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Biomedical subjects

S C Finch

Publications and source records attributed to S C Finch.

At least 19 recordsLinked to original sources
PubMed2003

Molecular analysis of two cytochrome P450 monooxygenase genes required for paxilline biosynthesis in Penicillium paxilli, and effects of paxilline intermediates on mammalian maxi-K ion channels.

The gene cluster required for paxilline biosynthesis in Penicillium paxilli contains two cytochrome P450 monooxygenase genes, paxP and paxQ. The primary sequences of both proteins are very similar to those of proposed cytochrome P450 monooxygenases from other filamentous fungi, and contain several conserved motifs, including that for a haem-binding site. Alignment of these sequences with mammalian and bacterial P450 enzymes of known 3-D structure predicts that there is also considerable conservation at the level of secondary structure. Deletion of paxP and paxQ results in mutant strains that accumulate paspaline and 13-desoxypaxilline, respectively. These results confirm that paxP and paxQ are essential for paxilline biosynthesis and that paspaline and 13-desoxypaxilline are the most likely substrates for the corresponding enzymes. Chemical complementation of paxilline biosynthesis in paxG (geranygeranyl diphosphate synthase) and paxP, but not paxQ, mutants by the external addition of 13-desoxypaxilline confirms that PaxG and PaxP precede PaxQ, and are functionally part of the same biosynthetic pathway. A pathway for the biosynthesis of paxilline is proposed on the basis of these and earlier results. Electrophysiological experiments demonstrated that 13-desoxypaxilline is a weak inhibitor of mammalian maxi-K channels (Ki=730 nM) compared to paxilline (Ki=30 nM), indicating that the C-13 OH group of paxilline is crucial for the biological activity of this tremorgenic mycotoxin. Paspaline is essentially inactive as a channel blocker, causing only slight inhibition at concentrations up to 1 microM.

Amino Acid Sequence↗
PubMed1997

Leukemia: lessons from the Japanese experience.

Probably more has been learned about radiation-induced leukemia from intensive study of Japanese atomic bomb survivors than about radiation damage to any other organ system. This has been the result of an intensive binational effort at the Atomic Bomb Casualty Commission and the Radiation Effects Research Foundation in Hiroshima and Nagasaki to monitor the occurrence of leukemia in a large group of atomic bomb survivors over a period of more than 50 years (the Life Span Study). The focus in the leukemia studies has been on disease latency, time of peak incidence rates, clinical course, shape of the dose-response curve and changes in risk over time for various types of leukemia in relationship to shielded kerma and bone marrow radiation dose, age at time of exposure, and gender. The extreme understanding and cooperation of the Japanese atomic bomb survivors, control subjects, physicians of Hiroshima and Nagasaki, government authorities, and the citizens of both cities has resulted in an epidemiological study that is almost unparalleled in medical history.

Foundations↗
PubMed1992

Chronic leukaemias.

In recent years many subtypes of CLL and some CML variants have been recognized throughout the world by means of careful clinical, epidemiological, immunological, molecular biological and viral studies. Most striking has been the establishment of a close association between certain immunophenotypical subtypes of CLL and infection with HTLV-I and possibly HTLV-II. CLL has consistently been shown to have a strong genetic component and a low incidence among Asians, but a growing body of evidence also links this major leukaemia type with environmental factors including solvents, unidentified farming and other occupational exposures. In contrast, CML is characterized by few genetic associations, relatively homogenous world-wide distribution, greater frequency in Blacks than in Whites, little evidence of viral aetiology, and evidence that exposures to ionizing radiation, benzene and possibly other chemical agents are important aetiological factors. Most studies suggest that acquired rather than genetic factors are of greater importance in the aetiology of CML, but this conclusion is somewhat difficult to reconcile with the relatively small variation in incidence rates internationally. Common to both disorders in most populations are an increasing incidence with age, male predominance, and stability of incidence, survival and mortality over the years, exclusive of improved survival of CML following allogeneic bone marrow transplantation.

Adult↗
PubMed1992

Radiation-related ophthalmological changes and aging among Hiroshima and Nagasaki A-bomb survivors: a reanalysis.

The relationship of ionizing radiation to the age-related ophthalmological findings of the 1978-1980 ophthalmological examination of A-bomb survivors of Hiroshima and Nagasaki has been reanalyzed using DS86 eye organ dose estimates. The main purpose of this reevaluation was to determine whether age and radiation exposure, as measured using the recently revised dosimetry information (DS86), have an additive, synergistic, or antagonistic effect. The data in this study are limited to axial opacities and posterior subcapsular changes, for which a definite radiation-induced effect has been observed in Hiroshima and Nagasaki A-bomb survivors. The best model fitting for axial opacities gives a significant positive effect for both linear dose and linear age-related regression coefficients and a significant negative effect for an interaction between radiation dose and age. Such a negative interaction implies an antagonistic effect in that the relative risks in relation to radiation exposure doses become smaller with an increase in age. On the other hand, the best-fitting relationship for posterior subcapsular changes suggested a linear-quadratic dose and linear age-related effect. The estimate of the quadratic dose coefficient shows a highly negative correlation with age, but the negative quadratic dose term is extremely small and is of little biological significance.

Adult↗
PubMed1990

Phagocytic and bactericidal activities of leukocytes in whole blood from atomic bomb survivors.

This study evaluated the phagocytic and bactericidal activities of peripheral blood leukocytes from Hiroshima and Nagasaki atomic bomb survivors for Staphylococcus aureus. The data were analyzed by multiple linear regression for age, sex, radiation exposure, city of exposure, and neutrophil counts. No significant radiation effect was observed for either blood phagocytic or bactericidal activities. The only significant variable for these functions was the neutrophil count.

Adult↗
PubMed1988

Reclassification of leukemia among A-bomb survivors in Nagasaki using French-American-British (FAB) classification for acute leukemia.

The concordance rate for diagnoses of atomic bomb-related cases of leukemia in Nagasaki was determined using the French-American-British (FAB) classification for acute leukemias and myelodysplastic syndromes (MDS). Two Radiation Effects Research Foundation (RERF) hematologists and one of the members (JMB) of the FAB cooperative group reviewed independently the peripheral blood and/or bone marrow smears from 193 people with leukemia or a related disorder. There was 85% agreement in the identification of types and subtypes of acute leukemia. There was almost complete agreement for the diagnoses of non-FAB disorders (chronic myeloid leukemia (CML), adult T-cell leukemia (ATL) and others) resulting in overall concordance of 88.2%. The present study suggests that the previously established leukemia types for about a quarter of the cases of acute leukemia and related disorders except CML should be changed. Considerable numbers of cases of ATL and MDS were involved in this series. The frequency of the former disease was not high in the high-dose irradiated group, but that of the latter was considerably high. All subtypes of AML except M3 and M6 were present in the high-dose group. The striking difference in CML incidence between Nagasaki and Hiroshima may continue to be a problem in relation to biological response to radiation exposure.

Acute Disease↗
PubMed1987

Studies on semi-synthetic 7 alpha-formamidocephalosporins. III. Synthesis and antibacterial activity of some 7 beta-[D-2-(aryl)-2-[(4-ethyl-2,3-dioxopiperazin-1-yl)carbonyl amino] acetamido]-7 alpha-formamidoceph-3-em-4-carboxylate derivatives.

The synthesis and antibacterial activity of 7 beta-[D-2-(aryl)-2-[(4-ethyl-2,3-dioxopiperazin-1-yl) carbonylamino] acetamido]-7 alpha-formamidocephalosporins with various substituents at the C-3 position of the cephalosporin nucleus is described. Inhibition of Gram-positive and Gram-negative bacteria including beta-lactamase producing strains was observed with phenyl as the aryl residue. The 3,4-dihydroxyphenyl group further enhanced the activity against Gram-negative organisms; in this series, the 3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl] and 3-[(1-carboxymethyl-1H-tetrazol-5-yl)thiomethyl] analogues (2 and 12b) exhibited exceptional activity against Gram-negative bacteria, including Pseudomonas aeruginosa.

Cephalosporins↗
PubMed1985

Effect of colchicine on the migration of human lymphocyte subpopulations under agarose.

The effect of colchicine on the random migration of human peripheral blood mononuclear cells under agarose gel was studied. Separated T cell and non-rosetting sheep red blood cell fractions were incubated in the presence of colchicine at concentrations ranging from 10(-8)M to 10(-2)M, and then allowed to migrate for 72 hours. Significant inhibition of migration was not observed at colchicine concentrations less than 10(-3)M. At 10(-3)M, significant impairment of both T cell (p less than 0.01) and non-rosetting cell (p less than 0.001) migration was observed. At 10(-2)M colchicine, migration was completely inhibited. Enhancement of migration of any type of human mononuclear cells by colchicine was not observed at any concentration. The results are consistent with the hypothesis that microtubules are not required for the random migration of these cells.

Cell Movement↗
PubMed1983

Ophthalmologic changes related to radiation exposure and age in adult health study sample, Hiroshima and Nagasaki.

A 2-year ophthalmologic study of age and radiation-related ophthalmologic lesions among the atomic bomb survivors in Hiroshima and Nagasaki was conducted in 1978-80. The study sample in both cities was composed of all persons exposed to 100+ rad, their controls, and all other persons with a previous record of axial opacities or posterior subcapsular changes. Most of the losses were due to persons who refused to participate or for whom it was not possible to arrange for an ophthalmologic examination at the time of the regularly scheduled medical examination. It should be emphasized, however, that the loss of persons in both the control and the 100+ rad groups did not change systematically with increasing age by city. Increased lenticular opacities, other lens changes, and loss of visual acuity and accommodation occurred with increasing age in both exposed and control subjects as manifestations of the normal aging process. A highly significant excess risk for all age categories in the 300+ rad group in comparison to those in the control group was observed for both axial opacities and posterior subcapsular changes in Hiroshima, but not in Nagasaki. A stronger radiosensitive aging effect for persons who were under 15 years old at the time of the bombing (ATB) was observed for both axial opacities and posterior subcapsular changes in Hiroshima.

Adult↗
PubMed1983

A study of leukemic cell migration by an agarose plate method.

By means of inducing random migration of leukemic cells in human peripheral blood by an agarose plate method, a study was made to see how migration distance and cell morphology after migration differed with the type of leukemia. After 3 days of incubation, the distance of random migration in cells of lymphocytic leukemia patients was on the average 0.41 mm for the cells of 13 patients with adult T-cell leukemia/lymphoma and 0.03 mm for the cells of four patients with chronic lymphocytic leukemia which were all of B-cell origin. Thus leukemic cells of T-cell origin migrated farther than those of B-cell origin. In the cases of myelocytic leukemia, the distance of random migration was on the average 0.54 mm for the cells of five patients with acute myelocytic leukemia, 2.42 mm for the cells of three patients with acute myelomonocytic leukemia, 1.69 mm for the cells of four patients with chronic myelocytic leukemia at blastic crisis and 3.78 mm for the cells of one patient with chronic monocytic leukemia. Thus, cells of monocyte origin migrated quite well. Migrating cells differing from cells of smear samples retained their original natural morphology and were considered to serve as an aid in the differentiation of types of leukemia.

Adult↗
PubMed1982

An evaluation of certain factors which influence the in vitro migration of subpopulations of human lymphocytes.

The effect on the migration of subpopulations of human lymphocytes of variations in a number of factors known to influence granulocyte migration in the agarose plate system is described. The number of cells and the concentration of serum in the media had a profound effect on the migration of all lymphocyte subpopulations. However, the characteristics of the migration surface and various constituents of the agarose such as the type of serum or the addition of antibiotics or glutamine appeared to have little effect. Factors associated with homologous and heterologous sera which significantly affect granulocyte migration had little influence on the extent of lymphocyte migration, suggesting that there is some difference in the factors which regulate the migratory behavior of these cells.

Blood↗
PubMed1981

Human T and B lymphocyte migration under agarose: differences in the characteristics of migrating cells and migration patterns.

The morphologic and migration characteristics of separated human peripheral blood T and B lymphocytes were evaluated by means of an agarose plate technique. The motile T cells migrated in a tightly packed and regularly arranged monolayer, while the B cell monolayer appeared much more disorganized with the cells forming a loose spongy network. Fixed and stained preparations following 2-3 days of incubation showed that the T cells maintained mature lymphocyte features throughout the period of migration. Although many of the B cells were indistinguishable from the T cells, many were irregular in size and shape with monocytic characteristics. It is suggested that the differences in T and B cell in vitro migration patterns may reflect fundamental differences in the mechanisms of locomotion for these cells.

B-Lymphocytes↗