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Biomedical subjects

P Sherman

Publications and source records attributed to P Sherman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Outcome after ileoanal anastomosis in pediatric patients with ulcerative colitis.

BACKGROUND: To review the outcome after restorative proctocolectomy among children and adolescents with ulcerative colitis at a pediatric inflammatory bowel disease center. METHODS: The records of all patients with ulcerative colitis undergoing colectomy and ileoanal anastomosis at The Hospital for Sick Children, Toronto, Canada, were reviewed. Questionnaires concerning functional results were sent to patients with restored transanal defecation. RESULTS: Seventy three patients (mean age, 13.2 years; range, 2.6-18.8 years) underwent ileoanal anastomosis (19 straight ileoanal anastomosis, 41 J pouch, 13 S pouch) between January 1980 and June 1995 and were observed 5.8+/-3.3 years. The ileoanal anastomosis is nonfunctional in 19 (26%) patients. Excision rates according to type of restorative procedure were J pouch, 7% (3 of 41); S pouch, 32% (4 of 13); and straight ileoanal anastomosis, 32% (6 of 19). Failure was usually attributable to intractable diarrhea among patients with straight ileoanal anastomosis but was caused by anastomotic leak or pelvic-perianal sepsis among patients with pouch procedures. Failure rates did not vary with age at ileoanal anastomosis. Among patients retaining ileoanal continuity, continence problems reported in the questionnaire were frequent and tended to be more extreme among younger patients. Overall, 90% of respondents reported satisfaction with the functional outcome of the restorative operation. CONCLUSIONS: The success rate of the ileoanal anastomosis/J-pouch procedure is comparable to that in adult series. The ileoanal anastomosis/J-pouch procedure is the operation of choice for children and adolescents who want ileoanal continuity restored after colectomy for ulcerative colitis.

Adolescent↗
PubMed1998

Campylobacter upsaliensis: waiting in the wings.

Despite strong epidemiological evidence supporting an important role for Campylobacter upsaliensis as a human enteropathogen, it remains relatively unknown in the realm of clinical microbiology. Clinical studies indicate that infection with this organism usually is associated with benign self-limiting diarrhea. However, more serious illnesses, including spontaneous abortion and hemolytic-uremic syndrome, recently have been associated with human infections. Understanding of the virulence properties and molecular biology of C. upsaliensis is beginning to evolve. There is now a pressing need for controlled, prospective epidemiologic studies in addition to further in-depth investigation of the pathogenesis of this enteric campylobacter to more precisely define its role in human disease. Furthermore, since C. upsaliensis is sensitive to the antibiotics routinely used in Campylobacter selective media, widespread appreciation of the importance of this organism will rely on the development of widely applicable, effective techniques for its isolation.

Adult↗
PubMed1998

Pentoxifylline inhibits hypoxia-induced upregulation of tumor cell tissue factor and vascular endothelial growth factor.

Tissue factor (TF), the membrane glycoprotein that initiates blood coagulation, is constitutively expressed by many tumor cells and is implicated in peri-tumor fibrin deposition and hypercoagulability in cancer. Upregulation of tumor TF correlates with enhanced metastatic potential. Furthermore, TF has been colocalized with VEGF in breast cancer, specially at sites of early angiogenesis. There are no data on the effect of hypoxia on tumor cell TF expression. Since hypoxia is known to stimulate VEGF production, we studied whether this also induces tumor cell TF expression. Confluent monolayers of A375 melanoma, MCF-7 breast carcinoma and A549 lung carcinoma were cultured in either 95% air, 5% CO2 (normoxic) or 95% N2, 5% CO2 (hypoxic; 25-30 mmHg) for 24 h. Procoagulant activity (PCA) was measured by amidolytic and clotting assays, surface TF antigen by flow cytometry, early apoptosis by annexin V binding and VEGF levels in culture supernatants by ELISA. Hypoxia significantly increased tumor cell PCA in all three cell lines tested and TF antigen on A375 cells was increased four-fold (P <0.05). Pentoxifylline (PTX), a methylxanthine derivative, significantly inhibited the hypoxia-induced increase in PCA as well as VEGF release in all three cell lines tested. In A375 cells, PTX significantly inhibited TF antigen expression by both normoxic and hypoxic cells. Hypoxia induced a slight (5%) but not significant, increase in early apoptosis. Intravenous injection of hypoxic A375 cells into nude rats produced more pronounced thrombocytopenia (n = 5, P <0.01) and more lung metastases (n = 3, P <0.05) compared to normoxic cells. We conclude that hypoxia increases TF expression by malignant cells which enhances tumor cell-platelet binding and hematogenous metastasis. Hypoxia-induced upregulation of TF appears to parallel that of VEGF, although the mechanism remains unclear.

Animals↗
PubMed1997

In vivo binding of (+)-alpha-[3H]dihydrotetrabenazine to the vesicular monoamine transporter of rat brain: bolus vs. equilibrium studies.

The regional rat brain distribution of (+)-alpha-[3H]dihydrotetrabenazine was determined following (a) infusion to equilibrium between brain and blood or (b) bolus injection. Infusions provide for direct measurement of total distribution volumes. The free plus nonspecific distribution volume for the brain was determined using infusion of very low specific activity (+)-alpha-[3H]dihydrotetrabenazine; specific distribution volumes, which represent specific radioligand binding, were then calculated as total minus the free + nonspecific distribution volume. Both total and specific distribution volumes correlated very well (r2 > 0.99) with in vitro distributions of the vesicular monoamine transporter binding site. Bolus injection, and measurement of radioactivity at a single time point, also provided regional estimates of radioligand binding which correlated well (r2 > 0.98) with in vitro values. The bolus method shows a small positive bias (+ 10-15%) in regions of high binding site concentrations. Both infusion and bolus injection methods give acceptable in vivo measures of (+)-alpha-[3H]dihydrotetrabenazine binding to the vesicular monoamine transporter of rat brain.

Animals↗
PubMed1997

Potent inhibition of human neuronal nitric oxide synthase by N(G)-nitro-L-arginine methyl ester results from contaminating N(G)-nitro-L-arginine.

N(G)-Nitro-L-arginine methyl ester (L-NAME), inhibits the three isozymes of nitric oxide synthase (NOS) in vitro and in vivo. The mechanism of NOS inhibition by L-NAME is uncertain. L-NAME was a time-dependent inhibitor of neuronal NOS (nNOS). Concommitantly, L-NAME was hydrolyzed, non-enzymatically, to N(G)-Nitro-L-arginine (L-NA) during the enzyme assay. The time-dependent inhibition of nNOS by L-NAME was the result of this time-dependent formation of L-NA. Furthermore, N(G)-Nitro-L-arginine methyl amide, which is an isosteric analogue of L-NAME that is much less susceptible to hydrolysis, was a rapidly reversible weak inhibitor of NOS. These data suggested that L-NAME itself was a weak and rapidly reversible inhibitor of nNOS. Most of the inhibition of nNOS by a solution of L-NAME is the result of the formation of L-NA. L-NAME was a substrate for porcine liver esterase.

Animals↗
PubMed1997

Intrastriatal neurotoxin injections reduce in vitro and in vivo binding of radiolabeled rotenoids to mitochondrial complex I.

The in vivo and in vitro bindings of radiolabeled rotenoids to mitochondrial complex I of rat striatum were examined after unilateral intrastriatal injections of quinolinic acid or 1-methyl-4-phenylpyridinium salt (MPP+). Quinolinic acid produced significant, similar losses of in vivo binding of [11C]dihydrorotenol ([11C]DHROL: 40%) and in vitro binding of [3H]dihydrorotenone ([3H]DHR: 53%) in the injected striatal at 13 days after the injection of neurotoxin. MPP+ reduced in vivo binding of [11C]DHROL up to-55%) as measured 1.5 to 6 h after its administration. Reductions of in vivo [11C]DHROL binding after either quinolinic acid or MPP+ injections did not correlate with changes in striatal blood flow as measured with [14C]iodoantipyrine. These results are consistent with losses of complex I binding sites for radiolabeled rotenoids, produced using cell death (quinolinic acid) or direct competition for the binding site (MPP+). Appropriately radiolabeled rotenoids may be useful for in vivo imaging studies of changes of complex I in neurodegenerative diseases.

1-Methyl-4-phenylpyridinium↗
PubMed1997

Fracture healing in a rat osteopenia model.

Fracture healing is influenced by mechanical and biologic factors. The capacity for fracture repair has been reported to decrease with age, although the risk of fracture increases with age. Fracture healing in an animal model of postmenopausal osteoporosis or osteopenia would provide a useful technique to evaluate and develop new treatment protocols. The authors examined the tensile and bending properties of healing femoral fractures in normal and ovariectomized rats. Mechanical data from tensile and bending tests indicate ovariectomy impairs fracture healing, which was confirmed through histologic study. Bending and tensile data provide useful information concerning the mechanical properties of the healing fracture. Tensile tests were noted to be sensitive indicators of the properties of the healing fracture.

Animals↗
PubMed1996

FTIR microspectroscopic analysis of human osteonal bone.

Fourier Transform Infrared Microspectroscopy (FTIRM) has been used to study the changes in mineral and matrix content and composition in replicate biopsies of nonosteoporotic human osteonal bone. Spectral maps in four orthogonal directions (in 10 microm steps) from the centers towards the peripheries of individual osteons were obtained from iliac crest biopsies of two necropsy cases. Mineral to matrix ratios, calculated from the ratio of integrated areas of the phosphate nu1,nu3 band at 900-1200 cm-1 to the amide I band at 1585-1725 cm-1, increased from the center to the periphery of the osteon. The total carbonate (based on the nu2 band at approximately 850-900 cm-1) to phosphate nu1,nu3 ratio decreased as the mineral to matrix ratio increased. Analysis of the nu2 CO32- band with a combination of second-derivative spectroscopy and curve fitting revealed a decrease in "labile" carbonate, a slight decrease in Type A and a slight increase in Type B carbonate from the center to the periphery of the osteon. Similar analysis of the components of the nu1,nu3 phosphate band with a combination of second-derivative spectroscopy and curve fitting revealed the presence of 11 major underlying moieties. These components were assigned by comparison with published frequencies for apatite and acid-phosphate containing calcium phosphates. The most consistent variations were alterations in the relative percent areas of bands at approximately 1020 and approximately 1030 cm-1, which had previously been assigned to nonstoichiometric and stoichiometric apatites, respectively. This ratio was used as an index of variation in crystal perfection throughout the osteon. This ratio decreased as the mineral to matrix ratio increased. The reproducibility of these parameters at multiple sites in multiple biopsies suggests their applicability for the analysis of mineral changes in disease.

Aged↗
PubMed1996

Synthesis of carbon-11- and fluorine-18-labeled 1-methyl-4-piperidyl-4'-fluorobenzoate and their biodistribution in mice.

Carbon-11- and fluorine-18-labeled forms of 1-methyl-4-piperidyl-4'-fluorobenzoate were prepared as potential in vivo substrates for brain acetylcholinesterase. The 1-methyl-4-piperidyl-4'-[18F]fluorobenzoate was prepared by aromatic nucleophilic substitution using the nitro precursor and no-carrier added [18F]fluoride ion. The 1-[11C]methyl-4-piperidyl-4'-fluorobenzoate was synthesized by N-[11C]methylation of the appropriate nor-methyl precursor. Biodistribution studies in mice showed high brain uptake of these radiotracers followed by a fast washout with no significant retention of radioactivity in areas of high acetylcholinesterase enzymatic activity. This is contrasted with 1-[11C]methyl-4-piperidylacetate, which is rapidly trapped in brain tissues through hydrolysis by AChE. Further in vivo and in vitro studies demonstrated that 1-methyl-4-piperidyl-4'-fluorobenzoate was not a substrate for AChE, and thus not suitable as an in vivo radiotracer for studying this enzyme in the brain.

Acetates↗
PubMed1996

Polysaccharide side chains are not required for attaching and effacing adhesion of Escherichia coli O157:H7.

Escherichia coli of the serotype O157:H7 is an enterohemorrhagic human pathogen which demonstrates attaching and effacing adhesion to colonocytes in vivo and to epithelial cells grown in tissue culture. Transposon TnphoA mutants of E. coli O157:H7 strain CL-8 were produced. Two of 300 alkaline phosphatase positive mutants, designated JB6 and JB27, did not express O157 side chains as assessed by agglutination with specific polyclonal O157 antiserum, silver staining of lipopolysaccharide extracts separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and Western immunoblots with polyclonal O157-specific antiserum. Both O157-negative mutants and the parent strain demonstrated localized adherence to HEp-2 cells when examined by Giemsa staining and bright-field microscopy. Furthermore, both O157-negative mutants showed enhanced adherence to HEp-2 cells compared with the parent strain when assessed by quantification of adherent bacterial CFUs. The parent strain, CL-8, and both of the mutants produced fluorescent foci when adherent bacteria and HEp-2 cells were stained with fluorescein isothiocyanate-labelled phalloidin. Transmission electron microscopy confirmed attaching and effacing adherence of strain CL-8 and the OO7-negative mutants to HEp-2 cells. These findings indicate that mutants deficient in O157 polysaccharide repeats exhibit adherence to tissue culture cells in vitro and that O157 polysaccharide repeats are not required to produce the attaching and effacing lesion.

Agglutination Tests↗
PubMed1996

Supplementary enteral nutrition maintains remission in paediatric Crohn's disease.

BACKGROUND: Liquid diets given enterally combined with "bowel rest' are efficacious in the treatment of active Crohn's disease, but rapid recrudescence of gastrointestinal symptoms after resumption of a normal diet is common. AIMS: This study examined whether continuation of enteral nutrition as a nocturnal supplement to an ad libitum daytime intake of a normal diet increased the length of remission of Crohn's disease in children. PATIENTS AND METHODS: Children and adolescents with active Crohn's disease treated successfully with exclusive enteral nutrition were classified retrospectively according to whether they continued supplementary enteral nutrition or not. Time to relapse and linear growth were compared between the two cohorts. RESULTS: Between January 1986 and December 1992, 65 patients aged 7-17 years (mean (SD) 13.6 (2.1) years) (36 males, 29 females) with Crohn's disease in exacerbation were treated for > or = four weeks by bowel rest and nasogastric tube feeding of an oligopeptide or amino acid based formula. At first follow up visit, remission (fall in Paediatric Crohn's Disease Activity Index, PCDAI to < or = 20) was achieved in 47 of 65 (72%) patients. Subsequently, 20 of these 47 (43%) relapsed by six months and 28 of 47 (60%) by 12 months. Patients who continued nasogastric supplementary feeding (n = 28) after resumption of an otherwise normal diet remained well longer than those who discontinued nocturnal supplements completely (n = 19) (p < 0.02). Furthermore, continued use of nasogastric supplements before completion of puberty was associated with improved linear growth. CONCLUSION: After successful treatment of active Crohn's disease by exclusive enteral nutrition, supplementary enteral nutrition without restriction of normal diet is associated with prolongation of remission and improved linear growth in children and adolescents.

Adolescent↗
PubMed1995

Expression of interleukin 8 and CD54 by human gastric epithelium after Helicobacter pylori infection in vitro.

BACKGROUND/AIMS: Helicobacter pylori is associated with neutrophil infiltrates, although the mechanism of their recruitment is only partially defined. The aim of the study was to determine if Kato III, a human gastric epithelial cell line, expressed cytokines and the intercellular adhesion molecule 1 (ICAM-1), which could contribute to the initiation of inflammation during infection with H. pylori. METHODS: Kato III cells were stimulated with H. pylori and were examined for evidence of infection, cytokine production, and the expression of ICAM-1. RESULTS: The expression of interleukin 8 messenger RNA and immunoreactive protein by Kato III cells was significantly increased over constitutive levels within 3 hours of infection with H. pylori. Infected Kato III supernatants activated neutrophils as evidenced by increased CD11b/CD18 and decreased L-selectin that could be blocked by anti-interleukin 8. In contrast, Campylobacter jejuni, lipopolysaccharide, killed H. pylori, and supernatants from cultures of H. pylori did not increase interleukin 8. Interleukins 2 and 6; interferons alfa, beta, and gamma; and tumor necrosis factor were not produced by resting or H. pylori-stimulated Kato III cells. In addition to producing interleukin 8, Kato III constitutively expressed surface ICAM-1, which acts as an intercellular adhesion molecule for neutrophils. CONCLUSIONS: Our results indicate that H. pylori stimulates the gastric epithelium to initiate inflammation and neutrophil recruitment and activation.

Base Sequence↗
PubMed1995

Synthesis, in vivo biodistribution and dosimetry of [11C]N-methylpiperidyl benzilate ([11C]NMPB), a muscarinic acetylcholine receptor antagonist.

4-N-Methylpiperidyl benzilate (NMPB), a high affinity antagonist for the muscarinic cholinergic receptor, has been synthesized in carbon-11-labeled form through the N-[11C]methylation of 4-piperidylbenzilate. The product was isolated by HPLC, and obtained in yields (> 100 mCi) and specific activities (500-3000 Ci/mmol) sufficient for in vivo evaluation in small animals. Time-dependent regional brain distributions in rats and mice showed high radiotracer uptake and retention in striatum and cortex, and low in cerebellum, consistent with muscarinic cholinergic receptor distributions. Radiotracer retention in tissues could be significantly reduced by pretreatment of animals with a large dose of a competing antagonist, quiniclidinyl benzilate. Whole body biodistribution in rats was used to calculate the expected human internal radiation dosimetry for this new radiopharmaceutical. These animal experiments formed the basis for subsequent introduction of [11C]NMPB into human use with positron emission tomography.

Animals↗
PubMed1995

Physical and genetic map of the genome of Campylobacter upsaliensis.

A physical map of Campylobacter upsaliensis ATCC 43954 was constructed from DNA fragments generated by SalI (5' G/TCGAC), NarI (5' GG/CGCC) and BssHII (5' G/CGCGC) restriction digests separated using pulsed-field gel electrophoresis. The size of the C. upsaliensis genome was approximately 2000 kb, providing evidence of the largest Campylobacter genome sized to date. Twenty-one fragments created from these restriction digests were assembled into a physical map using a combination of complementary methods including cross-Southern hybridization, hybridization fingerprint analysis and hybridization with homologous and heterologous (from Campylobacter jejuni) gene probes. The position of ten genetic loci, including that of the iron-uptake regulatory (fur) gene, were localized to the physical map. A genomic library of C. upsaliensis ATCC 43954 was constructed in lambda Gem-11 vector. Fifty thousand recombinants with an average size of 16 kb represent a library about 200 times the size of the genome. Using C. jejuni DNA probes, clones representing C. upsaliensis flaA, fur and ftsZ genes were isolated and localized to the physical map.

Blotting, Southern↗