The gonadal steroid withdrawal of menopause is associated with neuronal hypertrophy and increased tachykinin gene expression in the hypothalamic infundibular nucleus. Previous studies have shown that secretion of hypothalamic b -endorphin is modified by gonadal steroids, and there are consistent age-related changes in b -endorphin neurons in rodents. Therefore, in situ hybridization was used to determine if the expression of POMC mRNA, the precursor for b -endorphin, is altered in the hypothalamus of postmenopausal women. The number of POMC mRNA-containing neurons/section in the infundibular nucleus was reduced by 65% in postmenopausal women. In contrast, there was no significant difference in the number of neurons expressing POMC gene transcripts in the retrochiasmatic region. Our findings support the hypothesis that the activity of hypothalamic POMC neurons is decreased in the infundibular nucleus of postmenopausal women. In a second study, we examined the effects of hormone replacement therapy (HRT) on the hypothalamus of young, ovariectomized cynomolgus monkeys. HRT dramatically suppressed tachykinin gene expression while having no detectable effects on POMC neurons. These results provide strong support for the hypothesis that alterations in tachykinin neurons in postmenopausal women are secondary to estrogen withdrawal. Conversely, postmenopausal changes in POMC gene expression may reflect hypothalamic aging. Finally, we found no evidence that HRT, in doses designed to mimic currently prescribed regimens, produces signs of estrogen toxicity in the primate infundibular nucleus. Degenerative changes, including neuron loss, have been reported in the arcuate nucleus of aging rodents, and hypothalamic aging has been shown to contribute to reproductive decline in these species. In addition, in the infundibular nucleus of postmenopausal women, there is an age-associated decline in proopiomelanocortin gene expression. To evaluate the possibility of neuron loss associated with reproductive aging, unbiased stereological methods were used to compare the total number of infundibular neurons between groups of premenopausal and postmenopausal women. The mean neuronal volume was increased by 40% in postmenopausal women but there was no change in the total number of neurons. These data suggest that the neuronal hypertrophy observed in the postmenopausal human hypothalamus is not a pathological process secondary to degeneration of adjacent infundibular neurons.

Estimation of antemortem body weight is difficult to ascertain from skeletal material. In this analysis, I examine 49 right tali. T-tests run on right and left tali from the same sample show no significant differences between the two sides. Incorporation of data from various individuals, including both males and females, allows for the statistical assessment obtained through Pearson's correlation coefficient between estimated antemortem body weight and 21 measurements conducted on the surface of the talus. All correlations ranged from R = -.1706 to +.4811, suggesting no strong relationship between estimated antemortem body weight and variables utilized in this analysis. A multiple regression was applied and provided an adjusted R square of +.2150. This suggests the measurements incorporated into the statistical run only accounted for twenty-one percent of the total variance in estimated body weight. The surface anatomy of the talus relates more to an interplay between form and function than to weight-bearing.

The study of patients has shown that certain higher cognitive processes, such as those involved in the monitoring and the manipulation of information within working memory, depend on the integrity of both the dorsolateral frontal cortex and the medial temporal lobe memory system, as well as on their functional interaction (Petrides, 1994). Small surgical removal of the anterior temporal region, including the entorhinal cortex, is not sufficient to interrupt that fronto-hippocampal relationship. More extensive removals, however, that include a sizeable portion of the hippocampus and the surrounding parahippocampal cortex do disrupt such a fronto-hippocampal functional interaction (Petrides and Milner, 1982). Based on these data, it was postulated that the fronto-hippocampal functional interaction is not entirely dependent upon the integrity of the entorhinal cortex. To test this hypothesis, injections of tritiated amino acids were placed within individual cytoarchitectonic units of the frontal cortex, and the resulting labeling in the hippocampal region was analyzed. It was shown that the mid-dorsolateral frontal cortex, together with its medial cortical extension, is the only frontal region that sends efferent fibers, running caudally as part of the cingulum bundle, to the presubiculum, the posterior parahippocampal gyrus, as well as to the retrosplenial cortex. A light contingent of these fibers, congregating in the outermost layer of both the retrosplenium and the presubiculum, course into the molecular layer of the hippocampus proper. In complete agreement with the work with patients, these findings have confirmed the hypothesis that the mid-dorsolateral frontal cortex is closely affiliated with the hippocampal system, and demonstrated that this hodological relationship bypasses the entorhinal cortex. / Another major contribution of the present work has been to provide the first architectonic analysis of a gross morphological region, referred to as the caudomedial lobule, which receives inputs from the mid-dorsolateral frontal cortex and its medial extension. This architectonic analysis has revealed that the caudomedial lobule is nothing but the postero-ventral extension, below the splenium of the corpus callosum, of areas 29 and 30, which together form the retrosplenial cortex, and of area 23, which partly forms the posterior cingulate cortex. Among the cortical fields that comprise the postero-ventral part of the retrosplenial cortex, area 30 is the major recipient of the mid-dorsolateral frontal inputs. / By virtue of the close anatomical relation of area 30 with the mid-dorsolateral frontal cortex and its medial extension, it is suggested that this part of the retrosplenial cortex may be a critical relay-station along the dorsomedially directed fronto-hippocampal pathway. In order to validate this hypothesis, the connections of area 30 were investigated by placing injections of anterograde and retrograde tracers within the limits of this retrosplenial area. This study has demonstrated that area 30 is bi-directionally connected with and only with that part of the lateral frontal cortex that lies above the sulcus principalis, namely the mid-dorsolateral frontal cortex, along with all the structures of the posterior hippocampal region that are the recipients of the inputs from the mid-dorsolateral frontal cortex. Since the fronto-hippocampal association fiber system described in the present thesis is most probably subserving certain aspects of working memory, area 30, by virtue of its bi-directional connections with both the mid-dorsolateral frontal cortex and the posterior parahippocampal cortex, is in a privileged position to exert a major influence in working memory processing.

The kinematics, temporal and sequential organization of the lower limb joints were assessed during jump downs at a constant height (45 cm) in seven practised subjects under four conditions: (SS) stiff takeoff and landing, (SC) stiff takeoff and compliant landing, (CS) compliant takeoff and stiff landing, and (CC) compliant takeoff and landing surfaces. The timing and sequencing of joint motions were unaffected by the compliance of the takeoff or landing surfaces. During takeoff ankle adjustments may have been influenced by proprioceptive inputs about the takeoff surface compliance, whereas knee adjustments could mean that the landing program interferes with the takeoff. Adjustments prior to, at, and post landing depended on the landing surface compliance and suggest that different strategies might have been employed to control joint motions. This study may provide valuable information on the coordinative strategies used to encounter various surfaces as found in the natural environment.

To determine whether muscle contractions can increase muscle blood flow independently from metabolic factors, we isolated the diaphragmatic vasculature of 16 anesthetized and mechanically ventilated dogs. Phrenic inflow (Qphr) was controlled with a constant pressure source and the pressure (Pa) was decreased in steps to obtain the pressure-flow relation (P-Q). The vasculture was maximally vasodilated and contractions occurred spontaneously (n = 6) or were induced by twitches (n = 12) or tetanic trains (n = 7). The P-Q relations with contractions were compared to those with vasodilatation alone. With spontaneous contractions, the pressure intercept decreased from 47.35 $ pm$ 17.44 to 33.77 $ pm$ 16.82 mmHg (p $<$ 0.05) and the slope remained unchanged so that at Pa = 100 mmHg, Qphr increased from 36.22 $ pm$ 34.85 to 43.91 $ pm$ 38.22 ml/min/100g (p $<$ 0.05). Flow increased slightly with twitches but not with trains. We also elicited twitches, 12/min and 60/min trains in vascularly isolated gastrocnemius muscles (n = 6) and found no change in flow. In conclusion, the muscle pump has only a small effect on muscle blood flow.

$ beta$-Hexosaminidase is a lysosomal enzyme which exists as two isoenzymes: Hex A ($ alpha beta$) and Hex B ($ beta beta$). Its presence in the testis and epididymis suggest important roles for this enzyme and their substrates in male fertility and reproductive functions. The main focus of this investigation was to analyze the effects of a deficiency of these isoenzymes within the male murine reproductive tract. Disruption of the Hexa gene encoding the $ alpha$-subunit of $ beta$-hexosaminidase led to the generation of a mouse model of human Tay-Sachs while disruption of the Hexb gene encoding the $ beta$-subunit of $ beta$-hexosaminidase led to a mouse model of human Sandhoff disease, thus providing the opportunity to analyze the effects of Hex A and Hex B deficiency on epithelial cellular morphology of the male reproductive tract. Analysis of the testis, efferent ducts and epididymidis of 5 weeks, 3, 5 and 12 month old Tay-Sachs (Hexa $-/-$) and 1 and 3 month old Sandhoff (Hexb, $-/-$) was performed; the wild-type (Hexa +/+, Hexb +/+) mice at all ages were also examined as controls. (Abstract shortened by UMI.)

The scientific aim of computational neuroanatomy using magnetic resonance imaging (MRI) is to quantify inter- and intra-subject morphological variabilities. A unified statistical framework for analyzing temporally varying brain morphology is presented. Based on the mathematical framework of differential geometry, the deformation of the brain is modeled and key morphological descriptors such as length, area, volume dilatation and curvature change are computed. To increase the signal-to-noise ratio, Gaussian kernel smoothing is applied to 3D images. For 2D curved cortical surface, diffusion smoothing, which generalizes Gaussian kernel smoothing, has been developed. Afterwards, statistical inference is based on the excursion probability of random fields defined on manifolds. / This method has been applied in localizing the regions of brain tissue growth and loss in a group of 28 normal children and adolescents. It is shown that children's brains change dramatically in localized areas even after age 12.

Most authors recommend drawing the mechanical axis on a three-foot (90 cm) full leg length x-ray for accurate assessment of knee alignment. Three foot x-rays are difficult to perform and reproduce and involve undue radiation to the gonads. The purpose of this project is to propose a new radiographic technique whereby the mechanical axis of the knee can be assessed on a short A/P x-ray of the entire tibia. / Methodology. 21 normal adults and 25 patients with malaligned knees were investigated in the following manner--the patient was x-rayed in standing position with the legs positioned exactly parallel to one another and vertical to the floor. Under these circumstances, the ankles were apart by a distance (distance F$ sb1$) equal to the distance between the femoral heads (distance F). The mechanical axes were hence parallel to one another and parallel to the long axis of the x-ray cassette and vertical to the floor. Two separate x-rays were taken, a three-foot (90cm) long x-ray and a short x- ray of the entire tibia. The mechanical axis was determined on the 90 cm, three-foot long x-ray. / A vertical line drawn on the short x-ray starting from the centre of the ankle and extended upwards and parallel to the long axis of the x-ray cassette could accurately identify the mechanical axis of the knee using either technique. (Fig. 1) / The technique has been called the "Parallel Mechanical Axes X-ray Technique". It has been validated and it will be demonstrated that such an x-ray technique: (1) Standardizes positioning of the lower extremities. (2) Is a precise, easily controllable method to assess knee alignment. (3) A short x-ray of the entire tibia is sufficient, thus reducing the cost of x-rays by 50%. (4) Obviates the need to visualize the pelvis thus minimizing net radiation exposure. (5) May be used in clinics and smaller hospitals, since it requires simple and inexpensive x-ray facilities.

Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2006. / Source: Dissertation Abstracts International, Volume: 68-02, Section: B, page: 1355. Adviser: Gabriele Gratton. Includes bibliographical references. Available on microfilm from Pro Quest Information and Learning.

These studies examined the pharmacokinetics of cocaine following its chronic subcutaneous (s.c.) administration to pregnant rats and the effects of this treatment on neurotensin/neuromedin (NT/N) mRNA expression in the brains of their offspring. First, I examined the distribution of cocaine and its metabolites benzoylecgonine (BE) and norcocaine in pregnant rats following twice-daily s.c. injections of 20 mg/kg cocaine from gestational day (GD) 8–GD 21. Following a single injection on GD 21, maternal and fetal trunk blood, fetal brains, and amniotic fluid (AF) were collected at 8 separate time points from 5 min to 12 h. Cocaine peaked in maternal plasma at 1 h and at 2 h in fetal plasma, fetal brain and AF. Peak BE levels were detected at 4 h in maternal plasma, fetal plasma, and fetal brain, and at 8 h in the AF. An additional group of dams given both injections on GD 21 and sacrificed 2 h later showed increased concentrations of BE in both fetal compartments and in the AF. Previously undetectable, norcocaine was now measurable in the AF. Chronic cocaine administration increases NT/N mRNA in the nucleus accumbens. To further understand the mechanisms involved, I conducted a dose response study evaluating the role of the D3 receptor on the expression of NT/N mRNA in the nucleus accumbens shell using in situ hybridization. Animals were sacrificed 3 h following an acute challenge with either the D3 agonist PD 128904 or the antagonist nafadotride. As neither compound significantly altered NT/N mRNA levels, no further work was performed with these drugs. To examine the effects of prenatal cocaine exposure on neurotensin expression, adult male offspring from either cocaine (40 mg/kg daily, GD 8–21) or saline-injected dams were treated with a single daily i.p. injection of cocaine or saline for 10 days and sacrificed 1 h after the last injection. This treatment resulted in increased NT/N mRNA in the nucleus accumbens, fundus, striati, and dorsomedial striatum regardless of prenatal treatment, and significantly greater NT/N mRNA expression within the medial preoptic nucleus (MPN) of offspring from pair-fed saline dams. Thus, prenatal cocaine exposure alters the NT/N response in the MPN to postnatal cocaine challenge.