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Biomedical subjects

P Harris

Publications and source records attributed to P Harris.

At least 91 records · Page 5Linked to original sources
PubMed1997

Primary structure of locust opsins: a speculative model which may account for ultraviolet wavelength light detection.

The sequences of two locust opsins have been determined by dideoxy nucleotide sequencing of PCR products from cDNA derived from eyecup tissue. The opsins (Lo1 and Lo2) are encoded by 381 and 380 amino acid residues, respectively, with hydropathy profiles and placement of key amino acid residues suggestive of a typical seven-transmembrane rhodopsin structure. The sequence alignment of Lo1 reveals significant homology to mantid opsin. These opsins contain retinal as their visual chromophore and have similarity to the Rh1 type sequences from Drosophila and Calliphora which use 3-hydroxy retinal. Lo2 is most closely related to the Rh3/4 type of visual pigments from Drosophila. The retinal-based opsins show reduced numbers of charged amino acids in the loop region connecting transmembrane segments V and VI compared to the 3-hydroxy retinal opsins. Sequence alignment of all the known insect visual pigments has shown that only those with maximal sensitivity in the blue/UV spectral range, Lo2 and the Rh3/4 opsins of Drosophila, have three charged amino acids in transmembrane segments II, IV and VII. The charged residue in transmembrane VII is two helical turns away from the positively charged Schiff base and could act directly as a counterion to it. From the secondary structure analysis of opsin, the two charged residues in transmembrane II and IV would be in close proximity to form a dipole. These polar motifs in Lo2 and Rh3/Rh4 could act in wavelength modulation of short wavelength sensitive pigments and substantiate the proposed external two-point charge model which accounts for the spectral sensitivity of visual pigments [Honig, B., Dinur, U., Nakanishi, K., Balogh-Nair, V., Gawinowicz, M.A. and Motto, M. (1979). Journal of the American Chemical Society, 101, 7084-7086].

Amino Acid Sequence↗
PubMed1997

Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains.

PKD1 is the major locus of the common genetic disorder autosomal dominant polycystic kidney disease (ADPKD). Analysis of the predicted protein sequence of the human PKD1 gene, polycystin, shows a large molecule with a unique arrangement of extracellular domains and multiple putative transmembrane regions. The precise function of polycystin remains unclear with a paucity of mutations to define key structural and functional domains. To refine the structure of this protein we have cloned the genomic region encoding the Fugu PKD1 gene. Fugu PKD1 spans 36 kb of genomic DNA and has greater complexity with 54 exons compared with 46 in man. Comparative analysis of the predicted protein sequences shows a lower level of homology than in similar studies with identity of 40 and 59% similarity. However key structural motifs including leucine rich repeats (LRR), a C-type lectin and LDL-A like domains and 16 PKD repeats are maintained. A region of homology with the sea urchin REJ protein was also confirmed in Fugu but found to extend over 1000 amino acids. Several highly conserved intra- and extra-cellular regions, with no known sequence homologies, that are likely to be of functional importance were detected. The likely structure of the membrane associated region has been refined with similarity to the PKD2 protein and voltage gated Ca2+ and Na+ channels highlighted over part of this area. The overall protein structure has therefore been clarified and this comparative analysis derived structure will form the basis for the functional study of polycystin and its individual domains.

Amino Acid Sequence↗
PubMed1997

Energy sources and requirements of the exercising horse.

This review outlines the energy sources available to the horse, from its diet and from its body stores, at rest and while exercising. It looks at the current ways of describing the energy potential of diets fed to horses and discusses the relative advantages and disadvantages of the digestible energy and net energy systems. The more empirical net energy system for calculating the energy available for maintenance and work is compared with a more physiological partitioning system. Finally, the energy requirements for maintenance and exercise are discussed, together with how they may be practically determined and achieved through different diets.

Animal Feed↗
PubMed1997

Oral hypoglycaemic agents. When, how and why.

Non insulin dependent diabetes mellitus (NIDDM) is often incorrectly viewed as a mild form of diabetes. Complications are as frequent as in insulin dependent diabetes and control of oral hypoglycaemic agents is integrated with other lifestyle changes in managing NIDDM.

Administration, Oral↗
PubMed1996

Cell cycle, DNA damage and heat shock regulate suc22+ expression in fission yeast.

The suc22+ gene of Schizosaccharomyces pombe encodes the small subunit of ribonucleotide reductase. Two transcripts that hybridise to suc22+ have previously been described: a constitutive transcript of 1.5 kb, and a transcript of approximately 1.9 kb that is induced when DNA replication is blocked by hydroxyurea. In this paper we show that both transcripts derive from the suc22+ gene, are polyadenylated, and have transcription initiation sites separated by approximately 550 nucleotides. The absence of translation initiation codons and predicted intron splice sites within this 550 nucleotide region suggests strongly that both transcripts encode the same protein. Under normal growth conditions, the larger suc22+ transcript is present at a very low level. This low level expression is periodic during the cell cycle, showing a pattern similar to that of other genes under regulation by MCB elements with a maximum in G1/S phase. Consistent with this, there are MCB elements upstream of the initiation site of the transcript. This pattern of expression contrasts with the continuous expression, at a much higher level, of the smaller suc22+ transcript. The larger suc22+ transcript is induced by exposure of cells to 4-nitroquinoline oxide (4-NQO),a UV-mimetic agent that causes DNA damage. The transcriptional response to 4-NQO is observed in cells previously arrested in G2 by a cdc2ts mutation, demonstrating that induction can occur outside S phase. We show that the rad1+ gene, part of the mitotic checkpoint, is required for induction of the large transcript. Exposure of cells to heat shock also induces the suc22+ large transcript: a consensus heat shock element has been identified upstream of the large transcript start site.

Cell Cycle↗
PubMed1996

BSE in Great Britain: consistency of the neurohistopathological findings in two random annual samples of clinically suspect cases.

Two annual, random samples of clinically suspect cases of bovine spongiform encephalopathy (BSE) were taken in 1992-93 (year 1, 1500 cases) and 1993-94 (year 2, 1000 cases). From each sample, 100 positive cases were examined in detail to establish the severity of the vacuolation in 17 specific neuroanatomical locations. The resultant 'lesion profiles' were compared with the profile obtained from a similar sample of BSE-affected cattle from early in the epidemic (1987-89); the comparison showed that the distribution and severity of vacuolation in BSE has remained unchanged. The cases not confirmed as BSE on histological examination (172 in year 1 and 162 in year 2) were examined for evidence of any alternative neurohistological diagnosis. As in previous studies, the majority of these cases showed no significant lesions (61.6 and 61.7 per cent). The remainder consisted of bilateral focal spongiosis of unknown significance (26.7 and 21.0 per cent), inflammatory conditions (8.1 and 11.1 per cent) and a small number of cases with tumours, cerebrocortical necrosis or idiopathic brainstem neuronal chromatolysis. No evidence was found of any cases of BSE with an atypical distribution of lesions. These findings support the theory that the BSE epidemic is sustained by a single, stable strain of the BSE agent, and confirm that the existing statutory diagnostic criteria continue to be appropriate.

Animals↗
PubMed1996

Effects of exercise intensity and environmental stress on indices of oxidative stress and iron homeostasis during exercise in the horse.

The effects of prolonged variable-intensity and short-term high-intensity exercise on indices of oxidative stress and iron homeostasis were compared in six fit horses under cool [20 degrees C, 40% relative humidity (RH)] or hot/humid (30 degrees C, 80% RH) environmental conditions. The exercise protocols were designed to simulate equine competition, including racing (intense exercise) or the speed and endurance phase of a 3-day event (prolonged exercise). Increased plasma concentrations of lipid hydroperoxides and haemolysate concentrations of oxidised glutathione (GSSG) were measured within 30 min of the completion of exercise, indicating production of reactive oxygen species (ROS) and lipid membrane peroxidation. The horses were unable to complete the prolonged exercise protocol at high temperature and humidity. This coincided with higher maximal values of lipid hydroperoxides [138.2 (17.7) microM and GSSG [110.6 (18.2) microM], compared to high-intensity [105.2 (14.9) microM and 63.6 (8.6) microM, respectively] or prolonged [100.7 (18.7) microM and 86.2 (9.1) microM, respectively] exercise performed under cooler environmental conditions. Significant correlations were found between the duration of the final stage of exercise during hot/humid environmental conditions and increased levels of lipid hydroperoxides (r = 0.85), GSSG (r = 0.94), xanthine (r = 0.92) and uric acid (r = 0.96). Exercise also decreased the iron (Fe)-binding antioxidant activity of the plasma and increased the total plasma Fe levels, although this was only significant for prolonged exercise in ambient conditions. There was no detectable free Fe in the plasma at any stage of exercise. Other changes in biochemical parameters had returned to pre-exercise levels within 24 h after exercise. The results show that exercise can induce changes in biochemical parameters that are indicative of oxidative stress in the fit horse and that this was, exacerbated during exercise at high temperature and humidity.

Animals↗
PubMed1996

Does clock-watching make you clockwise?

French and Richards (1993) found that subjects asked to draw from memory a clock that had Roman numerals on its face typically represented the number four on the clock face as "IV" rather than the correct "IIII", whereas those merely asked to copy it typically drew "IIII". The current experiments followed the methodology of French and Richards, but then went on to examine the subsequent memorial representation of the number four. Subjects drew a clock with Roman numerals on its face, either from memory (with or without forewarning) or while the clock remained in full view. Subsequently, subjects were asked to recall the exact form in which the numbers were represented on the clock (Experiment 1) or were asked to recognise which of two clocks had been presented earlier (Experiment 2). Findings supported the idea that subjects in the copy condition were more likely than subjects in other conditions to draw the clock without invoking schematic knowledge of Roman numerals. The basic effect reported by French and Richards was replicated in both experiments. Furthermore, in both experiments, subjects who correctly drew the clock with the number four represented as "IIII" were more likely to misrepresent it as "IV" in the subsequent memory task if they were in the copy condition rather than the two memory conditions. The results are interpreted in terms of schema theory.

England↗
PubMed1996

Delayed entry into health care for women with HIV disease.

OBJECTIVE: The primary objective was to evaluate factors that might influence delayed entry into health care for women with HIV. Implications of time of diagnosis for early medical intervention was a focused aspect. PROCEDURE: Structured clinical interviews were conducted with HIV-positive women (n = 48); these data were supplemented by medical chart reviews. MEASURES: Delayed entry into health care was operationalized as a difference of more than 3 months between diagnosis and entry into care. Measures of race, social class, risk behavior circumstances of HIV testing, and health status were included. RESULTS: Of women, 58% delayed entry into care following an HIV diagnosis. Upon entry into health care, 65% of women were symptomatic and 40% were severely immunocompromised (CD4 cells/mm3 < 200). Results from the logistic regression indicated that those who learned their HIV status prenatally were four times more likely to delay entry into care compared to those who self-referred for HIV testing, even after controlling for symptom status. CONCLUSIONS: HIV diagnosis is not enough to ensure that women with HIV will get adequate and timely health care. Counseling and testing recommendations should highlight the intrinsic value of early diagnosis.

Adolescent↗
PubMed1996

Managed care and the infectious diseases specialist.

There is growing demand to contain health care costs and to reassess the value of medical services. The traditional hospital, academic, and research roles of the infectious disease (ID) specialist are threatened, yet there is an increasing need for expertise because of growing antimicrobial resistance and emerging pathogens. Opportunities exist to develop and expand services for the care of patients infected with human immunodeficiency virus and in infection control, epidemiology, outcomes research, outpatient intravenous therapy, and resource management. It is important for ID physicians to appreciate the principles involved in managed care and the areas in which ID services can be valuable. To be effective, physicians need to know about tools such as practice guidelines, physician profiling, outcomes monitoring, computerized information management, risk sharing, networking, and marketing, as well as related legal issues. With a positive attitude toward learning, application, and leadership, ID physicians can redefine their role and expand their services through managed care.

Ambulatory Care↗
PubMed1996

Neuroendocrine response to standing and mild exercise in patients with untreated severe congestive heart failure and chronic constrictive pericarditis.

OBJECTIVES: Plasma hormones at rest in patients with untreated severe congestive cardiac failure are similar to those occurring during heavy exercise in healthy people. This study examines the hypothesis that the neuroendocrine effects of exercise are modified in untreated congestive cardiac failure. DESIGN: The effect of lying, standing, upright exercise, and recovery on several plasma hormones was measured in healthy controls and 2 groups of patients with severe untreated heart failure. The level of exercise was the same in all groups and low enough to be within the capacity of patients with severe failure. PATIENTS: There were 12 healthy controls, 9 patients with untreated severe congestive cardiac failure caused by myocardial disease, and 12 patients with untreated constrictive pericarditis. SETTING: A tertiary referral centre in North India. RESULTS: Heart rate, noradrenaline, renin activity, aldosterone, cortisol, growth hormone and atrial natriuretic peptide (ANP) were higher in the 2 groups of patients than in the healthy controls during both rest and exercise (P < 0.01 for both comparisons). In general, the effects of this mild degree of exercise were no greater than those of standing. The increase in heart rate during exercise was greater in the group with constrictive pericarditis than in the controls (P = 0.04) and (non-significantly) in congestive heart failure. Apart from these differences the pattern of responses to standing and exercise was similar in the three groups. CONCLUSIONS: While there was evidence of a broad neuroendocrine activation in patients with congestive cardiac failure, the only abnormal increase during exercise (of marginal significance) was found for renin activity in those with myocardial disease. In patients with untreated congestive failure, a substantially normal endocrine response to exercise was superimposed on abnormal resting concentrations.

Adult↗
PubMed1996

Hysterosalpingo-contrast sonography (HyCoSy) using Echovist-200 in the outpatient investigation of infertility patients.

This study describes the introduction of hysterosalpingo-contrast sonography (HyCoSy) as a first line outpatient investigation of uterine and tubal factors in two fertility units. 136 infertile women had transvaginal scanning before and during the intrauterine injection of contrast medium (Echovist-200). HyCoSy was successfully completed in 132 cases (97%) within a mean time of 12.6 +/- 8.4 (4-50) min. The uterus and its cavity appeared normal in 108 (82%) women. Uterine abnormalities in the remaining 24 women (18%) included structural abnormality (n = 7), fibroids (n = 12) and endometrial polyps (n = 5). A total of 261 fallopian tubes in 132 women were assessed: 186 (71%) appeared patent and 55 (21%) blocked. The remaining 20 (8%) could not be assessed for technical reasons. Polycystic ovaries and ovarian cysts were diagnosed in eight women. The most common adverse effect was mild/moderate pain, similar to period pain, with 24 (18%) women requiring simple analgesia. HyCoSy is a simple and well tolerated outpatient procedure. The technique provides clinically valuable information about tubal patency, ovarian and uterine abnormalities.

Ambulatory Care↗