Distributed changes in rat brain DNA synthesis with long-term habituation and potentiation of the perforant path-granule cell synapse.

The involvement of brain deoxyribonucleic acid (DNA) synthesis in adaptive neural events was studied in the adult rat during long-term habituation (LTH) or potentiation (LTP) of the perforant path-granule cell synapse. Male Long-Evans rats were given 50 muCi [3H]thymidine intraventricularly under urethane anesthesia. Soon thereafter, field excitatory postsynaptic potential (EPSP) slope and population spike were monitored from the right dentate gyrus before and at various times (5, 10, 15, 60 min) following the delivery to the ipsilateral perforant bundle of a low frequency (LFS: 1.0 Hz, 160 s) or a high-frequency train (HFS: 400 Hz, 200 ms), repeated once after 5 min. Unstimulated implanted rats served as controls. DNA synthesis was evaluated by the incorporation of the radioactive precursor into DNA of several brain areas at the end of a 1 h incorporation period. In CA1, LTH and LTP increased DNA synthesis by 30% on the stimulated side. In the entorhinal cortex, LTH but not LTP increased DNA synthesis (by 30%) on the stimulated side. Conversely, in the frontal cortex, LTP but not LTH increased DNA synthesis (by 100%) on both sides. Long-lasting changes in synaptic efficacy covaried non-linearly with DNA synthesis in mono- and polysynaptically stimulated hippocampal regions, and in functionally associated neocortical areas. The co-variations of population spike amplitude were positive for LTH and negative for LTP in the dentate gyrus and frontal cortex of both sides, and in CA3/CA1 of the stimulated side, indicating higher DNA synthesis at lower values of LTH and LTP, and viceversa. Further, regional cross-correlation analyses revealed a high degree of synchronization among brain sites, following low- or high-frequency train pulses, indicating that (i) extra-target sites participate on the stimulated and on the contralateral side, and (ii) small distributed changes take place across the sampled neural networks. A modulatory role of information flow on brain DNA synthesis is inferred to take place in a diffuse, distributed manner.     

Possible sex differences in the developing human fetal brain.

Left-right regional volumetric asymmetries in five telencephalic regions were studied in the developing human fetal brain. Complete series of coronal sections of 21 fetal brains were digitized and regional volumes were integrated. Five regional indices of asymmetry and two overall indices of asymmetry were calculated and compared across the fetal sample. The two most asymmetrical regions in the developing fetal brain were region 1, roughly equivalent to prefrontal cortex, and region 5, which includes striate and extrastriate cortices. Region 5 also manifested a statistically significant sex difference (p less than .02) in the degree of volumetric asymmetry. It appears that striate-extrastriate cortices are far more asymmetrical in male brains than in their female counterparts (M = 33%; F = 13%). Overall indices of asymmetry indicated that, on the average, volumetric asymmetries in the male brain favor the right hemisphere. In contrast, the human fetal female is likely to have two hemispheres of the same size or a left hemisphere that is slightly larger than its right counterpart. We believe that these results support the hypothesis that testosterone in utero may lead to a more rapid growth of the right hemisphere or, alternatively, retard the growth of the left hemisphere.     

Adenotonsillar enlargement in pediatric organ transplant recipients: a cross-sectional analysis.

OBJECTIVE: Our goal was to statistically correlate adenotonsillar hypertrophy (ATH) in the pediatric posttransplant population with potential risk factors and to monitor the progression of ATH over time. STUDY DESIGN AND SETTING: Participants were evaluated for ATH through a standardized 65-point questionnaire and an 8-point physical examination. They were also evaluated for current age, age at time of transplantation, type of organ transplant, gender, tacrolimus use, history of transplant rejection, Epstein-Barr virus (EBV) serology, and cytomegalovirus (CMV) serology. We evaluated 243 pediatric solid organ transplant recipients, with 116 patients undergoing repeat evaluation. RESULTS: A statistically significant negative correlation was noted between age at time of transplantation and both questionnaire scores (P = 0.0075) and examination scores (P = 0.013). A significant negative correlation was also seen between age at time of evaluation and questionnaire score (P = 0.028) but not examination score (P = 0.49). Recipient EBV seronegativity significantly increased questionnaire score (P = 0.05). Liver transplant recipients also had a significantly higher questionnaire score than did kidney transplant recipients (P = 0.0048). Gender, CMV recipient status, and tacrolimus (immunosuppressant) use did not significantly impact questionnaire or examination scores. Repeat evaluation of 116 patients after a 2- to 9-month interval did not demonstrate any significant increases in questionnaire scores. A statistically significant drop in examination scores was noted (P = 0.003). Conclusions and Significance: These findings support previous reports in the literature that correlate EBV seronegativity, younger age at transplant, and liver versus kidney transplantation with increased incidence of PTLD.     

知母中呋甾皂甙的研究

自知母 Anemarrhena asphodeloides Bge.根茎的乙醇提取物中,经硅胶柱层析和制备型HPLC分得四种呋甾皂甙。用化学反应和波谱(IR,FAB-MS,EI-MS,¹HNMR,¹³CNMR,DEPT,一维多重接力CoSY,二维接力HOHAHA,¹H-¹H COSY,¹H-¹³C COSY和NOE差谱)解析,确定其结构为知母皂贰B(anemarsaponinB,I),(25S)-26-O-β-D-吡喃葡萄糖基-5β-呋甾-20(22)-烯-3β,26-二醇-3-O-β-D-吡喃葡萄糖基(1→2)-β-D-吡喃哺葡萄糖甙(Ⅱ),(25S)-26-O-β-D-吡喃葡萄糖基-22-羟基-5β-呋甾-3β,26-二醉-3-O-β-D-吡喃葡萄糖基(1→2)-β-D-吡喃半乳糖甙(Ⅲ),(25S)-26-O-β-D-吡喃葡萄糖基-22-甲氧基-5β-呋甾-3β,26-二醇-3-O-β-D-吡喃葡萄糖基(1→2)-β-D-吡喃半乳糖甙(Ⅳ)。Ⅱ为一新的呋甾皂甙,命名为知母皂甙C;化合物Ⅳ为首次从知母中分离得到,命名为知母皂甙E。初步的药理实验显示,化合物1～Ⅳ均有一定的清除羟自由基的作用。     

Presence of calbindin and lack of parvalbumin in progesterone receptor-containing neurons of the monkey mediobasal hypothalamus.

All of the progesterone receptor-containing cells of the monkey hypothalamus are GABAergic. The aim of this study was to further characterize these GABAergic progesterone receptor-containing neurons based on their calbindin or parvalbumin content. These calcium-binding proteins are characteristic markers of different populations of GABAergic neurons in the central nervous system. Double-immunolabeling for progesterone receptor and either calbindin or parvalbumin was performed on hypothalamic Vibratome sections of estrogen primed African green monkeys (Cercopithecus aethiops). Progesterone receptor-containing calbindin-immunoreactive neurons were observed in the ventromedial and periventricular areas of the hypothalamus. Forty-one per cent of the progesterone receptor-containing cells in this area were calbindin immunopositive. No double-immunolabeled neurons could be detected in the infundibular (arcuate) nucleus. In tissue double-immunolabeled for progesterone receptor and parvalbumin, none of the progesterone receptor-containing neurons exhibited immunoreactivity for parvalbumin. Electron microscopic double-immunostaining for progesterone receptor and calbindin confirmed the light microscopic results. Furthermore, a large number of asymmetric synaptic contacts were observed on the calbindin-immunoreactive neurons. These observations demonstrate that progesterone receptor-containing cells in the monkey mediobasal hypothalamus consist of at least two different types of GABA neurons, and indicate that progesterone receptor-containing calbindin cells may be postsynaptic targets of excitatory fibers.     

Erythromycin-induced hepatitis: simulator of malignancy

A 67-year-old patient was admitted with a 2-week history of epigastric discomfort that began after an episode of upper respiratory tract infection treated with erythromycin. Results of liver function tests were abnormal. Abdominal ultrasound (US) and computed tomography showed multiple, poorly demarcated irregular lesions in both hepatic lobes, suggestive of diffuse metastatic invasion. Histologic examination of the biopsy specimen revealed drug-induced hepatitis. Ten weeks after withdrawal of the erythromycin, US showed complete resolution of the hyperechogenic liver lesions.     

Effect of two synthetic alpha-gliadin peptides on lymphocytes in celiac disease: identification of a novel class of opioid receptors

Two synthetic peptides containing residues 43-47 and 43-49 of alpha-gliadin were tested for inhibition of leukocyte migration in 47 patients with celiac disease. In nineteen patients, all on a normal diet, leukocyte migration was inhibited by the peptides and naloxone blocked this effect. In twenty-eight patients (24 of whom were on strict gluten-free diet) leukocyte migration was not affected by the peptides. Our results suggest that alpha-gliadin-(43-49), Tyr-Pro-Gln-Pro-Gln-Pro-Phe, is closely related to the active fragment, or to one of the active fragments of alpha-gliadin, and that it interacts with receptors that are similar to but not identical with the known opiate receptors.     

Human pituitary corticotroph adenomas in vitro: morphologic and functional responses to corticotropin-releasing hormone and cortisol

We examined the direct effects of corticotropin-releasing hormone (CRH) and cortisol on the morphology of cells from 6 functioning human pituitary corticotroph adenomas in culture using both light and electron microscopic morphometry and correlated the structural changes with alterations in adrenocorticotropin (ACTH) release in each case. During incubations lasting 2 or 24 h, ACTH release was increased by CRH and reduced by cortisol. After incubations lasting from 2 to 72 h, light microscopic morphometric analysis showed no significant differences in cell size, nuclear area, cytoplasmic area or nuclear/cytoplasmic ratio between treated and control adenoma cells. Ultrastructural morphometry documented increased cytoplasmic volume density (CVD) of rough endoplasmic reticulum and/or Golgi apparatus and reduced CVD of secretory granules in cells incubated with CRH. There was no consistent change in CVD of endoplasmic reticulum, Golgi apparatus or secretory granules in adenoma cells incubated with cortisol, but in all tumors there were marked filament accumulations indicating a direct effect of cortisol on adenomatous corticotrophs. The changes were similar after 2- and 72-hour exposures. These results indicate that (1) some adenomatous corticotrophs can respond to CRH and cortisol; (2) the morphologic changes observed in cells treated with CRH correlate with increased ACTH release, and (3) accumulation of filaments is the direct effect of cortisol and is associated with reduced ACTH release.