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Biomedical subjects

J Smith

Publications and source records attributed to J Smith.

At least 469 records · Page 26Linked to original sources
PubMed1997

sfi-independent filamentation in Escherichia coli Is lexA dependent and requires DNA damage for induction.

In Escherichia coli, damage to DNA induces the expression of a set of genes known collectively as the SOS response. Part of the SOS response includes genes that repair DNA damage, but another part of the response coordinates DNA replication and septation to prevent untimely cell division. The classic SOS gene product that inhibits cell division is SfiA (or SulA), which binds to FtsZ and prevents septum formation until the DNA damage has been repaired. However, another pathway acts to coordinate DNA replication and cell division when sfiA, or the sfi-dependent pathway, is inoperative. Until recently, little was known of this alternative pathway, which is called the sfi-independent pathway. We report here that sfi-independent filamentation is suppressed by lexA(Ind-) mutations, suggesting that derepression of the LexA regulon is necessary for sfi-independent induction. However, expression of LexA-controlled genes is not sufficient; DNA damage is also required to induce this secondary pathway of cell division inhibition. Furthermore, we postulate that loss of the common regulatory circuitry of the sfi-dependent and sfi-independent pathways by recA or lexA mutants uncouples cell division and DNA replication.

Bacterial Proteins↗
PubMed1997

Planning for the future: the experience of implementing a children's day assessment unit in a district general hospital.

A paediatric day assessment unit was opened in May 1995. An audit of the first year's activity showed that, despite an increase in emergency admissions of 8.4%, the number of children admitted as an emergency overnight was reduced by 3% in paediatrics and 7.2% in surgery. In the first year, 1731 children were assessed as an emergency of whom 658 did not require admission to the inpatient ward. Midnight occupancy fell 17.7% in paediatrics and 25.4% in surgery. The nurse staffing costs fell over Pounds 32,000 in the first year. No adverse events occurred during the first year of operation; this type of facility could lead to a more efficient use of resources in any children's unit.

Bed Occupancy↗
PubMed1997

Interleukin-15 signals T84 colonic epithelial cells in the absence of the interleukin-2 receptor beta-chain.

Interleukin-15 (IL-15) shares many biological functions with interleukin-2 (IL-2) due to common receptor components. IL-15 binds to the IL-2 receptor (IL-2R) beta-chain and the common gamma-chain receptor in addition to one other IL-15 binding receptor protein (IL-15R alpha). Both IL-2R beta- and gamma-chains are required to promote cell growth in hematopoietic cells. The colonic cryptlike epithelial cell line T84 contains the common gamma-chain but lacks the IL-2R beta-chain. We report IL-15R alpha-chain mRNA in T84 cells with the use of reverse transcriptase-polymerase chain reaction. T84 and normal colonic epithelial cells bind a FLAG-IL-15 fusion protein in immunoperoxidase and flow cytometric experiments. In addition, IL-15, but not IL-2, accelerates and enhances the development of transepithelial resistance across T84 monolayers in a dose-dependent fashion. We conclude that normal and T84 colonic epithelial cells express IL-15R alpha and are able to bind IL-15. IL-15 can deliver a nonproliferative functional signal in the absence of IL-2R beta-chain in T84 cells.

Cell Division↗
PubMed1997

Maspin is an intracellular serpin that partitions into secretory vesicles and is present at the cell surface.

The tumor suppressor maspin (mammary serpin) was originally identified as a component of human mammary epithelial cells that is downregulated as mammary tumor cells progress from the benign to the invasive and metastatic states. Maspin inhibits cellular invasion, motility, and proliferation, but its mechanism of action is currently unknown. Because the cellular machinery responsible for these processes is cytoplasmic, we have reexamined the tissue distribution and subcellular localization of maspin. We find that maspin, or a maspin-like protein, is present in many human organs, in which it localizes to epithelia. In cultured human mammary myoepithelial cells, maspin is predominantly a soluble cytoplasmic protein that associates with secretory vesicles and is present at the cell surface. In vitro assays show that the vesicle association is due to the existence of an uncleaved facultative secretion signal that allows small amounts of maspin to partition into the endoplasmic reticulum. These results demonstrate that maspin is more widespread than previously believed. The subcellular localization studies indicate that soluble intracellular and vesicle-associated maspin probably play an important role in controlling the invasion, motility, and proliferation of cells expressing it, whereas extracellular maspin may also regulate these processes in adjacent cells.

Blotting, Northern↗
PubMed1997

Activation of adenylyl cyclase in human myometrial smooth muscle cells by neuropeptides.

The levels of intracellular cAMP in human myometrial smooth muscle cells in serum-free medium, or medium that contained FBS (1%, vol/vol), were determined after treatment with the homologous peptides, calcitonin gene-related peptide (CGRP), adrenomedullin (ADM), and amylin, without or with added isobutylmethylxanthine (IBMX). These cells were sensitive to CGRP, responding in a dose-dependent manner, with maximal levels of cAMP being attained with 5 nM CGRP in the presence of IBMX (1 mM). In the absence of IBMX, the level of cAMP attained in cells treated with CGRP (5 nM) (675.3 +/- 58.8 pmol.mg protein.15 min; mean +/- SEM, n = 3) was approximately 90x that in nontreated cells (7.5 +/- 0.4 pmol.mg protein.15 min). The level of cAMP in myometrial cells treated with CGRP (5 nM)+IBMX (1 mM), 1998 +/- 420 pmol.mg protein.15 min, was 29x that in cells treated with IBMX alone (69.2 +/- 10.2). The maximum level of cAMP achieved by treatment with ADM+IBMX was similar to that with CGRP+IBMX, but the dose of ADM required (1 microM) was approximately 200x that of CGRP. Amylin amide also caused an increase in cAMP but with considerably less potency; at a concentration of 500 nM, amylin amide+IBMX effected a 2.3-fold increase in cAMP relative to IBMX alone. CGRP8-37, an antagonist of CGRP via the CGRP1 receptor, inhibited the action of CGRP, ADM, and amylin in myometrial cells. Treatment with [cys(ACM)2-7]-CGRP, a CGRP2 receptor agonist, did not cause an increase in the levels of cAMP in these cells. These findings are indicative that CGRP, ADM, and amylin act via that the CGRP1 receptor in human myometrial cells. Vasoactive intestinal peptide and pituitary adenylate cyclase activating polypetide also caused a dose-dependent increase in cAMP in myometrial cells. The findings of this study are indicative that multiple neuropeptides, acting by way of heptahelical receptors linked to the G alpha s-subunit of the G-proteins, may contribute to the maintenance of uterine quiescence during some period of human pregnancy.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Ultrasound-based quantification of emboli during conventional and endovascular aneurysm repair.

PURPOSE: To differentiate and quantify the type and number of lower limb emboli occurring during endovascular aneurysm repair, as compared to conventional surgery. METHODS: Thirty-eight patients underwent elective infrarenal aneurysm repair using a conventional surgical approach in 18 and an endovascular procedure in 20. Emboli were detected using a Doppler ultrasound system with a 2-MHz transducer interrogating the mid superficial femoral artery. Lower limb emboli were differentiated as particulate or gaseous based on the physical distance traversed by the embolic signal. RESULTS: Significantly more particulate (median 108 versus 59, p = 0.015) and gaseous (134 versus 46, p = 0.008) emboli were detected during endovascular aneurysm repair as compared to conventional surgery. Clinically, no case of massive microembolization occurred in either group, but one patient in the conventional group required a femoral embolectomy, and three patients undergoing endovascular repair developed self-limiting trash feet postoperatively. In patients undergoing endovascular aortomonoiliac aneurysm repair, there was only a poor correlation between the number of particulate emboli and either procedural duration or operator experience. CONCLUSIONS: The apparent lack of a relationship between particulate embolization and operative time or technical experience suggests that manipulation of endoluminal devices within the aneurysm sac may not be the sole determinant of intraprocedural embolization. Other as yet undetermined factors may predict patients at high risk for massive embolization.

Aged↗
PubMed1997

Software for the competitive edge.

In choosing computer software and hardware that will help their agencies run smoothly, providers face a sometimes overwhelming task. One agency shares its success in achieving a competitive edge using "off-the-shelf" software rather than spending money on more expensive, customized solutions.

Computer Communication Networks↗
PubMed1997

Role of hyperpronation as a possible risk factor for anterior cruciate ligament injuries.

OBJECTIVE: The purpose of this study was to examine the relationship between hyperpronation and the occurrence of noncontact injury to the anterior cruciate ligament (ACL). DESIGN AND SETTING: Subjects were categorized as either ACL injured (ACLI) or ACL uninjured (ACLU). All ACLI subjects received their injuries from a noncontact mechanism. To justify using the ACLI subjects' uninjured legs as representative of their preinjury state, a t test was used to compare the differences between the left and right foot for the ACLU group on both measurements. Based on the results of the t test, a regression analysis was performed to determine whether group membership could be predicted from navicular drop. All measures were performed in a university athletic training room. SUBJECTS: Fourteen ACLI subjects (age = 21.07 +/- 0.83 yr, ht = 174.81+/-8.29 cm, wt = 72.32+/-13.47 kg) and 14 ACLU subjects (age = 21.14+/-2.03 yr, ht = 177.35+/-11.31 cm, wt = 72.99+/-14.81 kg) participated. MEASUREMENTS: Hyperpronation was assessed via the navicular drop test and the calcaneal stance test. RESULTS: No significant difference (p > .05) between feet for the navicular drop test was found. However, there was a significant difference (p < .05) between feet for the calcaneal stance test, and, thus, this measure was not used in the regression analysis. Using the navicular drop score, the regression analysis was unable to predict group membership. CONCLUSIONS: Hyperpronation as measured by the navicular drop test was not a predictor of ACL injury, and, thus, may not be a predisposing factor to noncontact ACL injuries.

Journal Article↗
PubMed1997

Effect of the non peptide angiotensin II antagonist, GR117289C on the vasoconstrictor actions of angiotensin II in the human forearm.

AIMS: GR117289C is a non peptide, selective angiotensin (AT1) receptor antagonist. The purpose of this study was to determine whether this agent, given orally, could attenuate the vasoconstrictor effects of angiotensin II(AII) infused locally into the forearm circulation in man. METHODS: Eight healthy male subjects were studied on four occasions in a randomized, double-blind, placebo controlled, crossover study. Five hours (approximate time of peak dynamic effect) following dosing with GR117289C (300 mg, 100 mg, 10 mg or placebo), A II was infused in incremental doses (0, 0.1, 0.4, 1.6, 6.2, 25 and 100 pmol min-1) into the left brachial artery, each for 10 min. Forearm blood flow was measured using venous occlusion plethysmography. RESULTS: GR117289C inhibits the vasoconstrictor effects of A II in a dose dependent manner. The active treatment: placebo ratios of forearm blood flow in the infused arm during the highest dose of AII (100 pmol min-1) were: GR117289C 10 mg, 1.12 (95% C.I. 0.81-1.55; P = 0.478), 100 mg, 1.43 (95% C.I. 1.01-2.01; P = 0.042) and 300 mg, 1.62 (95% C.I. 1.17-2.24; P = 0.006). There was no significant difference in blood pressure between each of the treatment groups and placebo. CONCLUSIONS: GR117289C is a pharmacologically active, oral A II antagonist in healthy men.

Administration, Oral↗
PubMed1997

An evaluation and improvement program for inpatient anticoagulant control.

To improve the management and therapeutic control of inpatients on anticoagulant drugs, combined prescription and monitoring charts have been developed for both heparin and warfarin which incorporate clinical guidelines. These have been introduced throughout a 700-bedded acute teaching hospital via a structured program of change management. We have demonstrated improvements in the quality of anticoagulant control (assessed with a custom-written computer program), adherence to clinical guidelines and quality of monitoring and prescribing of anticoagulants in inpatients. The percentage time spent under-anticoagulated with heparin (activated partial thromboplastin time ratio < 1.5) fell from 32.7% to 18.5% (p < 0.0001), whereas there was no change in percentage time over-anticoagulated (5.1% vs. 5.8%; p = ns). The percentage time spent under-anticoagulated with warfarin was unaltered (26.3% vs. 29.8%; p = ns) but the percentage time spent over-anticoagulated (International Normalised Ratio > 4.5) was halved from 5.4% to 2.7% (p < 0.001). We conclude that the introduction of the charts led to significant improvements in anticoagulant control.

Aged↗
PubMed1997

Stable integration of an mdx skeletal muscle cell line into dystrophic (mdx) skeletal muscle: evidence for stem cell status.

We have previously described a method for the derivation of long term cultures of undifferentiated myoblasts from the skeletal muscle of dystrophic (mdx) mice (J. Smith and P. N. Schofield, Exp. Cell Res., 210: 86-93, 1994). We now show that a clonal mdx-derived skeletal muscle cell line labeled with a retrovirus conferring beta-galactosidase activity and G418 resistance (PD50A) is capable of incorporation into mdx skeletal muscle myofibers for up to 14 months with no incidence of tumor formation. After a lag period of 5 days, injected PD50A cells disperse throughout the injected tibialis anterior muscle and take up satellite cell positions on the perimeter of myofiber bundles. PD50A cells begin to incorporate into fused muscle syncitium as early as 8 weeks after injection and persist for at least 14 months. We have rederived myoblasts expressing beta-galactosidase from PD50A-injected muscles 12 months after injection, demonstrating that a reserve of mononuclear proliferation-competent PD50A cells are present in host muscle up to a year after their original introduction. These data support the contention that myoblasts derived by this culture method are functionally representative of a class of skeletal muscle "stem cells" and thus have potential both as agents for cellular therapy of intransigent diseases such as Duchenne muscular dystrophy as well as being a useful tool for the further investigation of normal muscle development.

Animals↗
PubMed1997

Heel blood perfusion responses to pressure loading and unloading in women.

Heel pressure ulcers are significant and costly problems causing suffering and potential limb loss from infection and compromised blood flow. Heel blood perfusion (HBP) deficits accompanying loading likely affect the skin breakdown process, but little is known about the loading and off-loading changes. To clarify this issue, combined laser-Doppler Imaging (LDI) and Fluxmetry were used to assess HBP before, during, and after 40 minutes of continuous heel loading in 11 female volunteers (32-60 years). During loading, an initial decrease in HBP was followed by a gradual small recovery (p < 0.001). Off-loading resulted in a significant hyperemic response with HBP exceeding baseline by a factor of 4.72 +/- 0.63 (p = 0.001) and remaining elevated for about 10 minutes. Spatial LDI data showed that hyperemic responses are maximum near the pressure center and diminish radially. These results suggest a localized, pressure-related tissue trauma, which is compensated for by a substantial hyperperfusion. The dependence (and adequacy) of this response on clinical variables including heel pressure and duration, limb vascular status, and patient health are unknown. The present seminal data and associated methods provide a platform from which these and other important clinical parameters can be systematically studied and compared.

Adult↗
PubMed1997

Endoscopic ovariohysterectomy in two lions (Panthera leo).

Endoscopic techniques were used to ovariohysterectomize two hybrid Asian lions (Panthera leo) in order to reduce the risk of postoperative wound complications associated with standard surgical techniques. One of the lions was aged, overweight, and considered an anesthetic risk. The animals were anesthetized, intubated, catheterized intravenously, and placed in dorsal recumbency with the head lower (Trendelenburg position). Ventilation was assisted mechanically. Following abdominal insufflation, a surgical trocar was placed in the abdominal cavity. Two additional 12-mm surgical trocars were placed under direct visualization using a videoscope. The ovaries and uterus were removed endoscopically, and the abdominal cavity was inspected for hemorrhage under decreased insufflation pressure before closure. The surgery was complicated by obesity, by uterine enlargement from cystic endometrial hyperplasia and endometrial polyps, and by ovarian enlargement and fragility because of bilateral cystic rete ovarii. The procedure and anesthetic recovery were uneventful. Postsurgical recovery time and convalescence lasted less than 3 days, and the animals were reintroduced to an exhibit mate and placed on exhibit within 8 days. The technique is appropriate for use in lions, even those with pathologic reproductive changes, in zoos.

Animals↗
PubMed1997

Geometric, shape and area measurement considerations for diabetic neuropathic plantar ulcers.

Though neuropathic plantar ulcers are known to be "round-like," systematic quantitative data on their shape and geometric features are not readily available. A sample of 305 ulcers were retrospectively assessed to provide distribution data on quantitative geometric and shape parameters. After tracing the ulcer during the patient's initial visit, the following parameters were determined: surface area (A), maximum length (L), maximum perpendicular width (W), perimeter (p), shape factor (SF), and an ulcer regularity index (URI). SF assesses ulcer "circularity" and URI measures ulcer perimeter "smoothness" in comparison to a fictitious circle with the same contained area. SF and URI values of 1.0 correspond to 100 percent circularity and regularity. These data and the associated distributions, which are derived from a reasonably large random sample, provide a useful quantitative description of plantar ulcer geometry and shape.

Anthropometry↗
PubMed1997

Variability in skin microvascular vasodilatory responses assessed by laser-Doppler imaging.

Skin blood perfusion (SBP) responses to pressure loading and other traumatic and noxious stimuli are used to help identify patients at-risk of skin breakdown, evaluate preventive strategies and help clarify patho-physiological mechanisms in pre-ulcerative and ulcerative conditions. Often, laser-Doppler methods are used to compare vasodilatory responses at differing skin sites to evaluate skin parameter changes. Significant variations in skin microvasculature are known to be normally present, even in closely separated skin zones. In this study, spatial variability and temporal responses of SBP were evaluated with a widely used topical vasodilator (methylnicotinate, MN). A mask with nine holes (1.25 cm2 each) was placed on the volar forearm of ten volunteers. SBP was measured with laser-Doppler Imaging (LDI) prior to applying MN (15 ul, 50 mM) to six zones and 5, 10, 15, 20 and 30 minutes afterwards. Inter-zone mean SBP and inter- and intra-zone coefficients of variation (CV) were determined at each time. Results show that MN responses, when determined as zone LDI means, reached maximum at 15 minutes with no significant differences in relative responses among treated zones. Inter-zone perfusion CV's (range 0.11-0.13) were about 50 percent of intra-zone CV's (p < 0.01). We conclude that LDI perfusion responses can be obtained at different forearm skin sites with reasonable and acceptable levels of spatial variation if zone mean SBP values are used.

Adult↗