Functional transplantation of the rat pituitary gland

OBJECTIVE: These studies evaluated the ability of transplanted pituitary cells to restore pituitary function in hypophysectomized rats. METHODS: The pituitary glands of neonatal Lewis rats were rapidly removed, enzymatically dispersed, and stereotactically introduced into the third ventricle of hypophysectomized adult male Lewis rats. Four weeks after implantation, plasma levels of anterior pituitary hormones in implanted animals were compared with those of sham-transplanted control animals. RESULTS: Plasma levels of prolactin, growth hormone, thyroid-stimulating hormone, and beta-endorphin were below the range of detection in 14 sham-operated animals. In implanted animals, restitution of serum prolactin occurred in 100% of the animals tested, with levels of 2.6 +/- 1.0 ng/ml (mean +/- standard error of the mean; normal, 2-4 ng/ml). Growth hormone was assayable in 71% of the animals, with a mean value of 29 +/- 13 ng/ml over all animals (normal, 1-100 ng/ml); thyroid-stimulating hormone was restored in 68%, with mean resting levels of 79 +/- 13 ng/ml (normal, 100-400 ng/ml); luteinizing hormone levels were found in 53%, with mean levels over all animals of 0.2 +/- 0.1 ng/ml (normal, 0.5-1.0 ng/ml); and beta-endorphin was restored in 45% to high resting levels of 163 +/- 31 pg/ml (normal, 20-30 pg/ml). A challenge with hypothalamic releasing factor and a cold stress test were performed on the animals that had received transplants. Positive hormone responses to both of these tests suggested sensitivity of the pituitary grafts to both endogenous and exogenous sources of stimulation. Histological sections of paraformaldehyde-fixed brains from implanted animals clearly demonstrated survival of clusters of grafted pituitary cells. Positive immunohistochemical staining for adrenocorticotropic hormone and thyroid-stimulating hormone was demonstrated in sections of the grafted tissue. CONCLUSION: These data suggest survival of neonatal pituitary transplants in the third ventricle of adult hypophysectomized rats with concomitant restoration of anterior pituitary hormone function.     

Centromere-linkage analysis and consolidation of the zebrafish genetic map

The ease of isolating mutations in zebrafish will contribute to an understanding of a variety of processes common to all vertebrates. To facilitate genetic analysis of such mutations, we have identified DNA polymorphisms closely linked to each of the 25 centromeres of zebrafish, placed centromeres on the linkage map, increased the number of mapped PCR-based markers to 652, and consolidated the number of linkage groups to the number of chromosomes. This work makes possible centromere-linkage analysis, a novel, rapid method to assign mutations to a specific linkage group using half-tetrads.     

Age-dependent effects of muscle vibration and the Jendrassik maneuver on the patellar tendon reflex response

OBJECTIVE: To explore possible effects of aging on the excitability of spinal reflexes. DESIGN: Using a cross-sectional design, the influences of muscle vibration and the Jendrassik maneuver on patellar tendon reflex function were compared between 30 young adults and 15 older adults. SETTING: Motor control research laboratory. SUBJECTS: The young adults were volunteers of college age. The older adults (74.5 +/- 4.14 yr) were volunteers from the local community. All subjects were free of medications and neurological conditions that would affect normal neuromuscular responses. MAIN OUTCOME MEASURES: A force-time curve analysis of the patellar tendon reflex response was used to assess the inhibition and facilitation of spinal reflexes. In the experimental protocol to assess spinal reflex inhibition, 100 Hz vibration was applied to the right quadriceps muscle. In another experimental protocol, spinal reflex facilitation was assessed using the Jendrassik maneuver. To perform the Jendrassik maneuver, subjects were instructed to grasp their hands together and to pull as hard as possible while breathing normally. After a 2-second count, the tendon tap was delivered to the right leg and the subject was instructed to relax. In both experimental protocols, control patellar tendon reflexes were collected. RESULTS: Analysis of variance for reflex peak force revealed a significant 30% reduction in the amount of vibration-induced reflex inhibition with increasing age, and a similar 33% reduction in the amount of Jendrassik maneuver facilitation observed for the older adults as compared with the younger adults. CONCLUSION: These results support the hypothesis that inhibitory and excitatory influences acting on the alpha motoneuron pool are different in young and older adults.     

Fewer bone histomorphometric abnormalities with intermittent than with continuous slow-release sodium fluoride therapy

To help resolve the uncertainty whether sodium fluoride (NaF) therapy should be given intermittently or continuously, we examined iliac crest bone biopsies (before and after treatment) and fragility fracture rates in 35 intermittently treated (group I) and 69 continuously treated (group C) patients; all received calcium. The following statistically significant results were obtained. Reduction in vertebral fracture rate was similar in the two groups. Trabecular thickness and the structurally more important mineralized thickness increased only in group I. Group I also accumulated less excess osteoid (surface, volume). Mean osteoid thickness did not change in either group because of a bimodal distribution of wide seams with osteoblasts and double tetracycline labels, and thin seams without osteoblasts or labels. Osteoid was lamellar. Osteoid in abnormal sites (within bone marrow or bone, or around osteocytes) was found less frequently in group I. Adjusted apposition rate declined and mineralization lag time increased in both groups because of extended unlabelled osteoid seams. Erosion surface increased only in group C. Hook and/or tunnel erosion was seen less frequently in group I; it was closely associated with osteoid in abnormal sites and correlated with osteoid surface. Extended osteoid surface may have forced osteoclasts to hollow out trabeculae, leaving the empty osteoid shell in marrow. Excess osteoid volume and eroded surface and osteoid and erosion in abnormal sites correlated with bone fragility in group C. We conclude that intermittent therapy is to be preferred because it (1) increased mineralized trabecular thickness, (2) did not cause excessive osteoid accumulation and erosion, (3) showed less osteoid and erosion in abnormal sites and (4) led to a similar reduction in the vertebral fracture rate as did continuous treatment. The question of whether intermittency of therapy has some other effect independent of the cumulative dose of fluoride administered cannot be answered by this study.     

Suppressed UDP-galactose: ceramide galactosyltransferase and myelin protein mRNA in twitcher mouse brain

To investigate the role of temporal processing in language lateralization, we monitored asymmetry of cerebral activation in human volunteers using positron emission tomography (PET). Subjects were scanned during passive auditory stimulation with nonverbal sounds containing rapid (40 msec) or extended (200 msec) frequency transitions. Bilateral symmetric activation was observed in the auditory cortex for slow frequency transitions. In contrast, left-biased asymmetry was observed in response to rapid frequency transitions due to reduced response of the right auditory cortex. These results provide direct evidence that auditory processing of rapid acoustic transitions is lateralized in the human brain. Such functional asymmetry in temporal processing is likely to contribute to language lateralization from the lowest levels of cortical processing.     

Involvement of vitamin E and protein thiols in the inhibition of microsomal lipid peroxidation by glutathione

Iron-ascorbate stimulated lipid peroxidation in rat liver microsomes can be inhibited by glutathione (GSH). The role of protein thiols and vitamin E in this process was studied in liver microsomes isolated from rats fed diets either sufficient or deficient in vitamin E and incubated at 37 degrees C under 100% O2. Lipid peroxidation was induced by adding 400 microM adenosine 5'-triphosphate, 2.5 to 20 microM FeCl3, and 450 microM ascorbic acid. One mL of the incubation mixture was removed at defined intervals for the measurement of thiobarbituric acid reactive substances (TBARS), protein thiols and vitamin E. In vitamin E sufficient microsomes, the addition of GSH enhanced the lag time prior to the onset of maximal TBARS accumulation and inhibited the loss of vitamin E. Treatment of these microsomes with the protein thiol oxidant diamide resulted in a 56% loss of protein thiols, but did not significantly change vitamin E levels. However, diamide treatment abolished the GSH-mediated protection against TBARS formation and loss of vitamin E during ascorbate-induced peroxidation. Liver microsomes isolated from rats fed a vitamin E deficient diet contained 40-fold less vitamin E and generated levels of TBARS similar to vitamin E sufficient microsomes at a 4-fold lower concentration of iron. GSH did not affect the lag time prior to the onset of maximal TBARS formation in vitamin E deficient microsomes although total TBARS accumulation was inhibited. Similar to what was previously found in vitamin E sufficient microsomes [Palamanda and Kehrer, (1992) Arch. Biochem. Biophys. 293, 103-109], GSH prevented the loss of protein thiols in vitamin E deficient microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased child abuse in families with twins

Close spacing of children may be a significant risk factor for subsequent abuse in some families. Twin births are an extreme example of close spacing. Therefore, the authors hypothesized that twin births may predispose to an increased incidence of child abuse. Thirty-eight families with twins were compared with 97 single birth families and matched for birthdate, maternal age, race, and socioeconomic status. Families with twins experienced a significantly higher incidence of child abuse and neglect than did those with single births (p less than .003). A written questionnaire designed to study mothers' feelings and perceptions of support systems showed a significant difference only in greater difficulty in feeding twins as compared with single infants (p less than .001). Mothers of abused children were more likely not to answer the questionnaire at all (p less than .005). Neither mothers of single births nor those of twins felt that health professionals provided adequate education or support following the birth of their infants.