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Biomedical subjects

J T Wright

Publications and source records attributed to J T Wright.

At least 91 records · Page 5Linked to original sources
PubMed1995

Insulinlike growth factor-1 (IGF-1)-induced stimulation of porcine preadipocyte replication.

Insulinlike growth factor-1 (IGF-1) is both adipogenic and mitogenic to preadipose cell lines as well as primary stromalvascular (SV) cells. The precise effect of IGF-1 on primary preadipocytes per se, however, has not been elucidated directly. In this study, primary porcine preadipocytes were exposed to IGF-1 while at three culture densities. The proportion of replicating preadipocytes was determined by labeling cells with an antiadipocyte/preadipocyte monoclonal antibody (MAb) concomitant with DNA measurement with propidium iodide. Flow cytometric analysis revealed that different seeding densities did not affect the relative proportion of preadipocytes (AD-1 positive) in cultures. However, IGF-1 treatment increased the proportion of preadipocytes at all densities but to a greater extent in more dense cultures. The resultant number of fat cell clusters formed was greater at higher densities and on IGF-1 treatment. The proportion of replicating cells in cultures decreased with increasing density. IGF-1 significantly increased replication at all densities and increased the number of replicating preadipocytes to the same extent independent of density. These results provide direct evidence of hormonal regulation of primary preadipocyte replication.

Adipocytes↗
PubMed1995

Odontogenic tumours in the v-Ha-ras (TG.AC) transgenic mouse.

A line of homozygous transgenic mice (TG.AC) carrying a v-Ha-ras gene fused to the promoter of the zeta globin gene produces a variety of mesenchymal and epithelial neoplasms including odontogenic tumours. The 1-year incidence of odontogenic tumour formation in these mice was approx. 35%. Tumours formed more often in the mandible than maxilla. The various types of tumours frequently presented with: (1) primarily mesenchymal cells in a dense fibrous-like matrix, or (2) loose stroma surrounded by anastomosing cords of epithelial cells that exhibited squamous differentiation, or (3) odontomas forming mineralized tooth structures by well-differentiated odontoblasts and ameloblasts. Some tumours had areas with all three of these characteristics. Mineralized dentine and enamel in the odontomas were morphologically similar to those of normal murine teeth. Odontogenic tumours expressed the v-Ha-ras transgene that was primarily localized to the mesenchymal cells. Proliferating-cell nuclear antigen immunohistochemistry showed that the mesenchymal cells adjacent to the epithelial cords not only expressed the ras transgene but were also actively proliferating. The TG.AC mouse provides an excellent model for the study of odontogenic tumours and tooth development.

Animals↗
PubMed1995

Effects of losartan on a background of hydrochlorothiazide in patients with hypertension.

The purpose of this multicenter trial was to compare the antihypertensive efficacy and safety of losartan potassium (losartan), a selective angiotensin II receptor antagonist, when added to hydrochlorothiazide in hypertensive patients whose blood pressure was not adequately controlled by 25 mg hydrochlorothiazide monotherapy. After a 4-week monotherapy period of 25 mg hydrochlorothiazide, 304 patients with trough (22 to 26 hours postdose) sitting diastolic pressure between 93 and 120 mm Hg were maintained on 25 mg hydrochlorothiazide and randomized double-blind into treatment arms consisting of either 25, 50, or 100 mg losartan or placebo once daily for 12 weeks. The reductions in sitting diastolic pressure for patients treated with 25, 50, or 100 mg losartan concomitantly administered with 25 mg hydrochlorothiazide were significantly greater (P < or = .05) than the reductions observed in the 25 mg hydrochlorothiazide plus placebo group beginning 1 week after randomization. The antihypertensive response in all groups was greater at week 3 than week 1, with some additional decrease in blood pressure in some groups at later times. Sitting systolic pressures were also significantly reduced in each group over time. Standing blood pressures at week 12 were similar to sitting blood pressures. A dose-response relationship to losartan was observed in this patient population. The percentages of the total drug-related clinical adverse experiences as assessed by the investigator were generally similar in the 25, 50, and 100 mg losartan plus 25 mg hydrochlorothiazide groups (10.3%, 24.4%, and 20.0%, respectively) compared with the placebo plus 25 mg hydrochlorothiazide group (24.7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1995

Biogenic amines in the hypothalamus of rats after diethyldithiocarbamate or AIMAX treatment, an alternative for norepinephrine depletion.

The objective of this study was to determine whether AIMAX (a dithiocarbamoylhydrazine derivative) is suitable for determining the effects of norepinephrine (NE) depletion on reproduction in domestic animals. Therefore, the effect of AIMAX (n = 6) on concentrations of biogenic amines in the medial basal hypothalamus (MBH) and anterior hypothalamic area (AHA) of ovariectomized (OVX) rats primed with ovarian steroids was compared to that of diethyldithiocarbamate (DDC; n = 5), a potent dopamine-beta-hydroxylase (DBH) inhibitor, which is chemically similar to AIMAX. Rats that received only ovarian steroids and saline injections served as controls (n = 6). Treatment with DDC resulted in sedation and reduced body temperature. In contrast, rats behaved normally after AIMAX treatment. AI-MAX reduced (P < .05) NE but increased (P < .05) dopamine (DA) concentrations in MBH and AHA compared with controls. Similar changes in NE and DA concentrations were observed in DDC-treated rats. However, elevated epinephrine (EPI) levels were measured in MBH and AHA of only DDC-treated rats. Serum LH concentrations were suppressed (P < .005) in both AIMAX- and DDC-treated rats compared with control animals. Because AIMAX, like DDC, suppressed hypothalamic NE content and LH secretion, AIMAX should be useful in studying effects of NE depletion on gonadotropin secretion in domestic animals.

Animals↗
PubMed1995

The mineral and protein content of enamel in amelogenesis imperfecta.

The purpose of this investigation was to characterize the enamel composition of teeth affected with the hereditary enamel disorders known as amelogenesis imperfecta. Teeth from 10 individuals representing all 3 major AI types (hypocalcified, n = 3; hypomaturation, n = 3; hypoplastic, n = 4) and 10 normal teeth were studied. Half of each tooth was used for histological and biochemical studies. The enamel protein content was estimated by amino acid analysis. The enamel mineral content (volume %) was determined from the calcium and/or phosphorus content. Calcium was measured using atomic absorption and phosphorus was determined colorimetrically. The mean enamel mineral content was reduced for all hypomaturation and hypocalcified AI teeth while hypoplastic AI enamel varied from normal to reduced compared with normal enamel. The enamel protein content was increased in all but one AI case (7 cases were examined for protein) compared with the normal enamel. The mineral and protein content in AI enamel showed a significant inverse relationship (R = -0.939, P = 0.001). This study shows that all three of the major AI groups can have subtypes associated with substantial decreases in the enamel mineral content, although hypomineralization appears most severe in the hypomaturation and hypocalcified AI types. The decreased mineral content was associated with an increased protein content in AI enamel. These findings provide further evidence that altered enamel mineralization in AI teeth likely involves abnormal post-secretory processing of the enamel proteins.

Amelogenesis Imperfecta↗
PubMed1995

Influence of age and fetal hypophysectomy on porcine preadipocytes: insulin-like growth factor-I (IGF-I) response, receptor binding and IGF binding proteins secretion.

The effects of fetal hypophysectomy (hypox) and age on insulin-like growth factor-I (IGF-I) response, receptor binding and IGF-I & IGF binding protein secretion by porcine preadipocytes was examined. Primary cultures of stromal vascular (S-V) cells derived from fetal and postnatal adipose tissue were established and exposed to test media (different concentrations of pig serum with or without IGF-I) for morphological study or to serum-free media for measuring IGF-I receptor binding and IGF-I & IGFBPs secretion. Conditioned media were collected and subjected to IGF-I RIA and ligand blot and immunoblot analysis. IGF-I significantly stimulated total cell growth (determined by DNA levels) and increased fat cell cluster number and lipid deposition in porcine S-V cultures (determined by image analysis). Although the pattern of response to IGF-I was similar in fetal and postnatal cultures, the response was greater in fetal cultures. The mitogenic and adipogenic response of fetal preadipocytes to IGF-I was impaired by fetal hypox. Specific IGF-I binding sites on fetal preadipocytes had a higher binding affinity for IGF-I (Kd = 2.82 +/- 0.28 nM) than did postnatal preadipocytes (Kd = 7.28 +/- 1.52 nM, P < 0.05). Preadipocytes secreted IGF-I and four IGF-BPs (BP-1, -2, -3, and -4) in a developmentally regulated manner. For example, IGFBP-2, and -3 were predominant binding proteins secreted by fetal preadipocytes which represented 47% and 30% of the total, respectively. IGFBP-1 was the major binding protein secreted by postnatal preadipocytes. Furthermore, fetal cells secreted greater amounts of IGF-I in cultures than did postnatal cells (2428 +/- 205 pg/ml vs. 870 +/- 31 pg/ml, P < 0.05). Fetal hypox caused a decrease from 47% to 68% of control values in all four IGFBPs secreted by preadipocytes. The changes in IGF-I receptor binding and IGF-I and IGFBP secretion by preadipocytes may account for altered response of preadipocytes to IGF-I. Thus, secretion of IGF-I and IGFBPs, IGF-I binding and response of porcine preadipocytes were affected by age and fetal hypox. The results indicated that locally produced IGF-I and IGFBPs may play a critical paracrine/autocrine role during fetal adipose development.

Adipose Tissue↗
PubMed1994

The influence of hydrocortisone (HC) on differentiation of adipose tissue is dependent on fetal age.

Elevated serum hydrocortisone (HC) levels are associated with larger fat cells and elevated levels of lipogenic and associated enzymes in late term pig fetuses from genetically obese dams. We have investigated the influence of HC status per se on these and other adipose tissue traits by chronically treating pig fetuses hypophysectomized (hypox) on day 70 with HC between either day 70 and 90 or 90 and 105 of gestation. Treatment with HC during both periods increased serum HC levels (P<.05) and increased fat cell size (P<.05) in the perirenal (PERI) and subcutaneous (SQ) depots, but failed to influence body weights, insulin-like growth factor-1 and insulin levels. Quantitative analysis of sections of PERI and SQ adipose tissue indicated that HC increased lipoprotein lipase (LPL), esterase and glucose-6-phosphate dehydrogenase (G6PDH) activities. The degree of esterase and G6PDH, but not LPL response to HC, was greater during the 90- to 105-day period than during the earlier period. HC significantly increased lipid accretion only in the SQ depot between 90 and 105 days. Overall, HC significantly augmented hypox-induced alterations in cellular and metabolic traits of developing adipose tissue. The general increase in fat cell size (21%) with moderate (SQ-105d) or no (PERI-90, 105d; SQ-90d) increase in lipid accretion indicates that HC either did not influence or decreased apparent fat cell number. Regardless, these data indicate that changes in serum HC per se may account for adipose tissue traits that characterize fetuses from genetically obese dams.

Adipose Tissue↗
PubMed1994

Tricho-dento-osseous syndrome. Features of the hair and teeth.

Tricho-dento-osseous syndrome is a rare autosomal dominant hereditary disorder characterized by curly hair, enamel hypoplasia, taurodont teeth, and thickened cortical bone. A large kindred with this syndrome has been identified in North Carolina and characterized by pedigree analysis and clinical evaluation. Hair samples (N = 3) and an exfoliated primary tooth (N = 1) from persons with tricho-dento-osseous syndrome and hair and teeth from unaffected persons were examined. Scanning electron microscopy showed that the hair shaft morphology, diameter, and cuticular pattern and periodicity were similar for the tricho-dento-osseous syndrome and control samples. The affected tooth was examined using light microscopy and a scanning electron microscope that showed pitting hypoplasia of the enamel surface, an extremely large pulp chamber, and dentin that appeared structurally normal. The affected enamel was uniformly thin, only 10% the thickness of the control enamel. The bulk of this enamel showed no prism formation. This study indicates that although hair with tricho-dento-osseous syndrome often is clinically curly, it can be straight, and it does not appear to have unique ultrastructural features that are of diagnostic benefit. The dental characteristics of tricho-dento-osseous syndrome were the most consistent feature seen in this kindred.

Abnormalities, Multiple↗
PubMed1994

Developing guidelines for local use: algorithms for cost-efficient outpatient management of cardiovascular disorders in a VA Medical Center.

Local use of practice guidelines requires paying close attention to the concerns of the patient within the framework of society, to the professional and educational needs of the provider, and to the realities of cost. One Veterans Affairs facility took the challenge of balancing these factors and developed their own algorithms for three cardiovascular disorders.

Algorithms↗
PubMed1994

In situ binding and immunocytochemistry of insulin-like growth factor I receptors in primary cultures of porcine adipose tissue stromal vascular cells treated with indomethacin.

An autoradiographic technique for localizing [125I]IGF-I binding was adapted to primary cultures of pig stromal-vascular (S-V) cells to study the effects of pig serum (PS) and (or) indomethacin (Indo) on IGF-I and fibronectin (FN) receptors. Computer assisted image analysis revealed that the percentage of [125I]IGF-I binding decreased (P < .001) in cultures (7 d) treated with Indo compared with 2% PS alone. Binding of [125I]IGF-I analog (low-binding affinity for the IGF-I binding proteins) also decreased (P < .001) in 7-d cultures treated with Indo. The unlabeled IGF-I analog was more effective than unlabeled IGF-I at decreasing (P < .001) binding of [125I]IGF-I. Number of fat cell clusters and fat cell area (total lipid deposition) increased (P < .001) with PS + Indo compared with PS or Indo alone. Immunocytochemical staining (fluorescein isothiocyanate) of IGF-I receptors with a polyclonal antibody (flow cytometric analysis) decreased (P < .001) from 1 to d 3 and did not change from 3 to 7 d with PS alone. However, the percentage of reactive cells decreased (P < .05) when Indo was added to PS. In contrast, the number of cells detected with the FN receptor antibody increased fourfold (P < .01) from 1 to 7 d in cultures with PS alone and decreased (P < .05) when Indo was present. Undifferentiated cells around fat cell clusters were reactive for the IGF-I receptor, but fat cells showed no reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1994

Flow cytometric analysis of porcine preadipocyte replication.

In the present study, a technique is described for measuring proliferation of primary porcine preadipocytes. Cultures of stromal-vascular (S-V) cells from dorsal subcutaneous adipose tissue were maintained under several growth conditions. Cells were isolated from cultures at various times and DNA was labeled with propidium iodide (PI) and analyzed by flow cytometry. Treatment of cultures with colchicine allowed identification of S-V cells in mitosis. The relative proportion of replicating cells was dependent on several factors, including serum concentration and cell density at the time of harvest. Using the AD-1 anti-preadipocyte/adipocyte monoclonal antibody, the preadipocyte subpopulation within the S-V cells was identified. Furthermore, by labeling cells with PI concomitant with AD-1, the proportion of replicating preadipocytes was quantified. It is now possible to identify and quantify replicating preadipocytes rapidly under various experimental conditions.

Adipocytes↗
PubMed1994

Hereditary epidermolysis bullosa.

Epidermolysis bullosa (EB) is a diverse group of disorders having blister formation as their common feature. Tissue separation occurs at variable depths in the skin and/or mucosa depending on the specific EB type. Marked oral involvement of the soft and hard tissues can produce potentially devastating alterations, with oral tissue fragility and blistering common to all EB types. Oral debilitation resulting from soft tissue scarring is limited primarily to the recessive dystrophic EB subtypes. Individuals with generalized recessive dystrophic EB typically have microstomia, obliteration of the oral vestibule, and ankyloglossia. Generalized enamel hypoplasia appears to be limited to junctional EB, whereas rampant dental caries afflicts many individuals having either junctional or generalized recessive dystrophic EB. Although systemic treatment remains primarily palliative, it is possible to prevent destruction and subsequent loss of the dentition through appropriate interventions and dental therapy. The severely affected soft and/or hard tissues frequently seen in patients having generalized recessive dystrophic and junctional EB often require aggressive dental intervention to maintain optimal oral health. Even the most severely affected individuals with EB can retain their dentition through the use of modern dental restorative techniques delivered using general anesthesia.

Dental Enamel Hypoplasia↗
PubMed1993

Oral involvement of recessive dystrophic epidermolysis bullosa inversa.

The inversa subtype of autosomal recessive dystrophic epidermolysis bullosa (EBDR-I) is a rare variant characterized by lesions involving primarily the flexural areas of the body. The purpose of this investigation was to characterize the oral manifestations of this unusual dermatologic condition. Ten individuals having EBDR-I were evaluated and compared with an age and sex-matched population of unaffected individuals that served as controls. The diagnosis of EBDR-I was confirmed by skin biopsy that demonstrated tissue separation below the lamina densa and the clinical presentation of blister formation that typically localized to flexural areas. There was clinical variability in the severity and distribution of skin involvement; however, none of the affected individuals demonstrated pronounced digital webbing, severe generalized blistering or growth retardation characteristic of the Hallopeau-Siemens form of EBDR. Oral involvement was seen in all cases with ankyloglossia, loss of tongue papillae and obliteration of the oral vestibule between the lips and gingiva being typical. The oral opening was significantly reduced in older EBDR-I individuals compared with matched controls, confirming that acquired microstomia is a characteristic of EBDR-I. The teeth were not clinically abnormal or malformed and showed no evidence of generalized enamel hypoplasia. Despite this, the prevalence of dental caries in EBDR-I individuals was significantly higher than the control group. The inversa form of EBDR presents with oral findings that are similar but generally milder than those seen in the Hallopeau-Siemens variant of EBDR.

Epidermolysis Bullosa Dystrophica↗
PubMed1993

The influence of human growth hormone (GH) and thyroxine (T4) on the differentiation of adipose tissue in the fetus.

Late term fetuses from genetically obese dams have slightly larger fat cells, greater adipose tissue lipoprotein lipase (LPL) activities, elevated levels of thyroid hormones, and depressed growth hormone (GH) levels when compared to fetuses from lean dams. We have investigated the influence of thyroid hormone and GH status per se on these and other adipose tissue traits by chronically treating hypophysectomized (hypox) fetuses (day 70) between day 90 and 105 of gestation with either thyroxine (T4) or human GH. Treatment with T4 decreased body weights (P<.05), increased serum T4 levels (P<.05), and enhanced skin and hair development (P<.05). Quantitative analysis of sections of perirenal and subcutaneous adipose tissue indicated that T4 increased LPL activity (P<.05), slightly increased fat cell size, and more than doubled (P<.05) lipid accretion. A hypox induced deficit in fat cell cluster number in the outer layer of subcutaneous tissue was normalized by T4 (P<.05). Conversely, human GH (hGH) treatment had no influence on body weight, increased serum hGH levels, decreased fat cell size (P<.05) and LPL activity (P<.05) but had no influence on lipid accretion. Quantitative analysis of adipose tissue sections provided direct and indirect evidence of a "critical" or "sensitive" period between 90 and 105 days, since fetal hypox at day 70 severely impeded preadipocyte recruitment/replication during this period. Furthermore, T4 but not GH effectively normalized this hypox-induced deficiency in preadipocyte development. Therefore, T4 may have a major role in preadipocyte recruitment/replication during late fetal life.

Adipocytes↗
PubMed1993

Development defects of enamel in humans with hereditary epidermolysis bullosa.

Developmental defects of enamel are often reported as a feature of the more severe forms of epidermolysis bullosa (EB). The purpose of this investigation was to determine the prevalence and character of enamel defects in each of the major hereditary EB types. Clinical evaluations were made on 237 individuals representing all of the major EB types and 58 unaffected individuals. All EB cases were categorized by phenotype, mode of inheritance and skin biopsy. The frequency of individuals having developmental enamel defects ranged from 8.6% in recessive dystrophic EB to 100% in junctional EB; 27.5% of the control population had these defects. Generalized hypoplasia characterized by either severe pitting and/or thin enamel was seen in all junctional EB cases but not in any other EB type. There was a tendency for the severe Herlitz form of junctional EB to have thin enamel while non-Herlitz junctional EB cases had less severe pitting and generally no reduction in enamel thickness. The prevalence of individuals with hypoplastic enamel bands was greater in the EB population (9.7%) than controls (1.9%). Thus individuals with simplex and dominant dystrophic EB typically have enamel defects that are similar in frequency and distribution to those of unaffected individuals. Developmental defects of enamel are a consistent feature of junctional EB, although the clinical expression is highly variable.

Adolescent↗