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Biomedical subjects

M Webb

Publications and source records attributed to M Webb.

At least 55 records · Page 3Linked to original sources
PubMed1997

Glove powder--a risk factor for the development of latex allergy?

Studies are described which compare the prevalence of sensitisation against latex proteins in medical personnel in different hospitals. The objective of these studies was to find out whether the use of powdered or unpowdered gloves could be related to the prevalence of latex allergy. Employees of one of the investigated hospitals (Germany) were using only powdered latex gloves, and in the other two hospitals (Great Britain) low protein powder-free latex gloves were used. Methods by which latex allergy can be avoided are suggested.

Allergens↗
PubMed1996

Surface labelling of the type I methyltransferase M.EcoR124I reveals lysine residues critical for DNA binding.

The type IC methyltransferase M.EcoR124I consists of a specificity subunit (HsdS) and two methylation subunits (HsdM). Using chemical modifications, we have investigated the accessibility of lysine residues in the free enzyme and in the complex with its DNA recognition sequence. A total of 41 of the 109 lysine residues in the enzyme are susceptible to modification, of which 19 are located in the HsdS subunit and 11 in each of the two HsdM subunits. DNA binding results in extensive protection of lysine residues in the HsdS subunit, while those in the HsdM subunit are only protected weakly. The DNA binding activity of the methylase is abolished when a small fraction of the accessible lysine residues are modified. Peptide mapping and N-terminal sequencing has been used to locate the rapidly modified lysine residues in HsdS that are critical for DNA binding. Highly modified residues (K297, K261 and K327) are found in the C-terminal variable domain that is responsible for DNA recognition, but others (K196, K203 and K210) are found in the conserved regions that had not previously been implicated in DNA binding.

Amino Acid Sequence↗
PubMed1996

Transplant-associated autoimmune mechanisms in human hepatitis C virus infection.

In order to define factors which are important for the development of hepatitis C virus (HCV) infection and disease in transplant patients, we examined the role of class II MHC antigen restriction in viral antigen presentation to support a hypothesis of the association of this disease with an autoimmune pathogenesis. A greater degree of histocompatibility match between these donors and their HCV-negative recipients was associated with a greater predisposition to recipient HCV liver disease (ALT elevation) posttransplant. The HCV carrier state could be identified with significant amplification of autologous mixed lymphocyte reactivity (AMLR) in both long-term hemodialysis and long-term renal transplant patients, but the AMLR was absent in end-stage liver disease patients with HCV-associated cirrhosis and was insignificantly elevated in these patients with persistent infection in the first 2 years after a new liver was transplanted. There was also a moderate reduction in autologous reactivity as well as serum HCV titers among renal transplant patients who displayed biochemical evidence of chronic liver disease as opposed to those who did not. This appeared later in the course of the disease. HCV RNA could be detected in peripheral blood mononuclear cells (PBMC) of only a portion of HCV-infected renal transplant patients and these showed significantly higher autologous reactivity. In contrast, despite the fact that observations were earlier after de novo liver transplantation, HCV RNA (i.e., earlier in the course of a new or recurrent disease process) was found in PBMC of all liver transplant recipients tested. The AMLR of noninfected laboratory volunteers could be amplified by preincubating their stimulating cells (APCs) with enriched HCV possibly in immune complex (pHCV-IC). This amplification appeared only with specific combinations of HCV strains with HLA DR serotypes. In addition, HCV-primed T cells could be generated to the virus which displayed accelerated activation kinetics. Liver infiltrating lymphocytes extracted from HCV-positive end-stage diseased livers had significantly higher proliferative and cytotoxic reactivity to autologous (HCV-infected) hepatocytes than the extracted lymphocytes responding to autologous hepatocytes from HCV-negative livers. These findings offer evidence of dynamic autoimmune mechanisms in the spectrum of progression of HCV disease and may help to predict the effect of intervention at various intervals in this progression in organ transplant recipients.

Autoimmune Diseases↗
PubMed1996

Mechanical and structural properties underlying contraction of skeletal muscle fibers after partial 1-ethyl-3-[3-dimethylamino)propyl]carbodiimide cross-linking.

We show prolonged contraction of permeabilized muscle fibers of the frog during which structural order, as judged from low-angle x-ray diffraction, was preserved by means of partial cross-linking of the fibers using the zero-length cross-linker 1-ethyl-3-[3-dimethylamino)propyl]carbodiimide. Ten to twenty percent of the myosin cross-bridges were cross-linked, allowing the remaining 80-90% to cycle and generate force. These fibers displayed a well-preserved sarcomeric order and mechanical characteristics similar to those of intact muscle fibers. The intensity of the brightest meridional reflection at 14.5 nm, resulting from the projection of cross-bridges evenly spaced along the myofilament length, decreased by 60% as a relaxed fiber was deprived of ATP and entered the rigor state. Upon activation of a rigorized fiber by the addition of ATP, the intensity of this reflection returned to 97% of the relaxed value, suggesting that the overall orientation of cross-bridges in the active muscle was more perpendicular to the filament axis than in rigor. Following a small-amplitude length step applied to the active fibers, the reflection intensity decreased for both releases and stretches. In rigor, however, a small stretch increased the amplitude of the reflection by 35%. These findings show the close link between cross-bridge orientation and tension changes.

Actins↗
PubMed1996

Routine use of the piggyback technique in pediatric orthotopic liver transplantation.

The theoretical advantages of the piggyback technique over conventional orthotopic liver transplantation are as follows. (1) Continuous venous decompression during the anhepatic phase is provided without venovenous bypass. (2) Warm ischemia time can be shortened because there is no need for the infrahepatic vena cava anastomosis. The following report is a review of the authors' experience with this method in children during the past year at their institution. Analyses of intraoperative hemodynamics and blood loss, postoperative renal function, patient and graft survival, and length of hospital stay have shown excellent results. There were no intraoperative deaths, and causes of death and graft loss were not related to the technique. The authors conclude that children who undergo liver transplantation can be very satisfactorily managed with the piggyback operation, and this technique may be more advantageous than the conventional method.

Adolescent↗
PubMed1996

The detection of rhodamine 123 efflux at low levels of drug resistance.

Although many cell models of multidrug resistance (MDR) have been developed, most have been high-resistance models which generate up to 100-fold increases in drug resistance. However, the drug concentrations required to achieve these levels of resistance are much higher than those found in vivo. In this paper we describe the development of a cell model that reflects the resistance levels that are likely to be found clinically. We then investigated the methods used to detect MDR1 expression at these low levels of drug resistance. We demonstrated that the immunological and PCR-based methods are unable to detect increased MDR1 expression in cells with a < 5.2- and 6.5-fold increase in vinblastine resistance, respectively, in our drug-resistant sublines. The rhodamine 123 (Rh 123) efflux assay was able to discriminate the vinblastine-sensitive parent cells from all the vinblastine-resistant sublines, including cells with a 1.7-fold increase in resistance. However, this assay is non-specific to the MDR1 gene and may detect the activity of other drug efflux proteins such as the MDR-associated protein (MRP). Our results show that the Rh 123 efflux assay is able to detect the activity of drug efflux proteins such as the P-glycoprotein, MRP or other efflux systems at the low levels of drug resistance that are likely to be attained in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

New antihistamines: substituted piperazine and piperidine derivatives as novel H1-antagonists.

Structural manipulation of polycyclic piperazinyl imide serotonergic agents led to the synthesis of compound 8, 2-[4-[4-[bis(4-fluorophenyl)methyl]-1-piperazinyl]-4, 4a,5,5a,6,6a-hexahydro-4,6-ethenocycloprop[f]isoindole-1,3(2H,3 aH)-dione, which demonstrated good H1-antagonist activity. Substitution of a xanthinyl moiety for the polycyclic imide group led to the identification of novel xanthinyl-substituted piperazinyl and piperidinyl derivatives with potent antihistamine H1-activity without the undesirable antidopaminergic activity of 8. One compound, 24, 7-[3-[4-(diphenylmethoxy)-1-piperidinyl]propyl]- 3,7-dihydro-1,3-dimethyl-1H-pyrine-2,6-dione (WY-49051), is a potent, orally active H1-antagonist with a long duration of action and a favorable central nervous system profile.

Animals↗
PubMed1995

Probing the domain structure of the type IC DNA methyltransferase M.EcoR124I by limited proteolysis.

Limited proteolysis has been used to probe the domain structure of the type I DNA methyltransferase M.EcoR124I. Trypsin digestion of the methyltransferase generates two fragments derived from the HsdS subunit, a 28 kDa N-terminal domain and a 19 kDa C-terminal domain, leaving the HsdM subunit intact. Extensive digestion by chymotrypsin, however, removes 59 amino acid residues from the N terminus of the HsdM subunit to leave a 52 kDa C-terminal domain. Binding of the cofactor S-adenosyl methionine has no appreciable effect on the rate of cleavage, but binding of a 30 bp DNA duplex containing the cognate recognition sequence confers almost total protection. Following trypsin cleavage of the methyltransferase, a stable proteolytic product is produced which has been purified for biochemical characterisation. The trypsinised enzyme is shown to be a multimeric complex containing two intact HsdM subunits and both fragments of the HsdS subunit, consistent with the circular model proposed for the organisation of domains in the specificity subunit in type IC methyltransferases. Gel retardation studies show that the proteolysed enzyme still retains DNA binding activity, but its specificity for the DNA recognition sequence is dramatically reduced.

Amino Acid Sequence↗
PubMed1995

Orthotopic liver transplantation for benign hepatic neoplasms.

OBJECTIVE: To evaluate the frequency and outcome of liver transplantation for symptomatic, unresectable, benign hepatic neoplasms. DESIGN: Retrospective study. SETTING: Presbyterian University Hospital, a tertiary care referral center for liver transplantation affiliated with the University of Pittsburgh (Pa). PATIENTS: All 3239 liver transplant recipients at the University of Pittsburgh from January 1981 until January 1993. RESULTS: Twelve (0.37%) of 3239 patients required liver transplantation for benign, highly symptomatic hepatic neoplasms that were unresectable. Origins included adenoma (n = 6), mesenchymal hamartoma (n = 2), massive hepatic lymphangiomatosis (n = 1), hilar fibrous angiodysplasia (n = 1), focal nodular hyperplasia (n = 1), and hemangioma (n = 1). There were three perioperative deaths and two late deaths at 56 and 84 months. The remaining patients are alive, with follow-up ranging from 36 to 145 months. Median survival for the nine patients who survived the perioperative period is 88 months. The early deaths were attributable to hemorrhagic complications (n = 2) and necrotizing pancreatitis (n = 1). The two late deaths were due to disseminated aspergillosis and hepatitis-associated cirrhosis. CONCLUSION: Patients with severe symptoms from benign hepatic neoplasms that are not resectable can be treated by total hepatectomy and orthotopic liver transplantation, with the expectation of good long-term results.

Adenoma↗
PubMed1995

The effete in the heat: heat-related hospital presentations during a ten day heat wave.

BACKGROUND: Severe heat-related illness can result in hospitalisation and possibly death. These illnesses are potentially preventable; in Australia high environmental temperatures are common. AIMS: To identify (i) possible risk factors for hospital attendance with heat-related illness during a heat wave, (ii) problems with diagnosis and therapy, (iii) issues in prevention, and (iv) areas for further study. METHODS: A retrospective descriptive survey from four major teaching hospitals in Adelaide, South Australia (SA), was conducted during a ten day period of exceptional heat in February 1993, in order to review all emergency department presentations (i.e. deaths, casualty treatment or hospital admissions) with a heat-related illness as determined by attending doctors' documentation. Demographic, clinical, management and outcome data were collected. RESULTS: Ninety-four patients were classified as having a heat-related illness of whom 78% had heat exhaustion. Eighty-five per cent were age 60 years or over; 20% came from institutional care; 48% lived alone; 30% had poor mobility. Peak presentation followed high daily temperatures for four consecutive days. Severity was related to pre-existing cognitive impairment, diuretic use and presenting temperature, heart rate, blood pressure, plasma sodium and plasma creatinine. Treatment tended to be non-standardised. Mortality was 12%. Seventeen per cent required a more dependent level of residential care upon discharge. CONCLUSION: Problems were identified in accuracy of diagnosis and appropriate intervention. Awareness of the risk factor profile is needed among health workers, to ensure early preventative strategies. Populations to target for future prevention include elderly people (including those in institutional care), patients with cognitive impairment and patients taking diuretics, multiple medication and/or with other severe co-existing illnesses. Treatment could be more standardised.

Adult↗