Biomedical subjects

J T Wright

Publications and source records attributed to J T Wright.

At least 73 records · Page 4Linked to original sources

PubMed1997

The role of the cytochrome P450-dependent metabolites of arachidonic acid in blood pressure regulation and renal function: a review.

Arachidonic acid metabolism through the cytochrome P450-dependent monooxygenase system has been the subject of considerable research interest over the last several years. This article reviews the biological actions of the metabolites generated through this pathway and explores their role in the regulation of renal function and systemic blood pressure. Arachidonic acid is metabolized by the cytochrome P450-dependent monooxygenase system in three ways: epoxidation, resulting in the formation of 5,6-, 8,9-, 11,12-, 14,15-epoxyeicosatrienoic acids; allylic oxidation, resulting in the formation of 5,8,9,11,12,15-hydroxyeicosatetraenoic acids (HETE); and hydroxylation, resulting in the formation of 19,20-HETEs and 20-carboxyl arachidonic acid. Elements of this pathway have been localized in the kidney and several extrarenal sites. Vasodilation, vasoconstriction, inhibition of Na+,K+-ATPase, inhibition of ion transport and modulation of cell growth have been some of the diverse physiological actions demonstrated by metabolites produced by this pathway. As a physiological correlate of these properties, considerable evidence has accumulated regarding the role of the cytochrome P450-dependent metabolites of arachidonic acid in the pathogenesis of hypertension in the spontaneously hypertensive rat. Data in humans are limited, but in small studies increased production of these metabolites has been shown in hypertensive persons. In summary, several properties of products of this "third" pathway of arachidonic acid metabolism suggest a role in cardiovascular and renal function. Additional studies are needed to precisely define the role of this pathway in human hypertension.

Animals↗

PubMed1997

Genetic linkage of the tricho-dento-osseous syndrome to chromosome 17q21.

Tricho-dento-osseous syndrome (TDO), MIM# 190320, is transmitted as a highly penetrant autosomal dominant trait that is characterized by variable clinical expression. The principal clinical features include kinky/curly hair in infancy, enamel hypoplasia, taurodontism, as well as increased thickness and density of cranial bones. Possible genetic linkage has been reported for TDO with the ABO blood group locus, but the gene defect remains unknown. We have identified four multiplex families (n = 63, 39 affected, 24 unaffected) from North Carolina segregating TDO. We previously have excluded a major locus for TDO in the ABO region for these families. Utilizing a genome-wide search strategy, we obtained conclusive evidence for linkage of the TDO syndrome locus to markers on chromosome 17q21 (D17S791, Z max = 10.54, Theta = 0.00) with no indication of genetic heterogeneity. Multipoint analysis suggests the TDO locus is located in a 7 cM chromosomal segment flanked by D17S932 and D17S941. This finding represents the first step towards isolation and cloning of the TDO gene. Identification of this gene has important implications for understanding normal and abnormal craniofacial development of hair, teeth and bone.

Abnormalities, Multiple↗

PubMed1996

Influence of thyroxine in vivo on preadipocyte development and insulin-like growth factor-I and IGF binding protein secretion in fetal stromal vascular cell cultures.

Studies were conducted to determine the influence of thyroxine (T4) in vivo on preadipocyte development and insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs) secretion in stromal-vascular (S-V) cultures. Fetal pigs were hypophysectomized (hypox) at 70 days of gestation, implanted with T4 pellets, and fetuses from the dam at 75 days of gestation. In a second experiment, hypox and T4 implantation were performed at 75 days and fetal pigs removed at 95 days of gestation. Primary cultures of stromal vascular (S-V) cells derived from fetal adipose tissue were established. Cultures were stained for morphological analysis and conditioned media were collected for IGF-1 determination by radioimmunoassay (RIA) and IGFBP analysis by Western blotting. After only 5 days of T4 treatment, fat cell cluster number and size and lipid deposition in cultures were significantly increased compared to cultures from untreated hypox fetuses. Fetal hypox reduced IGF-I secretion by preadipocytes at both ages and T4 treatment completely normalized IGF-I secretion (p < 0.05). Four IGFBPs (BP-1, BP-2, BP-3 & BP-4) detected in S-V cultures derived from 95-day fetuses were decreased in concentration by hypox by 44 +/- 9.4%, 32 +/- 9.7%, 42 +/- 12% and 53 +/- 6.9%. In cultures derived from T4 treated hypox fetuses, the levels of these four IGFBPs were increased by 187 +/- 25%, 239 +/- 38%, 190 +/- 5% and 347 +/- 43% over control values, respectively. In cultures from 75-day fetuses, only IGFBP-2 (major one) and BP-1 (minor one) were detected and their secretion was also decreased by hypox and elevated by T4 treatment (190 +/- 49.5%, 156 +/- 30%, respectively, of controls). The results provide direct evidence that T4 has a major influence on fetal preadipocyte development. T4 stimulated production of IGF-I and IGFBP in fetal S-V cultures, which in turn, may have mediated the capability of T4 to enhance fetal adipose tissue development.

Adipocytes↗

PubMed1996

Ontogeny of the response to thyroxine (T4) in the porcine fetus: interrelationships between serum T4, serum insulin-like growth factor-1 (IGF-1) and differentiation of skin and several adipose tissues.

The temporal aspect of thyroxine (T4) enhanced development of several fetal adipose tissue depots (locations) and skin was examined in the present study. On day 70 of gestation pig fetuses were either hypophysectomized (hypox), hypoxed and implanted with T4 pellets or left intact (control). Subsequently, fetuses were removed for study at either 73, 75, 80, 85 and 90 days of gestation. Serum levels of T4 and insulin-like growth factor I (IGF-I) were significantly elevated by T4 after 3 days of treatment and throughout the study. T4 treatment enhanced development of skin, inner and outer subcutaneous (SQ) adipose tissue and adipocyte lobules around hair follicles (HFL's) but degree of response and response time were tissue or depot dependent. The T4 response time was shortest for skin and HFL's, longest for inner SQ and intermediate for the outer SQ. Considering the entire treatment period, magnitude of the T4 response was much greater for skin and HFL's than for outer and inner SQ tissues. Possibly, these developmental characteristics indicate that T4 directly influences skin and HFL's and indirectly influences inner SQ adipose tissue by increasing production of a locally produced adipogenic growth factor. Furthermore, developmental characteristics (morphological) indicated that putative local growth factor mediation of T4 action may depend on stage of development or maturity of the tissue. IGF-I is clearly the most logical candidate as a putative local mediator of T4, but evidence at the molecular level is needed to prove this suggestion. Regardless, the particular adipose tissue location or depot is an important aspect of hormone responsiveness during the critical or sensitive period of fetal adipose tissue development.

Adipose Tissue↗

PubMed1996

Rationale and design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). ALLHAT Research Group.

Are newer types of antihypertensive agents, which are currently more costly to purchase on average, as good or better than diuretics in reducing coronary heart disease incidence and progression? Will lowering LDL cholesterol in moderately hypercholesterolemic older individuals reduce the incidence of cardiovascular disease and total mortality? These important medical practice and public health questions are to be addressed by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind trial in 40,000 high-risk hypertensive patients. ALLHAT is designed to determine whether the combined incidence of fatal coronary heart disease (CHD) and nonfatal myocardial infarction differs between persons randomized to diuretic (chlorthalidone) treatment and each of three alternative treatments--a calcium antagonist (amlodipine), an angiotensin converting enzyme inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). ALLHAT also contains a randomized, open-label, lipid-lowering trial designed to determine whether lowering LDL cholesterol in 20,000 moderately hypercholesterolemic patients (a subset of the 40,000) with a 3-hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor, pravastatin, will reduce all-cause mortality compared to a control group receiving "usual care." ALLHAT's main eligibility criteria are: 1) age 55 or older; 2) systolic or diastolic hypertension; and 3) one or more additional risk factors for heart attack (eg, evidence of atherosclerotic disease or type II diabetes). For the lipid-lowering trial, participants must have an LDL cholesterol of 120 to 189 mg/dL (100 to 129 mg/dL for those with known CHD) and a triglyceride level below 350 mg/dL. The mean duration of treatment and follow-up is planned to be 6 years. Further features of the rationale, design, objectives, treatment program, and study organization of ALLHAT are described in this article.

Antihypertensive Agents↗

PubMed1996

Assessing medication adherence by pill count and electronic monitoring in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

The Medication Event Monitoring System (MEMS), an electronic monitor which records the date and time of bottle cap openings, and pill counts were used to assess patterns of adherence for the primary antihypertensive drug in the African American Study of Kidney Disease and Hypertension Pilot Study (AASK). Blacks with hypertension and moderately reduced renal function were randomized to one of two levels of blood pressure control and to one of three antihypertensive drug regimens: primary therapy with a calcium channel blocker, an angiotension converting enzyme inhibitor, or a beta-blocker. Of the 94 participants in AASK, 91 had MEMS recordings and pill counts for 313 regularly scheduled monthly follow-up visits. The average length of follow-up was 4.6 months. An acceptable level of adherence by pill count was achieved if 80% to 100% of the prescribed pills were not returned to the clinic. Adherence by MEMS to a once-a-day drug dosing schedule was acceptable if 80% of the time intervals between MEMS openings were within 24 +/- 6 h. Acceptable adherence by pill count was observed at 68% of the follow-up visits; MEMS indicated nonadherence at 47% of those visits. Blood pressure was within goal in 50% of the participants who were adherent by both pill count and MEMS throughout their follow-up visits, and only 14% of the participants who were identified nonadherent by one or both methods. These findings suggest that electronic monitoring is a useful adjunct to pill counts in assessing adherence to antihypertensive drugs. Feedback of electronically collected information on dosing intervals to participants and staff may enhance adherence.

Adolescent↗

PubMed1996

Design and baseline characteristics of participants in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

Hypertension and end-stage renal disease (ESRD) are major causes of morbidity and mortality in the United States, especially among African Americans. The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study evaluated the feasibility of conducting a long-term clinical trial to compare the effects of two levels of blood pressure control and three different antihypertensive drug regimens on the rate of decline in glomerular filtration rate (GFR) in African Americans with clinically diagnosed hypertensive renal disease. African American men and women aged 18-70 years with a GFR of 25-70 ml/min/ 1.73m2 and hypertension were randomized in a 3 x 2 factorial design to initial treatment with either an angiotensin-converting enzyme inhibitor (enalapril), a calcium channel blocker (amlodipine), or a beta blocker (atenolol) and to a mean arterial blood pressure (goal MAP) of either 102-107 mm Hg or < or = 92 mm Hg. Furosemide, doxazosin, clonidine, hydralazine, and minoxidil were added sequentially until goal MAP was achieved. To compare the pathologic diagnosis with the clinical diagnosis of renal disease, study participants without contraindication were also asked to undergo a renal biopsy. The goals of the AASK Pilot Study were to evaluate recruitment techniques, adherence to prescribed antihypertensive drug regimens, ability of the antihypertensive regimens to achieve blood pressure goals, rates of participation in scheduled clinic visits and procedures, and variability of GFR measurements. A further goal was to obtain renal biopsy data in at least 75% of the randomized study participants. Compared to the ESRD patient population whose renal disease is caused by hypertension, women were underrepresented in the AASK Pilot Study. AASK Pilot Study participants had higher unemployment rates and lower income levels than African Americans in the general U.S. population.

Adult↗

PubMed1996

Craniofacial morphology of the tricho-dento-osseous syndrome.

Tricho-dento-osseous syndrome (TDO) is characterized by abnormal bone, hair, and tooth morphology. However, the reported craniofacial abnormalities are not well characterized. The purpose of this study was to compare the craniofacial parameters of 25 subjects affected with TDO (A) with those of 15 unaffected relatives (U). Standardized lateral cephalograms were traced and digitized. Each subject's data were compared by age and sex to cephalometric standards (Bolton, Behrents); severity was scored by standard deviations from the standard mean, and then grouped into A vs. U. All cephalograms were evaluated for frontal sinuses, mastoid pneumatization, diploe, and bone density, and cranial thickness was measured. Cranial base length (SN; NBa), cranial base angle (BaSN), and mandibular body length (GoPg) were greater in A than in U (p < or = 0.05). Both groups had longer total and lower facial heights (NMe; ANSMe) compared with normal standards. Frontal sinuses, mastoid pneumatization and diploe were visible less often in A than in U (p < or = 0.05). Parietal bone and bone at lambda was significantly thicker (p < or = 0.05) in A than in U. Variability was substantial in many measures in both A and U. The major TDO craniofacial features involve the cranial base, mandibular body length, absence of visible pneumatized mastoids, frontal sinuses and diploe, and thicker cranial bone.

Abnormalities, Multiple↗

PubMed1996

Abnormal enamel development in a cystic fibrosis transgenic mouse model.

Cystic fibrosis (CF) is a hereditary condition that affects cAMP-regulated chloride channels in epithelial tissues due to a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Recently, a transgenic CF mouse model was developed at UNC that exhibits no CFTR expression. Interestingly, the CF mouse demonstrates abnormal incisor enamel. Therefore, the purpose of this investigation was to characterize the enamel in this CF mouse model. Incisors from CF and normal mice were evaluated by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The enamel proteins were examined by amino acid analysis, SDS-PAGE, and Western blot. Gross examination showed that 100% of CF mice had soft, chalky white incisor enamel, while the enamel of normal mice was hard and yellow-brown. LM indicated that the ameloblasts in the CF mice underwent premature degeneration shortly after completion of the secretory phase. The CF mouse enamel appeared to be of relatively normal thickness and showed a prism structure similar to that of normal mouse enamel. However, the CF mouse enamel crystallites appeared to have a rough granular surface compared with normal enamel. SDS-PAGE indicated that mature CF enamel retained low-molecular-weight material (approximately 20 kDa), whereas normal mature enamel did not. This low-molecular-weight material cross-reacted with anti-amelogenin antibodies in Western blot analysis. This investigation shows that abnormal CFTR expression in the mouse results in developmental abnormalities in the incisor enamel. Although further investigation is required to determine the mechanism leading to abnormal enamel formation, the CF mouse provides a potentially useful animal model for investigating aberrant enamel development.

Amelogenesis↗

PubMed1996

The chemical composition of tooth enamel in recessive dystrophic epidermolysis bullosa: significance with respect to dental caries.

Previous reports have linked the prevalence of tooth abnormalities with high caries experience in the different types of epidermolysis bullosa (EB). However, it is not known to what extent the apparent susceptibility to enamel caries is due to disease-related altered enamel chemistry in these cases. The aim of this study was to characterize the enamel of teeth from patients suffering from recessive epidermolysis bullosa dystrophica (rEBD) in terms of its mineral content, carbonate content, protein content, and amino acid composition. The results showed that dental enamel from these patients was essentially normal in terms of its chemistry. It is therefore concluded that the high caries experience in recessive dystrophic epidermolysis bullosa patients is probably related to other factors, such as compromised oral hygiene and prolonged oral clearance due to extensive oral soft tissue damage and a cariogenic diet.

Amino Acids↗

PubMed1996

Protein characterization of fluorosed human enamel.

Despite extensive investigation, the development mechanism or mechanisms resulting in dental fluorosis are unknown. Several hypotheses suggest abnormal matrix synthesis, secretion, and delayed and/or defective matrix degradation with retention of enamel protein. The purpose of this study was to characterize the protein composition of fluorosed human enamel. Nine permanent moderately fluorosed (developed in a 3.2 ppm H2O area) and ten permanent normal control teeth (from individuals with < 0.2 ppm F in their drinking water) were evaluated. The enamel fluoride concentration, protein content, and amino acid composition were determined for each tooth. The enamel proteins were further characterized by gel electrophoresis and by Western blot analysis by means of polyclonal antibodies raised against recombinant amelogenin protein. Fluorotic enamel had significantly elevated (p = 0.0001) F levels compared with normal enamel (mean [F-] fluorosed = 431 ppm; mean [F-] control = 62 ppm). While there was a significantly greater protein content by weight in fluorosed enamel compared with normal enamel (mean fluorosed = 0.27%; mean control = 0.11%), the amino acid profiles were similar for fluorosed and normal enamel. Gel electrophoresis showed fluorosed enamel to have a greater diversity of primarily low-molecular-weight proteins compared with normal enamel. Western blot analysis did not indicate retention of amelogenin in either fluorosed or normal enamel. This investigation showed that the protein content of fluorosed enamel was greater than that of normal enamel; however, the amino acid compositions were similar for fluorosed and normal enamel. Furthermore, there does not appear to be retention of significant amounts of amelogenin in fully mature, moderately fluorosed human enamel. Although delayed removal of the enamel matrix proteins may play a role in the hypomineralization defects seen in fluorosed enamel, the majority of these proteins are absent in the mature tissue of these moderately fluorosed teeth.

Amelogenesis↗

PubMed1996

Enamel mineral composition of normal and cystic fibrosis transgenic mice.

The ability of ameloblasts and the enamel organ to control the influx of ions into the developing enamel is of considerable interest. The development of transgenic mice lacking a cAMP-regulated chloride channel, the cystic fibrosis transmembrane conductance regulator (CFTR), provides a model that may prove valuable for the study of ion regulation in developing teeth. The purpose of this investigation was to characterize the mineral content of normal and CF mice. Five homozygous and five heterozygous adult mice having the CFTR knockout transgene were evaluated. The mice were killed with CO2 and their mandibular incisors removed, embedded in methacrylate, and sectioned, and enamel particles from the incisal region were then dissected for analysis. Each particle was analyzed for its calcium, phosphorus, and magnesium content. The normal mice had a mean mineral content of 80.5%, in contrast to the CF mice, that had markedly hypomineralized enamel (mean = 51.5%). The calcium/phosphorus ratios were similar for both groups of mice and were compatible with the enamel consisting primarily of hydroxyapatite mineral. The enamel magnesium content was significantly elevated in the CF mice (mean = 3560 ppm) compared with the normal mice (mean = 2280 ppm). Normal mouse enamel was highly mineralized, while the CF mouse enamel mineral content was significantly reduced and had an elevated level of magnesium. The altered mineral content of CF mouse enamel indicates that CFTR could play an important role in ion regulation and consequently mineralization of mouse enamel.

Ameloblasts↗

PubMed1996

Hormonal regulation of insulin-like growth factor binding proteins and insulin-like growth factor I (IGF-I) secretion in porcine stromal-vascular cultures.

We examined the time course of insulin-like growth factor binding protein (IGFBP) secretion and hormonal regulation of IGFBP and IGF-I secretion in porcine stromal vascular (S-V) cultures. Primary cultures of S-V cells derived from porcine adipose tissue were exposed to serum-free media with or without hormone treatment. Time course studies indicated that secretion of four IGFBP (IGFBP-1, -2, -3 and -4) by porcine S-V cells increased with time during the first 3 d after the switch to serum-free conditions and then decreased gradually. Growth hormone treatment stimulated secretion of each IGFBP by 47 +/- 4.7, 46 +/- 10.2, 70 +/- 13.2, and 49 +/- 5.6%, respectively, over control levels. The secretion of IGFBP-1, -2, -3, and -4 was enhanced by 91 +/- 18, 80 +/- 16, 74 +/- 12, and 263 +/- 48%, respectively, in T4-treated S-V cultures compared with untreated cultures. In contrast, dexamethasone reduced the abundance of the IGFBP by 28 to 50% of control levels. Insulin-like growth factor I secretion (844.63 +/- 35.98 pg/mL) in vitro (3 d conditioned media) was increased (P < .05) by GH (1,302.45 +/- 12.95 pg/mL) and T4 (1,291.60 +/- 86.4 pg/mL) and decreased (P < .05) by dexamethasone (552.5 +/- 30.2 pg/mL) (n = 4, S-V cell pools, P < .05). In addition to preadipocytes, other cells in S-V cultures also secrete IGFBP. In conclusion, the secretion of IGF-I and IGFBP by S-V cells is differentially regulated by hormones in vitro.

Adipocytes↗

PubMed1996

Cytochemical studies of adipose tissue-associated blood vessels in untreated and thyroxine-treated hypophysectomized pig fetuses.

Fetal hypophysectomy (hypox) slightly enhances lipid accretion in adipose tissue and markedly increases fat cell size and de novo lipogenesis. Thyroxine (T4) treatment (14 to 20 d) had no influence on fat cell size but markedly increased lipogenesis, lipid accretion, and apparent fat cell number in hypox fetuses. Although vascular development is intimately associated with preadipocyte development in the fetus, little is known concerning the regulation of vascular development per se by T4 and other adipogenic hormones. Therefore, the purpose of the present study was to evaluate the development of qualitative traits of the adipocyte-associated vasculature after fetal hypox with and without T4 treatment. Type IV collagen immunoreactivity of and lectin binding by capillaries in large fat cell clusters was reduced by hypox, and binding of the soybean agglutinin lectin was completely lost. Reactivity for cytosolic markers in capillaries was also reduced by fetal hypox. These blood vessel traits were not influenced by T4 treatment. The qualitative aspects of capillary development in large fat cell clusters were not influenced by hypox or T4 treatment. On a qualitative basis, blood vessels in the skin and in small fat cell clusters were not affected by hypox. Lectin binding by adipocytes was enhanced by hypox regardless of the size of clusters, and T4 augmented this response to hypox. These studies demonstrate that endocrine regulation of the differentiation of the adipocyte-associated vasculature is more complex than the endocrine regulation of adipocyte differentiation per se.

Acid Anhydride Hydrolases↗

PubMed1996

The influence of extracellular matrix substrata on preadipocyte development in serum-free cultures of stromal-vascular cells.

The influence of the extracellular matrix (ECM) and ECM components on preadipocyte development was examined in primary cultures of adipose tissue stromal-vascular (S-V) cells. Extracellular matrix derived from Engelbreth-Holm-Swarm (EHS) cells or tumors enhanced several aspects of adipogenesis in vitro. In comparison to uncoated and fibronectin substrata, EHS-ECM substratum markedly increased attachment, spreading, and hypertrophy of preadipocytes while antagonizing spreading of non-preadipocytes. In addition, adipocyte number increased (P < .05) on these substrata despite no increase in total cell number: this resulted in a greater (P < .05) proportion of preadipocytes. These effects of EHS-ECM were also observed with laminin substrata per se, whereas types I and IV collagen and fibronectin had no influence. In contrast to all other substrata, adipocyte number decreased and total cell number increased 2.5-fold on ECM derived from corneal endothelial cells; this resulted in the lowest proportion of preadipocytes. Challenging cultures with adipogenic media (+serum) did not counter the inhibitory influence of corneal endothelial ECM, whereas dexamethasone partially neutralized the inhibitory influence of this ECM. These studies clearly show that source or type of the ECM dictated the influence of ECM substrata on preadipocyte development in primary S-V cultures. However, these studies indicated that the ECM and in particular laminin may play a critical role in morphological aspects of preadipocyte development.

Adipocytes↗

PubMed1996

Structural and compositional alteration of tooth enamel in hereditary epidermolysis bullosa.

Epidermolysis bullosa (EB) is a group of conditions characterized by basement membrane and cellular defects that result in skin fragility and variable extra-cutaneous involvement. The teeth can be severely affected with marked enamel malformations. The purpose of this study was to characterize the structure and composition of teeth from individuals representing the major EB groups (EB simplex, dystrophic EB and junctional EB). Teeth were examined from 28 individuals with EB and 10 healthy people unaffected by EB. Teeth from individuals with junctional EB had marked enamel hypoplasia with varying abnormalities in the enamel structure. Minor structural defects of enamel, including areas of surface pitting, were seen in the other EB types. Although there was a slight reduction (approximately 10%) in the enamel mineral content in several dystrophic EB and junctional EB teeth, the mean mineral content was similar for all EB enamel types and normal enamel. This study shows that while individuals with junctional EB have marked alteration of the enamel structure, the composition may be normal to only mildly altered. Laminin-5, the molecular defect in junctional EB, is associated primarily with alteration in the amount and/or structure of enamel while the mineralization process appears relatively intact. The marked enamel hypoplasia in this EB type suggests that laminin-5 plays an important role in the secretory phase of enamel development.

Calcium↗

PubMed1996

Essential hypertension: racial/ethnic differences in pathophysiology.

Essential hypertension is a complex polygenetic disorder with different "intermediate phenotypes" among diverse racial/ethnic groups. Differences have been identified in the renin-angiotensin system, prevalence of salt sensitivity, ion-transport mechanisms, and calcium homeostasis, yet no unifying hypothesis as to the genetic mechanisms responsible for the excess prevalence and severity of hypertension among African Americans has emerged. Environmental factors, such as access to health care, socioeconomic status, stress, diet, and obesity, account for some of the differences in the prevalence of hypertension worldwide.

Black or African American↗

PubMed1995

Monoclonal antibody-mediated cytotoxicity of adipocytes.

Monoclonal antibodies (MAbs) raised against porcine adipocyte plasma membranes were used to demonstrate complement-mediated cytotoxicity of adipocytes and preadipocytes in primary stromal-vascular (SV) cultures. Five of the six MAbs tested significantly reduced the number of fat cell clusters in cultures maintained in medium supplemented with pig serum and dexamethasone (PS/DEX) but not in cultures supplemented with insulin, transferrin, and selenium (ITS). Neither MAb nor complement alone affected fat cell cluster number. Treatment of both ITS and PS/DEX cultures with pools of 2 or more MAbs, in combination with complement, eliminated fat cell clusters in all instances. Treatment of cultures prior to appearance of cells containing lipid demonstrated that preadipocytes, or adipose lineage cells, could also be eliminated by MAb/complement treatment. Finally, injection of young rats with a pool of three of the MAbs produced a 30% reduction in inguinal fat pad weight without affecting other tissues. Adipocyte/preadipocyte-depleted cultures can now be used as a model system to examine progression of cells through the adipose cell lineage at a time not previously possible with primary cells.

Adipocytes↗