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Biomedical subjects

S White

Publications and source records attributed to S White.

At least 217 records · Page 12Linked to original sources
PubMed1991

Neutron structure of subtilisin BPN': effects of chemical environment on hydrogen-bonding geometries and the pattern of hydrogen-deuterium exchange in secondary structure elements.

The neutron structure of subtilisin BPN' has been refined and analyzed at 2.0-A resolution. The structure studied was a mutant variant of subtilisin, Met222----Gln, and was used because large, uninhibited crystals could be grown, which was not the case for the native molecule. Comparison of the structure with that of the native molecule indicated that the two structures are essentially the same. Using the capability of the neutron method to locate hydrogen and deuterium atoms, the protonation states of the six histidine residues were assigned. The active site histidine, His64, was found to be neutral at the pH of the analysis (pH 6.1). This group has an unexpectedly low pKa compared to assignments made by other techniques. The altered pKa of the group could result from electrostatic effects of other molecules in the crystal lattice. The dihedral conformations of a majority of the hydroxyl rotors were assigned. The preferred orientation was trans (180 degrees) with the other two low-energy conformers (60 degrees, 300 degrees) about equally populated. For the serines, about 21% of the hydroxyls act exclusively as H-bond acceptors and 37% as H-bond donors, and in 42% the group functions as both. The experimentally observed dihedral conformations were compared to predicted conformations based on calculated energy criteria and showed a strong correspondence. Deviation from low-energy states could usually be explained by local electrostatic effects. The hydrogen exchange pattern of subtilisin identified the beta-sheet and alpha-helix secondary structure elements to be the most resistant to exchange. Fifty-five percent of the peptide amide hydrogens were fully exchanged, 15% unexchanged, and 30% partially exchanged. The largest concentration of unexchanged sites was in the seven-stranded parallel beta-sheet, in which there were 11 fully protected groups. Little correlation was found between H-bond length and angle and a peptide group's susceptibility toward exchange. Of the five alpha-helices the most protected from exchange is the one defined by residues 224-236. The pattern of exchange identifies regions in this helix where the H-bonding regularity is disrupted.

Binding Sites↗
PubMed1991

A de novo unbalanced reciprocal translocation identified as paternal in origin in the Prader-Willi syndrome.

Interstitial cytogenetic deletions involving the paternally derived chromosome 15q11-13 have been described in patients with the Prader-Willi syndrome (PWS). We report a child with PWS and a de novo unbalanced karyotype -45,XY,-9,-15,+der(9)t(9;15)(q34;q13). Molecular studies with the DNA probe pML34 confirmed that only a single Prader Willi critical region (PWCR:15q11.2-q12) copy was present. Hybridisation of patient and parental DNA with the multi-allelic probe CMW1, which maps to pter-15q13, showed that the chromosome involved in the translocation was paternal in origin. This is the first example of a paternally-derived PWCR allele loss caused by an unbalanced translocation that has arisen de novo.

Blotting, Southern↗
PubMed1991

Agar disk diffusion susceptibility tests with cilofungin (LY 121019).

Cilofungin (LY 121019) is a semi-biosynthetic lipopeptide agent which is active both in vitro and in vivo against isolates of Candida species. The purpose of this study was to demonstrate the usefulness of experimental 10- and 20-micrograms cilofungin disks in predicting probable in vitro susceptibility to this drug. Fifty-two isolates of pathogenic yeasts, which included 34 isolates of Candida albicans, 10 isolates of Candida tropicalis and eight isolates of Candida glabrata, were tested. Both agar dilution minimal inhibitory concentration (MIC) tests and matched agar disk diffusion tests were performed using 14-h-old broth cultures grown in single strength yeast nitrogen base (YNB) supplemented with asparagine and dextrose. Both tests were incubated at 35 degrees C and the results were read after 24 h. Regression analysis was used to measure the degree of correlation between MIC values and matched averaged zones of inhibition, and demonstrated that both the 10-micrograms (r = 0.9278) and 20-micrograms (r = 0.9082) disks can predict probable MIC values.

Antifungal Agents↗
PubMed1991

Hidden posttraumatic stress disorder in the mother of a boy with traumatic limb amputation.

Posttraumatic stress disorder (PTSD) is usually diagnosed in the primary victim of a psychologically distressing event who demonstrates the criteria symptomatology. Presented here is a case study of PTSD symptoms in a mother whose 4-year-old boy underwent bilateral arm amputation. Discussed is how the mother became the primary PTSD victim and why the particular injury (electrical shock) can be explained as readily giving rise to her problems. Consultants to pediatric and trauma services are reminded that the primary patient's medical care may suffer if disorders such as PTSD are not recognized in those responsible for making treatment decisions for the young victim.

Amputation, Traumatic↗
PubMed1991

A developmental history of the Society of Pediatric Psychology.

Presented history of the field of pediatric psychology in general and, more specifically, the development of the Society of Pediatric Psychology. Review began with 1896 concepts of Lightner Witmer and followed with 1960 activities by Logan Wright which led to the formation of the Society. The developmental phases of the Society are described with respect to goals, publications, financial status, training issues, and awards established. Present activities of liaisons with numerous outside organizations and agencies and regional conferences are detailed.

History, 19th Century↗
PubMed1991

DNA synthesis is reduced in selected fetal tissues during prolonged hypoxemia.

The effects of 24 h of reduced maternal uterine blood flow (RUBF) on relative DNA synthesis rates in different tissues and on blood glucose and lactate concentrations were studied in fetal sheep. In six sheep, RUBF was induced for 24 h, whereas in another six sheep (controls), uterine blood flow was not reduced. To estimate DNA synthesis rate, [3H]thymidine (1 mCi/kg) was injected intravenously into each fetus 8 h before the end of the 24-h experimental period. Fetal arterial oxygen saturation decreased from 59.1 +/- 3.3 to 25.7 +/- 5.6% after 1 h of RUBF and remained significantly reduced for the duration of the experiment. Fetal blood lactate concentrations were significantly increased by RUBF from 14.3 +/- 6.5 to 57.8 +/- 12.4 mg/dl at 1 h and remained elevated, whereas fetal blood glucose concentrations were not affected. A 24-h period of RUBF did not significantly alter fetal body weights, tissue weights, tissue-to-body weight ratios, or tissue DNA content. Over the last 8 h of the 24-h experimental period, RUBF was found to significantly reduce the relative rate of DNA synthesis (as assessed by [3H]thymidine incorporation into DNA) in the lung (104.7 +/- 26.6 vs. 17.1 +/- 3.1 dpm/micrograms DNA), quadriceps muscle (92.8 +/- 20.7 vs. 14.4 +/- 5.3 dpm/micrograms DNA), and thymus gland (87.5 +/- 7.1 vs. 32.9 +/- 12.2 dpm/micrograms DNA). Relative DNA synthesis rates in the fetal liver, kidney, small intestine, cerebral cortex, cerebellum, placenta, thyroid gland, and adrenal gland were not significantly affected by RUBF. In this study, we have shown that DNA synthesis was greatly reduced in selected fetal tissues (lung, quadriceps muscle, and thymus gland) by a 24-h period of RUBF, although it is not known why a reduction was only observed in these tissues.

Adrenal Glands↗
PubMed1990

Combinations of anti-transferrin receptor monoclonal antibodies inhibit human tumor cell growth in vitro and in vivo: evidence for synergistic antiproliferative effects.

Thirty-two murine monoclonal antibodies (MAbs) against the external domain of the human transferrin (Tf) receptor have been obtained using human Tf receptor glycoprotein produced in a baculovirus expression system as immunogen. The MAbs were tested separately, and in combination, for their ability to inhibit growth of CCRF-CEM leukemic T-cells in tissue culture. One MAb, D65.30, an IgG1, inhibited growth of CCRF-CEM cells as effectively as the anti-Tf receptor MAb 42/6, an IgA, previously found to have the highest antiproliferative activity in this assay. Some combinations of two or more MAbs inhibited the in vitro growth of CCRF-CEM much more effectively than single MAbs. Eleven IgG1 anti-Tf receptor MAbs, when combined individually with D65.30, increased the inhibition of CCRF-CEM growth from approximately 65% to greater than 90% in a 7-day growth assay. Similarly, many IgG MAbs in combination with 42/6 also inhibited CCRF-CEM growth by greater than 90%. The growth-inhibitory effects of certain combinations of MAbs were clearly synergistic, because either one or both MAbs tested separately were inactive. These pairs of MAbs also inhibited the growth of HL-60 and KG-1 leukemic cells by greater than 90% and partially inhibited the growth of K562 erythroleukemia and M21 melanoma cells, which are resistant to MAb 42/6. However, not all combinations of anti-Tf receptor MAbs were more effective; eight MAbs markedly antagonized the antiproliferative effects of D65.30, whereas 12 others had little or no effect. Preincubation of HL-60 cells with three different pairs of MAbs, D65.30 and A27.15, B3/25 and 42/6, and B3/25 and TR3A, inhibited subsequent colony formation by greater than 95%, demonstrating that their action is cytotoxic, not cytostatic. The antiproliferative activity of these pairs of MAbs correlates with their ability to block Tf-mediated 59Fe uptake and perturb Tf receptor expression. Treatment of nude mice bearing established s.c. CCRF-CEM tumors with a combination of MAbs D65.30 and A27.15 inhibited tumor growth and in some animals led to complete tumor regression. Each MAb administered separately was much less effective. We conclude that combinations of two or more anti-Tf receptor MAbs can interact synergistically to inhibit cell growth in vitro and tumor growth in vivo.

Animals↗
PubMed1990

Skin hyperkeratosis and papilloma formation in transgenic mice expressing a ras oncogene from a suprabasal keratin promoter.

The promoter region of the suprabasal keratin 10 gene has been used to direct expression of a mutant human Harvey-ras oncogene to the differentiating cells of the mouse epidermis. Transgenic animals develop hyperkeratosis of the skin and forestomach--the two sites known to express high levels of the keratin 10 polypeptide in vivo. Papillomas subsequently develop on the skin surface, initially at sites subject to biting or scratching such as the base of the tail or behind the ears. The results suggest that the "second event" involved in tumor development in these transgenic animals is the local induction of a mild wounding stimulus. Furthermore, because the H-ras transgene is expressed in suprabasal cells, it appears that cells which have left the stem cell compartment can be induced to form at least benign tumors in vivo.

Animals↗
PubMed1990

An electrocardiographic midterm follow-up study after anatomic repair of transposition of the great arteries.

Prospective studies of rhythm and conduction, before and after 1-stage anatomic repair of simple transposition of the great arteries, were performed on 24 survivors. Pre- and postsurgical serial standard electrocardiograms were obtained on each patient. Fourteen patients underwent perioperative 24-hour electrocardiograms; all had follow-up 24-hour electrocardiograms. Rare atrial or occasional ventricular premature complexes were detected in 3 (11%) patients before operation. After surgery, 1 patient developed right bundle branch block. Two patients developed a left bundle branch block. One patient had a QS pattern in V6, which disappeared on follow-up electrocardiogram. Transient second-degree atrioventricular block was detected in 1 patient. A normal P-R interval and P-wave axis were present in all but 1 patient. Mild sinus bradycardia or rare atrial or ventricular premature complexes were detected in 4 of twenty-nine 24-hour electrocardiograms performed in the first 2 years after surgery. At 3 years after repair, 5 patients had a normal 24-hour electrocardiogram and 1 had low-grade ectopy (rare atrial and ventricular premature complexes). At 4 years, all 4 patients studied had normal 24-hour electrocardiograms. During a mean follow-up of 3 years, we have yet to document any symptomatic arrhythmias.

Arrhythmias, Cardiac↗
PubMed1990

Single intrauterine fetal death in a suspected monozygotic twin pregnancy.

The antepartum death of a fetus in a twin pregnancy is associated with significant risk of mortality and morbidity in the surviving infant. A recent case of single intrauterine death in a suspected monozygotic twin pregnancy at a regional hospital prompted a study of similar cases in the hospital's recent experience and a review of the current literature. We report the successful conservative management of fetal death in a monozygotic twin pregnancy.

Adolescent↗
PubMed1990

A potassium channel in the apical membrane of rabbit thick ascending limb of Henle's loop.

We used the patch-clamp technique to study the activity of single potassium channels in the apical membrane of isolated thick ascending limbs of Henle's loop (TAL) of rabbit kidneys. In cell-attached patches with NaCl Ringer or high-K+ solution in the bath and 140 mM K+ in the pipette, an inwardly rectifying K+ channel was observed with an inward slope conductance of 22.0 +/- 0.5 pS and outward slope conductance of 10.2 +/- 0.3 pS at 22 degrees C (n = 15). The channel was highly selective for K+, with a calculated permeability ratio for K(+)-to-Na+ of 20:1 (n = 4). The open probability (Po) of the channel was 0.89 +/- 0.03 (n = 15) and was not voltage dependent. In inside-out patches with 140 mM K+ in both the bath and the pipette solutions, both Po and conductance of the channel were similar to that in cell-attached patches. Addition of 0.1 mM Ba2+ to the pipette solution reduced Po of the channel in a voltage-dependent manner. Lowering the pH of the bath solution from 7.4 to 6.9 or increasing Ca2+ concentration from 0 to 0.5 mM in inside-out patches did not alter either Po or conductance of the channel. Addition of 2 mM ATP to the bath solution completely inhibited channel activity. This ATP-induced inhibition was fully reversible and was found to be dependent on the ratio of ATP to ADP, since adding 1 mM ADP to the bath solution relieved the ATP-induced blockade. The property of this small-conductance K+ channel make it a likely candidate for recycling of K+ across the apical membrane of TAL of the rabbit kidney. ATP and ADP are possible intracellular regulators of the channel's activity.

Adenosine Triphosphate↗
PubMed1990

Corporate objectives and the planning process.

The embodiment of corporate objectives in a workable planning process enables all employees to develop an identity larger than themselves. This results in a more cohesive body and makes it easier to implement the organization's strategy and mission. The senior executives at University Hospital have a long history with the organization and therefore know it well. Whether the new process makes planning more coordinated and comprehensive will be measured by both the subjective and the objective assessment of these executives.

Hospital Departments↗