Biomedical subjects

J G Scott

Publications and source records attributed to J G Scott.

At least 55 records · Page 3Linked to original sources

PubMed1996

The medical and epidemiologic effects on workers of the levels of airborne Thermoactinomyces Spp. spores present in Australian raw sugar mills.

The objectives of the study were to determine whether there was a significant risk of members of the work force of raw sugar mills developing bagassosis. Airborne Thermoactinomyces sacchari spores were measured to determine whether they were sufficient to cause acute bagassosis, and whether there was any evidence of previous exposure to sufficient airborne T. sacchari spores to cause the development of chronic bagassosis in any of the work force. Monitoring of total airborne bacteria spore concentrations was undertaken in and around two cane sugar mills before, during, and after the 1992 cane processing season. Viable airborne bacteria counts were also obtained to confirm the presence of Thermoactinomyces sacchari. Area or zone samples at various sites around the mills and personal breathing zone samples from selected workers were obtained. The results showed that the total airborne bacteria spore count was lower than similar counts reported in other industries, such as cotton milling and wood chip handling, during normal operations. It was also found that the airborne counts during specific activities that generated higher than usual airborne spore levels were lower than expected from literature reports of handling similar material. Complementary medical examination of the entire full-time work forces of the two mills was carried out on a number of occasions during 1992. The medical data showed that no cases of acute bagassosis were detected, and that there was no evidence of the development of chronic bagassosis in any members of the work forces of either mill. Therefore, there is no significant risk of workers in the Australian sugar industry developing bagassosis.

Air Microbiology↗

PubMed1995

Allele-specific PCR reveals that CYP6D1 is on chromosome 1 in the house fly, Musca domestica.

A cytochrome P450, termed P450lpr, is the major P450 responsible for pyrethroid resistance in the Learn-PyR (LPR) strain of house fly. Recently, the putative gene (CYP6D1) coding for P450lpr has been sequenced from the LPR and aabys strains of house fly. Allele-specific polymerase chain reaction (ASPCR) was used for linkage group analysis with backcross progeny from the wild type LPR strain and a multiple marker strain (aabys). We found that CYP6D1 is linked to chromosome 1. The possible role of regulatory or modifying genes responsible for elevated P450lpr expression is discussed in relation to the chromosomal linkage of CYP6D1.

Alleles↗

PubMed1995

cDNA and deduced protein sequence of CYP6D1: the putative gene for a cytochrome P450 responsible for pyrethroid resistance in house fly.

A microsomal cytochrome P450 from the house fly (Musca domestica), termed P450lpr, is involved in P450 monooxygenase-mediated pyrethroid resistance and is expressed at 8-fold higher levels in the insecticide resistant LPR strain compared to a susceptible strain. An internal cDNA sequence was amplified by polymerase chain reaction (PCR) using degenerate primers based on known P450lpr polypeptide sequences, and the remainder of the sequence was amplified by single side-specific PCR. A 1.8 kb cDNA sequence was obtained from 3 overlapping PCR products, with an open reading frame encoding a P450 protein of 516 residues (M(r) 59,182). This gene has been designated CYP6D1 within the P450 gene superfamily. CYP6D1 exhibits most similarity (28.2-29.8% positional identity) to butterfly CYP6B1, house fly CYP6A1 and Drosophila CYP6A2, and also exhibits comparable similarity (24.7% identity) to rat CYP3A1. The deduced protein sequence contains a hydrophobic N-terminal region and conserved sequences thought to be involved in heme-binding and electron donor-protein interactions. Comparison of CYP6D1 with its four most similar proteins (CYP6B1, CYP6A1, CYP6A2 and CYP3A1) reveals the presence of extensive stretches of residues in an alignment row in 2 possible substrate-binding regions. Three introns of 74, 66 and 64 bp, having 5'-GT and AG-3' ends, split the CYP6D1 coding region in genomic DNA. Results indicate that CYP6D1 is likely the P450lpr gene.

Amino Acid Sequence↗

PubMed1995

Molecular mechanisms involved in increased expression of a cytochrome P450 responsible for pyrethroid resistance in the housefly, Musca domestica.

Cytochrome P450 Ipr is a developmentally regulated P450 responsible for monooxygenase-mediated pyrethroid resistance in the LPR strain of housefly. CYP6D1, the gene coding for P450 Ipr, has recently been sequenced. We investigated the molecular basis for CYP6D1-mediated pyrethroid resistance by comparison of mRNA levels, gene sequences, and gene copy number between LPR and pyrethroid susceptible strains of housefly. CYP6D1 mRNA levels were elevated in the LPR strain to a similar level as P450 Ipr protein, suggesting that over-expression of this important P450 in the resistant strain is probably due to increased transcription. Southern blots of susceptible and LPR strain DNA suggest that gene amplification is probably not involved in the increased expression of CYP6D1 protein. Five alleles of CYP6D1 were discovered and their possible role in resistance is discussed.

Amino Acid Sequence↗

PubMed1995

Resistance to avermectins: extent, mechanisms, and management implications.

The avermectins represent a group of natural compounds with potent pesticidal activities. Because of their novel mode of action, they represent an important resource for pest control and resistance management. In the Colorado potato beetle, the house fly, and the two-spotted spider mite, resistance to abamectin is usually autosomal, recessive, and polygenic. Although these aspects are beneficial in resistance management, the fact that resistance could be readily selected for suggests that abamectin needs to be used in moderation. Furthermore, several major resistance mechanisms (e.g. excretion, oxidative metabolism, penetration) and minor factors (e.g. altered target site, conjugation, hydrolysis/sequestration) have been implicated in abamectin resistance. Thus, the question is not whether resistance to abamectin will occur but is simply when and how it will occur. To address this problem, we have gathered information on the genetics, biochemical mechanisms, effectiveness of synergists, and cross-resistances to other insecticides from three abamectin-resistant insects. Judicious implementation of this information may prove useful in the resistance management of this natural pesticide.

Animals↗

PubMed1995

Memory deficits in a demented patient with probable corticobasal degeneration.

Anterograde and retrograde amnesia in a patient with probable corticobasal degeneration (pCBD) and dementia were studied in a university medical center setting. The patient with pCBD and four comparison patients of comparable global mental status (Mini-Mental State Exam) who met NINCDS-ADRDA criteria for Alzheimer's disease (AD) were included. Standard neuropsychological tests of naming, intelligence, achievement, verbal fluency, anterograde and remote verbal and visuospatial memory, and motor skill learning were given. The pCBD patient exhibited a progressive asymmetric akinetic-rigid syndrome, which was unresponsive to Sinemet. His initially mild, intellectual deficits consisted of apraxia, slowed speech, and word-finding and memory difficulties. Over a 2-year period, a dementia syndrome developed, which involved more-serious deficits in praxis and naming, as well as impairments in spelling, calculation, verbal fluency, IQ, anterograde verbal and visuospatial memory, and motor skill learning. When tested by recall methods, the pCBD patient exhibited marked deficits on several tests of remote memory; however, on recognition testing, he performed normally on the Famous Faces Test and on a test of geographical knowledge, which measures remote visuospatial memory. By contrast, the four AD patients, who showed equivalent naming difficulties, less-severe fluency deficits, and normal motor skill learning, showed severe impairments in recalling and recognizing the names of famous people from photographs. A magnetic resonance imaging (MRI) scan of the pCBD patient showed marked frontal and parietal lobe atrophy and central atrophy, with ventriculomegaly that was greater on the left side of the brain. The temporal lobes were relatively spared, and the amygdalae, hippocampi, and temporal horns were of normal size.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Mini-BEAM as salvage therapy for relapsed or refractory Hodgkin's disease before intensive therapy and autologous bone marrow transplantation.

PURPOSE: To evaluate the efficacy of carmustine (BCNU), etoposide, cytarabine (Ara-C), and melphalan (mini-BEAM) as salvage therapy in patients with relapsed or refractory Hodgkin's disease who were potentially eligible to undergo intensive therapy and autologous bone marrow transplantation (ABMT). PATIENTS AND METHODS: Forty-four patients with refractory or relapsed Hodgkin's disease after front-line combination chemotherapy referred for consideration of ABMT were treated with mini-BEAM (BCNU 60 mg/m2 on day 1, etoposide 75 mg/m2 on days 2 to 5, Ara-C 100 mg/m2 twice per day on days 2 to 5, and melphalan 30 mg/m2 on day 6) to maximum response. Eleven patients were refractory to primary chemotherapy. Twenty-three patients were treated in first relapse and 10 in second or subsequent relapse; 21 received mini-BEAM as their first salvage regimen. Patients were restaged to determine disease status immediately before intensive therapy and transplant. RESULTS: The overall response rate was 84% (exact 95% confidence interval [CI], 70% to 92%), with a complete response (CR) rate of 32% (95% CI, 20% to 47%) and a partial response (PR) rate of 52%. No treatment-related deaths were observed. Myelosuppression was the major toxicity. Almost all patients required platelet transfusions. Eighty-four percent were given RBC transfusions, and 54% required intravenous antibiotics for fever while neutropenic. CONCLUSION: Mini-BEAM is a safe and effective regimen for treatment of refractory or relapsed Hodgkin's disease. Further studies are required to determine if responding patients have improved disease-free survival (DFS) after intensive therapy and ABMT.

Adolescent↗

PubMed1995

DICE (dexamethasone, ifosfamide, cisplatin, etoposide) as salvage therapy in non-Hodgkin's lymphomas.

Between April 1988 and April 1992 we conducted a study of DICE (dexamethasone 10 mg q6h, ifosfamide 1 g/m2, cisplatin 25 mg/m2, etoposide 100 mg/m2, and mesna uroprotection daily x 4 given every 28 days) in thirty six patients with intermediate or high-grade non-Hodgkin's lymphomas (NHL's). All patients had disease refractory to anthracycline-based chemotherapy and were ineligible for our dose intensive salvage chemotherapy program including autologous bone marrow transplant (ABMT). Twenty six men and 10 women aged 21-79 years (median 61) were given 100 courses of treatment in hospital. Twenty three patients had stage IV, 7 stage III and 6 stage II disease. Fourteen patients had bone marrow involvement and 11 had B symptoms. Thirty two patients had received only 1 previous chemotherapy regimen. After a follow-up of 1-70 months (median 7), 8 of the 34 (23%) patients evaluable for response had complete remission (CR) of their disease for 8-70+ months (med 24) and 15/34 (44%) partial remission (PR) for 2-55+ months (med 13), giving an overall response rate of 67% (23/34). Eight of the 36 patients are alive 34-70 months (median 48) after being enrolled on study, 6 of whom relapsed and responded to subsequent treatment. The estimated survival rates for all patients at 1 and 2 years are 50% and 36% respectively (Kaplan Meier). Response to prior chemotherapy was the only baseline characteristic statistically predictive (p = 0.04) of response to DICE by logistic regression analysis. Myelosuppression was the dose limiting toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Immunogold labelling of leukemic hairy cells with the B-ly7 monoclonal antibody: an SEM and TEM study.

Two cases of hairy cell leukemia have been studied by immuno-TEM and immuno-SEM after immunogold labelling of the cell surface antigen recognized by the B-ly7 monoclonal antibody. Most hairy cells appeared significantly labeled, although the density of the expression of the antigen, as demonstrated by immunogold labelling, seems variable from cell to cell. Moreover, some cells with the morphology of hairy cells and which could not be identified as monocytes were not labeled. Labelling for the antigen identified by the B-ly7 mAb does not seem to correlate with the presence of ribosome lamellae complexes which were present only in one of the two cases studied. Rare lymphocytes of unidentified lineage were labeled. Monocytes were significantly absent from the samples of peripheral blood of the two patients studied. In one normal control sample, monocytes were observed unlabelled. The results are discussed in reference to the pathogenesis of hairy cell leukemia, its surprisingly low mitotic rate, and its distinct response to chemotherapy.

Adult↗

PubMed1994

Treatment outcomes in patients with adult thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.

BACKGROUND: Plasma treatment has improved the outcomes in adults with thrombotic thrombocytopenic purpura (TTP)-hemolytic uremic syndrome (HUS). We reviewed our experience in treating unselected patients to determine the clinical outcomes and to evaluate the treatments given in addition to plasma. METHODS: A chart review of all cases of TTP and HUS in adults treated at the Toronto (Ontario) Hospital, the largest treatment center for adults with TTP-HUS in the province of Ontario, was conducted. RESULTS: Sixty-seven episodes of TTP-HUS in 52 consecutive adult patients were treated during a 12-year period. Plasma was the primary form of therapy, and most patients received plasma exchange. A complete hematologic remission was achieved in 65 of 67 episodes; however, two patients in remission were brain-dead. The time to complete remission varied from 3 to 58 days (median, 13 days). The death rate during the acute illness was 8%. Long-term sequelae included relapses, persisting renal impairment, hepatitis, and transfusion-associated acquired immunodeficiency syndrome. Relapses occurred in 21% of patients during a median follow-up of 1.1 years (range, 0.1 to 18 years). Analyses of the treatment given in addition to plasma did not demonstrate a significant benefit in terms of reducing the illness duration, mortality, or long-term sequelae. CONCLUSION: While most patients recovered from TTP-HUS, deaths still occurred and many patients suffered long-term complications. The role of the treatments given in addition to plasma is uncertain.

Adolescent↗

PubMed1994

Cytochrome b5 involvement in cytochrome P450 monooxygenase activities in house fly microsomes.

The involvement of cytochrome b5 in different cytochrome P450 monooxygenase and palmitoyl CoA desaturase activities in microsomes from insecticide-resistant (LPR) house flies was determined using a specific polyclonal antiserum developed against house fly cytochrome b5. Anti-b5 antiserum inhibited the reduction of cytochrome b5 by NADH-cytochrome b5 reductase. The antiserum also inhibited palmitoyl CoA desaturase, methoxycoumarin-O-demethylase (MCOD), ethoxycoumarin-O-deethylase (ECOD), and benzo[a]pyrene hydroxylase (aromatic hydrocarbon hydroxylase, AHH) activities. However, methoxyresorufin-O-demethylase (MROD) and ethoxyresorufin-O-deethylase (EROD) activities were not affected by this antiserum. These results demonstrate that cytochrome b5 is involved in fatty acyl CoA desaturase activities and in certain cytochrome P450 monooxygenase activities (i.e., MCOD, ECOD, and AHH) in LPR house fly microsomes. Other cytochrome P450 monooxygenase activities (i.e., MROD and EROD) may not require cytochrome b5. The results suggest that cytochrome b5 involvement with cytochrome P450 monooxygenase activities is dependent upon the cytochrome P450 isoform involved.

Animals↗

PubMed1994

Detection of cytochrome b5 from the house-fly, Musca domestica: comparison of immunological and spectrophotometric methods.

Spectrophotometric assay of microsomal cytochrome b5 in house-flies produces different results depending on whether sodium dithionite or NADH is used as the reducing agent and whether or not detergent is present. Microsomes assayed for cytochrome b5 with dithionite in the presence of detergent gave the highest values, followed by dithionite alone, NADH plus detergent, and then NADH alone. Isopropanol treatment of microsomes extracted cytochrome b5 free of spectrophotometrically interfering cytochrome P-450. Studies using immunoblotting and rocket immunoelectrophoresis with polyclonal antisera raised against the purified cytochrome b5 showed that isopropanol treatment quantitatively extracted cytochrome b5.

1-Propanol↗

PubMed1994

Linkage of kdr-type resistance and the para-homologous sodium channel gene in German cockroaches (Blattella germanica).

Pyrethroids are an important class of insecticides for controlling insect pests, including the German cockroach. Unfortunately, many insects have developed resistance to pyrethroids. One of the most important mechanisms of resistance is kdr (knockdown resistance) which is characterized by neural insensitivity to pyrethroids and DDT. To investigate whether the voltage-dependent sodium channel is involved in kdr-type resistance in the German cockroach, we isolated a 120 bp DNA fragment of the para-homologous sodium channel gene from German cockroaches. Using this fragment as a probe, we identified a restriction fragment length polymorphism (RFLP) of the para-homologous sodium channel gene between susceptible and kdr-type resistant German cockroaches. RFLP analysis of F2 and backcross cockroach populations (total of 331 individuals) showed that all homozygous resistant individuals had a 3.7 kb EcoRI fragment, all homozygous susceptible individuals had a 3.0 kb EcoRI fragment, and all heterozygous individuals had both 3.7 and 3.0 kb fragments. No recombination was detected between the kdr-type resistance locus and the para-homologous sodium channel gene. This suggests that the kdr-type resistance locus and para-homologous sodium channel gene are identical or tightly linked (< 0.2 cM) in German cockroaches. Our results provide strong evidence that modification of para-homologous sodium channels is associated with kdr-type resistance.

Amino Acid Sequence↗

PubMed1994

Relative sensitivity of the WAIS-R subtests and selected HRNB measures to the effects of brain damage.

Reitan has argued that Halstead-Reitan Neuropsychological Battery measures are more sensitive to the effects of brain damage than are measures from the Wechsler intelligence scales. This proposal was investigated in groups of 65 brain-damaged subjects and 45 nonbrain-damaged controls equated for age and level of education and subgroups of 34 brain-damaged subjects and 34 nonbrain-damaged controls closely matched on age and WAIS-R full Scale IQ. Differences on Halstead-Reitan measures found in the larger groups were not found in the subgroups matched on age and IQ. Further, discriminant analyses showed that 11 Halstead-Reitan measures were equivalent to the 11 WAIS-R subtests in discriminating brain-damage and nonbrain-damaged subjects. Thus, the proposal for poorer sensitivity of the WAIS-R subtests was not supported.

Journal Article↗

PubMed1993

Purification and characterization of a cytochrome P-450 from insecticide susceptible and resistant strains of housefly, Musca domestica L., before and after phenobarbital exposure.

A cytochrome P-450 (P-450) was purified from abdominal microsomes of untreated and phenobarbital treated susceptible (S+) and insecticide-resistant (LPR) houseflies using HPLC purification procedures. The purified P-450s exhibited the same apparent molecular masses (54,400 dalton) and could not be distinguished from each other on the basis of HPLC chromatographic properties, reduced CO-difference absorbance maxima (447 +/- 0.5 nm), or partial NH2-terminal sequences (MLLLLLLIVVTTLYIFAKL). Since these P-450s were indistinguishable and were immunologically identical to cytochrome P-450lpr we conclude that these P-450s are in fact cytochrome P-450lpr. The level of P-450lpr was increased twofold after PB exposure in the S+ strain, while the level of P-450lpr did not change in the LPR strain. Immunoinhibition of ECOD activity with anti-P-450lpr antiserum suggests that PB treatment in S+ house flies induced P-450lpr, and other forms of cytochromes P-450 with high activity toward this substrate.

Amino Acid Sequence↗

PubMed1993

Tissue distribution of microsomal cytochrome P-450 monooxygenases and their inducibility by phenobarbital in the insecticide resistant LPR strain of house fly, Musca domestica L.

Cytochrome P-450s, cytochrome b5, P-450 reductase, and four P-450 monooxygenase activities were abundant in proximal intestine (PI), Malpighian tubules (MT), and fat bodies (FB) in the insecticide resistant (LPR) strain of house fly. Insecticide resistance in LPR flies was associated with increases in P-450 monooxygenase activities in nearly all of these tissues relative to an insecticide susceptible strain. Cytochrome P-450lpr was present in all tissues and at higher levels in LPR than in susceptible flies suggesting that the role of P-450lpr in monooxygenase-mediated insecticide resistance is not due to its higher levels in a single tissue. However, it appears that fat bodies may have a major role in resistance due to their relatively large size and the abundance of P-450lpr in this tissue. Total cytochrome P-450s, cytochrome P-450lpr and P-450 monooxygenase activities were generally refractory to phenobarbital (PB) induction in LPR. This contrasts with a previous report in susceptible house flies showing that P-450 monooxygenases were induced by PB. It appears that total P-450s, cytochrome P-450lpr and monooxygenase activities were expressed at constitutive high levels in several tissues of LPR house flies.

Animals↗

PubMed1993

High-dose etoposide and melphalan, and autologous bone marrow transplantation for patients with advanced Hodgkin's disease: importance of disease status at transplant.

PURPOSE: To evaluate an intensive therapy regimen of high-dose etoposide and melphalan and autologous bone marrow transplantation (ABMT) in advanced Hodgkin's disease; and to determine possible prognostic factors that predict for long-term disease-free survival (DFS). PATIENTS AND METHODS: Seventy-three patients with advanced Hodgkin's disease who had failed to achieve remission with front-line chemotherapy (n = 16) or who had relapsed (n = 57) were treated with high-dose etoposide 60 mg/kg and melphalan 160 mg/m2 and ABMT. Previous therapy included mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) alternating with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), or hybrid MOPP/ABV. All patients received pretransplant cytoreduction with conventional-dose salvage chemotherapy and 40 also received pretransplant extended-field radiation to areas of bulky nodal disease (> 5 cm). RESULTS: Response to high-dose etoposide and melphalan was determined at 3 months post-ABMT. The complete response (CR) rate was 75% (95% confidence interval [CI], 64% to 84%), including 35 of 50 patients with measurable disease before ABMT (70%; 95% CI, 60% to 86%). There were three early deaths (septicemia) and four late deaths (three interstitial pneumonitis, one intracerebral hemorrhage). Actuarial DFS is 38.6% at 4 years. Multivariate regression analysis showed that disease status at the time of ABMT (no evidence of disease [NED], nonbulky residual disease [NBRD], or bulky disease) was the most important factor determining DFS: 68% of those transplanted with NED versus 26% for patients with NBRD and 0% for bulky disease (P = .0002, log-rank test). Relapse in a previous radiation field was the only other significant prognostic factor. CONCLUSION: Etoposide and melphalan is an effective and well-tolerated intensive therapy regimen in advanced Hodgkin's disease. Patients in complete remission after conventional-dose salvage therapy transplanted with this regimen enjoy superior long-term DFS.

Adolescent↗

PubMed1993

Trachoma in Africa.

Explore the source record for details and available documents.

History, 20th Century↗