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Biomedical subjects

W B Neaves

Publications and source records attributed to W B Neaves.

At least 19 recordsLinked to original sources

Effect of age on the composition of seminiferous tubular boundary tissue and on the volume of each component in humans.

Seminiferous tubular boundary tissue thickens with age. The objective was to characterize the composition of boundary tissue in 16 young adult (20 to 29 years) and 18 older adult (51 to 84 years) men. Testes were perfused with glutaraldehyde, placed in osmium, and embedded in Epon 812 (Ladd Research Industries, Burlington, VT). Paired testicular weight, length of tubules, volume of seminiferous epithelium, and daily sperm production were significantly reduced in older men. Although the thickness of boundary tissue was greater (P less than 0.01) in older men, the volume of boundary tissue per man was similar between age groups. The percentages and volumes per man of boundary tissue myoid cells, collagen, microfibrils, and other components also were similar (P greater than 0.05) between age groups. This study confirms that age-related thickening of boundary tissue occurs without the new deposition (augmentation) of collagen or other extracellular components.

Actin Cytoskeleton

Seminiferous tubules and daily sperm production in older adult men with varied numbers of Leydig cells.

Previous studies of adult men have failed to reveal a relationship between numbers of Leydig cells in the testes and rates of sperm production, perhaps because of a functional excess of these cells in younger men. Hence, a possible relationship between Leydig cell numbers and sperm production was sought in 50 older men, aged 50-90 years, in whom the Leydig cell population had been depleted by age-related attrition. When these men were sorted by increasing numbers of Leydig cells per man into two, three, or five groups, no difference could be found between or within these groups when daily sperm production per man (DSP); seminiferous tubular volume, diameter, or length; or seminiferous epithelial volume was examined. Furthermore, no significant correlation could be detected between Leydig cell numbers and DSP in these 50 men. The only relationship between numbers of Leydig cells and spermatogenesis appeared to be a threshold effect, in that men with fewer than 60 million Leydig cells (4 in this study) had drastically reduced DSP. Men with few Leydig cells tended to have larger Leydig cells, and the increased size was due to more cytoplasm instead of nucleoplasm. There were weak but significant positive correlations between total Leydig cell cytoplasm per man and DSP and between average size of a Leydig cell and DSP. These findings suggest that a relationship may exist between sperm production and the amount of cytoplasm containing testosterone-producing organelles in surviving Leydig cells of older men.

Aged

Quantification of human spermatogenesis: germ cell degeneration during spermatocytogenesis and meiosis in testes from younger and older adult men.

Germ cell degeneration during spermatocytogenesis and meiosis was investigated to explain the age-related decline in daily sperm production (DSP). Numbers of Types A-dark, A-pale, and B-spermatogonia, potential daily sperm production per g parenchyma (PDSP) based on type B-spermatogonia, early primary spermatocytes, and late primary spermatocytes, and DSP per g based on early spermatids were determined in 15 men aged 20 to 48 yr (mean +/- SEM, 33 +/- 2 yr) and 15 men aged 52 to 90 yr (65 +/- 3 yr). Testes obtained within 15 h of death (largely due to trauma or heart failure) were perfused vascularly with glutaraldehyde. The number of each cell type per g parenchyma was calculated as the product of the percentage of nuclei in the parenchyma times a correction factor for section thickness and nuclear diameter divided by the volume of a single nucleus of that cell type. Paired testicular weight was lower (p less than 0.01) in older men (33 +/- 3 g) than in the younger men (49 +/- 3 g). Younger and older men had similar numbers of A-dark, A-pale, and B-spermatogonia per g parenchyma. PDSP based on late primary spermatocytes and DSP based on early spermatids were lower (p less than 0.01) in older men than in younger men. In younger men, PDSP was similar (p greater than 0.05) between B-spermatogonia and late primary spermatocytes, whereas DSP measured at the spermatid level was abruptly lower than that estimated from younger cell types. Older men showed reduction in PDSP between early and late primary spermatocytes, with further reduction occurring in DSP at the spermatid level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Characterization of the testicular abnormality in 5 alpha-reductase deficiency.

The testes of five phenotypic women (from four families) with 5 alpha-reductase deficiency were studied. In one of the patients, the enzyme deficiency was similar in the testis and epididymis and in fibroblasts cultured from the labia majora. In testes from four of the patients, the concentrations of the 5 alpha-reduced steroids dihydrotestosterone and 3 alpha-androstanediol were less than 10% of those in normal subjects. We conclude that the testis is involved in 5 alpha-reductase deficiency. Impaired spermatogenesis was evident in testicular biopsies from all five subjects, and in two, sperm production, as estimated in testicular homogenates, was less than 10% of normal. The extent to which spermatogenic arrest is due to 5 alpha-reductase deficiency or testicular maldescent is not clear.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase

Muscle fiber necrosis and regeneration induced by prolonged weight-lifting exercise in the cat.

For periods ranging from 26 to 87 weeks, the morphological characteristics of the flexor carpi radialis (FCR) muscle were examined in four cats trained to perform weight-lifting exercise. Four untrained, sex and weight-matched cats served as controls. The right FCR from each cat was surgically isolated, attached to a tension transducer, and set at its optimal length. The forelimb was perfused with 2% glutaraldehyde in 0.1 M cacodylate buffer. Small bundles of fibers were teased from their origin and insertion tendons and embedded in Epon. Spaced serial sections were used to examine the morphological features of the fibers for trained and control animals. Ultrastructural examination revealed muscle fiber degenerative changes, such as pyknotic nuclei, disruption of the sarcolemma, vacuolation, and disorganization of myofilaments. Such changes were observed at a higher frequency in trained muscle than in control muscle. Spaced serial sections of fiber bundles showed that the degree of degeneration varied along the length of the fiber. Fiber area measurements showed that trained muscle had both larger and smaller fibers than control samples. The very small fibers observed in the trained muscle were considered to be regenerating or "new" fibers since they had not undergone degenerative changes. "Satellite-like" cells were observed in trained muscle. Such cells resembled satellite cells but also contained developing myofilaments. Since evidence of degeneration-regeneration was observed in control samples, but at a lower frequency, it was postulated that weight-lifting exercise accelerates muscle fiber turnover in the cat FCR.

Animals

Age-related change in numbers of other interstitial cells in testes of adult men: evidence bearing on the fate of Leydig cells lost with increasing age.

The number of Leydig cells in the adult human testis declines as a function of increasing age, but whether these cells disappear by transforming into another cell type or by undergoing death and dissolution has not been resolved. This question was addressed in 30 men between 20 and 76 years of age who were known as a group to have experienced significant age-related loss of Leydig cells. If the loss of Leydig cells resulted from transformation into another cell type, other testicular interstitial cells in these men should have increased with age. Testes obtained at autopsy were perfused with glutaraldehyde less than 15 h after sudden death due to trauma or heart attack. Numbers of other interstitial cells were determined by quantitative histometric estimation of the proportion of testicular parenchyma occupied by other interstitial cell nuclei of measured average volume. Other interstitial cell nuclei declined significantly with advancing age (rho = -0.41, P less than 0.05). Mean number of other interstitial cell nuclei per individual was significantly reduced in the 15 men 50 yr old or older compared to the 15 younger men (460 +/- 34 million vs. 609 +/- 43 million; P less than 0.05). There was no tendency for individuals with reduced numbers of Leydig cells to have increased numbers of other interstitial cells. These findings argued against the persistence of Leydig cells in aged testes as dedifferentiated mesenchymal elements. Instead, light and electron microscopic observation of testes from these men revealed evidence of Leydig cell degeneration and dissolution.

Adult

The annual testicular cycle in an equatorial colony of lesser rock hyrax, Heterohyrax brucei.

Adult males from a colony of lesser rock hyrax found near the equator in Kenya exhibited an annual cycle of testicular activity characterized by intense spermatogenesis and elevated androgen status from May to July. Average masses of testes and seminal vesicles taken in these months were almost fourfold greater than those from September to January. During the months of peak testicular activity average diameters of Leydig cells and seminiferous tubules were increased by approximately one half and total tubule length was doubled, compared with values for the quiescent months. Variable testicular development occurred during transitional intervals preceding and following peak testicular activity. From February to Aril thickening of the seminiferous epithelium and appearance of spermatozoa in the caput epididymidis signalled re-establishment of sperm production. In August shedding of germinal cells from the epithelium heralded impending failure of spermatogenesis. Evidence of an annual testicular cycle contradicted the prevalent belief that equatorial hyrax breed all year and suggested that the testicular cycle is a conservative element of hyracoid reproductive strategy.

Animals

The lymphatic drainage of the rat prostate and its status as an immunologically privileged site.

Recent suggestions that the rat prostate is an alymphatic, immunologically privileged site stimulated further investigation of its status using a variety of techniques. Fixation of certain organs by vascular perfusion of glutaraldehyde followed by plastic embedding avoids the distortion and stromal reorganization that often obscures evidence of lymphatic vessels in conventional histological preparations. When applied to the rat prostate, this technique revealed small lymphatic vessels at irregular intervals throughout the sparse stroma. Ink injected into the prostate drained from the organ into iliac lymph nodes within 3 to 4 hr. Enlargement of iliac lymph nodes within 1 week after injection of parental strain lymphoid cells into the prostate of F1 rats confirmed the drainage pattern. Ink and lymphoid cell injections into the bladder wall yielded comparable results, although ink reached iliac nodes sooner than it did in prostate injections. Immunological privilege was investigated by determining survival of skin allografts implanted in the prostate. Skin-into-prostate grafts bearing either major or minor histocompatibility antigens were rejected within a few days of similar orthotopic grafts. The inability of the rat prostate to allow significantly prolonged allograft survival as well as its demonstrated lymphatic drainage argues against an immunologically privileged status.

Animals

Attrition of the human Leydig cell population with advancing age.

Existing evidence suggests that the aging human male experiences a gradual decline in testosterone production, a phenomenon that should be reflected in the Leydig cell population of the testis. It has been proposed that Leydig cells diminish in number with increasing age, but conflicting claims characterize reports of this topic. We have reinvestigated this possibility by histometric analysis of perfused testes from 25 men ranging from 18 to 87 years of age. Average single Leydig cell volume (2,943 +/- 623 micrometer 3, X +/- S.D.) did not change significantly with increasing age (r = 0.24, P greater than 0.2), suggesting that surviving cells remain active. Total testis weight (43.5 +/- 13.9 g) also did not change with age (r = 0.04, P greater than 0.5). However, both total Leydig cell volume and the absolute number of Leydig cells per individual decreased significantly as functions of age (r = -0.71, P less than 0.002, and r = -0.61, P less than 0.005, respectively). Analysis of relationship between these two parameters indicates that the total volume of Leydig cell cytoplasm contained within the human testis is determined by the number of cells present. Our results show that a pair of young adult testes endowed with more than 700 million Leydig cells at 20 years of age may be expected to undergo an attrition rate of approximately 80 million cells per subsequent decade of life. Thus, Leydig cell attrition is an important correlate of declining androgen status in aging men.

Adolescent

Clinical and endocrinological evaluation of patients with congenital microphallus.

Eight patients with congenital microphallus were investigated. Plasma luteinizing hormone, follicle-stimulating hormone, testosterone and androstenedione levels were obtained in all cases. In addition, the response to the administration of human chorionic gonadotropin, luteinizing horomone-releasing hormone and adrenocorticotropic hormone, the assessment of testicular histology by electron microscopy and the measurement of dihydrotestosterone formation by preputial skin were determined in some patients. The results of these studies were compared to similar studies in 6 normal prepubertal boys, 4 boys with bilateral cryptorchidism, 1 male infant with anorchia and 1 adult with hypogonadotropic hypogonadism. The clinical and endocrinological findings in the 8 patients with microphallus can be divided into 2 distinct categories. In 5 patients the disorder is familial, gonadotropin levels are low and there is a normal response to stimulation with chorionic gonadotropin. The data are compatible with the possibility that 3 (possibly 5) of the 8 patients with microphallus have hypogonadotropic hypogonadism. In the other group the cases are sporadic, serum luteinizing hormone and follicle-stimulating hormone levels are elevated and plasma testosterone failed to increase after short-term treatment with chorionic gonadotropin. In these patients a primary testicular disorder appears to be responsible. Experimental and clinical evidence suggests that microphallus results from defective testicular function during the second and third trimesters of pregnancy, either as the result of defective gonadotropin secretion or defective androgen synthesis.

Adolescent

Studies on the subsynaptosomal localization of luteinizing hormone-releasing hormone and thyrotropin-releasing hormone in the rat hypothalamus.

In the current investigation, subcellular particles (synaptosomes) of hypothalamic homogenates were isolated by differential centrifugation and discontinuous sucrose density gradient fractionation and found to be rich in LHRH, TRH, and the neuronal marker, norepinephrine (NE). Of the total quantity of LHRH, TRH, or NE in the nuclei-free homogenate, 52-65% was recovered in synaptosomes, whereas the cytosol, myelin/microsomes, and mitochondria contained only 1-12%. To determine the subsynaptosomal localization of LHRH and TRH, purified synaptosomes were lysed and the resulting suspensions were fractionated on discontinuous sucrose density gradients. LHRH (30-40%) was found to be localized primarily in subsynaptosomal particles which banded at sucrose densities between 0.6-1.0 M. Electron micorscopic analysis of these particles revealed the presence of dense-cored granules (70-80 nm diameter) and synaptosomal membrane remnants. Norepinephrine was found in two pools within the isolated nerve endings: 15-25% of synaptosomal NE was associated with the synaptic vesicles (45-55-nm diameter); about 40% was in the cytosol. TRH was present primarily as a soluble component of the nerve ending. No apparent association of TRH with dense-cored granules was demonstrable in this study; however, there may be some TRH in synaptic vesicles.

Animals

The effect of vasectomy on the testes of inbred Lewis rats.

By 3 months after surgery, testicular weights were 12-14% below control values in a large series of vasectomized rats of the inbred Lewis strain. Testicular sperm concentrations in the vasectomized rats were 25-29% below those in the sham-operated animals. Although modest in magnitude, these differences were highly significant (P less than 0.001). Histometric analysis of testes from a smaller series of vasectomized Lewis rats revealed various proportions of abnormal seminiferous tubules. The degenerative changes included reduction in tubule diameter, fusion of spermatids, and depletion of advanced germinal elements. In the most severely affected tubules, leakiness of the blood-testis barrier was indicated by penetration of lanthanum through Sertoli-cell tight junctions.

Animals