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N Doshi

Publications and source records attributed to N Doshi.

At least 19 recordsLinked to original sources
PubMed2007

Comparison of clinical and environmental isolates of Legionella pneumophila obtained in the UK over 19 years.

Between January 1980 and December 1998, 3458 cases of Legionnaires' disease were reported to the national surveillance scheme in England and Wales. Of these, 463 (13.4%) were reported as proven by culture and isolation of Legionella spp., with 96.3% being Legionella pneumophila. Serogroup (Sgp), monoclonal antibody (mAb) subgrouping and restriction fragment length polymorphism (RFLP) analysis data were obtained for 321 (69.3%) of these, of which 284 were classified as being unrelated to any other isolate in the study. Typing data were also available for 117 unrelated environmental isolates of L. pneumophila obtained from England and Wales, giving a total of 401 unrelated isolates in the study. Of the clinical isolates, 88.0% were Sgp1, compared with only 42.7% of environmental isolates (p <0.001); 79.6% of clinical isolates were subgrouped as mAb2+, compared with only 12.8% of environmental isolates (p <0.001). RFLP typing identified 67 types among the 401 isolates, with clinical isolates showing significantly less diversity than environmental isolates (index of diversity (IOD) 0.944 vs. 0.958; p <0.05), with three RFLP types (1, 5 and 14) accounting for 40.0% of all clinical isolates. Combining the phenotypic and genotypic data resulted in 173 distinct phenons, with clinical isolates showing significantly less diversity than environmental isolates (IOD 0.964 vs. 0.996; p <0.01). Three phenons accounted for 30% of all clinical isolates. These data strongly suggest that some strains of L. pneumophila are more likely to cause human infection than would be expected from their distribution in the environment.

Disease Outbreaks↗
PubMed2001

Evaluation of the Bartels Legionella Urinary Antigen enzyme immunoassay.

The Bartels Legionella Urinary Antigen enzyme immunoassay (Intracel, USA) is intended for the presumptive diagnosis of past or current Legionnaires' disease by qualitative detection of Legionella pneumophila serogroup 1 antigen in human urine. This test was evaluated using single urine samples collected from 349 patients with lower respiratory tract infection of known aetiology. Specificity was estimated as 100% (181 samples, 95% CI: 98%-100%); sensitivity for Legionella pneumophila serogroup 1 was 98.8% (167 samples, 95% CI: 95.7%-99.9%). Assessing assay results using a Visual Interpretation Card provided by the manufacturer in place of a photometer gave rise to one false-positive result among the 78 control samples examined. Providing the endpoint of this assay is determined photometrically, the Bartels Legionella Urinary Antigen enzyme immunoassay appears to be a highly specific and sensitive kit for the diagnosis of infection caused by Legionella pneumophila serogroup 1.

Antigens, Bacterial↗
PubMed2001

Detector development for microPET II: a 1 microl resolution PET scanner for small animal imaging.

We are currently developing a small animal positron emission tomography (PET) scanner with a design goal of 1 microlitre (1 mm3) image resolution. The detectors consist of a 12 x 12 array of 1 x 1 x 10 mm lutetium oxyorthosilicate (LSO) scintillator crystals coupled to a 64-channel photomultiplier tube (PMT) via 5 cm long optical fibre bundles. The optical fibre connection allows a high detector packing fraction despite the dead space surrounding the active region of the PMT. Optical fibre bundles made from different types of glass were tested for light transmission, and also their effects on crystal identification and energy resolution, and compared to direct coupling of the LSO arrays to the PMTs. We also investigated the effects of extramural absorber (EMA) in the fibre bundles. Based on these results, fibre bundles manufactured from F2 glass were selected. We built three pairs of prototype detectors (directly coupled LSO array, fibre bundle without EMA and fibre bundle with EMA) and measured flood histograms, energy resolution, intrinsic spatial resolution and timing resolution. The results demonstrated an intrinsic spatial resolution (FWHM) of 1.12 mm (directly coupled), 1.23 mm (fibre bundle without EMA coupling) and 1.27 mm (fibre bundle with EMA coupling) using an approximately 500 microm diameter Na-22 point source. Using a 330 microm outer diameter steel needle line source filled with F-18, spatial resolution for the detector with the EMA optical fibre bundle improved to 1.05 mm. The respective timing and energy FWHM values were 1.96 ns, 21% (directly coupled), 2.20 ns, 23% (fibre bundle without EMA) and 2.99 ns, 30% (fibre bundle with EMA). The peak-to-valley ratio in the flood histograms was better with EMA (5:1) compared to the optical fibre bundle without EMA (2.5:1), due to the decreased optical cross-talk. In comparison to the detectors used in our current generation microPET scanner, these detectors substantially improve on the spatial resolution, preserve the timing resolution and provide adequate energy resolution for a modern high-resolution animal PET tomograph.

Animals↗
PubMed1999

Serological evidence of Bartonella spp. infection in the UK.

We reviewed serological and epidemiological data relating to 1000 consecutive patients from whom specimens were submitted for estimation of bartonella antibodies, using MRL Diagnostics Bartonella IFA IgM and IgG kits. Using 289 control sera, we estimated the specificity of the kits as > or = 99.0%. Evidence of bartonella infection was found in 16.3% of patients examined. Rates varied by patient group: 20% of patients for whom a diagnosis of cat scratch disease (CSD) was considered probable had evidence of infection, as did 10.4% of patients with 'possible CSD', 8.1% of patients with possible bacillary angiomatosis, 18.2% of patients with 'culture negative' endocarditis and 17.6% of patients with possible bartonellosis with ophthalmic involvement. An IgM response was seen in 6.6% of patients and IgG in 15.1%. Cases were more frequent among males than females (18.5% vs. 13.9%). Analysis by age showed that although rates of infection were highest in the decades 0-9 years (19.4%) and 10-19 years (20.7%), they fell only slightly in the next three decades. MRL bartonella kits appears to provide a useful and specific approach to the diagnosis of these infections.

Adolescent↗
PubMed1999

Robustness of protein folding kinetics to surface hydrophobic substitutions.

We use both combinatorial and site-directed mutagenesis to explore the consequences of surface hydrophobic substitutions for the folding of two small single domain proteins, the src SH3 domain, and the IgG binding domain of Peptostreptococcal protein L. We find that in almost every case, destabilizing surface hydrophobic substitutions have much larger effects on the rate of unfolding than on the rate of folding, suggesting that nonnative hydrophobic interactions do not significantly interfere with the rate of core assembly.

Amino Acid Substitution↗
PubMed1999

Survey of Bartonella species infecting intradomicillary animals in the Huayllacallán Valley, Ancash, Peru, a region endemic for human bartonellosis.

The natural cycle of Bartonella bacilliformis remains uncertain, and the suspected existence of animal reservoirs for the bacterium has never been convincingly demonstrated. We conducted a survey of Bartonella species infecting intradomicillary animals in a bartonellosis-endemic region of Peru, obtaining blood from 50 animals living in the homes of 11 families whose children had recently had bartonellosis. Bartonella-like bacteria were recovered from four of nine small rodents included in the study, but from none of the 41 domesticated animals. Identification and comparison of these isolates, and two Bartonella-like isolates obtained from Phyllotis mice in a different endemic region of Peru using serologic and genotypic methods indicated that although none were strains of B. bacilliformis, five were probably representatives of three previously unrecognized Bartonella species and one was a likely strain of the pathogenic species B. elizabethae.

Animals↗
PubMed1997

Functional rapidly folding proteins from simplified amino acid sequences.

Early protein synthesis is thought to have involved a reduced amino acid alphabet. What is the minimum number of amino acids that would have been needed to encode complex protein folds similar to those found in nature today? Here we show that a small beta-sheet protein, the SH3 domain, can be largely encoded by a five letter amino acid alphabet but not by a three letter alphabet. Furthermore, despite the dramatic changes in sequence, the folding rates of the reduced alphabet proteins are very close to that of the naturally occurring SH3 domain. This finding suggests that despite the vast size of the search space, the rapid folding of biological sequences to their native states is not the result of extensive evolutionary optimization. Instead, the results support the idea that the interactions which stabilize the native state induce a funnel shape to the free energy landscape sufficient to guide the folding polypeptide chain to the proper structure.

Amino Acid Sequence↗
PubMed1992

Further evidence that genotypically closely related strains of Legionella pneumophila can express different serogroup specific antigens.

The relationship between serogroup and genotype of Legionella pneumophila strains was investigated by restriction fragment length polymorphism (RFLP) typing with a previously standardised method. Of the 51 RFLP types identified, 19 comprised strains of more than one serogroup. Several RFLP types included strains of five or more serogroups. To determine if sharing the same RFLP type indicates that strains are genotypically indistinguishable or merely that they are superficially similar, 31 strains were selected for further analysis with an extended range of restriction endonucleases and nucleic acid probes. In some cases, strains of a particular RFLP type were indistinguishable, while in others the restriction fragment patterns showed minor differences. It is possible that in the latter case the strains are diverging representatives of a parent clone. We conclude that analysis of restriction fragment patterns, either probed or unprobed, provides a more accurate measure of the ancestral relationship between strains than can be obtained with serological methods.

Antigens, Bacterial↗
PubMed1992

A second serogroup of Legionella erythra serologically indistinguishable from Legionella rubrilucens.

Twenty-two red-autofluorescent Legionella strains were identified serologically as either Legionella rubrilucens or L. erythra. A rRNA probe was used for restriction fragment length polymorphism (RFLP) analysis of the strains and the patterns generated were used as an additional method of identifying the strains to species level. In two instances strains which were identified as L. rubrilucens by serology appeared to belong to the species L. erythra by RFLP analysis. This apparent contradiction was resolved by measurements of DNA/DNA homology which confirmed the existence of a second serogroup of L. erythra serologically indistinguishable from L. rubrilucens.

DNA, Bacterial↗
PubMed1992

Observer variation in an audit of charts of patients with rheumatoid arthritis.

Arthritis Society physiotherapists (PTs) in Ontario adopted Problem Oriented Records (POR) to monitor patient care; goals were to encourage patient specific treatment plans and standardized records. After nine months in practice, the POR system was evaluated by an audit on charts of patients with Rheumatoid Arthritis. Audit teams of two PTs were created within each of five geographic areas. Auditors attended an audit instruction workshop. Two charts, selected randomly from the discharged patients of each of 38 therapists, were independently scored on 56 items by an audit team. The extent of agreement within the auditor team (observer variation) was measured, and adequacy scores computed for each chart. Adequate reliability of the audit instrument was established before examination of adequacy scores and making inferences about quality of care. The auditor agreement measures (kappa) varied from 0.13 to 0.97, mean = 0.74 and SD = 0.16; these estimates were indicative of adequate reliability of the audit form, although agreement scores were different amongst the five areas (P2 less than .01). POR adequacy scores varied from 10.0 to 93.1, mean = 64.5 and SD = 16.9. There were no differences in adequacy scores amongst the five areas (P2 = .61). To reduce observer variation, increased pre-audit emphasis is needed on auditor guidelines and training for items relating to assessment findings, problem identification, and treatment planning.

Analysis of Variance↗
PubMed1991

Beemer-Langer syndrome with manifestations of an orofaciodigital syndrome.

We report on an infant girl with hydrops, macrocephaly, high forehead, flat face, hypertelorism, broad nasal bridge, median cleft lip and alveolar ridge, grooved palate, accessory frenula, small tongue, milia, severe rib and limb shortness, brachydactyly, talipes equinovarus, Dandy-Walker malformation, accessory spleen, unfixed mesentery, ectopic pancreas, and renal cysts. This patient resembles seven previously reported patients with the Beemer-Langer syndrome, a distinct lethal short rib syndrome characterized by hydrops, markedly short ribs and limbs, median cleft lip with or without cleft palate, flat face, and macrocephaly. Polydactyly is usually absent. Our patient's oral anomalies suggest an orofaciodigital syndrome, but the severe rib and limb shortness distinguish it from those disorders.

Adult↗
PubMed1991

Second serogroup of Legionella quinlivanii isolated from two unrelated sources in the United Kingdom.

A series of strains, presumptively identified as legionellas on the basis of their nutritional requirements and biochemical reactivity, were isolated from two unrelated environmental sources in the UK. Representatives of each of these series had a restriction endonuclease digest pattern indistinguishable from that of the Legionella quinlivanii type strain (1442-AUS-E) and the identity of these strains was confirmed by DNA homology studies. Serological examination of the two strains showed that they were distinct from the type strain 1442-AUS-E but indistinguishable from each other. A second serogroup, L. quinlivanii serogroup 2 (type strain LC870; NCTC 12434), is proposed to accommodate these strains.

Air Conditioning↗
PubMed1990

Typing of Legionella pneumophila serogroups 2-14 strains by analysis of restriction fragment length polymorphisms.

A typing method based on analysis of restriction fragment length polymorphisms has previously been developed for Legionella pneumophila serogroup 1. Here data are presented demonstrating the utility of this method for typing strains of all other L. pneumophila serogroups described to date. The method, which is highly discriminatory, should be of considerable value in epidemiological investigations of legionella infections.

Bacterial Typing Techniques↗
PubMed1989

Infiltrating lobular carcinoma: mammographic patterns with pathologic correlation.

Of the five identified radiographic patterns of ILC, the most common was a poorly defined asymmetric density with architectural distortion. Areas of ILC frequently are of low density, not much greater than that of the surrounding parenchyma. The mammographic appearance may reflect the behavior of ILC tumor cells, which travel in linear array ("single file") along and around the arborizing ducts that serve as scaffolding for these small, malignant cells that permeate the parenchyma without a central nidus. This feature of ILC may also help explain why tumors may be palpable as areas of vague induration or thickening rather than as discrete masses. When tumors are hidden in dense breast tissue (pattern 3) and not well imaged by mammography or when there are subtle mammographic changes (pattern 1), sonography may help confirm the presence of a solid mass. Most of the suspected tumors imaged by sonography were palpable as discrete masses or areas of induration.

Adult↗
PubMed1988

Serological diversity within the species Legionella spiritensis.

A strain of Legionella isolated from the environment which could not initially be identified was shown by restriction fragment length polymorphisms to be a Legionella spiritensis. This was confirmed by DNA homology studies, cell wall fatty acid composition and isoprenoid quinone analysis. This strain, which is only the second reported representative of the species, was shown to be serologically distinct from the type strain of L. spiritensis and all other serogroups of Legionella.

Antigenic Variation↗
PubMed1988

The significance of atypical cervical smears.

The significance of and approach to cervical smears showing cytologic atypia without dyskaryosis remains controversial. A review of 139 colposcopies performed for atypical cytology revealed cervical intraepithelial neoplasia (CIN) in 25%. Of the CIN found, 85% was CIN I and 15%, II. No case of more advanced disease was found. The type and severity of the cytologic atypia correlated with the presence of CIN. However, all degrees of atypia were found to have a significant association with CIN, and the degree of cytologic atypia therefore cannot be used to exclude colposcopy in any women with atypical smears. This study suggested that cytologic atypia is an expression of early CIN, and the results support our endorsement of routine colposcopy in the evaluation of women with persistent atypia.

Adolescent↗