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Biomedical subjects

C Martin

Publications and source records attributed to C Martin.

At least 361 records · Page 20Linked to original sources

Positional cloning of ZNF217 and NABC1: genes amplified at 20q13.2 and overexpressed in breast carcinoma.

We report here the molecular cloning of an approximately 1-Mb region of recurrent amplification at 20q13.2 in breast cancer and other tumors and the delineation of a 260-kb common region of amplification. Analysis of the 1-Mb region produced evidence for five genes, ZNF217, ZNF218, and NABC1, PIC1L (PIC1-like), CYP24, and a pseudogene CRP (Cyclophillin Related Pseudogene). ZNF217 and NABC1 emerged as strong candidate oncogenes and were characterized in detail. NABC1 is predicted to encode a 585-aa protein of unknown function and is overexpressed in most but not all breast cancer cell lines in which it was amplified. ZNF217 is centrally located in the 260-kb common region of amplification, transcribed in multiple normal tissues, and overexpressed in all cell lines and tumors in which it is amplified and in two in which it is not. ZNF217 is predicted to encode alternately spliced, Kruppel-like transcription factors of 1,062 and 1,108 aa, each having a DNA-binding domain (eight C2H2 zinc fingers) and a proline-rich transcription activation domain.

Amino Acid Sequence↗

Molecular epidemiology of HIV-1 infection in the Philippines, 1985 to 1997: transmission of subtypes B and E and potential emergence of subtypes C and F.

The molecular epidemiology of HIV-1 infection in the Philippines from 1985 to 1997 was investigated following subtyping of 54 (33 women, 21 men) prospectively collected clinical specimens using the heteroduplex mobility assay (HMA). In contrast with other Asian countries, subtype B accounted for most (70%) of the infections in the population studied, among female commercial sex workers (CSWs, 18 of 28), overseas contract workers (OCWs, 7 of 10), and men who have sex with men (MSM, 8 of 10). However, although viral specimens from HIV-seropositive persons diagnosed before 1993 (n = 16) were all of subtype B, diagnoses in more recent years (1993-present, n = 38) indicate the existence of subtypes E (29%), F (8%), and C (5%) in the population. Since its estimated introduction in the early 1990s, subtype E has accounted for 60% of the infections among female CSWs diagnosed after 1992 (n = 15). This genotype distribution shift occurred in parallel with a shift in transmission focus from the U.S. military bases to the the Philippine national capital region. So far, both events appear to have had no significant effect on the stability of HIV-1 transmission in the country. The recent identification of non-B subtypes in the Philippines may present novel insights on the dynamics of HIV-1 transmission in a high-risk but low-HIV prevalence setting in Asia.

Adult↗

The Henry Ford Health System.

The Henry Ford Health System is a large, vertically integrated health care delivery system, with its core service delivery team comprised of a 1000-person salaried medical group. Oncology services are coordinated through its Cancer Center, which organizes regional distribution of oncology services for residents of southeast Michigan. Oncology services are delivered through five regionally distributed sites, affording a vast majority of cancer services to be provided for patients a short distance from their homes. The System owns the largest health maintenance organization in Michigan (Health Alliance Plan) and its organizational structure affords the opportunity of offering purchasers specific oncology service contracting opportunities. Advantages of providing comprehensive oncology services through an integrated health system include: 1) standardized cancer care guidelines, 2) medical information exchange through an electronic medical record, 3) interdisciplinary cancer care provided by salaried physicians, minimizing potentially conflicting financial issues in treatment decisions, 4) state-of-the-art care afforded through availability of involvement in a large number of National Institutes of Health-sponsored clinical trials, 5) high standards of credentialing for oncology physicians, and 6) integrative managed care perspectives and continuous attention to cost and quality of care issues.

Cancer Care Facilities↗

Association of genes encoding P fimbriae, CS31A antigen and EAST 1 toxin among CNF1-producing Escherichia coli strains from cattle with septicemia and diarrhea.

Fifty-six CNF1-producing Escherichia coli strains isolated from cattle with diarrhea or septicemia were screened by PCR for the detection of pap, sfa, afa, clpG, or f17 adherence factor and EAST 1 toxin genes. All the isolates were pap-positive, in accordance with the close association of pap, CNF1 and alpha-hemolysin genes observed on human and porcine E. coli. Only the gene encoding the P adhesin of class III (PrsG) was detected. Genes encoding CS31A antigen (71%) and S fimbriae (34%) (but not Afa or F17) were detected among the bovine isolates. E. coli producing both CNF1 and plasmid-encoded CS31A is a new example of association between bacterial clones and plasmid-mediated virulence factors. The EAST 1 toxin-encoding gene was detected on 66% of the CNF1-producing isolates but was linked to CS31A rather than to CNF1. These results suggest a close association between EAST 1 toxin and the adherence factor CS31A among pathogenic bovine E. coli.

Adhesins, Escherichia coli↗

Surgical treatment of low-grade gliomas in the intraoperative magnetic resonance imager.

Radical resection of low-grade gliomas can decrease the incidence of recurrence, the time to tumor progression, and the incidence of malignant transformation. The authors present a series of 25 patients who underwent craniotomy and resection of low-grade tumor in an intraoperative magnetic resonance (MR) imager. This is an open configuration 0.5-tesla imager developed by The Brigham and Women's Hospital and General Electric, in which a patient can be placed to undergo surgery. Gross-total removal was accomplished under real-time image guidance. These intraoperative images allow definitive localization and targeting of the lesions and accommodate anatomical changes that may occur during surgery. The authors consistently found that the extent of abnormality seen on the intraoperatively obtained films of resection was larger than that apparent in the surgical field of view alone. Intraoperative imaging made accurate surgical identification of these abnormal areas and subsequent resection possible. Patients with tumors adjacent to or within motor or language cortex underwent resection while awake, with monitoring of neurological function. In these cases, an aggressive resection without increased neurological morbidity was accomplished using the image guidance in conjunction with serial testing. A 1-month postoperative MR image was obtained in all patients. These correlated with the final intraoperative images obtained after the resection was completed. Only one patient had a mild postoperative deficit that remained at the 1-month follow-up examination. As the long-term outcome in patients with low-grade gliomas has been shown to correspond to the degree of resection, surgical resection in which intraoperative MR imaging guidance is used can be an invaluable modality in the treatment of these tumors.

Journal Article↗

No association of apolipoprotein epsilon 4 allele with schizophrenia even in cognitively impaired patients.

Given the strong association of the apolipoprotein E (apoE) allele epsilon 4 (epsilon 4) with Alzheimer's disease or cognitive decline in elderly, we tested whether cognitive performance in schizophrenic subjects is associated with an increase in the frequency of the ApoE epsilon 4 allele. Our data indicate that in our sample: (1) there is no association between schizophrenia and the ApoE epsilon 4 allele; and (2) the ApoE epsilon 4 allele is not of major importance with regard to the cognitive decline observed in schizophrenia.

Adult↗

Cerebrospinal fluid mononuclear cell counts influence CSF HIV-1 RNA levels.

This study evaluated the relation between cerebrospinal fluid (CSF) mononuclear cells (MNC) and CSF HIV-1 RNA levels. HIV-1 RNA levels in plasma and CSF were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) in 58 consecutive patients with neurologic symptoms and late HIV-1 infection. The majority of the patients had no central nervous system (CNS) complication (n = 36), 11 had AIDS dementia complex (ADC) and 11 had CNS opportunistic infection (CNS OI). CSF cell counts were analyzed using a method that also evaluated hypocellular CSF (i.e., from 0.1 x 10(6) cells/L). A strong correlation was found between CSF MNC and CD4+ lymphocyte counts in blood (r = 0.58; p < .0001). HIV-1 RNA was detected in all plasma samples and in 38 of 58 (66%) of the cell-free CSF samples. CSF HIV-1 RNA was less frequently detected in patients with hypocellular CSF than in patients with normocellular or pleocytic CSF (13 of 28 patients [46%] versus 10 of 14 patients [71%] versus 15 of 16 patients [94%], respectively). The levels of CSF HIV-1 RNA correlated with the CSF MNC count (r = 0.61; p < .0001). The correlation also remained strong within the clinical subgroups of CNS asymptomatic patients (r = 0.55; p < .001) and ADC patients (r = 0.79; p < .001), but not among CNS OI patients (r = 0.19). Patients with CNS OI were found to have higher CSF HIV-1 RNA levels than the patients without evidence of CNS complication. Thus, a close relation was found between CSF HIV-1 RNA levels and CSF MNC counts. These data support the hypothesis that a substantial part of the virus in the CSF of HIV-1-infected patients is locally produced by CSF MNC.

AIDS Dementia Complex↗

Identification of novel L1CAM mutations using fluorescence-assisted mismatch analysis.

The L1CAM gene, which is located in Xq28 and codes for a neuronal cell adhesion molecule, is involved in three distinct conditions: HSAS (hydrocephalus-stenosis of the aqueduct of Sylvius), MASA (mental retardation, aphasia, shuffling gait, adductus thumbs), and SPG1 (spastic paraplegia). Molecular analysis of the L1CAM gene is labor-intensive because of the size of the coding region, which is fragmented in numerous exons, and because of the great allelic heterogeneity and distribution of the mutations. The FAMA (fluorescent assisted mismatch analysis) method combines the excellent sensitivity of the chemical cleavage method for scanning PCR fragments larger than 1 kb and the power of automated DNA sequencers. In order to optimize this method for L1CAM, we divided the gene into nine genomic fragments, each including three to four exons. These fragments were PCR-amplified using nine sets of primers containing additional rare universal sequences. A second-stage PCR, per formed with the two dye-labeled universal primers, allowed us to generate 1-kb-labeled fragments, which were then submitted to the chemical cleavage analysis. Among 12 French families with HSAS and/or MASA, we identified nine distinct L1CAM mutations, seven of which were novel, and an intronic variation. This study demonstrates that FAMA allows rapid and reliable detection of mutations in the L1CAM gene and thus represents one of the most appropriate methods to provide diagnosis for accurate genetic counseling in families with HSAS, MASA, or SPG1.

Aphasia↗

Cerebral vasoconstriction during sustained ventricular tachycardia induces an ischemic stress response of brain tissue in rats.

Arterial hypotension can cause cerebral ischemia when the autoregulation of the cerebral circulation is exhausted. We hypothesized that sudden cerebral vasoconstriction induced by moderate hypotensive, but hemodynamically stable, sustained ventricular tachycardias (MHT-VT) further compromises cerebral blood flow (CBF) and induces an ischemic stress response of the brain. CBF-measurements and morphological studies were performed without and with blockade of alpha-adrenergic receptors in order to determine the impact of MHT-VF on brain perfusion and brain tissue. Using a model of MHT-VT, CBF was measured with colored microspheres in 71 rats during control conditions. after the onset of MHT-VT, after the onset of moderate hypotensive hypovolemia (MHH), and after additional non- selective (alpha-blockade with phentolamine and selective alpha1-blockade with prazosin, respectively (0.2-0.4 mg/kg body weight). Plasma catecholamine concentrations were measured in 18 additional rats during control conditions. during MHT-VT and during MHH. The occurrence of heat shock protein (hsp) 72 and activated microglia in the brain was analysed in 18 additional rats in controls, after MHT-VT and MHH. After 20 min of the respective induced hypotension, control conditions were restored for a period of 8 h, by stopping VT or by infusion of isotonic saline solution. CBF was 0.98+/-0.16 (mean+/-S.D.) ml/g/min during control conditions at an arterial pressure of 118+/-13 mmHg, 0.50+/-0.05 ml/g/min (P<0.05 v control) during MHT-VT (76+/-4 mm Hg) and 0.75+/-0.14 ml/g/min (P<0.05 v control and v MHT-VT ) during MHH (71 +/- 8 mm Hg). CBF was better preserved with non-selective alpha-blockade during MHT-VT (0.78+/-0.15 ml/g/min, P<0.05 v MHT-VT and control) as well as with selective alpha1-blockade (0.67+/-0.08 ml/g/min, P<0.05 v MHT-VT and control). Plasma catecholamines were elevated during MHT-VT (P<0.05 v control) but not during MHH (P = N.S. v control). hsp 72 and activated microglia were found in hippocampal regions only after MHT-VT (P<0.05 v control and MHH). These morphological changes were prevented by non-selective alpha-blockade. Stable sustained MHT-VT further reduce the already compromised CBF leading to morphological alterations in the brain which are characteristic of an early ischemic stress response. alpha-Blockade prevents alpha1-adrenergic vasoconstriction and attenuates cerebral hypoperfusion.

Adrenergic alpha-Antagonists↗

Descriptive anatomy of the human auditory tube.

The aim of this study was to correlate current morphologic data relating to the lumen of the auditory tube. Four methods were used: dissection under the operating microscope; microendoscopy of the tubal lumen; optical and electron microscope histology; and MR or CT imaging. The auditory tube consists of two unequal cones, a small posterior third, fixed and osseous (protympanum), and a mobile fibrocartilaginous anterior two-thirds, both joined by the tubal isthmus, a short constriction which is pseudosphincteric at endoscopy. The tensor veli palatini muscle (TVPM) and the levator veli palatini muscle (LVPM) are the chief muscles that vary the tubal lumen of the fibrocartilaginous portion, which is collapsed at rest. CT and especially MR imaging allows their observation in static conditions. Serial histologic sections reveal the continuity between the TVPM and the tensor tympani muscle. The main cartilage framing the lumen varies in shape according to the level surveyed. The tubal mucosa is lined with an epithelium combining ciliated and mucus cells, involved in mucociliary drainage and gas exchanges in the auditory tube. These morphologic elements represent a basis for study of tubal physiology and for planning treatment in dysfunctions of the auditory tube.

Adolescent↗

FK506 (Tacrolimus) decreases the cytotoxicity of cyclosporin A in rat hepatocytes in primary culture: implication of CYP3A induction.

Tacrolimus (FK506) and cyclosporin A (CsA) are two potent immunosuppressants mainly metabolized by hepatic cytochrome P-450 3A (CYP3A) monooxygenase. The aim of this study was to compare the toxic effects of the two drugs on hepatocytes in primary culture as a function of their metabolism and to explore the variations of cytotoxicity when both drugs are associated. The cytotoxicity of FK506 and CsA, as expressed by their IC50 values, was of the same order but with a switch according to whether hepatocytes were induced or uninduced by dexamethasone, CsA being more toxic in its native form and FK506 through its metabolism. Similar results were obtained with the intracellular calcium content. When both drugs were associated at their IC50 values, the expected additive cytotoxic effect was not observed. Moreover, when small quantities of FK506 were added to CsA at its IC50, cell viability improved in the induced cultures. It is hypothesized that the interaction between the two drugs relies on a mechanism involving both competition of FK506 and CsA for CYP3A and of their immunophilin complexes for a common site on the calcineurin-calmodulin complex.

Animals↗

Antenatal rupture of a diverticular rectal duplication with neonatal perineal fistulization.

A cystic pelvic malformation was found in a fetus on antenatal sonography (US) at 26 weeks of gestational age that was no longer present 3 weeks later on control US. The male child presented at birth with a right-sided perineal mass that fistulized with meconial drainage. A radiopaque enema showed a low posterior rectal fistula filling a poorly delineated pouch. Surgery performed through a posterior sagittal approach allowed identification and closure of the fistula and pouch drainage. The diagnosis of a diverticular rectal duplication was considered, although no intestinal lining was observed macroscopically or histologically. The child's anorectal function was normal after a 20-month follow-up. Labeling of the malformation and embryological hypotheses are discussed since the case does not fulfill all the criteria of an intestinal duplication. Surgical techniques are discussed, with an emphasis on the sagittal posterior approach.

Diverticulum↗

IL-10 inhibits ICAM-1 expression on human Langerhans cells but not on keratinocytes, dermal endothelial cells or fibroblasts.

Intercellular adhesion molecule-1 (ICAM-1) is regularly expressed or inducible on all major cutaneous cell populations including Langerhans cells, keratinocytes, endothelial cells and dermal fibroblasts. ICAM-1 is induced in the skin under inflammatory conditions and plays an important role in the activation of T cells. Interleukin-10 (IL-10) is a pluripotent immunosuppressive cytokine that inhibits proliferation of T cells via inhibition of antigen-presenting cells including Langerhans cells. We demonstrates that IL-10 inhibits baseline and also cytokine-stimulated ICAM-1 expression on human Langerhans cells, which has previously been shown in the murine system. No effect of IL-10 was seen on human dermal vascular endothelial cells, which like Langerhans cells are also able to present antigen. Additionally, no inhibitory effect of IL-10 was observed on the ICAM-1 expression of keratinocytes and dermal fibroblasts. As IL-10 only weakly suppresses MCH II on human Langerhans cells, inhibition of ICAM-1 and other accessory molecules by IL-10 seems to be an important mechanism inhibiting the antigen-presenting function of human Langerhans cells.

Dermis↗

Bilateral dissection of the internal carotid artery at the base of the skull due to blunt trauma: incidence and severity.

Between January 1, 1992 and December 31, 1996, a total of 1095 head trauma vicims were admitted in our intensive care unit. If CT scans demonstrated ischemic brain lesions, arteriography to visualize supraaortic vessels was performed. Carotid artery dissection was observed in ten patients (0.91%) and was bilateral in eight patients (0.73%). In the bilateral carotid artery dissection (BCAD) group, there were five women and three men, with a mean age of 35.2 years (range: 17 to 54 years). Injuries resulted from traffic accidents in seven patients and a fall in one patient. Upon admission, six patients presented with alteration of consciousness and three with hemiplegia or hemiparesia, associated with aphasia in two cases. In two other cases, hemiplegia occurred 24 hr and 13 days after the accident. All patients had brain infarction, which was unilateral in five cases and bilateral in three cases. The severity of lesions was graded on the basis of arteriographic findings as follows: Type I, wall involvement without significant stenosis or dilation; Type II, arterial dissection with stenosis >70% (Type IIA) or dilatation >50% (Type IIB) and the normal diameter of the proximal or distal internal carotid artery; and Type III, thrombosis of the internal carotid artery. Lesions were asymmetrical in six patients, including two with Type II and III lesions and four with Type I and II lesions, and symmetrical in two patients, including one with bilateral Type III lesions and one with bilateral Type II lesions. Surgery was performed in two patients with Type II lesions, including one case associated with contralateral carotid thrombosis. The intrapetrous carotid artery was exposed by an ear-nose-throat (ENT) surgeon and repaired by interposition grafting. Follow-up in these two surgical cases was 28 and 31 months. In the remaining six cases, medical treatment was performed. Outcome in nonsurgical cases was variable: death in two cases at 31 and 43 days after the accident, severe permanent hemiplegia in two cases, and minimal or no sequels in two cases. Following blunt trauma, arteriography of supraaortic vessels should be performed to detect BCAD in any patient with immediate or delayed neurologic symptoms that cannot be explained by CT-scan findings. To better understand the natural course of these lesions and define the indications for surgery, we propose a three-grade classification according to arteriographic findings. If surgery is undertaken, vein grafting should be performed following resection of the carotid artery lesions.

Adult↗

[Virtual laparoscopic anatomy of the esophagogastric junction].

The anatomy of the GE junction is represented by computer synthetised pictures. This method allows to represent different organs from different angles, emphasis being put on the laparoscopic angle of vision. This should improve anatomical comprehension. The synthetic pictures have been constructed in a figurative representation. Fatty tissues have been omitted whereas the peritoneal layers covering organs and defining spaces are enhanced.

Anatomy↗