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M Morley

Publications and source records attributed to M Morley.

At least 37 records · Page 2Linked to original sources

A resource of mapped human bacterial artificial chromosome clones.

To date, despite the increasing number of genomic tools, there is no repository of ordered human BAC clones that covers entire chromosomes. This project presents a resource of mapped large DNA fragments that span eight human chromosomes at approximately 1-Mb resolution. These DNA fragments are bacterial artificial chromosome (BAC) clones anchored to sequence tagged site (STS) markers. This clone collection, which currently contains 759 mapped clones, is useful in a wide range of applications from microarray-based gene mapping to identification of chromosomal mutations. In addition to the clones themselves, we describe a database, GenMapDB (http://genomics.med.upenn.edu/genmapdb), that contains information about each clone in our collection.

Chromosome Mapping↗

Permanent effects of neonatal estrogen exposure in rats on reproductive hormone levels, Sertoli cell number, and the efficiency of spermatogenesis in adulthood.

This study aimed to identify the mechanism(s) for impairment of spermatogenesis in adulthood in rats treated neonatally with estrogens. Rats were treated (days 2-12) with 10, 1, or 0.1 microg diethylstilbestrol (DES), 10 microg ethinyl estradiol (EE), 10 mg/kg of a GnRH antagonist (GnRHa), or vehicle and killed in adulthood. DES/EE caused dose-dependent reductions in testis weight, total germ cell volume per testis, and Sertoli cell volume per testis. Sertoli cell number at 18 days of age in DES-treated rats was reduced dose dependently. GnRHa treatment caused changes in these parameters similar to those in rats treated with 10 microg DES. Plasma FSH levels were elevated (P < 0.001) to similar levels in all treatment groups regardless of differences in Sertoli cell number and levels of inhibin B; the latter reflected Sertoli cell number, but levels were disproportionately reduced in animals treated with high doses of DES/EE. Neonatal estrogen treatment, but not GnRHa, caused dose-dependent reductions (40-80%) in plasma testosterone levels in adulthood, but did not alter LH levels. Preliminary evidence suggests that the decrease in testosterone levels in estrogen-treated rats is not due to reduced Leydig cell volume per testis. GnRHa-treated rats exhibited a significant increase in germ cell volume per Sertoli cell and a reduction in germ cell apoptosis, probably because of the raised FSH levels. Despite similar raised FSH levels, rats treated with DES (10 or 1 microg) or EE (10 microg) had reduced germ cell volume/Sertoli cell and increased germ cell apoptosis, especially when compared with GnRHa-treated animals. The latter changes were associated with an increase in lumen size per testis, indicative of impaired fluid resorption from the efferent ducts, resulting in fluid accumulation in the testis. Rats treated neonatally with 0.1 microg DES showed reduced germ cell apoptosis comparable to that in GnRHa-treated animals. The changes in apoptotic rate among treatment groups occurred across all stages of the spermatogenic cycle. It is concluded that 1) neonatal estrogen treatment results in dose-dependent alterations in Sertoli cell numbers, germ cell volume, efficiency of spermatogenesis, and germ cell apoptosis in adulthood; 2) the relatively poor spermatogenesis in estrogen-treated animals is most likely due to altered testis fluid dynamics and/or altered Sertoli cell function; 3) as indicated by FSH (LH) and testosterone levels, the hypothalamic-pituitary axis and Leydig cells are probably more sensitive than the Sertoli cells to reprogramming by estrogens neonatally; and 4) elevated FSH levels in adulthood may improve the efficiency of spermatogenesis.

Animals↗

Quantification of the effects of astrocytes on oligodendroglial morphology.

Oligodendrocytes in neonatal rat forebrain cultures grow either in isolation of other cells or upon astrocytes. Populations of both types of oligodendrocytes were used to quantify the effects of astrocytes on oligodendroglial morphology. Changes in oligodendroglial size and shape were determined by measurement of total process length, cell area, growth area, and fractal dimension. The directionality of process growth, quantified by measurement of the axes of growth, was also compared. Isolated oligodendrocytes exhibited greater total process length, greater cellular area, larger growth area, and a more complex boundary than oligodendrocytes growing upon astrocytes. Analysis of the axes of cellular growth revealed that the processes of isolated oligodendrocytes exhibited radial symmetry, whereas the processes of oligodendrocytes growing upon astrocytes were limited to an area demarcated by the astrocytic processes. These data suggest that, in neuron-free culture, the growth of oligodendroglial processes is modified by underlying astrocytic processes.

Animals↗

Complexity analysis of oligodendroglial processes expressing myelin-associated glycoprotein.

Oligodendroglia synthesize myelin in the mammalian central nervous system. Mature oligodendroglia have been identified in culture by two criteria; the expression of molecules characteristic of myelin, such as galactocerebroside (galC) and myelin-associated glycoprotein (MAG), and the elaboration of complex processes. Myelin gene expression can be documented by the binding of specific antibodies and antisera to the myelin-specific molecules; process complexity can be described by the fractal dimension, D. In this study, anti-MAG antisera was used to document MAG expression in the processes of oligodendroglia. Eighty percent of the galC+ oligodendroglia bound anti-MAG antiserum. With time in culture, MAG immunoreactivity seemed to extend from the cell soma into the oligodendroglial processes. To quantify this observation, fractal dimensions were calculated using either galC or MAG immunoreactivity to visualize oligodendroglial processes. A fractal dimension of 1.5 was calculated for O1+ processes by day 4 of culture; this value for D remained constant over the course of 1 month in culture. The fractal dimension calculated for MAG+ processes increased from 1.2 to 1.5 over the course of 28 days in culture. This change in fractal dimension confirms our visual impression that galC-containing processes acquire MAG slowly over the course of several weeks in culture.

Animals↗

Psychological status of diabetic people with or without lower limb disability.

The aim of this study was to compare the quality of life between diabetic people with chronic foot ulceration or lower limb amputation and diabetic controls. Each participant was interviewed using the Psychosocial Adjustment to Illness Scale, the Hospital Anxiety and Depression (HAD) scale, a specifically designed foot questionnaire and a quality of life ladder. Thirteen diabetic unilateral lower limb amputees (DA) were matched for age and sex with 13 unilateral diabetic patients with chronic foot ulceration (DU). Twenty six age- and sex-matched diabetic people with no history of foot ulceration were the controls (DC). Significantly poorer psychosocial adjustments to illness were found in DU and DA compared to diabetic controls (both P < 0.05). DU were also significantly more depressed than the DC (P < 0.05) using the HAD scale. The quality of life ladder revealed that DU were significantly more dissatisfied with their personal lives than DC (P < 0.05). Finally, the foot questionnaire showed that DU had a significantly more negative attitude towards their feet than DC and DA (P < 0.05). This study showed that the psychological status of mobile amputees was better than that of the diabetic foot ulcer patients but not as good as diabetic controls.

Adaptation, Psychological↗

Myelin gene expression in glia treated with oligodendroglial trophic factor.

Oligodendroglia synthesize myelin in the CNS. In vitro, oligodendroglia may be identified by the binding of monoclonal antibodies against galactocerebroside, a myelin-specific galactolipid. Oligodendroglial trophic factor is a protein mitogen for cells of the oligodendroglial lineage. When oligodendroglia in cerebral white matter cultures are treated with oligodendroglial trophic factor, galactocerebroside-positive cells undergo mitosis but fail to express the myelin structural proteins, myelin basic protein and proteolipid protein. Oligodendroglia treated with oligodendroglial trophic factor, however, do express 2',3'-cyclic nucleotide 3'-phosphodiesterase and myelin-associated glycoprotein in a manner similar to oligodendroglia treated with platelet-derived growth factor. Oligodendroglial trophic factor, therefore, generates a population of somewhat 'immature' oligodendroglia, which are galactocerebroside, myelin-associated glycoprotein and 2', 3'-cyclic nucleotide 3' phosphodiesterase positive but myelin basic protein and proteolipid protein negative.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗

Cis-platinum chemotherapy for ocular basal cell carcinoma.

We have used intravenous cis-platinum chemotherapy in the treatment of three patients with basal cell carcinoma of the lid extending into the orbit. Cis-platinum chemotherapy caused a reduction in tumour size and thereby delayed surgery in all cases. It allowed for local resection in one case, appeared to delay a patient's exenteration in a second case, and was used prior to radiotherapy in a third case. While not curative, cis-platinum may be useful as an adjuvant to decrease tumour mass prior to local excision and for patients who refuse or must delay exenteration.

Aged↗

Immunocytochemical detection of ricin. I. Preliminary immunofluorescence studies.

Ricin injected into rat muscle in vivo can be localized within a few hours using routine immunofluorescence techniques on formalin-fixed tissues. However, the level of sensitivity decreases with increase in size of animal injected, time after administration and decrease in dose given. These findings are discussed in relation to the known chemistry and subcellular mode of action of ricin.

Animals↗

Independent regulation of nonallelic pancreatic amylase genes in diabetic mice.

Administration of streptozotocin produces a diabetic condition in mice characterized by a specific decrease in amylase synthesis in the pancreas as well as a substantial reduction in amylase mRNA concentration. We have studied this effect in mice of the congenic strains C3H.AmyYBR and C3H.AmyCE with multiple active copies of the pancreatic amylase structural gene. When mice of these strains are treated with streptozotocin, the magnitude of reduction in the synthesis of each amylase isozyme is different. These differences are reflected in the relative activities of isozyme-specific mRNAs in an in vitro translation assay. Administration of insulin results in partial restoration of normal phenotypes. The results provide genetic evidence that individual copies of the amylase structural gene are associated with divergent cis-acting insulin-responsive sequences.

Alleles↗

An assessment of the immunofluorescence technique as a method for demonstrating the histological localization of tetrahydrocannabinol in mammalian tissues.

The use of the indirect immunofluorescence technique as a method for demonstrating the histological localization of tetrahydrocannabinol (delta-THC) has been examined. The experimental protocol was designed in order that optimal staining conditions with respect to temperature, the length of time of incubations and washes, and the dilution of the antisera should be defined. No marked differences were detected between frozen sections of liver from normal and delta-THC-injected mice. Results from radiotracer experiments using human liver suggest that the success of the method is dependent upon the solubility characteristics of the antigen-antibody complex.

Animals↗

The influence of dissolved oxygen on the mitogen responses of mouse lymphocytes.

Mouse spleen cells incubated at either 30 mm Hg dissolved oxygen partial pressure (pO2) or 160 mm Hg did not differ significantly in their survival or in their proliferative response to the mitogens concanavalin A, phytohemagglutinin or bacterial endotoxin in a subsequent static culture. If the mitogen was added prior to exposing the cells to the controlled dissolved oxygen environment the incorporation of thymidine was always substanstially lower in cells held at 160 mm Hg pO2. This toxic effect of oxygen increased with the time of incubation and was not reversed by the inclusion of 2-mercaptoethanol in the medium. Incubation of cells with mitogen in the absence of oxygen had no deleterious effect on the proliferative response. A comparison of DNA, RNA and protein synthesis in Con A stimulated cells indicated that the predominant effect of oxygen was on DNA synthesis.

Animals↗