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Biomedical subjects

W Wilson

Publications and source records attributed to W Wilson.

At least 109 records · Page 6Linked to original sources

Syngeneic bone marrow transplantation and adoptive transfer of peripheral blood lymphocytes combined with zidovudine in human immunodeficiency virus (HIV) infection.

OBJECTIVE: To examine the role of syngeneic bone marrow transplantation and peripheral blood lymphocyte infusions combined with zidovudine in the treatment of patients with human immunodeficiency virus (HIV) infection. DESIGN: A partially randomized outpatient trial. SETTING: Outpatient and inpatient facility of the Clinical Center of the National Institutes of Health, a research-based referral facility. PATIENTS: Sixteen patients with HIV infection (15 symptomatic, 1 asymptomatic). INTERVENTIONS: Symptomatic patients were treated with zidovudine, 500 mg orally every 4 hours for 12 weeks, combined with six peripheral blood lymphocyte infusions (four at week 10, two at week 12) and bone marrow transplantation (at week 12) using HIV-seronegative identical twins as donors. After transplantation, patients were randomly assigned to receive either zidovudine, 100 mg every 4 hours, or placebo for 12 months. The asymptomatic patient received zidovudine for the first 12 weeks, discontinuing therapy after transplantation. Immunologic and virologic monitoring were done monthly. MEASUREMENTS AND MAIN RESULTS: Immediately after lymphocyte infusions and bone marrow transplantation, there was an increase in the mean (+/- SE) CD4 cell percent (19.1% +/- 3.1% to 28.1% +/- 3.0%), an increase in the fraction of patients with delayed-type hypersensitivity responses to tetanus toxoid (4 of 13 to 11 of 13) and the development of delayed-type hypersensitivity to keyhole-limpet hemocyanin (a primary immunogen to which only the donor had been immunized) in 8 of 12 patients tested. No significant clinical improvement was noted, however, and there was no overall sustained immunologic improvement. No differences in CD4 cell percents, delayed-hypersensitivity skin tests, HIV cultures, or p24 antigenemia were seen between patients treated with zidovudine or placebo after transplantation. CONCLUSIONS: Although they establish the feasibility of combining zidovudine with cellular immune reconstitution in treating patients with HIV infection, our results show that any benefits from such combination therapy are at best transient. Future attempts at cellular immune reconstitution may need to use improved antiretroviral regimens as well as immunization of donors with HIV-specific antigens.

Adult↗

Nocturnal and early morning secretion of ACTH and cortisol in humans.

It is well established that the adrenocorticotropic hormone (ACTH) stimulates the synthesis and release of cortisol from the adrenal cortex, but the role of ACTH in the physiological regulation of basal cortisol secretion has received surprisingly little study. The authors studied the nocturnal and early morning secretory pulses of cortisol and ACTH in normal subjects. A pulse detection algorithm was developed. The relationship between ACTH and cortisol pulses in terms of temporal and proportional relationship is described. Pulse concomitance for ACTH with cortisol was 47% and for cortisol with ACTH pulses it was 60%. The first description of the relationship between concomitant ACTH and cortisol pulse magnitudes in humans is presented. A highly significant linear relationship between the magnitudes of ACTH and cortisol pulses is shown. Putative reasons for dissociated pulses and the potential implication of these findings are discussed.

Adrenocorticotropic Hormone↗

De novo direct tandem duplication of the short arm of chromosome 7(p21.1-p14.2).

We report on a 6-year-old boy with moderate developmental retardation and unusual dermatoglyphics. Cytogenetic analysis demonstrated a duplication of chromosome sub-region 7p21.2-p14.2. Confirmation of the specific duplicated region was determined by quantitative Southern blotting by using a DNA fragment previously localized to the portion of chromosome 7 thought to be duplicated. This patient did not have the internal malformations seen with other dup(7p) patients.

Blotting, Southern↗

Kaposi's sarcoma of the rectum in patients with the acquired immunodeficiency syndrome.

We retrospectively reviewed eight patients with biopsy-proven anorectal Kaposi's sarcoma (KS) treated between 1984 and 1989 at San Francisco General Hospital. All patients were homosexual men with the acquired immunodeficiency syndrome (AIDS). The average age was 34 years. Three patients had primary rectal KS without metastases. Five patients had disseminated KS with lesions throughout the alimentary tract, viscera, skin, or local lymph nodes. Three patients were treated with radiation or chemotherapy. Five patients had disseminated KS with lesions throughout the alimentary tract, viscera, skin, or local lymph nodes. Three patients were treated with radiation or chemotherapy. Five patients with advanced AIDS received no specific treatment for anorectal KS. Follow-up ranged from 1 month to 5 years. Three of the untreated patients and the three patients treated with chemotherapy or radiotherapy were alive 1 month to 5 years after diagnosis. Aggressive surgical treatment of anorectal KS is not indicated.

Acquired Immunodeficiency Syndrome↗

Bulk compounding in Canadian hospitals--a survey.

A five-page English survey was mailed to 350 Canadian hospitals with 100+ beds to identify aspects of pharmacy bulk compounding services. The survey used open-ended questions to determine demographic and background information of the hospitals surveyed, availability of bulk compounding services and associated personnel requirements, products and dosage forms compounded, and compliance with "CSHP Guidelines for Bulk Compounding of Products in Hospitals". A 47.4 percent response rate was achieved. Sixty-six percent of respondents provided bulk compounding services. Proportionately, teaching hospitals were more likely to compound (84.6%) than other types of hospitals. Hospitals with 400+ beds were more likely to compound (85.7%) than hospitals with less than 400 beds (55.7%). No pattern was determinable for personnel requirements necessary for bulk compounding services. Items compounded most frequently were topical (80%) or oral (79.1%) preparations. Dosage forms most likely to be compounded were solutions (81.8%), ointments (69.1%) and suspensions (68.2%). Cocaine solution was the most commonly prepared product (47.3%). Compliance with CSHP standards was generally good (50-90%).

Canada↗

HIV-1 TAT "activates" presynthesized RNA in the nucleus.

Replication of the human immunodeficiency virus (HIV-1) depends upon the viral TAT protein. TAT stimulates gene expression via a target response sequence (TAR) located within the HIV-1 LTR. As TAR is located in the transcribed region it could act as a signal in either the DNA, the RNA, or both. To test whether TAT acts on transcription and/or posttranscriptionally, we produced TAT in yeast and monitored its activity after microinjection into the nucleus or cytoplasm of Xenopus oocytes. The TAT protein stimulated TAR-dependent expression, but this activation was not inhibited by transcriptional inhibitors. Furthermore, TAR-containing RNA, produced in vitro, was "activated" by TAT after coinjection into oocytes. This activation only occurred, however, when the RNA was injected into the nucleus and not into the cytoplasm. Our data indicate, therefore, that in the Xenopus system TAT acts on presynthesized RNA and that the nucleus is involved in this action.

Animals↗

Cardiac MRI of elite junior Olympic weight lifters.

Cardiac magnetic resonance imaging was performed on 14 junior elite Olympic weight lifters and 14 controls (means +/- Se, age = 18.4 +/- 0.5 and 17.8 +/- 0.4 years, weight = 76.5 +/- 3.6 and 78.8 +/- 3.3 kg, % fat = 6.5% +/- 0.8% and 11.5% +/- 1.7%, respectively). Controls were individually matched to the lifters to within 2 years of age and 2.5 kg of body weight. Systolic (S) and diastolic (D) left posterior wall thickness (LPW), left ventricular short axis (LSA), left ventricular transverse long axis (LLA), spetal wall thickness (SW), right ventricular wall thickness (RWT), and right ventricular short axis (RSA) were determined. Variables were examined in absolute (mm), relative to body surface area (BSA, mm/m2), total body weight (BW, mm/kg), and lean body mass (LBM, mm/kg) terms. In absolute terms S LPW (21.1 +/- 1.7 vs 13.3 +/- 0.5 mm), S SW (15.3 +/- 1.3 vs 11.7 +/- 0.6 mm), and D LLA (75.2 +/- 1.6 vs 69.1 +/- 2.4 mm) were significantly greater and S LSA (23.4 +/- 2.4 vs 36.7 +/- 2.3 mm) and S LLA (46.5 +/- 3.7 vs 58.2 +/- 3.8 mm) were significantly less in the lifters vs the controls. S LPW/BW, S LPW/BSA, S LPW/LBM, S SW/BW, S SW/BSA, S SW/LBM, D LSA/BSA, and D LLA/BSA were significantly greater and S LSA/BW, B LSA/BSA, S LSA/LBM, S LLA/BSA, S LLA/LBM, and D SW/LBM were significantly less in the lifters than the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Is the priming principle both effective and safe?

This study determined the priming dose of vecuronium (V), pancuronium (P) and atracurium (A) that resulted in the most rapid onset of neuromuscular blockade (NMB) in 150 patients given either V 0.08 mg/kg, P 0.1 mg/kg or A 0.6 mg/kg. Patients were further divided (n = 10 per group) to receive no prime or 5%, 10%, 15% or 20% of the total dose as a prime followed 5-7 minutes later by the remaining (intubating) dose. A further 10 patients received 0.04 mg/kg d-tubocurarine followed by 1.5 mg/kg succinylcholine (S). Priming significantly shortened the onset of NMB. The priming doses producing the most rapid onset were 0.012 mg/kg for V, 0.015 mg/kg for P and 0.09 mg/kg for A. The S resulted in significantly greater NMB at 60 sec than any priming dose of A, V or P. There was no difference between the three nondepolarizing neuromuscular blockers in shortening the onset of NMB produced by priming. To evaluate both the effect of the "optimal" priming dose in awake patients and the effect of increasing intubating doses on NMB an additional 40 patients were given V 0.012 mg/kg followed by V 0.08, 0.1, 0.12 or 0.15 mg/kg. Increasing the intubating dose did not improve onset of NMB. The "optimal" priming dose, however, resulted in a high incidence of symptoms of muscle weakness. We conclude that priming shortens the onset of NMB similarly between V, P and A but the priming dose producing the most rapid onset of NMB also results in a high incidence of side effects and therefore the priming principle should be used with caution.

Atracurium↗

Synchronous hepatocellular carcinoma and adenocarcinoma of the colon.

It is not uncommon for patients with colon cancer to have a second primary neoplasm. The reported incidence of synchronous colon tumors is approximately about 3 to 4 per cent. Colon cancer also may be associated with a synchronous extra-colonic neoplasm; this incidence is less well defined and certainly is less emphasized in the literature. The authors recently treated a patient who had a synchronous hepatoma and adenocarcinoma of the colon. This appears to be the first report of these tumors presenting synchronously. The patient had both tumors resected and has no evidence of recurrence ten months later. This case illustrates the need to seek both colonic and extra-colonic synchronous tumors in patients discovered to have a colon cancer.

Adenocarcinoma↗

HIV expression strategies: ribosomal frameshifting is directed by a short sequence in both mammalian and yeast systems.

The pol gene of the human immunodeficiency virus (HIV-1) is expressed as a gag:pol fusion, arising from a ribosomal frameshift that brings the overlapping, out-of-phase gag and pol genes into translational phase. In this study, we show that HIV frameshifting is mediated by a very short sequence in the viral RNA. We demonstrate the importance of a homopolymeric run within this sequence and conclude that HIV frameshifting is not dependent on stem-loop structures downstream from the frameshift site. Our analysis also indicates that the sequence requirements are identical in mammalian and yeast systems.

Animals↗

Chromosomal and c-K-ras oncogene alterations induced by a chemical carcinogen and phorbol ester in skin fibroblasts of individuals with familial polyposis coli.

Skin fibroblasts derived from three patients with familial polyposis coli (FPC) were treated in vitro with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) alone or in combination with the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA). None of the cultures treated four times with MNNG alone (1 microgram/ml) or in combination with TPA (eight applications, 0.1 microgram/ml each) showed either morphological transformation or anchorage-independent growth for 18 months after treatments. FPC cells treated with MNNG alone showed cell growth inhibition, breakage and loss of chromosomes, as well as the deletion of 5.7 kilobase (kb) EcoRI fragment in the c-K-ras locus as detected by Southern blot analysis with v-K-ras specific probe (clone KBE-2). The control cells contained two EcoRI fragments of 5.7 and 4.2 kb. On the other hand, cells treated with MNNG first and then followed by treatment with TPA not only showed an increase in the rate of cell growth but also exhibited two novel EcoRI fragments of 9.4 and 12 kb. Treatment with TPA alone appeared to stimulate cell division long after application and to induce chromosomal aberrations but had no effect on c-K-ras sequences. The most likely explanation for the appearance of chromosome pulverization and hyperploidy in FPC cells treated with TPA is the induction of premature chromosome condensation of the S phase cells due to fusion with the mitotic chromosomes.

Adenomatous Polyposis Coli↗

Ciprofloxacin therapy of experimental endocarditis caused by methicillin-susceptible or methicillin-resistant Staphylococcus aureus.

Ciprofloxacin was more effective (P less than 0.01) than either imipenem or nafcillin therapy of experimental methicillin-susceptible Staphylococcus aureus endocarditis in rabbits after 2 or 3 days of treatment. There was no significant difference between results of treatment of methicillin-susceptible S. aureus experimental endocarditis with ciprofloxacin and results with the combination of nafcillin and gentamicin. Ciprofloxacin was more effective (P less than 0.01) than vancomycin therapy of experimental methicillin-resistant S. aureus endocarditis after 3 days of treatment. After 5 days of treatment, there was no significant difference between the results of treatment of experimental methicillin-resistant S. aureus endocarditis with ciprofloxacin and results with vancomycin.

Animals↗

Complete nucleotide sequence of a mouse VL30 retro-element.

The complete nucleotide sequence of a mouse retro-element is presented. The cloned element is composed of 4,834 base pairs (bp) with long terminal repeats of 568 bp separated by an internal region of 3,698 bp. The element did not appear to have any open reading frames that would be capable of encoding the functional proteins that are normally produced by retro-elements. However, some regions of the genome showed some homology to retroviral gag and pol open reading frames. There was no region in VL30 corresponding to a retroviral env gene. This implies that VL30 is related to retrotransposons rather than to retroviruses. The sequence also contained regions that were homologous to known reverse transcriptase priming sites and viral packaging sites. These observations, combined with the known transcriptional capacity of the VL30 promoter, suggest that VL30 relies on protein functions of other retro-elements, such as murine leukemia virus, while maintaining highly conserved cis-active promoter, packaging, and priming sites necessary for its replication and cell-to-cell transmission.

Amino Acid Sequence↗

A pulmonary artery endothelial factor causes unidirectional alignment of smooth muscle cells.

Pulmonary artery and aorta endothelial and smooth muscle cells harvested from near term Rambouillet lambs were cultured. To determine whether cultured endothelial cells produce a factor which alters the shape and alignment of smooth muscle cells, rhodamine phalloidin staining of F-actin filaments was carried out, as well as time-lapse cinematography. We were able to demonstrate, with pulmonary artery but not with aortic cells in culture, an endothelial-derived factor which causes the smooth muscle cells to migrate and align in uniform direction. The effect could not be enhanced by making the endothelial cells hypoxic and was similar to that produced by exposing smooth muscle cells to KCl or directly to hypoxia.

Animals↗

The genetic organization of the yeast Ty element.

The genetic organization of the yeast transposon Ty resembles that of higher eukaryotic retroviruses and other elements such as the copia-like sequences of Drosophila. The Ty genome is 5.9 kb (10(3) bases) long. It has 340 bp (base pairs) terminal repeats known as delta sequences and it produces a terminally redundant 5.7 kb RNA that starts in the 5' delta and ends in the 3' delta. Ty transcription is directed by signals upstream and downstream of the major RNA start site and is regulated by the mating-type configuration of the cell. The 5.7 kb transcriptional unit is divided into two overlapping open reading frames, TYA and TYB. TYA occupies approximately the first quarter of the transcriptional unit while TYB occupies the rest. TYB overlaps TYA by either 38 or 44 nucleotides, depending on the element, and is in the plus one reading frame with respect to TYA. TYA is expressed to produce protein p1 (50 x 10(3) Mr) and TYB is expressed as a TYA:TYB fusion protein, p3 (190 x 10(3) Mr). Both of these proteins are subsequently cleaved to produce proteins p2, p4, p5, p6, reverse transcriptase and a protease that is responsible for some of these cleavage events. These proteins are assembled into virus-like particles (Ty-VLPs) that contain Ty RNA and reverse transcriptase activity. It is likely that the Ty-VLPs are units of transposition as Ty transposes via an RNA intermediate.

DNA Transposable Elements↗