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Biomedical subjects

J Davis

Publications and source records attributed to J Davis.

At least 199 records · Page 11Linked to original sources
PubMed1996

Genomic sequence, organization, and chromosomal localization of human JAK3.

Members of the Janus (JAK) protein tyrosine kinase family including JAK3 have recently emerged as important components in cytokine signal transduction. Mutations of JAK3 have been found in a number of patients who present with severe combined immunodeficiency. To facilitate the further identification of JAK3-SCID patients and to understand the structure of JAK3 better, we undertook the determination of the genomic sequence, organization, and chromosomal localization of the JAK3 gene. The JAK3 gene was found to consist of 19 exons and 18 introns. Interestingly, the organization of the kinase-(JH1) and pseudokinase-(JH2) domains were found to be dissimilar. In addition, the JAK3 gene was localized to human chromosome 19p13.1. These data should facilitate the identification of patients with this new form of immunodeficiency and will provide insight into the structure of this kinase.

Chromosome Mapping↗
PubMed1996

Changes in bone mineral content in male athletes. Mechanisms of action and intervention effects.

OBJECTIVES: To determine changes in bone mineral content (BMC) in male athletes, to examine the mechanisms of changes, and to evaluate the effects of intervention. DESIGN: Dual-energy x-ray absorptiometry (DEXA) tests were administered over a 2-year period, and calcium loss during training was determined by analysis of sweat and urine. Calcium supplementation was administered during year 2. SETTING--A midsouth university. PARTICIPANTS: Eleven members of a college Division I-A basketball team. INTERVENTION: Based on observed calcium loss, athletes received differential levels of calcium supplementation. Intervention commenced the week prior to the fall training season and continued through postseason play. MAIN OUTCOME MEASURE--Changes in BMC. RESULTS: Total body BMC decreased 3.8% from preseason to midseason of year 1 (mean decrease, 133.4 g, P = .02), increased nonsignificantly by 1.1% (mean increase, 35.3 g, P = .22) during the offseason, but decreased an additional 3.3% during summer months when practices resumed (mean decrease, 113.1 g, P = .01). Dermal calcium loss averaged 247 mg [corrected] per training session. From preseason to late summer, there was an overall decrease of 6.1% in total BMC and a 10.5% decrease in BMC of the legs. Calcium supplementation was associated with significant increases in BMC and lean body mass. CONCLUSIONS: Bone loss is calcium related and exercise is positively related to BMC provided that calcium intake is sufficient to offset dermal loss.

Absorptiometry, Photon↗
PubMed1996

Enhanced pathologic properties of Dutch-type mutant amyloid beta-protein.

Cerebrovascular amyloid beta-protein (Abeta) deposition is a pathological feature of several related disorders including Alzheimer disease and hereditary cerebral hemorrhage with amyloidosis Dutch-type (HCHWA-D). HCHWA-D is caused by a point mutation in the gene that encodes the Abeta precursor and results in a Glu --> Gln substitution at position 22 of Abeta. In comparison to Alzheimer disease, the cerebrovascular Abeta deposition in HCHWA-D is generally more severe, often resulting in intracerebral hemorrhage when patients reach 50 years of age. We recently reported that Abeta(1-42), but not the shorter Abeta(1-40) induces pathologic responses in cultured human leptomeningeal smooth muscle cells including cellular degeneration that is accompanied by a marked increase in the levels of cellular Abeta precursor and soluble Abeta peptide. In the present study, we show that the HCHWA-D mutation converts the normally nonpathologic Abeta(1-40) into a highly pathologic form of the peptide for cultured human leptomeningeal smooth muscle cells. These findings suggest that these altered functional properties of HCHWA-D mutated Abeta may contribute to the early and often severe cerebrovascular pathology that is the hallmark of this disorder.

Alzheimer Disease↗
PubMed1996

Cataract extraction after silicone oil repair of retinal detachments due to necrotizing retinitis.

Cataract is common after silicone oil repair of retinal detachment due to necrotizing retinitis in acquired immunodeficiency syndrome. Surgical management has not been reported. Twenty-two eyes of 19 patients were reviewed. The majority underwent phacoemulsification with a posterior chamber convexoplano implant without iridotomy Complications included capsular fibrosis and hyphema. Unpredictable refractions in the first 16 eyes prompted refinement of lens calculations and resulted in a reduction in refractive errors. A 3-step modification of intraocular lens calculations is recommended: (1) use of specific sound velocities to calculate axial length; (2) use of convexoplano lenses; and (3) addition of a constant to the lens power to compensate for the refractive index of silicone oil. Good surgical technique and accurate lens calculations should improve management of cataracts that arise after retinal detachment repair with silicone oil in patients with acquired immunodeficiency syndrome.

AIDS-Related Opportunistic Infections↗
PubMed1996

Diagnostic role of cytology in screen-detected breast cancer.

Fine-needle aspiration cytology (FNAC) of the breast was performed in 491 patients over a 3-year period. Some 365 examinations (74.3 percent) were performed by palpation and the remaining 126 (25.7 percent) by stereotaxis. Ninety-six patients were excluded because of inadequate follow-up. Using a standard method of reporting the results 247 smears were classified as C1 and C2, but based on clinical and radiological criteria excision biopsy was recommended and performed in 122 patients with these lesions. Twenty-two per cent of C2 lesions were found to be malignant after histological examination. Forty-two patients with C3 or C4 cytology were advised to have excision biopsy and 41 had surgery. In all but one case the lesion was found to be malignant histologically. Definitive surgery was performed on 106 patients with C5 cytology and the diagnosis of malignancy was confirmed histologically in 105 of them. FNAC is a useful diagnostic tool in breast screening but in view of the number of false-negative results, cytology alone is unreliable and, therefore, full triple assessment is recommended.

Adenocarcinoma↗
PubMed1996

Erythropoietin therapy in neonates at risk of having bronchopulmonary dysplasia and requiring multiple transfusions.

OBJECTIVES: To determine whether treatment with recombinant human erythropoietin (r-HuEPO) reduces transfusion requirements in premature neonates at risk of having bronchopulmonary dysplasia and requiring multiple transfusions. STUDY DESIGN: A double-blind, randomized, controlled trial. SUBJECTS: Fifty-five infants appropriate in weight for gestational age (less than 1250 gm birth weight) who, at 10 days of age, were predicted to have a greater than 75% probability of having bronchopulmonary dysplasia. This criterion had previously been shown to identify infants requiring multiple transfusions. Twenty-seven infants were randomly assigned to receive r-HuEPO therapy and 28 to a control group. r-HuEPO was administered in a dosage of 20 U/kg body weight, subcutaneously, three times a week for 6 weeks. Control infants received sham treatment. RESULTS: Infants treated with r-HuEPO required significantly fewer transfusions than control infants during their entire hospital stay (mean 3.48 +/- 1.58 vs 5.68 +/- 2.30; p = 0.0001) and had a higher mean reticulocyte count (p < or = 0.0005) and a higher mean hemoglobin concentration (p < or = 0.005) during the treatment period. At follow-up, 4 months after term, there were no significant differences between the groups in mean reticulocyte count (p = 0.86) or mean hemoglobin concentration (p = 0.56). However, two infants in each group had low serum ferritin values indicative of depleted iron stores. CONCLUSIONS: Treatment with r-HuEPO effectively stimulated erythropoiesis in premature infants at high risk of having bronchopulmonary dysplasia and requiring multiple transfusions; the result was a reduction in transfusion requirements. This treatment, together with other strategies to reduce the need for transfusions, is appropriate in this population. Unrelated to r-HuEPO treatment, these infants may be at risk of having iron deficiency later in infancy.

Bronchopulmonary Dysplasia↗
PubMed1996

A vector for expressing foreign genes in the brains and hearts of transgenic mice.

An expression plasmid (MoPrP.Xho), for use in transgenic mice, was developed from the promoter, 5' intronic, and 3' untranslated sequences of the murine prion protein gene. Analyses of mice harboring the MoPrP.Xho construct with cDNA genes encoding the amyloid precursor protein (APP) and human presenilin 1 demonstrated that this vector provides relatively high levels of transgene-encoded polypeptides in brains and hearts of transgenic mice. The MoPrP.Xho vector should be very useful in strategies designed to overexpress a variety of wild-type and disease related mutant transgenes in the heart and brain.

Amyloid beta-Protein Precursor↗
PubMed1996

The cold sensitivity of a mutant of Saccharomyces cerevisiae lacking a mitochondrial heat shock protein 70 is suppressed by loss of mitochondrial DNA.

SSH1, a newly identified member of the heat shock protein (hsp70) multigene family of the budding yeast Saccharomyces cerevisiae, encodes a protein localized to the mitochondrial matrix. Deletion of the SSH1 gene results in extremely slow growth at 23 degrees C or 30 degrees C, but nearly wild-type growth at 37 degrees C. The matrix of the mitochondria contains another hsp70, Ssc1, which is essential for growth and required for translocation of proteins into mitochondria. Unlike SSC1 mutants, an SSH1 mutant showed no detectable defects in import of several proteins from the cytosol to the matrix compared to wild type. Increased expression of Ssc1 partially suppressed the cold-sensitive growth defect of the SSH1 mutant, suggesting that when present in increased amounts, Ssc1 can at least partially carry out the normal functions of Ssh1. Spontaneous suppressors of the cold-sensitive phenotype of an SSH1 null mutant were obtained at a high frequency at 23 degrees C, and were all found to be respiration deficient. 15 of 16 suppressors that were analyzed lacked mitochondrial DNA, while the 16th had reduced amounts. We suggest that Ssh1 is required for normal mitochondrial DNA replication, and that disruption of this process in ssh1 cells results in a defect in mitochondrial function at low temperatures.

Amino Acid Sequence↗
PubMed1996

Experimental Bacillus cereus post-traumatic endophthalmitis and treatment with ciprofloxacin.

BACKGROUND: Bacillus species remain an important cause of post-traumatic endophthalmitis, often causing permanent visual loss. METHODS: Twenty two rabbits were used to evaluate the clinical and histological findings of Bacillus cereus experimental post-traumatic endophthalmitis. Eyes that had received a scleral laceration and surgical repair were inoculated with Bacillus cereus. Thirty four other rabbits were used to evaluate the efficacy of intravitreal ciprofloxacin in treating experimental disease. RESULTS: Animals developed a post-traumatic endophthalmitis that closely mimicked human disease, characterised by a rapidly progressive and destructive endophthalmitis. Histological evaluation revealed retinal detachment, retinal necrosis, and the infiltration of inflammatory cells into the subretinal space. Intravitreal ciprofloxacin (100 micrograms) prevented the development of disease when given 1 hour and 6 hours after trauma and inoculation. CONCLUSIONS: Clinical and histological examination of experimental Bacillus cereus post-traumatic endophthalmitis suggests that retinal detachment and retinal necrosis play important roles in visual loss. Ciprofloxacin may be of benefit in the management of certain intraocular infections following penetrating injury.

Animals↗
PubMed1996

Highly purified CD34-positive cells reconstitute hematopoiesis.

PURPOSE: The objective of this study was to characterize CD34+ cell grafts, obtained using a novel technique, from children undergoing autologous bone marrow transplantation (BMT) for cancer therapy. In particular, we wanted to determine if the CD34+ marrow cell grafts generated hematopoietic reconstitution, since a positive result would motivate further development and use of this methodology. PATIENTS AND METHODS: This pilot feasibility clinical trial involved 13 patients < or = 25 years of age with advanced solid tumors, including seven children with neuroblastoma. Harvested bone marrow underwent immunomagnetic CD34+ selection. RESULTS: In three of 13 enrolled patients, low purities of the CD34+ preparations disqualified the use of the CD34+ marrow grafts. Ten patients received myeloablative chemotherapy with etoposide, carboplatin, and cyclophosphamide, then were transplanted with CD34+ marrow grafts. In the 10 patients transplanted with CD34(+)-selected cells, the CD34+ cell purity (nucleated RBCs excluded) in the cell graft preparation was 91% total cell recovery from the starting light-density cells 2.2%, CD34+ cell recovery 38%, colony-forming unit-granulocyte-macrophage (CFU-GM) recovery 23%, and estimated tumor-cell depletion 2.6 logs (medians). The CD34+ marrow grafts administered to these patients contained a median of 2.3 x 10(6) nucleated cells, 1.4 x 10(6) CD34+ cells, and 1.3 x 10(4) CFU-GM per kilogram patient weight. Most patients experienced only the toxicities previously observed with this myeloblative chemotherapy regimen, although two unusual toxicities were observed. All 10 patients transplanted with CD34+ cell grafts engrafted. CONCLUSION: The CD34+ purified grafts were enriched in stem/progenitor cells, with five of these 10 preparations containing > or = 94% CD34+ cells. Engraftment with CD34(+)-purified cell grafts as pure as 99% confirms that autologous CD34+ cells, alone, are sufficient to provide hematopoietic rescue for myeloablated patients. The best purification results were obtained on small marrow harvests from patients with neuroblastoma. The engraftment of highly purified CD34+ cells obtained by this technology and the antitumor effect of the transplant, by which two of 10 poor prognosis patients remain clinically free of tumor, have stimulated further clinical trials.

Adolescent↗
PubMed1996

New method for breast cancer detection using TC-99m sestamibi scintimammography.

The combination of breast examination and radiographic mammography (XRMM) are the established methods for breast cancer detection. However, XRMM lacks sensitivity and specificity in women with dense breasts, leading to false positive findings in 80% and false negative findings in 10% to 15% of the cases. Tc-99m Sestamibi (MIBI) scintimammography (SMM) is a new breast-imaging technique. This study shows that SMM has a positive predictive value of 83% and negative predictive value of 93%, which is similar to that reported by others. This supports other published reports that SMM is a potential excellent complimentary imaging technique to XRMM in improving the accuracy of breast cancer detection.

Adult↗
PubMed1995

Visual cortical mechanisms detecting focal orientation discontinuities.

Neurons in the primary visual cortex (V1) respond in well defined ways to stimuli within their classical receptive field, but these responses can be modified by stimuli overlying the surrounding area. For example patch-suppressed cells respond to gratings of a specific orientation within their classical receptive field, but the response diminishes if the grating is expanded to cover the surrounding area. We report here more complex effects in many such cells. When stimulated at their optimal orientation, introducing a surrounding field at a significantly different (for example, orthogonal) orientation enhanced their output by both a disinhibitory mechanism and an active facilitatory mechanism producing 'supra-optimal' responses. Importantly, some cells responded well if the orientations of centre and surround stimuli were swapped. The output reflected the discontinuity because neither stimulus component alone was effective. Under these stimulus conditions simultaneously recorded cells with orthogonally oriented receptive fields showed correlated firing consistent with neuronal binding to the configuration. We propose a mechanism integrating orientation-dependent information over adjacent areas of visual space to represent focal orientation discontinuities such as junctions or corners.

Animals↗
PubMed1995

A critical incident study of general practice trainees in their basic general practice term.

OBJECTIVE: To obtain information on the experiences of general practice (GP) trainees during their first general practice (GP) attachment. DESIGN: Critical incident technique--a qualitative analysis of open-ended interviews about incidents which describe competent or poor professional practice. SUBJECTS: Thirty-nine Western Australian doctors from the Royal Australian College of General Practitioners' (RACGP) Family Medicine Program who were completing their first six months of general practice in 1992. RESULTS: Doctors reported 180 critical incidents, of which just over 50% involved problems (and sometimes successes) with: difficult patients; paediatrics; the doctor-patient relationship; counselling skills; obstetrics and gynaecology; relationships with other health professionals and practice staff; and cardiovascular disorders. The major skills associated with both positive and negative critical incidents were: the interpersonal skills of rapport and listening; the diagnostic skills of thorough clinical assessment and the appropriate use of investigations; and the management skills of knowing when and how to obtain help from supervisors, hospitals and specialists. Doctors reported high levels of anxiety over difficult management decisions and feelings of guilt over missed diagnoses and inadequate management. CONCLUSION: The initial GP term is a crucial transition period in the development of the future general practitioner. An analysis of commonly recurring positive and negative critical incidents can be used by the RACGP Training Program to accelerate the learning process of doctors in vocational training and has implications for the planning of undergraduate curricula.

Adult↗