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Biomedical subjects

H Clark

Publications and source records attributed to H Clark.

At least 37 records · Page 2Linked to original sources
PubMed2001

Surfactant proteins A and D protect mice against pulmonary hypersensitivity induced by Aspergillus fumigatus antigens and allergens.

Allergic bronchopulmonary aspergillosis (ABPA) is an allergic disorder caused by an opportunistic fungal pathogen, Aspergillus fumigatus (AFU:). Lung surfactant proteins SP-A and SP-D can interact with the glycosylated antigens and allergens of AFU:, inhibit specific IgE binding to these allergens, and block histamine release from sensitized basophils. We have now examined the therapeutic effect of exogenous administration of human SP-A, SP-D, and a recombinant fragment of SP-D (rSP-D), in a murine model of pulmonary hypersensitivity induced by AFU: antigens and allergens, which resembles human ABPA immunologically. The ABPA mice exhibited high levels of AFU:-specific IgG and IgE, blood eosinophilia, extensive infiltration of lymphocytes and eosinophils in the lung sections, and a Th2 cytokine response. Treatment with SP-A, SP-D, and rSP-D lowered blood eosinophilia, pulmonary infiltration, and specific Ab levels considerably, which persisted up to 4 days in the SP-A-treated ABPA mice, and up to 16 days in the SP-D- or rSP-D-treated ABPA mice. The levels of IL-2, IL-4, and IL-5 were decreased, while the level of IFN-gamma was raised in the splenic supernatants of the treated mice, indicating a marked shift from Th2 to Th1 response. These results clearly implicate pulmonary SP-A and SP-D in the modulation of allergic reactions.

Allergens↗
PubMed2001

Long-term efficacy of sildenafil and tachyphylaxis effect.

PURPOSE: We observed that patients who initially responded to sildenafil frequently became resistant to it with time. We evaluated the long-term efficacy of sildenafil. MATERIALS AND METHODS: A telephone survey was conducted of patients during the first year of sildenafil usage, and another one was completed 2 years later of the same group. RESULTS: During the first survey, the etiology of impotence included post radical prostatectomy in 25, arterial insufficiency in 26, diabetes in 19, neurogenic impotence in 12, suspected venous leak in 9, proved venous leak in 7, Peyronie's disease in 6 and unspecified in 47 patients. The overall improvement rate, which was defined as the ability to initiate and maintain erections for successful intercourse, was 74%. The dose necessary to achieve this response was 100 mg. sildenafil in 15% of patients, 50 mg. in 83% and 25 mg. in 2%. During the second survey, information was collected on 82 patients and only 43 (52%) had continued treatment. Of the 69 patients who reported an initial good response 41 (59%) were still using sildenafil, and of the 43 who were still using it 16 (37%) had to increase the dose by 50 mg. to achieve an adequate result. There was no significant relationship between the need to increase the dose and frequency of treatment per month. Reduction in efficacy ranged from 15% to 50% (mean 36 +/- 12%) and the time to loss of efficacy ranged from 1 to 18 months (mean 11 +/- 5). Of the 82 patients in the second surgery, 39 (48%) stopped using sildenafil. A total of 28 (74%) patients reported a good initial response on the first survey, and 6 had spontaneous erections and no longer needed treatment. However, 14 (50%) patients discontinued sildenafil because of the loss of efficacy. In this group 10 patients had side effects, mainly headache and flushing of the face and nose, and only 2 discontinued treatment because of them. CONCLUSIONS: Our data suggest that there is a possible tachyphylaxis effect with sildenafil. Of the patients who were followed for 2 years 20% had to increase the sildenafil dose to have the same effect and 17% discontinued use due to loss of efficacy.

Adult↗
PubMed2000

Histologic evaluation of the inflammatory response around implanted hollow fiber membranes.

Hollow fiber membranes are enjoying widespread use as barrier materials in many implanted applications. In order to predict in vivo device behavior, it is important to understand and quantify the changes to the membrane and to the tissue immediately surrounding it that occur following implantation. We have considered a range of commercially available hollow fiber membranes for their suitability as candidates for subcutaneously implanted applications. Through analysis of excised tissue sections by light microscopy, membranes were screened at 3, 6, and 12 weeks post-implantation for the ability to maintain integrity, foreign-body reaction, and thickness of the external fibrotic capsule layer. The polysulfone microfiltration membranes and cellulose diacetate membranes investigated were found to be unsuitable owing to extensive degradation. All membranes exhibited typical foreign body reaction with fibrotic capsule formation. The thinnest capsules were observed on the regenerated cellulose microdialysis membranes and the polysulfone ultrafiltration membranes. Extensive cellular penetration into the membrane matrix of the latter was observed, but did not appear to affect the foreign body reaction. A heat-sealing method was also considered for thermoplastic membranes and found to effectively prevent cellular penetration into the lumen of the hollow fiber for the duration of the 12-week implantation.

Animals↗
PubMed1999

Description and evaluation of an experimental model to examine changes in selection between high-protein, high-carbohydrate and high-fat foods in humans.

OBJECTIVE: To develop and test an experimental model designed to detect changes in selection between foods individually enriched in protein, carbohydrate and fat in human subjects. DESIGN: Randomised counterbalanced (Latin square) design. SETTING: The metabolic suite at the Rowett Research Institute's Human Nutrition Unit. SUBJECTS: 16 normal-weight men (mean BMI = 23.5). INTERVENTIONS: Subjects were each studied 4 times in a 2-day protocol. On day 1 subjects received a fixed maintenance diet; on day 2 they received a mandatory intake as breakfast (08.30) plus a drink at 10.30. This comprised 80% of resting energy requirements as high-protein (HP), high-carbohydrate (HC) or high-fat (HF) foods (60% of energy in each case) or an equal mixture (M) of macronutrients, 33% by energy. All mandatory treatments contained the same energy content and density. From 12.30 onwards, subjects had ad libitum access to a counter-balanced selection of three groups of familiar foods (10 HP, 10 HC and 10 HF; 30 foods in total). Most energy in each food was derived from one macronutrient (approximately 60%), the remainder being equally split between the other two macronutrients. RESULTS: Subjects were significantly less hungry before lunch on the HP and M (33% protein) treatments (F3.44 = 7.35; P < 0.001). At lunch, they ate more energy after the HF treatment than after any of the other treatment (F1,38 = 9.00; P = 0.005). This was largely in the form of fat and protein, and to a lesser extent carbohydrate. Subsequent energy intake (EI) were lower on the HF treatment, largely through selection of less fat in the afternoon (F1.42 = 6.90; P=0.012). Daily EIs were similar across treatments. CONCLUSION: This design appears sensitive meal-to-meal to changes in both nutrient and EIs.

Adult↗
PubMed1999

Localization of a candidate surfactant convertase to type II cells, macrophages, and surfactant subfractions.

Pulmonary surfactant exists in the alveolus in several distinct subtypes that differ in their morphology, composition, and surface activity. Experiments by others have implicated a serine hydrolase in the production of the inactive small vesicular subtype of surfactant (N. J. Gross and R. M. Schultz. Biochim. Biophys. Acta 1044: 222-230, 1990). Our laboratory recently identified this enzyme in the rat as the serine carboxylesterase ES-2 [F. Barr, H. Clark, and S. Hawgood. Am. J. Physiol. 274 (Lung Cell. Mol. Physiol. 18): L404-L410, 1998]. In the present study, we determined the cellular sites of expression of ES-2 in rat lung using a digoxygenin-labeled ES-2 riboprobe. ES-2 mRNA was localized to type II cells and alveolar macrophages but not to Clara cells. Using a specific ES-2 antibody, we determined the protein distribution of ES-2 in the lung by immunohistochemistry, and it was found to be consistent with the sites of mRNA expression. Most of the ES-2 in rat bronchoalveolar lavage is in the surfactant-depleted supernatant, but ES-2 was also consistently localized to the small vesicular surfactant subfraction presumed to form as a consequence of conversion activity. These results are consistent with a role for endogenous lung ES-2 in surfactant metabolism.

Animals↗
PubMed1998

Identification of a putative surfactant convertase in rat lung as a secreted serine carboxylesterase.

In the alveolar lumen, pulmonary surfactant converts from the contents of secreted lamellar bodies to tubular myelin to apoprotein-depleted vesicles during respiration. Using an in vitro system, researchers have reported that the conversion of tubular myelin to vesicles is blocked by inhibitors of serine hydrolase activity and have tentatively ascribed "convertase" activity to a diisopropyl fluorophosphate (DFP)-binding protein in mouse bronchoalveolar lavage (BAL). We purified and sequenced the homologous enzyme from rat BAL fluid. Amino acid sequence from the amino terminus and an internal cyanogen bromide peptide of the purified rat DFP-binding protein perfectly match the sequence of the carboxylesterase ES-2. Although ES-2 was initially cloned from liver, we found a 1.8-kilobase mRNA for ES-2 in decreasing relative abundance in rat liver, kidney, and lung but not in heart or spleen. Although further studies are required to establish the identity between "convertase" and ES-2 or a homologous member of the carboxylesterase family, our results raise the possibility that a protein with esterase/lipase activity plays a role in extracellular surfactant metabolism.

Amino Acid Sequence↗
PubMed1997

Developmental regulation of Zbu1, a DNA-binding member of the SWI2/SNF2 family.

The SWI2/SNF2 gene family has been implicated in a wide variety of processes, involving regulation of DNA structure and chromatin configuration, mitotic chromosome segregation, and DNA repair. Here we report the characterization of the Zbu1 gene, also known as HIP116, located on human chromosome band 3q25, which encodes a DNA-binding member of this superfamily. Zbu1 was isolated in this study by its affinity for a site in the myosin light chain 1/3 enhancer. The protein has single-stranded DNA-dependent ATPase activity, includes seven helicase motifs, and a RING finger motif that is shared exclusively by the RAD5, spRAD8, and RAD16 family members. During mouse embryogenesis, Zbu1 transcripts are detected relatively late in fetal development and increase in neonatal stages, whereas the protein accumulates asynchronously in heart, skeletal muscle, and brain. In adult human tissues, alternatively spliced Zbu1 transcripts are ubiquitous with highest expression in these tissues. Gene expression is also dramatically induced in human tumor lines and in Li-Fraumeni fibroblast cultures, suggesting that it is aberrantly regulated in malignant cells. The developmental profile of Zbu1 gene expression and the association of the protein with a tissue-specific transcriptional regulatory element distinguish it from other members of the SWI2/SNF2 family and suggest novel roles for the Zbu1 gene product.

Adenosine Triphosphatases↗
PubMed1997

A semi-solid drug delivery system for epidermal growth factor in corneal epithelial wound healing.

PURPOSE: To examine the effects of EGF, delivered from a semi-solid drug delivery system, on corneal epithelial wound healing following anterior keratectomy wound creation in the eyes of New Zealand white rabbits. METHODS: A semi-solid drug delivery system based on a Carbopol gel was developed. Following creation of a 7.5 mm circular anterior keratectomy wound, 50 microL of either a placebo gel or an EGF-containing gel, was instilled in the inferior fornix. The gel remained in the eye for 8 hours, at which time it was removed. Anaesthesia was maintained for the entire 8-hour period. Wound healing was evaluated by quantitative morphometry. We evaluated 0.04, 0.1, 0.2, 0.4, and 1% EGF concentrations in the gel. Tear EGF concentrations and histology of the healing corneas were also examined. RESULTS: The enhancement factor (ratio of the healing rate with the EGF gel and control gel) was 1.13 +/- 0.12, 1.40 +/- 0.14, 1.29 +/- 0.12, 1.80 +/- 0.22, and 1.09 +/- 0.12 for the gels containing 0.04, 0.1, 0.2, 0.4, and 1% EGF by mass, respectively. The increases in the rate of wound healing were significant with the 0.1, 0.2 and 0.4% gel formulations. Histologically, the 0.4% gels resulted in cellular hyperplasia after 5 days of healing. Differences between the placebo gel-treated and EGF-containing gel-treated eyes were evaluated at both 2 and 5 days. The concentration of EGF in the tears during the treatment period was approximately constant for both the 1% and 0.04% gels. The average tear concentration during the instillation period was 2.87 +/- 0.36 micrograms/mL and 200.61 ng/mL +/- 116.10 for the 1% and 0.04% gels respectively. CONCLUSIONS: Treatment with EGF in a Carbopol gel carrier for a period of 8 hours results in significant wound healing enhancement (p < 0.05). The optimum EGF loading in the gel was determined to be 0.4%. A slow release gel may be an effective way to deliver EGF to the corneal surface.

Animals↗
PubMed1995

Femorotibial bypass: the learning curve.

Femorotibial bypass is still infrequently performed in many district hospitals, because it is time consuming and the risk of failure is high, especially during the learning curve. This article reviews the results of a single consultant surgeon and his team after starting femorotibial bypass de novo in a district general hospital. During the period 1987 to 1992, 85 femorotibial grafts were performed in 76 patients for ulceration and gangrene (57), rest pain (19) and severe claudication (9). Sixty-six were autogenous vein, 15 were PTFE with distal vein cuff, two were composites and two were umbilical vein. Overall, 22 grafts (26%) failed within the first 30 days (two were salvaged) and 21 amputations were required (five despite patent grafts). There were three early deaths (mortality 3.9%). At the end of 1993, 39 limbs had been amputated and 24 patients had died (eight with amputations). Twenty-three (44% of survivors) were alive with patent grafts. These disappointing early results were due to an initial technical learning curve, after which increased confidence may have led to reconstructing some patients with inadequate distal arteries. A more selective approach is now used. Limb salvage can be achieved in a worthwhile proportion of these patients and 3-year primary patency rates are similar to those of teaching hospitals in this country.

Aged↗
PubMed1994

A postal survey evaluation of prostatectomy.

BACKGROUND: The aims of this study were to determine the prevalence of urinary symptoms after prostatectomy, and the relationship between pre- and post-operative symptoms. METHODS: A retrospective postal survey was carried out, on an unselected series of patients in Leicestershire, one to two years after transurethral resection. Four hundred and sixty-five men received a questionnaire, and of these 78 per cent responded. RESULTS: The operation relieved 92 per cent of all preoperative urge-incontinence, but 3 per cent of those who were continent beforehand developed urge-incontinence. Urgency and hesitancy also responded well. Nocturia, frequency and dribbling were the least responsive. There was a general tendency for symptoms to persist rather than develop post-operatively. CONCLUSIONS: Prostatectomy is an effective intervention, particularly for cases with urge-incontinence, urgency, incontinence or hesitancy. These results are consistent with those of other, prospective, studies. Postal surveys may provide a cheap and effective method of evaluating local prostatectomy services.

Aged↗
PubMed1991

Is adult-onset coeliac disease due to a low-grade lymphoma of intraepithelial T lymphocytes?

Enteropathy-associated T-cell lymphoma commonly presents with malabsorption, and debate continues as to whether adult-onset coeliac disease (CD) is itself a form of low-grade lymphoma. A 59-year-old man with adult-onset CD required resection of a segment of oedematous jejunum. Histological examination of this tissue revealed an intense intraepithelial lymphocytosis. Immunophenotypic (CD3-, CD4-, CD8-, CD34-, and CD45 RO-) and cytogenetic (deletion of the Y chromosome and chromosome 9) abnormalities were found, together with monoclonal T-cell-receptor gene rearrangements. Some patients with adult-onset CD may have low-grade lymphoma from the outset of their illness.

Biopsy↗
PubMed1991

Psychological determinants of health and performance: the tangled web of desirable and undesirable characteristics.

Correlations were determined for male (n = 225) and female (n = 242) college students between sets of undesirable personality traits (anxiety, stress reactivity, anger, and alienation) and desirable personality traits (instrumentality, achievement strivings, and optimism measured by the Scheier-Carver [1987] Life Orientation Test), and a series of outcome variables related to health (self-reported health complaints and health maintenance behaviors and beliefs) and academic performance (academic expectations and actual grade point average). Significant correlations were found between many of the personality variables and the outcome variables. However, partial correlations revealed different relationships for the various criteria. With other variables held constant, health complaints were related to several undesirable characteristics, whereas health maintenance behaviors and beliefs were related to several desirable attributes. Only achievement strivings made an independent contribution in both sexes to the 2 measures of academic performance. The theoretical and methodological wisdom of using measures of multiple personality constructs and outcome variables is discussed.

Achievement↗
PubMed1990

Medical research.

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New Zealand↗