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Biomedical subjects

J M Jones

Publications and source records attributed to J M Jones.

At least 127 records · Page 7Linked to original sources
PubMed1992

Localization of insulin-2 (Ins-2) and the obesity mutant tubby (tub) to distinct regions of mouse chromosome 7.

A DNA mapping panel derived from an interspecific backcross was used to position the mouse insulin-2 locus (Ins-2) on Chromosome 7, near H19 (0/114 recombinants) and Th (1/114 recombinants). Ins-2 is part of a human-mouse conserved linkage group that includes Th, H19, and Igf-2. Analysis of segregation in the F2 generation from the cross C57BL/6J-tub/tub x CAST/Ei demonstrated that Ins-2 and the obesity mutant tubby (tub) are distinct loci, thus eliminating Ins-2 as a candidate gene for tub. These results also refine the estimated genetic distance between tub and Hbb to 2.4 +/- 1.4 cM. The predicted location for a human homolog of tubby is HSA 11p15.

Animals↗
PubMed1992

Glomerular basement membrane thinning in adults: clinicopathological correlations of a new diagnostic approach.

We have studied glomerular basal laminar thickness in biopsy material, using a simple technique involving 16 selected measurements per case. Twenty-nine biopsied cases of adult glomerular haematuria were examined together with 'diseased' controls represented by a variety of glomerulopathies including minimal-change disease and IgA nephropathy. 'Normal' control populations were provided by 13 patients with acute-onset renal failure of non-glomerular origin and nine patients undergoing nephrectomy. Analysis of groups determined by the presence or absence of haematuria, the degree of proteinuria and presence or absence of a diagnostically characteristic immunofluorescence pattern showed that the nine patients with haematuria and proteinuria of less than 200 mg/24 h represented a distinct subpopulation with a mean membrane thickness of 225 nm compared to the control mean of 343 nm (P less than 0.0001). All members of this subpopulation had mean values below an arbitrary cut-off value of 270 nm. Within other specific disease categories, sporadic cases had mean membrane thicknesses below this critical value, indicative of an overlap of pathologies. On short-term follow-up there is no evidence that the 'pure' thin-membrane population are subject to any deterioration in renal function. It is of further interest that eight of nine thin-membrane 'syndrome' cases were O Rh positive. This finding may provide a starting point for investigation of a specific genetic defect.

ABO Blood-Group System↗
PubMed1992

Protein kinase C regulates activation of mitogen-activated protein kinase and induction of proto-oncogene c-fos by endothelin-1.

Endothelins (ETs) are potent regulatory peptides that cause numerous phenotypic changes in glomerular mesangial cells including differential regulation of gene expression and mitogenesis. Although the second messengers produced by activated ET receptors are well characterized, little is known about pathways of nuclear signaling. In this report, we evaluate the role of a well-characterized effector linked to ET receptor activation, protein kinase C, in the stimulation of mitogen-activated protein kinase (p42-44mapk) and the induction of protooncogene c-fos. Stimulation of protein kinase C by phorbol ester was sufficient to increase p42-44mapk activity and induce c-fos. When ET-1 was added to mesangial cells depleted of protein kinase C, the increase in p42-44mapk was attenuated and the induction of c-fos was abolished. Taken together with previous data, these experiments suggest that protein kinase C, p42-44mapk, and c-fos constitute a pathway by which ET-1 regulates expression of mesangial cell genes. These effectors might have relevance to the role of ET-1 in cell growth and vascular remodeling.

Animals↗
PubMed1992

Measuring the quality of junior hospital doctors in general medicine.

During the course of a larger study aimed at relating staffing levels of junior doctors in general medicine to the safety of the care provided, it became clear that consultant doctors considered the quality of their junior staff as being at least as important as the quantity. This paper describes several attempts to develop a feasible and valid method of measuring the quality of senior house officers (SHOs) and registrars using routinely available data. Having rejected three methods and had difficulties with three other methods, a modified Delphi survey was used to explore the extent to which consultants agreed on the key attributes of a high quality SHO or registrar. Sixty-seven (60%) of all consultants in the South-West Thames and Trent regions responded to two rounds of questionnaires which revealed communication skills as being consistently the most significant factor. This was confirmed in a second, anonymous survey of 198 (78%) SHO and registrar posts in the North-West Thames region. It also became clear that consultants viewed the quality of their own SHOs and registrars as generally high. This being so it is argued that the requirement to adjust for quality, when comparing SHO and registrar levels between hospitals, is of minor importance. These results also suggest that the explicit teaching of communication skills should have a high priority in undergraduate and postgraduate education.

Clinical Competence↗
PubMed1992

Long term follow up of women after hysterectomy with a history of pre-invasive cancer of the cervix.

OBJECTIVE: A long term review of women after hysterectomy with a history of pre-invasive carcinoma of the cervix. DESIGN: 193 women had cervical intra-epithelial neoplasia and two had adenocarcinoma in situ either at hysterectomy or at previous cone biopsy. These were followed up by annual cytology. SETTING: South Glamorgan Health Authority. SUBJECTS: Of 195 women who had a hysterectomy, 143 have been followed up cytologically for more than 10 years and 43 for more than 20 years: a total of 2800 women years of experience. MAIN OUTCOME MEASURES: Timing of abnormal smears. RESULTS: A detailed review of the five women with abnormal smears. The estimated percentage of women who remain negative is 98% at five years, 98.4%, at 10 years and 96.5% at 20 years. CONCLUSION: Cytological screening of all women who had a hysterectomy with a history of CIN is indicated for the first two years after hysterectomy. Thereafter the estimated incidence of 0.7 per 1000 women years is higher than the general population but it is not a sufficient reason to screen more frequently. We recommend screening for the carcinoma of the vagina to be every three years which is the same screening frequency as for cervical carcinoma in the general population.

Adenocarcinoma↗
PubMed1992

WI-1, a novel 120-kilodalton surface protein on Blastomyces dermatitidis yeast cells, is a target antigen of cell-mediated immunity in human blastomycosis.

A large body of experimental data has demonstrated the central role of T cells in acquired resistance to the dimorphic fungus Blastomyces dermatitidis. We examined the human T-cell response to WI-1, a 120-kDa B. dermatitidis yeast cell surface protein recently shown to be an immunodominant antigen of the B-cell response in infected humans. Peripheral blood lymphocytes from 10 blastomycosis patients studied proliferated in response to WI-1 (mean, 19,431 cpm) and to the standard, crude cell wall antigen, Blastomyces alkali- and water-soluble antigen (B-ASWS) (mean, 19,131 cpm); lymphocytes from 10 histoplasmosis patients and 10 normal control subjects did not respond to WI-1. WI-1 stimulation of patient lymphocytes and rechallenge with WI-1 or B-ASWS showed that the antigens share immunodominant epitopes. Of 100 WI-1-responsive T-cell clones derived from peripheral blood, 10 were studied in detail to assess the phenotype, function, and ligands recognized. The clones exhibit the CD3+ CD4+ phenotype of helper T cells; 2 of 10 clones (and 21% of antigen-stimulated peripheral blood lymphocytes) use the V beta 8 T-cell receptor gene element to respond to WI-1. All the clones proliferate in response to both WI-1 and B-ASWS but not other fungal antigens, and some mediate potent cytolytic effects on WI-1- and B-ASWS-labeled targets. WI-1 recognition requires antigen processing and presentation of epitopes in association with HLA-DR (to noncytolytic clones) and HLA-DP (to cytolytic clones). From these findings, we conclude that CD4+ T cells with regulatory and cytolytic properties are involved in the development of acquired resistance of B. dermatitidis, that the cells are directed against WI-1, and that the manner of display of WI-1 peptide epitopes in conjunction with major histocompatibility complex class II may influence the profile of the immune response.

Antigens, Fungal↗
PubMed1992

Posterior lymph heart pressure and rate and lymph flow in the toad Bufo marinus in response to hydrated and dehydrated conditions.

Posterior lymph heart pressure, rate and flow were measured in chronically cannulated Bufo marinus during normal hydrated and dehydrated conditions. A new surgical technique was developed which allowed direct and constant measurement of the functioning of the posterior lymph hearts with minimal disruption to normal lymph drainage. The mean intra-lymph-heart systolic pressure was 2.29 +/- 0.12 kPa for hydrated animals at rest, decreasing to 1.01 +/- 0.10 kPa after 24 h of dehydration. Similarly, lymph heart rate, which was 48.2 +/- 1.7 beats min-1 under hydrated conditions, decreased to 31.8 +/- 4.6 beats min-1 after 18 h of dehydration. Lymph flow decreased almost to zero during dehydration from a hydrated rate of 1.11 +/- 0.04 ml h-1 100 g-1. This is the first study to measure directly and to correlate these variables in an amphibian and to show specifically that pressure, rate and lymph flow are significantly reduced during periods of dehydration.

Animals↗
PubMed1992

The evolution of chronic pain among patients with musculoskeletal problems: a pilot study in primary care.

Little is known about the evolution of chronic pain in primary care. Forty five patients with a four week history of musculoskeletal pain were assessed and followed up over 26 weeks by a research nurse using a structured interview and formal assessment instruments. Patients aged 18 to 65 years were recruited on presentation at two semirural Cheshire general practices and subsequently interviewed on a domiciliary visit. Twenty patients (44%) continued to have pain at 26 weeks and these patients were considered to have chronic pain. Nineteen patients had no pain after 12 weeks and a further six had no pain after 26 weeks; these patients together formed the group with acute pain. Comparing the two groups at entry into the study (pain of four weeks' duration) demonstrated significantly higher visual analogue scale scores for intensity of pain (P < 0.01) and a higher incidence of depression (P < 0.01) in the group which subsequently developed chronic pain. In this group, the presence of depression at 12 weeks was associated with higher visual analogue scale scores (P < 0.05) but at 26 weeks scores were similar in depressed and non-depressed patients. The correlation between visual analogue scale score for intensity of pain and the use of passive coping strategies to cope with pain appeared more strongly positive with duration of pain (P < 0.05 at 26 weeks). It is suggested that high pain intensity scores, the presence of depression, and the increasing use of passive coping strategies may be identifiable associations with the development of chronic pain. Areas for further research are identified.

Adolescent↗
PubMed1991

Effects of acetate dialysate on transforming growth factor beta 1, interleukin, and beta 2-microglobulin plasma levels.

To evaluate potential adverse effects of acetate use in hemodialysis (HD), we measured plasma interleukin (IL-1 alpha, IL-1 beta, IL-6), TNF alpha, TGF beta 1, and beta 2-microglobulin levels with ELISA assays in normal (N = 9), CRF (N = 6), CAPD (N = 7) and HD (N = 8) subjects and compared the effects of acetate (Ac) and acetate-free (Ac-free) dialysate. TGF beta 1 was the only cytokine consistently detected. Compared to normals (median 57, range 53 to 68 pg/ml, one undetected; N = 8), TGF beta 1 was higher in the CRF (75, 70 to 97 pg/ml, one undetected) and CAPD (75.5, 66 to 116 pg/ml, N = 6) groups (P less than 0.05), and was somewhat higher in the HD (68, 52 to 88 pg/ml) group (P less than 0.10). Acutely, TGF beta 1 pre-HD (70, 63 to 88 pg/ml) increased above normals post AcHD [79.5, 65 to 140 pg/ml uncorrected for ultrafiltration (UF)] and was higher after AcHD versus Ac-free HD both uncorrected (79.5, 65 to 140 pg/ml vs. 70, 52 to 86 pg/ml) and corrected for UF (68, 51 to 115 pg/ml vs. 57, 43 to 69 pg/ml; P less than 0.05). beta 2-microglobulin was not different after AcHD (81.2 +/- 8.0 mg/ml) versus Ac-free HD (72.5 +/- 6.9 mg/ml). Significantly lower serum inorganic phosphorus was also found four hours post-AcHD compared to four hours post-Ac-free HD (0.87 mmol +/- 0.10 SEM vs. 1.05 mmol +/- 0.07 SEM; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗
PubMed1991

Altered expression of HLA antigens and CD16 Fc receptors on leukocytes of alcoholic subjects and uremic patients.

The possible influences of ethanol and its metabolic product acetate on the surface expression of HLA class I and class II antigens and CD16 Fc receptors were examined. Fluorescent-labeled monoclonal antibodies and flow cytometry were used to measure these antigens on leukocytes from reference controls, subjects admitted for alcohol detoxification, uremic patients undergoing hemodialysis using Cu-prophan dialyzers and fluids containing 4 to 37 mM acetate, and uremic patients that were not hemodialyzed. In comparison to the controls, the mean intensity of staining for class I antigens was not changed significantly on lymphocytes or monocytes from alcoholics but was depressed on cells from eight of 12 uremic patients. Interferon-gamma above 5 units/ml was detected in less than 15% of plasma samples from controls, uremic patients or alcoholics on admission but was detected in four of eight samples from alcoholics at discharge (2-4 days after admission). The intensity of staining for class II antigens was depressed by more than 50% on lymphocytes from alcoholics and uremic patients. The expression of HLA class I and class II antigens was depressed whether uremic patients were hemodialyzed or not. The percentage of lymphocytes expressing CD16 was depressed in three of seven alcoholics and five of seven hemodialyzed patients. In contrast, the percentage of monocytes expressing CD16 was increased in six of seven hemodialyzed patients and three of five uremic patients not undergoing hemodialysis suggesting activation of monocytes in these patients. Plasma levels of beta 2-microglobulin were elevated by 61% in alcoholics, 50-fold in hemodialyzed patients, and 26-fold in nonhemodialyzed uremic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Some factors affecting the efficacy of oviduct tissue-conditioned medium for the culture of early bovine embryos.

Oviduct tissue-conditioned medium was evaluated for the culture of IVM-IVF bovine zygotes to the compact morula (cM) and blastocyst (BL) stages. Development was unaffected (P greater than 0.50) by freezing and thawing of conditioned medium: no. cM + BL/no. cleaved ova obtained after culture in nonfrozen, frozen-thawed, and control treatments were 31/148 (21%), 26/124 (21%) and 5/86 (6%), respectively. The greatest proportion of normal development was obtained after a conditioning period of 48 h (P less than 0.05): no. of cM + BL/no. cleaved ova in media conditioned for 5, 24, 48 and 96 h were 23/114 (20%), 38/112 (34%), 43/115 (37%) and 36/125 (29%), respectively. Development declined with increasing dilutions of conditioned media (P less than 0.005): no. cM + BL/no. cleaved ova for 100, 75, 50, 25 and 0% conditioned medium were 32/94 (34%), 29/94 (31%), 17/82 (21%), 10/94 (11%) and 11/73 (15%), respectively. The oestrous cycle stage from which oviducal tissue was obtained did not affect development (P greater than 0.75); no. cM + BL/no. cleaved ova was 21/63 (33%) at oestrus and 21/79 (27%) in the luteal phase.

Animals↗
PubMed1991

Transgenic mice carrying a murine amylase 2.2/SV40 T antigen fusion gene develop pancreatic acinar cell and stomach carcinomas.

The mouse pancreatic amylase Amy-2.2 gene was fused to the structural gene for SV40 T antigen, and 51 independent transgenic founder mice carrying the fusion gene were generated. The majority of the founders and 100% of their offspring in the derived transgenic lines developed pancreatic acinar cell carcinomas and stomach carcinomas. Transgenic animals also had a high incidence of metastatic carcinomas in other tissues. The development of stomach carcinomas was unexpected because the Amy-2.2 promoter was not previously known to be expressed in stomach. Northern blot analyses and ribonuclease protection assays showed that Amy-2.2 is expressed in stomach, at approximately 0.05% of the level in pancreas. Expression of the fusion gene in stomach, therefore, appears to represent a previously unrecognized activity of the Amy-2.2 promoter. Examination of young transgenic mice demonstrated that preneoplastic lesions were present in pancreas and stomach before the development of neoplastic lesions in either tissue, consistent with the notion that stomach neoplasms are primary neoplasms and not metastases from the pancreas. Ribonuclease protection assays demonstrated that properly initiated large T and small t antigen transcripts were present in pancreas and stomach during tumorigenesis. T antigen protein was also detected in pancreas and stomach by immunohistochemistry. A time course for tumorigenesis was established for several transgenic mouse lines in which distinct types of lesions appeared at predictable times. This study provides the basis for future analysis of the role of SV40 T antigen in the progression and maintenance of pancreatic and stomach carcinomas.

Amylases↗
PubMed1990

Perceptions of pain relief after surgery.

OBJECTIVE: To assess patients' satisfaction with postoperative pain relief. DESIGN: A descriptive and questionnaire study of patients' experience. SETTING: Two surgical and two gynaecological wards. PATIENTS: 50 Patients admitted to hospital for cholecystectomy and 51 admitted for hysterectomy. MAIN OUTCOME MEASURES: Visual analogue scales with no divisions were completed by the patients immediately after each dose of postoperative analgesia was administered throughout their stay in hospital. A questionnaire completed on the fifth postoperative day recorded patients' recollections of their experience. Opinions were also sought from medical and nursing staff. RESULTS: During the first 24 hours after surgery recorded pain levels were 60% of the maximum and were not influenced by age, sex, or the type of operation performed. The median interval between the return of pain and a further injection of analgesic was 2 hours (interquartile range 1 to 3.5 hours). Expectations of pain relief were low, and for 70% of the patients the pain was at least as bad as they had expected. Only half of the medical and nursing staff questioned thought that postoperative analgesia should relieve pain completely; drugs were prescribed and administered with too little attention to the patient's response and too much concern about adverse effects and opioid dependence. CONCLUSIONS: The results suggest that the standard of postoperative pain relief is poor because of inadequate education of patients in what to expect (and demand), and of medical and nursing staff in how to prescribe and administer analgesia with reference to individual drug response.

Analgesics↗