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Biomedical subjects

M S Harris

Publications and source records attributed to M S Harris.

At least 19 recordsLinked to original sources
PubMed2001

Crystallization and preliminary X-ray analysis of UDP-N-acetylenolpyruvylglucosamine reductase (MurB) from Staphylococcus aureus.

UDP-N-acetylenolpyruvylglucosamine reductase (MurB) is an essential enzyme in the bacterial cell-wall biosynthetic pathway, making it a potential therapeutic target for novel antibiotics. Diffraction-quality crystals of both the native and Se-methionine-expressed MurB from Staphylococcus aureus have been prepared by sitting-drop vapour diffusion from solutions containing polyethylene glycol (PEG) 8000, ammonium sulfate, sodium cacodylate pH 6.5 and dimethyl sulfoxide (DMSO). Crystals belong to the cubic space group I2(1)3, with unit-cell parameters a = b = c = 178.99 A. X-ray data from these crystals were collected at the Advanced Photon Source 17-ID beamline and were used to solve the MurB structure to 2.3 A resolution.

Carbohydrate Dehydrogenases↗
PubMed2001

A structural variation for MurB: X-ray crystal structure of Staphylococcus aureus UDP-N-acetylenolpyruvylglucosamine reductase (MurB).

The X-ray crystal structure of the substrate free form of Staphylococcus aureus UDP-N-acetylenolpyruvylglucosamine reductase (MurB) has been solved to 2.3 A resolution with an R-factor of 20.3% and a free R-factor of 22.3%. While the overall fold of the S. aureus enzyme is similar to that of the homologous Escherichia coli MurB X-ray crystal structure, notable distinctions between the S. aureus and E. coli MurB protein structures occur in residues involved in substrate binding. Analysis of available MurB sequences from other bacteria suggest that the S. aureus MurB structure is representative of a distinct structural class of UDP-N-acetylenolpyruvylglucosamine reductases including Bacillus subtilis and Helicobacter pylori that are characterized by a modified mechanism for substrate binding.

Amino Acid Sequence↗
PubMed2001

Effects of fetal bovine serum on ferrous ion-induced oxidative stress in pheochromocytoma (PC12) cells.

Ferrous ion (Fe2+) has been considered to be a cause of neuronal oxidative injury. Since body fluids contain protein and serum is an essential component of tissue culture medium, we have examined the role of serum protein on Fe2+-mediated oxidative stress using PC12 cells and rat cerebral cortices. Fe2+ or the combination of ascorbate and Fe2+ increased concentrations of thiobarbituric acid reactive substances (TBARS) in PC12 cells and cerebrocortical homogenates in medium (RPMI 1640), but did not increase TBARS when the medium was supplemented with 10% fetal bovine serum. Treatment with ascorbate/Fe2+ in serum-free medium reduced endogenous glutathione (GSH) concentration in PC12 cells. However, the medium supplemented with serum did not reduce GSH concentrations. PC12 cell death induced by ascorbate/Fe2+ was alleviated by increasing serum or bovine albumin concentrations in the medium. These observations indicated that oxidative injury caused by the transition metal ion could be lessened by adding fetal bovine serum to culture medium.

Animals↗
PubMed2000

Comparison among the perforation rates of Maloney, balloon, and savary dilation of esophageal strictures.

BACKGROUND: Traditionally, mercury-filled rubber bougies are used for dilation of simple or mild-to-moderate esophageal strictures, whereas through-the-scope balloon dilators and wire-guided polyvinyl bougies have become standard for more complex strictures. Because few comparative trials are available, the choice of dilator and technique is largely based on the training and experience of the operator. METHODS: We reviewed 348 esophageal dilation procedures performed on a total of 142 patients over a 4-year period (January 1, 1993, to January 1, 1997). The location and cause of stricture, the maximum diameter of the instrument used per session, the rate of perforation, and the rate of fluoroscopy use were recorded. RESULTS: Maloney, balloon (hydrostatic and pneumatic type), and Savary dilations were performed in 102, 156, and 90 sessions, respectively. Perforations occurred in 4 patients. All of these perforations occurred when Maloney dilators were passed blindly into complex strictures (Fisher's exact test, p = 0.011, two-tailed). Three of these four patients had undergone endoscopy with conscious sedation immediately before the dilation. The immediate outcome of surgery was good in all 4 patients with no deaths. CONCLUSION: Perforation was most commonly associated with the blind passage of Maloney bougies into complex strictures.

Adult↗
PubMed2000

Marketing health care to minorities: tapping an emerging market.

A number of myths have prevented the development of a formal health care marketing strategy for the 100 million-plus racial and ethnic group members in the United States, despite their relatively greater need for health services. This market continues to grow in numbers, resources, and influence as the majority market level off. Marketers must look to minorities for new business, but traditional health care marketers have a long way to go before they are in a position to truly maximize this opportunity.

Health Services Needs and Demand↗
PubMed1998

Characterisation of fibrous sheath and midpiece fibre network polypeptides of marsupial spermatozoa with a monoclonal antibody.

In this study cytoskeletal antigens common to brushtail possum and tammar wallaby spermatozoa were characterised using a monoclonal antibody (PSA-10). Using indirect immunofluorescence, the PSA-10 antibody detected antigens predominantly associated with the midpiece and principal piece of mature, permeabilised marsupial spermatozoa. The principal piece determinant, shared by a variety of other species, was found to arise in the marsupial testis. Midpiece localisation of the PSA-10 epitope was detected only in marsupial spermatozoa and shown to arise in the epididymis. Immunogold labelling demonstrated that the PSA-10 antigens were predominantly associated with the fibrous sheath and midpiece fibre network of both possum and wallaby spermatozoa. Western blotting suggested that two major possum and wallaby sperm polypeptides of 158 and 182 kDa were associated with the midpiece fibre network, a cytoskeletal structure unique to marsupial spermatozoa. A 32 kDa polypeptide was associated with the principal piece fibre network and/or fibrous sheath. The finding that these marsupial sperm cytoskeletal proteins share a common linear epitope suggests that they share some sequence similarity. The midpiece fibre network of marsupial sperm, like the fibrous sheath, has been proposed to have a structural role in providing passive stiffening for the flagellum (Harding et al., 1975, 1979; Olsen, 1975). The PSA-10 monoclonal antibody may provide a tool for comparative studies of mammalian sperm cytoskeletal proteins, particularly the marsupial midpiece fibre network. It may also allow the formation of this unique marsupial cytoskeletal structure, and its fate during the fertilisation process, to be followed by immunological means.

Animals↗
PubMed1997

Hypericin inhibits choroidal endothelial cell proliferation and cord formation in vitro.

PURPOSE: To evaluate the effect of hypericin on bovine choroidal endothelial cell proliferation and cord formation and on protein kinase C activity. METHODS: The effect of hypericin (0.1-5 microM) on bovine choroidal endothelial cell proliferation was determined by cell number counting and a 3H-thymidine uptake assay in media containing 1, 5 or 10% serum. For the cord formation assay, bovine choroidal endothelial cells were seeded on basement membrane matrix, and the lengths of the capillary-like structures (cords) formed were quantified by image analysis. The effect of hypericin on cord formation was evaluated in the presence of serum or vascular endothelial growth factor. The effect of hypericin on protein kinase C activity was also measured in the presence or absence of light. RESULTS: Hypericin inhibited bovine choroidal endothelial cell proliferation in a dose-dependent manner in the presence of light but not in the dark. Serum dose-dependently masked the inhibition of DNA synthesis by hypericin. Cord formation by bovine choroidal endothelial cells was stimulated by serum or vascular endothelial growth factor and inhibited by hypericin in the presence of light. Protein kinase C activity was completely inhibited by hypericin in the presence of light but only mildly inhibited in the absence of light. CONCLUSIONS: Hypericin inhibits bovine choroidal endothelial cell proliferation and cord formation and choroidal endothelial cell protein kinase C activity. These results suggest that hypericin should be further investigated in animal models for its potential to inhibit subretinal neovascularization.

Animals↗
PubMed1997

Irritable bowel syndrome. A cost-effective approach for primary care physicians.

Recognition and appropriate treatment of IBS can be challenging. A rational approach to management focuses on a positive diagnosis based on the characteristic pattern of symptoms and the exclusion of organic disorders. Dietary modification and pharmacologic therapy may be useful for relieving symptoms. Patient education and reassurance about the benign course of the disease are important aspects of effective treatment. In severe cases, referral to a psychologist or psychiatrist may be warranted. As our understanding of the pathophysiologic processes in IBS increases, more effective therapies will likely emerge.

Colonic Diseases, Functional↗
PubMed1997

cis-Hydroxyproline inhibits proliferation, collagen synthesis, attachment, and migration of cultured bovine retinal pigment epithelial cells.

PURPOSE: Proliferative vitreoretinopathy (PVR) is characterized by the proliferation and migration of retinal pigment epithelial (RPE) and other cells into the vitreous cavity. The PVR membrane formation also is associated with collagen production by RPE. The authors examined the effect of a proline analog, cis-hydroxyproline (CHP), on proliferation, collagen synthesis, attachment, and migration of bovine RPE in vitro. METHODS: The effect of CHP on cell proliferation was determined as a function of dosage and days in culture by counting the cell numbers on days 3, 6, and 9. Collagen synthesis was determined by trichloroacetic acid precipitation of the radiolabeled samples before and after bacterial collagenase digestion. The attachment assay involved type I collagen or fibronectin substrates or both (2.5 micrograms/well). For migration experiments, RPE cells were removed from a defined area of a confluent culture, and migration was quantitated by counting the number of cells migrating into the denuded area over 30 hours. RESULTS: The addition of CHP inhibited RPE proliferation in both a dose- and a time-dependent manner; collagen synthesis, attachment, and migration also were inhibited by CHP in a dose-dependent manner. When the culture plates were coated with collagen, < 100 micrograms/ml of CHP had no effect on cell attachment. Higher doses of CHP resulted in mild inhibition of attachment on collagen-coated plates. Simultaneous addition of L-proline to the cultures resulted in blockade of these inhibitory effects on proliferation, collagen synthesis, attachment, and migration. CONCLUSIONS: The results show that RPE functions critical to the development of PVR are inhibited by CHP, suggesting the possibility that this drug may have potential clinical application.

Animals↗
PubMed1996

Myoelectric activity and absorptive capacity of rat small intestinal isografts.

The effect of transplantation on small intestinal absorption, digestive capacity, myoelectric activity, and morphology was assessed in inbred Lewis rats. Electrodes were sutured to the duodenum and isografted jejunoileum or to the native jejunoileum in controls. The frequency of migrating myoelectric complexes (MMCs) in the duodenum was 3.3 +/- 0.3/hr in controls and 1.8 +/- 0.4/hr in transplants (P < 0.05). MMC frequency in the jejunoileum was 5.1 +/- 1.3/hr in controls and 3.2 +/- 0.9/hr in transplants (P > 0.05). MMCs appeared to migrate from the duodenum to the jejunoileum 80 +/- 3% of the time in controls and 59 +/- 7% of the time in transplant rats (P < 0.05). Absorption in the transplanted jejunoileum demonstrated a 35-40% decrease in glucose and electrolytes absorption. Villus height and number of nuclei per villus was reduced. Intestinal length (dry) was 103 +/- 6 cm for controls and 51 +/- 3 cm for transplant rats (P < 0.05). Brush border sucrase activity was unchanged. We conclude that small intestinal isografts display similar myoelectric activity as controls, but the decreased absorptive capacity and villus height may require longer segments of intestine to be transplanted in order to support normal nutrition.

Animals↗
PubMed1996

Hypericin inhibits cell growth and induces apoptosis in retinal pigment epithelial cells: possible involvement of protein kinase C.

Proliferative vitreoretinopathy (PVR) is characterized by the proliferation and migration of retinal pigment epithelial (RPE) cells in the vitreous cavity. The drug hypericin, which is already in clinical use as an antidepressant, has shown promise as an antiviral and antineoplastic agent. To investigate the therapeutic potential of hypericin in PVR, we incubated RPE cells in standard medium with various serum concentrations containing 0.5 to 5 microM hypericin. In some experiments we studied the effects of hypericin in conjunction with the RPE growth stimulating cytokine tumor necrosis factor alpha (TNF-alpha). Dose-dependent inhibition of RPE cell proliferation with IC50 values of 0.7 microM and 3.3 microM in 1% and 5% serum respectively, was found. Even in conjunction with TNF-alpha, hypericin inhibited RPE proliferation with an IC50 value of 1.5 microM. The drug inhibited PKC activity in cells treated with a 2.5 microM dose by 72% after 30 min and by 100% after 180 min. Finally, hypericin induced RPE cells to undergo apoptotic cell death, as shown by the presence of DNA laddering. These results suggest that hypericin may have potential as a therapeutic drug for PVR and that its antiproliferative and apoptotic effects on RPE cells in vitro are in part mediated by PKC.

Animals↗
PubMed1996

Sacrospinous colpopexy in the management of uterovaginal prolapse.

OBJECTIVE: To investigate the morbidity and results of vaginal hysterectomy with concomitant sacrospinous colpopexy for uterovaginal prolapse. STUDY DESIGN: An observational study was carried out from June 17, 1986, to September 22, 1992. Patients were selected if it was thought that the cardinal-uterosacral ligaments could not be relied upon for vaginal vault support. RESULT: During the study period, 265 vaginal hysterectomies were performed. Forty-five (17%) were with concomitant sacrospinous colpopexy. The mean patient age was 54 years. There was one incidental cystotomy during hysterectomy, and two patients required transfusion. Postoperatively, eight patients were treated for soft tissue infection, one developed new-onset urinary incontinence, and no apparent nerve injuries were diagnosed. The mean day of discharge was 4.4. Six patients were lost to follow-up after the early postoperative period. The mean follow-up for the remaining patients was 29 months (12-66). One patient required subsequent vaginal repair for recurrent cystocele and enterocele. Four patients had persistent stress urinary incontinence. CONCLUSION: Sacrospinous colpopexy at the time of vaginal hysterectomy is reasonably safe and effective for reestablishing upper vaginal support.

Adult↗
PubMed1996

Enteroscopy. Outcomes.

Outcomes studies are important to determine the role of enteroscopy in the management of patients with obscure gastrointestinal bleeding. This article discusses the current available data and identifies areas for further research.

Endoscopes, Gastrointestinal↗
PubMed1995

Effect of tecogalan sodium on angiogenesis in vitro by choroidal endothelial cells.

PURPOSE: To examine the possible inhibitory effect of tecogalan sodium, derived from bacteria, on three important components of in vitro angiogenesis (endothelial proliferation, migration, and tube formation in a collagen gel) using bovine choroidal endothelial cells (CECs). METHODS: The effects of tecogalan sodium (1, 5, 25, 125, and 250 micrograms/ml) on cultured CECs were examined when basic fibroblast growth factor (bFGF, 10 ng/ml), vascular endothelial growth factor (VEGF, 50 ng/ml), a combination of bFGF (10 ng/ml) and VEGF (50 ng/ml) (bFGF/VEGF) and 10% fetal calf serum (FCS) were used as angiogenic stimulants. For the proliferation assay, CECs were cultured and the cell numbers counted on days 1, 3, and 5. For migration assay, CECs were seeded in the upper half of a Boyden chamber while an angiogenic growth factor was loaded in the lower half. After 6 hours of incubation, cell migration was evaluated by counting the numbers of migrated cells per microscopic field on the lower side of the filter. For the tube-forming assay, CECs were seeded in a type I collagen gel, and the length of the tube-like structures (an indicator of angiogenesis) formed by CECs per microscopic field was quantified by image analysis. The effect of neutralizing antibody for bFGF also was tested in these three assays. RESULTS: All tested angiogenic stimulants induced CEC proliferation. The stimulatory effect of bFGF and bFGF/VEGF was reduced by tecogalan sodium (IC50 for bFGF effect, 26.1 micrograms/ml). However, the effect of VEGF and of 10% FCS was not altered by low doses of tecogalan sodium (< 25 micrograms/ml). Chemotaxis of CECs was stimulated by bFGF alone and by bFGF/VEGF, and this effect was inhibited by tecogalan sodium (IC50 for bFGF, 3.2 micrograms/ml). Stimulation of chemotaxis by VEGF alone and by 10% FCS was not affected by tecogalan sodium in low doses but was inhibited by high doses. Tube formation was stimulated by administration of each of the factors. Stimulation of tube formation by bFGF and by bFGF/VEGF was inhibited by tecogalan sodium (IC50 for bFGF, 18.2 micrograms/ml). High doses of tecogalan sodium (125 and 250 micrograms/ml) also inhibited 10% FCS-induced proliferation, migration, and tube formation. CONCLUSION: bFGF, VEGF, and a combination of bFGF and VEGF stimulated proliferation, migration, and tube formation by CECs in vitro. These stimulatory effects, but especially those of bFGF, were inhibited by tecogalan sodium. If tecogalan sodium can be shown to have a similar effect in vivo, it might have the potential for pharmacologic control of subretinal neovascularization.

Animals↗
PubMed1993

Cytogenetic and molecular identification of a de novo direct duplication of the long arm of chromosome 4(q21.3-->q31.3).

We report on a 3-year-old boy with moderate developmental retardation, microcephaly, and malformations of ears, lids, mouth, and thumbs. Cytogenetic analysis demonstrated a direct duplication of chromosome subregion 4(q21.3-->q31.3). Confirmation of this specific rearrangement was performed by fluorescent in situ hybridization (FISH) with a chromosome painting probe and by means of quantitative Southern hybridization with DNA probes localized within the chromosome 4 region presumed to be duplicated.

Abnormalities, Multiple↗
PubMed1991

Seroepidemiology of hepatitis B infection in children in Vanuatu. Implications for vaccination strategy.

Four hundred and eighty-two unvaccinated children from three different age groups (12-18 months, 30-42 months, 54-115 months) in a hepatitis B virus (HBV) endemic area were tested for markers of HBV infection. HBV seromarkers were detected in 52.3% of children and 26.9% were hepatitis B surface antigen (HBsAg) positive. Evidence of infection was related to age, with HBV seromarker rates highest (67.5%) in school children aged 56-115 months. The HBsAg positive rate was highest (30.1%) in children 30-42 months of age. However, even children in the youngest age group (12-18 months) had high seromarker (26.8%) and HBsAg positive (17.0%) rates. A high proportion of HBsAg positive children (83.8%) were also hepatitis Be antigen (HBeAg) positive. Mothers of children in the youngest age group (12-18 months) were also tested, and 24.5% were HBsAg positive. Factors associated with higher rates of infection in children included maternal HBeAg positivity (for children in the youngest age group), increasing age, and residence on the islands of Emao or Nguna. Higher rates of HBsAg positivity were associated with these factors and with being male. Crossinfection between children is probably the most important source of infection, based on the evidence of the high rate of HBeAg positivity in children and the rising infection rate with age. A possible vehicle of spread is through skin infections and skin sores which are highly prevalent in children in Vanuatu. Since this study indicates that both perinatal and early child-to-child transmission are occurring, the most practical strategy to prevent the majority of infections is to vaccinate all children, commencing at birth and completing the course early in the first year of life.

Child↗
PubMed1990

Delorme's transrectal excision for internal rectal prolapse. Patient selection, technique, and three-year follow-up.

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term "placebo" effect attends many therapies, this report describes results of transrectal excision only after a three-year postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.

Adult↗