Assessment of changes in regional cerebral blood flow in patients with major depression using the 99mTc-HMPAO single photon emission tomography method

Regional cerebral blood flow was investigated in 14 patients with major depression diagnosed according to the DSM-III-R criteria (six patients with single and eight patients with recurrent episodes) and in ten healthy volunteers. The mean ages of the patients and the controls were 33.5 ± 2.7 and 31.6 ± 2.6 years, respectively. The severity of the depression was assessed using the 17-item Hamilton Depression Scale (mean: 23.2 ± 1.5). None of the patients was under medication. After administration of 500 MBq technetium-99m hexamethylpropylene amine oxime, a single photon emission tomography study was performed and then transaxial, sagittal and coronal slices were obtained. For the semiquantitative analysis of the data, the ratios of the mean counts/pixel to the whole slice were calculated for 24 regions on three consecutive transaxial slices in the orbitomeatal plane. Additionally, left/right and frontal/occipital ratios were calculated. Both sides of the temporal region had a significantly decreased cerebral blood flow (CBF) when compared to the controls. The left/right ratio of the prefrontal region was also significantly lower in the patients than in the controls. The Hamilton score had a negative correlation with blood flow in the anterofrontal and left prefrontal regions. According to our results, regional CBF seems to be decreased in the left prefrontal and in both temporal regions in major depression. The severity of depression is correlated with the reduction in CBF in the regions of the anterofrontal and left prefrontal cortex.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

The effect of Bosentan on healing of colonic anastomosis

Background  

Ischemia is the most important factor compromises wound healing in colonic anastomosis. Mesenteric vessels are ligated at first while performing colonic resection and following anastomosis. Therefore blood supply of the related segments of colon temporarily interrupted and ischemia can easily occur. This study was carried out to explore whether Bosentan, an endothelin-receptor antagonist, can eliminate vasoconstruction, increase blood flow in the splanchnic area and anastomotic region and therefore possibly facilitate wound healing and prevent intra-abdominal adhesion formation.     

Genetic control of the immune response to haemoglobin. II. Studies using purified alpha-chain and beta-chain as immunogens

Mice of independent haplotypes and several recombinant inbred strains were immunized with highly purified preparations of either the alpha-chain or beta-chain subunit of human adult haemoglobin. Cells from the sensitized lymph nodes were challenged in vitro with the appropriate subunit (or in some cases both chains) and cell proliferation assessed by 3H-thymidine incorporation. Mice of the H-2b and H-2d haplotypes were high responders to alpha-chain while mice of the H-2f, H-2j, H-2k, H-2r, H-2s, H-2u, and H-2v haplotype were low responders. the low responsivenesss of B10.A(4R) and B 10.MBR and high responsiveness of B10 indicated that the Ir gene(s) determining responsiveness to the alpha-chain subunit resides in the I-A subregion of the mouse major histocompatibility complex. Mice of the H-2d, H-2f, and H-2s haplotypes were high responders and H-2b, H-2j, H-2a, and H-2u haplotype mice were low responders to beta-chain. H-2k, H-2p, H-2r, and H-2v haplotype mice were intermediate responders to beta-chain. The low responsiveness of B10.S(8R) and B10.TL and the high responsivenes of B10.S(9R) mapped the Ir gene(s) to beta-chain to the I-A subregion. Data collected from challenging high responder cells with both subunit indicated that alpha-chain and beta-chain do not crossreact. These results are discussed in reference to earlier observations suggesting that the low responsiveness of some strains of mice to priming and challenging using the intact haemoglobin molecule might be due to a negative regulatory influence mediated by one of the subunits. In the absence of this influence these mice would respond normally.     

大鼠胸腺降黑素受体的鉴定及生物学特性

应用放射配体结合法证实大鼠胸腺内存在降黑素特异结合部位，该结合位点可以满足特异结合部位的基本条件：１．低结合容量；２．高亲和力；３．可饱和性；４．可逆性；５．对降黑素高度特异性。此外，该特异结合位点具昼夜节律；亚细胞分布的研究表明以细胞核含量最高，线粒体次之，并具有年龄依赖性降低，以出生时最高。     

Conservative management of early endometrial adenocarcinoma with repeat curettage and hormone therapy under assistance of hysteroscopy and laparoscopy

We report a rare case of early-stage endometrial adenocarcinoma in a 22 year old nullipara with polycystic ovaries undergoing conservative treatment. Pretreatment evaluation including tumour grade, depth of myometrial invasion, tumour size, hormone receptor status and flow cytometric analysis indicated a favourable prognosis. The patient underwent repeat endometrial curettage and a 6 month period of therapy with megestrol acetate and tamoxifen. A combination contraceptive pill was then prescribed to ensure withdrawal of the menstrual cycle thereafter. Now, 1 year after the last curettage, there is no evidence of disease. During the treatment period, hysteroscopy allowed for a more precise approach in panoramically examining the tumour nest in the endometrial cavity, and the subsequent endometrial response to hormone therapy. Laparoscopy using bulldog clamps applied to the isthmic portion of the Fallopian tubes prevented i.p. spread of endometrial tissue from retrograde regurgitation during hysteroscopy. Laparoscopic ovarian electrocautery resulted in the reduction of abnormal hypervascularization on the surface of polycystic ovaries postoperatively but caused a peri-ovarian adhesion complication. It is interesting that this case posed a unique opportunity to demonstrate the tumour regression under the assistance of laparoscopy and hysteroscopy.      

Frequent administration by inhalation of salbutamol and ipratropium bromide in the initial management of severe acute asthma in children

A study was performed to compare the efficacy and safety of two therapeutic regimens for the treatment of children presenting to the emergency department with acute asthma. A regimen of inhaled salbutamol alone was compared to inhaled salbutamol combined with ipratropium bromide. Twenty-five children ranging in age from 5 to 15 years were enrolled in the study. Children with FEV1 less than or equal to 55% predicted were eligible to participate in the study. Subjects were randomized in a double-blind fashion into one of two treatment groups. Both groups received an initial dose of salbutamol by nebulizer of 150 micrograms/kg (0.03 cc/kg), followed by six consecutive doses of 50 micrograms/kg (0.01 cc/kg) at 20-minute intervals. In one group of subjects, 250 micrograms (1.0 ml) of ipratropium bromide respirator solution was added to the salbutamol administered at the time of the initial inhalation, and at 40 and 80 minutes, whereas the remaining subjects received a placebo with salbutamol at those times. Formal one-way statistical ANOVA with change in percent predicted FEV1 as a response variable confirmed there was a statistically significant difference at all time points caused by drug regimen during the 150-minute observation period. There was no significant difference in side effects reported in the two groups. Significant additional bronchodilation achieved with salbutamol and ipratropium bromide together indicates that there is likely a substantial cholinergic element to the bronchospasm observed in acute exacerbations of asthma in the pediatric age group.     

Association of TNF-beta polymorphism with disease severity among patients infected with hepatitis C virus

The pathogenesis of chronic hepatitis C virus (HCV) infection remains unclear. Tumour necrosis factor alpha (TNF-alpha) is alleged to contribute in the pathogenesis of chronic HCV infection. Single nucleotide polymorphism in TNF-alpha and -beta genes could influence the outcome of HCV infection. The aim was to study single nucleotide polymorphism in TNF-alpha promoter region and Nco I polymorphisms in the TNF-beta gene in patients with chronic hepatitis C. Fifty-two patients with histologically proven chronic hepatitis, who had raised ALT levels (>1.5 x ULN) and were HCV RNA positive, were studied. Genotyping of -308 promoter variant of TNF-alpha was performed by PCR with primers that incorporated an Nco I restriction site. For PCR typing of the TNF-beta Nco I restriction fragment length polymorphism, sequence specific primers were used. Polymorphism in the TNF-alpha G/G, G/A and A/A allele was not different between HCV patients and healthy controls. TNF-beta A/A allele was significantly more common (P = 0.02) in patients (28.8%) as compared to controls (12.8%), whereas no significant difference was observed for TNF-beta G/A and G/G alleles [corrected]. Nco I TNF-beta A/A was strongly associated with -308 TNF-alpha G/G (RR of HCV persistence = 4.9), indicating possible linkage between TNF-beta A/A and TNF-alpha G/G allele. Patients with severe hepatic fibrosis more frequently had the TNF-beta A/A allele as compared to patients with mild disease (P = 0.04). Immunogenetic factors, such as single nucleotide polymorphisms in TNF-beta (A/A allele), may affect the natural course of HCV infection, in particular, the disease progression. Larger studies including cytokine expression profiles are needed to fully understand the contribution of the polymorphisms described in the pathogenesis of chronic hepatitis C.