Biomedical subjects

J G Scott

Publications and source records attributed to J G Scott.

At least 19 recordsLinked to original sources

PubMed1992

Anti-P450lpr antiserum inhibits specific monooxygenase activities in LPR house fly microsomes.

Monooxygenase activity in microsomes from the LPR strain of house fly (Musca domestica L.) was inhibited by anti-P450lpr, and antiserum specific for house fly cytochrome P450lpr. Anti-P450lpr did not inhibit house fly cytochrome P450 reductase or rat cytochrome P450 monooxygenase assays, consistent with specific inhibition of P450lpr. Anti-P450lpr inhibited the ability of cytochrome P450 reductase to reduce carbon monoxide treated LPR microsomal cytochrome P450, up to 49% of the total, showing that inhibition of cytochrome P450 reduction is the major mechanism of inhibition. Anti-P450lpr inhibited 98% of methoxyresorufin-O-demethylase activity and all the benzo(a)pyrene hydroxylase activity in LPR microsomes, but none of the pentoxyresorufin-O-dealkylase activity. The antiserum partially inhibited ethoxyresorufin-O-dealkylase and ethoxycoumarin-O-dealkylase activity. These results demonstrate that methoxyresourfin-O-demethylase activity and benzo(a)pyrene hydroxylase activity are characteristic substrates for P450lpr activity in the LPR strain of house fly.

7-Alkoxycoumarin O-Dealkylase↗

PubMed1992

Susceptibility of house flies (Diptera: Muscidae) and five pupal parasitoids (Hymenoptera: Pteromalidae) to abamectin and seven commercial insecticides.

Assays of five commercial insecticides applied as residual sprays at label rates to plywood indicated the most toxic insecticide overall for pteromalid parasitoids of house flies, Musca domestica L., was Atroban (permethrin), followed by Ciodrin (crotoxyphos), Rabon (tetrachlorvinphos), Ectrin (fenvalerate), and Cygon (dimethoate). Insecticide-susceptible house flies were susceptible to all five insecticides (mortality, 62-100%). Flies that were recently colonized from populations on dairy farms in New York were susceptible only to Rabon. Urolepis rufipes (Ashmead) was the most susceptible parasitoid species overall to these insecticides, followed by Muscidifurax raptor Girault & Sanders, Nasonia vitripennis Walker, Pachycrepoideus vindemmiae (Rondani), and Spalangia cameroni Perkins. Compared with susceptible flies, newly colonized flies showed moderate resistance to avermectin B1a (abamectin). Abamectin was more toxic to all of the parasitoids except N. vitripennis and S. cameroni than to newly colonized house flies when exposed for 90 min to plywood boards treated with 0.001-0.1% abamectin. Space sprays with Vapona (dichlorvos) killed all of the parasitoids and susceptible flies and 64% of the newly colonized flies when insects were placed directly in the path of the spray; mortality was substantially lower among flies and parasitoids protected under 5 cm of wheat straw. Space sprays with Pyrenone (pyrethrins) killed greater than 86% of all insects exposed to the spray path except for the newly colonized flies (1% mortality); mortality of insects protected under straw was low (less than 12%) except for S. cameroni (76%). Because responses of the five parasitoids to the different insecticides varied considerably, general conclusions about parasitoid susceptibility to active ingredients, insecticide class, or method of application were not possible.

Animals↗

PubMed1992

Enhanced activation is the mechanism of negative cross-resistance to Chlorpyrifos in the Dicofol-IR strain of Tetranychus urticae (Acari: Tetranychidae).

The mechanism responsible for negative cross-resistance to chlorpyrifos was examined in isogenic dicofol susceptible (Orchard-12) and resistant (Dicofol-IR) two-spotted spider mites, Tetranychus urticae Koch. The acetylcholinesterase of both strains was equally sensitive to inhibition by chlorpyrifos oxon. However, the Dicofol-IR strain showed increased oxidative activation of chlorpyrifos to chlorpyrifos oxon relative to the Orchard-12 strain, suggesting this mechanism is responsible for the observed negative cross-resistance.

Animals↗

PubMed1992

Biochemical characterization of hydrolytic and oxidative enzymes in insecticide resistant and susceptible strains of the German cockroach (Dictyoptera: Blattellidae).

We have identified resistance mechanisms in the German cockroach, Blattella germanica (L.), for propoxur and chlorpyrifos in strains of cockroaches that display multiresistance to several organophosphate and carbamate insecticides. The resistance mechanisms involve the combined effects of increased oxidative and hydrolytic metabolism and both strains are resistant to chlorpyrifos and propoxur. Experiments designed to test for similarity in metabolic enzymes suggest that, although the mechanisms involve similar processes, the enzymes responsible for insecticide detoxification are different in the two strains. Both resistant strains exhibited enhanced activity toward alpha-naphtholic esters relative to a standard susceptible strain; however, analysis of the progeny from resistant X susceptible crosses suggests that this general esterase activity is inherited differently than propoxur or chlorpyrifos resistance. Hybrids of the propoxur-resistant strain displayed the highest activity of all cockroaches tested, in contrast to hybrids of the chlorpyrifos-resistant strain, which were similar to the susceptible strain. Native gel electrophoresis of cytosolic preparations provided further evidence for differences in the pattern of hydrolytic enzymes and inheritance of resistance in the two strains. Analysis of components of the cytochrome P450-dependent monooxygenase system and activities toward model substrates indicate that the two resistance mechanisms also involve different oxidative processes. The propoxur-resistant strain displayed significantly higher levels of total cytochrome P450, but no other components were correlated with resistance. In contrast with the chlopyrifos-resistant strain, which was similar to the susceptible strain in all parameters measured, activity toward model substrates was higher in the propoxur-resistant strain than in any of the other strains and hybrids tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Synergism of chlorpyrifos against the German cockroach, Blattella germanica.

Of fifteen compounds tested as synergists for chlorpyrifos against susceptible and resistant strains of Blattella germanica, the German cockroach, eleven were active against the resistant strain but only seven were synergistic against the susceptible strain. Overall, the most effective synergist was S,S,S-tributyl phosphorotrithioate (DEF) followed by phenyl saligenin cyclic phosphonate (PSCP) and two substituted N,N-dimethylcarbamates: SK-102 and SK-37. The most effective synergist for overcoming chlorpyrifos resistance was SK-37 which reduced the resistance ratio by 3.2-fold. Four other synergists which reduced chlorpyrifos resistance, in order of their effectiveness, were: SK-102 > PSCP > DEF > tridiphane. The potential usefulness of these synergists for German cockroach control is discussed.

Animals↗

PubMed1991

Selection of high-level abamectin resistance from field-collected house flies, Musca domestica.

Abamectin is a novel, highly promising insecticide with activity against many pests. To determine if resistance to abamectin could occur, we collected house flies from several New York dairies and selected them in the laboratory. Resistance developed rapidly and to a high level (36 or greater than 60,000-fold, depending upon test technique and/or adjuvant) that could not be overcome by the synergists piperonyl butoxide or S,S,S-tributylphosphorotrithioate. There was no increase in (cross)resistance to crotoxyphos, dichlorvos, dimethoate, tetrachlorvinphos, permethrin, dieldrin or lindane following abamectin selection. Our results suggest the potential for abamectin resistance is high, at least in house flies, and that the judicious use of abamectin will be needed to prolong its usefulness as an insecticide.

Animals↗

PubMed1991

Expression of cytochrome P-450lpr is developmentally regulated and limited to house fly.

Expression of house fly cytochrome P-450lpr was examined using immunoblotting in male and female adult LPR house flies, mixed sex adult house flies at 12 different ages, larvae, and pupae. P-450lpr was expressed in both male and female adult house flies. P-4501pr was clearly present in all adult stages examined, was barely detectable in pupae, and could not be detected in larvae. Thus, cytochrome P-450lpr is developmentally regulated and present in both sexes of house fly. Expression of cytochrome P-450, immunologically homologous to house fly cytochrome P-4501pr, was examined in other species using immunoblot analysis. Eleven animal species were tested in the orders Diptera, Hymenoptera, Lepidoptera, Orthoptera, Acari, and Rodentia, using microsomes in some species from both induced and noninduced animals or insecticide-resistant and susceptible strains. P-450lpr appears to be restricted to house flies, as none of these species contained cytochrome P-450 that reacted with antiserum to cytochrome P-450lpr.

Animals↗

PubMed1991

Translocation (14;19) in acute biphenotypic leukemia.

Translocation (14;19)(q32;q13.1) is an acquired chromosomal rearrangement that has been associated with chronic lymphocytic leukemia of B-cell phenotype frequently progressing to lymphoma. Molecular analysis suggests that the translocation involves the immunoglobulin heavy chain gene on chromosome 14 and the BCL3 oncogene on chromosome 19. We present the first case of t(14;19) in a patient with acute leukemia. Correlation of detailed cytogenetic and molecular genetic studies, cell surface marker analysis, cytochemistry, and electron microscopy indicated that the leukemic cells were biophenotypic, with characteristics consistent with both myeloid and B-lineage lymphoid differentiation.

Adult↗

PubMed1991

Dexamethasone/ifosfamide/cisplatin/etoposide (DICE) as therapy for patients with advanced refractory non-Hodgkin's lymphoma: preliminary report of a phase II study.

Twenty-two patients with refractory intermediate- or high-grade non-Hodgkin's lymphoma were treated with dexamethasone 10 mg every six hours and ifosfamide 1 g/m2, cisplatin 25 mg/m2, etoposide 100 mg/m2 (DICE), and mesna uroprotection daily x4 every 3 to 4 weeks. Pretreatment with prochlorperazine and metoclopramide was given to prevent nausea and vomiting. Eighteen men and four women, aged 21 to 74 years (median age, 65) have received a total of 64 cycles. Seventeen patients had stage IV, one had stage III, and four patients had stage II disease. Seven patients had B symptoms and 11 had marrow involvement. Only two patients had had more than one previous chemotherapy regimen. Median time from last chemotherapy to DICE was 7 months (range 1 to 41). Two patients who suffered early treatment-related deaths (from sepsis) were classified as nonresponders. Six of 22 patients (27%) achieved complete remission (2 to 22+ months), and 11 (50%) had partial remissions (1 to 8+ months) for an overall response rate of 77%. Median survival has not been reached yet, and 12 patients are alive 1 to 22 months from the start of treatment. Nine patients had nadir granulocyte counts less than 0.5 x 10(9)/L; six required RBC transfusions and five, platelet transfusions. The platelet nadir was less than 50 x 10(9)/L in 13 patients. Four patients had microscopic hematuria, two had grade 3 gastrointestinal toxicity, and one had a transient episode of delirium and blurred vision.

Adult↗

PubMed1991

Comparative toxicity of seven insecticides to immature stages of Musca domestica (Diptera: Muscidae) and two of its important biological control agents, Muscidifurax raptor and Spalangia cameroni (Hymenoptera: Pteromalidae).

The toxicity of seven insecticides was evaluated against unparasitized Musca domestica L. pupae and pupae parasitized by Muscidifurax raptor Girault & Sanders or Spalangia cameroni Perkins, two important biological control agents. Only pyrethrins + piperonyl butoxide (Pyrenone) was less toxic to M. raptor compared with house flies. Conversely, all of the insecticides except crotoxyphos were less toxic to S. cameroni compared with house flies. A plateau in the tetrachlorvinphos bioassay line for S. cameroni suggested that this colony had approximately 45% resistant individuals. The selectivity observed between immature stages of house flies and M. raptor or S. cameroni is different from that reported against adult stages of these same species, suggesting that selectivity of an insecticide varies considerably between different life stages.

Animals↗

PubMed1991

Influence of total body irradiation on infections after autologous bone marrow transplantation.

Infectious complications were analysed in 50 consecutive autologous bone marrow transplant (ABMT) patients treated with high dose etoposide and melphalan, 30 of whom also received total body irradiation (TBI). Fever developed in 44 patients and bacteremia was documented in 13 (26%). Patients given TBI had increased susceptibility to bacteremia; 11 of 30 patients who received TBI had positive blood cultures, in contrast to two of the 20 who did not (p = 0.035). In addition, patients who received TBI had significantly more severe diarrhea (p = 0.037) when compared with those who received chemotherapy alone. Thirty-five patients treated with trimethoprim-sulfamethoxazole prophylaxis had a signficantly lower incidence of gram-negative bacteremia (p = 0.024). However, when those patients who received trimethoprim-sulfamethoxazole until neutrophil recovery were analysed alone, those who were also given TBI still had significantly more bacteremia (p = 0.047). Forty-seven patients with follow-up of more than 12 months are available for analysis of varicella zoster (VZV) infections. Of the 29 patients who received TBI, 11 (38%) developed VZV infections, in contrast to one of 18 patients (6%) treated with chemotherapy alone (p = 0.013). These results suggest that addition of TBI to the intensive therapy regimen for ABMT is associated with significantly more bacteremia and late VZV infections.

Adolescent↗

PubMed1991

GM-CSF therapy for delayed engraftment after autologous bone marrow transplantation.

Based on previous observations that granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes granulocyte recovery following chemotherapy, we evaluated the effect of recombinant human GM-CSF on hematopoietic progenitors and clinical outcome in six patients with delayed engraftment (greater than 55 days) after high-dose therapy and autologous bone marrow transplantation (ABMT). Three patients responded to a 14-day course of GM-CSF (10 micrograms/kg body weight/day) with at least a sevenfold rise in circulating granulocytes and a corresponding increase in granulopoietic activity in the bone marrow. A fourth patient died of infection on the 8th day of GM-CSF therapy with no evidence of response, and the remaining two, one of whom received a lower dose of GM-CSF (5 micrograms/kg/day), did not respond. There was no change in platelet or red cell transfusion requirements in any patient during the treatment. In two of the three responders, the granulocyte counts returned to pretreatment levels by 4 and 7 weeks after stopping the drug, respectively. We observed a marked increase in marrow-derived as well as in circulating granulocyte-macrophage progenitors (granulocyte-macrophage colony-forming units, CFU-GM) by the end of the 14-day course of GM-CSF in the three responders. There was no change in the frequency of circulating or marrow-derived erythroid (erythroid burst-forming units, BFU-E) or multilineage (multilineage colony-forming units, CFU-GEMM) progenitors. The results indicate that GM-CSF therapy in patients with markedly delayed engraftment after ABMT may stimulate granulopoiesis, but the effect is transient in some patients.

Acute Disease↗

PubMed1990

Autosomal sex-associated pyrethroid resistance in a strain of house fly (Diptera: Muscidae) with a male-determining factor on chromosome three.

Mechanisms and genetics of resistance to pyrethroid insecticides were investigated in a strain of house fly (ASPR) collected from a cattle ranch in Miyagi, Gunma Prefecture, Japan. Flies were selected in the laboratory with the pyrethroid insecticide permethrin. Both sexes were resistant to pyrethroids; however, females were 22- to 245-fold more resistant than males. Permethrin resistance could be partly suppressed by the monooxygenase inhibitor piperonyl butoxide in females, but not in males. In this strain, sex was determined by a male factor on the third autosome. The relationship of the autosomal male factor to the lower resistance levels observed in the males and the mechanisms of resistance expressed in each sex are discussed.

Animals↗

PubMed1990

Insecticide toxicity, synergism and resistance in the German cockroach (Dictyoptera: Blattellidae)

The toxicity of synergism of and resistance to insecticides in four strains of German cockroach, Blattella germanica (L.), were investigated. Toxicity of nine insecticides by topical application to the susceptible strain varied greater than 2,000-fold, with deltamethrin (LD50 = 0.004 micrograms per cockroach) and malathion (LD50 = 8.4 micrograms per cockroach) being the most and least toxic, respectively. Resistance to pyrethrins (9.5-fold) in the Kenly strain was unaffected by the synergists piperonyl butoxide (PBO) or S,S,S-tributylphosphorotrithioate (DEF), suggesting that the metabolism is not involved in this case. Malathion resistance in the Rutgers strain was suppressible with PBO, implicating oxidative metabolism as a resistance mechanism. The Ectiban-R strain was resistant to all the pyrethroids tested, and cypermethrin resistance was not suppressible with PBO or DEF. These findings support results of previous studies that indicated this train has a kdr-like mechanism. Bendiocarb resistance in both the Kenly and Rutgers strains was partially suppressed by either PBO or DEF, suggesting that oxidative and hydrolytic metabolism are involved in the resistance. Trends between the effects of the synergists on the susceptible versus resistant strains are discussed.

Animals↗

PubMed1990

Acute transient parotitis after high dose etoposide and autologous bone marrow transplantation.

Etoposide is an important component of several intensive therapy regimens in allogeneic and autologous bone marrow transplantation for advanced hematologic malignancies. We observed the occurrence of transient acute parotid and submandibular sialoadenitis in nine of 19 patients receiving high dose etoposide and melphalan followed by autologous bone marrow rescue. Manifestations included pain, tenderness and swelling of the parotid and submandibular glands. Symptoms arose 4-16 h after completion of etoposide infusion and resolved within 72 h. Elevation of serum amylase accompanied the symptoms, and was also observed in some patients who were asymptomatic. Discomfort was controlled with analgesics and the clinical course was uncomplicated in all cases. Transient parotitis is a relatively frequent and benign complication of high dose etoposide therapy.

Acute Disease↗

PubMed1990

Analysis of factors affecting hematopoietic recovery after autologous bone marrow transplantation for lymphoma.

Thirty patients with relapsed lymphoma (14 Hodgkin's disease, 16 non-Hodgkin's lymphoma) who underwent autologous bone marrow transplantation (ABMT) were assessed for the effect of different parameters on the rate of hematologic recovery post-ABMT. There was no correlation between nucleated cells count or numbers of CFU-GM or BFU-E in the infused marrow on either neutrophil or platelet recovery times. Patients with lymphoma who received more salvage chemotherapy (greater than six cycles) prior to marrow harvest took significantly longer to recover neutrophils to greater than 0.5 x 10(9)/l (p = 0.0229) and platelets to greater than 20 x 10(9)/l (p = 0.0007) than patients who received less than five cycles of salvage chemotherapy prior to harvest. There was no significant correlation between underlying disease, use of total body irradiation or status of cytomegalovirus serology and recovery times post-ABMT. The results suggest that extensive salvage chemotherapy may result in considerable stem cell damage to marrow, and that potential ABMT candidates with lymphoma should undergo harvest of tumor-free bone marrow as soon as possible following first relapse.

Adolescent↗

PubMed1990

Evaluation of cytoreductive therapy prior to high dose treatment with autologous bone marrow transplantation in relapsed and refractory Hodgkin's disease.

Based on observations that bulky disease at autologous bone marrow transplantation (ABMT) may be correlated with poor outcome in Hodgkin's disease, we have assessed the ability of conventional-dose chemoradiotherapy to reduce tumour burden to a minimum prior to ABMT. Thirty-seven patients with relapsed or refractory Hodgkin's disease referred for intensive therapy and ABMT were treated initially with one to five cycles of DHAP chemotherapy. All patients had previously received MOPP and ABVD chemotherapy or similar regimens. Four patients achieved complete remission (CR) and 12 partial remission (PR), for a total response rate of 43%. Eight partial responders and four non-responders to DHAP achieved significant further tumour reduction with local radiotherapy (five CR, seven PR). Six of 10 non-responders to DHAP responded to alternative salvage chemotherapy (mini-BEAM, CEP or augmented CVP). Overall, 24/37 patients (65%) achieved effective cytoreduction (nine CR, 15 PR with minimal disease) and have proceeded to ABMT. Patients with bulky disease at relapse or limited stage (II, IIIA) at diagnosis were less likely to respond to DHAP, but some of these could be cytoreduced with alternative therapy. In addition, the number of prior chemotherapy regimens correlated inversely with likelihood of response to DHAP. The results indicate that approximately two-thirds of patients with Hodgkin's disease who relapse after MOPP and ABVD-like regimens can achieve effective cytoreduction with conventional-dose chemoradiotherapy and proceed to ABMT in CR or PR with minimal disease.

Adolescent↗

PubMed1990

Isochromosome 7q as the sole abnormality in an unusual case of T-cell lineage malignancy.

We present a case of large cell lymphoma in a 20-year-old Oriental male who presented with massive splenomegaly and mild anemia. Surface marker and molecular genetic analyses of lymphomatous cells obtained from the spleen indicated a T-cell origin. Chromosomal analysis identified an isochromosome 7q as the sole abnormality. This is the first report of isochromosome 7q as the sole cytogenetic abnormality in a T-lineage malignant clonal expansion.

Adult↗