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Biomedical subjects

J Bell

Publications and source records attributed to J Bell.

At least 163 records · Page 9Linked to original sources
PubMed1996

High-dose hydroxyurea and G-CSF to collect Philadelphia-negative cells in chronic myeloid leukemia: preliminary results.

Five patients with Ph+ chronic myeloid leukemia and no detectable diploid cells in the marrow received 6 g hydroxyurea twice daily for 7 days followed by G-CSF to harvest Ph-cells 1-84 months after diagnosis. Three were in first chronic phase, and two in accelerated phase. One stopped hydroxyurea after 4 doses due to intractable vomiting and was not apheresed, while two stopped hydroxyurea after 9 and 11 doses because of mucositis and skin rash. Two tolerated all doses; one with no significant side effects, and one with mucositis and painful plantar rash. The nadir leukocyte, neutrophil, and platelet counts were 0.4-0.8, 0-0.1, and 2-19 x 10(9)/L respectively. Apheresis was commenced when the leukocytes were 1.2-3.8 x 10(9)/L 9-10 days after starting G-CSF, and 6 aphereses were performed. Four collections were 100% Ph+, and two 22% and 90% Ph-. The total nucleated cell, CD34+/CD34-subset, CD34+/CD33+ subset, and CFU-GM yields per kg per collection were 0.48-2.38 (median 1.18) x 10(8), 0-0.48 (median 0.012) x 10(6), 0.028-10.19 (median 0.92) x 10(6), and 0.29-41.81 (median 21.78) x 10(4) respectively. We conclude that hydroxyurea in the dose we used is poorly tolerated, and is associated with significant adverse effects including severe myelosuppression. It is possible to harvest diploid cells during recovery, but achievement of Ph-negativity appears to be erratic and cell yields are poor.

Adult↗
PubMed1995

Bladder tumours following chemotherapy and radiotherapy for ovarian cancer: a case-control study.

A collaborative group of cancer registries and hospitals carried out a case-control study of tumours of the bladder in women who had previously been treated for ovarian cancer. A total of 63 cases of bladder tumours were identified, and 188 controls were selected matching for age, year of ovarian cancer diagnosis and survival time. Full details of the treatment for ovarian cancer were sought for both cases and for controls. The risk of bladder tumours was increased for patients who had been treated by radiotherapy alone (1.9; 95% confidence interval, 0.77-4.9), by chemotherapy alone (3.2; 0.97-10), and by chemotherapy and radiotherapy (5.2; 1.6-16), when comparison was made with patients treated only by surgery. Patients treated by chemotherapy were separated into 2 groups according to whether they had received cyclophosphamide. Among those who had, there was a clear increase in risk (approximately 4-fold) regardless of whether or not they had also received radiotherapy. For those who received only other drugs, risk was increased substantially among patients who had also been treated by radiation, as compared with patients treated by surgery alone, and those who had received radiotherapy only. Both melphalan and thiotepa were implicated as potential bladder carcinogens on the basis of these results. The estimated risk of bladder tumours due to cyclophosphamide was more than twice the risk following radiation to the bladder, and it appeared substantially earlier. For both agents, the risk continued to increase more than 10 years after treatment began.

Aged↗
PubMed1995

The irreversible inactivation of two copper-dependent monooxygenases by sulfite: peptidylglycine alpha-amidating enzyme and dopamine beta-monooxygenase.

Peptidylglycine alpha-amidating enzyme (alpha-AE) and dopamine beta-monooxygenase (D beta M), two copper-dependent monooxygenases that have catalytic and structural similarities, are irreversibly inactivated by sodium sulfite in a time- and concentration-dependent manner. Studies with alpha-AE show that the sulfite-mediated inactivation is dependent on the presence of redox active transition metals free in solution, with Cu(II) being the most effective in supporting the inactivation reaction. Sulfite inactivation of alpha-AE is specific for the monooxygenase reaction of this bifunctional enzyme and amidated peptides provide protection against the inactivation. Consequently, the sulfite-mediated inactivation of alpha-AE and D beta M most likely results from the transition metal-catalyzed oxidation of sulfite to the sulfite radical, SO3-.

Amino Acid Sequence↗
PubMed1995

Creutzfeldt-Jakob disease after liver transplantation.

We report a 57-year-old woman who died from Creutzfeldt-Jakob disease 2 years after a liver transplantation. The liver donor had no history of neurological disease. In one albumin donor, possible Creutzfeldt-Jakob disease developed 3 years later. The patient initially had cerebellar symptoms. Neuropathology included "Kuru-type" plaques and prion protein (PrP) deposits involving the cerebellum predominantly. The patient was homozygote valine at codon 129 of the PrP gene while the liver was homozygote methionine. This observation raises the possibility of transmission of Creutzfeldt-Jakob disease by the graft itself or the associated albumin transfusions and, on a wider extent, by nonneural tissue.

Creutzfeldt-Jakob Syndrome↗
PubMed1995

Purification and characterization of endogenous peptides extracted from HLA-DR isolated from the spleen of a patient with rheumatoid arthritis.

We have purified HLA-DR from the spleen of a patient with rheumatoid arthritis. The patient had Felty's syndrome and was heterozygous for the DR4Dw4 antigen. We have isolated endogenous peptides from purified HLA-DR molecules. The peptides were purified by reverse phase HPLC and the major peaks were subjected to N-terminal sequencing. The peptides were derived from a variety of proteins: human serum albumin, human erythroid protein 4.1, 60S ribosomal proteins L31 and L35, VCAM-1, human immunoglobulin lambda chain and cathepsin-S. A peptide corresponding to the sequence of human serum albumin (HSA) residues 106-120 was synthesized and shown to bind to HLA-DR4Dw4 (IC50 = 1.41 microM). We have confirmed and refined current ideas about the structural motif for the binding of peptides to HLA-DR and HLA-DR4Dw4.

Amino Acid Sequence↗
PubMed1995

A new immunohistochemical antibody for the assessment of estrogen receptor status on routine formalin-fixed tissue samples.

We describe a method for the immunocytochemical assessment of estrogen receptor (ER) status on routinely processed, formalin-fixed tissue using a recently developed commercially available monoclonal antibody (Dako 1D5) with a microwave antigen retrieval technique. A series of 90 cases of human breast carcinoma was analyzed and the staining was assessed using a semiquantitative microscopic scoring method and by assessment of the percentage of nuclei showing positive staining. The results were compared with assessment using another commercially available antibody (Abbott H222) and with clinical response to tamoxifen therapy. Direct comparison of the paired sets of H scores and the percentage of positively stained nuclei using the two different techniques showed a significant correlation. By assigning an arbitrary cut-off for positivity of H score = 50, assessment of ER status using DAKO 1D5 antibody was found to correlate with response to tamoxifen therapy with a sensitivity of 90% and a specificity of 51%, similar to values in previous studies using other methods. We conclude that assessment of ER status using this new antibody and technique gives accurate results on routinely processed, formalin-fixed tissue and may be used as an alternative to other methods.

Adult↗
PubMed1995

Serotonergic sprouting into transplanted C-6 gliomas is blocked by S-100 beta antisense gene.

S-100 beta, a calcium binding protein produced by astrocytes, has been proposed to be a neuronotropic agent. In order to test the tropic effects of S-100 beta in vivo, the technique of cell transplantation was used. C6 glioma cells and C6 cells containing a S-100 beta antisense gene (C6AS) were transplanted into contralateral hippocampi. 5-HT immunoreactive, varicose fibers with a normal appearance penetrated into the glioma mass and were seen in high density around the C6 cell mass. However, 5-HT fibers with enlarged, abnormal varicosities were seen bordering C6AS tissue and were very rarely observed within the C6AS cell mass. Extracellular S-100 beta from normal C6 cells may function as a growth factor on sprouting serotonergic fibers.

Animals↗
PubMed1995

Investigating the influence of treatment philosophy on outcome of methadone maintenance.

This study is based on a 'natural experiment' in which a cohort of heroin users was assessed at one unit, then referred on geographic grounds for treatment to one of two clinics--one orientated to long-term maintenance (Clinic 2, with 61 subjects), the other to time-limited treatment aimed at achieving abstinence from all drugs including methadone (Clinic 1, 141 subjects). The outcome measure was heroin use as measured by urine testing performed regularly at both clinics. Overall, 25% of urine tests from Clinic 1 were positive for heroin compared to 18% in Clinic 2. This difference reflected in part a high rate of heroin use during the period of mandatory withdrawal from treatment in clinic 1. Statistical models were developed to identify factors associated with heroin use. There was a strong association between methadone dose and heroin use; relative to a daily dose of 40 mg, a dose of 80 mg/day of methadone was less likely to be associated with a heroin-positive urine (OR 0.55, 95% CI [0.45, 0.68]). Average doses prescribed in Clinic 1 were lower, reflecting the clinic's orientation to abstinence. Adjusting for dose, and for the fact that certain individuals tend to use heroin heavily while others do not, there was no difference between the clinics in risk of heroin use during maintenance treatment. The higher rates of heroin use in the abstinence-orientated clinic were attributable to time-limited treatment and the use of lower doses of methadone. This finding confirms that in investigating the effects of treatment factors, the powerful influence of methadone dose needs to be taken into account.

Adult↗
PubMed1995

Measuring heroin use in methadone maintenance programmes.

This study compares a number of self-reported measures of drug use with the results of urine testing in a group of patients receiving methadone maintenance treatment. One hundred and twenty-nine subjects were interviewed and 4-5 months later, a second interview was obtained from 87 of these. At each interview subjects were asked about drug use on each of the preceding 7 days and also about the number of days of drug use in the previous month. It was found that most patients were continuing to use heroin, usually fairly infrequently. Direct comparisons of urine test results and self-reported drug use indicate substantial positive correlations. However, there was a tendency for self-report to underestimate drug use in this patient sample. It appears that urine testing is the single most useful measure of drug use. This supports the notion that it is a valid tool in evaluation research. However, the combination of self-report and urine tests provides more information about drug use than any single measure.

Journal Article↗
PubMed1995

Primary angiosarcoma of the spleen: a case report and review of the literature.

We describe a 47-year-old man with shoulder pain, multiple bony lesions, and a 1-cm lesion in the spleen. T-1 facetectomy revealed a poorly differentiated malignant neoplasm. Several months after chemotherapy, multiple splenic lesions were found by computed tomography and liver-spleen scan. A splenectomy showed a malignant spindle-cell neoplasm forming irregular vascular spaces. Tumor cells were positive for factor VIII-related antigen and vimentin. This patient died of extensive metastases from this primary angiosarcoma of the spleen. Splenic angiosarcoma is a rare neoplasm that often has a cryptic presentation and a dismal prognosis.

Hemangiosarcoma↗
PubMed1995

Comparison of propofol and fentanyl anaesthesia in coronary artery versus valve surgery.

Total intravenous anaesthesia with propofol and fentanyl was used in 23 patients undergoing coronary artery and 16 patients undergoing valve surgery and the haemodynamic effects in the two groups were compared. Baseline values showed that the valve surgery group had a higher mean heart rate, pulmonary artery wedge pressure and pulmonary artery pressure and smaller mean stroke volume than the coronary artery surgery group. In both groups, heart rate, arterial pressure, pulmonary artery wedge pressure, pulmonary artery pressure and cardiac index decreased during surgery. In the valve surgery group there were greater percentage decreases in heart rate, mean arterial pressure and diastolic arterial pressure. Overall, propofol and moderate-dose fentanyl anaesthesia was no more detrimental to the haemodynamics in patients undergoing valve surgery when compared to those undergoing coronary artery surgery.

Aged↗
PubMed1995

Association between HLA DQB1 * 03 and cervical intra-epithelial neoplasia.

BACKGROUND: Cervical intraepithelial neoplasia (CIN) and cervical cancer have been shown to be strongly associated with infection by human papillomavirus (HPV). However, other factors may be contributory in the progression from normal epithelium to CIN and cervical cancer, since not all women with HPV infection develop disease. Recently, it was demonstrated that there is a high risk for cervical cancer and CIN in women with HLA DQB1 * 03 (RR = 7.1, p < 0.0009) (1). Subsequent reports have been conflicting, due to sample size, genetic heterogeneity and differences in the techniques employed for the detection of HLA DQB1 * 03. MATERIALS AND METHODS: DNA from cervical smears of 178 women with CIN and 420 controls with normal cervical cytology was analyzed by polymerase chain reaction (PCR) with type-specific primers for HPV 16, 18, 31, and 33. The DNA from test and control samples were also analyzed by a novel PCR technique, which mutates the first base of codon 40 (DQ alleles) from T to G to create an artificial restriction site for an enzyme Mlu I that distinguish DQB1 * 03 from other alleles and are confirmed by digestion of amplified DNA with Mlu I. Further analysis of individual DQB1 * 03 alleles was performed using PCR and allele-specific primers. RESULTS: One hundred forty-four (34%) out of 420 controls (all HPV 16, 18, 31, or 33 negative and normal cytology), 37/66 (56%) of CIN I and 72/112 (64%) of CIN III were positive for DQB1 * 03 (trend test, p < 0.001, chi 2 = 37.3). A significant association was observed between DQB1 * 03 and CIN (odds ratio 3.03; 95% CI 2.11-3.45). Of women with CIN, 131/178 (73.5%) had HPV (types 16, 18, 31, or 33) infection. There was a significant association between DQB1 * 03 and presence of HPV (odds ratio 3.43; 95% CI 2.25-5.10). Homozygosity for DQB1 * 03 was more strongly associated with CIN than heterozygosity (odds ratios 4.0 and 2.63, respectively); and for the presence of HPV (odds ratio 4.47; 95% CI 2.58-7.77). HLA DQB1 * 0301 was the most strongly associated allele with CIN and HPV (odds ratios 2.53 and 2.63, respectively). CONCLUSIONS: HLA DQB1 * 03 is associated significantly with CIN and may be permissive for HPV infection. Further analysis of class II HLA typing in CIN is necessary to evaluate this association.

Base Sequence↗