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Biomedical subjects

H E Chemes

Publications and source records attributed to H E Chemes.

At least 19 recordsLinked to original sources

Developmental changes in testicular interstitial cell populations, LH receptors and in the response to hCG in the rat.

High doses of hCG were administered to immature rats of different ages and the animals killed 48 h later. Serum testosterone increased 2 to 4-fold over control values 48 h after hCG. In-vitro androgen production showed different patterns according to age. Animals younger than 35 days, when treated with hCG, retained the ability to respond to in-vitro gonadotrophic stimulation. This ability was lost in testes from rats aged 45 days. The number of free LH-receptors 48 h after hCG diminished with increasing age to become non-detectable at 35 and 45 days. In control animals the proportion of differentiated Leydig cells in relation to their mesenchymal precursors increased progressively with age to reach highest values at 45 days. hCG administration induced a shift of the cellular composition of the interstitium toward the more mature cell types. hCG has a predominantly trophic action on mesenchymal precursors in young rats, promoting their differentiation. These effects are minimal in the differentiated Leydig cells in older animals. It is proposed that the observed biochemical responses are the result of the balance between the increase in LH receptors and steroidogenic enzymes in the developing new generation of young Leydig cells and the down-regulation of receptors and enzymatic lesions in fully differentiated Leydig cells.

Aging

Extreme asthenozoospermia and chronic respiratory disease: a new variant of the immotile cilia syndrome.

Two patients suspected of suffering from ciliary dyskinesis were investigated. They consulted for primary infertility and chronic respiratory disease. Functional lung studies showed obstructive changes in one patient. Both had immotile sperm with short, thick and rigid tails. Ultrastructural studies of nasal biopsies showed abnormal cilia with almost complete lack of inner dynein arms (mean number of inner arms per axoneme 0.67 +/- 1.21 in patient 1 and 1.49 +/- 1.17 in patient 2, compared with normal values of 5.3 +/- 0.13). Other abnormalities included lack of parallel orientation of cilia and central translocation of microtubular doublets. Electron microscopy of sperm revealed hyperplasia of the fibrous sheath and axonemal disruption. This is the first report of an association of different anomalies in cilia and flagella leading to clinical manifestation of the immotile cilia syndrome. These findings emphasize the need for ultrastructural examination of respiratory cilia in men suffering from fibrous sheath alterations of sperm which so far have not been described in patients with the classical form of immotile cilia syndrome.

Adult

Lack of a head in human spermatozoa from sterile patients: a syndrome associated with impaired fertilization.

Three patients with primary sterility in whom the majority of spermatozoa lacked a normally implanted head are presented. A small cephalic knob was evident in most of them by routine colorimetric techniques, and the Feulgen reaction failed to show any deoxyribose nucleic acid. The morphologic features of the tails was normal. Few loose sperm heads were observed in the ejaculates. Even though motility was decreased, there were numerous acephalic sperms with different degrees of forward motility. Electron microscopy showed a well-organized structure of the centrioles and connecting piece, which were located in the neck region within a small cytoplasmic mass, but no chromatin was detected in any case. Studies on immature spermatids present in semen evidenced an independent anomalous development of heads and tails and suggested that they became separated at the end of spermatid maturation. This anomaly, of probable genetic origin, is interpreted to be due either to an alteration in the mechanism of migration and positioning of the tail on the caudal pole of the nucleus or to an interference with the formation of the implantation fossa of the head, which normally accommodates the connecting piece.

Adult

Dysplasia of the fibrous sheath: an ultrastructural defect of human spermatozoa associated with sperm immotility and primary sterility.

A study of a group of five patients presenting with primary sterility and showing severe sperm immotility is presented. Most spermatozoa in these patients showed rigid, short, thick, and/or irregular tails and 95 to 100% were immotile. Electron-microscopy disclosed a common pattern of flagellar abnormalities. There was a dysplastic development of the fibrous sheath, which appeared hyperplastic and disorganized. The axoneme was either missing or grossly distorted. In a few instances, a normal flagellum could be identified. Similar alterations also were detected in maturing spermatids, suggesting that the described defect develops during spermiogenesis. Two of the five patients had recurrent bronchial and sinusal infections and bronchiectasis, suggesting the possible existence of an associated abnormality in respiratory cilia. The existence of a common ultrastructural defect affecting most spermatozoa, its presence in two brothers, and the possibility of association with immotile respiratory cilia point to the existence of a syndrome (namely the "dysplasia of the fibrous sheath") of possible familial transmission.

Adult

The association of Wilms' tumor, male pseudohermaphroditism and diffuse glomerular disease (Drash syndrome): report of eight cases with clinical and morphologic findings and review of the literature.

In 8 children (6 males) at least 2 of 3 disorders were found--male pseudohermaphroditism (MPH), Wilm's tumor, and glomerular disease. MPH was present in the 6 males; they had abdominal cryptorchidism (6/6), ambiguous genitalia (6/6), negative sex chromatin (5/5), and 46XY karyotype (2/2). The gonads examined microscopically in 3 patients were dysgenetic testes. The renal tumor present in 7 was nephroblastoma (NB) of the classical type without anaplasia or nephroblastomatosis, bilateral in 1, and unilateral but multinodular in 2. Five underwent nephrectomy for a renal mass, and in 2 NB was found at open biopsy or at autopsy. The mean age at diagnosis was 10 months. Glomerular disease in 6 patients began with onset of the nephrotic syndrome between 20 days and 39 months of age; it was resistant to steroid therapy and led to death from renal failure. Microscopically the glomerular process was a diffuse mesangial sclerosis (DMS). The 2 children with NB and MPH, but without DMS are healthy 2 1/2 and 9 years postnephrectomy. Neither familial incidence nor parental consanguinity was found. This syndrome has complete and partial forms, and its early recognition is important both for patient management and for assessment of prognosis.

Child, Preschool

Acute hCG administration induces seminiferous tubule damage in the adult rat.

In order to study the early (or short time) effects of an hCG stimulation on the seminiferous tubules of the adult rat, a single dose of 100, 200 or 400 IU hCG was administered to eighty to ninety day old rats of the Sherman strain. The histological analysis revealed a tubular damage already noticeable six hours after the injection. This precocious lesion becomes more pronounced two to five days later, consisting of degeneration and hypocellularity of the germinal epithelium, margination of the chromatin in round spermatids and formation of multinuclear giant cells. This damage involves big areas of the testis, particularly of peripheral location. The analysis performed three months after the acute stimulation still showed tubular regressive changes, thus indicating an incomplete reversion of the damage. Changes in the hormonal environment of hCG treated rats were found. Serum testosterone significantly increased from 6 to 72 hours following a 200 IU hCG injection. A severe diminution of serum FSH levels and a significant increase of the serum estradiol were observed. Intratesticular administration of estradiol benzoate was able to reproduce the tubular damage in some animals, while restoration of FSH circulating levels by simultaneous administration of hCG and purified hFSH did not prevent the changes induced by hCG alone. These results suggest that the high intratesticular level of estradiol and not the lowering of serum FSH might be the mechanism responsible for the described testicular injury.

Animals

Testicular testosterone and dihydrotestosterone during sexual development in humans.

The concentrations of testosterone and dihydrotestosterone was determined in the human testis at different stages of sexual development, in patients with undescended testis or in subjects who had been treated for acute lymphoblastic leukemia. Patients were divided in three groups, prepubertal (Tanner's stage I), early puberty (Tanner's stages 2 + 3) and late puberty (Tanner's stages 4 + 5). Even though tubular diameter and serum testosterone followed the expected gradual rise during sexual maturation, testicular testosterone increased abruptly at early puberty, resulting in a high testicular: serum testosterone ratio at this stage. The testicular dihydrotestosterone:testosterone ratio was also high at early puberty. These data suggest that, at initiation of sexual development, seminiferous tubules receive a high androgen load, at a time when other androgen target organs are barely stimulated.

Adolescent

Steroid metabolism by a tumour of the specific gonadal stroma in a child.

A study of steroid metabolism by a tumour of the specific gonadal stroma was carried out in a 10 year old boy. Tumours developed in the two testes from multiple foci, and clinically, no signs of sexual development were evident. Four testicular enzymes necessary for testosterone biosynthesis were estimated in the child, in two adult controls, and in three pre-pubertal boys with male pseudohermaphroditism but normal tests of Leydig cell function. 17 alpha-Hydroxylase and 17 beta-hydroxysteroid dehydrogenase were similar in the five controls and in the gonad with the tumour, while 17,20-desmolase and 3 beta-hydroxysteroid dehydrogenase were grossly deficient in the child with the tumour. These enzyme deficiencies might explain the absence of peripheral virilization in a boy with a tumour of Leydig and Sertoli cells.

17-Hydroxysteroid Dehydrogenases

Changes in distribution of nuclear pores during differentiation of the male germ cells.

Changes in number of nuclear pores in different states of physiologica activity have been reported, but little is known about changing patterns of distribution in the course of cell differentiation. Pore distribution in male germ cells was studied in freeze fracture preparations of immature and mature rodent testis. As in other somatic cells, pores were uniformly and apparently randomly distributed in Sertoli cell nuclei. The nucleus of gonocytes and spermatogonia showed varying degrees of pore clustering. Spermatocytes invariably exhibited very striking pore aggregation with close hexagonal packing in pore-rich areas, and large pore-free areas. In early spermatids, pores appeared to be randomly distributed. As the acrosome formed and spread over the apical pole of the nucleus, pores disappeared ahead of its advancing margin and became more concentrated in the post-acrosomal region. The relationship of pore complexes to the chromosomes and the role of the fibrous lamina are discussed. The question as to whether the changing patterns observed involve movement of pores within fluid nuclear membranes, or a dissolution and reformation of new pores remains unanswered.

Animals

Is FSH required for maintenance of spermatogenesis in adult rats?

Administration of FSH antiserum to adult rats for 14 or 30 days had no or little effect on body, testis or accessory sex gland weights, androgen-binding protein, testosterone levels, germ cell numbers or fertility, thus indicating a relative insensitivity of the testis to withdrawal of FSH. Unlike immature rats, therefore, which do require FSH to initiate spermatogenesis, adult rats do not need this hormone to maintain spermatogenesis.

Age Factors

Unusual features of the nuclear envelope in human spermatogenic cells.

Different types of human germ cells show unusual features of the nuclear envelope. Spermatogonial nuclei demonstrate two kinds of modifications. The first one is a series of intranuclear flattened cisterns, parallel to each other and to the inner aspect of the nuclear envelope. The second one is a nuclear envelope protrusion into the cytoplasm occupied by a double membrane-limited vesicle. Pores are found on the membrane of the vesicle facing the interior of the nucleus. In spermatocytes the nuclear pores are concentrated over certain areas and completely absent from others. In the regions where they are absent a single cytoplasmic cistern of rough endoplasmic reticulum is closely apposed to the outer membrane of the nuclear envelope. Early modifications of the nuclear surface appear in spermatids before the attachment of the acrosomic vesicle and may indicate an active role of the nuclear envelope in the morphogenesis of the acrosome. In round spermatids nuclear pores are absent from the area which is first related to the Golgi and later covered by the acrosomal cap. Single or multiple layers of cytoplasmic annulate lamellae are closely associated with the nuclear envelope over the pore rich areas. Frequently there are intranuclear accumulations of dense material adjacent to the annulate lamellae-nuclear pore complex. The chromatoid body is usually present on the cytoplasmic side of this complex. In the elongating spermatids most annulate lamellae are free in the cytoplasm, often in relation with Golgi and chromatoid body remnants near the axial filament. Few stacks of annulate lamellae are noted adjacent to the pore rich nuclear regions. It is suggested that the described modifications are related to an active nuclear-cytoplasmic interaction.

Adult