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Biomedical subjects

H Martin

Publications and source records attributed to H Martin.

At least 91 records · Page 5Linked to original sources
PubMed1999

[Age related changes in cellular signal transduction of glucocorticoid hormones in rat brain].

Chronic or repeated stress can induce a damage of neurons, especially in hippocampus, by which the degree of damage differs in various species. Sapolski has reported that there is a correlation between hippocampal degeneration, disturbed feedback reaction, and hypersecretion of glucocorticoids. The aim of this study was to investigate if the signal transmission via glucocorticoid receptors (GR) in the brain of male wistar rats of two age groups (5-6 and 17-24 months, respectively) is changed in aging and which cytoplasmic factors/modulators participate in this process. The binding of 3H-dexamethasone to cytosolic GR, the transformation, translocation, and nuclear binding of GR complexes (GRC) were studied before and after physiological stress. The influence of cytoplasmic modulators ASTP1) and HSP 70(1)), isolated from brain cytosol and purified, and of exogenous PK C1) was also tested in parallel incubation systems. Whereas old control animals showed a higher cytosolic concentration of unoccupied GR than young ones, this was significantly reduced only in old stressed rats 60 min after stress compared to old controls. The part of transformed GRC, bound to isolated nuclei, was somewhat lower in old than in young rats before and after stress. The nuclear GRC binding could be slightly elevated by addition of ASTP and HSP 70, resp., at the heat transformation of GRC; however, by simultaneous addition of PK C it was significantly increased in both age groups. The GRC binding also rose significantly in stressed animals compared to controls, after simultaneous addition of PK C to more than double of initial assays in young animals. Purified ASTP, isolated from brain cytosol of young animals, showed a higher 32P-incorporation after phosphorylation in vitro than that from old animals. The reduced phosphorylation of ASTP could be one possible cause of the retarded transformation/translocation and the reduced nuclear binding of GRC together with the restricted expression of HSP 70 and decreased PK C activity in the old rat brain.

Adrenocorticotropic Hormone↗
PubMed1999

[Clinical laboratory diagnosis and aging. 1: Results of data evaluation of clinico-chemical laboratory values in a study of aging].

The results of the determination of 24 basic blood chemistry variables from 262 men and 239 women, half of each group 44.4 +/- 0.9 and 63.0 +/- 0.9 (men) and 44.4 +/- 0.9 and 62.8 +/- 0.8 years old (women), resp., are compared. In men, only 6 analytes show significant differences between the age groups: Alanine aminotransferase decreases, aspartate aminotransferase decreases, iron decreases with p < 0.05; sodium increases, calcium decreases, protein (serum) decreases with p < 0.001. In women, 16 analytes, compared between both groups, are significantly different: Urea, uric acid, creatinine, triglycerides, total cholesterol, LDL cholesterol, LDL-C/HDL-C ratio, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, sodium and ferritin are increased in the older group, whereas HDL cholesterol, iron, transferrin, and total protein are decreased. The sex differences are more distinct in the group of 44 years old persons than in the 63 years old one. These results will be completed by the comparison with the evaluation of the stored laboratory values of 9923 patients between 20 and 89 years old.

Adult↗
PubMed1999

[Clinical laboratory diagnosis and aging. 2: Suitability of clinico-chemical basic parameters as markers ob biological aging].

In 262 men (about half of them 44.4 +/- 0.9 and 63.0 +/- 0.9 years old, resp.) and 239 women (about half of them 44.4 +/- 0.9 and 62.8 +/- 0.8 years old, resp.) the results of 12 clinical chemical analytes were used to calculate laboratory indices which were compared with the biological age in accordance with Ries. The indices were calculated by using concentrations of alkaline phosphatase, iron, total protein, total cholesterol, glucose, uric acid, urea, HDL cholesterol, creatinine, LDL cholesterol, transferrin, and triglycerides. Only in the younger group of women are the correlations between laboratory indices and biological age significant. In the same group, several single parameters also significantly correlate with pre-aging. Among them are alkaline phosphatase, the LDL-C/HDL-C ratio, bilirubin, triglycerides, and glucose.

Adult↗
PubMed1999

How often do parenteral nutrition prescriptions for the newborn need to be individualized?

BACKGROUND: Parenteral nutrition is commonly given in the newborn period to premature infants or those with gastrointestinal disorders. Computer-assisted prescribing is widely used, with prescriptions for each patient being varied on a daily basis. It has previously been suggested that 'individualization' of feeds may have little clinical benefit whilst increasing pharmacy workload and costs. However, the scope for use of standard feed solutions as an alternative remains uncertain. METHODS: To assess the potential for using standardized pre-mixed feeds we prospectively reviewed 148 computer assisted prescriptions for newborn infants in order to establish how often the prescribing clinician adhered to the computer protocol, and the reason for modification when this occurred. RESULTS: Only one-fifth of feeds were based strictly on the computer recommendation with no, or minimal, modification. However, many of the deviations in the other four-fifths of feed prescriptions reflected a routine use of higher carbohydrate, sodium and phosphate intakes implying that a higher proportion of feeds could be 'standardized' if the computer regimens were modified to reflect current nutritional practices on the unit. CONCLUSIONS: This study suggests that the introduction of standard PN feeds could considerably reduce the use of computer assisted individualized PN prescriptions on the neonatal unit. The practical implications of such a system for pharmacy and the potential cost benefits deserve further investigation.

Decision Making, Computer-Assisted↗
PubMed1999

Defective apoptosis due to a point mutation in the death domain of CD95 associated with autoimmune lymphoproliferative syndrome, T-cell lymphoma, and Hodgkin's disease.

Apoptosis via CD95 and its ligand is an important mechanism that prevents uncontrolled proliferation of activated lymphocytes and regulates lymphocyte homeostasis. The apoptosis receptor CD95 is a transmembrane protein with an intracellular domain well conserved between CD95 and tumor necrosis factor receptor I, another apoptosis-inducing protein. Because of its functional importance, this domain was designated the death domain. We describe the molecular analysis of the CD95 death domain in a family with autoimmune lymphoproliferative syndrome (Canale-Smith syndrome), T-cell lymphoma, and Hodgkin's disease. A functional defect in apoptosis was detected in cells from the index patient, a 5-year-old girl suffering from Canale-Smith syndrome and a T-cell lymphoma, as well as in her father, who had a history of splenomegaly and mild hemolysis, and her paternal uncle who had been cured of Hodgkin's disease (HD). Expansion of double-negative T cells (CD4-CD8-) was only seen in the index patient. All family members with a functional defect in apoptosis were heterozygous for a point mutation in the death domain of CD95 (A1009G, E256G). We conclude that, within the same family, a defect in apoptosis due to a mutation in the CD95 death domain can be associated with diverse clinical phenotypes, including mild, reversible symptoms and different malignancies.

Apoptosis↗
PubMed1999

Flexible management system for occupational safety and quality.

In the 10 analysed companies it is necessary to create a management for flexible processes and a structured flexibilisation of these processes. This represents the basis for the retention of existing flexibility and occupational safety. The strategy for a management of flexible processes leads, firstly, to a structuring of company procedures whilst still retaining the necessary flexibility and certification ability as laid down by standards No. DIN EN ISO 9000ff. and, secondly, to the keeping of the demands of an occupational safety management system. In this article the inclusion of co-workers stands in the foreground. This will be combined with the goal to utilise their experience and their acceptance of the solutions worked out.

Ergonomics↗
PubMed1999

Studies of human immunodeficiency virus type 1 mucosal viral shedding and transmission in Kenya.

If human immunodeficiency virus type 1 (HIV-1) vaccines are to be highly effective, it is essential to understand the virologic factors that contribute to HIV-1 transmission. It is likely that transmission is determined, in part, by the genotype or phenotype (or both) of infectious virus present in the index case, which in turn will influence the quantity of virus that may be exchanged during sexual contact. Transmission may also depend on the fitness of the virus for replication in the exposed individual, which may be influenced by whether a virus encounters a target cell that is susceptible to infection by that specific variant. Of interest, our data suggest that the complexity of the virus that is transmitted may be different in female and male sexual exposures.

Adult↗
PubMed1999

Biogenesis of Tim proteins of the mitochondrial carrier import pathway: differential targeting mechanisms and crossing over with the main import pathway.

Two major routes of preprotein targeting into mitochondria are known. Preproteins carrying amino-terminal signals mainly use Tom20, the general import pore (GIP) complex and the Tim23-Tim17 complex. Preproteins with internal signals such as inner membrane carriers use Tom70, the GIP complex, and the special Tim pathway, involving small Tims of the intermembrane space and Tim22-Tim54 of the inner membrane. Little is known about the biogenesis and assembly of the Tim proteins of this carrier pathway. We report that import of the preprotein of Tim22 requires Tom20, although it uses the carrier Tim route. In contrast, the preprotein of Tim54 mainly uses Tom70, yet it follows the Tim23-Tim17 pathway. The positively charged amino-terminal region of Tim54 is required for membrane translocation but not for targeting to Tom70. In addition, we identify two novel homologues of the small Tim proteins and show that targeting of the small Tims follows a third new route where surface receptors are dispensable, yet Tom5 of the GIP complex is crucial. We conclude that the biogenesis of Tim proteins of the carrier pathway cannot be described by either one of the two major import routes, but involves new types of import pathways composed of various features of the hitherto known routes, including crossing over at the level of the GIP.

Amino Acid Sequence↗
PubMed1999

Human CYP2B6: expression, inducibility and catalytic activities.

Human cytochrome (CYP)2B6 cDNA was cloned and expressed in bacteria and in yeast. Its expression in Saccharomyces cerevisiae enabled us to obtain, at a high level, an active yeast-expressed CYP2B6 protein, so as to assess its role in the metabolism of ethoxyresorufin, pentoxyresorufin, benzyloxyresorufin, ethoxycoumarin, testosterone and cyclophosphamide. Kinetic analysis showed that human CYP2B6 preferentially metabolized benzyloxyresorufin and pentoxyresorufin, although other CYPs also metabolized these substrates in human liver microsomes. CYP2B6 also manifested a strong 4-hydroxycyclophosphamide activity. Its expression in Escherichia coli enabled us to produce a very specific anti-human CYP2B6 antibody. No cross reactivity of this antibody was observed with CYPs1A1, 1A2, 3A4, 3A5, 2C8, 2C9, 2C18, 2C19, 2D6 or 2E1. This antibody enabled us to study the hepatic and extrahepatic expression of CYP2B6 in man, as well as its expression and inducibility in primary cultured human hepatocytes and in different human cell lines. Immunoblot analysis revealed that the CYP2B6 protein was expressed in 43 of the 48 human liver samples tested, with levels ranging from 0.4 to 8 pmol/mg of microsomal protein with a mean of 1.7 pmol/mg protein. CYP2B was also expressed in human brain, intestine and kidney, and at a lower level in the lung. CYP2B mRNA was detected in human liver, kidney, lung, trachea and intestine. We also found that CYP2B6 is induced at protein and mRNA levels by phenobarbital (2 mM) and cyclophosphamide (1 mM), an anticancer drug known to be metabolized by CYP2B6. No expression or inducibility of CYP2B6 was observed in any of the human cell lines tested.

Aryl Hydrocarbon Hydroxylases↗
PubMed1999

Validation of in vitro assays for botulinum toxin: a case study.

Ensuring the reliability and precision of assay results requires careful attention to assay design. In this case study we describe validation studies of an in vitro assay for botulinum neurotoxin type A based on its endopeptidase activity towards immobilised synthetic substrate. This assay, in common with many in vitro assays, is sensitive to changes in reagents and assay conditions and is time dependent. In addition, the toxin is not stable in solution. Differences in estimates of potency, resulting from positional factors, which are not significant in individual assays, are shown to be consistent and statistically significant over a longer series of assays. This study emphasizes that assay validation should not be viewed as a single step in assay development but must be considered as a continuing process if assay results are to be reliable and reproducible.

Analysis of Variance↗
PubMed1998

The yeast mitochondrial intermembrane space: purification and analysis of two distinct fractions.

We have developed a protocol for the sequential release of the intermembrane space (IMS) content of Saccharomyces cerevisiae mitochondria. Two distinct fractions were obtained: a soluble IMS with cytochrome b2 as key marker and a salt-extractable IMS with cytochrome c as key marker. The identity of several proteins was determined by amino-terminal amino acid sequencing. The IMS fractions were devoid of contaminations from cytosol and mitochondrial outer and inner membranes. By subtraction analysis, the protein profiles of soluble and salt-extractable IMS fractions were depleted of contaminating bands derived from matrix proteins. The fractionation method will provide the basis for the further analysis of IMS proteins and characterization of their functions in bioenergetics, mitochondrial biogenesis, and regulatory processes.

Cell Fractionation↗
PubMed1998

Precipitation of trace elements in parenteral nutrition mixtures.

Trace elements are an essential additive to parenteral nutrition (PN) mixtures. Previous studies have indicated that certain trace elements, in particular copper and iron, may interact with complete PN mixtures leading to precipitate formation. The causes of these incompatibilities have not been fully elucidated. The purpose of this study was to determine factors responsible for common trace element incompatibilities, using X-ray energy dispersive spectroscopy to examine the elemental content of precipitates isolated from stored PN mixtures with added trace elements. Results indicated that copper sulphide precipitated most rapidly in PN mixtures containing Vamin 9 and in mixtures stored in multilayered bags. Copper sulphide precipitation was delayed in PN mixtures containing Vamin 14 and was not observed in PN mixtures stored in EVA bags. Iron phosphate precipitates were observed in Synthamin-containing PN mixtures after storage, but this was prevented in mixtures containing vitamins stored in multilayered bags.

Amino Acids↗
PubMed1998

Stability of cocarboxylase in parenteral nutrition mixtures stored in multilayer bags.

The aim of this study was to determine the stability of cocarboxylase, a thiamine derivative employed as a vitamin B1 source in multivitamin additives, in parenteral nutrition (PN) mixtures containing different commercial amino acid infusions. In particular, the influence of a metabisulphite-containing amino acid product, Freamine III, was investigated. A liquid chromatographic assay method for cocarboxylase was developed and employed to investigate cocarboxylase degradation during extended storage of PN mixtures at 5 degrees C in multilayered bags. Results indicated that cocarboxylase was relatively stable over the 28-day storage period in PN mixtures containing Synthamin or Vamin products as amino acid source. In contrast, degradation was accelerated in PN mixtures containing Freamine III, suggesting that cocarboxylase is degraded by sodium metabisulphite, showing similar sensitivity to thiamine.

Amino Acids↗
PubMed1998

Non-accidental burns in children.

A retrospective review of five hundred and seven consecutive admissions to a state-wide paediatric burns unit over a three year period was made to assess the characteristics of the burn injuries and to see which, if any, characteristics would help to distinguish accidental burns from burns which were due to abuse or neglect. In 86% of admissions (the 'accident group') it was considered that the injury was accidental, with no evidence of deliberate injury or gross neglect. Eight percent of admissions (the 'abuse/neglect group') were referred to the State Department of Community Services for abuse or neglect resulting in the Department becoming involved in the family's management. In six percent of cases (the 'concern group') the Unit had concerns that the family's emotional or social situation was a significant factor in the child's injury, or made further injury more likely, and discussed the family's situation with the Department, but formal intervention was not undertaken by the Department. There were no differences between the groups in age or mortality. Children in the 'abuse/neglect' and the 'concern' groups were more likely to require skin grafting and treatment in the intensive care unit. They were more likely to come from single parent families and were more likely to have burns involving both hands or both legs. There were few other distinguishing factors. The incidence of prior notification for abuse and neglect was four percent for the 'accident' group, 14% for the 'concern' group and 46% for the 'abuse/neglect' group. This is considerably higher in the 'concern' and 'abuse/neglect' groups than the annual state incidence of 1.73% for abuse and neglect notifications. While the clinical features of a burn may often not be helpful in reaching a diagnosis of abuse or neglect as a cause of the burn, it appears that many children who have non-accidental burns have also had prior notifications for other types of abuse or neglect.

Accidents↗
PubMed1998

Crystalloids, colloids and kids: a review of paediatric burns in intensive care.

This is a retrospective review of all burns patients admitted to a paediatric intensive care unit (PICU) over a 7 year period. Resuscitation fluid therapy and clinical course are presented. Ninety-eight new burns victims were admitted with a mortality rate of 10.2%, all in burns of greater than 25% body surface area (BSA). The incidence of ARDS was 20%, with an 18% mortality rate. Of 85 patients with burns greater than 5% BSA, 33 received the hospital-recommended colloid-based resuscitation formula, 46 received a combination of crystalloids and colloids and in 6 patients the resuscitation regimen was not able to be determined. The aetiology, age distribution, sex ratio, severity of burns and length of stay in hospital did not alter significantly over the study period. The number of burns admissions to PICU increased, as did their duration of intubation and ICU stay. The hospital-recommended resuscitation formula consistently underestimated the fluid volume required for adequate resuscitation. No statistically significant difference in adverse effects was found between the resuscitation groups. This study is unable to recommend a definitive approach to the fluid resuscitation of burns shock in paediatrics and the best approach is one of meticulous fluid resuscitation titrated on clinical effect.

Adolescent↗
PubMed1998

The influence of amino acid source on the stability of ascorbic acid in TPN mixtures.

This study was undertaken to investigate the stability of ascorbic acid and its primary degradation product, dehydroascorbic acid, in total parenteral nutrition (TPN) mixtures. The influence of the type of bag and the commercial source of amino acid on ascorbate degradation was examined, using a stability-indicating high-pressure liquid chromatography (HPLC) method. Ascorbic acid was most stable in multilayered bags, compared with ethylvinyl acetate (EVA) bags. Results indicated that, in multilayered bags, the initial rapid ascorbic acid degradation was greatest in TPN mixtures containing amino acid infusions without reducing activity. In contrast, degradation in TPN mixtures containing amino acids with reducing compounds (Vamin 14 and Freamine III 8.5%) was less than 10% of the added amount. Dehydroascorbic acid degraded approximately in parallel with ascorbic acid, and it contributed to the total available ascorbate activity. The addition of air to TPN mixtures in multilayered bags caused accelerated degradation of both ascorbic acid and dehydroascorbic acid. It is concluded that TPN mixtures compounded in multilayered bags can be safely assigned extended shelf lives, especially if compounded using an amino acid with reducing activity. This is principally due to the protective effect of the bag wall in preventing oxygen transmission, the cause of ascorbic acid oxidation, because oxygen transmission through the bag wall is minimized during storage. TPN mixtures stored in EVA bags should be administered within 2-4 d of compounding, depending on the amino acid infusion used.

Air↗
PubMed1998

Recombinant human granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) administered following cytotoxic chemotherapy have a similar ability to mobilize peripheral blood stem cells.

The availability of hematopoietic growth factors has greatly facilitated the mobilization and collection of peripheral blood stem cells (PBSC). It was the aim of this double-blind study to compare the PBSC-mobilizing efficacy of recombinant human G-CSF and GM-CSF when administered post-chemotherapy. Twenty-six patients with relapsed Hodgkin's disease were included in the study. Their median age was 31 years (range, 22-59) and 14 patients were males and 12 were females. Patients were pretreated with a median of eight cycles of cytotoxic chemotherapy, while 18 patients had undergone extended field irradiation. The patients received dexamethasone 24 mg days 1-7, melphalan 30 mg/m2 day 3, BCNU 60 mg/m2 day 3, etoposide 75 mg/m2 days 4-7, Ara-C 100 mg/m2 twice daily days 4-7 (Dexa-BEAM). Twelve patients were randomized to receive 5/microg/kg/day G-CSF and 14 patients to receive 5 microg/kg/day GM-CSF, both administered subcutaneously starting on day 1 after the end of Dexa-BEAM. Primary endpoints of the study were the number of CD34+ cells harvested per kg body weight on the occasion of six consecutive leukaphereses and the time needed for hematological reconstitution following autografting. Twenty-one patients completed PBSC collection, and six patients of the G-CSF group and nine of the GM-CSF group were autografted. No difference was observed with respect to the median yield of CFU-GM and CD34+ cells: 32.5 x 10(4)/kg vs 31.3 x 10(4)/kg CFU-GM, and 7.6 x 10(6)/kg vs 5.6 x 10(6)/kg CD34+ cells, for G-CSF and GM-CSF, respectively (U test, P= 0.837 and 0.696). High-dose chemotherapy consisted of cyclophosphamide 1.7 g/m2 days 1-4, BCNU 150 mg/m2 days 1-4, etoposide 400 mg/m2 days 1-4. All patients transplanted with more than 5 x 10(6) CD34+ cells/kg had a rapid platelet recovery (20 x 10(9)/l) between 6 and 11 days and neutrophil recovery (0.5 x 10(9)/1) between 9 and 16 days, while patients transplanted with less than 5 x 10(6)/kg had a delayed reconstitution, regardless of the kind of growth factor used for PBSC mobilization. In conclusion, our data indicate that in patients with Hodgkin's disease G-CSF and GM-CSF given after salvage chemotherapy appear to be not different in their ability to mobilize PBSC resulting in a similar time needed for hematological reconstitution when autografted following high-dose therapy.

Adult↗