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Biomedical subjects

J White

Publications and source records attributed to J White.

At least 379 records · Page 21Linked to original sources

Transcriptional regulation of the redD transcriptional activator gene accounts for growth-phase-dependent production of the antibiotic undecylprodigiosin in Streptomyces coelicolor A3(2).

Transcription of redD, the activator gene required for production of the red-pigmented antibiotic undecylprodigiosin by Streptomyces coelicolor A3(2), showed a dramatic increase during the transition from exponential to stationary phase. The increase in redD expression was followed by transcription of redX, a biosynthetic structural gene, and the appearance of the antibiotic in the mycelium, and coincided with the intracellular appearance of ppGpp. However, ppGpp production elicited either by nutritional shift-down of, or addition of serine hydroxamate to, exponentially growing cultures had no stimulatory effect on redD transcription. The presence of redD on a multicopy plasmid resulted in elevated levels of the redD transcript and production of redX and undecylprodigiosin during exponential growth; the normal growth-phase-dependent production of undecylprodigiosin appeared to be mediated entirely through the redD promoter, which shows limited similarity to the consensus sequence for the major class of eubacterial promoters.

Amino Acid Sequence↗

Neuromuscular disease, respiratory failure and cor pulmonale.

Respiratory muscle weakness is an uncommon cause of chronic respiratory failure and a rare cause of cor pulmonale. The problem may not be apparent unless specific physical signs are sought or appropriate investigations performed. We present three patients who presented diagnostic difficulty for prolonged periods until the presence of respiratory muscle weakness was considered. Once the diagnosis was established treatment with nocturnal nasal intermittent positive pressure ventilation produced a dramatic improvement in symptoms and allowed a return to a near normal lifestyle.

Adult↗

Mesenchymal cells isolated after acute lung injury manifest an enhanced proliferative phenotype.

After acute lung injury, mesenchymal cells migrate into the alveolar airspace where they proliferate and deposit connective tissue macromolecules. Early in the disease process, inflammatory cell-derived trophic factors modulate these mesenchymal cell functions. However, in those patients who die, even as the inflammatory response abates, the fibroproliferative response continues, resulting in extensive intraalveolar fibrosis. We therefore hypothesized that lung mesenchymal cells obtained from individuals dying with acute alveolar fibrosis would manifest an enhanced proliferative capacity that was independent of persistent exogenous signals. To examine this hypothesis, the in vitro growth properties of mesenchymal cells prepared from patients dying with acute lung injury (n = 3) were analyzed in defined medium and compared with those of mesenchymal cells similarly prepared from patients dying with histologically normal lungs (n = 3). Isolates were characterized as mesenchymal cells by using morphological and immunohistochemical criteria. In accord with the hypothesis, mesenchymal cells isolated from lung-injured patients doubled within 3 d in the complete absence of exogenous peptide growth factors, reaching a saturation density of approximately 15 x 10(3) cells/cm2. As expected, lung mesenchymal cells from normal individuals failed to significantly increase in number. Consistent with this proliferative phenotype, the immediate early cell division cycle genes c-fos and c-jun were constitutively expressed in each cell strain prepared from injured lungs, but not in those from control lungs. The observed proliferative phenotype was stable through the fifth subcultivation of the cells. Despite these proliferative properties, three separate criteria indicated the mesenchymal cells from injured lungs were not transformed: normal karyotype; finite lifespan in vitro (9-10 subcultivations); and inability to disseminate in mice with severe combined immunodeficiency. These data support the hypothesis that mesenchymal cells manifest an enhanced proliferative state after acute lung injury.

Acute Disease↗

Smoking cessation interventions by family physicians in Texas.

A survey of 1,292 family physicians in Texas indicates that most of them (99%) ask patients about their smoking behavior. Fewer physicians, however, participate in further activities recommended by the National Cancer Institute: arranging follow-up visits, providing self-help materials, prescribing nicotine gum, engaging patients in discussion, referring patients to a program for smoking cessation, and involving other office personnel in counseling. Almost 80% of the respondents cited such obstacles to their involvement in counseling/advising patients as patient attitudes or patient preferences for smoking. The survey was conducted to acquire baseline data on the involvement of family physicians in Texas in counseling their patients who smoke and the obstacles they meet in their efforts.

Adult↗

Emergent properties of odor information coding in a representational model of the salamander olfactory bulb.

In the salamander olfactory bulb, mitral output cells exhibit a variety of responses to electrical and odor stimulation, but the cellular interactions within the bulb that give rise to these responses are not completely understood. We have developed a computer model to investigate whether available data are sufficient for formulating a simulated bulb circuit that can generate realistic mitral cell output. A set of coupled difference equations incorporating mathematical descriptions of anatomical and physiological data was used to calculate changes in membrane potentials of olfactory bulb neurons over time. Model mitral cells showed responses to simple orthodromic and antidromic electrical stimuli that were similar to salamander intracellular responses. Without changing the parameters of the equations, simulated odor stimuli were applied that elicited complex patterns of mitral depolarization, spike activation, and hyperpolarization that emerged from the interactions among the numerous elements in the model. As with the electrical stimuli, model mitral responses to odor were also strikingly similar to those of real mitral cells. As an initial test of how different circuit components contribute to the responses, the lateral interactions between mitral cells and bulbar interneurons were manipulated. Tests with reduced lateral interactions and other tests with no inhibitory synaptic connections both produced mitral cell outputs that were uncharacteristic of salamander recordings. The similarity of the model's output to the complex properties of salamander single-cell recordings suggests that several critical features of the bulb circuit responsible for shaping mitral cell responsivity have been captured.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambystoma↗

Measurement and standards in continuous quality improvement.

So where does all of this lead us? Many QA professionals are currently concerned that CQI will displace their role. Nurses are concerned that they will have to learn an entirely new process and language. In a National Association of Quality Assurance Professionals position paper, Martin (1990) points out that CQI builds on and strengthens the weaknesses of traditional quality assurance approaches. Quality improvement is not a substitute for quality assurance; it is a supplement to expand health care providers' understanding of the components of excellent patient care. Change and variation surrounds us at all times. Continuous quality improvement teaches the premises of variation and change. Through a better understanding of variation and application of this understanding to continuous improvement of the system of care, we will help assure better outcomes for our clients. Nurse administrators and staff nurses should endorse the arrival of continuous quality improvement. As leaders in QA, we are indeed positioned to become leaders in CQI.

Clinical Protocols↗

A method for production of antibodies to human T-cell receptor beta-chain variable regions.

Mouse T-cell hybridomas bearing human V beta elements were produced by transfection of human/mouse hybrid T-cell receptor beta-chain genes into a mouse T-cell hybridoma lacking an endogenous beta-chain gene. These hybridomas were entirely mouse in origin except for the human V beta region. These cells were used to immunize mice against human V beta elements. Mouse monoclonal antibodies have thus been generated against human V beta 13.1 and -13.2. We expect that the method outlined in this paper will be useful in the production of monoclonal antibodies specific for other human V beta or V alpha elements.

Animals↗

Examination of the roles of glycoprotein Ib and glycoprotein IIb/IIIa in platelet deposition on an artificial surface using clinical antiplatelet agents and monoclonal antibody blockade.

The mechanism of platelet thrombus growth on an artificial surface is incompletely understood. While glycoprotein (GP)Ib and GPIIb/IIIa are required for normal attachment and thrombus formation on subendothelium, their roles in platelet deposition to artificial surfaces remain unclear. Using selected platelet inhibitors (aspirin [ASA], low molecular weight dextran, monoclonal antibodies 10E5 [v GPIIb/IIIa], and 6D1 [GPIb]) we examined the mechanism of platelet deposition to polyethylene (PE) surfaces under steady laminar and oscillatory flow conditions. Polyethylene-100 (PE-100) tubes (0.86 mm internal diameter) were perfused under steady laminar flow with citrated human whole blood reconstituted with 111indium-labeled platelets at 312 seconds-1 shear rate in the presence and absence of platelet inhibitors. The effect of oscillatory flow on platelet deposition was examined in a microwell system using 3/16-inch diameter discs of National Heart, Lung, and Blood Institute primary reference PE as the test surface. ASA and dextran did not significantly (P greater than .05) inhibit platelet deposition in laminar flow (not tested in oscillatory). Antibody 10E5 was a potent inhibitor (laminar less than 1%, P less than .0001, oscillatory less than 1.6%, P less than .01) of platelet deposition in both systems, and in this case, true adhesion (first attached layer) was blocked. Antibody 6D1 unexpectedly inhibited 70% of platelet deposition (P less than .01) in steady laminar flow and 56.5% in oscillatory flow (P less than .01). Scanning electron microscopy demonstrated platelets atop platelets in the controls, rare platelets in the 10E5 group, and a patchy monolayer of platelets in the 6D1 group. Transmission electron microscopy of cross-sections confirmed these observations. We conclude that the adhesion of the first platelet layer to an artificial surface requires GPIIb/IIIa. The data also suggest that GPIb is required for the development of the second layer in vertical platelet thrombus growth.

Adenosine Diphosphate↗

Morphometric study of the human endometrium following continuous exposure to levonorgestrel released from vaginal rings during 90 days.

The effects of vaginal devices releasing levonorgestrel (LNG) at a constant rate of approximately 20 micrograms/24 hrs on the human endometrium were studied in a group of 69 normally menstruating women during a period of 90 days of continuous use. Peripheral blood samples were withdrawn three times weekly starting at day 10 of a pretreatment (control) cycle and then three times weekly from day 60 to 90 of the treatment period. The levels of LNG, estradiol, progesterone and sex hormone binding globulin (SHBG) were analyzed by radioimmunoassay techniques. Endometrial biopsies were obtained in the luteal phase of the pretreatment cycle and on day 84-87 of the treatment period. Increased bleeding occurred in most subjects exposed to the LNG-releasing device; the mean number of bleeding and spotting days was 26.4 +/- 8.9 S.D. which exceeded that found in their control cycle. Morphometric analyses of the endometrial biopsies using 9 quantitative indices, revealed highly significant changes in glands and stroma following the use of the LNG-releasing vaginal device. Irrespective of the circulating steroid levels, the administration of LNG significantly diminished the glandular diameter (p less than 0.001), reduced the volume density of the glands (p less than 0.001) and of the glandular epithelium (p less than 0.001). and modified the ratio glandular epithelium: glands (p less than 0.001). It is concluded that levonorgestrel released at a rate of 20 micrograms/24 hrs, induces characteristic changes in the histologic structure of the human endometrium. Although no simple correlation has been found between any of the endometrial indices and the numbers of bleeding/spotting days or bleeding days, the changes as such may represent biochemical alterations which could be predisposing factors for intermenstrual bleeding and spotting. To prove a causal relationship between morphological and biochemical changes and changes in bleeding patterns, further in-depth studies may be required.

Contraceptive Agents, Female↗

Snake venom variability: methods of study, results and interpretation.

The causes and implications of venom variability are discussed with a review of the literature. Venom variability may have an impact on both primary venom research and management of snakebite, including selection of antivenoms and selection of specimens for antivenom production. Choice of venom is reviewed, including venom collection, maintenance, and pooled venom versus venom milked from individual specimens, the latter being more reliable in many applications. Intraspecific variability resulting in clinical variability of envenomation occurs and is reviewed. Venom variability is considered at several levels; interfamily, intergenus, interspecies, intersubspecies and intraspecies, geographical variation, between individual specimens, and in individual specimens, due to seasonal variation, diet, habitat, age-dependent change, and sexual dimorphism. It is concluded that venom researchers must be aware of venom variability both in selecting their sources of venom and in interpretation of results. Producers of antivenom must utilize an understanding of such variability in selecting sources of venom for antivenom production to ensure representation of all venom types required within each antivenom. Furthermore, clinicians treating snakebite should understand the influence of venom variability on both the presentation of envenomation and the treatment implications.

Animals↗

Phosphine-mediated Heinz body formation and hemoglobin oxidation in human erythrocytes.

In this work the in vitro reactions of phosphine with intact red blood cells and membrane-free hemoglobin extracts are reported. We demonstrate that phosphine or phosphine derivatives induce dense aggregates of denatured hemoglobin known as 'Heinz bodies' in intact red blood cells. The reaction products include irreversible hemichrome formation. We further demonstrate an oxygen requirement for these effects. PH3 appears to act as a novel type of O2 radical chain initiator or propagator with heme proteins.

Erythrocytes↗

Inheritance of P-element regulation in Drosophila melanogaster.

The ability to repress P-element-induced gonadal dysgenesis was studied in 14 wild-type strains of D. melanogaster derived from populations in the central and eastern United States. Females from each of these strains had a high ability to repress gonadal dysgenesis in their daughters. Reciprocal hybrids produced by crossing each of the wild-type strains with an M strain demonstrated that repression ability was determined by a complex mixture of chromosomal and cytoplasmic factors. Cytoplasmic transmission of repression ability was observed in all 14 strains and chromosomal transmission was observed in 12 of them. Genomic Southern blots indicated that four of the strains possessed a particular type of P element, called KP, which has been proposed to account for the chromosomal transmission of repression ability. However, in this study several of the strains that lacked KP elements exhibited as much chromosomal transmission of repression ability as the strains that had KP elements, suggesting that other kinds of P elements may be involved.

Animals↗

Storage of platelets in balanced salt solutions: a simple platelet storage medium.

When a commercially available intravenous solution, plasmalyte-A, was added to platelet pellets as a platelet storage medium (PSM) after more than 85 percent of the plasma had been expressed, the platelets functioned equally well, after 5 days of storage, in platelet aggregation, release reaction, and serotonin uptake as did platelets stored in plasma. The level of fibrinopeptide A was significantly different in the PSM. Similarly, lower levels of kallikrein and complement components in the PSM-stored platelets indicated reduced activation of plasma enzyme systems. Morphology scores showed better shape maintenance in PSM, with values of 255 versus values of 185 in plasma (time zero, 280); electron microscopy also showed somewhat better structural maintenance in PSM. Glucose consumption, lactate and ammonia production, and fatty acid oxidation were also reduced in PSM. No significant differences in pH, white cell count, pO2, pCO2, or lactic dehydrogenase were observed after 5 days of storage in plasma or PSM; however, platelet counts were reduced after 5 days in plasma but remained constant in PSM. The beta-thromboglobulin release was significantly lower in the PSM-stored platelets after 5 days. The volume of platelet membrane glycoprotein lb (which is responsible for platelet adhesion) decreased 15 percent in plasma following storage, whereas a decrease of only 5 percent was noted in PSM. There was less leaching of plasticizers in PSM than in plasma. Survival and recovery using 51Cr-labeled autologous platelets showed that, after 5 days of storage, the recovery of PSM-stored platelets was 63 percent and the survival was 7.7 +/- 0.8 days (multiple hit model).(ABSTRACT TRUNCATED AT 250 WORDS)

Ammonia↗

TOPS: a consumer approach to Alzheimer's respite programs.

Time Off Promotes Strength (TOPS), a program for caregivers of Alzheimer's victims, provides in-home and day program services. Through application of a service/training model adapted from the Global Deterioration Scale (Reisberg, 1983), the TOPS program maintains a high quality of services with a limited but highly trained professional staff. Caregiver independence and autonomy are emphasized, as is a flexible system that accommodates the ever-changing needs of both caregivers and care recipients.

Allied Health Personnel↗

Desmoplastic medulloblastoma metastatic to the pancreas: case report.

A case is reported in which a desmoplastic medulloblastoma metastasized to the pancreas and to the surrounding soft tissues but did not recur locally or disseminate within the central nervous system. Multidrug chemotherapy and local radiation therapy resulted in a complete remission. In all four previously reported cases of medulloblastoma metastasizing to the pancreas, the diagnosis was not made until the postmortem examination, and all of these patients also had extensive metastases in other organ systems. Modification of the Weiss criteria defining extraneural metastases from tumors of the central nervous system is suggested.

Cerebellar Neoplasms↗

Reconstruction of failed lumbar surgery with narrow AO DCP plates for spinal arthrodesis.

Forty-five patients underwent surgical reconstruction with transpedicular fixation of the lumbar spine with narrow AO DCP plates. Preoperatively, all patients underwent spinal imaging with either magnetic resonance imaging, computed tomography, or myelogram as well as provocative discography to determine the location and the number of symptomatic segments. The minimum follow-up in this series was 2 years. The determination of solid posterior fusion in the presence of plate instrumentation was difficult. The patients in the series were classified as having 1) solid fusion; 2) radiographic flaws within the posterolateral fusion without implant failure; or 3) frank pseudarthrosis with implant failure. Thirty-six (80%) of the patients had a solid fusion, 9 of whom required an additional anterior interbody fusion to obtain symptom control. Twenty percent of the patients in the series had radiographic evidence of reabsorption without implant failure. Four patients in the series (8.8%) had screw breakage, three of which required anterior interbody fusions. The highest rate of reabsorption and pseudarthrosis implant failure was in the 12 patients who had three-level instrumentation; 33% of these patients required anterior interbody fusion to obtain a solid arthrodesis. The average preoperative pain scale was 8.9, and the average postoperative pain scale was a 3.3. Twenty-two patients in the series were cigarette smokers and had a slightly lower fusion rate than non-smokers. They did, however, have a higher use of narcotics after surgery. Forty percent of the patients in this series continued to have radiculopathy after their reconstruction. This study demonstrates the utility of transpedicular fixation in salvage lumbar surgery in obtaining a solid arthrodesis with a beneficial clinical result. Anterior interbody fusions are highly successful in the management of pseudarthrosis and implant failure after transpedicular instrumentation.

Adult↗