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Biomedical subjects

A Lee

Publications and source records attributed to A Lee.

At least 577 records · Page 32Linked to original sources

Helicobacter muridarum sp. nov., a microaerophilic helical bacterium with a novel ultrastructure isolated from the intestinal mucosa of rodents.

Helical organisms with novel ultrastructural characteristics were isolated from the intestinal mucosa of rats and mice. These bacteria were characterized by the presence of 9 to 11 periplasmic fibers which appeared as concentric helical ridges on the surface of each cell. The cells were motile with a rapid corkscrewlike motion and had bipolar tufts of 10 to 14 sheathed flagella. The bacteria were microaerophilic, nutritionally fastidious, and physiologically similar to Helicobacter species and Wolinella succinogenes but could be differentiated from these organisms by their unique cellular ultrastructure. Using 16S rRNA sequencing, we found that strain ST1T (T = type strain) was related to previously described Helicobacter species, "Flexispira rappini," and W. succinogenes. The closest relatives of strain ST1T were Helicobacter mustelae and "F. rappini" (average similarity value, 96%). On the basis of phylogenetic data, strain ST1T (= ATCC 49282T) represents a new species of the genus Helicobacter, for which we propose the name Helicobacter muridarum.

Animals↗

An ultrastructural study of Helicobacter mustelae and evidence of a specific association with gastric mucosa.

The ultrastructure of Helicobacter mustelae, a natural inhabitant of the ferret stomach, has been studied and compared with the human gastroduodenal pathogen H. pylori. H. mustelae is a short, slightly curved rod, 2 microns x 0.5 micron, with four or more sheathed flagella. The most common flagellar configuration is a single flagellum at one terminus, bipolar arrangement at the other end and a lateral flagellum. Dense inclusion bodies were observed below the flagellar insertion sites. It is suggested that this configuration is a specialised adaptation to motility in a viscous environment. On examination of the ferret gastric mucosa, similarities to H. pylori were observed such as adherence to gastric tissue and the formation of adhesion pedestals. However, unlike H. pylori, significant numbers of bacteria were intracellular. Furthermore, a much greater proportion of H. mustelae were attached to the mucosa with few bacteria lying free in the mucus, as is seen with H. pylori. It is concluded that the ferret is an important model for the study of adherence of bacteria to gastric mucosa and their possible role in peptic ulceration.

Animals↗

Haemagglutination profiles of Helicobacter species that cause gastritis in man and animals.

Thirty-five Helicobacter pylori isolates, 21 H. mustelae isolates and four strains of H. felis were compared for their ability to agglutinate red blood cells (RBCs). Isolates were examined in a slide haemagglutination assay with RBCs from 11 animal species, including rodents, carnivores and primates, as well as man. RBCs were agglutinated by 65-90% of H. mustelae isolates and 16-57% of H. pylori isolates. Treatment of H. mustelae with pronase and heat inhibited haemagglutination (HA) whereas heating only of H. pylori inhibited HA. Treatment of all strains of H. mustelae with trypsin inhibited agglutination of human RBCs; 75% of the treated strains did not agglutinate ferret RBCs. These results suggested that protein(s) may be important haemagglutinins for these bacteria. Variable HA profiles together with varying results after treatment of RBCs with fetuin, D-mannose, and neuraminidase suggested that multiple receptors may be involved in HA reactions with H. pylori and H. mustelae. The observation that H. mustelae and H. pylori agglutinated RBCs of several species and closely adhered to gastric epithelium supported the hypothesis that adherence plays a role in the colonisation and pathogenicity of H. mustelae and H. pylori. H. felis did not adhere to gastric epithelium and did not agglutinate RBCs of any species; nevertheless, H. felis can readily colonise and produce gastritis in several mammals.

Animals↗

Roles of rpoD, spoIIF, spoIIJ, spoIIN, and sin in regulation of Bacillus subtilis stage II sporulation-specific transcription.

Bacillus subtilis strains containing defects in the sporulation gene spoIIF (kinA), spoIIJ (kinA), or spoIIN (ftsA) cannot transcribe the sigma E-dependent gene spoIID. Results presented here and by other workers demonstrate that the spoIIF, spoIIJ, and spoIIN gene products control spoIID transcription indirectly by coordinating the induction of the spoIIGAB, spoIIE, and spoIIAC operons, which are required for sigma E synthesis and processing. Sporulation competence and spoIIGAB, spoIIE, and spoIIAC transcription were restored in spoIIF, spoIIJ, and spoIIN mutants by introduction of crsA47, a mutation in the major vegetative sigma factor sigma A. crsA mutations are known to restore sporulation in certain spo0 mutants. crsA suppression of kinA and ftsA mutations was achieved through inhibition of the transcription of sin, a gene involved in the selection between several post-exponential-phase cell states. A deletion of sin restored sporulation competence in spoIIF, spoIIJ, or spoIIN mutant strains. A sin deletion was also able to restore sporulation competence in the crsA suppressible stage 0 mutant spo0K141.

Bacillus subtilis↗

PDGF induces tyrosine phosphorylation in osteoblast-like cells: relevance to mitogenesis.

We have studied the association between protein tyrosine phosphorylation and the mitogenic effect induced by platelet-derived growth factor (PDGF) in the osteoblast-like cell line MC3T3-E1. PDGF caused a dose-dependent increase in [3H]thymidine incorporation in MC3T3-E1 cells, reaching a plateau at 10 ng/ml. Vanadate, a potent phosphatase inhibitor, induced a twofold increase in thymidine incorporation. The combination of vanadate and PDGF resulted in a dose-dependent synergistic effect on thymidine incorporation. Genistein, a tyrosine kinase inhibitor, inhibited in a dose-related manner (2-20 microM) the mitogenic effect induced by either PDGF or the combination of vanadate and PDGF. These observations suggest that tyrosine kinases are involved in mediating the mitogenic effect of PDGF in these cells. PDGF treatment of MC3T3-E1 cells and subsequent immunoblotting with antiphosphotyrosine antibodies resulted in a marked phosphorylation of the PDGF receptor. Vanadate had a lesser effect on PDGF receptor phosphorylation, but given together with PDGF it induced a significant increase in the intensity of receptor phosphorylation. Preincubation with genistein abrogated these effects. Taken together, these findings indicate a direct correlation between thymidine incorporation and tyrosine phosphorylation in MC3T3-E1 cells and suggest that tyrosine phosphorylation plays a role in PDGF-induced mitogenic activity in osteoblast-like cells.

Animals↗

Cholecystokinin and satiety: effect of hypothalamic obesity and gastric bubble insertion.

Cholecystokinin (CCK) is a gut peptide whose proposed effect on satiety is thought to be related to gastric volume and to be signaled through vagal afferent fibers to the medial hypothalamus. To test these hypotheses we infused CCK C-terminal octapeptide (CCK-8) or saline in a random double-blind fashion in three groups of subjects: 17 obese subjects, 6 of whom subsequently received a gastric bubble, and 5 obese subjects whose obesity was due to hypothalamic injury. The number of sandwich canapes eaten after saline or CCK-8 infusion was recorded during three consecutive 10-min eating periods. Each subject served as his/her own control. The prior infusion of CCK-8 significantly decreased the consumption of sandwich canapes in the first eating period in both the control obese subjects and the subjects with obesity due to hypothalamic injury. Insertion of a gastric bubble did not enhance the satiety effect of CCK-8. These studies support the hypothesis that CCK produces satiety in a time-dependent manner that is not enhanced after the insertion of a gastric bubble but is operative in obese subjects with hypothalamic injury.

Cholecystokinin↗

Serological identification of HLA-B13 subtypes.

A serological approach is used to confirm subtypes of HLA-B13 originally observed by one-dimensional isoelectric focusing (1D-IEF). Sixty anti-B13 alloantibody sera were screened against Chinese panel cells. Two clusters of sera showing distinct reactive patterns were identified. One is a shorter reactive pattern than the other. Using these serological reaction patterns, the B13 antigen can be divided into two subtypes, B13.1 and B13.2, in the Chinese population. These serological subtypes appear to correlate well with the 1D-IEF patterns of B13 subtypes. The serological subtyping is also in agreement with the differences in nucleotide sequence previously determined to exist in B13 antigen subtypes. Family studies show that both B13.1 and B13.2 segregate as HLA-B locus alleles. Gene frequencies for B13.1 and B13.2 were 0.0676 and 0.0612, respectively, in our study population of 337 southern Han Chinese.

Alleles↗

Efficacy of antihypertensive medication in orthotopic heart transplant recipients and its effect on renal function.

The authors looked at 77 patients following orthotopic heart transplant who received a triple immunosuppressive regimen including cyclosporine to see the effect of various antihypertensive medications on mean arterial blood pressure and renal function. There were 62 men and 15 women retrospectively classified into three groups according to the antihypertensive medications they received. Group 1 included 26 patients followed up for 10.7 +/- 2.7 months who received hydralazine therapy. Group 2 included 32 patients followed up for 9.0 +/- 3.4 months who received angiotensin-converting enzyme inhibition therapy. Group 3 included 19 patients followed up for 10.1 +/- 3.3 months who received beta-adrenergic blocking agents. Mean arterial pressure (MAP), serum blood urea nitrogen (BUN), and serum creatinine (CR) were determined for each group at the start and end of the follow-up period. The MAP at the start of the study was 107 +/- 14 in group 1, 110 +/- 13 in group 2, and 100 +/- 11 in group 3. It was not statistically significantly different in any of the groups. At the end of the follow-up period, MAP was 112 +/- 10, 111 +/- 10, and 106 +/- 12 for the three groups respectively, and it was not significantly different in any group. The serum BUN in group 3 was 25 +/- 8 mg/dL at the start of the study, and it was not significantly lower than that in group 1, 28 +/- 6, but it was significantly different from that in group 2, 34 +/- 9, P less than 0.05. At the end of the follow-up period, the difference was still maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Role of Helicobacter felis in chronic canine gastritis.

Five gnotobiotic Beagle dogs were orally inoculated with a pure culture of Helicobacter felis. The remaining two littermates served as contact controls. Thirty days after infection, all animals were euthanatized and specimens were collected for evaluation. In infected dogs, H. felis was recovered from all areas of the stomach. Colonization was heaviest in the fundus and antrum. H. felis was not cultured from any segment of the gastrointestinal tract distal to the duodenum. Two weeks after infection, all five infected dogs had detectable IgM and IgG serum antibody to H. felis, whereas control dogs had no measurable H. felis serum antibody throughout the study. Histopathologic changes in the stomachs of infected dogs included large numbers of lymphoid nodules throughout all regions of the gastric mucosa and were most numerous in the fundus and body. A mild, diffuse lymphocytic infiltrate with small numbers of plasma cells and eosinophils was also present in the subglandular region of all portions of the gastric mucosa. Electron microscopic examination revealed large numbers of spiral-shaped H. felis in gastric mucus adjacent to or superimposed over the areas of inflammation. Occasionally, however, H. felis was observed within the canaliculi of gastric parietal cells. Histopathologic changes in the stomachs of the contact control dogs were limited to focal infiltrates of eosinophils and small aggregates of lymphocytes in the subglandular portions of the gastric mucosa in one animal. Infection with H. felis is a likely cause of naturally occurring lymphofollicular gastritis.

Animals↗

Links between early post-partum mood and post-natal depression.

The Edinburgh Postnatal Depression Scale (EPDS) was used to rate 217 patients at five days and six weeks post-partum. There was a highly significant positive correlation between the two scores, together with similar symptom profiles. Of the 25 women who suffered post-natal depression (6-week EPDS score greater than or equal to 13), 17 had similar symptoms in the first week post-partum (5-day EPDS score greater than or equal to 10). Low birth weight of the baby, delivery by Caesarean section, a delivery much more difficult than expected, and bottle feeding were all significantly associated with a high EPDS score in the first week post-partum. Bottle feeding and delivery by Caesarean section were the only factors associated with depression at the sixth week. A recollection of low mood after a previous birth was also associated with post-natal depression after the current birth. This, together with an EPDS score of 13 or more at five days post-partum, increased the risk of post-natal depression at six weeks 85-fold.

Adult↗

Diurnal variation in glucose tolerance. Cyclic suppression of insulin action and insulin secretion in normal-weight, but not obese, subjects.

The relative roles of insulin sensitivity, insulin secretion, and glucose effectiveness to the diurnal rhythm of glucose tolerance were examined in normal-weight (n = 12) and obese (n = 11) subjects. Two frequently sampled intravenous glucose tolerance tests were performed in each subject at 0800 on one occasion and 1800 on a separate day. Tests were preceded by identical fasts of 10-12 h. In nonobese subjects, glucose tolerance, expressed as the 10- to 16-min KG value (KGs), was much reduced in the evening (AM 2.98 +/- 0.45, PM 1.86 +/- 0.33 min-1, P less than 0.002). In the obese subjects, tolerance was lower in the morning than normal-weight subjects (2.19 +/- 0.31 min-1), but unlike in nonobese subjects, tolerance was not significantly reduced during the day (1.90 +/- 0.18 min-1, P greater than 0.40). The reduction in glucose tolerance in the normal-weight subjects was caused by diminished insulin sensitivity (parameter S1, AM 15.4 +/- 2.9, PM 10.2 +/- 1.9 x 10(-5) min-1/pM, P less than 0.01) and reduced beta-cell responsivity to glucose. The evening decrease in the latter was reflected both in first-phase plasma insulin (AM 2466 +/- 441, PM 1825 +/- 381 pM/10 min, P less than 0.05) and the potentiation slope (AM 462 +/- 68, PM 267 +/- 35 pM/mM, P less than 0.01). In contrast, consistent with no diurnal variation in glucose tolerance, obese subjects exhibited no decline in insulin sensitivity in the evening (AM 3.6 +/- 0.7, PM 4.9 +/- 1.0 x 10(-5) min-1/pM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A case of prenatal diagnosis of hemophilia A.

Classic hemophilia, (hemophilia A), is an X-linked hereditary bleeding disorder affecting half of the male offspring of female carriers. Prenatal diagnosis offers an option, namely to restrict abortions to hemophilic fetuses only, and thus retain the chance of bearing normal sons. Recently, the authors have made a prenatal diagnosis of hemophilia A in an obligate carrier with a male fetus at 24 weeks of gestation by pure fetal sampling and accurate factor VIII coagulant assay, which was repeatedly less than 1% at 28 weeks of gestation.

Adult↗

Oxyntic and antral gastritis in the People's Republic of China: diagnosis and relationship to Helicobacter pylori.

This study investigates the relationship between gastritis and Helicobacter pylori infection in the Chinese population. Particular focus was placed upon the grading of gastritis, using the recently developed "Sydney system." Five diagnostic procedures were used to establish H. pylori status, all of which were found to be highly sensitive and specific. Histological chronic gastritis was reported in 93/108 (86.1%) of the patients examined, H. pylori infection being present in 73/93 (78.5%), and in no patient with histologically normal mucosae. There was a relatively high incidence of idiopathic antral gastritis within the gastritic population, 20/93 (21.5%). In the H. pylori-positive group, 10/73 (13.7%) had pangastritis, 57/73 (78.1%) had pangastritis-antrum-predominant, and 6/73 (8.2%) had antral-only gastritis. The level of activity was significantly higher in the antrum; however, the distribution of bacteria between the antrum and body was not significantly different. There is a need for additional studies examining the specific topographical relationship between H. pylori, the histology, and gastroduodenal disease.

Adolescent↗

Sequential NMR resonance assignment and structure determination of the Kunitz-type inhibitor domain of the Alzheimer's beta-amyloid precursor protein.

Certain precursor proteins (APP751 and APP770) of the amyloid beta-protein (AP) present in Alzheimer's disease contain a Kunitz-type serine protease inhibitor domain (APPI). In this study, the domain is obtained as a functional inhibitor through both recombinant (APPIr) and synthetic (APPIs) methodologies, and the solution structure of APPI is determined by 1H 2D NMR techniques. Complete sequence-specific resonance assignments (except for P13 and G37 NH) for both APPIr and APPIs are achieved using standard procedures. Ambiguities arising from degeneracies in the NMR resonances are resolved by varying sample conditions. Qualitative interpretation of short- and long-range NOEs reveals secondary structural features similar to those extensively documented by NMR for bovine pancreatic trypsin inhibitor (BPTI). A more rigorous interpretation of the NOESY spectra yields NOE-derived interresidue distance restraints which are used in conjunction with dynamic simulated annealing to generate a family of APPI structures. Within this family, the beta-sheet and helical regions are in good agreement with the crystal structure of BPTI, whereas portions of the protease-binding loops deviate from those in BPTI. These deviations are consistent with those recently described in the crystal structure of APPI (Hynes et al., 1990). Also supported in the NMR study is the hydrophobic patch in the protease-binding domain created by side chain-side chain NOE contacts between M17 and F34. In addition, the NMR spectra indicate that the rotation of the W21 ring in APPI is hindered, unlike Y21 in BPTI, showing a greater than 90% preference for one orientation in the hydrophobic groove.

Amino Acid Sequence↗

Fetal heart rate and neonatal condition related to epidural analgesia in women reaching the second stage of labour.

The relationship between epidural analgesia and a number of labour and delivery factors, relevant to fetal and neonatal condition, was considered in a prospective study of 200 labours reaching the second stage of labour. The group was representative of the hospital population with regard to the proportion of nulliparous women, the incidence of instrumental vaginal deliveries and the incidence of epidural analgesia (37%). The 8% of labours requiring fetal blood sampling during the first stage, and the labours with fetal heart rate (FHR) decelerations in the hour prior to second stage (25%) and during pushing (50%) were significantly more likely to have been given an epidural. Nulliparity (55%), induced labour (34%), a first stage longer than eight hours (37%), a second stage longer than 60 min (43%), maternal pushing for longer than 36 min (50%), forceps delivery (28%) and a 1 min Apgar score less than 7 (12%) were also factors associated with significantly higher rates of epidural analgesia whereas meconium (15%), a small baby (16%) and umbilical arterial metabolic acidaemia (13%) were not. FHR decelerations in labours reaching the second stage with an epidural reflect adjustments to fetal cardiovascular control and not acidaemia.

Adult↗

Sympathetic neuron factors involved in bradykinin-induced plasma extravasation in the rat.

Previous studies have demonstrated that bradykinin (BK) produces a sympathetically dependent plasma extravasation into the rat knee joint which is, in part, dependent upon the production of a prostaglandin. In the present study, co-administration of the specific prostaglandin, PGE2, markedly enhanced the BK-induced plasma extravasation. In this study we also report that after chemically induced sympathectomy, by chronic pretreatment with 6-hydroxydopamine (6-OHDA), both the plasma extravasation produced by BK and the enhancing effect of PGE2 are markedly attenuated. Plasma extravasation induced by PGE2 alone was small and was not significantly attenuated by sympathectomy. We conclude that BK-induced extravasation involves production of at least two sympathetic postganglionic neuron (SPGN) terminal-dependent factors, one of which is a cyclo-oxygenase product of arachidonic acid metabolism, probably PGE2, (Coderre et al., J. Neurophysiol., 62 (1989) 45-58) and another that is unidentified.

Animals↗