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Biomedical subjects

J Pierce

Publications and source records attributed to J Pierce.

At least 37 records · Page 2Linked to original sources
PubMed1997

Meningitis due to Ochrobactrum anthropi: an emerging nosocomial pathogen. A report of 3 cases.

We describe 3 cases of Ochrobactrum anthropi meningitis following the implantation of pericardial allograft tissue to cover dural defects following craniotomy. Following an extensive epidemiologic investigation, the tissue allograft was found to have been contaminated with this unusual organism during the harvesting and processing of the tissue in the tissue bank. This organism was only susceptible to imipenem, tetracycline, gentamicin, and ciprofloxacin. The clinical presentation of these patients was subacute. Two of the patients developed osteomyelitis of the bone flap; while another developed a relapse of infection along a former ventriculoperitoneal shunt track 6 months after the initial infection. Appropriate clinical outcome was only observed after removal of tissue allograft implants, debridement of devitalized tissue and bone, removal of shunt devices, and prolonged courses of antibiotics. No deaths were observed.

Adolescent↗
PubMed1997

A new experimental model: the vascular pedicled cutaneous flap over the mid-dorsum of the rat.

The cutaneous vascular anatomy of the mid-dorsum in the rat and its role in flap design was studied in the rat. The investigation consisted of anatomic dissection, methylene blue injection into the axial artery, and flap harvesting in live animals. Dissection and injection revealed that the mid-dorsum of the rat derives its blood supply largely from the 10th intercostal artery, here referred to as the middle dorsal artery, which originates from the lateral aspect of the thoracic aorta. The cutaneous vascular territory of the middle dorsal artery was defined as follows: the medial border, midline of the dorsum; the lateral border, midaxillary line; the cephalic border, a line joining the medial and lateral borders midway between the level of the axilla proximally and 1 cm above the base of the rib cage distally; and the caudal border, a line drawn midway between the latter point proximally and the anterior superior iliac spine distally. Both unilateral and bilateral vascular pedicled island cutaneous flaps were harvested in living rats based on and exceeding the vascular territory delimited by methylene blue injection. Flaps limited to this territory with intact middle dorsal arteries showed total survival, while oversized flaps underwent partial necrosis peripherally. Because of its simplicity, reliability, and consistent vascularity, this flap has potential applications in the study of flap hemodynamics.

Animals↗
PubMed1996

The proto-oncogene product c-Crk associates with insulin receptor substrate-1 and 4PS. Modulation by insulin growth factor-I (IGF) and enhanced IGF-I signaling.

The Crk proto-oncogene product is an SH2 and SH3 domain-containing adaptor protein which we have previously shown to become rapidly tyrosine phosphorylated in response to stimulation with insulin-like growth factor I (IGF-I) in NIH-3T3 cells. In order to further characterize the role of Crk in the IGF-I signaling pathway, NIH-3T3 and 293 cells were stably transfected with an expression vector containing the Crk cDNA. The various resultant 3T3-Crk clones expressed Crk at approximately 2-15-fold higher levels than parental 3T3 cells. In 3T3-Crk cells, Crk immunoreactivity was detected in insulin receptor substrate-1 (IRS-1) immunoprecipitates. Stimulation with IGF-I resulted in a dissociation of Crk protein from IRS-1. In contrast, the association of the related adaptor protein Grb2 with IRS-1 was enhanced by IGF-I stimulation. Similar results were obtained in stably transfected 293-Crk cells, which express both IRS-1 and the IRS-1-related signaling protein 4PS. In these cells, IRS-1 and 4PS both associated with Crk, and this association was also decreased by IGF-I treatment, whereas the association of Grb2 with IRS-1 and 4PS was enhanced by IGF-I. Overexpression of Crk also enhanced IGF-I-induced mitogenesis of NIH-3T3 cells, as measured by [3H]thymidine incorporation. The levels of IGF-I-induced mitogenesis were proportional to the level of Crk expression. These results suggest that Crk is a positive effector of IGF-I signaling, and may mediate its effects via interaction with IRS-1 and/or 4PS.

3T3 Cells↗
PubMed1996

The mental health care reform debate: a content analysis of position papers.

Traditional and ethnographic content analyses of 23 position papers on mental health care reform issued during 1993 yield a comprehensive overview of the specific subjects and broad policy issues that were of concern at that time. Five concrete aspects of mental health service delivery systems and eight policy issues were identified as most important in position papers by service provider organizations and advocacy groups. These analyses identified overall similarities in the content of the position papers, although interesting differences among organizations emerged. The analyses also identified a measure of the quality of policy discussions that is derived from comparing the frequency of concrete references to aspects of mental health care with references to broader policy issues.

Bibliometrics↗
PubMed1996

Orthonasal and retronasal odorant identification based upon vapor phase input from common substances.

Subjects were trained to identify by assigned number common substances presented as vapor phase stimuli via an orthonasal or a retronasal route. Following training, odorant identification learning was evaluated by measuring ability to correctly identify to a criterion. Those who met the criterion were then tested first with the stimuli presented to the nares that differed in location from the nares used in training, and second to the nares that corresponded in location to the nares used in training. It was found that, under conditions of natural retronasal breathing, orthonasally trained subjects made correct identifications on approximately 80% of the trials upon retronasal testing, but for the following orthonasal testing identifications were significantly more frequent, approaching 100% correct. After subsequent retronasal training, the same subjects' orthonasal identifications remained significantly higher, although identifications improved to approximately 92% correct on retronasal trials. Other subjects were instructed in a breathing technique designed to enhance retronasal stimulation. After orthonasal training, retronasal testing of these subjects still gave significantly fewer correct identifications than orthonasal testing, notwithstanding the modified retronasal breathing, but after subsequent retronasal training correct identifications by these subjects no longer differed significantly between orthonasal and retronasal testing. Efficacy of modified retronasal breathing was confirmed in two subsequent experiments. The observed substantial positive transfers between retronasal and orthonasal odorant identification training and testing loci demonstrate that these odorant pathways do not subserve completely independent olfactory systems, while the less accurate identifications via the retronasal route, unless instruction in retronasal breathing was given, suggest a difference in the efficiency with which odorants are normally delivered to the olfactory mucosa.

Adolescent↗
PubMed1995

Only late, nonmitotic stages of granulocyte differentiation in 32Dcl3 cells are blocked by ectopic expression of murine c-myb and its truncated forms.

In murine leukemia virus-induced myeloid leukemias, insertional mutagenesis of the c-myb locus has been shown to occur frequently. Proto-oncogene activation is achieved in most leukemias by integration of murine leukemia virus upstream of exons 3 or 4 or by integration into exon 9 with consequent truncation of the protein. The present study investigates the effect of ectopic expression of full-length c-myb or c-myb containing amino- or carboxyl-terminal truncations (minus 47 and 248 amino acids, respectively) on granulocyte differentiation in vitro. Recombinant myb retroviruses were used to infect an interleukin 3-dependent progenitor cell line, 32Dcl3, which undergoes terminal differentiation to mature neutrophilic granulocytes in the presence of granulocyte colony-stimulating factor. Overexpression of c-myb did not abrogate the interleukin 3 dependency of the parental cell line. However, cells expressing all forms of c-myb were blocked at an intermediate stage of granulocyte differentiation and continued to proliferate in the presence of granulocyte colony-stimulating factor. After 14 days in medium with granulocyte colony-stimulating factor, myb-expressing cultures predominantly consisted of promyelocytes with some myelocytes and almost undetectable numbers of neutrophilic granulocytes. This suggested that early stages of granulocyte differentiation were not inhibited, a finding that was further supported by the induction of myeloperoxidase, a biochemical marker of promyelocytes. Interestingly, the expression of lactoferrin, known to be a marker of late stages of granulocyte differentiation, was completely inhibited in the cells infected with myb viruses. It was concluded that c-myb expression blocked granulocyte differentiation to the terminal mitotic stages and that deletion of the NH2-terminal 47 amino acids and/or the COOH-terminal 248 amino acids of c-myb neither enhanced nor diminished this effect.

Animals↗
PubMed1994

Crystal structure of scytalone dehydratase--a disease determinant of the rice pathogen, Magnaporthe grisea.

BACKGROUND: Rice blast is caused by the pathogenic fungus,-Magnaporthe grisea. Non-pathogenic mutants have been identified that lack enzymes in the biosynthetic pathway of dihydroxynapthalene-derived melanin. These enzymes are therefore prime targets for fungicides designed to control rice blast disease. One of the enzymes identified by genetic analysis as a disease determinant is scytalone dehydratase. RESULTS: The three-dimensional structure of scytalone dehydratase in complex with a competitive inhibitor has been determined at 2.9 A resolution. A novel fold, a cone-shaped alpha + beta barrel, is adopted by the monomer in this trimeric protein, burying the hydrophobic active site in its interior. The interactions of the inhibitor with the protein side chains have been identified. The similarity of the inhibitor to the substrate and the side chains involved in binding afford some insights into possible catalytic mechanisms. CONCLUSIONS: These results provide a first look into the structure and catalytic residues of a non-metal dehydratase, a large class of hitherto structurally uncharacterized enzymes. It is envisaged that a detailed structural description of scytalone dehydratase will assist in the design of new inhibitors for controlling rice blast disease.

Ascomycota↗
PubMed1994

Activation of the Axl receptor tyrosine kinase induces mitogenesis and transformation in 32D cells.

axl is a transforming receptor tyrosine kinase isolated from DNA of patients with chronic myelogenous leukemia. Association of axl expression with myelogenous leukemias and its expression in primitive hematopoietic cells suggests a role for axl in myeloid biology. To study the cellular function of axl, we constructed a chimeric receptor tyrosine kinase composed of the extracellular and transmembrane domains of the EGF receptor and the cytoplasmic domain of axl; this chimera was named EAK for EGFR-Axl-Kinase. The EAK chimeric receptor was expressed in the mouse myeloid progenitor cell line 32D, which is dependent on interleukin 3 (IL-3) for proliferation and survival. Treatment of the 32D-EAK cells with EGF stimulated the tyrosine phosphorylation of the axl kinase domain and enabled proliferation through EGF rather than IL-3. Thus, axl can effectively couple with mitogenic signaling pathways intrinsic to 32D myeloid cells. Assay of proteins phosphorylated in response to different cytokine treatments showed that IL-3 and EGF exposure produced unique profiles in the 32D-EAK cells. Furthermore, Jak-2 is phosphorylated only in response to IL-3 treatment in these cells. This suggests that IL-3 receptor and axl transduce mitogenic signals through separate pathways. In addition, exposure of cells expressing the chimeric receptor to EGF for 19 days converted the cells to factor-independent growth, a phenomenon not seen with other receptor tyrosine kinases. Generation of this transformed phenotype is absolutely dependent on axl activation by foster ligand. The tyrosine phosphorylation level of the axl kinase domain in the factor-independent subclones is 40-fold greater than the factor-dependent cells. The association of a unique axl phosphorylation level with the factor-independent phenotype suggests that there is a threshold phosphorylation level of the axl kinase for transformation. The fact that activation of the axl receptor leads to transformation of 32D cells suggests that axl can play a role in leukemic conversion of myeloid cells, either through inappropriate expression or improper activation.

Animals↗
PubMed1993

Preliminary crystallographic studies on scytalone dehydratase from Magnaporthe grisea.

Magnaporthe grisea are pathogenic, directly penetrating fungi which cause rice blast disease. Isolated, non-pathogenic mutant strains which are defective in the biosynthesis of dihydroxynapthalene-derived melanin fail to infect host plants and have been shown to lack certain key enzymes in melanin biosynthesis. One such enzyme is scytalone dehydratase that converts scytalone to 1,3,8-trihydroxy-naphthalene. Crystallization trials of scytalone dehydratase were undertaken with the expectation that structural information on this enzyme would facilitate design of high affinity inhibitors which might find use in the control of rice blast disease. We now report that recombinant scytalone dehydratase, complexed with a tight binding inhibitor, has been crystallized with PEG 4000 as a precipitant. The crystals are trigonal and belong to the space group P321 with the cell dimension: a = b = 75.5 A, c = 73.8 A. The observed diffraction extends to 2.5 A. Analysis of the packing in the cell suggests that scytalone dehydratase forms a symmetric trimer. These results are consistent with sedimentation equilibrium experiments indicating that the solution aggregation state of scytalone dehydratase was trimeric over a 24,000-fold concentration range.

Ascomycota↗
PubMed1993

Lower levels of cigarette consumption found in smoke-free workplaces in California.

OBJECTIVE: We examined the relationship between workplace smoking policies and smoking prevalence and cigarette consumption. METHODS: California residents were questioned by telephone with the 1990 California Tobacco Survey. All respondents (11,704) above age 18 years who were employed indoors were used. Respondents were asked about smoking status, workplace smoking policy, desire to quit, and smoking history. Logistic regression was used to determine the relationship of workplace smoking policy to smoking status, accounting for demographic variables. RESULTS: Prevalence of regular smokers was significantly lower in smoke-free workplaces than in those with no restrictions (13.7% vs 20.6%, P < .001). Continuing regular smokers in smoke-free workplaces smoked fewer cigarettes than those in workplaces with no restrictions (296 vs 341 packs per year, P < .001). More comprehensive smoking policies were associated with smokers more likely to contemplate quitting (P = .014). CONCLUSIONS: Employees in smoke-free workplaces have a lower smoking prevalence and, among continuing smokers, lower cigarette consumption than individuals working where smoking is permitted. We estimate cigarette consumption among employees indoors is 21% below that if there were no smoking restrictions in California workplaces. Furthermore, if all California workplaces were smoke-free, cigarette consumption among employees would be 41% below that if there were no workplace smoking restrictions, approximately a $406 million annual loss in sales to the tobacco industry. This study supports the hypothesis that smoke-free workplace policies are an effective public health measure for decreasing smoking prevalence and cigarette consumption among continuing smokers.

Adolescent↗
PubMed1993

Genetic diversity from a limited repertoire of mutations on different common allelic backgrounds: alpha 1-antitrypsin deficiency variant Pduarte.

alpha 1-Antitrypsin (alpha 1AT) is one of the most polymorphic gene loci in the human genome. alpha 1AT variants are typically identified by their migration position in an isoelectric focusing gel at pH 4-5. Heterogeneity of the isoelectric point of alpha 1AT variants, hence variant migration, most often results from amino acid substitutions which alter the net charge of the molecule. We identified an individual heterozygous for an alpha 1AT variant migrating in the "P" variant region which differs from other known "P" variants. Using isoelectric focusing on an immobilized pH gradient at pH 4.50-4.85 the novel P allele, Pduarte, migrates between Pst. albans and Plowell. Densitometric analysis of normal "M" type alpha 1AT and the deficiency variant Plowell major bands separated by isoelectric focusing demonstrates that Pduarte contributes approximately 41% as much alpha 1AT to the total serum alpha 1AT concentration as the normal "M" alpha 1AT, similar to Plowell. Direct DNA sequencing of the proband's genomic DNA demonstrates that the Pduarte allele differs from the normal M1 (V213) allele by two amino acid substitutions, R101 (CGT)-->H(CAT) and D256 (GAT)-->V(GTT). Individually, these amino acid substitutions characterize the normal M4 allele (R101-->H) and the deficient Plowell allele (D256-->V). Thus the Pduarte allele differs from the Plowell allele only by the normal allelic background in which the V256 mutation occurs. Comparison of amino acid sequences among several alpha 1AT variants demonstrates that Pduarte is an example of a more general observation regarding diversity within the PI (protease inhibitor) system.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Stressors experienced by relatives of patients in an innovative rehabilitation program.

The social work component of this study was conducted for ethical reasons to monitor the impact on relatives of providing therapy to severely brain-injured patients on an innovative rehabilitation treatment program in an acute care hospital. The authors identify stressors experienced by the family caregivers. Findings are based on 450 interviews conducted by three research social workers during the 18-month study period with 78 family caregivers of the 37 patients. The results indicate that involvement in providing treatment was stressful, because of both the demands on the family and the unproven efficacy of the treatment. The authors recommend that a family's ability to provide treatment be clearly assessed before recruitment and that relatives' stress be monitored during their involvement. The findings emphasize the important role social workers can perform in identifying and monitoring such stress.

Brain Injuries↗
PubMed1993

Restoration of spermatogenesis by follicle-stimulating hormone despite low intratesticular testosterone in photoinhibited hypogonadotropic Djungarian hamsters (Phodopus sungorus).

By exposing male Djungarian hamsters to short-day photoperiods, a hypogonadotropic condition resembling that of hypophysectomized animals can be achieved without resorting to surgery. By use of this animal model, differential effects of gonadotropins on spermatogenesis have been studied revealing that FSH selectively restimulates spermatogenesis up to the level of spermatids. In the present study, we investigated whether FSH (6 IU/day) also restores fertility in hamsters exposed to short-day photoperiods (8L:16D). Animals kept under long-day photoperiod (16L:8D) served as controls. After 8 wk under 8L:16D, gonads were involuted and the animals (n = 9-10 per group) were treated with FSH, or testosterone implants, or both for the following 33 days. An additional group received FSH for 33 days and, for the last 12 days only, FSH plus testosterone to induce copulatory and ejaculatory behavior. The implants caused no increase in intratesticular testosterone as compared to that in short-day controls. All males were paired with adult females for the last 5 days of treatment, and killed thereafter. Litter sizes were determined 22 days later. The examination of the testes by flow-cytometrical techniques revealed qualitatively normal spermatogenesis in animals receiving FSH, whereas testosterone caused an insignificant increase to a few round spermatids. In most FSH-treated animals, sperm were present in the epididymides. In hamsters receiving FSH along with testosterone, treatment resulted in restoration of full fertility as compared to long-day controls. Fertility was also restored in animals receiving testosterone only for the last 12 days of FSH treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗