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Biomedical subjects

G Fisher

Publications and source records attributed to G Fisher.

At least 73 records · Page 4Linked to original sources
PubMed1990

The effect of low-dose X-irradiation on numerical and structural chromosome anomaly induction in mouse immature oocytes.

The ability of low doses of X-rays to induce numerical and structural chromosome anomalies in immature oocytes was examined in two experiments. In the first, 10-11-day-old females were given 0.1 or 0.2 Gy of X-rays and sampled at intervals up to 32 weeks later. In the second, 4-5-week-old females were given 0.1 Gy of X-rays and sampled up to 36 weeks post-irradiation. Chromosome anomalies were assessed in metaphase II oocytes. In the first experiment, there was evidence of dose-related increases in both hyperhaploidy (n + 1) and structural chromosome anomalies. In the second experiment, only the frequency of structural chromosome anomalies was found to increase consistently after irradiation. There was no indication that radiation-induced depletion of the oocyte population was associated with an early onset of the maternal age effect on nondisjunction.

Analysis of Variance↗
PubMed1990

UM4D4+ (CDw60) T cells are compartmentalized into psoriatic skin and release lymphokines that induce a keratinocyte phenotype expressed in psoriatic lesions.

UM4D4 (CDw60), the surface molecule of a novel antigen-independent T-cell activation pathway, was found to be highly expressed on lesional psoriatic T cells. To examine whether UM4D4 represents a T-cell activation pathway for psoriatic T cells, a T-cell line was initiated from an acute skin lesion and cloned by limiting dilution. Clonality was verified by analysis of T-cell receptor gene rearrangement. All T-cell clones tested, whether CD4+2H4+CD8-, CD4+2H4-CD8-, or CD4-CD8+CD11b-, expressed UM4D4 and were activated by the monoclonal antibody anti-UM4D4. Lesional psoriatic T-cell clones were heterogeneous in the degree of anti-UM4D4-induced proliferation and in their production of IL-2 and gamma-interferon. Lymphokines released by anti-UM4D4 activation were capable of inducing ICAM-1 and HLA-DR expression on cultured normal keratinocytes. Thus, the high expression of UM4D4 on T-cells in psoriatic skin provides an alternative mechanism for T-cell activation that may be operative in the psoriatic lesional milieu. Indeed, activation of lesional T-cells through the UM4D4 molecule resulted in release of lymphokines that directly induced keratinocytes to express a phenotype displayed in psoriatic skin lesions.

Antigens, CD↗
PubMed1990

Interleukin-1 in human skin: dysregulation in psoriasis.

Cytokine dysregulation is an attractive concept to explain many of the observed abnormalities in psoriasis. IL-1, in particular, can potentiate immune cellular activation, activate fibroblasts, and increase endothelial cell adhesiveness to leukocytes. Here, we review IL-1 regulation in normal and psoriatic skin in vivo in relation to normal skin and cultured keratinocytes. Contrary to expectations, IL-1 functional activity in psoriatic lesions is reduced, not increased, relative to normal skin. The reduction is attributable to the presence of IL-1 inhibitors, reduced IL-1alpha levels, and an IL-1beta that lacked function in T-cell assays. IL-1beta protein is actually significantly increased in psoriatic lesions, but the mechanism of its non-functionality remains unclear. Unlike cultured keratinocytes, which accumulate large, inactive IL-1beta precursors, both normal and psoriatic skin process IL-1beta to a mature form. Novel mechanisms of post-translational processing by epidermis in vivo may generate a novel form of IL-1beta with unknown functions. The marked abnormalities of IL-1 regulation in psoriatic skin suggest that this molecule may be important in normal skin homeostasis.

Humans↗
PubMed1990

The role of immune system in the pathogenesis of psoriasis.

Psoriatic involved skin contains an increased number of activated T cells. The mechanism through which these T cells achieve and maintain their activated state is unknown, and both antigen-dependent and -independent mechanisms may contribute. Recently a novel pathway of antigen-independent T-cell activation has been described. This pathway is identified by a monoclonal antibody that binds to a T-cell membrane surface molecule termed "UM4D4." This molecule is expressed on a minority (20%) of psoriatic peripheral blood T cells but on a majority (75%) of the T cells in lesional skin. Thus, UM4D4 could play a role in antigen-independent T-cell activation in psoriasis. Indeed the monoclonal antibody anti-UM4D4 consistently induces proliferation of psoriatic UM4D4+ T-cell clones. The activity of antigen-dependent pathways are also enhanced in psoriatic epidermis in as much as involved skin relative to uninvolved skin contains an increased number and function of antigen-presenting cells. Upon activation, the lesional T cells release lymphokines. Central to the immune hypothesis of psoriasis is that some of these T-cell lymphokines act on keratinocytes to induce changes characteristic of psoriasis. Indeed lymphokines from lesional psoriatic T-cell clones directly alter in vitro keratinocyte phenotype through induction of intercellular adhesion molecule-I (ICAM-1) and HLA-DR cell-surface expression. Furthermore, the lymphokines also enhance keratinocyte growth. These data suggest a critical role for the immune system in the pathogenesis of psoriasis.

Antigens, CD↗
PubMed1990

Rates of energy processing by blowflies: the uses for a joule vary with food quality and quantity.

Data on the variation of crop volumes with time for blowflies (Phormia regina Meigen) fed various volumes and concentrations of fructose or sucrose (from Gelperin, 1966, and Edgecomb et al. 1987) were used to characterize energy processing rates to test the assumption of food energy addivity of optimal foraging theories. Six regression models (linear, square root, cube root, hyperbolic, inverse cube root and exponential) were compared for data from Edgecomb et al. (1987) with measurements of crop volumes from 10 min to 5 h after blowflies were fed 9.7 or 14.5 microliters of 0.25 moll-1 sucrose. Only the hyperbolic regression could be discriminated as statistically different, and the linear model was selected as most parsimonious for examining rates of energy processing. About the same volume bypassed the crop for flies fed 9.7 or 14.5 microliters. Volume rates of crop emptying (from Gelperin, 1966) did not change at intermediate concentrations but decreased from lowest and to highest concentrations. Energy processing patterns indicate that long-term storage rates increase with meal size and at intermediate concentrations and decrease (3.0 moll-1 fructose) or remain constant (2.0 moll-1 sucrose) at high concentrations, so the uses for a unit of energy are not additive across concentrations and meal sizes. Animals that process energy in this way should attempt to maximize meal size and include high-energy foods in their diet out of proportion to the amount of energy gained for the time spent foraging.

Animals↗
PubMed1989

Familial colorectal cancer and the screening of family members.

A case-control study was undertaken of the family histories of colorectal cancer in 128 patients with colorectal cancers and those of 61 patients with colorectal adenomas and matched surgical control patients who were attending a regional surgical service in Western Australia. One family with multiple polyposis of the colon was excluded from the study. A history of colorectal cancer in one or more first-degree relatives was associated with a relative risk of colorectal cancer of 2.5 (95% confidence interval, 0.8 to 8.0), of adenoma of 2.0 (95% confidence interval, 0.5 to 8.0) and of any colorectal neoplasm of 2.3 (95% confidence interval, 0.9 to 5.6). Four patients with colorectal cancer and one patient with colorectal adenoma had more than one first-degree relative with colorectal cancer, whereas no control subject gave this history. The five families that were represented by these cases each showed some other features of non-polyposis familial colorectal cancer. It was estimated that familial factors could explain 60% of colorectal cancer in persons with a family history of the disease in a first-degree relative and 5% of colorectal cancer in the population as a whole. Haemoccult II tests were posted to 629 living first-degree relatives of the patients with colorectal cancers and adenomas; 44% of these relatives returned the completed tests. Four relatives with positive results of tests both before and after dietary restriction were investigated; all four subjects had colorectal adenomas. In addition, one subject had a short segment of ulcerative colitis. A further mailing of Haemoccult II tests one year later gave a 39% response rate; no further cases of colorectal neoplasia were found. One relative developed carcinoma of the caecum 10 months after a negative result in the first round of Haemoccult screening. Persons with two or more first-degree relatives with colorectal cancer, with or without other features of non-polyposis familial colorectal cancer, are at a high risk of the development of colorectal cancer. The comparatively-poor response to an offer of Haemoccult II testing and its known insensitivity and lack of specificity suggest that it is not a satisfactory method of screening these high-risk subjects.

Adenoma↗
PubMed1989

Further examination of the production-line hypothesis in mouse foetal oocytes. II. T(14; 15)6Ca heterozygotes.

Pachytene oocytes from foetal mice heterozygous for the translocation T(14; 15)6Ca were screened for evidence of a "production-line" effect on chromosome pairing. Metaphase I oocytes from adult heterozygotes were also examined to determine whether any such effect on pahytene chromosome pairing is subsequently repeated during adult reproductive life as anticipated by the production-line hypothesis. It was found that as gestation proceeded the proportion of pachytene oocytes with a translocation quadrivalent declined and that with a trivalent and univalent correspondingly increased. That is, there was evidence of variation in pairing behaviour of the translocation at different times of gestation. In contrast, the proportions of metaphase I cells with either a quadrivalent or a trivalent plus univalent did not vary between adult females of different ages. Thus if the variation observed at pachytene was the result of a production-line effect, clearly this was not reflected in the behaviour of the translocation at metaphase I. Our observations therefore do not support the production-line hypothesis for the maternal age effect on nondisjunction.

Aging↗
PubMed1988

Case management service provision and client change.

The present study examines the relationship between case management service provision to the chronically mentally ill and consequent client change. Subjects were clients who had been in the Mississippi case management system for at least six months. It was predicted that the services of linkage/referral and advocacy would account for the most change in the number of problems and severity of problems on the part of the client. However, less than three percent of the variance in overall client change was explained by all five services combined. Results are discussed in light of certain constraints within the system.

Adolescent↗
PubMed1987

High activity of an unstable form of glucose phosphate isomerase in the mouse.

Quantitative electrophoretic studies of the three allozymes of glucose phosphate isomerase (GPI-1) produced by Gpi-1sa/Gpi-1sc heterozygous mice revealed two opposing influences on GPI-1 activity. First, the GPI-1AC heterodimer is less stable than GPI-1AA but more stable than the GPI-1CC homodimer. Second, a genetic determinant that maps close to or within the Gpi-1s structural gene causes elevated activity of GPI-1AC and probably also GPI-1CC dimers. The relative lability of these allozymes masks this elevated activity in some tissues but the effect is probably ubiquitous. The significance of these observations is discussed.

Alleles↗
PubMed1986

Further examination of the production-line hypothesis in mouse foetal oocytes. I. Inversion heterozygotes.

Chromosome pairing has been examined in foetal oocytes of mice heterozygous either for an X-linked inversion, In(X)1H, or an autosomal inversion, In(2)2H. The patterns of chromosome pairing have been screened systematically in foetuses of different gestational ages in a search for a "production-line" effect particularly affecting the inversion-bearing bivalents. The proportion of pachytene oocytes with a loop fell with increasing gestational age for both inversions. The decrease was linear for In(X)1H but best described by a quadratic function for In(2)2H. Examination of late zygotene cells and a comparison of loop frequency in early, mid and late pachytene oocytes suggested this age-related decrease to be principally due to synaptic adjustment and not to a production-line effect. However, two particular observations were somewhat at variance with this conclusion. Firstly, in In(X)1H heterozygotes, the presence of an inversion loop and the occurrence of partial pairing of long/long-medium bivalents at pachytene were independent of each other only on day 19. Secondly, although the proportion of oocytes with a loop fell overall, there was a rise at 19 days in In(2)2H heterozygotes. Thus in both inversions there is some evidence of a change in pairing behaviour affecting the inversion-bearing bivalents at the latest gestational age, as would be expected under the production-line hypothesis.

Animals↗
PubMed1986

Investigation of the potential for mitotic recombination in the mouse.

A variation of the mouse spot test is described that is designed to distinguish between spots of altered coat colour that arise by reciprocal mitotic recombination and those caused by somatic mutation or non-disjunction. Mouse fetuses that were heterozygous for two, linked coat colour genes were irradiated (1.5 Gy X-rays) in utero at 10.25-10.50 days post coitum (p.c.) or left untreated. Subsequently, the coats were classified for the presence of spots of altered colour. The irradiated embryos were heterozygous for the linked genes pink-eyed dilution (p) and albino (c) and were produced by both the repulsion and coupling crosses. Half of the reciprocal recombination events between the centromere and the proximal marker (p), in heterozygotes with p and c in repulsion, should produce twin spots. No such twin spots would be expected from a similar event in the coupling heterozygotes. The coats of 238 irradiated and 208 untreated repulsion heterozygotes plus 107 irradiated and 314 untreated coupling heterozygotes were classified for spots. One irradiated, repulsion heterozygote had a diffuse twin spot that was only recognisable by microscopic examination of the hairs. We conclude that if the treatment described induces mitotic recombination in the mouse, it does so with low efficiency.

Animals↗
PubMed1986

Further experience of the mouse dominant cataract mutation test from an experiment with ethylnitrosourea.

6 mice with inherited cataracts and 1 new allele of microphthalmia were recovered from 923 progeny of untreated, outbred, PT stock females that had been mated to inbred C3H/HeH strain males, whose spermatogonia had been exposed to 250 mg/kg of ethylnitrosourea (ENU). The cataract phenotypes were quite variable in expression and 5/6 showed a similar range of phenotypes. 2 of the 6 mutant mice were daughters of the same ENU-treated C3H/HeH male and probably represent repeats of the same mutation. One mutation, designated lens opacity-4 (Lop-4), has been genetically mapped to the distal region of chromosome 2. The yield of 5 presumably independent cataract mutations from 923 F1 offspring is a little higher than that reported by others in similar but larger scale experiments. Approximately 3-5% of the F1 mice examined had cataracts, yet only 6/49 (12%) of these, in the experimental group, were inherited as simple Mendelian traits. We consider that this high frequency of false positives (88%), and the incomplete penetrance and variable expressivity of the cataract mutations that were found, pose serious problems that could undermine the objective nature of the dominant cataract mutation test. We suggest that further studies be made to evaluate whether the use of inbred strains would reduce the variability in the system and so make the test more objective. However, it seems likely that the high false positive rate will continue to be a serious drawback to this test system.

Animals↗
PubMed1986

X-ray-induced chromosome aberrations in immediately preovulatory oocytes.

The effects of relatively small doses of X-rays (up to 100 cGy) to immediately preovulatory mouse oocytes have been examined by screening chromosome aberrations at metaphase I. Dose-related responses for the induction of aberrations were found. These were mainly of the quadratic or power-law types, and therefore similar in nature to the dose-responses described elsewhere for dictyate oocytes. The frequencies of the various categories of structural aberration have been compared to the previously determined rates of radiation-induced non-disjunction in immediately preovulatory oocytes in order to examine the potential involvement of structural chromosome aberrations in radiation-induced non-disjunction.

Animals↗
PubMed1986

Dansyl lysine, a new probe for assaying heat-induced cell killing and thermotolerance in vitro and in vivo.

Heat induces an increase in the fraction of cells staining with the nontoxic fluorescent membrane dye dansyl lysine (DL). The fraction of cells excluding DL can, under certain circumstances, be closely correlated to the fraction of cells surviving a heat treatment. Dansyl lysine has previously been shown to select for cholesterol-free membrane domains. We now describe the use of DL to provide rapid estimates of the kinetics of thermotolerance development and decay in vitro and in vivo. Following a 45 degree C-10-min heat shock, Chinese hamster ovary cells develop resistance to the lethal effects of a second heat treatment. This thermotolerance, as measured by both clonogenicity and resistance to DL staining, is maximal at approximately 12 h and gradually decays with a t1/2 of 2 to 3 days. DL staining also has utility in predicting the heat survival response in vivo. Radiation-induced fibrosarcomas grown in C3H mice were heated to 43 degrees C for 30 min. From 1 to 3 days later the tumors were excised and a single cell suspension was prepared. Tumor cells were then heated in vitro and assayed for survival or scored microscopically for DL staining. The two assays again yielded similar results showing maximal resistance by 19 h which decreased toward control heat sensitivity by 49 h. The evaluation of intrinsic heat sensitivity and induced thermotolerance is critical to rational treatment design in clinical hyperthermia. DL staining is rapidly quantitated by flow cytometry and can be applied to biopsy samples to provide estimates of heat sensitivity within hours.

Animals↗
PubMed1986

Small eyes (Sey): a homozygous lethal mutation on chromosome 2 which affects the differentiation of both lens and nasal placodes in the mouse.

Small eyes (Sey) is a semidominant, homozygous lethal mutation in the mouse (Roberts, 1967). It is allelic with SeyH, a radiation-induced homozygous prenatal lethal which has been mapped on chromosome 2. The effect of the Sey mutation is apparently limited to the growth and differentiation of the presumptive lens and nasal placodes. Homozygous Sey/Sey embryos can be distinguished as early as 10.5 days post coitum (p.c.); the optic vesicles grow out, but the ectoderm does not give rise to a lens and nasal pits never form. Immunohistochemical studies show that the distribution of the extracellular matrix glycoprotein laminin is not significantly different in the cephalic region of Sey/Sey versus Sey/+ or +/+ embryos. Sey/Sey embryos develop to term but without eyes or nose, and die soon after birth. Further analysis of Sey/Sey embryos may throw light on the mechanisms underlying morphogenesis of craniofacial structures in mammals.

Animals↗