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Biomedical subjects

Paul Martin

Publications and source records attributed to Paul Martin.

At least 127 records · Page 7Linked to original sources
PubMed2002

Dynamic analysis of dorsal closure in Drosophila: from genetics to cell biology.

Throughout development a series of epithelial bendings, sweepings, and fusions occur that collectively give shape to the embryo. These morphogenetic movements are driven by coordinated assembly and contraction of the actomyosin cytoskeleton in restricted populations of epithelial cells. One well-studied example of such a morphogenetic episode is dorsal closure in Drosophila embryogenesis. This process is tractable at a genetic level and has recently become the focus of live cell biology analysis because of the availability of flies expressing GFP-fusion proteins. This marriage of genetics and cell biology is very powerful and is allowing the dissection of fundamental signaling mechanisms that regulate the cytoskeletal reorganizations and contractions underlying coordinated tissue movements in the embryo.

Actins↗
PubMed2002

Wound healing recapitulates morphogenesis in Drosophila embryos.

The capacity to repair a wound is a fundamental survival mechanism that is activated at any site of damage throughout embryonic and adult life. To study the cell biology and genetics of this process, we have developed a wounding model in Drosophila melanogaster embryos that allows live imaging of rearrangements and changes in cell shape, and of the cytoskeletal machinery that draws closed an in vivo wound. Using embryos expressing green fluorescent protein (GFP) fusion proteins, we show that two cytoskeletal-dependent elements -- an actin cable and dynamic filopodial/lamellipodial protrusions -- are expressed by epithelial cells at the wound edge and are pivotal for repair. Modulating the activities of the small GTPases Rho and Cdc42 demonstrates that these actin-dependent elements have differing cellular functions, but that either alone can drive wound closure. The actin cable operates as a 'purse-string' to draw the hole closed, whereas filopodia are essential for the final 'knitting' together of epithelial cells at the end of repair. Our data suggest a more complex model for epithelial repair than previously envisaged and highlight remarkable similarities with the well-characterized morphogenetic movement of dorsal closure in Drosophila.

Actins↗
PubMed2002

Hepatitis C infection and the patient with end-stage renal disease.

Hepatitis C virus (HCV) remains common in patients with end-stage renal disease (ESRD) and is an important cause of liver disease in this population. Acquisition of HCV infection continues to occur in dialysis patients because of nosocomial spread. The natural history of HCV in dialysis patients remains controversial because the course of HCV typically extends over decades, whereas dialysis patients have higher morbidity and mortality rates than those of the general population limiting long-term follow-up. However, recent reports suggest that HCV infection affects the survival of chronic dialysis patients as well as renal transplant (RT) recipients. The severity of preexisting liver disease on pretransplantation liver biopsy may provide useful prognostic information about clinical outcome after RT; liver biopsy should be incorporated in the evaluation and management of RT candidates with HCV. Recent surveys with long-term follow-up have documented adverse effects of HCV on patient and graft survival. Use of renal grafts from HCV-infected donors in recipients with HCV does not appear to result in a greater burden of liver disease albeit with short-term follow-up. There is only limited data about interferon (IFN) therapy in chronic dialysis patients, although sustained responses are reported. Preliminary data on IFN plus ribavirin therapy in dialysis patients with hepatitis C have given encouraging results, but randomized trials are needed. Interferon remains contraindicated post-RT because of concern about precipitating graft dysfunction.

Cross Infection↗
PubMed2002

Hepatitis B surface antigenemia in chronic hemodialysis patients: effect of hepatitis B immunization.

OBJECTIVE: Hemodialysis patients with hepatitis B surface antigen (HBsAg) are considered to have the hepatitis B virus (HBV) and are segregated to limit transmission. However, transient de novo HBsAg has been identified in hemodialysis patients shortly after vaccination. Our hypothesis is that immunization rather than actual HBV infection is the most common cause of de novo HBsAg among hemodialysis patients. METHODS: We performed a prospective study between January, 1998 and June, 2000 of de novo HBV infection in over 2400 hemodialysis patients who were screened monthly for HBsAg using a standard enzyme immunoassay. Positive results were confirmed with a neutralization assay. If the confirmatory test was positive, anti-hepatitis B core antibody IgM testing was performed. RESULTS: We identified nine patients with de novo HBsAg confirmed with the neutralization assay. In eight of the nine patients with de novo HBsAg (89%), HBsAg was temporally related to HBV immunization. In none of these eight patients was there a detectable anti-hepatitis B core antibody IgM, an elevated ALT level, or clinical history suggestive of recent hepatitis. The mean age (+/- SD) of the four men and four women was 56.4 +/- 18.8 yr. HBsAg was detectable within 3 days of immunization in most patients. CONCLUSION: Our results suggest that HBV immunization is the most common cause of detectable HBsAg in hemodialysis patients. Hemodialysis patients should not be screened for HBV within a week of immunization, and caution should be exercised when interpreting HBsAg seropositivity within 4 wk of HBV immunization.

Adult↗
PubMed2001

Chronic Hepatitis C.

Infection with hepatitis C virus (HCV) accounts for 40% of cases of chronic liver disease in the United States and is now the most common indication for liver transplantation. Estimates suggest that 4 million people (1.8%) of the American population are or have been infected with HCV. Currently, the treatment of choice for patients with chronic HCV infection is recombinant interferon alfa with ribavirin. Pegylated interferons are a promising new development, and in combination with ribavirin, they will rapidly become the standard of care. The goals of therapy are to slow disease progression, improve hepatic histology, reduce infectivity, and reduce the risk of hepatocellular carcinoma. Sustained virologic response, which generally implies the absence of viremia for 6 months or more following completion of therapy, is increasingly being regarded as a cure, with evidence of slowing or even regression of fibrosis on follow-up liver biopsy. A number of factors have been shown to be predictive of a sustained response, including viral genotype other than 1, low serum HCV RNA levels, absence of cirrhosis, younger age, female gender, and shorter duration of infection. Disease severity as assessed by liver biopsy, comorbidities, and possible contraindications to therapy should be weighed in the decision to begin treatment. Counseling patients regarding transmission, natural history, and drug and alcohol abstinence also should be included in management. Close monitoring should be done during treatment for side effects of interferon, including depression and bone marrow suppression. Hemolytic anemia is the major side effect of ribavirin.

Journal Article↗
PubMedDate not supplied

Peak resolution and tailing in alpha-particle spectrometry for environmental samples.

Peak resolution in alpha-particle spectrometry is generally quoted as full-width-at half maximum. However, the extent of tailing of alpha particle peaks into regions of lower energy is often a critical factor for accurate spectral analysis, particularly given the relatively low count rates observed for many environmental samples. In this paper we examine the influence of various factors on peak resolution and tailing for spectra collected using solid-state alpha detectors, in particular chamber gas pressure and source deposit thickness.

Alpha Particles↗
PubMedDate not supplied

Hepatocellular carcinoma: the high-risk patient.

Hepatocellular carcinoma (HCC) is the most common hepatic malignancy worldwide. The primary risk factor for the development of HCC is cirrhosis. Even patients without cirrhosis who develop HCC are typically found to have some underlying hepatic abnormality, such as steatohepatitis or chronic viral hepatitis. Although cirrhosis of any cause increases the risk of developing HCC, cirrhosis associated with chronic hepatitis B or C virus infection or hemochromatosis carries the greatest risk. Additional factors such as patient age and sex, duration and severity of liver disease, concurrent alcohol or aflatoxin exposure, liver histology, and alpha-fetoprotein levels also contribute to the relative risk of developing HCC. Vaccination programs aimed at preventing hepatitis B virus infection have been very successful in lowering the incidence of HCC in some areas of the world. Interferon-based therapy, which may control the inflammatory activity in chronic hepatitis C, also holds promise in preventing HCC. Other novel chemopreventative agents, such as glycyrrhizin and polyprenoic acid, may also have a role in preventing HCC, but they require further study before they can be recommended for widespread use.

Antineoplastic Agents↗
PubMedDate not supplied

Isolated heart and liver transplant recipients are at low risk for polyomavirus BKV nephropathy.

BACKGROUND: BKV infection and nephropathy is a significant cause of allograft dysfunction in kidney transplantation. BKV viremia, rather than viruria, corresponds to BKV nephropathy. The prevalence of BKV viremia in non-renal solid organ transplants has not been systematically evaluated. METHODS: We determined prevalence of BKV viremia in kidney, combined kidney-heart, kidney-liver, kidney-pancreas, kidney-heart-liver, and heart and liver transplant recipients using BKV-PCR. RESULTS: Seven out of 173 (4%) kidney transplant recipients had BKV viremia, with BKV>2 x 10(5) copies/mL in 6/7 and 1.9 x 10(3) in the remaining one patient. BKV viremia was not found in 24 heart transplant recipients, whereas 1/37 (2.7%) liver transplants showed low copy numbers (< or =10(3)). BKV-PCR< or =10(3) copies/mL were also found in one of each combined kidney-heart and kidney-liver transplant recipients. BKV nephropathy was proven by biopsy in 4/6 patients with high BKV viral loads. All six patients showed renal dysfunction, requiring reduction in immunosuppression and antiviral therapy. All four patients with low BKV viral loads (1.9 x 10(3) or < or =10(3)) showed stable renal function after reduction of immunosuppression or no treatment, respectively. CONCLUSION: Higher BKV levels in plasma are associated with renal dysfunction. Kidney transplant recipients are at high risk compared with recipients of isolated heart or liver allografts, for development of BKV nephropathy.

BK Virus↗
PubMedDate not supplied

Setting the pace.

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Health Knowledge, Attitudes, Practice↗
PubMedDate not supplied

A shot at the title?

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Career Mobility↗
PubMedDate not supplied

Management of hepatitis B after renal transplantation: an update.

Hepatitis B Virus (HBV) infection remains an important cause of liver disease in renal transplant (RT) recipients and the outcome of HBV infected RT recipients is less favorable than that of noninfected RT recipients. The concern about graft loss induced by interferon (IFN) therapy precludes its use; lamivudine, a second-generation analog, has been recently approved for the treatment of hepatitis B and promises to be highly effective in this setting. Several uncontrolled trials have reported a high rate of biochemical (ranging between 80% and 100%) and virological (ranging between 67% and 100%) response in RT recipients, comparable to immunocompetent patients. Lamivudine has an excellent safety profile in RT recipients. However, the emergence of viral mutations leading to resistance has been reported during lamivudine therapy in RT recipients. In addition, numerous issues remain to be clarified about lamivudine use after RT including the management of viral resistance, the role of HBV genotypes in the response to lamivudine, and the duration of therapy and response. The combination of newer nucleoside analogues with lamivudine, analogous to HIV, may further improve the efficacy of antiviral therapy against HBV after RT.

Antiviral Agents↗
PubMedDate not supplied

Hepatitis B virus infection in hemodialysis: recent discoveries.

Controlling the spread of HBV infection in dialysis units has been one of the major advances in the treatment of patients with ESRD. The frequency of HBsAg carriers on maintenance dialysis is low in developed countries. However, prevalence and incidence rates of HBV infection among dialysis patients in less developed countries remain very high. Patients on maintenance dialysis and chronic HBsAg carriage are typically anicteric and rarely develop symptoms of hepatitis. The relationship between HBsAg and aminotransferase activity in dialysis population is stronger than has so far been recognized. HBsAg positivity is significantly associated with hepatocellular damage in dialysis patients. Aminotransferase activity in dialysis population is usually depressed; this hampers the recognition of HBV-related liver disease among dialysis patients by biochemical tests. The HBV viral load in HBsAg positive patients is low and stable over time; the low mortality attributable to liver disease in dialysis patients could be related to this finding. Numerous assays for detecting HBV DNA in serum of dialysis patients are available; they should not be used for purposes of routine screening within dialysis units. Continued implementation of the long-recommended infection control procedures against HBV within dialysis units is strongly suggested.

DNA, Viral↗
PubMedDate not supplied

Transplanting kidneys from donors with prior hepatitis B infection: one response to the organ shortage.

While the number of cadaveric organ donors remains relatively stable, the number of patients awaiting transplantation continues to increase, creating a shortage of donor organs. To address this imbalance, there is interest in transplanting organs formerly considered marginal or undesirable. Thus, more organs are currently transplanted from living donors, older donors, hemodynamically unstable donors, non-heart-beating donors and donors with markers of prior hepatitis B virus (HBV) infection. A large number (up to 93.8%) of liver transplant seronegative recipients from anti-HBc antibody positive donors have acquired HBsAg after liver transplantation in the absence of immunoprophylaxis. Based on experience in liver transplantation programs, transmission of HBV from donors without HBsAg but with antibody to HBV core antigen (anti-HBc), although conventionally defined as evidence of resolved infection, can have adverse consequences on both graft and recipient. On the contrary, HBV appears to be in-frequently transmitted from HBsAg negative/anti-HBcAb positive kidney donors: the incidence of de novo HBsAg seropositivity after renal transplantation ranges between 0 and 5.2%. A significantly higher incidence of anti-HBc antibody seroconversion (without developing HBsAg) after renal transplantation with anti-HBc antibody positive donors was seen. However, anti-HBc antibody positive renal allografts should be considered, especially for recipients who have been successfully immunized with HBV vaccine. Prospective long-term studies are in progress to assess the risk of de novo HBV infection (HBsAg seroconversion) in renal transplant recipients who have not been successfully immunized with vaccine against HBV.

Cadaver↗