Biomedical subjects
R F Weber
Publications and source records attributed to R F Weber.
Pyopneumothorax: a rare complication of Wegener's granulomatosis.
We present a case of Wegener's granulomatosis, complicated by the development of pyopneumothorax due to the rupture of a cavity. This complication occurred despite treatment with corticosteroids and cyclophosphamide. Active vasculitis and impaired tissue repair are possible explanations for the occurrence of this complication and the fatal outcome in our patient.
Effects of adrenocorticotropin and corticosterone on the negative feedback action of testosterone in the adult male rat.
Injections of ACTH (Synacthen depot) to intact male rats resulted in high serum levels of corticosterone and progesterone, and decreased levels of LH, FSH, and testosterone. In gonadectomized rats with low serum testosterone levels (approximately 1 ng/ml) induced by a small testosterone-filled silicone elastomer capsule, ACTH inhibited the postcastration rise in LH and FSH and reduced the wts of the prostate and seminal vesicles. After adrenalectomy the inhibitory effects of ACTH on serum gonadotropins and organ wts were almost totally absent. Administration of corticosterone acetate (10 mg/day) to gonadectomized and adrenalectomized male rats resulted in high serum levels of corticosterone (approximately 400 ng/ml) which were about 3 times higher than those measured in intact control animals. Nevertheless, in these rats the serum levels of LH and FSH were as high as those measured in gonadectomized and adrenalectomized oil-treated rats. However, when in addition to the injections of corticosterone acetate, a small testosterone-filled capsule was implanted, the postcastration rise in FSH was fully inhibited, whereas the serum levels of LH were below the level of detection. Significant inhibition of the postcastration rise in LH and FSH also occurred when smaller quantities of corticosterone acetate were given. Since in gonadectomized and adrenalectomized male rats similar testosterone-filled capsules did not prevent the postcastration rise in LH and FSH, it is concluded that a high serum level of corticosterone increases the sensitivity to the negative feedback effects of testosterone.
LH-RH and dopamine levels in hypophysial stalk plasma and their relationship to plasma gonadotrophins and prolactin levels in male rats bearing a prolactin- and adrenocorticotrophin-secreting pituitary tumor.
The present study was concerned with the effects of a transplantable pituitary tumor secreting prolactin (PRL) and adrenocorticotrophin (ACTH) on the levels of LH and FSH in peripheral plasma and on the hypothalamic release of LH-RH and dopamine in the male rat. Male rats of the same age not inoculated with the tumor served as controls. Hypophysial stalk blood was collected from urethane-anesthetized rats 4-5 weeks after tumor inoculation to measure their LH-RH and dopamine content. A peripheral blood sample was withdrawn from the animals just before sectioning the hypophysial stalk to measure their content of LH, FSH and PRL. It was found that in the tumor-bearing rats the levels of PRL increased 17-fold, whereas plasma levels of LH and FSH decreased by 45 and 70% respectively, when compared with the control rats. In the tumor-bearing rats, the secretion rate of dopamine in hypophysial stalk plasma increased from 1.4 to 4.1 ng/h, whereas the secretion rate of LH-RH decreased from 122 to 61 pg/h. However, when at the time of tumor inoculation adrenalectomy was performed, the tumor did not decrease plasma levels of LH and FSH and the secretion of LH-RH into hypophysial stalk blood any longer. The effect of the tumor on hypothalamic dopamine secretion was, however, still present in the adrenalectomized rats. It is concluded that the effect of the PRL- and ACTH-secreting pituitary tumor on plasma levels of LH and FSH requires the presence of the adrenal gland and that this effect is mediated through an inhibition of the hypothalamic release of LH-RH. Furthermore, this tumor increases the hypothalamic release of dopamine independent of the presence of the adrenal gland.
Effects of prolactin on testicular functions using an intratesticular pituitary graft.
Pituitary glands were grafted under the capsule of the left testis of rats to induce high levels of prolactin in this organ. One hundred days after implantation, significantly increased levels of prolactin were found in the tissue and the venous plasma of the left testis. Although the levels of testosterone in testicular venous plasma were not raised, the testicular content of testosterone was increased when compared to the right testis. The ratio of testosterone and dihydrotestosterone was not affected in the pituitary-grafted testis. Since the seminiferous tubules adjacent to the pituitary graft appeared to be completely normal, it is concluded that in the rat high levels of prolactin have no direct inhibitory effect on testicular functions.
In vitro fertilizing capacity of human spermatozoa with the use of zona-free hamster ova: interassay variation and prognostic value.
The average fertilization percentage, with the use of zona-free hamster ova, of a donor group was 54% (range 11% to 100%). Nineteen sperm suspensions (24%) from a group of 79 infertile patients with semen abnormalities and 23 from a second group of 43 patients (54%) whose partner showed evidence of reproductive dysfunction, fertilized as well as spermatozoa from fertile donors. The interassay variation of the fertilization rates was found to be less than 20%. Spermatozoa from 10 patients with normal semen characteristics failed to penetrate. Six spontaneous conceptions were reported in the first group. Sperm from four of these patients had low fertilization percentages. This indicates that fertility prognosis cannot be made on the basis of a low in vitro fertilization percentage only. The fertilization rate negatively correlated with the duration of infertility. No positive assays were found after 6 years of infertility.
Effects of a prolactin- and adrenocorticotropin-secreting tumor on gonadotropin levels and accessory sex organ weights in adult male rats: a possible role of the adrenals.
The presence of the transplantable PRL- and ACTH-secreting tumor 7315a in intact male rats resulted in very high serum PRL levels, decreased levels of LH and FSH, and reduced weights of testes and accessory sex organs. In gonadectomized rats bearing a small testosterone-filled capsule, the tumor inhibited the postcastration rise in gonadotropins and reduced the weights of the prostate and seminal vesicles. However, after adrenalectomy of intact or gonadectomized male rats bearing a small testosterone-filled capsule, inhibitory effects of the tumor on serum gonadotropin levels or on reproductive organ weights were totally absent. These results show that in adrenalectomized male rats hyperprolactinemia in itself doses not affect gonadotropin secretion and the androgenic action of testosterone. Rather, the tumor might exert a gonadotropin inhibitory action through elevated levels of PRL combined with progesterone, which is secreted by the ACTH-stimulated adrenal.
Effects of prolactin-secreting tumour on copulatory behaviour in male rats.
The effect of the transplantable prolactin- and ACTH-secreting tumour 7315a on male copulatory behaviour was investigated. Castrated tumour-bearing rats implanted with testosterone-filled capsules exhibited significantly longer latencies to first mount or intromission and to ejaculation than castrated control animals. In contrast to the number of intromissions, the number of mount before ejaculation of the tumour-bearing rats was considerably increased. However, when castration was carried out in addition to adrenalectomy, the differences in copulatory behaviour between tumour-bearing rats and control rats were no longer present. During the last tests for copulatory behaviour the tumour-bearing rats had serum prolactin concentrations or more than 4000 ng/Ml while control rats had less than 100 ng/ml. Plasma testosterone levels produced by silicone elastomer capsules were neither affected by the presence of the tumour nor by adrenalectomy. It was concluded that hyperprolactinaemia does not suppress the copulatory behaviour of adrenalectomized rats.
Failure of clinical remission after transsphenoidal removal of a microadenoma in a patient with Cushing's disease: multiple hyperplastic and adenomatous cell nets in surrounding pituitary tissue.
A patient with Cushing's disease is described who underwent transsphenoidal adenomectomy of a basophilic microadenoma with a diameter of 3 mm. In a piece of surrounding normal pituitary tissue removed at operation, multiple small nests of adenomatous basophilic cells were found both in the adeno- and neurohypophysis. No clinical improvement was observed. Cortisol secretory rate, plasma ACTH, the absent response of plasma cortisol to insulin-induced hypoglycemia, and the responses of plasma cortisol to lysine vasopressin and TRH remained unchanged. The observations in this patient point to the presence of multiple ACTH-secreting adenomatous cell nests and microadenomas throughout pituitary gland and bring back into view the concept of primary stimulation of hypothalamic corticotropin-releasing factor as the primary derangement in some patients with Cushing's disease.
The preleukemic syndrome. I. Clinical and hematological findings.
A long-term prospective study including 151 patients with preleukemia was performed in 1958--79. The series comprised 78 women and 73 men with a mean age of 79 and 72 years, respectively. Acute leukemia was the cause of death in 35 patients, 61 died of infections and/or hemorrhage or of unrelated causes. The mean interval between the initial diagnosis and death from acute non-lymphocytic leukemia was 36 months (range 2--121). Pitfalls in diagnosis are extensively discussed. The most striking was the advanced age of the patients. The presence of pancytopenia at the time of diagnosis was not predictive for subsequent blastic transformation.
The preleukemic syndrome. II. Cytogenetic findings.
Out of 151 patients with preleukemic syndrome, bone marrow chromosome studies were carried out in 88 during the preleukemic phase and in 10 after blastic transformation. Out of 54 cases studied without banding techniques, 13 (24%) were abnormal, while 17 (50%) out of 34 banded cases showed abnormalities. This highly significant increase in yield of aberrations was not restricted to structural abnormalities. During the preleukemic phase of the disease, only 5 of the abnormal patients had no normal metaphases in their bone marrow. Four types of chromosome aberrations were observed more than once: -Y, +8, del 5q and del F or del 20q. They are all frequently observed in myeloproliferative disorders. After blastic transformation, 15 out of 19 patients were abnormal and the abnormalities were more complex. It seems, therefore, that a qualitative and quantitative difference exists between this group of patients and the published series of patients with ANLL. Small abnormal cell lines with the same chromosome abnormalities as in the bone marrow were observed in PHA-stimulated blood cultures of 9 patients. Unstimulated cultures of the same blood sample did not show any mitosis. It is suggested that small subpopulations of lymphocytes arose from the same pluripotent stem cell as the leukemic myelogenous cells, although there may be other explanations.
Androgen receptor immunoexpression in the testes of subfertile men.
The localization and intensity of androgen receptor immunostaining was studied in the testes of 37 subfertile men with oligozoospermia and normal serum gonadotropin levels using a polyclonal antibody raised against a synthetic peptide corresponding to the first 20 N-terminal amino acid residues of the androgen receptor (AR). Furthermore, we investigated whether or not the immunoexpression of the AR in human Sertoli cells, in histologically normal testis tissue, is dependent on the stage of the spermatogenic cycle, as has been found in the rat. In the human testis, AR immunoexpression was observed in Sertoli cells, peritubular myoid cells, Leydig cells, and periarteriolar cells, but not in germinal cells. We found no evidence for a stage-dependent immunoexpression of AR in Sertoli cells. The intensity of AR immunoexpression varied substantially between biopsy specimens of different patients. There was, however, no correlation of the intensity of AR immunoexpression in either Sertoli cells or peritubular myoid cells with spermatogenic adequacy as measured by the method of Johnsen. When, in this study, the intensity of peritubular myoid cell staining was used as a standard to evaluate the intensity of Sertoli cell staining, no correlation was detected as well. Furthermore, serum gonadotropin levels were not correlated with AR immunoexpression levels in Sertoli cells and peritubular myoid cells. These results indicate that immunodetectability of the AR is not related to the condition of the spermatogenic epithelium in patients with oligozoospermia. Inappropriate expression of the AR is neither a cause nor a consequence of idiopathic infertility in the present group of patients.
Comparison of the response of rat testis and accessory sex organs to treatment with testosterone and the synthetic androgen methyltrienolone (R1881).
We have studied the ability of the synthetic androgen methyltrienolone (R1881) to maintain testis and accessory organ weights, as compared to the effect of testosterone propionate (TP). In contrast to TP, R1881 is not metabolized and does not significantly bind to androgen-binding protein (ABP). Thirty-six rats were treated with ethane dimethane sulphonate (EDS) and GnRH antagonist (Org30267) to abolish all testicular androgen production, and recombinant human FSH (rec-hFSH, Org32489) was administered to ensure adequate FSH levels. Of these rats, five groups of four rats were treated daily with 0-, 50-, 100-, 200-, and 400-microgram TP, s.c., and four groups of four rats were treated daily with 150-, 300-, 600-, and 1200-microgram R1881, s.c. One control group of four rats received vehicle injections only. EDS treatment, followed by GnRH antagonist and rec-hFSH treatment for 17 days, significantly reduced testis, prostate, and seminal vesicle weights (P < 0.001, P < 0.01, P < 0.001, respectively). Simultaneous treatment with androgens prevented this organ weight decrease, in a dose-dependent manner. In all TP-treated animals, relative weights (% of control) of the acces, sory sex organs were significantly higher than the relative testis weights (P < 0.001). However, there was no difference in relative weights between testis and accessory sex organs in the R1881-treated animals. In another series of experiments, we investigated the effect of treatment with Finasteride, a 5 alpha-reductase inhibitor, on testis and accessory sex organ weights in rats treated with EDS and TP. Treatment with EDS, TP (300 micrograms/day) and Finasteride (40 mg/kg/day) did not alter testis weight as compared to the effect of treatment with EDS and TP alone. Prostate and seminal vesicle weights were, however, markedly reduced (significantly different from rats treated with EDS and TP alone; P < 0.01 and P < 0.05, respectively). Immunohistochemical analysis of androgen-receptor (AR) expression in the testis revealed that testicular AR immunoexpression is androgen dependent and that FSH alone is not able to maintain AR immunoexpression. Furthermore, the stage-dependent pattern of AR immunoexpression in Sertoli-cell nuclei, during the spermatogenic cycle, is identical in all TP- and R1881-treated rats. It is concluded that testes, prostate, and seminal vesicles are equally stimulated when the androgen receptor in these tissues is exposed to the same intracellular concentration of free androgen and that the low 5 alpha-reductase activity in the testis plays a critical role in the differential response of the testis and the accessory sex organs to T. Furthermore, stage-dependent AR immunoexpression in Sertoli cells does occur in the absence of testicular androgen production and is not due to androgen metabolism or local differences in androgen concentration.
Early effects of streptozotocin-induced diabetes on insulin-like growth factor-I in the kidneys of growth hormone-transgenic and growth hormone-deficient dwarf mice.
BACKGROUND: The renal growth and hyperfiltration observed in humans and animals with early diabetes might be dependent on growth hormone (GH) and insulin-like growth factor (IGF)-I. The aim of this study was to investigate the early changes in kidney IGF-I in experimental diabetes in mice transgenic for bovine GH and in genetically GH-deficient Ames dwarf mice. METHODS: At 2, 4 and 8 days after a single intraperitoneal injection with streptozotocin, animals were weighted, bled and killed; plasma was analyzed for glucose and IGF-I. IGF-I levels were determined in tissue from snap-frozen kidney and liver. RESULTS: Body weight decreased significantly after the induction of diabetes. Kidney weight increased significantly in GH-transgenic, but not in normal or dwarf mice. Plasma IGF-I was significantly decreased at day 2 in GH-transgenic and normal mice, while liver IGF-I was increased at day 4 in all mice. Kidney IGF-I increased significantly in normal and GH-transgenic mice and was increased more than 3-fold at day 4 in GH-transgenic mice. In dwarf mice, no kidney IGF-I was detectable. CONCLUSION: The diabetes-induced increase in renal IGF-I is dependent on the presence of GH. GH deficiency may protect diabetic animals from early changes in the kidney.