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Biomedical subjects

D Lewis

Publications and source records attributed to D Lewis.

At least 109 records · Page 6Linked to original sources
PubMed1997

Spatial and temporal variation in abundance of Anopheles (Diptera:Culicidae) in a malaria endemic area in Papua New Guinea.

Abundance of anophelines in 10 villages in the Wosera area of Papua New Guinea was monitored during 1990-1993. Of 85,197 anophelines collected in 1,276 paired indoor and outdoor landing catches, 40.4% were Anopheles koliensis Owen, 36.7% An. punctulatus Donitz, 14.3% An. karwari (James), 4.9% An. farauti s.l. Laveran, 3.1%, An, longirostris Brug, and 0.7% An. bancroftii Giles. Maps of average indoor biting rates were produced using a Bayesian conditional autoregressive model which allowed for heterogeneities in sampling effort over time and space. Differences in spatial distributions among species were observed among and within villages and were related to the distribution of larval habitats and vegetation. Abundance of An. punctulatus and An. koliensis decreased with distance from the main waterway and probably from a sago swamp forest at 6 villages in North Wosera. Abundance of An. punctulatus was associated negatively with those of An. farauti s.l., An. longirostris, and An. bancroftii. The latter 3 species also had relatively low ratios of indoor-to-outdoor biting rates, and earlier biting times than An. punctulatus. Human blood indices of at least 0.79 were observed for all species except An. bancroftii. Abundance of all 6 species was correlated temporally with recent rainfall, but An. koliensis, An. karwari, and An. longirostris showed greater temporal variability than the other species. An punctulatus and An. koliensis tended to occur together in time and space (index of association, I = 0.85). Weaker associations were seen between An. farauti s.l. and An. longirostris (I = 0.44) and An. koliensis and An. karwari (I = 0.34). The most frequently collected species occurred together and were concentrated near the Amugu river; the remaining species tended to occur together but in different parts of the Wosera area. The importance of understanding ecological requirements of the different Anopheles vectors and their association with key household and landscape features are discussed in relation to malaria transmission and control.

Animals↗
PubMed1996

Short and long range functions of amino acids in the transmembrane region of the sarcoplasmic reticulum ATPase. A mutational study.

Mutational analysis of several amino acids in the transmembrane region of the sarcoplasmic reticulum ATPase was performed by expressing wild type ATPase and 32 site-directed mutants in COS-1 cells followed by functional characterization of the microsomal fraction. Four different phenotype characteristics were observed in the mutants: (a) functions similar to those sustained by the wild type ATPase; (b) Ca2+ transport inhibited to a greater extent than ATPase hydrolytic activity; (c) inhibition of transport and hydrolytic activity in the presence of high levels of phosphorylated enzyme intermediate; and (d) total inhibition of ATP utilization by the enzyme while retaining the ability to form phosphoenzyme by utilization of P(i). Analysis of experimental observations and molecular models revealed short and long range functions of several amino acids within the transmembrane region. Short range functions include: (a) direct involvement of five amino acids in Ca2+ binding within a channel formed by clustered transmembrane helices M4, M5, M6, and M8; (b) roles of several amino acids in structural stabilization of the helical cluster for optimal channel function; and (c) a specific role of Lys297 in sealing the distal end of the channel, suggesting that the M4 helix rotates to allow vectorial flux of Ca2+ upon enzyme phosphorylation. Long range functions are related to the influence of several transmembrane amino acids on phosphorylation reactions with ATP or P(i), transmitted to the extramembranous region of the ATPase in the presence or in the absence of Ca2+.

Amino Acid Sequence↗
PubMed1996

A randomized study of VAD therapy with either concurrent or maintenance interferon in patients with newly diagnosed multiple myeloma.

This randomized study was designed to determine whether response to VAD chemotherapy could be prolonged by using rh alpha-2b-interferon (IFN) at a dose of 3 mU three times per week, either concurrently with VAD (VIC) or as maintenance after completion of VAD (VIF). Maintenance IFN was given for 9 months in order for the duration of IFN therapy to be similar in both groups. 72 patients were randomized between December 1988 and August 1993. The majority of patients had poor prognostic features. The objective response rate was similar in each arm, 78% in VIF and 77% in VIC. Of the 56 responders, 33 have relapsed, three died in remission, and 18 proceeded to high-dose therapy, withdrew for other reasons or were lost to follow-up and were censored from analysis at the relevant time point. Only two patients remain in remission (both in partial remission). Median PFS was 15 months for both VIF and VIC, compared with 16.5 months for a historic control group treated with VAD alone (n.s.). The estimated median survival in VIF was 43 months and in VIC 22 months, compared with 45 months in the historic controls (n.s.). These findings indicate that neither maintenance nor concurrent IFN prolongs response to VAD.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Fetal cocaine exposure: analysis of vernix caseosa.

Preliminary data regarding the use of vernix caseosa (VC) as an alternative to other biological specimens for the determination of fetal cocaine exposure are presented. Advantages of VC analysis include its presence on all newborn babies, historical record of drug exposure, and ease of collection and storage. Fifteen samples of vernix caseosa-five from babies known to be cocaine-exposed because of a positive benzoylecgonine result from the urine and umbilical cord blood and ten from nonexposed neonates-were analyzed for the presence of cocaine and metabolites. VC samples from three of the five neonates known to be cocaine-exposed were positive for cocaine or its metabolites, the other two had little or no remaining specimen. The remaining ten were negative.

Chromatography, Gas↗
PubMed1996

Hepatitis C virus reinfection in orthotopic liver transplant patients with or without concomitant hepatitis B infection.

Although recurrence of hepatitis C virus (HCV) in orthotopic liver transplant (OLT) patients is frequent, the relationship between HCV recurrence and graft pathology, particularly in patients who also have a history of hepatitis B virus (HBV), is unclear. The recurrence of HCV after OLT was determined by reverse transcriptase-nested polymerase chain reaction (RT-PCR) in the sera and livers of 41 patients with OLT, 32 of whom underwent transplants for HCV or HBV-related disease. Results were compared with liver function tests, liver histology (including HBV immunohistochemistry), and antibody status. HCV PCR was more frequently positive in OLT patients with a history of HCV only (59%) than in those with a history of both HCV and HBV (41%) or no history of viral infection (2%). Recurrent HCV (60% overall) was associated with mild elevation of liver function tests and mild to moderate hepatitis. In patients who underwent transplants for both HCV and HBV disease, hepatitis on biopsy was more frequently associated with recurrent HBV than with recurrent HCV. We conclude that graft reinfection with HCV, which is frequent in OLT patients with or without HBV recurrence, is usually associated with only mild to moderate hepatitic changes compatible with graft survival.

Base Sequence↗
PubMed1996

Aetiological factors for oral manifestations of HIV.

OBJECTIVES: Describe the oral diseases in HIV-infected individuals in London, UK and identify social and medical factors related to the presence of specific oral diseases. DESIGN: Dental clinics. SUBJECTS: Consecutive sample of 456 patients with HIV infection. METHODS: Social and medical history and clinical examinations. Univariate and logistic regression analysis. OUTCOMES: Presence of HIV-associated oral disease. RESULTS: 80% of patients with AIDS and 50% of patients with HIV had a specific oral disease. The most common diseases were hairy leukoplakia (30%), erythematous candidiasis (24%), pseudomembranous candidiasis (14%), angular chielitis (6%), necrotising periodontal disease (8%) and non-recurrent ulceration (6%). CONCLUSIONS: The presence of erythematous candidiasis was not related to advanced HIV disease. Pseudo-membranous candidiasis, hairy leukoplakia and mucosal ulceration were significantly associated with advanced HIV disease. Smoking was also identified as a strong aetiological factor in oral diseases. Longitudinal studies are required to further explore the prognostic significance of oral diseases in HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Improvement in the polyneuropathy associated with familial amyloid polyneuropathy after liver transplantation.

OBJECTIVE: To study, following liver transplantation, the neurologic progression or regression of the polyneuropathy in a cohort of patients with familial amyloidotic polyneuropathy (FAP). BACKGROUND: FAP is characterized by the relentless progression of neurologic and cardiac impairment, leading to death within 7 to 15 years after disease onset. No effective treatment to slow or halt the progression of this disease has been found to date. DESIGN/METHODS: Over the past 3 years, our FAP patients were offered liver transplantation as treatment. We report on nine patients who were followed longitudinally with serial neurologic examinations since transplantation. RESULTS: Clinically, all patients evaluated for neurologic progression reported significant improvement in general well being. No patient showed any progression in neurologic disease since receiving a liver transplant. Improvements are documented in symptomatic, autonomic, and sensorimotor neurologic disease in all patients. CONCLUSION: Our experience suggests that liver transplantation may offer hope for arrest of progression and neurologic improvement in patients with FAP.

Adult↗
PubMed1996

A retreat: the benefits to nurse education.

The informality of an educational retreat can break down traditional barriers to learning and self-knowledge. A retreat can encourage autonomy, teamwork and reflection

Education, Nursing, Baccalaureate↗
PubMed1995

PCR analysis of HIV-seronegative, heterosexual partners of HIV-infected individuals.

A cohort of human immunodeficiency virus (HIV)-discordant couples was established to evaluate risk factors associated with heterosexual viral transmission. Polymerase chain reaction (PCR) was utilized to document the HIV-uninfected status among members of discordant heterosexual couples and to rule out immunosilent infection. HIV DNA PCR specific for a gag gene region was performed on peripheral blood mononuclear cell samples from 203 HIV antibody-negative adults who have long-term heterosexual relationships with HIV-infected partners. The results were negative for 200 but consistently positive in three individuals. More extensive evaluation of these three individuals with an additional primer pair specific for the envelope gene, quantitative DNA PCR, multiple additional time points, and variable nucleotide tandem repeat analyses revealed specimen processing problems in two cases but an apparent true positive PCR assay in the third case. This subject remains antibody and PCR negative for a 32-month follow-up period. These results confirm previous studies that document a negligible incidence of occult HIV infection as delineated by PCR in antibody negative heterosexual partners of HIV-infected individuals. Specimen processing errors occur at a low rate (1% in this study) and require careful evaluation. The possibility of transient, aborted infection versus successful infection with a long immunosilent period was observed in a single individual. Definitive resolution of infection status will require long-term evaluation.

Adult↗
PubMed1995

Mutational analysis of the peptide segment linking phosphorylation and Ca(2+)-binding domains in the sarcoplasmic reticulum Ca(2+)-ATPase.

The sarcoplasmic reticulum ATPase segment extending from the phosphorylation site (Asp-351) to the preceding transmembrane helix M4 (which is involved in Ca2+ binding in conjunction with transmembrane helices M5, M6, and M8) retains a marked sequence homology to the corresponding segments of other cation ATPases. We made 26 point mutations in this segment and found that nonconservative mutations of residues that are homologous in various cation ATPases result in strong inhibition of catalytic and transport function. Mutations of nonhomologous residues to match the corresponding residues of other cation ATPases are not inhibitory and, in some cases, produce higher activity. The inhibitory mutations affect the phosphorylated intermediate turnover, which is associated with the vectorial translocation of bound Ca2+. The same mutations do not affect the kinetics of ATPase activation by Ca2+ following enzyme preincubation with EGTA. This suggests that activation of the phosphoryl transfer reaction by Ca2+ binding and vectorial displacement of bound Ca2+ by enzyme phosphorylation do not occur simply as the forward and reverse directions of the same process, but are linked to distinct structural features of the enzyme. The peptide segment extending from the phosphorylation site in the enzyme extramembranous headpiece through the M4 helix in the membrane-bound region sustains a prominent role in transmission of the phosphorylation signal for displacement of bound Ca2+. A critical structural role of this segment is also demonstrated by the interference of specific mutations with membrane assembly of the expressed protein.

Animals↗
PubMed1995

Detection and characterisation of bisegmented double-stranded RNA viruses (picobirnaviruses) in human faecal specimens.

The prevalence of picobirnaviruses (PBVs) in human stools was investigated by polyacrylamide gel electrophoresis (PAGE) analysis of 832 faecal specimens collected between 1982 and 1993 from patients in various clinical groups. Similar prevalences (9-13%) were detected in patients with or without gastroenteritis and throughout the age range of 3 to > 65 years. Two methods for the extraction of nucleic acid, a phenol/chloroform method and a guanidinium thiocynate (GTC)/silica method, were compared. Detection of PBVs by PAGE was three times more sensitive following RNA extraction by the GTC/silica method. Characterisation of three strains was carried out. Segment sizes ranged from 1.625 to 1.95 kilo base pairs (Kbp) and 2.2 to 2.5 Kbp for the fast and slow migrating bands, respectively. The nuclic acid was shown to be double-stranded RNA (dsRNA) by nuclease digestion. PBV-like particles were detected by electron microscopy in two PAGE-positive stools. Virion diameters ranged from 35 to 41 nm and a buoyant density of 1.38-1.4 g/ml in caesium chloride (CsCl) was demonstrated. These findings suggest that PBVs are widespread in humans in the United Kingdom. However, no disease association could be demonstrated.

Adolescent↗
PubMed1995

Broadly reactive reverse transcriptase polymerase chain reaction for the diagnosis of SRSV-associated gastroenteritis.

A limitation to date of reverse transcriptase polymerase chain reactions (RT-PCRs) for the detection of small, round structured viruses (SRSVs) has been that they have detected only a narrow range of SRSVs due to the marked genomic diversity among strains. A total of 331 faecal samples collected from 136 separate incidents of gastroenteritis occurring in the UK between 1992 and 1994 were examined by RT-PCR employing a single primer pair (N1/E3). SRSV RNA was detected in samples from 93 of 101 (91%) incidents shown to be SRSV-associated by electron microscopy (EM) and in 5 of 35 (14%) SRSV-negative incidents. Amplification products were tested by Southern blot hybridisation with a pool of four digoxigenin (DIG)-labelled oligonucleotides derived from genomic sequence data of SRSV SPIEM types UK 1 to 4. Products from approximately 5% of amplified strains did not hybridise. The N1/E3 primer pair were shown to be SRSV-specific by their failure to amplify other faecal viruses including other human caliciviruses with typical calicivirus morphology. Hybridisation of PCR products with the individual oligonucleotides relating to SRSV SPIEM types UK 1-4 was investigated: 1 of 60 (1.7%) reacted with the UK1 probe, 2/60 (3.4%) reacted with the UK2 probe, 51/60 (85%) with the UK3 probe, and 27/60 (45%) reacted with the UK4 probe. All PCR products that hybridised with the UK4 probe hybridised with the UK3 probe; 6 (10%) failed to hybridise. Identification of this primer pair facilitates routine diagnosis of SRSV infection by RT-PCR and offers the potential for direct detection in food and environmental samples.

Animals↗
PubMed1995

Ca2+ binding and translocation by the sarcoplasmic reticulum ATPase: functional and structural considerations.

Three experimental systems are described including sarcoplasmic reticulum (SR) vesicles, reconstituted proteoliposomes, and recombinant protein obtained by gene transfer and expression in foreign cells. It is shown that the Ca(2+) ATPase of sarcoplasmic reticulum (SR) includes an extramembranous globular head which is connected through a stalk to a membrane bound region. Cooperative binding of two calcium ions occurs sequentially, within a channel formed by four clustered helices within the membrane bound region. Destabilization of the helical cluster is produced following enzyme phosphorylation by ATP at the catalytic site in the extramembranous region. The affinity and orientation of the Ca2+ binding site are thereby changed, permitting vectorial dissociation of bound Ca2+ against a concentration gradient. A long range linkage between phosphorylation and Ca2+ binding sites is provided by an intervening peptide segment that retains high homology in cation transport ATPases, and whose function is highly sensitive to mutational perturbations.

Animals↗
PubMed1995

Successful prenatal management of hydrops, caused by congenital cystic adenomatoid malformation, using serial aspirations.

Congenital cystic adenomatoid malformation (CCAM) is a lung lesion that is now commonly diagnosed in utero with fetal ultrasonography. The described treatment of this lesion includes observation with treatment delivery, a single aspiration, thoraco-amniotic shunts, and fetal resection. This patient had an in utero diagnosis of a Stocker type I CCAM associated with hydrops. Fetal resection was not an option because of patient refusal. The fetus was treated with multiple serial aspirations. There was marked improvement of the anasarca, and subsequently the baby was born without respiratory distress. On the second day of life the CCAM began to expand, and the right lower lobe was resected. The baby's postoperative course was uneventful. CCAM with hydrops is associated with a high mortality rate. Current recommended therapy for these lesions is fetal resection or thoracoamniotic shunt. The authors' patient was treated with serial fetal thoracocenteses, with an excellent outcome. This therapy may be an alternative to fetal surgery or an adjunct to fetal surgery in selected cases.

Adult↗