Cerebral microgyria, thalamic cell size and auditory temporal processing in male and female rats

Induction of microgyria by freezing injury to the developing somatosensory cortex of neonatal rats causes a defect in fast auditory processing in males, but not in females. It was speculated that early damage to the cortex has sexually dimorphic cascading effects on other brain regions mediating auditory processing, which can lead to the observed behavioral deficits. In the current series of experiments, bilateral microgyri were induced by placement of a freezing probe on the skulls of newborn male and female rats, and these animals were tested in adulthood for auditory temporal processing. Control animals received sham surgery. The brains from these animals were embedded in celloidin, cut in the coronal plane and the following morphometric measures assessed: microgyric volume, medial geniculate nucleus (MGN) volume, cell number, and cell size, and, as a control, dorsal lateral geniculate nucleus (dLGN) volume, cell number and cell size. There were no sex differences in the cortical pathology of lesioned animals. However, microgyric males had more small and fewer large neurons in the MGN than their sham-operated counterparts, whereas there was no difference between lesioned and sham-operated females. There was no effect on dLGN cell size distribution in either sex. Microgyric males were significantly impaired in fast auditory temporal processing when compared to control males, whereas lesioned females exhibited no behavioral deficits. These results suggest that early injury to the cerebral cortex may have different effects on specific thalamic nuclei in males and females, with corresponding differences in behavioral effects.      

Induction of tumor-specific T cell response by cognating tumor cells with foreign antigen-primed Th cells

Sufficient CD4+ T cell help is very important in generating specific cytotoxic T cell responses. The inadequate activation of tumor-specific Th cells leads to failure of antitumor immunity. In general, each individual consists of some primed Th cells responding to certain antigens. If these tumor non-specific pre-primed Th cells can provide sufficient help, the generation of tumor-specific T cells may be enhanced. In the present study, we tested this hypothesis by cognating and reactivating pre-primed ovalbumin (OVA)-specific Th cells with OVA- pulsed tumor cells which could simultaneously present both OVA and tumor-associated antigen on the same cell. We clearly demonstrated that immunization of OVA-sensitized mice with OVA-pulsed P388 cells, but not unpulsed P388 cells, led to the induction of P388-specific cytotoxicity and tumor resistance. Both CD4+ and CD8+ tumor-specific cytotoxic T cells were detected in vitro, but only CD8+ T cells played the major effector role in preventing the growth of challenged tumor in vivo. Taken together, our study demonstrated that the immunogenicity of tumor cells can be enhanced effectively by cognating pre-primed foreign antigen-specific Th cells with tumor cells. These findings have potential implications in developing methods to control tumor growth.      

Drug use and other problems of residents in projects for the young, single homeless

One hundred people who make use of an organization housing the young, single homeless were interviewed using a semi-structured interview. There was a high prevalence of problems, including substance abuse and dependence, other mental health problems, extensive use of health services and extensive experience of crime both as victim and perpetrator. Most people said they had become homeless because they did not get on with their parents. Since becoming homeless, most had not spent more than a month sleeping rough, but most had spent time staying with friends or staying in other hostels for the homeless. It is concluded that most young, single homeless people who seek help have problems beyond a lack of permanent shelter. The extent to which the sample is representative of all homeless people is considered and implications for service provision are discussed.     

Glioblastoma: catheter techniques for isolated chemotherapy perfusion

Techniques have been developed for isolated perfusion of chemotherapeutic agents in patients with glioblastoma. Three catheters that facilitate crossing the carotid siphon have been developed; two are based on an everting or toposcopic principle, and one uses microjets for deflectability and improved mixing. Blood from the ipsilateral jugular vein is aspirated at high volumes (300 ml/min) for extracorporeal circulation through an adsorption column (for recovery of carmustine) or dialysers (for recovery of cisplatin). Preliminary experience in 10 patients suggests that high doses of chemotherapeutic agent can be administered using these catheters, with reduced retinal and systemic toxicity.     

T2 estimates in healthy and diseased brain tissue: a comparison using various MR pulse sequences

Fourteen patients and five healthy individuals underwent magnetic resonance (MR) imaging to determine an effective multiple spin echo pulse sequence for estimating T2. Lesions examined included infarction, glioma, multiple sclerosis, and acute hematoma. A pulse repetition time (TR) of 1,500 msec and echo delays (TEs) of 25, 50, 75, and 100 msec were used. Computed T2 images were derived from all four echoes, the first two echoes, and the first and fourth echoes. T2 values were obtained from specific brain locales using region-of-interest analysis. Use of either the first two echoes or the first and fourth in the T2 fit provided T2 estimates which closely correlated with that of the four-echo analysis. The noise level in T2 maps constructed from the 25- and 100-msec echoes was modestly (typically 10%) higher than that from four echoes; noise level from the 25- and 50-msec echoes was markedly higher, typically 60%. This behavior is remarkably consistent with that predicted from theory. All 19 subjects displayed consistent relative T2 values for specific brain structures; in 13, the absolute T2 values fell within a limited range. Despite the high sensitivity of T2 images, their specificity in the detection of most brain disease appears limited except in acute intracerebral hematoma, which exhibited a decreased T2 relaxation time using high-field-strength MR imaging.     

High prevalence of a missense mutation of the glucokinase gene in gestational diabetic patients due to a founder-effect in a local population

Summary A high proportion of the female patients who are members of maturity onset diabetes of the young (MODY) pedigrees, and whose diabetes mellitus is due to a glucokinase mutation, originally presented with gestational diabetes. To establish whether glucokinase mutations could be a common cause of gestational diabetes, we studied 50 subjects who presented with gestational diabetes and on follow-up had hyperglycaemia (5.5–10.0 mmol/l). Screening for glucokinase mutations using single-stranded conformational polymorphism (SSCP) analysis detected a missense mutation at position 299 (Gly²⁹⁹→ Arg) in three subjects. As two pedigrees in the Oxford area had the same glucokinase mutation, we suspected the role of a founder-effect, and carried out pedigree extension, haplotype construction (using microsatellite markers GCK1 and GCK2) and mutation screening of at-risk subjects from the same geographical area. One of the gestational diabetic subjects was found to be related to one of the previous pedigrees via her paternal grandmother. Subjects with the mutation were found to have the Z + 4/2 (GCK1/GCK2) haplotype, suggesting that the observed high prevalence of the Gly²⁹⁹→ Arg glucokinase mutation in the Oxford region was due to a founder-effect. Since glucokinase mutations predominantly induce subclinical hyperglycaemia, it is likely that in the locality of other pedigrees there will be undiagnosed subjects with the same glucokinase mutation, which remains undetected unless pregnancy occurs. [Diabetologia (1996) 39: 1325–1328] Received: 13 February 1996 and in revised form: 7 May 1996     

正交试验法优选冬凌草的提取工艺

目的：研究冷浸提取法中冬凌草的最佳提取条件。方法：采用正交试验法，以溶剂用量，提取时间和提取次数３个因素，每个因素选取３个水平进行实验。结果：因素Ａ和因素Ｂ对冬凌草甲素的含量均有显著的影响，因素Ｃ则有一定的影响。结论：最佳工艺Ａ３Ｂ３Ｃ２，即倍量９５％，ＥｔＯＨ提取２次，每次６ｄ。