Search PubMed⌕ Search

Biomedical subjects

J Crawford

Publications and source records attributed to J Crawford.

At least 55 records · Page 3Linked to original sources
PubMed2000

Y-receptor-like genes GPR72 and GPR73: molecular cloning, genomic organisation and assignment to human chromosome 11q21.1 and 2p14 and mouse chromosome 9 and 6.

Two novel G-protein-coupled receptors, one from human, GPR72, and one from mouse, GPR73 have been isolated, sequenced and their genomic organisation determined. Non-isotopic in situ hybridisation and radiation hybrid mapping have identified GPR72 to be localised on human chromosome 11q21.1, and GPR73 on human chromosome 2p14. Interspecific mouse backcross mapping has localised the genes to mouse chromosomes 9 and 6, respectively. Northern analysis reveals GPR72 mRNA expression only in brain tissue. However, GPR73 mRNA can be found in heart, skeletal muscle and pancreas. Both receptors are closely related with 36 and 33% overall amino acid identity, respectively, to the Y-receptor family. However, although successful cell surface expression in a heterologous expression system can be achieved no specific binding to this ligand family can be detected, indicating that perhaps additional factors are required for binding.

Animals↗
PubMed2000

Fine-needle aspiration of a metaplastic breast carcinoma with extensive melanocytic differentiation: a case report.

Metaplastic carcinomas of the breast are uncommon breast tumors with aberrant cellular differentiation, most commonly showing ductal, squamous, and mesenchymal components. A breast carcinoma composed of both epithelial and melanocytic differentiation is rare, with only four previously reported cases in the literature. We present the fifth reported case, where the diagnosis was suggested by fine-needle aspiration (FNA) and later confirmed after the surgical specimen was excised. Histologically, this neoplasm revealed multidirectional differentiation, consisting primarily of squamous and melanocytic cell types, with focal glandular and osseous metaplasia. Based on the morphologic, immunohistochemical, and ultrastructural findings, we conclude that such tumors fall within the spectrum of metaplastic carcinomas of the breast. We believe that this case will further contribute to the understanding of this enigmatic tumor.

Antigens, Neoplasm↗
PubMed2000

A pilot trial assessing the efficacy of paroxetine hydrochloride (Paxil) in controlling hot flashes in breast cancer survivors.

BACKGROUND: Many breast cancer survivors suffer debilitating hot flashes. Estrogen, the drug of choice in perimenopausal women, is generally not recommenced to breast cancer survivors. Nonhormonal treatments are mostly disappointing. Anecdotal reports in our institution suggested that the selective serotonin-reuptake inhibitor, paroxetine hydrochloride, might be efficacious in alleviating hot flashes. PATIENTS AND METHODS: Thirty women with prior breast cancer who were suffering at least two hot flashes a day entered a single institution pilot trial to evaluate paroxetine's efficacy in reducing the frequency and severity of hot flashes. After completing daily diaries for one week on no therapy, the women received open-label paroxetine, 10 mg daily for one week, followed by four weeks of paroxetine, 20 mg daily. The women completed hot-flash daily diaries throughout the study period, and a health-related symptom-assessment questionnaire and a quality-of-life rating scale in the first and sixth week of the study. RESULTS: Twenty-seven women completed the six-week study period. The mean reduction of hot flash frequency was 67% (95% confidence interval (95% CI): 56%-79%). The mean reduction in hot flash severity score was 75% (95% CI: 66%-85%). There was a statistically significant improvement in depression, sleep, anxiety, and quality of life scores. Furthermore, 25 (83%) of the study participants chose to continue paroxetine therapy at the end of study. The most common adverse effect was somnolence, resulting in drug discontinuation in two women, and dose reduction in two women. One woman discontinued drug due to anxiety. CONCLUSIONS: Paroxetine hydrochloride is a promising new treatment for hot flashes in breast cancer survivors, and warrants further evaluation in a double-blind randomized placebo-controlled trial.

Adult↗
PubMed2000

A scale of optimism-scepticism in the context of HIV treatments.

The aim of this research was to develop a brief scale of gay men's optimism-scepticism in the context of new HIV treatments. Following comprehensive literature search and communication with other researchers, 34 items about viral load testing, HIV therapies and concern about HIV infection were generated. By way of anonymous, self-complete questionnaires, these items were put to 532 gay men recruited at the Sydney Gay and Lesbian Mardi Gras Fair Day in February 1999. Principal axes factor analysis and item refinement yielded an optimism-scepticism scale based on 12 items (range 12-48, with higher scores indicating greater optimism). The sample mean was 19.8 (SD = 4.7). The scale had high internal consistency reliability (Cronbach's alpha = 0.79). Providing preliminary evidence of validity, men who reported unprotected anal intercourse with a causal partner 'in the past six months' had a significantly higher mean score (21.3) than those who did not report this risk practice (19.5, p < 0.001). Similar validation was provided from separate samples of gay men in Queensland and Sydney. Our scale of optimism-scepticism in the context of new HIV therapies is a brief, reliable instrument which can be incorporated within broader questionnaires and interview schedules. It is a useful tool to monitor attitudes toward HIV therapies and possible associations with risk practices.

Adolescent↗
PubMed2000

Condom use and 'withdrawal': exploring gay men's practice of anal intercourse.

Some gay men who have unprotected anal intercourse avoid ejaculation-they practise 'withdrawal'. Using data collected in 1997 from a sample of Sydney gay men (n=625), we explored the relation between men's practice of ejaculation and their use of condoms. We also investigated whether men who had unprotected withdrawal but not unprotected ejaculation were more likely to think unprotected withdrawal was safe, liked condoms less, liked anal intercourse more, or were more sexually adventurous. Considering separately insertive and receptive anal intercourse with regular and with casual partners, we found that the majority of men who practised unprotected withdrawal also practised unprotected ejaculation. Of those whose only unprotected sex was withdrawal ('true withdrawers'), most never used condoms (they did not also have protected sex with ejaculation). True withdrawers were compared with men who had unprotected ejaculation, who always used condoms, who had no anal sex and who had no partners. Those who were true withdrawers with casual partners were more likely to believe withdrawal was safe; no group effects were found with regular partners. No significant differences in condom attitudes were found. True withdrawers with regular partners liked anal intercourse less than other men, but true withdrawers with casual partners were indistinguishable from those who had unprotected ejaculation. True withdrawers did not differ in sexual adventurousness from other men who had anal intercourse. Most withdrawers avoided anal sex with ejaculation rather than use condoms. Converting them into reliable condom users may be a considerable challenge for health promotion.

Adult↗
PubMed2000

Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. The TAX 320 Non-Small Cell Lung Cancer Study Group.

PURPOSE: To confirm the promising phase II results of docetaxel monotherapy, this phase III trial was conducted of chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) who had previously failed platinum-containing chemotherapy. PATIENTS AND METHODS: A total of 373 patients were randomized to receive either docetaxel 100 mg/m(2) (D100) or 75 mg/m(2) (D75) versus a control regimen of vinorelbine or ifosfamide (V/I). The three treatment groups were well-balanced for key patient characteristics. RESULTS: Overall response rates were 10.8% with D100 and 6.7% with D75, each significantly higher than the 0.8% response with V/I (P =.001 and P =.036, respectively). Patients who received docetaxel had a longer time to progression (P =.046, by log-rank test) and a greater progression-free survival at 26 weeks (P =.005, by chi(2) test). Although overall survival was not significantly different between the three groups, the 1-year survival was significantly greater with D75 than with the control treatment (32% v 19%; P =.025, by chi(2) test). Prior exposure to paclitaxel did not decrease the likelihood of response to docetaxel, nor did it impact survival. There was a trend toward greater efficacy in patients whose disease was platinum-resistant rather than platinum-refractory and in patients with performance status of 0 or 1 versus 2. Toxicity was greatest with D100, but the D75 arm was well-tolerated. CONCLUSION: This first randomized trial in this setting demonstrates that D75 every 3 weeks can offer clinically meaningful benefit to patients with advanced NSCLC whose disease has relapsed or progressed after platinum-based chemotherapy.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy.

PURPOSE: To explore the use of SD/01 (a polyethylene glycol-conjugated filgrastim shown in preclinical studies to have a prolonged half-life) in patients with chemotherapy-induced neutropenia. PATIENTS AND METHODS: Thirteen patients with non-small-cell lung cancer were randomized to receive daily filgrastim (5 microg/kg/d) or a single injection of SD/01 (30, 100, or 300 microg/kg) 2 weeks before chemotherapy and again 24 hours after administration of carboplatin and paclitaxel. Pharmacodynamic, pharmacokinetic, and safety analyses were performed. RESULTS: Peak serum concentrations of SD/01 and the duration of increased serum concentrations were dependent on the SD/01 dose. SD/01 concentrations remained increased longer in patients with chemotherapy-induced neutropenia. Prechemotherapy median absolute neutrophil counts (ANCs) in patients receiving SD/01 were increased in a dose-dependent fashion, with the duration of this effect also being dose dependent. After chemotherapy, median ANC nadirs were similar in the filgrastim cohort and the cohort receiving SD/01 30 microg/kg, with higher nadirs seen in the cohorts receiving SD/01 100 or 300 microg/kg. Dose-limiting toxicities were not noted. CD34(+) cells were mobilized in all cohorts. CONCLUSION: A single dose of SD/01 increases the serum concentration of SD/01 for several days in a dose-dependent fashion and is not associated with significant toxicity. The effects of SD/01 on ANC and CD34(+) cell mobilization are comparable or greater than those achieved with daily filgrastim. The self-regulation of this molecule provides a potential therapeutic advantage in a variety of clinical settings associated with neutropenia.

Aged↗
PubMed2000

Gene therapy for lung cancer.

Gene therapy is emerging as a promising modality for the treatment of lung cancer. Diverse strategies employing gene therapy for lung cancer have been investigated in vitro and in animal models, and a number of these approaches have met with promising results. Several phase I and II clinical trials have been undertaken, and early results suggest that it may be safe to administer gene therapy to lung cancer patients. It remains to be determined whether this modality will be efficacious as primary or adjunctive therapy in the setting of lung cancer.

Journal Article↗
PubMed1999

Molecular cloning and chromosomal mapping of the human homologue of MYB binding protein (P160) 1A (MYBBP1A) to 17p13.3.

We have previously isolated and characterized murine MYB binding protein (p160) 1a, a protein that specifically interacts with the leucine zipper motif within the negative regulatory domain of the c-Myb proto-oncoprotein. We now describe the molecular cloning of the human MYBBP1A cDNA and chromosomal localization to 17p13.3 by fluorescence in situ hybridization analysis. Given the likely presence of a tumor suppressor gene (or genes) within this region of chromosome 17, the position of MYBBP1A was further mapped by radiation hybrid analysis and was found to lie between markers D17S1828 and D17S938. A P1 artificial chromosome clone containing the 5' region of MYBBP1A was isolated and indicates a physical linkage between MYBBP1A and the 15-lipoxygenase gene (ALOX15). A novel, polymorphic (CA)(25) dinucleotide repeat was also isolated from this PAC and may serve as a useful marker for MYBBP1A and this region of chromosome 17.

Alleles↗
PubMed1999

HIV treatments optimism and sexual behaviour among gay men in Sydney and Melbourne.

OBJECTIVES: To investigate associations between gay men's optimism and sexual behaviour in the context of new HIV treatments. METHODS: Cross-sectional surveys (using anonymous, self-completed questionnaires) were conducted in Sydney during February 1998 (n = 2200) and in Melbourne during January 1998 (n = 1891). Gay men were recruited at social and sex-on-premises venues, clinics and fair days/carnivals. RESULTS: In a multivariate analysis, unprotected anal intercourse with casual partners (UAIC) was associated with being recruited at a sex-on-premises venue (rather than a clinic or fair day/carnival), HIV positivity, having been tested for HIV less than 6 months ago (rather than over 2 years ago or never having been tested), and not having a regular partner. Over and above these factors, UAIC was associated with agreement with the statements 'An HIV-positive person who is on combination therapy is unlikely to transmit HIV' and 'I'm less worried about HIV infection than I used to be'. CONCLUSIONS: The data reveal a significant relationship between UAIC and certain aspects of optimism in the context of new HIV treatments. Whereas the direction of causality cannot be specified, there is a clear need for HIV and sexual health education programmes to clarify issues of viral load, new and drug resistant strains of HIV, and other infectious agents.

Attitude↗
PubMed1999

Characterization of copine VII, a new member of the copine family, and its exclusion as a candidate in sporadic breast cancers with loss of heterozygosity at 16q24.3.

In a search for candidate tumor suppressor genes within a 650-kb common region of loss of heterozygosity (LOH) at 16q24.3 in breast cancer tissues, a 2.6-kb cDNA, named copine VII (CPNE7), was characterized. The gene is 2654 bp and codes for a 633-residue protein with high homology to the other members of the copine family, such as copine I, copine III, and N-copine. The predicted amino acid sequence contains two copies of a C2 domain in the N-terminus. Since these domains have been found in several membrane-binding proteins involved in different intracellular processes, copine VII was viewed as a potential tumor suppressor gene. Mutation analysis was carried out by single-strand conformation polymorphism analysis of 18 breast tumor tissue samples with ascertained LOH on chromosome 16q24.3. Since only two polymorphisms were identified, no evidence was found to indicate that copine VII is the tumor suppressor gene at 16q24.3 involved in breast cancer.

Amino Acid Sequence↗
PubMed1999

Baculovirus-derived hemagglutinin vaccines protect against lethal influenza infections by avian H5 and H7 subtypes.

Baculoviruses were engineered to express hemagglutinin (HA) genes of recent avian influenza (AI) isolates of the H5 and H7 subtypes. The proteins were expressed as either intact (H7) or slightly truncated versions (H5). In both cases purified HA proteins from insect cell cultures retained hemagglutination activity and formed rosettes in solution, indicating proper folding. Although immunogenic in this form, these proteins were more effective when administered subcutaneously in a water-in-oil emulsion. One or two-day-old specific pathogen free (SPF) White Rock chickens, free of maternal AI antibodies, responded with variable serum HI titers, but in some cases the titers were comparable to those achieved using whole virus preparations. Vaccination of three-week-old chickens with 1.0 microg of protein per bird generated a more consistent serum antibody response with an average geometric mean titer (GMT) of 121 (H5) and 293 (H7) at 21 days postvaccination. When challenged with highly pathogenic strains of the corresponding AI subtypes, the vaccinated birds were completely protected against lethal infection and in some cases exhibited reduced or no cloacal shedding at 3 days postinfection. Vaccine protocols employing these recombinant HA proteins will not elicit an immune response against internal AI proteins and thus will not interfere with epidemiological surveys of natural influenza infections in the field.

Amino Acid Sequence↗
PubMed1999

Cloning, characterization, and chromosomal location of a novel human K+-Cl- cotransporter.

Differential display polymerase chain reaction has been used to isolate genes regulated in vascular endothelial cells by the angiogenic factor vascular endothelial cell growth factor (VEGF). Analysis of one of the bands consistently up-regulated by VEGF led us to the identification of a cDNA from a human umbilical vein endothelial cell library that is 77% identical to the human K+-Cl- cotransporter1 (KCC1). We have referred to the predicted protein as K+-Cl- cotransporter 3 (KCC3). Hydrophobicity analysis of the KCC3 amino acid sequence showed an almost identical pattern to KCC1, suggesting 12 membrane-spanning segments, a large extracellular loop with potential N-glycosylation sites, and cytoplasmic N- and C-terminal regions. The KCC3 mRNA was highly expressed in brain, heart, skeletal muscle, and kidney, showing a distinct pattern and size from KCC1 and KCC2. The KCC3 mRNA level in endothelial cells increased on treatment with VEGF and decreased with the proinflammatory cytokine tumor necrosis factor alpha, whereas KCC1 mRNA levels remained unchanged. Stable overexpression of KCC3 cDNA in HEK293 cells produced a glycoprotein of approximately 150 kDa, which was reduced to 120 kDa by glycosidase digestion. An increased initial uptake rate of 86Rb was seen in clones with high KCC3 expression, which was dependent on extracellular Cl- but not Na+ and was inhibitable by the loop diuretic agent furosemide. The KCC3 genomic localization was shown to be 15q13 by fluorescence in situ hybridization. Radiation hybrid analysis placed KCC3 within an area associated with juvenile myoclonic epilepsy. These results suggest KCC3 is a new member of the KCC family that is under distinct regulation from KCC1.

Amino Acid Sequence↗
PubMed1999

The PISSLRE gene: structure, exon skipping, and exclusion as tumor suppressor in breast cancer.

In sporadic breast cancer, loss of heterozygosity (LOH) frequently occurs in three discrete regions of the long arm of chromosome 16q, the most telomeric of which is located at 16q24.3. Among the genes mapped to this region, PISSLRE is a plausible candidate tumor suppressor gene. It codes for a putative cyclin-dependent kinase that, as with other members of this family, is likely to be involved in regulating the cell cycle and therefore may have a role in oncogenesis. We characterized the genomic structure of PISSLRE and found that the splicing of this gene is complex. A variety of different transcripts were identified, including those due to cryptic splice sites, exon skipping, insertion of intronic sequences, and exon scrambling. The last phenomenon was observed in a rare PISSLRE transcript in which exons are joined at a nonconsensus splice site in an order different from that predicted by the genomic sequence. To screen the PISSLRE gene in breast tumors with ascertained LOH at 16q24.3, we have analyzed each exon by single-strand conformational polymorphism. No variation was found in the coding sequence, leading us to conclude that another tumor suppressor must be targeted by LOH in sporadic breast cancer.

Alternative Splicing↗
PubMed1999

GPR56, a novel secretin-like human G-protein-coupled receptor gene.

A novel gene product, GPR56, with homology to the seven transmembrane-domain receptor superfamily, has been cloned by PCR amplification using degenerate oligonucleotide primers and subsequent screening of a human heart cDNA library. The isolated 2.8-kb cDNA clone encodes a protein of 693 amino acids that shows highest identity (32%) to HE6, a member of a subclass of the class B secretin-like G-protein-coupled receptors. Northern analysis of various human tissues revealed a wide distribution of the transcript with highest levels found in thyroid gland, brain, and heart. In situ hybridization analysis of human thyroid gland as well as rat heart and brain tissue confirms these results and identifies the hippocampus and hypothalamic nuclei as brain areas with particularly high expression of GPR56 mRNA. The high level of mRNA expression, its wide distribution, and the mucin-like extracellular domain of the receptor protein suggest a possible role for this receptor in cell-cell interaction processes. The human gene for GPR56 has been isolated and its exon-intron structure determined. The total length of the human GPR56 gene is approximately 15 kb, and it consists of 13 exons. Fluorescence in situ hybridization, PCR analysis of somatic cell hybrids, and interspecific mouse backcross mapping have localized the genes to human chromosome 16q13 and mouse chromosome 8.

Amino Acid Sequence↗
PubMed1999

Retained stenting material: an unusual cause of dacryocystorhinostomy failure.

OBJECTIVE: To highlight a troubling cause of dacryocystorhinostomy (DCR) failure and to alert ophthalmologists to the potential problems that can result when stenting material is not removed and becomes retained after DCR. DESIGN: Consecutive noncomparative case series. PARTICIPANTS: Twelve patients who underwent revision DCR from February 1994 to January 1997. INTERVENTION: Endoscopic DCR, pre- and postoperative nasal endoscopy, preoperative computerized tomography (CT), and pre- and postoperative Jones testing. RESULTS: Fourteen revision endoscopic procedures were performed on 12 patients with recurrent epiphora following DCR. Failure was due to retained stenting material in six patients, a small bony rhinostomy in three patients, excessive scar formation within the rhinostomy in two patients, and improper location of the rhinostomy in one patient. Preoperative endoscopy and CT scan each correctly identified the retained sponge or tubing in four of six patients. CONCLUSIONS: Fastening a small sponge to Silastic tubing and positioning it within the DCR site in an attempt to retard DCR stenosis can be associated with a poor outcome and should be avoided. The nasal endoscope provided excellent visualization of pathology within the lacrimal sac and was a valuable tool. Retained stenting material should be considered in patients with persistent epiphora following DCR or intubation prior to any decision to commit a patient to permanent Jones tube placement.

Adult↗