Search PubMed⌕ Search

Biomedical subjects

W Welch

Publications and source records attributed to W Welch.

At least 37 records · Page 2Linked to original sources
PubMed1995

Frameless stereotactic guidance. An intraoperative adjunct in the transoral approach for ventral cervicomedullary junction decompression.

METHODS: The application of a video-interactive frameless stereotactic guidance system for the treatment of ventral cervicomedullary junction compression is described in a patient with basilar invagination, odontoid dysgenesis, and a Chiari malformation who had irreducible impingement on the ventral brainstem by a partially fused mass of bone made up of the malformed odontoid peg, the inferior clivus, and dorsally protruding osteophytes at the odontoid-clival junction. RESULTS: This technology permitted instantaneous feedback of the surgeon's orientation in all planes, facilitating extensive removal of the dens and clival tip to achieve adequate ventral brainstem decompression. In view of the distortion of the craniovertebral anatomy produced by the patient's anomalies, the ability to visualize three dimensionally the location of the vertebral arteries also added an element of safety to the lateral bone removal. Similarly, the ability to localize the rostral limit of the clivus that needed to be resected and the caudal extent of C2 that needed to be removed to achieve an adequate decompression helped ensure that the extent of bone removal was appropriately tailored to the patient's anatomy. CONCLUSION: The authors believe this technique represents a significant advance over standard radiographic intraoperative localization techniques during transoral approaches to the ventral cervicomedullary junction for patients in whom the odontoid is fixed in position in relation to the clivus. This is based on the speed with which localization can be obtained, the accuracy of the information provided, the ability to obtain localization in multiple planes simultaneously, and the lack of radiation exposure during the procedure.

Brain Stem↗
PubMed1994

Structural determinants of high-affinity binding of ryanoids to the vertebrate skeletal muscle ryanodine receptor: a comparative molecular field analysis.

Ryanodine binds to specific membrane proteins, altering the calcium permeability of intracellular membranes. In this study 19 ryanoids were isolated or synthesized and the structures correlated to the strength of binding to vertebrate skeletal muscle ryanodine receptors. Global minima were determined by employment of molecular mechanics and dynamics augmented by systematic searching of conformational space. Overall, steric and electrostatic factors contribute about equally to the differences in the experimentally determined dissociation constants. The dominant electrostatic interaction is localized to a hydroxyl group in an apolar region of the molecule. The pyrrole and isopropyl groups located together at one pole of the molecule have the greatest effect on steric interactions between ligand and receptor. We suggest ryanodine binds to the receptor with the pyrrole and isopropyl groups buried deep inside a cleft in the protein. This arrangement places special importance on the conformation of the pyrrole and isopropyl groups. In contrast, the opposite pole appears to be positioned at the entrance of the binding pocket because bulky adducts placed in the 9 position of ryanodine alter binding minimally. For example, a fluorescent ryanodine adduct was synthesized which has a dissociation constant close to that of ryanodine. Detailed examination reveals subtle interactions between ryanoid and receptor. In many cases, the major factors altering the strength of binding were found to be conformational alterations in the molecule remote from the site of covalent modification.

Animals↗
PubMed1993

A cluster of coagulase-negative staphylococcal bacteremias associated with peripheral vascular catheter colonization in a neonatal intensive care unit.

BACKGROUND: A cluster of six neonatal cases of coagulase-negative staphylococcal bacteremias occurred in a Los Angeles County neonatal intensive care unit in March 1989. METHODS: A retrospective cohort study assessed the impact of host-and delivery-related variables, length of hospitalization, duration of antibiotic treatment, performance or duration of invasive procedures, and staffing variables on risk of coagulase-negative staphylococcal bacteremia. RESULTS: Unstratified analyses yielded eight risk factors with risk ratios greater than 2. After stratification by gestational age (less than 29 weeks) and low birth weight (less than 1500 gm), frequency of blood transfusions, duration of respiratory therapy, heparin lock and central vascular line placement, and hyperalimentation remained associated with elevated risk. Two species were identified, arguing against a common source of infection. Of four cohort months with more than 15 very low birth weight infants in the neonatal intensive care unit, an elevation of coagulase-negative staphylococcus-positive blood cultures and diagnosed bacteremias occurred in only two. CONCLUSIONS: This cluster of coagulase-negative staphylococcal bacteremia was probably caused by frequent manipulation of catheters in neonates who were at heightened risk because of low birth weight and prematurity.

Bacteremia↗
PubMed1993

The concentrations of collagen-associated amino acids are higher in GnRH agonist-treated uterine myomas.

OBJECTIVE: To test the hypothesis that the effects of estrogen reduction on uterine leiomyoma regression are mediated through changes in cell density or the extracellular matrix. METHODS: Uterine myomas were obtained from 20 women who had received randomly either the GnRH agonist leuprolide acetate depot for 3 months or placebo. The biochemical and morphologic characteristics studied included: total protein, DNA, and amino acid concentrations; histologic appearance; collagen content; and nuclear density. RESULTS: The absolute and relative concentrations of hydroxylysine, hydroxyproline, glycine, and proline were significantly greater (P < .05) in uterine myomas from patients pretreated with a GnRH agonist compared with placebo-treated controls. The GnRH agonist was also associated with trends toward increased mean total protein, DNA, and nuclear density, but the differences did not reach statistical significance. CONCLUSIONS: The concentrations of the amino acids contained in collagen were significantly greater in uterine myomas from patients treated with the GnRH agonist compared to myomas from placebo-treated controls. In addition, our observations suggest that the reduction in uterine myoma volume associated with GnRH agonist therapy is associated with alterations in the extracellular matrix.

Amino Acids↗
PubMed1993

High throughput DNA sequencing using an automated electrophoresis analysis system and a novel sequence assembly program.

The combination of high-resolution scanning, image-databasing technology and sequence assembly software makes it possible to assemble contiguous overlapping sequences of DNA in a fraction of the time required by manual methods. This paper describes and evaluates an assembly program that rapidly generates contigs from scanned images and provides a unique ability to verify disagreements between overlapping strands or fragments of complementary DNA sequences on-screen, further increasing sequencing throughput.

Base Sequence↗
PubMed1989

Binding of captan to DNA polymerase I from Escherichia coli and the concomitant effect on 5'----3' exonuclease activity.

Captan (N-[(trichloromethyl)thio]-4-cyclohexene-1,2-dicarboximide) was shown to bind to DNA polymerase I from Escherichia coli. The ratio of [14C] captan bound to DNA pol I was 1:1 as measured by filter binding studies and sucrose gradient analysis. Preincubation of enzyme with polynucleotide prevented the binding of captan, but preincubation of enzyme with dGTP did not. Conversely, when the enzyme was preincubated with captan, neither polynucleotide nor dGTP binding was blocked. The modification of the enzyme by captan was described by an irreversible second-order rate process with a rate of 68 +/- 0.7 M-1 s-1. The interaction of captan with DNA pol I altered each of the three catalytic functions. The 3'----5' exonuclease and polymerase activities were inhibited, and the 5'----3' exonuclease activity was enhanced. In order to study the 5'----3' exonuclease activity more closely, [3H]hpBR322 (DNA-[3H]RNA hybrid) was prepared from pBR322 plasmid DNA and used as a specific substrate for 5'----3' exonuclease activity. When either DNA pol I or polynucleotide was preincubated with 100 microM captan, 5'----3' exonuclease activity exhibited a doubling of reaction rate as compared to the untreated sample. When 100 microM captan was added to the reaction in progress, 5'----3' exonuclease activity was enhanced to 150% of the control value. Collectively, these data support the hypothesis that captan acts on DNA pol I by irreversibly binding in the template-primer binding site associated with polymerase and 3'----5' exonuclease activities. It is also shown that the chemical reaction between DNA pol I and a single captan molecule proceeds through a Michaelis complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Captan↗
PubMed1989

Similarity of an estrogen-induced protein and a luteinizing hormone releasing hormone-induced protein.

Estradiol induces a 70 kDa protein ('EI70') which is synthesized in vivo in the female rat ventromedial hypothalamus (VMH) and transported to the midbrain central gray, suggesting a role for EI70 in the female mating behavior, lordosis. Luteinizing hormone releasing hormone (LHRH), in addition to stimulating gonadotropin release, potentiates pituitary responsiveness to subsequent exposure to LHRH (the 'priming' effect), facilitates lordosis and induces the synthesis of a 70 kDa protein ('LHRH70') in pituitary in vitro. We now report that EI70 precisely co-migrates on two-dimensional (2-D) gels with the pituitary protein induced by LHRH both in vitro and in vivo. Furthermore, both proteins migrate on 2-D gels in the vicinity of a protein recognized after immunoblotting by antibodies to the heat-shock-70 kDa protein family. The induction of a common protein by estrogen or LHRH could represent a common mechanism by which these hormones facilitate secretion, and by which these hormones interact.

Animals↗
PubMed1988

The induction of the major heat-stress protein in purified rat glial cells.

Cultured purified oligodendroglia and astroglia exposed to heat stress (45 degrees C, 10 or 20 min) synthesized a 68-kDa heat-stress protein, which migrates on two-dimensional gel electrophoresis and reacts with a specific monoclonal antibody suggesting it is similar to a major 72-kDa heat-shock protein previously reported in other cell types. This protein was not detected in control glial cultures. Actinomycin D prevented synthesis of this protein demonstrating an absolute requirement for newly synthesized mRNA. The response was prolonged by increasing the period of heat stress from 10 to 20 min. In addition to the 68-kDa HSP protein, the incorporation of radioactivity into 70-, 89-, and 97-kDa proteins was also increased after heating, but in contrast to the 68 kDa protein these proteins appeared to be made in control glial cultures.

Animals↗
PubMed1988

Differential distribution of the adenovirus E1A proteins and colocalization of E1A with the 70-kilodalton cellular heat shock protein in infected cells.

Five distinct localization patterns were observed for the adenovirus E1A proteins in the nuclei of infected HeLa cells: diffuse, reticular, nucleolar, punctate, and peripheral. The variable distribution of E1A was correlated with the time postinfection and the cell cycle stage of the host cell at the time of infection. All staining patterns, with the exception of peripheral E1A localization, were associated with the early phase of infection since only the diffuse, reticular, nucleolar, and punctate staining patterns were observed in the presence of hydroxyurea. Because the E1A proteins (12S and 13S) stimulate the expression of the cellular heat shock 70-kilodalton protein (hsp70), we examined the intracellular distribution of hsp70 in the adenovirus-infected cells. Whereas hsp70 was predominantly cytoplasmic in the cells before infection, after adenovirus infection most of the protein was now found within the nucleus. Specifically, hsp70 was found within the nucleoli as well as exhibiting reticular, diffuse, and punctate nuclear staining patterns, analogous to those observed for the E1A proteins. Double-label indirect immunofluorescence of E1A and hsp70 in infected cells demonstrated a colocalization of these proteins in the nucleus. Translocation of hsp70 to the nucleus was dependent upon both adenovirus infection and expression of the E1A proteins. The localization of hsp70 was unaltered by infection with an E1A 9S cDNA virus which does not synthesize a functional E1A gene product. Moreover, the discrete nuclear localization patterns of E1A and the colocalization of E1A with hsp70 were not observed in adenovirus-transformed 293 cells which constitutively express E1A and E1B. E1A displayed exclusively diffuse nuclear staining in 293 cells; however, localization of E1A into the discrete nuclear patterns occurred after adenovirus infection of 293 cells. Immunoprecipitation of labeled infected-cell extracts with a monoclonal antibody directed against the E1A proteins resulted in precipitation of small amounts of hsp70 along with E1A. These data indicate that the adenovirus E1A proteins colocalize with, and possibly form a physical complex with, cellular hsp70 in infected cells. The relevance of this association, with respect to the function of these proteins during infection and the association of other oncoproteins with hsp70, is discussed.

Adenoviridae↗
PubMed1988

Aortocolic fistula caused by an ingested chicken bone.

Primary aortocolic fistulas are a rare but lethal complication of aortic or iliac aneurysms. A case of fistula between a nonaneurysmal aortic bifurcation and sigmoid colon caused by an ingested chicken bone is presented. This cause of rectal bleeding, which has never been described, might have been suspected after careful examination of abdominal x-ray films. Surgical management included removal of the foreign body and primary repair of the colonic and aortic rent and appeared to be adequate.

Aged↗
PubMed1987

Repair of pericardial rupture by abdominal transphrenic approach solely.

The abdominal transphrenic approach enabled us to repair a left lateral pericardial rupture on a polytrauma patient who also had a rupture of the spleen and a retroperitoneal hemorrhage. A pericardial exploration was necessary because of a sudden upper venous congestion syndrome during operation, suggestive of a cardiac tamponade.

Abdomen↗
PubMed1987

Comparison of auscultation, continuous wave Doppler imaging, intravenous digital subtraction angiography and conventional angiography in diagnosis of carotid artery disease.

The reliability of auscultation, continuous wave (CW) Doppler imaging, and intravenous digital subtraction angiography (IV DSA) in the assessment of carotid artery disease has been evaluated in comparison with conventional angiography in 30 patients. With auscultation, specificity and sensitivity for internal carotid artery (ICA) stenosis of 50% or more were 81% and 67% respectively. CW Doppler imaging detected ICA stenosis of 50% or more with a sensitivity of 83% and a specificity of 92% and ICA occlusion with a sensitivity of 60%. The specificity of IV DSA was 95% and the sensitivity for ICA stenosis of 50% or more and ICA occlusion were 75% and 100% respectively. Combining CW Doppler and IV DSA findings raised sensitivity for ICA stenosis of 50% or more and ICA occlusion to 89% and 100% respectively and specificity to 95%. The combination of CW Doppler and IV DSA is a safe and accurate test battery in the detection and categorization of carotid disease.

Adult↗
PubMed1986

Posterior mediastinal sarcoidosis.

We report two cases of enlargement of the posterior mediastinal lymph nodes due to sarcoidosis. Bilateral hilar enlargement, pulmonary parenchymal involvement, or extrathoracic manifestations of sarcoidosis were absent. A diagnostic thoracotomy had to be performed in both instances.

Adult↗
PubMed1985

Small artery syndrome in women.

During the past four years, 106 women underwent aortography and peripheral runoff studies for peripheral vascular disease. Eleven patients presented with "small vessels" and were selected for this study. They were significantly younger than the rest of the group (a mean age of 52 versus 66 years). A clear history of claudication was elicited in all patients. Rest pain was present in four patients. Most patients were small in stature but not obese. Weak or absent femoral and distal pulses and abdominal or femoral bruits were common. Angiography demonstrated a narrow infrarenal aorta, narrow iliac and common femoral arteries and a straight course of iliac arteries. Atherosclerotic lesions involved mainly the aortoiliac segment, but were confined to the superficial femoral artery in two patients. Reconstruction was achieved by endarterectomy or transluminal angioplasty in segmental aortoiliac disease and aortobifemoral or aortobi-iliac graft in diffuse disease. Femorpopliteal or iliopopliteal graft or lumbar sympathectomy was performed in patients with significant femoral disease. In one patient, an acutely occluded femoral segment was replaced by a venous interposition graft. Two patients were treated conservatively. There were no operative deaths. Nine patients were markedly improved at follow-up examination. Graft thrombosis occurred in one patient with combined aortobi-iliac and iliopopliteal graft. The high incidence of single bifurcating lumbar arteries at the fourth and fifth lumbar vertebrae supports the hypothesis that aortic hypoplasia may result from embryonic overfusion of the dorsal aortas. Lipid abnormalities existed in 54 per cent of the patients. All women were heavy smokers and 73 per cent had a positive family history of cardiovascular disease.

Aged↗