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Biomedical subjects

H Martin

Publications and source records attributed to H Martin.

At least 55 records · Page 3Linked to original sources
PubMed2001

Dose-reduced conditioning for allografting in 44 patients with chronic myeloid leukaemia: a retrospective analysis.

This retrospective study describes the outcome of patients with chronic myeloid leukaemia after allografting using dose-reduced conditioning with fludarabine and busulphan. Forty-four Philadelphia chromosome (Ph)-positive patients were transplanted in nine German centres; 26 patients were in chronic phase, 11 in accelerated phase and seven in blast crisis. Thirty-four patients achieved complete remission, with 18 alive and disease-free at a median follow-up of 562 d (range 244-922 d). Grade II-IV acute graft-versus-host disease (GVHD) incidence was 43%. Twenty patients died, 15 of causes unrelated to relapse. Risk factors predisposing to graft failure by univariate analysis were an unrelated donor (8/23 compared with a related donor 2/21, P = 0.07) and interferon therapy within 90 d of transplant (4/6 versus 3/17, P = 0.025). At the last follow-up, of 31 patients for whom molecular or cytogenetic data were available, 16 (52%) were polymerase chain reaction-negative, and seven (23%) were Ph-negative by fluorescent in situ hybridization. These findings demonstrate that dose-reduced conditioning with fludarabine and busulphan provides durable engraftment and a low rate of relapse. However, in this population, many of whom were not eligible for high-dose conditioning due to age, reduced performance status, previous complications or extensive pre-treatment, these data highlight the need for effective anti-infectious and GVHD prophylaxis. In addition, this study supports the discontinuation of interferon therapy at least 90 d before transplant

Adult↗
PubMed2001

A new approach to evaluating intestinal acute graft-versus-host disease by transabdominal sonography and colour Doppler imaging.

An objective and non-invasive method to assess the extent, severity, course and prognosis of acute graft-versus-host disease (aGvHD) of the gastrointestinal tract would be of great importance. As high-resolution ultrasonography (HRU) and colour Doppler imaging (CDI) are used in inflammatory and ischaemic bowel diseases, we introduced these techniques to evaluate acute intestinal GvHD. In this study, 12 patients with suspected intestinal and/or severe cutaneous aGvHD were investigated by HRU and CDI. The structure and thickness of the bowel wall and the blood flow pattern in the superior mesenteric artery (SMA) as well as in the bowel wall were evaluated. All patients showed thickened bowel wall segments, especially in the ileocaecal region. Even in patients without any clinical signs of intestinal involvement (3/12), sonographic changes were observed. In six patients with severe diarrhoea, sonographic signs of secretory diarrhoea were observed. In 4/12 patients, an increased arterial blood flow in the bowel wall was demonstrated as a typical characteristic of an inflammatory bowel process. In contrast, in 4/12 patients, ischaemic bowel wall lesions with high-resistance flow pattern in the SMA were found. These patients did not respond to immunosuppressive therapy and died. In conclusion, HRU is a useful tool for detecting acute bowel GvHD even before clinical symptoms. Moreover, HRU and CDI can be applied to define the severity of aGvHD and to identify patients with a poor prognosis.

Acute Disease↗
PubMed2001

Incidence of endomycoses in autopsy material.

From 1970 to 1993, 93 endomycoses confirmed by postmortem examination were diagnosed in the autopsy material of the Berlin Charité, a large hospital with an average of 1,500 Hospital beds and maximum medical care. These comprised 51 candidoses (54.8%), 24 aspergilloses (36.5%), five cryptococcoses (5.4%), one zygomycosis, one trichosporosis and one coccidioidomycosis. This corresponded to 0.7% of the 13,275 deceased persons autopsied during this period. The frequency of autopsy was 85.3%. In 3,770 cases (2,418 adults and 1,352 children), brain dissection was performed. An adequate clinical putative diagnosis was made in only six out of 28 patients (18 adults, 10 children) with histologically confirmed cerebral mycosis: 11 candidoses (39.3%), 10 aspergilloses (35.7%) five cryptococcosis (17.8%), one trichosporosis and one coccidioidomycosis. About 80% of the mycoses of the CNS thus remained undetected while the patients were alive. The observations made in the present paper underscore the importance of clinical autopsy in endomycoses.

Adult↗
PubMed2001

Intraductal component in invasive breast cancer: analysis of 250 resected surgical specimens.

The presence of an intraductal component together with an invasive carcinoma is known to be associated with a higher rate of local recurrence. The results of reviewing 250 resected surgical specimens from patients with breast cancer are reported. Two-hundred and fifty mastectomy specimens of invasive breast cancer were retrospectively analysed in order to determine intraductal components within the primary tumour as well as additional foci. In addition to the invasive carcinoma, a ductal carcinoma in situ (DCIS) of varying extent was identified in 127 instances. The intraductal components were marginal in 27.6% of the cases, extensive in 61.4%, and predominant in 11.0%. In addition, 21 patients had isolated DCIS only. Such in situ components were more frequently found in the age group younger than 41 years and in premenopausal patients. Seventeen percent of carcinomas associated with an intraductal component were multicentric in location as opposed to only 5% of the breast lesions without an intraductal component. The highest proportion of residual tumour was seen in poorly differentiated invasive carcinomas with DCIS. Intraductal carcinomas with intraductal component tended to have a higher incidence of a positive surgical margin. Small carcinomas with an extensive in situ component require careful surgical management in order to achieve a tumour-free margin.

Journal Article↗
PubMed2001

Peroxide sensors for the fission yeast stress-activated mitogen-activated protein kinase pathway.

The Schizosaccharomyces pombe stress-activated Sty1p/Spc1p mitogen-activated protein (MAP) kinase regulates gene expression through the Atf1p and Pap1p transcription factors, homologs of human ATF2 and c-Jun, respectively. Mcs4p, a response regulator protein, acts upstream of Sty1p by binding the Wak1p/Wis4p MAP kinase kinase kinase. We show that phosphorylation of Mcs4p on a conserved aspartic acid residue is required for activation of Sty1p only in response to peroxide stress. Mcs4p acts in a conserved phospho-relay system initiated by two PAS/PAC domain-containing histidine kinases, Mak2p and Mak3p. In the absence of Mak2p or Mak3p, Sty1p fails to phosphorylate the Atf1p transcription factor or induce Atf1p-dependent gene expression. As a consequence, cells lacking Mak2p and Mak3p are sensitive to peroxide attack in the absence of Prr1p, a distinct response regulator protein that functions in association with Pap1p. The Mak1p histidine kinase, which also contains PAS/PAC repeats, does not regulate Sty1p or Atf1p but is partially required for Pap1p- and Prr1p-dependent transcription. We conclude that the transcriptional response to free radical attack is initiated by at least two distinct phospho-relay pathways in fission yeast.

Activating Transcription Factor 1↗
PubMed2001

HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway.

HMG-CoA reductase inhibitors (statins) have been developed as lipid-lowering drugs and are well established to reduce morbidity and mortality from coronary artery disease. Here we demonstrate that statins potently augment endothelial progenitor cell differentiation in mononuclear cells and CD34-positive hematopoietic stem cells isolated from peripheral blood. Moreover, treatment of mice with statins increased c-kit(+)/Sca-1(+)--positive hematopoietic stem cells in the bone marrow and further elevated the number of differentiated endothelial progenitor cells (EPCs). Statins induce EPC differentiation via the PI 3-kinase/Akt (PI3K/Akt) pathway as demonstrated by the inhibitory effect of pharmacological PI3K blockers or overexpression of a dominant negative Akt construct. Similarly, the potent angiogenic growth factor VEGF requires Akt to augment EPC numbers, suggesting an essential role for Akt in regulating hematopoietic progenitor cell differentiation. Given that statins are at least as potent as VEGF in increasing EPC differentiation, augmentation of circulating EPC might importantly contribute to the well-established beneficial effects of statins in patients with coronary artery disease.

Animals↗
PubMed2001

Tescalcin, a novel gene encoding a putative EF-hand Ca(2+)-binding protein, Col9a3, and renin are expressed in the mouse testis during the early stages of gonadal differentiation.

To identify genes that are differentially expressed in the developing testis we used representational difference analysis of complementary DNA from gonads of mouse embryos at 13.5 days postcoitum (dpc). Three genes were identified. One of them was a novel gene termed tescalcin that encoded a putative EF-hand Ca(2+)-binding protein. The open reading frame consisted of 642 nucleotides encoding a protein with 214 amino acids. Analysis of the predicted amino acid sequence revealed an N:-myristoylation motif and several phosphorylation sites in addition to an EF-hand Ca(2+)-binding domain. TESCALCIN: messenger RNA (mRNA) was present in fetal testis, but not in ovary or mesonephros, and was restricted to the testicular cords. Its expression was first detected in the male gonad at 11.5 dpc and demonstrated a pattern consistent with a role in the testis at the early stages of testis differentiation. Tescalcin is expressed in the testis of Kit(W/W-v) mice, indicating that it is not dependent on the presence of germ cells. The other two genes identified were collagen IX alpha3 (Col9a3) and RENIN: Col9a3 expression was present at low levels in male and female gonads at 11.5 dpc. Thereafter, it was markedly up-regulated in the male, but remained very low in the female. Expression of Col9a3 was restricted to testicular cords and was also detected in testis of Kit(W/W-v) mice. RENIN: mRNA was first detected in testis at 12.5 dpc, increased thereafter, and reached a peak at 16.5 dpc. RENIN: mRNA was localized in cells of the interstitium and cells at the border between the gonad and mesonephros. Expression of RENIN: in the ovary was not detected using standard conditions.

Amino Acid Sequence↗
PubMed2001

Reactive hyperemia and interleukin 6, interleukin 8, and tumor necrosis factor-alpha in the diagnosis of early-onset neonatal sepsis.

OBJECTIVE: To evaluate the diagnostic value of peripheral circulatory reactive hyperemia and serum levels of interleukin-6 (IL-6), IL-8, and tumor necrosis factor-alpha (TNF-alpha) in early-onset neonatal sepsis. METHODS: Reactive hyperemia in the dorsal hand and serum levels of IL-6, IL-8, and TNF-alpha were studied in newborn infants (n = 32; gestational age 39 +/- 3 weeks) who had been admitted to the neonatal unit because of suspected sepsis <48 hours after birth. On admission, reactive hyperemia after a standardized arterial occlusion was measured with laser Doppler technique, and blood samples were taken for cytokine analyses. On the basis of predetermined criteria, the infants subsequently were classified as septic (n = 12) or not (n = 20). RESULTS: The degree of reactive hyperemia was higher in the group with sepsis (median + 170% perfusion increase) than in that without (+37%). On admission, serum levels of IL-6, IL-8, and TNF-alpha all were higher in septic (median values: 1620, 331, and 22 pg/mL, respectively) than in nonseptic neonates (median values: 42, 63, and 13 pg/mL, respectively). In the group with sepsis, the degree of reactive hyperemia correlated to log IL-6 (r = 0.80) and log IL-8 values (r = 0.71). CONCLUSION: Newborn infants with septicemia have increased reactive hyperemia and elevated cytokine levels very early in their disease. Reactive hyperemia in skin can be analyzed at the bedside and noninvasively and therefore may serve as an additional diagnostic tool in neonatal sepsis.

Biomarkers↗
PubMed2001

Colonic lymphoid hyperplasia in melanosis coli.

We describe the case of a patient with Rett syndrome, a syndrome characterized by progressive infant encephalopathy, developmental delay, dementia, autism, ataxia, microcephaly, spastic paraparesis, and autonomic neuropathy with constipation. At colonoscopy, multiple foci of tiny white, sessile, polypoid lesions were seen throughout the colon and rectum, mimicking the appearances of small hyperplastic or adenomatous polyps, associated with generalized melanosis coli. This is the first case to our knowledge describing melanosis coli in a patient with Rett syndrome. As melanosis pigment deposition is characteristically not seen in lymphoid tissue, the lymphoid tissue was identifiable at endoscopy as multiple white nodules mimicking generalized colonic polyposis throughout the colon. We discuss the likely mechanisms of lymphoid hyperplasia and coexistent melanosis coli in Rett syndrome.

Abdominal Pain↗
PubMed2000

Further studies on the GS element. A novel mycobacterial insertion sequence (IS1612), inserted into an acetylase gene (mpa) in Mycobacterium avium subsp. silvaticum but not in Mycobacterium avium subsp. paratuberculosis.

We have recently described the GS element, found in Mycobacterium avium subsp. paratuberculosis (MAP), Mycobacterium avium subsp. silvaticum (MAS) and some isolates of Mycobacterium avium subsp. avium serotype 2 (MAAs2), which contains a set of genes of low GC% content, putatively associated with the biosynthesis, modification and transference of fucose to cell wall glycopeptidolipids. Here we describe a further gene of low GC% content (mpa), within the GS element in MAP. mpa is a putative acetyltransferase with homology to genes directly responsible for host specificity and virulence in Salmonella typhimurium and Shigella flexneri. Unlike other GS genes, strong homologues of mpa have not been found in related species, including Mycobacterium tuberculosis (MTB). In MAP, mpa encodes an ORF of 445aa, however, in MAS and MAAs2 mpa contains a single inserted copy of a novel insertion sequence. This element (IS1612) has two sets of inverted repeats at each terminus and encodes two ORFs with good homologies to transposase and helper proteins of IS21 (E. coli) and IS1415 (R. erythropolis). Sequence comparisons between mpa in MAP and MAS indicate the target site for IS1612 is duplicated on insertion to give a direct repeat at each end of the element. Immediately, downstream of the mpa gene in both MAP and MAS are a group of three genes with good homology to the daunorubicin resistance cluster. This cluster has a high GC% content which suggests a 'border' for the GS element. A short motif present at the beginning of this cluster matches with an inverted repeat of this motif at the beginning of the first gene in the GS element. This encapsulates the whole of this group of low GC% genes in MAP and further suggests its cassette-like nature. Homologues of the GS element in MTB show a marked similarity of organisation, suggesting a parallel role for these genes in both pathogens.

Acetylesterase↗
PubMed2000

Impaired endothelial function and increased carotid stiffness in 9-year-old children with low birthweight.

BACKGROUND: Low birthweight (LBW) has been associated with an increased incidence of adult cardiovascular disease. Endothelial dysfunction and loss of arterial elasticity are early markers of hypertension and atherosclerosis. We studied the prevalence of these markers in 44 healthy, prepubertal (age 9+/-1.3 years) children, 22 with LBW for age. METHODS AND RESULTS: Endothelial function in skin was tested with the local application of acetylcholine (inducing endothelium-dependent vasodilation) and nitroglycerin (endothelium-independent vasodilation), and local perfusion changes were measured with the laser Doppler method. The elastic properties of the abdominal aorta and common carotid artery were measured with an ultrasonic vessel-wall tracking system. Endothelium-dependent vasodilation was lower in children with LBW (88+/-33 perfusion units [PU]) than in normal-birthweight controls (133+/-34 PU, P<0.001). There was no difference in aortic or carotid elasticity between the 2 groups, but a negative correlation was found between birthweight and stiffness of the carotid artery wall (r=-0.45, P<0.01). Endothelium-independent vasodilation and blood pressure were similar in the 2 groups. CONCLUSIONS: Schoolchildren with a history of LBW show impaired endothelial function and a trend toward increased carotid stiffness. These findings may be early expressions of vascular compromise, contributing to susceptibility to disease in adult life.

Acetylcholine↗
PubMed2000

The inhibition of flavoproteins by phenoxaiodonium, a new iodonium analogue.

Iodonium compounds, especially diphenylene iodonium and iodonium diphenyl are used extensively as inhibitors of NADH-ubiquinone reductase and NADPH oxidase activity. Here, the use of a new iodonium compound, phenoxaiodonium is reported. The IC(50) of neutrophil superoxide production, measured using the superoxide dismutase inhibitable rate of cytochrome c reduction, was approximately 0.75 microM, while 50% inhibition of mitochondrial respiration, measured by the rate of oxygen uptake using a Clark type oxygen electrode, was at approximately 20 microM. The inhibition of oxidation of xanthine to urate by xanthine oxidase was also studied, giving a K(i) of 0.2 microM. Inhibition of nitric oxidase synthase (NOS: from rat brain) by 0.2 microM phenoxaiodonium was equivalent to 1 mM N(G)-nitro-L-arginine methyl ester HCl (L-NAME), that is total abolition of activity. We conclude that phenoxaiodonium is an extremely good inhibitor of flavo-enzymes, but like diphenylene iodonium and iodonium diphenyl, will be of limited use as a pharmacological tool for the elucidation of the involvement of such enzymes in specific cellular functions.

Animals↗
PubMed2000

Early detection of aspergillus infection after allogeneic stem cell transplantation by polymerase chain reaction screening.

Invasive aspergillosis (IA) has become a major cause of mortality in patients after allogeneic stem cell transplantation. To assess the potential of prospective polymerase chain reaction (PCR) screening for early diagnosis of IA, 84 recipients of an allogeneic stem cell transplant were analyzed with the investigators blinded to clinical and microbiologic data. Of 1193 blood samples analyzed, 169 (14.2%) were positive by PCR. In patients with newly diagnosed IA (n=7), PCR positivity preceded the first clinical signs by a median of 2 days (range, 1-23 days) and preceded clinical diagnosis of IA by a median of 9 days (range, 2-34 days). Pretransplantation IA (relative risk [RR], 2.37), acute graft-versus-host disease (RR, 2.75), and corticosteroid treatment (RR, 6.5) were associated with PCR positivity. The PCR assay revealed a sensitivity of 100% (95% confidence interval [CI], 48%-100%) and a specificity of 65% (95% CI, 53%-75%). None of the PCR-negative patients developed IA during the study period. Thus, prospective PCR screening allows for identification of patients at high risk for subsequent onset of IA.

Adolescent↗
PubMed2000

Cryopreserved rat liver slices: a critical evaluation of cell viability, histological integrity, and drug-metabolizing enzymes.

The effects of a cryopreservation procedure on the biochemical, morphological and functional integrity of rat liver slices just after thawing and after 24 h culture were evaluated. Freshly prepared slices were incubated in modified University of Wisconsin solution containing 50% fetal calf serum and 10% dimethyl sulfoxide for 20 min on ice prior to a rapid cooling in liquid nitrogen. After 10-40 days, slices were thawed rapidly at 42 degrees C. Total protein content and (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) (MTT) reduction were well preserved at thawing, whereas ATP content was markedly decreased relative to freshly prepared slices (-83%). The major microscopic findings in sections of just-thawed liver slices consisted of hepatocellular dissociation and minimal apoptosis. The qualitative profile of antipyrine (AP) metabolism was well preserved in cryopreserved slices, but the amounts of phase I and phase II AP metabolites produced over a 3-h incubation period were markedly reduced relative to fresh slices (-58 to -71%). When cryopreserved slices were cultured for 24 h after thawing, the viability was markedly reduced, as reflected by the almost complete absence of MTT reduction and the loss of ATP content. Histological examinations showed extensive cellular necrosis. The amount of AP metabolites produced by cryopreserved slices was similar after a 3- or a 24-h culture period, indicating that AP metabolism capacities were lost at 24 h culture. In conclusion, our results suggest that cryopreserved rat liver slices may be a useful model for short-term in vitro determination of drug metabolism pathways. Further work is required to extend their use for toxicological studies.

Adenosine↗
PubMed2000

[Analysis of the dynamics of the ciliary muscle during accommodation].

BACKGROUND: The magnitude of anterioaxial shift of the human ciliary muscle during accommodation and its ceasing of ciliary function with advanced age are still unknown. PATIENTS AND METHODS: A total 105 patients (aged 10-91 years) were examined by high-resolution ultrasound biomicroscopy during disaccommodation and voluntary accommodation. Accommodative changes in the total area of the ciliary muscle and in the outer contour were quantified with a specially developed software program for automatic contour determination. RESULTS: A significant anterior shift independent of age was observed in the total area of the ciliary muscle and defined points on the outer contour of the muscle in the range of 56-121 microns, while the inward displacement was less obvious. A decrease in the magnitude of configurational changes during accommodation was observed with age. CONCLUSION: The new software program could be useful in further investigations of the accommodative process and evaluation of the potential causes of presbyopia.

Accommodation, Ocular↗
PubMed2000

[Significance of the markers of aging].

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 ageing and how can it be measured? For this, so-called markers or biological markers of ageing are used which are measurable indicators of ageing 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 discussion of the ILSE study.

Adult↗