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M Welch

Publications and source records attributed to M Welch.

At least 55 records · Page 3Linked to original sources
PubMed1998

Structure of the CheY-binding domain of histidine kinase CheA in complex with CheY.

Bacterial adaptation to the environment is accomplished through the coordinated activation of specific sensory receptors and signal processing proteins. Among the best characterized of these pathways are those which employ the two-component paradigm. In these systems, signal transmission is mediated by Mg(2+)-dependent phospho-relay reactions between histidine auto-kinases and phospho-accepting receiver domains in response-regulator proteins. Although this mechanism of activation is common to all response-regulators, detrimental cross-talk between different two-component pathways within the same cell is minimized through the use of specific recognition domains. Here, we report the crystal structure, at 2.95 A resolution, of the response regulator of bacterial chemotaxis, CheY, bound to the recognition domain from its cognate histidine kinase, CheA. The structure suggests that molecular recognition, in this low affinity complex (KD = 2 microM), may also contribute to the mechanism of CheY activation.

Amino Acid Sequence↗
PubMed1998

Histological study of colonic ischaemia after aortic surgery.

BACKGROUND: Colonic ischaemia is a well documented complication of abdominal aortic reconstruction. In this prospective study patients had routine preoperative and postoperative colonoscopy and biopsy, in order to determine the true incidence and implications. METHODS: Fifty-six patients undergoing elective infrarenal aortic surgery, 28 for aneurysm and 28 for occlusive disease, had colonoscopy and biopsy before and 1 week after operation. RESULTS: Colonic ischaemia was identified histologically in biopsies from 16 (30 per cent) of 53 patients. Almost half the patients had normal macroscopic appearances. Two factors exhibited a statistically significant association with the development of ischaemia: prolonged cross-clamp time (P < 0.05) and postoperative diarrhoea (P< 0.001). Co-morbidity was much higher in patients with colonic ischaemia (P< 0.005). Overall morbidity was significantly greater in the aneurysm group (P < 0.05). CONCLUSION: Colonic ischaemia is common after aortic reconstruction. When suspected, colonoscopy with biopsy is diagnostic.

Aged↗
PubMed1997

A short-range signal restricts cell movement between telencephalic proliferative zones.

During telencephalic development, a boundary develops that restricts cell movement between the dorsal cortical and basal striatal proliferative zones. In this study, the appearance of this boundary and the mechanism by which cell movement is restricted were examined through a number of approaches. The general pattern of neuronal dispersion was examined both with an early neuronal marker and through the focal application of DiI to telencephalic explants. Both methods revealed that, although tangential neuronal dispersion is present throughout much of the telencephalon, it is restricted within the boundary region separating dorsal and ventral telencephalic proliferative zones. To examine the cellular mechanism underlying this boundary restriction, dissociated cells from the striatum were placed within both areas of the boundary, where dispersion is limited, and areas within the cortex, where significant cellular dispersion occurs. Cells placed within the boundary region remain round and extend only thin processes, whereas progenitors placed onto the cortical ventricular zone away from this boundary are able to migrate extensively. This suggests that the boundary inhibits directly the migration of cells. To examine whether the signal inhibiting dispersion within the boundary region acts as a long- or short-range cue, we apposed explants of boundary and nonboundary regions in vitro. Within these explants we found that migration was neither inhibited in nonboundary regions nor induced in boundary regions. This suggests that the boundary between dorsal and ventral telencephalon isolates these respective environments through either a contact-dependent or a short-range diffusible mechanism.

Acridine Orange↗
PubMed1997

23S rRNA similarity from selection for peptidyl transferase mimicry.

RNAs from a randomized pool were selected by affinity elution for binding to the molecule CCdApPuro, a high-affinity ligand of ribosomal peptidyl transferase designed as a transition-state analogue of peptide formation. The selected RNAs show affinity for CCdApPuro comparable to that of the peptidyl transferase center itself (Kd approximately 10 nM). Chemical modification/protection experiments implicate bases completely conserved among the selected RNAs in CCdApPuro interaction, which appears to involve both CCdA and puromycin moieties, that is, both A- and P-site homologues. The apparent selected binding site shows up to 17 nucleotides with similarity to conserved nucleotides of the peptidyl transferase loop domain of 23S rRNA and is conserved when reselected under mutagenesis. Thus, these nucleotides of 23S rRNA likely provide elements of the peptidyl transferase active center that bind the reactants near the site of peptide bond formation. Binding of CCdApPuro by a peptidyl transferase-like motif in the absence of protein strengthens the hypothesis that peptidyl transfer originated in an RNA world.

Base Sequence↗
PubMed1997

Genital shedding of human immunodeficiency virus type 1 DNA during pregnancy: association with immunosuppression, abnormal cervical or vaginal discharge, and severe vitamin A deficiency.

The presence of human immunodeficiency virus type 1 (HIV-1) in genital secretions may be a determinant of vertical HIV-1 transmission. Cervical and vaginal secretions from HIV-1-seropositive pregnant women were evaluated to determine prevalence and correlates of HIV-1-infected cells in the genital tract. HIV-1 DNA was detected by polymerase chain reaction in 32% of 212 cervical and 10% of 215 vaginal specimens. Presence of HIV-1 DNA in the cervix was associated with cervical mucopus and a significantly lower absolute CD4 cell count (354 vs. 469, P < .001). An absolute CD4 cell count <200 was associated with a 9.6-fold increased odds of cervical HIV-1 DNA detection compared with a count > or = 500 (95% confidence interval, 2.8-34.2). Detection of vaginal HIV- 1 DNA was associated with abnormal vaginal discharge, lower absolute CD4 cell count, and severe vitamin A deficiency. Presence of HIV-1-infected cells in genital secretions was associated with immunosuppression and abnormal cervical or vaginal discharge.

Adolescent↗
PubMed1997

Patients rewarded: a consideration of the English Patient and the representation of nursing.

This paper explores the representation of nursing in the 1997 Academy Award winning film The English Patient (Director Minghella 1996). It examines the way in which the concerns and dilemmas that have become commonplace in nursing literature are represented through the experiences of the character Hana. In particular, it is concerned with the way in which the essence of what it means to be a nurse, and its loss and reclamation, is epitomized through Hana and her encounters with Count Almasy (the English patient) and the bomb-disposal expert Kip. Finally, it suggests that there is much to be gained from a close examination of the representation of nursing in popular culture.

Career Choice↗
PubMed1996

Signal termination in bacterial chemotaxis: CheZ mediates dephosphorylation of free rather than switch-bound CheY.

Chemotaxis in bacteria is controlled by regulating the direction of flagellar rotation. The regulation is carried out by the chemotaxis protein CheY. When phosphorylated, CheY binds to FliM, which is one of the proteins that constitute the "gear box" (or "switch") of the flagellar motor. Consequently, the motor shifts from the default direction of rotation, counterclockwise, to clockwise rotation. This biased rotation is terminated when CheY is dephosphorylated either spontaneously or, faster, by a specific phosphatase, CheZ. Logically, one might expect CheZ to act directly on FliM-bound CheY. However, here we provide direct biochemical evidence that, in contrast to this expectation, phosphorylated CheY (CheY approximately P), bound to FliM, is protected from dephosphorylation by CheZ. The complex between CheY approximately P and FliM was trapped by cross-linking with dimethylsuberimidate, and its susceptibility to CheZ was measured. CheY approximately P complexed with FliM, unlike free CheY approximately P, was not dephosphorylated by CheZ. However, it did undergo spontaneous dephosphorylation. Nonspecific cross-linked CheY dimers, measured as a control, were dephosphorylated by CheZ. No significant binding between CheZ and any of the switch proteins was detected. It is concluded that, in the termination mechanism of signal transduction in bacterial chemotaxis, CheZ acts only on free CheY approximately P. We suggest that CheZ affects switch-bound CheY approximately P by shifting the equilibrium between bound and free CheY approximately P.

Bacterial Proteins↗
PubMed1996

Is the function of the cdc2 kinase subunit proteins tuned by their propensities to oligomerize? Conformational states in solution of the cdc2 kinase partners p13suc1 and p9cksphy.

The cdc2 kinase subunit (cks) proteins play an essential function in the control of mitosis through their molecular complexes with the cdc2 kinase. In this work, we characterize the conformational state(s) in solution of the cks proteins p13suc1 from Schizosaccharomyces pombe and p9cksphy from Physarum polycephalum. Monomers of p13suc1 and p9cksphy were found to be markedly nonglobular, presumably with a long, nonfolded C-terminal moiety. This was in contrast to the previously published structure of p13suc1, derived from crystallographic studies on a zinc-promoted p13suc1 dimer, in which the individual p13suc1 subunits had a globular conformation. This disparity was resolved when we found that the globular p13suc1 fold undergoes a conformational transition into nonglobular monomers upon dissociation of the dimers following chelation of the zinc ions by ethylenediaminetetraacetic acid (EDTA). We also found that p13suc1, but not p9cksphy, forms stable dimers in the absence of metal ions. The topology of these EDTA-insensitive dimers likely resembles that of the human p9ckshs2 protein, characterized by beta 4 strand exchange from each nonglobular monomer.

Amino Acid Sequence↗
PubMed1996

Confluent and reticulated papillomatosis: response to minocycline.

BACKGROUND: Confluent and reticulated papillomatosis (CRP) of Gougerot and Carteaud is an uncommon disorder of unknown cause for which a variety of treatments have been proposed. OBJECTIVE: We attempted to evaluate the effectiveness of oral minocycline. METHODS: Nine patients with CRP were treated with oral minocycline, 50 mg twice a day, for 6 weeks. The average follow-up period was 11 months. Recurrence rate, side effects, and effectiveness of therapy were assessed. RESULTS: All patients except two had a 90% to 100% response to therapy. Recurrences were noted in three patients, all of whom responded to re-treatment with minocycline. None of the nine patients had an adverse reaction. CONCLUSION: Minocycline, 50 mg twice a day, is safe and effective for CRP.

Administration, Oral↗
PubMed1996

Histologic and immunohistochemical features in biopsy sites in which bovine collagen matrix was used for hemostasis.

BACKGROUND: Bovine collagen matrix (Helistat and Helatene), which is used primarily for hemostasis, decreases wound contracture in skin biopsy sites and promotes wound granulation. OBJECTIVE: Our purpose was to evaluate excision specimens of previous biopsy sites to determine whether there are histologic differences between cases in which bovine collagen matrix was used for hemostasis and those in which it was not used. METHODS: Thirty-two diagnostic punch biopsies were done with hemostasis obtained with bovine collagen matrix in 24 biopsies and by pressure alone in eight. The biopsy sites were reexcised at various time intervals, and the histologic and immunohistochemical features were evaluated and compared. RESULTS: In specimens in which collagen matrix was used, migration of stromal and epithelial cells along the bovine collagen matrix was evident by 2 days and had progressed rapidly by 4 days. Around and within the matrix hyaluronic acid increased during the first 8 to 10 days. Initially stromal cells stained with CD34 and reticulum fibers were present at 8 to 10 days. AT 12 to 15 days, factor XIIIa+ stromal cells were present within the matrix, and host collagen fibers were present and well-oriented within the degenerating matrix. Biopsy specimens allowed to heal without the matrix showed a delayed and an uneven increase in hyaluronic acid. Furthermore, the granulation tissue within the dermis showed no organization with a persistent acute inflammatory infiltrate and increased muscle actin-positive stromal cells as scar formation proceeded. CONCLUSION: Bovine collagen products appear to provide a matrix that promotes thrombosis. The collagen matrix also promotes migration and attachment of stomal and epithelial cells, thereby organizing and accelerating wound healing.

Actins↗
PubMed1995

Rotational asymmetry of Escherichia coli flagellar motor in the presence of arsenate.

The flagellar motor of Escherichia coli (E. coli) is driven by a proton-motive force (PMF), hence it was of interest to determine whether the motor is symmetrical in the sense that it can be rotated by any polarity of PMF. For this purpose the cells had to be deenergized first. Conventional deenergization procedures caused irreversible loss of motility, presumably due to ATP-dependent degradative processes. However, E. coli cells deenergized by incubation with arsenate manifested a slow, reversible depletion of PMF. In this procedure there was a sufficiently long time window, during which a considerable proportion of the cells lost their motility and could be made to rotate again by an artificially-imposed PMF. The motors of these cells rotated in response to any PMF polarity, but positive and negative polarities rotated different sub-populations of cells and the direction was almost exclusively counterclockwise. The reason for the unidirectionality of the rotation was not the intervention of the chemotaxis system. A number of potential reasons are suggested. One is the arsenate effect on the motor function found previously [Margolin, Y., Barak, R. and Eisenbach, M. (1994) J. Bacteriol. 176, 5547-5549]. A possible interaction between arsenate and the motor is discussed.

Adenosine Triphosphate↗
PubMed1995

An inhibitor of ribosomal peptidyl transferase using transition-state analogy.

The phosphoramidate of CCdAp and puromycin (CCdApPuro) is a potent inhibitor of ribosomal peptidyl transferase, as assayed by the fragment reaction. Inhibition is competitive at the ribosomal A-site. CCdApPuro protects P-site-associated bases in the peptidyl transferase loop region of 23S rRNA from carbodiimide modification. The Ki's of structural homologues of CCdApPuro suggest that both the CCdA and puromycin moieties participate in binding. Thus, CCdApPuro appears to bridge the A- and P-sites of the ribosome, implying that substrates are juxtaposed with a geometry suitable for direct reaction during peptidyl transfer.

Escherichia coli↗
PubMed1995

Fibrinolysis profiles and platelet activation after endothelial cell seeding of prosthetic vascular grafts.

There is no convincing evidence that endothelial cell seeding of prosthetic grafts in humans confers any of the advantages seen in animals. However, partial endothelial coverage might exert a subtle effect not detectable with indirect end points such as patency or scintigraphy. This study examined seeded cell function by measuring fibrinolytic and platelet activation markers in patients receiving seeded and control prosthetic grafts. Thirty-two patients were randomly assigned to seeded (n = 15) and control (n = 17) groups. Preoperatively and 3, 6, and 12 months postoperatively, plasma levels of fibrinopeptide A (FPA), B beta 1-42 fragment, cross-linked fibrin degradation products (XL-FDP), thromboxane A2 (TXA2), platelet factor 4 (PF4), and beta-thromboglobulin (beta TG) were measured. Patients with seeded grafts had significantly lower levels of FPA at 6 and 12 months (p < 0.05) and a significant overall group effect (p < 0.05). These patients also tended to have higher levels of XL-FDP (p < 0.1). No other significant differences were seen. The lower rate of conversion of fibrinogen to fibrin and the trend toward increased fibrinolysis seen in seeded grafts may be due to the metabolic effects of viable retained seeded cells. Although comparable platelet activation indicates that endothelial coverage remains limited, seeding may exert an antithrombotic influence at the graft surface.

Adult↗
PubMed1995

Evaluation of dopexamine hydrochloride as a renoprotective agent during aortic surgery.

Thirty-two patients undergoing elective infrarenal aortic surgery were randomly assigned to receive a perioperative infusion of either dopexamine hydrochloride at a rate of 2 micrograms/kg/min (n = 15) or 0.9% saline solution as placebo (n = 17). Renal function was monitored by regular measurements of serum creatinine levels. There were significant mean percentage increases in serum creatinine (p < 0.001) at all time points up to 3 days postoperatively in the placebo group but only at 2 and 12 hours in the dopexamine group. It was concluded that dopexamine hydrochloride confers renal protection in patients undergoing aortic reconstruction.

Aortic Aneurysm, Abdominal↗
PubMed1995

Receipt of recommended medical care in HIV-infected and at-risk persons.

The authors evaluated receipt of recommended medical care for 133 HIV-infected and 101 at-risk San Francisco public health clinic patients. Fewer than half the patients received syphilis and tuberculosis screening, hepatitis B immunity testing or vaccination, and tetanus boosters. The HIV-infected persons were significantly (p < or = 0.01) more likely than the at-risk persons to receive preventive care, except for interventions specific to women. More than 80% of the HIV-infected persons received CD4 testing, zidovudine and Pneumocystis carinii pneumonia prophylaxis, and pneumococcal vaccine. Only 40% of the at-risk persons reported having HIV-antibody testing recommended. Interventions to increase care delivery to HIV-infected and at-risk persons are needed.

Adult↗