[Recent development in the chemotherapy of metastasizing teratocarcinomas of the testis].
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We collected data on the 434 individuals reported with cancer of the testis to the New York State Tumor Registry, 1960-64, from upstate New York. We compared these with the 410 members of a random sample of the upstate population interviewed from 1959 to 1962. A high risk of developing cancer of the testis was associated with professional occupations, native-born parentage, rural residence, and having been married, especially while young. These findings paralleled some other studies, as well as our earlier inquiry. Each of these factors carried a higher risk even when considered in the context of the other traits, and risk increased with an increase in the number of characteristics possessed.
The interaction between enzymatically radioiodinated human follitropin and the follitropin receptors in testis homogenate was investigated in immature and adult rats. The 125I-labeled human follitropin exhibited high binding activity with specific binding of up to 17% in the presence of an excess of testis homogenate. Approx. 50% of the bound hormone could be eluted at pH 5, and the receptor purified tracer exhibited a 3.6-fold increase in binding activity when compared with the original tracer preparation. Quantitative analysis of equilibrium binding data was performed with corrections for the measured specific activity and maximum binding activity of the tracer hormone. The equilibrium association constants (Ka) determined 24 degrees C were not significantly different in immature and adult rat testis, and the mean value for Ka was 3.9 . 10(9) M-1. At 37 degrees C, the Ka value obtained using immature rat testis was 1.3 . 10(10) M-1. The association of 125I-labeled human follitropin with immature rat testis homogenate was time and temperature dependent. In the presence of an excess of unlabeled hormone, 30--60% of the preformed hormone . receptor complex was dissociated after 24 h incubation. A specific and sensitive radioligand-receptor assay for follitropin was developed using immature rat testis homogenate. The minimum detectable dose of purified human follitropin was 0.6 ng, and human urinary and pituitary follitropin, ovine follitropin and pregnant mare serum gonadotropin reacted in the assay with equivalent slopes. The potencies of highly purified pregnent mare serum gonadotropin and highly purified human follitropin were similar in the radioligand-receptor assay, consistent with the follitropin bioactivity of the equine gonadotropin.
A young man with a palpable ectopic testis underwent right testis biopsy and orchiopexy. Since histological findings of the biopsy specimen revealed an unsuspected intratubular carcinoma in situ and evidence of diminished spermatogenic potential, an inguinal orchiectomy was done. This appears to be the first reported case of a tumor of this type developing in an undescended testis.
Some aspects of the development of the human testis (and overy) are discussed and the main theories regarding gonadal differentiation summarized. The major part of this review deals with the origin and differentiation of the three groups of somatic cellular content: Sertoli cells, Leydig cells and peritubular cells. The most important role of the mesonephros in gonadal development is described. Under the influence of the mesonephros, a second type of meiosis-inducing Sertoli cell differentiates and becomes the opponent of a meiosis-preventing type of Sertoli cell which derives from the coelomic epithelium. All somatic cells are pooled in the central gonadal blastema which is part of the medulla. They migrate via the rete blastema to the sites of their final differentiation. Included are the precursors of the Leydig cells and the peritubular cells.
During early development of the human testis the male germ cell first appears as primordial germ cell or gonocyte and enters the prospermatogonial stage after the twelfth week of gestation. Prospermatogonia lack glycogen particles and are connected by intercellular bridges. During the same period in the ovary the female germ cell undergoes its oogonial stage. Prospermatogonial and oogonial development have been studied histologically in three laboratory species (white mouse, Acomys caharhinus dimidiatus. golden hamster). According to the therminolgy of Hilscher et al. (1974) proposed for the rat, prospermatogonia have to be subdivided into M- T (1)- and T (2)-prospermatogonia. In the ovary they correspond to oogonia, oocytes in the prophase of meiosis and oocytes in the diplotene stage.
Cellulose acetate zymograms of alcohol dehydrogenase (ADH) and sorbitol dehydrogenase (SDH) extracted from male reproductive tissues of inbred mice were examined. ADH isozymes were differentially distributed in these tissues of C3H/He mice; ADH-B2 was observed in all tissues and testis cellular preparations examined; ADH-C2 was localized predominantly in the epididymis but was also present in the seminal vesicles, coagulating gland, and prostate gland. SDH was broadly distributed in these tissues but exhibited highest activities in the seminal vesicles, coagulating glands, and germinal cells of mature testes. Genetic variants for ADH-C2 and SDH provided evidence for (1) the identity of a second form of SDH in epididymis with ADH-C2; (2) the genetic identity of kidney, seminal vesicle, and testis SDH; and (3) the gentic identity of stomach and epididymal ADH-C2. Developmental changes in testis and epididymal ADH isozymes during maturation were examined. ADH-C2 appeared in the mature epididymis whereas ADH-B2 exhibited no major changes in activity in testis and epididymis during development.
Nickel subsulfide (Ni3S2) was injected in various amounts into the testis of adult Fischer rats for the study of the acute and chronic effects of Ni3S2 on testicular cells. Rats given injections of 0.6 to 10 mg of Ni3S2 developed an immediate inflammatory response at the site of injection, followed by a delayed, slowly evolving coagulation necrosis of seminiferous tubules and interstitial cells. The extent of testicular necrosis was dose dependent, but at doses of 5 or 10 mg of Ni3S2 the rats invariably developed subtotal destruction of the testis. The testis became atrophic, without regeneration of seminiferous tubules. No damage was seen in the other testis, and no systemic effects were noted. Malignant testicular neoplasms developed in 16 of 19 rats within 20 months after an injection of 10 mg of Ni3S2. These neoplasms were classified by light and electron microscopy as fibrosarcomas, malignant fibrous histiocytomas, and rhabdomyosarcomas. None of the testicular neoplasms was derived from germ cells or genital cord cells. The occurrence of rhabdomyosarcomas in the testis, an organ normally devoid of striated muscle, suggests that Ni3S2 induces malignant transformation of undifferentiated, pluripotential mesenchymal cells.
Vasovasostomy to reverse a previous vasectomy for sterilization was attempted for 27 men, the procedure being technically impossible in only one case. A testicular biopsy was performed at the time of operation and a number were investigated for cell-mediated immunity to sperm and for the presence of circulating sperm-agglutinating and cytotoxic antibodies. The first 17 cases have been studied and of these there have been 11 pregnancies, ten of which have already come to term with the birth of normal infants, including one set of twins. Of the rest, two are known to have oligozoospermia and four have been lost to follow-up, although two of them were euspermic when last examined. In spite of these encouraging results, it is considered that there are no grounds for alterning the present basis of vasectomy counseling which is that the operation is likely to be irreversible.
Carcinoids of the testis are rare tumours developing in three different ways: 1. It may differentiate within a teratoma, 2. it may be a metastasis of a "loco alieno" seated carcubiud abd 3. it may represent a real primary carcinoid. The observation of a primary testicular carcinoid in a man aged 55 years afforded the opportunity to study such a tumor for the first time by electron microscopic and fluorescence microscopic methods. Thereby, it could bw shown, that this testicular carcinoid corresponds to the carcinoids of the lower small gut. According to the specific ultrastructure of the intracytoplasmic granules it must derive histogenetically from an EC-cell. At the moment it cannot be decided whether the primary testicular carcinoid represents an autochthonous tumor of the male gonad or solely a teratoma with one-sided differentiation in the sense of a simplified teratoma.
A case is reported of a forty-four-year-old man with spermatocytic seminoma with no evidence of metastasis for twelve years. This patient is the second to have undergone retroperitoneal lymph node dissection and the third to have histopathologic examination of these lymph nodes. Review of 52 cases of spermatocytic seminoma disclosed 70 per cent of patients were over fifty years of age; none developed in a cryptorchid testis, none occurred in associated with teratoma, and there was no histopathologic evidence of metastasis. Whether or not radiation therapy is necessary is questionalbe. Prognosis appears to be good if not better than in classic seminoma. Available data indicate that spermatocytic and classic seminoma are two distinct neoplasms with different histogenesis and pathologic, clinical, and biologic features.
To probe the structural change in the genome of the differentiating germ cell of the maturing rooster testis, the chromatin from nuclei at various stages of differentiation were transcribed with prokaryotic RNA polymerase from Escherichia coli or with eukaryotic RNA polymerase II from wheat germ. The transcription was performed under conditions of blockage of RNA chain reinitiation in vitro with rifampicin or rifampicin AF/013. With the E. coli enzyme, the changes in (1) the titration curve for the enzyme-chromatin interaction, (2) the number of initiation sites, (3) the rate of elongation of RNA chains, and (4) the kinetics of the formation of stable initiation complexes revealed the unmasking of DNA in elongated spermatids and the masking of DNA in spermatozoa. In both cases the stability of the DNA duplex in the initiation region for RNA synthesis greatly increased. In contrast with the E. coli enzyme, the wheat-germ RNA polymerase II was relatively inefficient at transcribing chromatin of elongated spermatids. Such behaviour can be predicted if unmasked double-stranded DNA is present in elongated spermatids.
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Two cases of epididymotesticular metastases are reported: one epididymal from a carcinoma of the kidney by retrograde venous spread and the other testicular secondary to a carcinoma of the prostate and apparently by arterial spread. Epididymotesticular metastases of carcinomas are rare. When the initial carcinoma is known, or even treated, the development of a large testis should lead to consideration of the possibility. Treatment should consist of inguinal orchidectomy with ligation of the spermatic cord as high as possible.
Partial decrease of venous drainage from the left testis in male rats induced development of destructive changes in the seminiferous epithelium at the site of operation and in the contralateral organ. Spermatogenesis disturbances in the rat testes (focal desquamation of seminiferous epithelium, disorganization and degeneration of germ cells, devastation of seminiferous tubules) resembles the lesion in men with varicocele. These data permit to consider the results of present experiment as varicocele modelling. Disturbance of permeability and of the fine blood-testis barrier structure in both testes was observed in experimental rats; the picture of morphological changes was similar to that of autoimmune orchitis; lymphocytes sensitized to spermatozoa antigens were revealed in the lymphoid organs of experimental rats. The results obtained permit to suggest the involvement of immunological mechanisms in the development of pathological changes in the testes affected with varicocele.
BACKGROUND: The Cut Homeobox 1 (CUX1) gene has been implicated in a number of developmental processes and has recently emerged as an important cause of developmental delay and impaired intellectual development. Individuals with variants in CUX1 have been described with a variety of co-morbidities including variations in sex development (VSD) although these features have not been closely documented. CASE PRESENTATION: The proband is a 14-year-old male who presented with congenital complex hypospadias, neurodevelopmental differences, and subtle dysmorphism. A family history of neurodevelopmental differences and VSD was noted. Microarray testing and whole exome sequencing found the 46,XY proband had a large heterozygous in-frame deletion of exons 4-10 of the CUX1 gene. CONCLUSIONS: Our review of the literature has revealed that variants in CUX1 are associated with a range of VSD and suggest this gene should be considered in cases where a VSD is noted at birth, especially if there is a familial history of VSD and/or neurodevelopmental differences. Further work is required to fully investigate the role and regulation of CUX1 in sex development.
The position of the testis, the relationship between the epididymis and the testis, as well as the development and regression of the gubernaculum were investigated in 18 testicles of children from the 26th week of pregnancy until a few weeks after birth. The most important role in descensus testiculorum is ascribed to the differentiation of the epididymis and the ductus deferens. It is androgen dependent. The testis descends in the processus vaginalis, being attached to its dorsal wall.
Although systemically administered testosterone can effect the postnatal maturation of elements in the seminiferous tubule in hypophysectomized rats and mice, it does not elicit the same degree of development which occurs in normal control animals. In view of reports of precocious spermatogenesis in androgen secreting Leydig cell tumors, the present study was designed to determine if high local levels of testosterone accelerate development of the seminiferous tubules. Testosterone pellets were inserted under the tunica albuginea of the right testis of 7 day old rats. At 17, 23 and 28 days of age development of the seminiferous tubules, as judged by the formation of tubule lumens, was more extensive in the treated testes than in contralateral and sham operated controls. Tubule diameters were not necessarily correlated with lumen formation. This study demonstrates that high local levels of testosterone accelerate seminiferous tubule development in the rat and indicates that tubule diameter may not be a valid basis for estimating development of the testis. It is suggested that testosterone exerts this effect through its actions on the Sertoli cells.