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Biomedical subjects

F W George

Publications and source records attributed to F W George.

At least 55 records · Page 3Linked to original sources
PubMed1983

Granulosa cell differentiation and estrogen synthesis in the fetal rabbit ovary.

Morphologic development of the granulosa cell and the capacity for estrogen biosynthesis were evaluated in ovaries from New Zealand white rabbit fetuses at 16, 17, 18, 19, 20, 24 and 28 days of gestation. By light microscopy, granulosa cells within the developing cortical cords showed extensive accumulation of lipid material in their cytoplasm at Days 18, 19 and 20. Electron microscopy confirmed the presence of abundant lipid in granulosa cells at these times and showed that lipid is present in cytoplasmic droplets, often in coalescent aggregates. Quantitative morphometric examination demonstrated a sixfold increase in lipid between Days 16 and 19 and a subsequent decrease to earlier values by Day 24. In parallel studies, estrogen formation from [1 beta-3H]testosterone was low in Days 17 and 18 ovaries, increased approximately sixfold by Day 20 and fell by Day 24. Thus, the capacity of granulosa cells of the fetal ovary to form estradiol correlates with their cytoplasmic lipid content.

Animals↗
PubMed1983

Preliminary report on phase III RTOG studies of extended-field irradiation in carcinoma of the prostate.

The radiation therapy oncology group (RTOG) has conducted two studies testing the value of extended-versus limited-fields in carcinoma of the prostate. RTOG protocol 75-06 tests the value of paraaortic irradiation in patients with locally advanced tumors limited to the pelvis. RTOG protocol 77-06 tests the value of pelvic irradiation in patients with tumors limited to the prostate. Two hundred sixty-eight evaluable patients have been entered on RTOG 75-06, and 219 on RTOG 77-06 prior to 1981. This is a preliminary report on treatment-related morbidity in patients followed for a minimum of 1 year. Treatment-related morbidity has been classified according to a five-grade severity classification schema and correlated with the protocol option assignment in order to determine whether the use of extended fields had an effect on the incidence of side effects. Thirty-one percent of 268 patients on RTOG 75-06 and 34% of 219 patients on RTOG 77-06 had some form of treatment side effects. The majority (over 80%) of these were mild (grade 1 and 2) and by definition did not interfere with the patients' performance (life style). Only three patients on RTOG 75-06 and one on RTOG 77-06 had grade 4 complications (by definition requiring a surgical intervention). No fatal (grade 5) complications have been recorded so far. The use of paraaortic fields in RTOG 75-06 and pelvic fields in RTOG 77-06 have not resulted in a significant increase of GI or GU morbidity at this time. The only statistically significant trend was the incidence of postirradiation genital and lower extremity edema which strongly correlated with the extent of staging lymphadenectomy.

Aged↗
PubMed1983

The effect of a 5 alpha-reductase inhibitor on androgen-mediated growth of the dog prostate.

The administration of testosterone cypionate (0.4 mg/kg BW . day) to castrated male dogs caused a doubling of prostate weight within 4 weeks and an increase in the content of testosterone and dihydrotestosterone in the prostate. When the 5 alpha-reductase inhibitor 17-N,N-diethylcarbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one (3 mg/kg BW . day) was administered simultaneously with testosterone cypionate, prostatic testosterone content increased from 0.5 +/- 0.2 to 4.1 +/- 1.3 ng/mg DNA, the increase in prostatic dihydrotestosterone content was prevented, and prostatic size decreased to half the starting weight. These results suggest that dihydrotestosterone formation plays a role in prostatic growth.

5-alpha Reductase Inhibitors↗
PubMed1982

Developmental pattern of increased aromatase activity in the Sebright bantam chicken.

Feathers in the male Sebright bantam chicken are feminized as the result of a mutation that causes an increase in the capacity for estrogen synthesis (aromatase activity) in skin. To determine when during development the increased aromatase activity is expressed, we measured the enzyme in tissue slices of Sebright bantam and control bantam chickens of days 3, 12, and 18 of embryogenesis, on day 1 after hatching, and in mature birds. An assay was used that measures the release of 3H2O from [1 beta-3H]testosterone during the aromatization process. Aromatase activity was expressed in the 3-day-old Sebright embryos, but was not detectable in control embryos of the same age. In older embryos and birds, aromatase activity was assayed in multiple tissues. Enzyme activity was detectable in all tissues examined from day 12 and day 18 Sebright embryos. In control embryos, aromatase was detectable in ovarian but not in extraglandular tissues. The enzyme activity in most tissues of the Sebright decreased within 1 day after hatching and continued to decrease thereafter so that in the adult Sebright, aromatase activity was high only in skin (and skin appendages) and ovary. We conclude that the normal allele of this gene acts to limit the rate of estrogen formation in extraglandular tissues.

Aging↗
PubMed1982

Changes in aromatase activity in the rat brain during embryonic, neonatal, and infantile development.

We assessed the activity of the aromatase enzyme complex in slices of brain from rats by measuring the release of 3H2O from [1 beta-3H]testosterone. In hypothalami from 12-day-old rats, the rate of aromatase activity was linear with time and amount of tissue. The reaction was saturated at a substrate concentration of 0.1 microM, and the apparent Km of the reaction was 27 nM. The production of 3H2O was inhibited by 4-hydroxyandrostenedione, with an apparent Ki of 20 nM. Aromatase activity was first detected in the diencephalon of 16-day-old fetuses and reached maximum rates in hypothalamic tissue between days 18 and 20 of gestation. The highest rate of activity per mg protein (approximately 4.8 pmol h-1 mg protein-1) was observed in the preoptic area (POA) on the 20th day of embryonic development. However, when expressed as a rate per tissue fragment, aromatase activity was as high in the medial basal hypothalamus as in the POA. After day 20 of gestation aromatase activity rapidly decreased in the POA and medial basal hypothalamus of both males and females. The lowest levels were observed between postnatal days 16 and 20. Aromatase activity was not detectable in cerebral cortex and cerebellum at any age studied. Since serum testosterone was higher in males than females during the first 4 days of postnatal life, and since aromatase activity is elevated in the hypothalamus at this time, our results support the current concept that local formation of estrogen mediates testosterone-induced masculinization of the brain during the neonatal period. However, our results also indicate that failure of the rat brain to undergo complete sexual differentiation before birth cannot be due to an inability of the fetal hypothalamus to aromatize androgens, since aromatase activity was higher in the hypothalamus than in any other fetal tissue.

Androstenedione↗
PubMed1982

Concanavalin A-induced human lymphocyte mitogenic factor: activity distinct from interleukin 1 and 2.

Fresh human mononuclear cells (MNL) cultured in serum-free medium and stimulated with concanavalin A (Con A) produce a lymphokine functionally similar to the previously described antigen-induced lymphokine human lymphocyte mitogenic factor (LMF). T lymphocytes appear to be the source of Con A-induced LMF and the presence of adherent monocytes is required for maximal production. The proliferative response to LMF, assayed either as supernatant fluids in the presence of alpha-methyl-D-mannoside or as partially purified 27,000 to 35,000 m.w. fractions from Bio-Gel P-100 columns, indicates LMF is distinct from Con A. LMF acts almost exclusively on B lymphocyte-enriched (E rosette-negative) MNL while exhibiting only minimal activity on T lymphocytes and no activity on monocytes. LMF preparations induce both B cell proliferation and the maturation and proliferation of E rosette-negative T cell progenitors into E rosette-positive cells. Assay of interleukin 1 (IL 1) and interleukin 2 (IL 2) preparations for LMF activity implicate IL 2 as the T cell progenitor stimulating factor. Assay of the proliferation of human IL 2-dependent alloreactive T lymphocyte line/ATLL) indicates that LMF preparations contain IL 2, IL 2 activity, however, is completely removed by absorption of LMF preparations by ATLL cells, whereas LMF activity (B cell proliferation) is unabsorbable, thus distinguishing LMF from IL 2. These absorbed LMF preparations contain no IL 1 activity as assayed by murine thymocyte proliferation, nor does IL 1 have LMF activity. These results indicate that Con A-induced LMF contains a functionally distinct lymphokine with the ability to act as a B cell growth factor.

Animals↗
PubMed1981

Increased estrogen formation and aromatase activity in fibroblasts cultured from the skin of chickens with the Henny feathering trait.

The henny feathering trait in chickens leads to a marked increase in the conversion of androgen to estrogen in skin and other peripheral tissues with the result that feathers of affected males are feminized. To gain insight into the mechanisms responsible for this increased estrogen synthesis, we studied the conversion of testosterone to estrogen in fibroblasts cultured from the skin of control chickens and from two breeds carrying the henny feathering trait, the Sebright bantam and the Campine. Estrogen synthesis was measured in suspensions of intact fibroblasts and in cell-free fibroblast extracts by two assays: 1) direct measurement of 17 beta-estradiol formation from [1,2,6,7-3H]testosterone, and 2) assessment of 3H2O release from [1 beta-3H]testosterone. Both assays gave comparable results. Estrogen formation was as much as several hundred-fold higher in fibroblasts cultured from skin of chickens carrying the henny feathering trait compared to that observed in fibroblasts from skin of control chickens. The current data indicate that increased estrogen formation in skin of chickens with the henny feathering trait is due to an enhanced activity of the aromatase complex of enzymes responsible for estrogen synthesis. The molecular basis for this increased activity is unclear.

Animals↗
PubMed1981

Role of gonadal hormones in development of the sexual phenotypes.

Male and female embryos develop in an identical fashion during the initial portion of gestation. If the indifferent gonad differentiates into an ovary (or if no gonad is present), a female phenotype is formed. Male phenotypic differentiation, however, requires the presence of an endocrinologically active testis. Two secretions of the fetal testis, Müllerian inhibiting substance and testosterone, are responsible for male development. Studies of single gene mutations that interfere with androgen action indicate that testosterone itself is responsible for virilization of the Wolffian duct system into the epididymis, vas deferens, and seminal vesicle, whereas the testosterone metabolite dihydrotestosterone induces development of the prostate and male external genitalia. Thus, impairment of dihydrotestosterone formation results in a characteristics phenotype consisting of predominantly female external genitalia but normally virilized Wolffian ducts. The molecular mechanisms by which testosterone and dihydrotestosterone act during fetal development appear to involve the same high affinity receptor, a protein that transports both testosterone and dihydrotestosterone to the nucleus of target cells. When this receptor is either absent, deficient, or structurally abnormal, the actions of both testosterone and dihydrotestosterone are impaired, and the resulting developmental anomalies involve both internal and external genital structures.

Anti-Mullerian Hormone↗
PubMed1981

Classification of human leukemia by membrane antigen analysis with xenoantisera.

Rabbit and monkey antisera after appropriate absorption were rendered specific for normal or leukemic lymphoid- and myeloid-associated antigens. Antisera defining a common peripheral blood T-cell antigen, a thymus leukemia antigen, HLA-DR or Ia-like antigen, common acute lymphoblastic leukemia antigen (CALLA), and a myeloid-monocyte (M) antigen were used in a microcytotoxicity assay to classify leukemic cells from 30 patients in a double blind study. The antisera to the M antigen reacted with adherent peripheral blood cells and polymorphonuclear leukocytes and failed to react with nonadherent mononuclear cells and enriched T-cells and chronic lymphocytic leukemia cells. The M antisera also reacted with U937, a monocytic-type cell line, and with HL60, a promyelocytic-type cell line, but failed to react with T and B lymphoblastoid cell lines. The specificities of the other antisera have been described in previous reports. Cells from three of the patients could not be phenotyped by microcytotoxicity testing. Cells from 25 patients had a consensus morphological or histochemical diagnosis of either acute lymphoblastic leukemia or acute nonlymphocytic leukemia. The serological classification of these patients using the five types of antisera listed above were consistent with the consensus diagnosis. In addition, the lymphoid cancers were further subclassified as to T-, B-, or thymus antigen types. There was no consensus lymphoid versus myeloid diagnosis on cells from two patient. The serological classification in both cases favored a diagnosis of myeloid rather than lymphoid leukemia.

Acute Disease↗
PubMed1980

Combination of external and interstitial irradiation in the primary management of breast carcinoma.

The authors treated 83 patients with carcinoma of the breast using a combination of external and interstitial irradiation at Los Angeles County--University of Southern California Medical Center and Southern California Cancer Center between February 1, 1974, and May 31, 1977. All 30 patients who had T1 and T2 lesions, and who were followed for a minimum period of 24 months (24-50 months) are clinically still free of disease. Thirty-nine of 53 patients with T3 and T4 lesions, who were followed for a minimum of 30 months (30-56 months) are still alive with local control. Details of treatment techniques, dosimetry, results and complications are presented.

Adult↗
PubMed1980

Afterloading interstitial implant in head and neck cancer.

Seventy-nine patients with head and neck malignancies were treated using afterloading interstitial iridium 192 techniques at Los Angeles County-University of Southern California Medical Center and Southern California Cancer Center from Feb 1, 1974 to Nov 30, 1975. Twelve of the 13 T1 and T2 lesions and 17 of 25 T3 and T4 lesions remain locally controlled to a minimum follow-up period of 24 months. Surgical salvage in case of treatment failure is possible with low morbidity because of relatively low external irradiation to the total volume. Twenty of 41 patients who were reirradiated for persistent or recurrent cancers still have local control to a minimum follow-up period of 24 months. We discuss sites of involvement, implantation techniques, reactions, and complications.

Brachytherapy↗