Biomedical subjects

M L Kashon

Publications and source records attributed to M L Kashon.

15 recordsLinked to original sources

PubMed2002

A method for reducing adaptor misalignment when testing gloves using ISO 10819.

OBJECTIVES: International standard ISO 10819 was established in order to quantify the vibration attenuation characteristics of anti-vibration gloves. One problem that exists with the standard is possible misalignment of the palm adaptor that is placed underneath the test glove. If the adaptor becomes misaligned, the measured glove transmissibility will be lower than the actual value. A tri-axial accelerometer was installed in the adaptor and was used as the basis for providing visual feedback of the adaptor alignment to the test subjects. The objective of this study was to test the hypothesis that adaptor misalignment could be reduced by providing feedback to the test subjects. METHODS: Eight male volunteers (mean age 24.8 yr) were used in the study. Each subject performed two sets of tests: the standard ISO 10819 glove test and the modified version. Three different anti-vibration gloves were tested. Glove transmissibility and adaptor misalignment were calculated for each glove. A three-way analysis of variance was used to analyze the results. RESULTS: A comparison of the two testing methods showed that the modified glove testing method did reduce misalignment significantly, which, in turn, resulted in an increase in the measured glove transmissibility. CONCLUSIONS: The proposed method greatly improved the standard deviation of transmissibility and made the test results more consistent.

Adult↗

PubMed2001

Quantitative relationship between arsenic exposure and AP-1 activity in mouse urinary bladder epithelium.

Because of the potential of arsenic for causing cancer in humans, and of the fact of widespread environmental and occupational exposure, deriving acceptable human-limit values has been of major concern to industry as well as to regulatory agencies. Based upon epidemiological evidence and mechanistic studies, it has been argued that a non-linear dose-response model at low-level exposures is more appropriate for calculating risk than the more commonly employed linear-response models. In the present studies, dose-response relationships and recovery studies employing a cancer precursor marker, i.e., activating protein (AP)-1 DNA-binding activity, were examined in bladders of mice exposed to arsenic in drinking water and compared to histopathological changes and arsenic tissue levels in the same tissue. While AP-1 is a functionally pleomorphic transcription factor regulating diverse gene activities, numerous studies have indicated that activation of the MAP kinase pathway and subsequently increased AP-1 binding activities, is a precursor for arsenic-induced cancers of internal organs as well as the skin. We observed previously that within 8 weeks of exposure AP-1 activation occurs in urinary bladder tissue of mice exposed to arsenic in the drinking water. In the present studies, C57BL/6 mice were exposed to sodium arsenite at various concentrations in the drinking water for 8 consecutive weeks. Minimal but observable AP-1 activity occurred in bladder tissue at exposure levels below which histopathological changes or arsenic tissue accumulation was detected. Marked AP-1 DNA-binding activity only occurred at exposure levels of sodium arsenite above 20 microg/ml, where histopathological changes and accumulation of arsenic in the urinary bladder epithelium occurred. Although the experimental design did not allow statistical modeling of the entire dose-response curve, the general shape of the dose-response curve is not inconsistent with the previously proposed hypothesis that arsenic-induced cancer follows a non-linear dose-response model.

Animals↗

PubMed2001

Chronic smoking enhances tachykinin synthesis and airway responsiveness in guinea pigs.

This study tests the hypothesis that the bronchial hyperreactivity induced by chronic cigarette smoke (CS) exposure involves the increased expression and release of tachykinins and calcitonin gene-related peptide (CGRP) from afferent nerve fibers innervating the airways. In guinea pigs chronically exposed to CS (20 min twice daily for 14-17 d), peak response in total lung resistance to capsaicin (1.68 microg/kg, intravenously) was significantly greater than that evoked by the same dose of capsaicin in control (air-exposed) animals. This augmented response in CS-exposed animals was abolished after treatment with CP-99994 and SR-48968, the neurokinin (NK)-1 and NK-2 receptor antagonists, suggesting the involvement of tachykinins in chronic CS-induced airway hyperresponsiveness (AHR). Further, substance P (SP)-like immunoreactivity (LI) and CGRP-LI in the airway tissue were significantly greater in the CS animals than in the control animals. Finally, beta-preprotachykinin (PPT, a splice variant from the PPT A gene encoding tachykinins including SP and NKA) messenger RNA levels as measured by in situ hybridization histochemistry displayed a significant increase in jugular ganglion neurons but not in dorsal root or nodose ganglion neurons. These data suggest that chronic CS-induced AHR is related to an increase in SP synthesis and release in jugular ganglion neurons innervating the lungs and airways.

Analysis of Variance↗

PubMed1998

Aging alters the rhythmic expression of vasoactive intestinal polypeptide mRNA but not arginine vasopressin mRNA in the suprachiasmatic nuclei of female rats.

Our laboratory has shown that the ability of the suprachiasmatic nuclei (SCN) to regulate a number of rhythmic processes may be compromised by the time females reach middle age. Therefore, we examined the effects of aging on the rhythmic expression of two neuropeptides synthesized in the SCN, vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP), using in situ hybridization. Because both VIP and AVP are outputs of the SCN, we hypothesized that age-related changes in rhythmicity are associated with alterations in the patterns of expression of these peptides. We found that VIP mRNA levels exhibited a 24 hr rhythm in young females, but by the time animals were middle-aged, this rhythm was gone. The attenuation of rhythmicity was associated with a decline in the level of mRNA per cell and in the number of cells in the SCN producing detectable VIP mRNA. AVP mRNA also showed a robust 24 hr rhythm in young females. However, in contrast to VIP, the AVP rhythm was not altered in the aging animals. The amount of mRNA per cell and the number of cells expressing AVP mRNA also was not affected with age. Based on these results we conclude that (1) various components of the SCN are differentially affected by aging; and (2) age-related changes in various rhythms may be attributable to changes in the ability of the SCN to transmit timing information to target sites. This may explain why the deterioration of various rhythmic processes occurs at different rates and at different times during the aging process.

Aging↗

PubMed1998

Estradiol protects against ischemic injury.

Clinical studies demonstrate that estrogen replacement therapy in postmenopausal women may enhance cognitive function and reduce neurodegeneration associated with Alzheimer's disease and stroke. This study assesses whether physiologic levels of estradiol prevent brain injury in an in vivo model of permanent focal ischemia. Sprague-Dawley rats were ovariectomized; they then were implanted, immediately or at the onset of ischemia, with capsules that produced physiologically low or physiologically high 17beta-estradiol levels in serum (10 or 60 pg/mL, respectively). One week after ovariectomy, ischemia was induced. Estradiol pretreatment significantly reduced overall infarct volume compared with oil-pretreated controls (mean+/-SD: oil = 241+/-88; low = 139+/-91; high = 132+/-88 mm3); this protective effect was regionally specific to the cortex, since no protection was observed in the striatum. Baseline and ischemic regional CBF did not differ between oil and estradiol pretreated rats, as measured by laser Doppler flowmetry. Acute estradiol treatment did not protect against ischemic injury. Our finding that estradiol pretreatment reduces injury demonstrates that physiologic levels of estradiol can protect against neurodegeneration.

Animals↗

PubMed1998

Sex differences in the daily rhythm of vasoactive intestinal polypeptide but not arginine vasopressin messenger ribonucleic acid in the suprachiasmatic nuclei.

The timing of the preovulatory surge of LH in female rodents is tightly coupled to the environmental light/dark cycle. This coupling is mediated by the circadian pacemaker located in the suprachiasmatic nuclei (SCN). Studies indicate that vasoactive intestinal polypeptide (VIP) and arginine vasopressin (AVP), which are synthesized in the SCN, transmit circadian information from the SCN to GnRH neurons, thereby regulating the timing of the LH surge. However, to date, the rhythmic expression of these two peptides in the SCN has only been examined in males. The pattern of VIP expression in males is difficult to reconcile with its role in the LH surge. The purpose of the present study was to assess the rhythm of VIP messenger RNA (mRNA) levels in the SCN of female rats under several endocrine conditions. We compared this rhythm to that in males and to AVP mRNA rhythms in all experimental groups. In all groups of females, VIP mRNA levels were rhythmic, with peak expression occurring during the light phase and a nadir occurring during the dark phase. The rhythm was approximately 12 h out of phase compared with that in males. The rhythmic expression of AVP mRNA in the SCN was virtually identical in all groups of animals. Based on these results, we conclude that 1) the rhythm of VIP seen in the SCN of females during the day may serve as a facilitory signal from the SCN to GnRH neurons; 2) the sex-specific pattern of VIP mRNA does not depend on estradiol; and 3) AVP gene expression within the SCN is not sexually differentiated or altered by estradiol.

Animals↗

PubMed1997

Brain region-specific regulation of luteinizing hormone-releasing hormone messenger ribonucleic acid in the male ferret: interactions between pubertal maturation and testosterone.

This study examined the regulation of LHRH messenger RNA (mRNA) during pubertal maturation and by testosterone in male ferrets. Prepubertal and postpubertal ferrets were either intact or were castrated and treated with daily injections of oil or 5 mg/kg testosterone propionate for 14 days. In situ hybridization for LHRH mRNA was performed using an 35S-labeled 48-base oligonucleotide complementary to the human LHRH-coding region. Computerized image analysis was performed on cells in the preoptic area, retrochiasmatic area, arcuate nucleus (ARC), and median eminence; cells were classified as labeled if the number of pixels representing silver grains over the cell was 5 or more times the number of background silver grain pixels. Both pubertal maturation of intact males and castration of prepubertal males resulted in an increase in the number of labeled cells in the ARC. These effects were not observed in any of the other three brain regions, suggesting that ARC LHRH-producing neurons are of primary importance in the presumed increase in LHRH release that occurs as a consequence of either pubertal maturation or castration of prepubertal males. Castration of adults did not increase the number of labeled cells in any brain area, but resulted in an increase in silver grains per labeled cell only in the preoptic area. Thus, LHRH mRNA is regulated during puberty primarily in the ARC, and the particular cell group in which LHRH mRNA is most strongly regulated by testosterone changes with pubertal maturation.

Animals↗

PubMed1997

Aging of the female reproductive system: a window into brain aging.

The menopause marks the permanent end of fertility in women. It was once thought that the exhaustion of ovarian follicles was the single, most important explanation for the transition to the menopause. Over the past decade, this perception has gradually changed with the realization that there are multiple pacemakers of reproductive senescence. We will present evidence that lends credence to the hypothesis that the central nervous system is a critical pacemaker of reproductive aging and that changes at this level contribute to the timing of the menopause. Studies demonstrate that an increasing de-synchronization of the temporal order of neuroendocrine signals may contribute to the accelerated rate of follicular loss that occurs during middle age. We suggest that the dampening and destabilization of the precisely orchestrated ultradian, circadian, and infradian neural signals lead to miscommunication between the brain and the pituitary-ovarian axis. This constellation of hypothalamic-pituitary-ovarian events leads to the inexorable decline of regular cyclicity and heralds menopausal transition.

Aged↗

PubMed1996

Distribution and hormonal regulation of androgen receptor immunoreactivity in the forebrain of the male European ferret.

The distribution and hormonal regulation of androgen-receptor-immunoreactive (AR-ir) cells in the male European ferret forebrain were examined. AR-ir cells were found in many limbic and hypothalamic structures, and their distribution was similar to that reported for cells that either bind androgen or contain AR protein or mRNA in other species. Regulation of brain AR immunoreactivity by gonadal steroids was brain-region dependent. In most regions examined, including the preoptic area, amygdala, and several hypothalamic nuclei, castration reduced the density of AR-ir profiles and the intensity of immunocytochemical staining, and long-term (days) androgen, but not estrogen, replacement restored these parameters of AR immunoreactivity. Other areas, such as the bed nucleus of the stria terminalis, appeared to be relatively resistant to modulation of AR immunoreactivity by castration and long-term androgen treatment. The ability of testosterone to increase AR-ir profile density is not a simple consequence of translocation of AR from the cytoplasm to the nucleus, because short-term (hours) treatment with testosterone did not result in an increase in AR-ir profile density equivalent to that seen after 10 days of testosterone treatment. Thus, androgens appear to be able to increase AR levels within certain brain cell groups, thereby altering target tissue responsiveness to their own action.

Animals↗

PubMed1996

Menopause: the aging of multiple pacemakers.

Menopause signals the permanent end of menstrual cyclicity in a woman's life. Its impact reaches far beyond just the reproductive system. An understanding of the factors that interact and govern the process of aging in the reproductive system will help us to develop strategies for alleviating the negative aspects of menopause and may help us to better comprehend the process of biological aging.

Animals↗

PubMed1995

Photoperiod times ontogeny of androgen receptor-immunoreactive cells in ferrets.

Regional increases in the density of androgen receptor-immunoreactive (AR-IR) brain cells are temporally correlated with pubertal maturation in male ferrets. If these increases in AR-IR cells are directly linked to pubertal maturation, then experimentally advancing the onset of puberty should similarly advance the timing of the increase in AR-IR cells. Photoinduction of pubertal maturation by transfer to long photoperiods advanced the onset of gonadal growth, elevated testosterone secretion and increased density of AR-IR cells in regions of the hypothalamus, relative to ferrets undergoing spontaneous pubertal maturation under short photoperiods. This experiment provides evidence that an increase in the density of AR-IR cells in specific brain regions is a neuroanatomical correlate of puberty that is also influenced by environmental day length.

Analysis of Variance↗

PubMed1995

Regulation of brain androgen receptor immunoreactivity by androgen in prepubertal male ferrets.

During pubertal maturation, there is an increase in the number of androgen receptor-immunoreactive (AR-IR) cells in the preoptic area (POA), arcuate nucleus (ARC), medial amygdala (mAMY), and ventromedial hypothalamic nucleus (VMH) of the male ferret brain. In contrast, the number of AR-IR cells in the bed nucleus of the stria terminalis (BNST) or lateral septum (ISEP) does not change with pubertal development. This experiment tested the hypothesis that the pubertal increase in AR-IR cells in certain brain regions is the result of the pubertal increase in circulating androgens. Prepubertal male ferrets were left intact or were castrated and treated daily (10 days) with s.c. injections of either oil, testosterone (T; 5 mg/kg), dihydrotestosterone (DHT; 5 mg/kg), or estradiol (E; 10 micrograms/kg). Brains were processed for AR immunocytochemistry, and the number of immunopositive cells was quantified in POA, ARC, mAMY, VMH, BNST, and ISEP. Overall, castration reduced the number of AR-IR cells below that seen in intact animals, and E administration did not restore AR-IR cell number. Treatment of castrates with androgens restored numbers of AR-IR cells to those of intact animals in the BNST, ISEP, and VMH. However, AR-IR cell numbers were significantly greater in androgen-treated castrates than in intact animals in POA, mAMY, and ARC. These data show that AR-IR cells in prepubertal male ferrets are sensitive to circulating levels of androgens, supporting the hypothesis that the pubertal rise in T is responsible for the pubertal increase in the number of AR-IR cells in the POA, mAMY, and ARC.

Amygdala↗

PubMed1994

Pubertal maturation is associated with an increase in the number of androgen receptor-immunoreactive cells in the brains of male ferrets.

Androgen receptor-immunoreactive (AR-IR) cells were identified in brains of male ferrets before and after the onset of pubertal maturation. There was a greater number of AR-IR cells after the onset of pubertal maturation in some, but not all, brain regions examined. Regions in which the number of AR-IR cells increased included the preoptic area and the amygdala, areas known to be involved in the control of male reproductive behaviors. The mechanisms responsible for the increase in AR-IR cells are unknown, but might be related to the higher circulating levels of testosterone that were present in the older animals. Testosterone may increase androgen receptor (AR) immunoreactivity both by concentrating already existing ARs within the nucleus and by stimulating de novo synthesis of receptor protein.

Aging↗

PubMed1992

Prenatal flutamide alters sexually dimorphic nuclei in the spinal cord of male rats.

The effects of prenatal exposure to the antiandrogen flutamide on two sexually dimorphic nuclei of the lumbar spinal cord, the dorsolateral nucleus (DLN) and the spinal nucleus of the bulbocavernosus (SNB), were investigated. Rat dams were given daily injections of 5 mg flutamide or vehicle alone from day 11 through 21 of pregnancy. The spinal cords and perineal morphology of their male and female offspring were examined in adulthood. Flutamide reduced the number of SNB and DLN neurons, reduced the somal and nuclear area of SNB neurons, and reduced the weight of the perineal muscles in males. Flutamide produced no effect in females. No sexual dimorphism was found in the mean somal area of DLN neurons, but a sexual dimorphism was found in the distribution of somal areas in our samples; females had proportionately more large neurons than males. Flutamide-treated males also had proportionately more large neurons than control males but fewer than females. A sexual dimorphism was found in the nuclear areas of DLN neurons but flutamide did not influence this trait.

Animals↗

PubMed1992

Prenatal beta-endorphin can modulate some aspects of sexual differentiation in rats.

Sexually dimorphic traits were studied in offspring of rats injected with 33 micrograms rat beta-endorphin (beta-END) three times daily from Day 14 to Day 21 of pregnancy. beta-END males had shorter neonatal anogenital distances than did controls and were more likely to show the female lordosis pattern as adults, but they did not differ in male copulatory behavior. When given a choice between spending time with an estrous female or a male, beta-END males showed a lower preference for the female than did control males. The number and somal size of neurons in the bulbocavernosus and dorsolateral nucleus of the lumbar spinal cord were unaffected by drug exposure. Elevated beta-END during fetal ontogeny apparently alters the differentiation of some, but not all, sexually dimorphic traits. The data suggest that endogenous opioids may contribute to the etiology of the prenatal stress syndrome.

Animals↗