) [Lp (a)] and other lipoproteins during chronic renal failure and once renal function is restored after kidney transplantation, we determined the serum levels of total lipoprotein, high-density lipoprotein, low-density lipoprotein, and very-low-density lipoprotein cholesterols, total and very-low-density lipoprotein triglycerides, apolipoproteins A-I, B, C-II, C-III, and E, and E, and Lp (a) in 30 patients with chronic renal failure before and 12 months after renal transplantation. During the 1st year after transplantation, all patients were treated only with ciclosporin and prednisone and had serum creatinine levels < 1.6 mg/dl (140 mumol/l) and proteinuria < 500 mg/day. No patients had chronic hepatic disease. To determine reference values we studied a control group of 60 healthy volunteers. Before renal transplantation, the study group showed higher concentrations of triglycerides, very-low-density triglycerides, very-low density lipoprotein cholesterol, apolipoproteins, C-II and C-III, and Lp(a) than the control group. There was no correlation between Lp(a) and any of the studied variables. After renal transplantation, the serum levels of total lipoprotein, high-density lipoprotein, and low-density lipoprotein and apolipoproteins A-I and B increased significantly. Apolipoproteins C-II and C-III and Lp(a) decreased and normalized. After these changes had taken place, there was no relationship between Lp(a) and other parameters of lipoprotein metabolism. We conclude that the increase in Lp(a) during the chronic renal failure phase is basically related to the loss of renal function and does not depend on the resultant alterations which are produced in other lipoprotein variables.

Adult↗
PubMed1995

Effects of chronic renal failure on enzymes of energy metabolism in individual human muscle fibers.

In order to improve knowledge about the mechanisms underlying the alterations of energy metabolism recently observed in the skeletal muscle of patients suffering from chronic renal failure, this study was designed to test (1) whether changes in the activity of key enzymes of energy metabolism occur in the muscle of these patients, and if so (2) whether the different muscle fiber types are equally altered in their metabolic machinery. For this, the maximum activities of 14 enzymes were measured in individual muscle fibers microdissected from biopsies of rectus abdominis muscle obtained from seven normal subjects and seven patients with end-stage renal failure before renal replacement therapy. A large decrease in the activities of beta-hydroxyacyl-coenzyme A dehydrogenase, a key enzyme of the beta-oxidation pathway, of citrate synthase, which initiates the tricarboxylic acid cycle, and of fructose-1,6-bisphosphatase, which contributes to the synthesis of glycogen from lactate, was observed in the three fiber types (slow-twitch oxidative, fast-twitch oxidative-glycolytic, and fast-twitch glycolytic). A smaller reduction of the activities of phosphofructokinase and/or pyruvate kinase, two key enzymes of glycolysis, was also observed in slow-twitch oxidative and/or fast-twitch oxidative-glycolytic fibers. These results demonstrate that the abnormalities of muscle energy metabolism observed in patients with chronic renal failure are due, at least in part, to intrinsic changes in the key enzymes of major energy-providing pathways; they also offer a satisfactory explanation for the defect of oxidative metabolism recently demonstrated in the muscle of these patients.

Adult↗
PubMed1995

Signal transduction by the IL-1 type I receptor: evidence for the involvement of a receptor-coupled protein kinase.

A novel serine/threonine specific protein kinase was found to be associated with the type I IL-1 receptor in the murine T cell lines D10N and EL-4. This kinase was identified in immunoprecipitates from IL-1 stimulated T-cells by its ability to phosphorylate exogenous substrates in the presence of radiolabeled ATP. An endogenous protein, most likely a member of the IL-1 R1 complex, was also phosphorylated. The activation of the kinase is specific for IL-1, neither TNF nor phorbol esters were able to activate the IL-1 RI associated kinase activity. The IL-1 receptor antagonist had no intrinsic activity and inhibited the activation of the kinase. The activation of the kinase was rapid and detectable after 30 seconds of IL-1 stimulation. A minimal model of the IL-RI signal transduction complex is discussed, presenting this novel serine/threonine kinase as a constituent of the complex.

Alkaloids↗
PubMed1995

Central venous oxygen saturation, arterial base deficit, and lactate concentration in trauma patients.

Our object was to explore the usefulness of central venous oxygen saturation, arterial base deficit, and lactate concentration in the evaluation of trauma patients. In busy urban trauma centers, limited operating room availability may necessitate that certain hemodynamically stable patients experience some delay between diagnosis of injury and surgery. Because hemodynamic compromise may occur before operation is undertaken, some means of identifying those patients who have the most severe injuries or who are at greatest risk for hemodynamic instability would be useful. We prospectively studied 40 patients with operative truncal injuries admitted to the Cook County Trauma Unit, Chicago, to examine the usefulness of postresuscitation central venous oxygen saturation (ScvO2), arterial lactate concentration, and arterial base deficit in this regard. Preoperative hypotension occurred in 12.5 per cent of these initially stable patients. ScvO2 did not significantly correlate with any of the parameters of blood loss and severity of injury examined. However, both base deficit and lactate concentration correlated with transfusion requirements; in addition, base deficit correlated with trauma score, and lactate correlated with peritoneal shed blood volume. Our data suggest that, after resuscitation, arterial base deficit and lactate concentration may be better indicators of blood loss than is ScvO2.

Abdominal Injuries↗
PubMed1995

Limiting cardiac evaluation in patients with suspected myocardial contusion.

A great deal of time and effort is spent attempting to diagnose myocardial contusion in patients with blunt thoracic trauma. Many diagnostic protocols have been proposed in the past. However, there is no test with sufficient specificity to predict which patients will develop complications that will require therapy. Recent studies have raised the question of limiting the cardiac evaluation in certain selected patients with blunt thoracic trauma. We prospectively studied the safety of limiting the cardiac evaluation in patients who were hemodynamically stable, had no history of cardiac disease, had a normal baseline ECG, did not require surgery or neurological observation for associated injuries, and were less than 55 years of age. These patients represent the majority of patients considered at risk for myocardial contusion when mechanism is the sole criterion. These patients were simply admitted for 24 hours of continuous cardiac monitoring. No patient developed any complications of myocardial contusion requiring therapy. We conclude that it is safe to limit the cardiac evaluation in this group of patients.

Adult↗