Hepatobiliary tuberculosis

Comparative genomic hybridization (CGH) has been proven to be an important tool in interphase cytogenetics of solid tumors. Although, because of methodological implications, balanced aberrations are not detected by CGH, the technique has uncovered a variety of new and interesting imbalanced karyotype changes. However, only a few studies deal with its application to hematologic disorders, although this is a main topic of cytogenetics. The aim of our study was, therefore, to evaluate the usefulness of CGH in the examination of hematologic neoplasms. For this purpose, bone marrow aspirates of 33 patients with different hematologic disorders were examined with CGH and the results compared with conventional cytogenetics (CC) and fluorescence in situ hybridization (FISH). CGH showed chromosome changes in 8 of 33 cases. CC found balanced aberrations in 4 of 33 and unbalanced changes in 9 of 33 samples. Differences between CGH and CC in unbalanced aberrations were seen in four cases. In these samples, either the number of aberrant cells found by CC was low and, therefore, difficult to detect by CGH, or complex aberrations in different cell clones as seen in CC were lumped together as one karyotype by CGH. In one sample, CC was not capable of giving any results at all, whereas CGH showed trisomy 8. CGH was also helpful in defining the bands involved in the structural aberrations, which was difficult by CC in some cases because of the low quality of metaphase spreads. All results obtained by CGH were confirmed by FISH, whereas CC and FISH were discordant in one case. Although CGH was not able to detect all aberrations, it gave important additional information for the correct localization of the aberrations found in CC, and it was most helpful in samples not processed successfully in CC. These advantages would open up a new field of application for CGH not only for research, but also for diagnostic purposes.     

CI-1007, a dopamine partial agonist and potential antipsychotic agent. I. Neurochemical effects

The receptor binding and biochemical effects of the putative dopamine (DA) partial agonist CI-1007 ([R(+)-1,2,3,6-tetrahydro-4-phenyl- 1-[(3-phenyl-3-cyclohexen-1-yl)methyl]pyridine] maleate) and potential antipsychotic were evaluated with a variety of biochemical methods. In receptor binding studies, CI-1007 bound to rat striatal DA receptors exhibiting a Ki of 3 nM as assessed by inhibition of [3H]N-propylnorapomorphine binding. CI-1007 also exhibited high affinity for cloned human D2L (Ki = 25.5 nM) and D3 (Ki = 16.6 nM) receptors with less affinity for D4.2 receptors (Ki = 90.9 nM). The affinity for serotonin-1A (5-HT-1A), alpha-2 adrenergic and 5-HT-2 receptors was moderate (submicromolar range) and slight or negligible for alpha-1, DA D1 and various other receptors. Unlike dopamine, the inhibition of [3H]spiperone binding was monophasic for CI-1007 and only slightly affected by the addition of Gpp-(NH)p. In vitro CI-1007 antagonized the forskolin-induced increases in cyclic AMP levels in GH4C1 cells expressing the human D2L receptor, having an intrinsic activity of 53% of that seen with the full agonist quinpirole. In vivo CI-1007 antagonized the gamma-butyrolactone (GBL)-induced accumulation of L-3,4-dihydroxyphenylalanine in striatum and mesolimbic regions of rat brain, causing a maximal 64% reversal in striatum, consistent with a partial agonist profile. In microdialysis studies it decreased DA overflow in both striatum and nucleus accumbens, indicating decreased release of DA. CI-1007 also reduced brain DA synthesis (DOPA accumulation), metabolism (DOPAC and HVA) and utilization (after tyrosine hydroxylase inhibition with alpha-methyl-p-tyrosine). CI-1007 did not affect striatal acetylcholine levels indicating lack of potent postsynaptic DA actions. CI-1007 seemed to be selective for DA neurons as it did not alter rat brain norepinephrine (NE) synthesis in the NE-enriched brainstem or NE utilization in the mesolimbic region. In addition, it did not affect in general 5-HT synthesis and metabolism in striatum and mesolimbic regions. These neurochemical results demonstrate that CI-1007 is a selective potent brain dopamine partial agonist with limited agonist activity at postsynaptic DA receptors.     

Osteogenic protein-1 protects against cerebral infarction induced by MCA ligation in adult rats

A series of studies using farnesyltransferase (FTase) inhibitors that the inhibition of FTase function suppresses the growth of ras-transformed cells in vitro and in vivo. However, whether FTase is directly involved in the regulation of cell proliferation remains to be demonstrated. To investigate whether overexpression of FTase results in altered cell growth and transformation, we thus used NIH3T3 cells transfected with cDNA constructs of both alpha and beta subunits of human FTase. FTase-overexpressing cells resulted in a 3- to 13-fold increase in the expression of the alpha and beta subunit protein of FTase and a 1.5- to 3-fold increase in the level of the enzyme activity compared with untransfected NIH3T3 cells or vector-transfected cells. Further investigations using metabolic labeling indicated that farnesylation of Ras was enhanced in FTase-overexpressing cells. Insulin-like growth factor-I, platelet-derived growth factor (PDGF), and basic fibroblast growth factor (bFGF) more potently enhanced DNA synthesis and anchorage-dependent growth in FTase-overexpressing cells than in control cells, in a dose-dependent manner. In particular, PDGF and bFGF also induced dose-dependently enhanced colony formation in soft agar in FTase-overexpressing cells. Furthermore, in FTase-transfectants, bFGF stimulated high activation of mitogen-activated protein kinase. Interestingly, FTase-transfectants developed progressive tumors in nude mice. Light and electron microscopy showed that the tumors were characteristic of fibrosarcoma, which were distinct from v-ras-induced tumors. Overexpression of FTase in NIH3T3 cells thus amplifies growth-factor-mediated cell growth and transformation, and FTase-overexpressing cells form tumors in nude mice.     

Investigations of anti-inflammatory activity of Jigrine

We report our experience with five lesions exclusively involving the entire cavernous sinus in which an essentially extradural surgical approach was used. There were two cases of cavernous haemangioma, two cases of meningioma and one case of fungal granuloma. The dural cover of the superior orbital fissure, and mandibular and maxillary divisions of the fifth nerve was dissected along with the dura of the lateral wall of the cavernous sinus. The presence of a relatively large intracavernous bulge due to the tumour assisted in this dissection. The contents of the cavernous sinus were exposed from an anterolateral, lateral and inferior approach. Through the corridor available between the splayed out cranial nerves, a radical resection of the tumour was accomplished in each case. The technical advantages of this approach are discussed in light of the anatomy of the dural configuration of the lateral wall of the cavernous sinus.     

Synthesis and in vivo evaluation of a 99m/99Tc-DADT-benzovesamicol: a potential marker for cholinergic neurons

Fifty-six asthmatics from an asthma ward or from an asthma out-patient clinic were challenged with two low concentrations (0.03 and 0.012 mg) of metacholine chloride in order to assess the relationship between pronounced hyper-responsiveness and asthma severity in a clinical setting. Only inhaled bronchodilators were stopped before challenge. Asthma severity was assessed retrospectively and prospectively on the basis of treatment, number of days in hospital, intensive care, number of emergency visits and days on sick-leave. The results show that pronounced hyper-responsiveness (n = 28) is not associated with asthma severity. It is concluded that a single simplified test of pronounced bronchial hyper-responsiveness, performed without taking into consideration the actual state of the disease and without stopping all medication, is of no help in identifying the patients with the clinically most severe asthma and worst prognosis.