Neurons of the lateral entorhinal cortex of the rhesus monkey: a Golgi, histochemical, and immunocytochemical characterization.

This study identifies the neuronal types of the rhesus monkey lateral entorhinal cortex (LEC) and discusses the importance of these data in the context of the connectional patterns of the LEC and the possible role of these cells in neurodegenerative diseases. These neuronal types were characterized with the aid of Golgi impregnation techniques. These characterizations were based upon their spine densities, dendritic arrays, and, where possible, axonal arborizations. The cells could be segregated into only spinous and sparsely spinous types. The most numerous spinous types were pyramidal neurons. Other spinous types included multipolar, vertical bipolar and bitufted, and vertical tripolar neurons. The sparsely spinous neuronal types consisted of multipolar, horizontal bipolar and bitufted, and neurogliaform cells. These cells were further classified with the aid of histochemical stains and immunocytochemical markers. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry stained multipolar, bipolar, and bitufted neurons. Stain for cytochrome oxidase (CO) was found in pyramidal and nonpyramidal cell types. Immunocytochemical techniques revealed several nonpyramidal neurons that contain somatostatin (Som) or substance P (SP). This study complements previous analyses of the neuronal components described in the LEC and adds further information about the distribution of selected neurochemicals within this cortex.

Quantitative maintenance of spermatogenesis in cyclosporine-treated rats by exogenous administration of testosterone propionate.

The authors had previously shown that the subcutaneous administration of cyclosporine (CsA) resulted in an impairment of spermatogenesis. Testosterone levels declined and gonadotropin levels increased, suggesting that CsA primarily affects the synthesis and secretion of testosterone. In this study, the authors attempted to determine whether the exogenous administration of testosterone would maintain spermatogenesis in animals treated with a very high dose of CsA. Sexually mature, male Sprague-Dawley rats were treated subcutaneously with CsA (40 mg/kg per day) alone, or in combination with testosterone propionate (TP; 2 and 5 mg/d per rat), for 14 days. As expected, CsA reduced the body and reproductive organ weights and the levels of serum testosterone, while elevating the levels of follicles-stimulating hormone (FSH) and luteinizing hormone (LH). Quantitative analysis of spermatogenesis revealed a decline in all the different types of germ cells in tubules at stage VII of the cycle of the seminiferous epithelium. Administration of TP in 2 and 5 mg/d per rat doses restored the body and reproductive organ weights and the circulating levels of FSH. The serum levels of LH were below the assay's minimum level of detectability. Analysis of spermatogenesis revealed a dose-dependent increase in the germ cell counts after the administration of 2 and 5 mg of TP. The circulating levels of CsA were also significantly reduced after TP administration. These results revealed that CsA-induced alteration in spermatogenesis can be prevented by the exogenous administration of testosterone.

Effects of subchronic treatment with cis-platinum on testicular function, fertility, pregnancy outcome, and progeny.

Cis-platinum-based chemotherapy is known to impair spermatogenesis, but the effects of paternal cis-platinum treatment on the progeny are unknown. To study this effect, sexually mature male Sprague-Dawley rats were administered intraperitoneal injections of saline or cis-platinum (0.5 mg/kg per day) for 9 weeks. Every week, one set of control and treated animals was mated with females in proestrus. Nineteen days later, the females were subjected to laparotomy, and the numbers of corpora lutea, resorptions, and normal and abnormal fetuses were noted. In conjunction, the effects of treatment on the hypothalamo-pituitary-gonadal axis of the treated males were evaluated. Cis-platinum-treated animals failed to grow; the weights of the reproductive organs and the sperm counts declined from week 2 onward, and sperm motility was reduced throughout the testing period. Circulating and intratesticular levels of testosterone declined from week 3 of treatment and follicle-stimulating hormone levels were not affected. Serum levels of luteinizing hormone declined from week 3 and were not detectable from week 6 onward. However, the pituitary response to gonadotropin-releasing hormone was intact in all treated groups. There was no significant decrease in fertility, but a prominent increase in pre- and postimplantation losses of fetuses after cis-platinum treatment was observed. There was also a decrease in the male-to-female ratio of the offspring. A small but significant number of malformed and growth-retarded fetuses was also found among the offspring of cis-platinum-treated males. These results suggest that subchronic treatment with low doses of cis-platinum may affect progeny; such effects are seen in addition to the apparent alteration in a number of measures of reproductive function of treated males.

Cyclosporine: its effects on testicular function and fertility in the prepubertal rat.

The authors examined the effects of the immunosuppressive drug cyclosporine (CsA) on the male reproductive system in prepubertal rats. Twenty-one-day-old rats were subcutaneously injected with either cremaphorsaline vehicle or CsA (1 and 2 mg/kg/d). The animals were treated until they were 66 days old. Cyclosporine did not affect the weights of the body or testis but decreased the weights of all sex accessory organs. Quantitative analysis of the tubules in stage VII of spermatogenesis revealed a decline in the cell counts of pachytene spermatocytes and step VII spermatids. Testicular and epididymal sperm counts and motility were decreased by 50% and fertility by 60%. Cyclosporine lowered serum testosterone despite an elevation of LH, indicating that the drug directly inhibited testosterone synthesis. Serum creatinine levels were normal in the treated animals, precluding renal failure as the cause for this impairment. Intratesticular concentrations of pregnenolone and 17-hydroxy progesterone were significantly elevated, while those of progesterone, androstenedione, and testosterone were markedly reduced. Determination of steroidogenic enzyme activities indicated that the administration of CsA inhibited the activity of delta 5-3B-hydroxy steroid dehydrogenase-delta 5-4 isomerase (3 beta-HSD). These results clearly indicate that CsA in the doses used is harmful to the male reproductive function in prepubertal rats.

Ultrastructural characterizations of olfactory pathway neurons in layer II of the entorhinal cortex in monkey.

The somatic size, shape, dendritic and axonal morphology, and synaptology of representative neurons in layer II of the primate entorhinal cortex (EC) were analyzed. Layer II "islands" contained large spinous multipolar cells with triangular somata and local circuit axons in addition to multipolar neurons with large, radially arrayed, aspinous, primary processes and thick tapering axons. Small pyramidal neurons with a single, spinous, apical primary segment that bifurcated a short distance from the somata were also found in layer II. Subsequent spinous segments of these neurons with long terminal segments exhibited a paucity of branching in addition to having thick axons tapering into subjacent layers. The importance of providing these additional axonal, dendritic, and synaptic characterizations lies in the contextual role these neurons play in the connectional patterns of the EC with regard to olfaction, olfactory memory, and pathological variations.

The role of academic discipline and gender in high school teachers' AIDS-related knowledge and attitudes.

Adolescents represent the fastest growing segment of HIV+ individuals in the United States. Therefore, high school teachers should be both knowledgeable of and comfortable with issues related to HIV/AIDS. This study examined high school teachers' AIDS-related knowledge and attitudes. One hundred forty-one high school teachers from nine central Massachusetts high schools participated. Participants completed the "HIV/AIDS Knowledge and Attitudes Scales for Teachers," as well as questions regarding their teaching experience and academic disciplines. Results indicated a direct relationship between teachers' knowledge of HIV/AIDS and positive or supportive attitudes toward HIV/AIDS. Significant differences were found based on academic discipline, with allied health teachers scoring significantly higher on the knowledge scale than teachers in any other discipline. Specific examples are discussed, as is the need for increased teacher training and comprehensive AIDS education.

Short term effects of cis-platinum on male reproduction, fertility and pregnancy outcome.

In order to find out the short term effects of cis-platinum treatment on reproductive function of the treated male rats and their progeny, sexually mature male Sprague-Dawley rats were given a single intra-peritoneal injection of either saline or cis-platinum (2, 4, 8 mg./kg.body wt.). One week following the treatment, the animals were mated with proestrus females of proven fertility. The females were scored positive or negative depending upon whether or not spermatozoa were seen in the vaginal smear after mating. However, all the females were watched until day 18, and on day 19, the females that became pregnant were subjected to laparotomy, and the number of corpora lutea, implantation sites and fetuses were counted. The fetuses were weighted and observed for the presence of any morphological abnormalities. Significant pre-implantation loss was seen in the treated groups. The weights of the fetuses were also significantly lower than those from the control group. Analysis of the effects of cis-platinum on the reproductive system of treated males revealed that cis-platinum reduced the reproductive organ weights, sperm counts, sperm motility, fertility and the levels of testosterone, LH and FSH. These results suggest that cis-platinum has a profound deleterious effect on the reproductive system and on the fertility potential of the treated male rats.

Effects of sialoadenectomy and epidermal growth factor on testicular function of sexually mature male mice.

The effect of sialoadenectomy (Sx) and epidermal growth factor (EGF) administration on testicular function was investigated in 8-week old C3H mice. Animals were divided initially into three groups: sham operated controls, Sx, and Sx + EGF treated (100 micrograms./kg./day subcutaneously for 28 days). Sialoadenectomy completely depleted the circulating levels of EGF and reduced body weight and reproductive organ weights. However, kidney weight was not affected. Quantitative analysis of spermatogenesis showed a decrease in preleptotene and pachytene spermatocytes and round spermatids, which resulted in a decrease in sperm counts. Sperm motility and fertility were also significantly decreased. Endocrinologic studies showed a 2- and 6-fold elevation in intratesticular and serum levels of testosterone and a decrease in luteinizing hormone (LH) levels. Follicle stimulating hormone levels were not altered. Administration of EGF to the Sx animals maintained reproductive organ weights, spermatogenesis and levels of LH and testosterone closer to control values; however, sperm motility was not maintained at control value. That sialoadenectomy resulted in a decline in androgen-dependent parameters, in spite of an elevation in testosterone levels, and EGF maintained them closer to the control value suggested that EGF may modulate androgen action. A comparison was therefore carried out between the effects of Sx and administration of flutamide (F), an androgen receptor blocker. Animals were subjected to Sx, F treatment (100 mg./kg./day subcutaneously for 28 days), Sx + F, or Sx + F + EGF. The effects of Sx and F treatment on organ weights, sperm counts and sperm motility were more or less similar. As expected, flutamide treatment increased LH and FSH levels, and testosterone levels were normal. The Sx + F animals showed no further decrease in organ weights, sperm count and motility. Treatment with Sx + F increased intratesticular and serum levels of testosterone by 2- and 10-fold. Circulating levels of LH and FSH were the same as in the flutamide-treated group. Administration of EGF to Sx + F maintained all these parameters, except sperm motility, closer to the control value. These results suggest that EGF either bypasses flutamide effects and acts directly or that EGF modulates androgen action at one or more steps in the signal transduction pathway in the male reproductive organs.

BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families and their implications for genetic counseling.

BACKGROUND: The Sardinian population is genetically homogeneous and could be useful in understanding better the genetics of a complex disease like breast cancer (BC). PATIENTS AND METHODS: Using a screening assay based on a combination of single-strand conformation polymorphism, denaturing high-performance liquid chromatography and sequence analysis, 47 Sardinian families with three or more BC cases were screened for germline mutations in BRCA1 and BRCA2 genes. RESULTS: Three BRCA1/2 germline sequence variants were identified. While BRCA2-Ile3412Val is a missense variant with unknown functional significance, BRCA2-8765delAG and BRCA1-Lys505ter are two deleterious mutations (due to their predicted effects on protein truncation), which were found in seven families (15%). BRCA2-8765delAG was found in six of eight (75%) BRCA1/2-positive families and seven of 501 (1.4%) unselected and consecutively collected BC patients. Prevalence of BRCA1/2 mutations in BC families was significantly correlated with the total number of female BCs (P <0.01) and increased by the presence of (i) at least one case of ovarian or male BC, or (ii) three generations affected, or (iii) bilateral BC. CONCLUSIONS: Identification of such features should address BC patients and their families to genetic counseling and BRCA1/2 mutational analysis. In addition, this is the first report of a detailed BRCA1/2 mutation screening in Sardinia, having immediate implications for the clinical management of BC families.