Biomedical subjects

J Green

Publications and source records attributed to J Green.

At least 271 records · Page 15Linked to original sources

PubMed1996

An outbreak of viral gastroenteritis following a wedding reception.

Thirty-five people developed gastrointestinal symptoms after a wedding reception attended by 147 guests and served by eight catering staff. A retrospective cohort study showed that illness was associated independently with consumption of a pasta dish and spring rolls. The descriptive epidemiology, obtained from interviews with the guests about foods they had eaten and the onset and duration of symptoms, suggested that the outbreak was likely to have been caused by a small round structured virus (SRSV). No pathogenic bacteria were isolated from cases or samples of food served at the reception. Electron microscopy of three stool specimens revealed no viruses, but SRSV was subsequently identified by reverse transcriptase polymerase chain reaction in one of two stool specimens. Environmental investigation in the kitchen revealed a number of deficiencies.

Disease Outbreaks↗

PubMed1996

Dental therapists.

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Dental Auxiliaries↗

PubMed1996

Reconstitution of the [4Fe-4S] cluster in FNR and demonstration of the aerobic-anaerobic transcription switch in vitro.

The FNR protein of Escherichia coli is a redox-responsive transcription regulator that activates and represses a family of genes required for anaerobic and aerobic metabolism. Reconstitution of wild-type FNR by anaerobic treatment with ferrous ions, cysteine and the NifS protein of Azotobacter vinelandii leads to the incorporation of two [4Fe-4S]2+ clusters per FNR dimer. The UV-visible spectrum of reconstituted FNR has a broad absorbance at 420 nm. The clusters are EPR silent under anaerobic conditions but are degraded to [3Fe-4S]+ by limited oxidation with air, and completely lost on prolonged air exposure. The association of FNR with the iron-sulphur clusters is confirmed by CD spectroscopy. Incorporation of the [4Fe-4S]2+ clusters increases site-specific DNA binding about 7-fold compared with apo-FNR. Anaerobic transcription activation and repression in vitro likewise depends on the presence of the iron-sulphur cluster, and its inactivation under aerobic conditions provides a demonstration in vitro of the FNR-mediated aerobic-anaerobic transcriptional switch.

Aerobiosis↗

PubMed1996

Cost effectiveness of treating primary care patients in accident and emergency: a comparison between general practitioners, senior house officers, and registrars.

OBJECTIVES: To compare outcome and costs of general practitioners, senior house officers, and registrars treating patients who attended accident and emergency department with problems assessed at triage as being of primary care type. DESIGN: Prospective intervention study which was later costed. SETTING: Inner city accident and emergency department in south east London. SUBJECTS: 4641 patients presenting with primary care problems: 1702 were seen by general practitioners, 2382 by senior house officers, and 557 by registrars. MAIN OUTCOME MEASURES: Satisfaction and outcome assessed in subsample of 565 patients 7-10 days after hospital attendance and aggregate costs of hospital care provided. RESULTS: Most patients expressed high levels of satisfaction with clinical assessment (430/562 (77%)), treatment (418/557 (75%)), and consulting doctor's manner (434/492 (88%)). Patients' reported outcome and use of general practice in 7-10 days after attendance were similar: 206/241 (85%), 224/263 (85%), and 52/59 (88%) of those seen by general practitioners, senior house officers, and registrars respectively were fully recovered or improving (chi2 = 0.35, P = 0.840), while 48/240 (20%), 48/268 (18%), and 12/57 (21%) respectively consulted a general practitioner or practice nurse (chi2 = 0.51, P = 0.774). Excluding costs of admissions, the average costs per case were 19.30 pounds, 17.97 pounds, and 11.70 pounds for senior house officers, registrars, and general practitioners respectively. With cost of admissions included, these costs were 58.25 pounds, 44.68 pounds, and 32.30 pounds respectively. CONCLUSION: Management of patients with primary care needs in accident and emergency department by general practitioners reduced costs with no apparent detrimental effect on outcome. These results support new role for general practitioners.

Consultants↗

PubMed1996

Garlic and associated allyl sulfur components inhibit N-methyl-N-nitrosourea induced rat mammary carcinogenesis.

Our previous studies demonstrated that dietary garlic powder supplementation inhibits N-nitrosamine induced DNA alkylation in liver and mammary tissue. The present studies compared the impact of dietary supplementation with garlic powder or two garlic constituents, water-soluble S-allyl cysteine (SAC) and oil-soluble diallyl disulfide (DADS), on the incidence of mammary tumorigenesis induced by N-methyl-N-nitrosourea (MNU). Female Sprague-Dawley rats were fed semi-purified casein based diets with or without supplements of garlic powder(20g/kg), SAC (57 micromol/kg) or DADS (57 micromol/kg) for 2 weeks prior to treatment with MNU (15 mg/kg body wt). Garlic powder, SAC and DADS supplementation significantly delayed the onset of mammary tumors compared to rats receiving the unsupplemented diet. Tumor incidence 23 weeks after MNU treatment was reduced by 76, 41 and 53% in rats fed garlic, SAC and DADS, respectively, compared to controls (P<0.05). Total tumor number was reduced 81, 35 and 65% by these supplements, respectively (P<0.05). In a separate study the quantity of mammary DNA alkylation occurring 3 h after MNU treatment was reduced in rats fed garlic, SAC or DADS (P<0.05). Specifically, O(6)-methylguanine adducts were reduced by 27, 18 and 23% in rats fed supplemental garlic, SAC and DADS, respectively, compared to controls. N(7)-Methylguanine adducts decreased by 48, 22 and 21% respectively, compared to rats fed the control diet. These studies demonstrate that garlic and associated allyl sulfur components, SAC and DADS, are effective inhibitors of MNU-induced mammary carcinogenesis.

Allyl Compounds↗

PubMed1996

Comparison of four RNA extraction methods for the detection of small round structured viruses in faecal specimens.

Four methods for extraction of the RNA genome of small round structured viruses (SRSVs) from faecal specimens by reverse transcription polymerase chain reaction (RT-PCR) were evaluated. The efficiency of recovery of viral RNA and removal of amplification inhibitors were compared. RNA extraction using the metal chelating agent Chelex-100 and Sephadex G200 column chromatography were the most sensitive, detecting a 10(-4) dilution of a known SRSV positive specimen. Guanidinium thiocyanate (GTC) with adsorption of viral RNA onto silica was 10-fold less sensitive. The fourth method, based on PEG precipitation followed by phenol/chloroform extraction with the addition of the detergent cetyltrimethylammonium bromide (CTAB), only detected a 1 in 10 dilution of the positive specimen. The CTAB method was 2- to 50-fold less sensitive than the GTC/silica method when dilution series of three further SRSV positive specimens were tested. Thirty-six SRSV negative faecal specimens were spiked with virus and RT-PCR performed following RNA extraction by each of the four techniques in order to assess the ability of these methods to remove amplification inhibitors. The GTC/silica method successfully removed inhibitors from all samples whereas partial or complete inhibition was observed in seven (19%) specimens following extraction by the CTAB method, 17 (47%) by the Sephadex method, and 20 (56%) by the Chelex method. We conclude that, of these four methods, the GTC/silica method is the most appropriate for the extraction of viral RNA from faecal samples prior to RT-PCR for detecting SRSVs.

Base Sequence↗

PubMed1996

Anosognosia in Alzheimer's disease.

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Agnosia↗

PubMed1996

Low incidence of androgen receptor gene mutations in human prostatic tumors using single strand conformation polymorphism analysis.

It is possible that structural changes of the androgen receptor (AR) contribute to the insensitivity of prostatic carcinomas to endocrine therapy. We have isolated DNA from 58 human prostate tumor specimens (31 carcinomas pretreatment, 13 carcinomas after relapse to hormonal therapy, and 14 benign prostatic hyperplasia), three established human prostate carcinoma cell lines and two transplantable human prostatic carcinoma xenografts. Twelve pairs of oligonucleotide primers were used to amplify the majority of the coding region of the AR gene and the products screened for mutations using single-strand conformation polymorphism (SSCP) techniques. In one tumor sample a cytosine to guanine transition in exon F which leads to substitution of glutamic acid for the wild type glutamine at position 798 of the ligand binding domain was detected. The same mutation was also found in the patient's genomic DNA and as been described in a patient with partial androgen insensitivity syndrome. Intronic mutations were detected in two of the benign prostatic hyperplasia samples, and a silent mutation at nucleotide 995 was found to be present in eight poorly differentiated carcinomas, one BPH specimen, as well as in the cell line DU145 (18% of the samples studied). In agreement with most of the literature, these studies indicate that AR mutations are rare both prior to therapy and even in androgen relapsed tumors.

Humans↗

PubMed1996

Treatment of advanced Parkinson's disease by posterior GPi pallidotomy: 1-year results of a pilot study.

The effects of posterior internal pallidal ablation (GPi pallidotomy) on parkinsonian signs and symptoms were studied in 15 patients with medically intractable Parkinson's disease (PD). The sensorimotor territory of the internal portion of the globus pallidus and the adjacent optic tract and internal capsule were identified with microelectrode recording and stimulation. Radiofrequency lesions were then created in the identified sensorimotor territory. Pallidotomy significantly improved all cardinal parkinsonian motor signs (tremor, rigidity, akinesia/bradykinesia, and gait dysfunction) and reduced drug-induced motor fluctuations and dyskinesias. The improvements occurred predominately contralateral to the lesion, but were also present ipsilaterally. Early postoperative (3-month), mean total United Parkinson's Disease Rating Scale scores improved by 30.1% from preoperative values. Mean combined "on/off" Schwab and England Scale scores, a measure of functional independence, increased from 48.8% to 73.0% postoperatively. The mean total United Parkinson's Disease Rating Scale and Schwab and England scores did not show a statistically significant decline over the 1-year postoperative period. Surgery resulted in little morbidity, including a lack of significant deficits on neuropsychological and psychiatric testing. Physical and social functioning and vitality measures on the Medical Outcome Scale also showed significant improvement over the postoperative period. The findings of this pilot study demonstrate that ablation of the sensorimotor portion of the internal pallidum is a highly effective treatment for advanced PD, with benefits sustained at 1 year.

Adult↗

PubMed1996

Event-related potential P3 change in mild Parkinson's disease.

The purpose was to determine if unmedicated, mildly affected patients with Parkinson's disease exhibited abnormality in the P3 component of the event-related potential, and whether such abnormality differed between younger and older patients. The study evaluated 10 younger (mean age = 43.7 years) and 10 older (mean age = 64.4 years) unmedicated patient volunteers diagnosed with idiopathic PD during the past 4 years and equal numbers of age-, gender-, and education-matched controls. The auditory oddball P3 was recorded, and P3 peak amplitude, peak latency, and the component score derived from principal components analysis were analysed. Neuropsychological measures focusing on frontal lobe and memory function were obtained. Although patients did not show neuropsychological deficits, they had significantly enlarged P3 amplitude measured at Cz (p < 0.01) or Pz (p < 0.01). The P3 amplitude abnormality among patients was not affected by age. Patient P3 latency was not prolonged. The results indicate that P3 amplitude may more sensitive than neuropsychological measures for detecting subtle brain dysfunction occurring early in PD. This measure has possible utility for detecting and tracking early disease. It is hypothesized that enlarged P3 amplitude reflects abnormality in use of attentional resources to compensate for brain dysfunction.

Adult↗

PubMed1996

Self-perceived unmet health care needs of persons enrolled in HIV care.

We examined the prevalence of, and factors associated with unmet health service needs among persons with HIV disease. Data were examined from 1,851 participants in the U.S. AIDS Cost and Service Utilization Study, drawn from 26 medical care providers in 10 cities. Geographic areas with large numbers of AIDS cases, and health care providers within them were chosen as study sites. After completing a screener questionnaire, potential participants at each site were stratifed by illness stage, HIV exposure route, and insurance status; a systematic random sample within those strata were selected for the study. Participants completed a comprehensive survey of HIV-related service use and costs, which also asked them to identify unmet health service needs. Analyses identified the relationship between unmet needs and: stage of illness, type of insurance, source of care, living arrangement, and AIDS prevalence of respondents' geographic region. At least one unmet need was reported by 20% of the sample. Needs for non-institutional services, e.g, dental care, mental health, and medications were more likely to be unmet than need for emergency room and hospital care. While most factors significantly affected the odds of having an unmet need, the greatest effects were found for private insurance and HIV asymptomatic status, both of which decreased the odds of unmet needs by approximately 50%. These findings suggest that insurance coverage for services required during the chronic phase of HIV illness is inadequate and should be augmented.

Acquired Immunodeficiency Syndrome↗

PubMed1996

Evaluation of a degenerate primer for the PCR detection of human caliciviruses.

Numerous outbreaks of gastroenteritis have been associated with Norwalk virus and Small Round Structured Viruses (SRSVs). These single-stranded RNA viruses, recently classified in the Caliciviridae, have been divided into three genogroups. Antigenic relationships also have been established among the different strains. As both an in vitro culture system and an animal model are lacking for these viruses, virus detection depends primarily on electron microscopy, immunological assays or molecular detection. In this study we first analyzed the genetic homology of the RNA polymerase region for 40 SRSV strains. From a consensus sequence for these strains, we designed a degenerate oligonucleotide to prime cDNA synthesis from viral RNA. We evaluated the degenerate primer in combination with three previously described primers in PCR reactions. A panel of 15 stools containing SRSVs, typed when possible by solid phase immune electron microscopy (SPIEM), were selected to represent all three genogroups and four different SPIEM antigenic types. Serial dilutions of the purified viral nucleic acids were amplified using the three different primer sets. Virus-specific probes were used to characterize the amplicons obtained. Virus-specific amplicons were obtained with at least one primer pair for each strain, but apparent viral RNA titers differed as much as 1000-fold between primer sets. Amplicons from all but one of the 15 strains were confirmed as virus-specific using a panel of 10 different probes. Correlations between the most sensitive primer pair and SPIEM type were seen. This study showed that a single degenerate primer could be used in cDNA synthesis for a variety of SRSVs but that the sensitivity of the RT-PCR assay depended upon the second primer and virus-specific probes used.

DNA Primers↗

PubMed1996

Evaluation of an antigen capture ELISA based on recombinant mexico virus capsid protein.

BACKGROUND: The diagnosis of gastrointestinal infections caused by small round structured viruses (SRSV) has relied upon electron microscopy and antigen/antibody assays based on Norwalk virus. We investigated cases of gastroenteritis associated with SRSVs employing a new sandwich enzyme-linked immunosorbent assay (ELISA) using hyperimmune animal anti-sera against recombinant Mexico virus capsid protein (rMXV). STUDY DESIGN: One hundred and thirty-five specimens from 86 episodes of gastroenteritis associated with SRSVs, collected in the UK between October 1993 and September 1994, were tested in the rMXV assay. RESULTS: Forty-seven (35%) specimens from 35 of 86 (41%) episodes were positive in the rMXV ELISA and these could further be divided into high and low reactors. Sequencing of a 266-base region of the RNA polymerase gene revealed that strains highly reactive in the rMXV assay demonstrated a high degree of similarity to MXV (97-99% at the nucleotide level), whereas low-reactive strains consist of Mexico-like strains and a heterogeneous group of viruses exhibiting 70-75% similarity to MXV. CONCLUSION: Our results indicate that the rMXV ELISA is predominantly a type specific assay, although some cross reactivity with other genogroup 2 SRSVs was observed. MXV was responsible for 26% of SRSV-associated gastrointestinal infections investigated in the UK during one year's surveillance.

Journal Article↗

PubMed1996

An investigation into perihilar inflammatory change on the chest radiographs of children admitted with acute respiratory symptoms.

PURPOSE: To determine the incidence, correlation with selected parameters and interobserver variability of radiographic perihilar inflammatory change (PIC) in previously well children under 3 years of age, who were hospitalized with acute respiratory symptoms. PATIENTS AND METHODS: A total of 113 previously well children under 3 years of age who were hospitalized with acute respiratory symptoms, and whose chest radiographs (CRGs) showed no focal pulmonary abnormality, were prospectively identified. The CRGs were read blindly by two radiologists. Each scored the degree of PIC on a five point scale as absent (0), borderline/equivocal/indeterminate (1), mild but definite (2), moderate (3) and severe (4). RESULTS: PIC was read as definitely present (mean PIC score greater than or equal to 2) in 65 (58%) patients. The mean PIC score correlated with overinflation (r = 0.45, P < 0.01) and patient temperature (r = 0.22, P < 0.05). The mean PIC score was significantly higher (2.1 vs 1.5, P < 0.01) in those receiving antibiotics (n = 69). It was also significantly higher (2.4 vs 1.7, P < 0.01) in those receiving supplemental oxygen (n = 26). PIC was not associated with duration of admission, presence of wheeze (n = 79), use of nebulized bronchodilators (n = 61) or RSV positivity (n = 32). The k value for interobserver variability indicated only fair agreement (k = 0.29) between the two readers on the five point scale and moderate agreement (k = 0.41) when the data was pooled into two groups (0 and 1 vs 2, 3 and 4). CONCLUSIONS: PIC is a common radiographic finding in children under 3 years of age who are hospitalized with acute respiratory symptoms. It is positively but weakly correlated with temperature, hyperinflation, antibiotic usage and supplemental oxygen administration. It is subject to substantial interobserver variability.

Acute Disease↗

PubMed1996

Nephrotic syndrome and renal insufficiency associated with lithium therapy.

Although the therapeutic administration of lithium in the psychiatric setting has been associated with various renal side effects, only a few reported cases have suggested a possible link to glomerular disease. We report two patients who, while taking lithium, developed heavy proteinuria caused by minimal change disease and acute renal insufficiency attributable to acute tubular necrosis. These clinical findings resolved on discontinuation of the drug, suggesting a role for lithium in their development. We also postulate that lithium, with its unique properties as a modulator of the phosphoinositol pathway, may play a key role in the pathogenesis of minimal change disease.

Acute Kidney Injury↗

PubMed1996

The importance of renal impairment in the natural history of Bardet-Biedl syndrome.

Bardet-Biedl syndrome is a rare autosomal recessive disease characterized by dysphormic extremities, retinal dystrophy, obesity, hypogenitalism in males, and renal structural abnormalities. Because the clinical outcome of these patients is not well known, 21 families with Bardet-Biedl syndrome (BBS) were studied to determine the natural history of the disease. In a prospective cohort study, 38 patients with the syndrome and 58 unaffected siblings were identified. Patients were studied in 1987 and again in 1993. Age of onset of blindness, hypertension, diabetes, renal impairment, and death was determined. The prevalence of obesity, gonadal dysfunction, and renal structural abnormalities was assessed. All but 5 BBS patients (86%) were legally blind, 26% being blind by the age of 13 years and 50% by 18 years. Eighty-eight percent were above the 90th percentile for height and weight. Twenty-five (66%) patients had hypertension, 25% of BBS patients by age 26 years, and 50% by age 34 years, whereas in the unaffected group, 25% had hypertension by age 49 years (P < 0.0001). Twelve (32%) BBS patients developed diabetes mellitus, compared with none of the unaffected group. Only 2 patients were insulin dependent. Twenty-five percent of BBS patients had diabetes by the age of 35 years. In 12 women of reproductive age, 1 (8%) had primary gonadal failure. In 10 men, 4 had primary testicular failure. Nine (25%) patients developed renal impairment, with 25% of the BBS group affected by the age of 48 years. Imaging procedures of the kidney were performed in 25 patients with normal renal function. Whereas fetal lobulation and calyceal cysts/diverticula/clubbing were characteristic, occurring in 96% of patients, 20% (n = 5) had diffuse and 4% (n = 1) focal cortical loss. Eight patients with BBS died, 3 with end-stage renal failure and 3 with chronic renal failure. On life-table analysis, 25% of BBS patients had died by 44 years, whereas at that age 98% of unaffected siblings were still alive (P < 0.0001). Bardet-Biedl syndrome has an adverse prognosis, with early onset of blindness, obesity, hypertension, and diabetes mellitus. Renal impairment is frequent and an important cause of death. Survival is substantially reduced.

Abnormalities, Multiple↗

PubMed1996

FNR-DNA interactions at natural and semi-synthetic promoters.

Two rapid and convenient methods have been developed for the amplification and purification of FNR, the anaerobic transcription regulator of Escherichia coli. The overproduced proteins resemble wild-type FNR in their basic properties: oligomeric state, iron contents (up to 2.7 atoms per monomer), DNA-binding affinities and ability to activate transcription. However, unlike previous preparations, FNR could be isolated in a form containing up to 0.25 atoms of acid-labile sulphur per monomer. Incorporation of iron increased the Mr of FNR from 28,000 to 40,000. Under anaerobic conditions, reconstituted FNR exhibited absorption maxima at 315 nm and 420 nm, which were replaced by a broad absorbance from 380 to 440 nm under aerobic conditions. These observations indicate that FNR contains one redox-sensitive [3Fe 4S] or [4Fe 4S] centre per monomer. Footprints of FNR-dependent promoters (ansB, fdn, fnr, narG, pflP6, pflP7 and nirB) showed protection at all of the predicted FNR sites except the pflP7 (-57.5), ansB (-74.5) and nirB (-89.5) sites. An unpredicted second binding site was detected at -57.5 in the narG promoter. Hypersensitive sites within regions of FNR protection indicated that FNR bends DNA in a similar way to CRP. Promoters containing binding sites for FNR (FF), CRP (CC) or hybrid sites (CF or FC) were footprinted with FNR and two derivatives (FNR-610 and FNR-573) which activate the CCmelR promoter in vivo. FNR preferentially protected the FNR site (FF) whereas FNR-610 preferred CC and FNR-573 interacted with equal affinity at all sites.

Amino Acid Sequence↗

PubMed1996

Comparative modelling and analysis of amino acid substitutions suggests that the family of pregnancy-associated glycoproteins includes both active and inactive aspartic proteinases.

The pregnancy-associated glycoproteins (PAGs) are secretory products synthesized by the outer epithelial cell layer (chorion) of the placentas of various ungulate species. The amino acid sequences of eight PAGs have been inferred from cloned cDNA of cattle and sheep, as well as of the non-ruminant pig and horse. We compare the PAG sequences and present results of the three-dimensional models of boPAG-1 and ovPAG-1 that were constructed on the basis of the crystal structures of homologous porcine pepsin and bovine chymosin using a rule-based comparative modelling approach. Further, we compare peptide binding subsites defined by interactions with pepstatin and a decapeptide inhibitor (CH-66) modelled on the basis of crystal structures of other aspartic proteinases. We have extended our analysis of the peptide binding subsites to the other PAG molecules of known sequence by aligning the PAG sequences to the structural template derived from the pepsin family and by making use of the three-dimensional models of the boPAG-1 and ovPAG-1. The residues that are likely to affect peptide binding in the boPAG-1, ovPAG-1 and other PAG molecules have been identified. Sequence comparisons reveal that all PAG molecules may have evolved from a pepsin-like progenitor molecule with the equine PAG most closely related to the pepsins. The presence of substitutions at the S1 and other subsites relative to pepsin make it unlikely that either bovine, ovine or the porcine PAG-1 have catalytic activity. Only two of the eight PAGs examined (porcine PAG-2 and equine PAG-1) retain features of active aspartic proteinases with pepsin-like activity. Our results indicate that in the PAGs so far characterized the peptide binding specificities differ significantly from each other and from pepsin, despite their high sequence identities. Analysis of the various peptide binding subsites demonstrates why both bovine and ovine PAG-1 are capable of binding pepstatin. The strong negative charge in the binding cleft of boPAG-1 and ovPAG-1 indicates a preference for lysine- or arginine-rich peptides. PAGs represent a family where the possible peptide binding function may be retained through their binding specificities, but where the catalytic activity may be lost in some cases, such as the boPAG-1, ovPAG-1 and the poPAG-1.

Amino Acid Sequence↗