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Biomedical subjects

M Hull

Publications and source records attributed to M Hull.

At least 37 records · Page 2Linked to original sources
PubMed1993

Ultrasound diagnosis of polycystic ovaries.

Ultrasound characterization of ovarian morphology has become an important aspect of gynecological endocrinology. The classic ultrasound features of polycystic ovaries are an increased number of small follicles together with abundant stroma. The exact criteria vary according to the ultrasound technique used. The method, however, has been validated both laparoscopically and histologically. Using laparoscopic inspection as a reference test, ultrasonography was calculated to have a sensitivity of 91% and a specificity of 100%. As a group, anovulatory women with PCO have the classic endocrine features of polycystic ovarian syndrome, but in a proportion of cases the finding of PCO at scan appears to be irrelevant to the presenting disorder. Ultrasound diagnosis of PCO is also limited by its inability to display either ovary in about 16% of women.

Female↗
PubMed1993

Evaluation of the developmental toxicity of trichloroethylene and detoxification metabolites using Xenopus.

Potential mechanisms of trichloroethylene-induced developmental toxicity were evaluated using FETAX (Frog Embryo Teratogenesis Assay--Xenopus). Early Xenopus laevis embryos were exposed to trichloroethylene for 96 h in two separate definitive concentration-response assays with and without an exogenous metabolic activation system (MAS) and inhibited MAS. The MAS was treated with either carbon monoxide or cyclohexene oxide to modulate mixed-function oxidase (MFO) or epoxide hydrolase activity, respectively. Trichloroethylene metabolites: dichloroacetic acid, trichloroacetic acid, trichloroethanol, and oxalic acid were also evaluated in two separate definitive, static renewal tests. Addition of the MAS decreased the 96 h LC50 and EC50 (malformation) of trichloroethylene 1.8-fold and 3.8-fold, respectively. Addition of the carbon monoxide inhibited MAS decreased the developmental toxicity of activated trichloroethylene to levels approximating that of the parent compound. Cyclohexene oxide-inhibited MAS substantially increased the developmental toxicity of trichloroethylene. In addition, each of the metabolites tested were significantly less developmental toxic than the parent compound, trichloroethylene. Results indicate that a highly embryotoxic epoxide intermediate, trichloroethylene oxide, formed as the results of MFO mediated metabolism may play a significant role in the developmental toxicity of trichloroethylene in vitro.

Animals↗
PubMed1992

The small GTP-binding protein rab4 controls an early sorting event on the endocytic pathway.

rab4 is a ras-like GTP-binding protein that associates with early endosomes in a cell cycle-dependent fashion. To determine its role during endocytosis, we generated stable cell lines that overexpressed mutant or wild-type rab4. By measuring endocytosis, transport to lysosomes, and recycling, we found that overexpression of wild-type rab4 had differential effects on the endocytic pathway. Although initial rates of internalization and degradation were not inhibited, the transfectants exhibited a 3-fold decrease in fluid phase endocytosis as well as an alteration in transferrin receptor (Tfn-R) recycling. Wild-type rab4 caused a redistribution of Tfn-R's from endosomes to the plasma membrane. It also blocked iron discharge by preventing the delivery of Tfn to acidic early endosomes, instead causing Tfn accumulation in a population of nonacidic vesicles and tubules. rab4 thus appears to control the function or formation of endosomes involved in recycling.

Animals↗
PubMed1992

Reversible phosphorylation--dephosphorylation determines the localization of rab4 during the cell cycle.

The ras-like GTP binding protein rab4 is the only known rab protein on endosomes that is phosphorylated during mitosis. Since a large fraction of rab4 accumulates in the cytosol in mitotic cells, we investigated the molecular mechanism controlling membrane association of rab4. We first show that human rab4 is phosphorylated by recombinant mammalian p34cdc2 kinase in vitro. Next, the actual site of phosphorylation and its functional significance were determined using stably transfected CHO cell lines producing high levels of wild type rab4 or rab4 mutants bearing alterations at Ser196, which occurs within a consensus site for p34cdc2 kinase phosphorylation (S196PRR). Mutation of Ser196 to glutamine or aspartic acid completely prevented rab4 phosphorylation in mitotic cells and also blocked its appearance in the cytosol. Neither C-terminal isoprenylation nor carboxymethylation of rab4 was affected by the mutations or by phosphorylation. Finally, dephosphorylation and reassociation of soluble rab4 with membranes occurred upon exit of cells from mitosis. Thus, phosphorylation of Ser196 is directly responsible for the reversible translocation of rab4 into the cytosol of mitotic cells.

Animals↗
PubMed1992

A neuromuscular monitoring system based on a personal computer.

We have developed a computerized neuromuscular monitoring system (NMMS) using commercially available subsystems, i.e., computer equipment, clinical nerve stimulator, force transducer, and strip-chart recorder. This NMMS was developed for acquisition and analysis of data for research and teaching purposes. Computer analysis of the muscle response to stimulation allows graphic and numeric presentation of the twitch response and calculated ratios. Since the system can store and recall data, research data can be accessed for analysis and graphic presentation. An IBM PC/AT computer is used as the central controller and data processor. The computer controls timing of the nerve stimulator output, initiates data acquisition, and adjusts the paper speed of the strip chart recorder. The data processing functions include establishing control response values (when no neuromuscular blockade is present), displaying force versus time and calculated data graphically and numerically, and storing these data for further analysis. The general purpose nature of the computer and strip chart recording equipment allow modification of the system primarily by changes in software. For example, new patterns of nerve stimulation, such as the posttetanic count, can be programmed into the computer system along with appropriate data display and analysis routines. The NMMS has functioned well in the operating room environment. We have had no episodes of electrocautery interference with the computer functions. The automated features have enhanced the utility of the NMMS.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Systems↗
PubMed1991

The small GTP-binding protein rab4 is associated with early endosomes.

Small GTP-binding proteins of the rab family have been implicated as playing important roles in controlling membrane traffic on the biosynthetic and endocytic pathways. We demonstrate that a distinct rab protein, rab4p, is associated with the population of early endosomes involved in transferrin-receptor recycling. An antibody to human rab4p was found to detect a doublet of approximately 24-kDa proteins on immunoblots from various cell types. Seventy-five percent of these proteins were tightly membrane bound and could be released only by detergent treatment. Upon isolation of early endosomes, late endosomes, and lysosomes, by free-flow electrophoresis and Percoll density-gradient centrifugation, most (70%) of the rab4p was found to cofractionate with early endosomes and endocytic vesicles containing 125I-labeled transferrin. The rab proteins previously localized to the endoplasmic reticulum and/or Golgi apparatus were not found in these fractions. We also localized rab4p to transferrin-receptor-containing early endosomes by immunofluorescence after expression of rab4 cDNA. The association of rab4p with early endosomes and other vesicles involved in the intracellular transport of transferrin receptor suggests that rab4p may play a role in regulating the pathway of receptor recycling.

Animals↗
PubMed1988

Derived protein sequence, oligosaccharides, and membrane insertion of the 120-kDa lysosomal membrane glycoprotein (lgp120): identification of a highly conserved family of lysosomal membrane glycoproteins.

The 120-kDa lysosomal membrane glycoprotein (lgp120) is an acidic, heavily glycosylated membrane protein enriched in the lysosomal membrane. To determine the basis for its selective transport to and stability in lysosomes, we have investigated the structure of lgp120. By using an oligonucleotide probe corresponding to the amino terminus of rat lgp120, we isolated and characterized cDNA clones containing the entire coding region. The deduced amino acid sequence demonstrates that lgp120 contains a putative signal peptide, 18 sites for N-linked glycosylation, a single membrane-spanning segment, and a short (11 amino acid) cytosolic tail. The sequence suggests a distinct domain organization, with two luminal glycosylated regions separated by a nonglycosylated proline-rich region. Proteolysis in detergent showed that the protein was not intrinsically resistant to exogenous or endogenous proteases. The N-linked oligosaccharides on lgp120, tetraantennary structures with two lactosamine repeats on one of the branches, were not different from those of glycoproteins on the plasma membrane. lgp120 was similar in its domain organization and portions of its amino acid sequence to the avian 100-kDa lysosomal membrane protein LEP100 [Fambrough, D. M., Takeyasu, K., Lippincott-Schwartz, J., Siegel, N. R. & Somerville, D. (1988) J. Cell Biol. 106, 61-67], and to a distinct 110-kDa lysosomal membrane protein (lgp110) that colocalizes with lgp120. The similarities between lysosomal membrane glycoproteins from diverse species, coupled with the fact that at least two distinct lysosomal membrane glycoproteins are expressed in a single species, indicate the existence of a conserved family of glycoproteins enriched in the lysosomal membrane.

Amino Acid Sequence↗
PubMed1986

Bioprosthesis in hand surgery.

In 1965, Carpentier coined the term bioprosthesis to distinguish the characteristics of glutaraldehyde-treated porcine heart valves from untreated or synthetic valves. Observation that the valves functioned normally but were not incorporated by the host has stimulated interest in similarly preserved materials for use in hand surgery. This report outlines work that was initiated to learn the effects of glutaraldehyde treatment on tendon and a reticular substitute. In over 56 experiments with a chicken model, experience with glutaraldehyde-treated tendon grafts shows no acute rejection. There is good function clinically by 8 weeks with proximal fibrous ingrowth seen histologically. By 12 weeks, distal ingrowth has occurred. There is no ingrowth into the tendon graft within the fibro-osseous tunnel. Mechanical testing of the implant system shows a peak load at failure of 1.86 +/- 0.43 pounds and at 24 weeks it is 6.53 +/- 2.6 pounds. The failure site at time zero was distal. By 12 weeks, the distal attachment strengthened and the proximal attachment failed at a greater load. An interpositional substance with potential uses in hand surgery has been prepared by glutaraldehyde treatment of mammalian pericardium. Possible uses include interposition between fractured phalanx and the extensor tendon. This has been evaluated in feasibility studies in a rabbit model.

Animals↗
PubMed1986

Evaluation of glutaraldehyde-treated tendon xenograft.

Glutaraldehyde-treated flexor tendon xenografts were implanted in 62 adult White Leghorn chickens. Animals were evaluated for implant integrity, function, mechanical tests, and histology serially to 24 weeks. Implant function improved dramatically throughout the 24 weeks. Gross examination at death showed intact proximal and distal attachments in all but two animals. The amount of fibrous ingrowth into the proximal end of the implant increased throughout the 24 weeks. Distal fibrous ingrowth also occurred, but at a slower rate. At no point was lateral ingrowth into the tendon seen within the fibro-osseous tunnel. Excision of the sheath and pulley system significantly limited tendon gliding by allowing vigorous formation of adhesions. Mechanical testing revealed that the distal attachment strengthened with time and that the proximal attachment became the failure point. Glutaraldehyde-treated mammalian tendon xenografts allow for fibrous ingrowth and may become incorporated by the host. In this animal model, it has allowed the xenograft to function as a tendon graft. Further studies are planned before clinical trials are undertaken.

Animals↗
PubMed1984

Impaired bacterial clearance and trapping in obstructive jaundice.

Sepsis is a major cause of mortality in patients with common bile duct obstruction. To define possible contributing factors to this phenomenon, this study evaluates the effect of biliary obstruction on the intravascular clearance and organ trapping of viable Escherichia coli using a rat model. Adult male Sprague-Dawley rats were placed in three groups: Group I controls had sham operation, Group II had division and ligation of common bile duct (CDL), and Group III underwent splenectomy. At 21 days following operation 10(9) radiolabeled E. coli were injected intravenously. At varying intervals after infusion, blood samples were obtained for clearance study. At 10 minutes, bacterial distribution in the liver, spleen, kidneys, and lungs was determined (expressed as the mean percentage of injected viable E. coli). Intravascular clearance was similar in all groups. There was a significant decrease in the trapping of bacteria by the liver of CDL rats 14.5% +/- 4.95 (vs. control = 70.0% +/- 13.3) (p less than 0.005). A significant increase of bacterial trapping by the lung was observed in the CDL animals: 63.1% +/- 7.06 (vs. controls 1.4% +/- 0.82) (p less than 0.005). There was no significant change in bacterial localization in splenectomized rats. These data suggest that biliary obstruction decreases hepatic phagocytosis and increases pulmonary localization of viable E. coli. As the Kupffer cells of the liver are usually effective in removal of blood borne bacteria, this phagocytic dysfunction may contribute to the increased susceptibility to infection noted in instances of biliary obstruction.

Animals↗
PubMed1983

Superoxide dismutase: a cellular protective enzyme in bowel ischemia.

Recent data suggest that the free-radical anion superoxide (O-2), an unstable, cytotoxic form of oxygen, is implicated in the pathogenesis of ischemic bowel injury. This study evaluates the role of superoxide dismutase (SOD), an enzyme specific for enzymatic conversion of O-2 in protecting the bowel from an ischemic insult. At laparotomy, the superior mesenteric artery was occluded for 1 min in 90-g weanling rats (n = 144). Animals were divided into four groups: I, untreated controls (n = 41); II, received aminophylline (AMN) 40 mg/kg ip, a substrate for (O-2) generation (n = 21); III, received superoxide dismutase (SOD) 2.5 mg/kg iv (n = 20); IV, received both AMN and SOD (n = 22). Rats were evaluated for bowel infarction, perforation, and mortality over a 7-day observation period. In 40 additional rats (10 per group) bowel ultrastructure was evaluated by scanning electron microscopy (EM) during occlusive ischemia and at various time intervals following reperfusion. Mortality was 63.4% in controls (26/41) with necrosis noted in 19 and perforation in 7. AMN resulted in a 90% mortality (19/21) (chi 2, P less than 0.05 vs control), with necrosis in 15 and perforation in 4. SOD reduced mortality to 25% (5/20) with necrosis in 4 and perforation in 1 (chi 2, P less than 0.02 vs controls) and, when added to AMN, 45.5% (10/22) (chi 2, P less than 0.01 vs AMN alone). On EM, tissue damage was minimal during occlusive ischemia, worsened by duration of reperfusion, enhanced by AMN, and reduced by SOD. These data suggest that following hypoxia, the injured bowel may be unable to appropriately handle reoxygenation. Tissue damage was related to duration of reperfusion and was worse following AMN, a xanthine derivative that might generate (O-2), a cytotoxic free radical. SOD detoxifies O2-, increases survival, and protects the bowel during reperfusion.

Aminophylline↗
PubMed1983

Ischemic bowel: the protective effect of free-radical anion scavengers.

Recent data indicates that the free-radical anion superoxide (O2-), an unstable cytotoxic form of oxygen, is implicated in the pathogenesis of ischemic bowel following reperfusion after low flow states. This report evaluates the effect of free radical scavengers on survival in an animal model with bowel ischemia. At laparotomy, the superior mesenteric artery (SMA) of 79 weanling rats (90 g) was occluded for one minute and released. Animals were divided into three experimental groups: group I acted as controls (n = 41), group II, received thiopental 5 mg/kg IV (n = 19), group III, received methohexital 2.5 mg/kg IV (n = 19). At one week animals were evaluated for mortality, mean survival time, evidence of bowel necrosis or perforation, and bowel appearance on scanning electron microscopy (EM). Mortality was 63.5% (26/41) in group I, 19 had necrotic bowel and 7 had gross perforation; 31.6% in group II (6/19) (p less than .05 versus control), with one necrotic bowel and 5 perforations; and 57.9% in group III (11/19) where 7 had necrotic bowel and 4 had perforations (p NS v control). Survival time (mean +/- SD in days) post SMA occlusion was 3.2 +/- 1.9 for group I; 4.0 +/- 1.7 for group II; and 2.5 +/- 2.0 for group III. EM showed mucosal destruction worsened by the duration of reperfusion, decreased by thiopental but not by methohexital. Thiopental, a free radical anion scavenger was cytoprotective in this animal model, as it decreased mortality and the incidence of bowel necrosis and perforation. These data support the thesis that following low flow states bowel ischemia may be related to a reperfusion injury due to the release of toxic free radical anions.

Animals↗