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Biomedical subjects

J Hunt

Publications and source records attributed to J Hunt.

At least 109 records · Page 6Linked to original sources
PubMed1995

Localization of transforming growth factor beta and its natural inhibitor decorin in the human placenta and decidua throughout gestation.

Transforming growth factor beta (TGF beta) produced at the human fetomaternal interface has been shown to play a crucial role in controlling trophoblast invasion of the uterus. Decorin, a naturally occurring chondroitin-dermatan sulphate proteoglycan which binds TGF beta can inhibit its activity. In this study, immunohistochemical techniques were used to determine the locations of TGF beta and decorin within the human placenta and decidua throughout normal gestation. In addition, sites of TGF beta 1 mRNA synthesis were identified in early and late placenta by in situ hybridization. Results revealed the presence of immunoreactive TGF beta in the cytoplasm of villous syncytiotrophoblast and extravillous trophoblast cells throughout gestation. TGF beta immunostaining was absent from villous cytotrophoblast at all gestational ages examined. The extracellular matrix (ECM) of the villous core at all stages of gestation and cells of the cytotrophoblastic shell of the term placenta were immunoreactive for TGF beta. Within decidual tissue, TGF beta was primarily localized in the ECM during the first trimester and only a small proportion of decidual cells exhibited intracellular labelling. At later gestational ages the majority of decidual cells showed intracellular labelling accompanied by a decrease in ECM staining. This switch may reflect increased TGF beta synthesis by the decidual cells, decreased release, or altered TGF beta binding to one or more ECM proteins. In situ hybridization indicated that TGF beta 1 mRNA was primarily localized to the syncytiotrophoblast cell layer with low intensity signals present in extravillous trophoblast cells, in trophoblast cell columns, and in large decidual cells. At term, TGF beta 1 mRNA was located in both the syncytiotrophoblast and villous mesenchymal cells. Decorin was immunolocalized to the ECM of the mesenchymal core of the chorionic villi throughout gestation and no immunoreactivity was observed in either villous or extravillous trophoblast. In the first trimester decidua, decorin was localized to the ECM whereas decidual cells, decidual leucocytes, and the uterine epithelium were negative. At later gestational ages, the ECM as well as a few decidual cells displayed weak immunoreactivity. A strong co-localization of TGF beta and decorin in the ECM of first trimester decidual tissue suggests that decorin may aid TGF beta storage or limit its activity in the ECM.

Decidua↗
PubMed1995

A double-blinded prospective evaluation of recombinant human erythropoietin in acutely burned patients.

OBJECTIVE: To evaluate the effects of recombinant human erythropoietin (r-HuEPO) in attempting to prevent anemia in acutely burned patients. DESIGN: Prospective double-blind randomized study of 40 patients. METHODS: Patients with burns from 25% to 65% total body surface were enrolled. r-HuEPO or a placebo was begun within 72 hours of admission. Cell blood count, reticulocyte counts, transfusion requirements, and blood loss were measured. Comparison was carried out by the unpaired t test. MAIN RESULTS: There was no statistically significant difference in hemoglobin, hematocrit, reticulocyte count, ferritin, serum iron, total iron blinding capacity, or transfusion requirements. In patients with burns from 25% to 35%, the reticulocyte counts were statistically significantly higher. CONCLUSION: In our work the administration of r-HuEPO in acutely burned patients did not prevent the development of postburn anemia or decrease transfusion requirements. Increased erythropoiesis in smaller burns (25% to 35%) was observed and may indicate a reason for further study.

Adolescent↗
PubMed1995

Outcome of patients with neurotrauma: the effect of a regionalized trauma system.

A system of regionalized trauma care was introduced to Sydney in early 1992. This study was carried out to assess the effect of regionalization on the outcome of patients suffering major head injury within the central Sydney area. A prospective before and after study extending over 3 years and centred on the time of designation of Royal Prince Alfred Hospital (RPAH) as a trauma centre, was the methodology used. The study group consisted of all patients admitted with head injury (Glasgow Coma Score < 9; admission systolic blood pressure > 90 mmHg; Injury Severity Score > 15) to RPAH from the central Sydney area. Outcome criteria include survival rates, transfer numbers, and time to definitive neurosurgical care. Fifty patients were entered during the first 18 months of the study, and 38 during the second 18 months. Fifteen in the first group required evacuation of intracranial mass lesions, as did nine in the second group. The overall mortality fell from 42 to 26% (P = 0.13). During the study period there were 77 primary retrievals and 20 required evacuation of mass lesions. The median time from injury to commencement of operation in these patients was 2 h 13 min (range 1 h 3 min-5 h 35 min). There were 11 transfers, four requiring craniotomy. The median time from injury to surgery was 7 h 24 min (range 3 h 2 min-10 h 25 min; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Irritable bladder syndrome: a void in the research?

There has been much interest in recent years in the effective treatment of functional or psychosomatic symptoms such as irritable bowel syndrome. Functional bladder disorders appear to have received little attention from psychologists, although they may account for as many as 20 percent of urology out-patient referrals. Evidence is presented to support the existence of an irritable bladder syndrome which is characterized by urgency and frequency of micturition. Aetiological factors are considered and treatment approaches are briefly described and evaluated. Research to date is reviewed and suggestions are made for future research in this area.

Evaluation Studies as Topic↗
PubMed1994

Studies of the reductive half-reaction of milk xanthine dehydrogenase.

The reductive half-reaction of milk xanthine dehydrogenase (XDH) with NADH and with xanthine has been studied at pH 7.5, 25 degree C. NADH reduces XDH to the two-electron reduced form at a rate of 18 s-1, independent of NADH concentration over the range studied. Further reduction by NADH to the four-electron state is inhibited by excess NADH. Subsequent binding of NADH to the four-electron reduced form of the enzyme causes the redistribution of one electron from the flavin to the molybdenum center. The four-electron reduced species reached through reduction by NADH is the same as the species obtained upon reaction of NAD with fully reduced XDH. In contrast, xanthine rapidly reduces XDH to the four-electron level; further reduction is comparatively slow and is inhibited by excess xanthine. Studies using substoichiometric xanthine show that the reaction of XDH with 1 equivalent of xanthine involves rapid substrate binding and rapid reduction of the molybdenum center of the enzyme. Before the release of urate from the molybdenum active site, an electron is transferred at 15 s-1 from the reduced molybdenum center to one of the iron-sulfur centers of XDH. Urate is then released at a rate of 13 s-1, followed by a rapid electron redistribution within the protein. The reductive half-reaction of XDH with xanthine is rate-limiting in xanthine/NAD turnover, which appears to occur between the two- and four-electron reduced enzyme species. The reduction of XDH by substoichiometric amounts of the fluorescent substrate xanthopterin was also studied. This reaction, monitored by changes in both absorbance and fluorescence, was found to involve the formation of two molybdenum complexes (an Eox.S complex and an Ered.P complex) followed by the release of the product, leucopterin.

Animals↗
PubMed1994

Genetic instability of microsatellite sequences in many non-small cell lung carcinomas.

We have analyzed DNA obtained from 38 lung tumors and normal lung or blood DNA for microsatellite instability. Instability was examined at 10 different microsatellite loci on chromosome 3p, as well as loci on 3q, 11p, 11q, and 13q, and two on Xq. We observed microsatellite instability at one or more loci in 13 of the lung tumors analyzed, and this instability ranged from tumors showing instability in only a single microsatellite to two adenocarcinomas that had alterations in all 16 tested microsatellites. Microsatellite instability could therefore play a significant role in the development of a sizable portion of lung tumors.

Alleles↗
PubMed1994

The fifth domain of beta 2-glycoprotein I contains a phospholipid binding site (Cys281-Cys288) and a region recognized by anticardiolipin antibodies.

We have identified a phospholipid binding site in the fifth domain of beta 2-glycoprotein I (beta 2-GPI). Using synthetic peptides spanning the fifth domain of beta 2-GPI, we have shown that the presence of the sequence Glu274-Cys288 caused a decrease in the binding of purified anticardiolipin (aCL) antibodies in a modified cardiolipin (CL)-ELISA by inhibiting the binding of beta 2-GPI to CL. This peptide bound to and could be eluted from a CL affinity column in a manner similar to native beta 2-GPI. Peptides corresponding to other regions of the fifth domain had no inhibitory effect. The inhibitory activity was restricted to the sequence Cys281-Lys-Asn-Lys-Glu-Lys-Lys-Cys288. Peptides in which the two flanking cysteine residues were deleted or substituted with serine residues possessed no inhibitory activity, indicating that the conformation of this highly positively charged sequence may be critical for phospholipid binding. aCL antibodies purified from patients with autoimmune disease were shown to bind directly to wells coated with native beta 2-GPI but not to wells coated with a preparation of beta 2-GPI cleaved between Lys317 and Thr318. The integrity of this sequence is therefore critical for these antibodies to recognize beta 2-GPI, and the putative epitope for aCL antibodies is most likely to be in this region.

Amino Acid Sequence↗
PubMed1994

Duplex scan surveillance of infrainguinal prosthetic bypass grafts.

PURPOSE: Surveillance protocols of infrainguinal vein bypass grafts have almost universal acceptance. To date corresponding studies of prosthetic grafts have not been carried out. We have performed a prospective 4-year duplex scan follow-up on polytetrafluoroethylene grafts to assess the usefulness of a surveillance program of prosthetic bypass grafts in preventing graft failure. METHODS: Over 4 years 69 infrainguinal polytetrafluoroethylene grafts in 56 patients were studied at six monthly intervals by our vascular laboratory. Full duplex scan mapping of the grafts and inflow and outflow arteries and standard ankle pressure measurements were performed. A midgraft peak flow velocity was also measured. RESULTS: Over 4 years 27 (39.1%) grafts occluded without any predictive changes in the preceding duplex scan examination. Of the 42 (60.9%) grafts that remained patent, only four developed stenoses (three at the proximal anastomosis and one at the distal anastomosis) that were amenable to intervention. Changes in ankle pressures or midgraft flow velocity did not predict failure. CONCLUSIONS: The low yield of remediable disease does not justify the cost of duplex scan surveillance of infrainguinal prosthetic bypass grafts.

Aged↗
PubMed1994

The reliability of self-report of behaviours associated with recurrent urinary tract infection.

OBJECTIVE: To examine the comparability of two forms of self-report of behaviours associated with recurrent urinary tract infection (UTI), using questionnaire estimations and diary recordings. SUBJECTS AND METHODS: A group of 26 women (mean age 36.5 years, SD 9.57) with recurrent UTI and a group of 25 comparison women (mean age 36.7 years, SD 8.82) were recruited. Behavioural factors were measured by questionnaire and diary-keeping. RESULTS: Questionnaire estimations appeared to be reliable for some behaviours associated with UTI. Significant errors in estimating fluid intake were noted. CONCLUSION: For research and clinical purposes, estimations of fluid intake using immediate self-report (e.g. questionnaires) should not be assumed to be reliable indications of true consumption. Suggestions are made for future research.

Adult↗
PubMed1993

Redox potentials of milk xanthine dehydrogenase. Room temperature measurement of the FAD and 2Fe/2S center potentials.

Xanthine oxidase (XO) and xanthine dehydrogenase (XDH), two forms of the same enzyme isolated from cow's milk, have differing redox potentials of their chromophores. Both XDH and XO are capable of accepting 8 electrons per active site cluster of redox acceptors. By titrating XDH with redox indicator dyes of various potentials, the potentials have been determined for the flavin as well as for the 2Fe/2S centers of the enzyme at pH 7.5, 25 degrees C. The redox potential for the FAD/FADH. half-potential was found to be -270 +/- 5 mV and that for the FADH./FADH2 half potential, -410 +/- 5 mV. The first flavin half potential is close to the value which has been reported for XO (Porras, A. G., and Palmer, G. (1982) J. Biol. Chem. 257, 11617-11626). However, the second FAD half-potential is 180 mV lower in XDH than in XO, creating a 140-mV separation between the FAD potentials in XDH. This separation gives rise to a maximum development of the flavin semiquinone in XDH near 0.9 equivalent as confirmed by EPR quantitation of FADH. formed during reductive titrations. The potentials of both the 2Fe/2S centers in XDH were determined and found to be identical to the values which were found for the iron-sulfur centers in XO.

Animals↗
PubMed1993

Anticonvulsant activity of the gamma-aminobutyric acid uptake inhibitor N-4,4-diphenyl-3-butenyl-4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol .

The N-4,4-diphenyl-3-butenyl derivative of the glial selective gamma-aminobutyric acid (GABA) uptake inhibitor 4,5,6,7-tetrahydroisoxazolo [4,5-c]pyridin-3-ol (N-DPB-THPO), was tested for its ability to block sound-induced seizures in the audiogenic seizure-susceptible Frings mouse model of epilepsy. Following intracerebroventricular (i.c.v.) administration, N-DPB-THPO blocked tonic hindlimb extension in a dose- and time-dependent manner. At the doses tested no gross behavioral effects were noted.

Acoustic Stimulation↗
PubMed1993

Recurrent uncomplicated urinary tract infection: a review of psychological factors.

Urinary tract infection (UTI) is a very common medical disorder among women, and is a chronic, recurrent problem for a cluster of sufferers. The factors involved in the aetiology of recurrent UTI are not adequately understood. Most research and treatment has focused on the influence of medical factors, although clinical impressions suggest that psychological factors (behavioural and personality variables) may play an important role. Evidence is reviewed for the involvement of psychological factors in the aetiology and treatment of recurrent UTI in women. It is difficult to draw any clear conclusions concerning the role of such factors in recurrent UTI, given the relatively small amount of research to date and a number of methodological issues. Suggestions for appropriate methodology and research concerning the interplay of physical and psychological factors are made.

Adaptation, Psychological↗
PubMed1993

Application of a pressure area risk calculator in an intensive care unit.

This study describes the use of a pressure area risk calculator designed specifically for intensive care (ICU) patients; the calculator used was that developed by Cubbin & Jackson (1991) (Table 1). This scale is a modified Norton scale with lower scores indicative of increased risk of pressure sore formation. The unit on which this study was undertaken is a six-bedded general adult ICU. A highly significant difference in lowest recorded scores was found between the group of patients who developed pressure sores compared with the group that did not (Mann-Whitney test, p < 0.01). The differences in scores between the two groups suggest that the calculator was measuring something useful, but it should be stressed that 40% (n = 100) of patients had scores below the threshold value and did not develop scores. Risk calculations were decisive in increasing the profile of pressure area care within the ICU and for this reason alone their use can be justified. There was a pressure sore incidence of 13% with 7% of patients having sores prior to admission to the ICU. Of the sores that were noted the commonest sites to be affected within intensive care were heels. The sacrum was the commonest site for sores that had occurred prior to admission. Pressure sore incidence can prove a useful audit tool in the management of pressure area care in intensive care, but variations in incidence over time must be examined with caution.

Adult↗
PubMed1993

The effect of gastric pH on the absorption of controlled-release theophylline dosage forms in humans.

The bioavailability of three marketed controlled-release dosage forms and a reference solution of theophylline was studied in eight subjects with normal gastric fluid acidity and seven subjects who were achlorhydric. Gastric pH was monitored with a Heidelberg capsule. One of the controlled-release dosage forms dissolved more rapidly in vitro when exposed to acid conditions, one dissolved more rapidly in pH 7.5 media, and the third dissolved at a rate independent of pH. Using a crossover design, each subject received each dosage form twice. Blood was sampled for up to 47 hr after each dose, and serum was assayed for theophylline by HPLC. The product which dissolved more rapidly under acid conditions in vitro exhibited a 3 hr longer Tmax in the achlorhydrics compared to the normal subjects. The product which dissolved more rapidly in the pH 7.5 media exhibited a relatively higher AUC(0-infinity) in the achlorhydric subjects than in normal subjects after the AUC data were normalized for clearance differences between the two subject groups. The in vivo bioavailability of these dosage forms could be related to the in vitro dissolution characteristics for some parameters. However, with the exception of the mean Tmax values, the mean bioavailability parameters differed by less than 20% between the two subjects groups.

Absorption↗
PubMed1993

Perceptions of unmet need in four community services for elderly people.

Home-care services particularly, and food services to a lesser extent, are seen by elderly people as being critically important for their capacity to live independently in western Sydney. Home nursing and transport services are valued but are less critical. Consumers, providers of services and referral agents all identify significant levels of unmet need for community services. The home care service particularly is stretched by pressures which are likely to be exacerbated by demographic change and by cost-shifting between state governments and the Commonwealth Governments.

Aged↗