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Biomedical subjects

D M Powell

Publications and source records attributed to D M Powell.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effect of hydralazine on myocardial plasma membrane fatty acid binding protein (PM-FABP) during diabetes mellitus.

Chronic treatment with the antihypertensive drug hydralazine did not affect the hyperglycemic state of streptozotocin (STZ)-diabetic rats but did prevent the serum hyperlipidemia that is synonymous with these diabetic animals. After 6 weeks, untreated STZ-diabetic rats exhibited a 659% increase in serum triglycerides and 292% increase in serum cholesterol versus age-matched non-diabetic rats. Hydralazine-treated STZ-diabetic rats had serum triglyceride and cholesterol levels that did not differ from controls. Myocytes from control rats showed a preference for binding of the unsaturated fatty acid analog cis-parinaric acid vs the saturated fatty acid analog trans-parinaric acid. This preference was not altered in STZ-diabetic rat myocytes; hydralazine-treatment of STZ-diabetic rats also showed no change in fatty acid preference. STZ-diabetes caused a decrease in the affinity (Kd) for the trans, but not the cis-parinaric acid. However, total binding of both analogs was increased in STZ-diabetes. Hydralazine treatment of STZ-diabetic rats resulted in even greater total binding of both analogs. Affinity for the trans analog was further decreased in these hydralazine-treated rats, but the affinity for the cis analog was increased beyond control animals. These results suggest that the diabetic state influences the binding characteristics of the myocardial PM-FABP and that hydralazine, while reducing serum lipids in diabetes, has complex effects on the fatty acid binding by this protein.

Animals↗
PubMed1995

A proposed classification of vaginal anomalies and their surgical correction.

A classification of vaginal anomalies has been derived, which permits logical operative decisions. This tool allows the assignment of increasingly involved reconstructive operations to progressively more complex vaginal anatomies. The outcome of this approach in 49 vaginal reconstructions performed in 36 patients over a 25-year period has been analyzed. The cause was found to be congenital adrenal hyperplasia in 21 patients, gonadal dysgenesis in four, and cloaca in two; nine children had other causes. Based on the following anatomic classification and the authors' clinical experience, the following approaches to reconstruction can be recommended. Eight infants with labial fusion (type I) underwent simple introitoplasty. Fourteen patients with distal urogenital sinus (type II) underwent flap vaginoplasty using labioscrotal tissue and/or a posteriorly based flap. Pull-through vaginoplasty was used in 10 children with distal vaginal atresia and proximal urethrovaginal fistula (type III). Four patients with absence of the vagina (type IV) required segmental colon vaginoplasty. Thirteen revisions have been required in nine patients thus far. The follow-up period is 1 to 17 years, and despite the need for reoperation, all but two patients have excellent or satisfactory results based on anatomic and functional considerations. The choice for and timing of vaginal reconstruction rests on precise anatomic evaluation. The complexity of vaginal reconstruction in the growing child and the essentiality of psychosocial adjustment to appropriate sexual identity and function mandate long-term comprehensive follow-up. Optimal care for each patient requires experience and continuity to take the child through diagnosis, surgical reconstruction, stressful adolescence, and into adulthood with full attention to anatomic, physiological, and psychological support.

Adrenal Hyperplasia, Congenital↗
PubMed1995

Congenital diaphragmatic hernia. Outcome of preoperative extracorporeal membrane oxygenation.

In recent years, increasing numbers of patients with congenital diaphragmatic hernia (CDH) have been offered extracorporeal membrane oxygenation (ECMO) preoperatively if they can not physiologically tolerate early surgical repair. These infants are sicker are more unstable than those repaired pre-ECMO and, in most cases, have not had a "honeymoon" period (i.e., PaO2>100 mm Hg at some point). ECMO before surgical repair was offered to 27 CDH patients in our institution; of the 16 (59%) survivors, 11 are now 2 years of age to older. To determine the outcome risk for this critical population, we compared 11 infants placed on ECMO pre-CDH repair (Group A) with our previous series of 22 survivors who had their surgery prior to ECMO (Group B). Both groups were similar in birth weight, gestational age, and Apgar scores. In Group A, a greater number were females (73% vs 23%), had right-sided hernia (64% vs 23%), and required patch repairs (82% vs 23%). The mean time on ECMO, time to extubation, and mean length of hospitalization were longer in group A. In both groups combined, the frequency of reherniation was higher in the patch-repair infants compared with those with a primary closure. Incidence of reflux was high in both groups, with increasing frequency of Nissen fundoplication in Group A patients (45% vs 6%). Both groups demonstrated similar delayed growth at 1 year of age. Although infants placed on ECMO presurgery are sicker, with more post-ECMO morbidity, their growth failure is similar to the less sick infants repaired pre-ECMO.(ABSTRACT TRUNCATED AT 250 WORDS)

Apgar Score↗
PubMed1993

Clearance of infused triglyceride by resting horses.

1. Clearance of infused lipid was observed in six mature resting horses, 2 to 6 hr after receiving a meal of alfalfa hay. 2. Intralipid, a 10% triglyceride emulsion, was infused at a rate of 0.2 ml/kg into the jugular vein. 3. Blood samples were obtained for 80 min post-infusion and assayed for plasma triglyceride concentration. 4. Clearance rate of the infused lipid was very slow (mean t1/2 = 269 min). 5. The clearance rate of the infused lipid in these horses was much slower than has been observed in other species. 6. The slow clearance of infused triglyceride in horses may suggest an inability to efficiently metabolize lipoproteins.

Animals↗
PubMed1992

Recombinant human mullerian inhibiting substance inhibits human ocular melanoma cell lines in vitro and in vivo.

Since Mullerian Inhibiting Substance (MIS) causes regression of the Mullerian duct, the anlagen of the uterus, vagina, and fallopian tube, we expected and have previously observed that purified recombinant human MIS causes regression of gynecological tumors. However, recent experiments indicating that neural crest derivatives might be responsive to MIS prompted study of a group of human ocular melanoma cell lines in 4 in vitro inhibition assays, and a subrenal capsule assay in vivo. Ocular melanoma cell lines that grew well in a respective assay were studied with MIS to determine whether this biological modifier could inhibit growth. Three human ocular melanomas, OM431 (P less than 0.01), OM467 (P less than 0.02), and OM482 (P less than 0.03), were growth-inhibited by highly purified human recombinant MIS in soft agarose. A dose-dependent tumor inhibition was noted when OM431 cells were incubated with MIS in a liquid colony inhibition assay (P less than 0.05). In addition, OM467 was inhibited (P less than 0.05) by MIS in a multicellular tumor spheroid assay. Cell cycle analysis indicated that OM431 cells were inhibited in monolayer by MIS while in G1. At 100-fold lower serum concentrations than required in the media of in vitro assays, MIS delivered via i.p. osmotic pumps inhibited (P less than 0.05) in vivo the growth of OM431 implanted beneath the renal capsule of nude and CD-1 irradiated mice when compared to mice given implants of pumps containing no MIS. The responsiveness of ocular melanoma to MIS broadens the spectrum of tumors that might be treated with MIS and suggests further investigation of other neural crest tumors.

Animals↗
PubMed1992

Extensive sequence-specific information throughout the CAR/RRE, the target sequence of the human immunodeficiency virus type 1 Rev protein.

The significance and location of sequence-specific information in the CAR/RRE, the target sequence for the Rev protein of the human immunodeficiency virus type 1 (HIV-1), have been controversial. We present here a comprehensive experimental and computational approach combining mutational analysis, phylogenetic comparison, and thermodynamic structure calculations with a systematic strategy for distinguishing sequence-specific information from secondary structural information. A target sequence analog was designed to have a secondary structure identical to that of the wild type but a sequence that differs from that of the wild type at every position. This analog was inactive. By exchanging fragments between the wild-type sequence and the inactive analog, we were able to detect an unexpectedly extensive distribution of sequence specificity throughout the CAR/RRE. The analysis enabled us to identify a critically important sequence-specific region, region IIb in the Rev-binding domain, strongly supports a proposed base-pairing interaction in this location, and places forceful constraints on mechanisms of Rev action. The generalized approach presented can be applied to other systems.

Base Sequence↗
PubMed1992

Skin infections in Tanna, Vanuatu in 1989.

Skin infections are an important health problem in Vanuatu and other Pacific island countries. In this study, 18,223 people, representing 90% of the population of the southern island of Tanna in Vanuatu, were examined. Scabies was found in 16% of those screened, with 24% of children under 10 years affected. Other skin infections were predominantly furuncles, abscesses, impetigo and cellulitis and were found in 12% overall and in 16% of children under 10 years of age. These infections were found to be more common in larger households and in the vicinity of the volcano Yasur. Strategies for prevention and management of skin infections in Vanuatu are discussed.

Adolescent↗
PubMed1991

Müllerian inhibiting substance blocks epidermal growth factor receptor phosphorylation in fetal rat lung membranes.

Neonatal males develop respiratory distress syndrome more frequently than females for unknown reasons. The fetal testis secretes testosterone and müllerian inhibiting substance (MIS); MIS has been shown to inhibit fetal lung maturation in vitro and in vivo and to block phosphorylation of epidermal growth factor (EGF) receptors in A431 cells. We hypothesized that MIS would also inhibit membrane phosphorylation of EGF receptors in fetal lung, and that ultrastructural study of MIS-exposed lung might complement the biochemical data by assessing the effect of MIS on tissue morphology. Lung membranes were prepared from 19.5-day fetal rats and phosphorylation assays performed with 3 to 4 micrograms of membrane protein, with or without EGF (26 nmol/L), 0.025 mCi AT32P (0.136 mumol/L), and either recombinant human MIS (rhMIS, 30 pmol) from media of Chinese hamster ovary (CHO) cells, rhMIS dialysis buffer, or wild-type CHO media. The 170,000 molecular weight EGF receptor, visualized by autoradiography of polyacrylamide gels, was phosphorylated in both female and male membranes. rhMIS, when added to EGF-stimulated membranes, caused significant inhibition of EGF receptor phosphorylation (females: 32.42% +/- 11.5%; males: 32.3% +/- 19.1%, P less than 0.001; rhMIS-treated v EGF-stimulated state, P = NS, male v female, Cerenkov counting). Electron microscopy (EM) of rhMIS-exposed lung showed decreased lamellar bodies (LB) in both male alveolar spaces and female parenchyma, and, unexpectedly, increased numbers in female alveoli. Immunoabsorption experiments using coincubation of rhMIS with anti-rhMIS IgG polyclonal antibodies or equiprotein normal IgG demonstrated MIS antibody-specific reversal of rhMIS activity in membrane phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Biomechanical performance of tapercut needles for oral surgery.

A new tapercut needle has been designed and developed for closure of the oral mucous membrane in oral surgery. It is a sharp needle with short cutting edges that easily penetrates through a small needle puncture hole. It is manufactured from a unique stainless steel alloy that resists bending and fracture. Biomechanical performance tests and clinical experience confirm its superiority over the standard reverse cutting edge needle for use in oral surgery.

Biomechanical Phenomena↗
PubMed1991

A new compound-curved needle for microvascular surgery.

A new compound-curved needle has been designed and developed for microvascular surgery from a unique stainless steel alloy, American Society for Testing Materials 45500. This needle has two distinct radii of curvature and a short tapered point, followed by a curved distal section. Despite its geometry, it exhibits similar resistance to bending and breakage as a curved needle with a single radius of curvature manufactured from the same alloy. The design of this new needle enables plastic surgeons to pass it through vessel walls with greater accuracy to a controlled depth and length of bite than a curved needle with a single radius of curvature.

Humans↗
PubMed1991

Biochemical performance of tapercut cardiovascular needles.

Standardized reproducible tests have been developed to determine the biomechanical performance of cardiovascular needles. The parameters used to assess performance were: 1) sharpness, 2) resistance to bending, and 3) ductility. Four comparable groups of tapercut and taper point cardiovascular needles were selected from different manufacturers for these biochemical studies. The results of this testing demonstrated that needle geometry, needle composition, and the manufacturer were important determinants of needle performance. When comparable needles were evaluated, the biochemical performance of cardiovascular needles manufactured by Ethicon, Inc. (Somerville, NJ) were superior to needles produced by other manufacturers. The superior performance characteristics of the cardiovascular needles produced by Ethicon, Inc. were related to their unique stainless steel alloy, American Society for Testing Materials 45500, which has greater yield and tensile strengths than the alloy used by the other manufacturers. This stainless steel alloy was ideal for the production of tapercut needles, which combined some of the features of a reverse cutting edge needle and taper point needle. Its very short cutting edges allowed it to penetrate the membrane at considerably lower penetration forces than were encountered with comparable taper point needles. In addition, the investigation indicated that the trocar point cardiovascular needles produced a large triangular defect whose diameter was much larger than that of the needle body. For this reason, the use of the trochar point needle is not recommended in cardiovascular surgery.

Biomechanical Phenomena↗
PubMed1991

Yaws infection in Tanna, Vanuatu 1989.

Yaws has been resurgent in the island of Tanna in southern Vanatu in the 1980's. Screening, conducted in 1988 and in 1989 during a mass treatment program identified a total of 464 clinical cases from the population of 20,200, a rate of 23 per thousand. Most of these (82%) were under 15 years of age. Serology was performed on 286 of which 23% were VDRL positive. Primary care services had been hampered in controlling yaws by difficulties with transport, isolation, community resistance and the lack of skilled personel to diagnose yaws and arrange prophylactic treatment. A mass screening and treatment program was implemented in 1989 with 91.8% coverage. This program was designed to work in the context of primary health care and thus has enhanced the relationship between the health services and local villagers. The program was successfully integrated with other health activities including health education, treatment of other diseases and vector control.

Age Factors↗
PubMed1990

Altered membrane structure in transfected mouse L-cell fibroblasts expressing rat liver fatty acid-binding protein.

Mouse L cell fibroblasts were transfected with cloned cDNA encoding rat liver fatty acid binding protein (L-FABP) also known as sterol carrier protein. Stable transfectant cell lines were selected and expression of L-FABP determined using Western blot analysis. The nontransfected controls and low expression cells did not differ significantly in any of the properties examined. All cell lines showed similar doubling times but cells expressing high levels of L-FABP attained 2-fold higher cell saturation density and differed significantly in their lipid metabolism as indicated by 1) higher cholesterol ester and phospholipid content, and 2) decreased sterol/phospholipid ratio. The observed changes in the lipid composition predicted a lower degree of membrane-lipid order (higher fluidity) in the plasma membranes of cells expressing high levels of L-FABP. Therefore, fluorescent molecule, 1,6-diphenyl-1,3,5-hexatriene, and multifrequency (1-250 MHz) phase and modulation fluorometry were used to probe the effect of L-FABP expression on membrane structure. Steady-state polarization and limiting anisotropy of diphenylhexatriene were significantly lower in the isolated plasma membrane vesicles from the high expression clones. The observed changes in L-cells as a result of de novo expression of L-FABP are consistent with the ability of this protein to bind sterols and fatty acids, stimulate sterol esterification, and stimulate phospholipid biosynthesis. This evidence is supportive of a physiologic role for L-FABP in modulating cellular lipid metabolism and membrane structure.

Animals↗
PubMed1990

Mullerian inhibiting substance ontogeny and its modulation by follicle-stimulating hormone in the rat testes.

Mullerian Inhibiting Substance (MIS) production in rat testes from the late fetal to the adult period and its modulation by gonadotropins in neonatal testes were studied using immunohistochemistry, northern analysis, and a graded organ culture bioassay for MIS. The intense immunohistochemical staining for MIS seen in fetal and newborn testes began to decrease gradually after the third postnatal day, then decreased dramatically on the fifth postnatal day. MIS immunohistochemical activity was then present at a low level until about the 20th postnatal day, after which it was barely detectable. The testes from rats treated with FSH at birth showed a considerable drop in MIS immunohistochemical activity on the third postnatal day to 29% of control testes, and a less profound decrease on the second and fourth postnatal days to 46% and 61% of control, respectively; thereafter MIS levels were the same in treated and untreated animals. With shorter courses of FSH treatment, immunohistochemical staining showed less depression of MIS on the third day, and no difference by the fourth postnatal day, indicating that the inhibitory effect on testicular MIS production may require continued FSH exposure. Three-day testes that had been treated with FSH for 2-1/2 days had less MIS messenger RNA compared to control testes of the same age, suggesting that the inhibitory effect of FSH on MIS production could be transcriptionally mediated. In contrast LH treatment produced no difference in either messenger RNA expression or immunohistochemical staining for MIS. These findings suggested that FSH may be a modulator of MIS production in neonatal testes.

Aging↗
PubMed1989

Functional analysis of CAR, the target sequence for the Rev protein of HIV-1.

Expression of high levels of the structural proteins of the human immunodeficiency virus type 1 (HIV-1) requires the presence of the protein encoded by the rev open reading frame (Rev) and its associated target sequence CAR (cis anti-repression sequence) which is present in the env region of viral RNA. Extensive mutagenesis demonstrated that CAR has a complex secondary structure consisting of a central stem and five stem/loops. Disruption of any of these structures severely impaired the Rev response, but many of the stem/loops contain material that was unnecessary for Rev regulation and must be retained in these structures to avoid disturbing adjacent structures critical for CAR function. Probably no more than two of the described structural components are involved in sequence-specific recognition by regulatory proteins.

Animals↗
PubMed1989

Malrotation of the intestines in children: the effect of age on presentation and therapy.

Because of the devastating consequences of midgut volvulus as a result of malrotation, we reviewed the charts of 70 consecutive children to define the spectrum of presentation. Although 27 patients (39%) had presenting symptoms within the first ten days of life, 35 (50%) were older than 2 months of age. In general, the older children had a longer course of vague, antecedent symptoms such as intermittent, nonbilious vomiting and chronic abdominal pain. Associated congenital anomalies were common, with 32 patients (46%) presenting with 56 anomalies, the most prevalent of which were intestinal atresia, imperforate anus, duodenal web, and cardiac and orthopedic anomalies. Upper gastrointestinal (GI) series revealed the diagnosis in 29 cases (41%), as did contrast enema in 24 (34%). It is important to note that volvulus, intestinal gangrene, and mortality occurred regardless of age or chronicity of symptoms. Fifteen patients (21%) were discovered serendipitously while being evaluated and treated for seemingly unrelated conditions. No morbidity of mortality occurred in those patients who underwent subsequent semielective Ladd's procedure. The majority of morbidity and all seven mortalities occurred in patients with volvulus and intestinal necrosis. This study emphasizes the need for consideration of Ladd's procedure for children of all ages. In addition, due to the broad range of initial symptoms, a high index of suspicion is required in evaluating children with possible malrotation. Because it remains impossible to predict which patients will have catastrophic complications (based on age or type of presentation), we urge that even incidentally discovered patients with intestinal malrotation undergo Ladd's procedure.

Abnormalities, Multiple↗