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B Gondos

Publications and source records attributed to B Gondos.

At least 19 recordsLinked to original sources

Ultrastructure of developing and malignant germ cells.

Ultrastructural studies have provided special insights on the growth and differentiation of normal and neoplastic germ cells. Prespermatogenic germ cells in the fetal and postnatal testis are large spherical to ovoid cells characterized by a central symmetrical nucleus, prominent reticular nucleoli and abundant cytoplasm with accumulation of glycogen and paucity of other organelles. Similar findings have been observed in seminoma and intratubular neoplasia. These observations support origin of the tumours from germ cells at early stages of differentiation. Evidence is presented to suggest that the pathogenesis of germ cell neoplasia involves excessive proliferation of precursor germ cells associated with loss of intercellular communication.

Cell Differentiation

Morphometric study of the prepubertal rabbit testis: germ cell numbers and seminiferous tubule dimensions.

Testes from rabbits aged 1-9 weeks were examined by light microscopy. Changes in seminiferous tubule dimensions, testicular volume, and volume fraction of tubules were assessed. Germ cells and Sertoli cells were counted in round tubular cross sections and total germ cell number in each testis was estimated. Mitotic, meiotic, and degenerative activities of germ cells as well as their basal or central positions within tubules were quantified. A marked, steady increase in testis volume and in tubular length and volume occurred over the prepubertal period; but diameter underwent no significant increase and in fact decreased until week 4. Overall, tubules lengthened 40-fold and testis volume increased 25-fold; the percentage volume of the testis occupied by tubules rose from one-third neonatally to three-fifths at the onset of spermatogenesis. The ratio of germ cells to total tubular (germ and Sertoli) cells was lowest at 3 weeks. However, the total number of germ cells increased little until 3 weeks, after which it rose at a sharp rate commensurate with testis volume. Percentage of germ cells in mitosis peaked sharply at 3 weeks, dropped in subsequent weeks, and then rose at 7 weeks at the initiation of spermatogenesis. Importantly, the surge in mitosis at 3 weeks was followed by a redistribution of germ cells to a predominantly basal location from 3 to 7 weeks. Meiotic activity was sparse at 7 weeks and became abundant by 9 weeks. Germ cell degeneration remained relatively constant during weeks 1 through 6, with an increase at 7 weeks.

Animals

Reproductive toxicity of 2,4-dinitrotoluene in the rat.

The present study was undertaken to evaluate the effects of the chemosterilant 2,4-dinitrotoluene (DNT) on the rat testis. Adult male rats were fed control, or 0.1%, or 0.2% DNT for 3 weeks. An ultrastructural study of the testes was performed, serum was assayed for testosterone and gonadotropins, and sperm reserve count was determined. A marked change in Sertoli cell morphology was found after 3 weeks of 0.2% DNT exposure. Varying sized vesicles associated with swollen mitochondria and distended endoplasmic reticulum were visible in cells from DNT-treated animals. Circulating levels of follicle stimulating hormone and luteinizing hormone were increased in 0.2% DNT-treated animals. Reduced weights of the epididymides and decreased epididymal sperm reserves were observed in DNT-treated animals. These results indicate that DNT is capable of inducing testicular injury, of directly or indirectly disturbing pituitary function, and of exerting a toxic effect at the late stages of spermatogenesis. These findings suggest that a locus of DNT action is the Sertoli cell, resulting in both inhibition of spermatogenesis and changes in testicular-pituitary endocrine activity.

Animals

Reproductive toxicity of 2,4-toluenediamine in the rat. 3. Effects on androgen-binding protein levels, selected seminiferous tubule characteristics, and spermatogenesis.

In previous studies we demonstrated reduced fertility, arrested spermatogenesis, and diminished circulating testosterone levels in rats fed 0.03% 2,4-toluenediamine (TDA) for 10 wk. These studies were extended in three experiments by determining TDA effects on androgen-binding protein (rABP) production and on seminiferous tubule structure, and on early changes in testes morphology and spermatogenesis. In the first experiment, rats fed 0.03% TDA for 10 wk showed a 7- to 9-fold increase in rABP content in testicular cytosol or in media of cultured seminiferous tubules, a 4-fold increase in serum rABP, but a two-thirds decrease in epididymal rABP levels. Testes examination by transmission electron microscopy revealed degenerative changes in Sertoli cells with, where present, normal spermatocytes and spermatids. In the second experiment, 0.03% TDA fed for 4, 6, or 8 wk resulted in a doubling of testes/body weight ratios and a highly correlated 2.5- to 2.9-fold increase in seminiferous tubule fluid volume. An approximately 50% decrease in epididymal sperm reserves was found after 6 or 8 wk of TDA exposure. After 10 wk of exposure to 0.03% TDA, testicular weight was the same as in control-fed rats but seminiferous tubule fluid volume was still elevated. These changes in testicular characteristics indicate TDA effects on Sertoli cell function, on RABP release from the testes (and epididymides), and possibly on tubular fluid transport. In the third experiment, rats fed 0.06% TDA for 1 wk showed a 25% decrease in epididymal sperm content, reduced epididymal weight, and minor structural changes in Sertoli cells. After 3 wk of 0.06% TDA feeding, sperm counts were further reduced, and were accompanied by a dramatic increase in testes weight, intense fluid accumulation, and ultrastructural changes in Sertoli cells. No significant changes in serum testosterone levels were noted in the TDA-treated rats. The results of this third experiment demonstrate TDA toxicity on testicular spermatogenesis within 3 wk of TDA feeding. The within 3 wk of TDA feeding. The findings in this study suggest that the early inhibition of spermatogenesis by TDA is mediated through Sertoli cell damage.

Androgen-Binding Protein

The role of second-look laparotomy in treatment of epithelial ovarian cancer.

Forty-two patients underwent a second-look laparotomy to assess response to systemic chemotherapy for epithelial ovarian cancer. In 20 cases the operation showed no histologic evidence of disease. None of these cases received additional treatment at the time of negative second-look laparotomy. There has only been one recurrence noted in an average follow-up interval of 38.5 months. The remaining 22 cases did have residual carcinoma and 16 have developed progressive carcinoma despite secondary treatment. We found second-look laparotomy to be a safe and reliable assessment tool. However, we could not demonstrate a medical benefit from the procedure.

Antineoplastic Combined Chemotherapy Protocols

Comparative studies of normal and neoplastic ovarian germ cells: 1. Ultrastructure of oogonia and intercellular bridges in the fetal ovary.

Electron microscopic studies were performed on human fetal ovaries to gain insight into the process of mitotic proliferation in developing germ cells. Three stages of germ cell differentiation are present during the early gestational period: primitive germ cells, oogonia, and oocytes. Oogonia, representing the mitotic stage of differentiation, are the predominant cell type present between 9 and 12 weeks' gestation and then progressively decrease in number as a result of transformation into oocytes in meiosis and degeneration. Mitotic division of oogonia, which is extensive during the late first and early second trimesters, is characterized by incomplete separation and persistence of intercellular bridges between germ cells. Intercellular bridges were found in large numbers from 10 weeks until the time of follicle formation at midgestation. The bridges contained microtubule arrays consistent with remnants of the spindle apparatus. The findings support the role of germ cell bridges in maintaining coordination of proliferative activity during the early developmental period.

Cell Differentiation

Comparative studies of normal and neoplastic ovarian germ cells: 2. Ultrastructure and pathogenesis of dysgerminoma.

A series of dysgerminomas of the ovary was examined by electron microscopy and the findings were compared with germ cells in the normal developing ovary. The ultrastructural characteristics of the neoplastic cells, including prominent reticular nucleoli and sparsely distributed cytoplasmic organelles, indicated a close resemblance to oogonia present in the fetal ovary. Occasional cells had localized collections of glycogen, resembling primitive germ cells, but the irregular ameboid appearance and eccentric nuclear location characteristic of cells in the early stage were not seen. Ultrastructural features of oocyte differentiation, such as synaptinemal complexes and perinuclear arrangement of mitochondria, were not found in any of the tumors. Intercellular bridges, a frequent finding at the oogonial stage in the normal ovary, were absent in all of the tumors. The lack of intercellular communication could be responsible for uncontrolled mitotic division leading to germ cell neoplasia.

Adult

Intratubular germ cell neoplasia.

Intratubular germ cell neoplasia is now well established as a precursor to invasive germ cell tumors of the testis. The lesion is usually associated with subsequent development of typical invasive tumors if orchiectomy is not performed. Pathologic findings in intratubular neoplasia consist of germ cell abnormalities within the seminiferous tubules. The atypical cells have large round nuclei, prominent nucleoli, and abundant clear cytoplasm. They have ultrastructural and immunohistochemical characteristics of spermatogenic precursor cells present in the fetal and postnatal testis. Intratubular collections of abnormal germ cells have been found adjacent to invasive germ cell tumors in a high proportion of cases. Intratubular neoplasia occurring in the absence of testicular enlargement has been found in the following situations: cryptorchidism, in testes of some infertile men, dysgenetic testes, and in the contralateral testis following orchiectomy for germ cell cancer. Recognition of intratubular germ cell neoplasia is of special importance because detection of the most common forms of testicular cancer can be accomplished at a preinvasive stage and, therefore, prior to the opportunity for metastasis.

Humans

Formation of the blood-testis barrier in the rabbit.

The time of establishment of the blood-testis barrier in the rabbit was studied by electron microscopy using lanthanum nitrate. This electron-dense tracer was present in the intercellular spaces in all regions of the seminiferous cords in 7- to 9-week-old animals. In 10- and 11-week-old rabbits, the penetration of lanthanum nitrate was restricted to the basal region of the seminiferous cords. Closer examination revealed the presence of numerous tight junctions between adjacent Sertoli cells. The morphological appearance of these junctions was similar to those described previously in other mammals. Entry of the tracer substance was restricted at these junctions. Pachytene germ cells, which reside beyond the junctions, were never surrounded by the tracer. Based on our observations it was concluded that the blood-testis barrier in the rabbit is formed between the 9th and 10th postnatal week, and that it is functionally effective by the 10th week.

Aging

Initiation of oogenesis in the human fetal ovary: ultrastructural and squash preparation study.

Ovaries from 27 human fetuses at less than or equal to 12 weeks' gestational age were examined with electron microscopy and squash preparation studies. The findings demonstrated that meiosis begins in the fetal ovary between 11 and 12 weeks of age. This is several weeks after gonadal sex differentiation, which can be recognized in the testis at 6 weeks. Ovaries at earlier ages included primitive germ cells and oogonia. With advancing fetal age, mitotic activity and germ cell degeneration became increasingly evident. Preleptotene cells were found as early as 9 to 10 weeks, suggesting that meiotic capacity is present soon after gonadal sex differentiation but further progression into meiosis is delayed until some specific inductive influence is exerted.

Female

Pituitary gonadotropin-independent male-limited autosomal dominant sexual precocity in nine generations: familial testotoxicosis.

A recently described, distinct form of male sexual precocity is characterized by premature Leydig and germinal cell maturation in the absence of pituitary gonadotropin stimulation. Analysis of a nine-generation kindred with at least 28 affected males supports sex-limited autosomal dominant transmission. Three boys, with precocious sexual development at 1 to 4 years of age, had low basal plasma gonadotropin values without pubertal-type pulsatility and a minimal rise in luteinizing hormone after acute stimulation with luteinizing hormone releasing factor or its potent analog D-Trp6-Pro9-NEt-LRF, distinguishing them from boys with true precocious puberty. Two affected adults had a mature luteinizing hormone response to LRF. Testicular biopsies showed a progression of abnormalities in the seminiferous tubules from childhood to maturity; in one adult this disorder was associated with marked oligospermia and selective elevation of plasma follicle-stimulating hormone. The findings are consistent with an inherited intratesticular defect. Furthermore, the majority of cases of familial male sexual precocity seem to be examples of this disorder rather than central or true precocious puberty.

Child

Testicular changes in gonadotropin-independent familial male sexual precocity. Familial testotoxicosis.

A recently described form of male sexual precocity characterized by active Leydig cell differentiation and premature onset of spermatogenesis in the absence of pituitary gonadotropin stimulation has been termed familial testotoxicosis. The clinical and endocrine findings in the condition are consistent with an inherited intratesticular defect rather than central or true precocious puberty. In this report, testicular changes in biopsy specimens from a series of affected patients are presented. In all of the cases, Leydig cells demonstrated nuclear and cytoplasmic features characteristic of fully differentiated steroidogenic cells. Reinke crystals were absent. Germ cells at all stages of spermatogenesis were present, but there was evident disorganization of maturation. Spermatids exhibited a variety of structural abnormalities. Sertoli cells were characterized by complex cytoplasmic differentiation, Charcot-Böttcher crystals, and tight junction formation. The morphologic changes indicate premature differentiation of all of the major testicular cell types and are consistent with a distinctive type of intratesticular abnormality.

Child, Preschool

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

Hamartoma.

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Female