Primary structure and biological activity of human brain-derived neurotrophic factor

Brain-derived neurotrophic factor (BDNF) is a 27-kDa basic protein of noncovalently linked 13.5-kD subunits related to nerve growth factor and is produced by the central nervous system (CNS). BDNF has been shown to promote the survival of neurons located in or directly connected with the CNS and is likely to function in adjusting the cell number within neuronal populations to the need of this projection field. Here we describe the primary structure of a human BDNF cDNA, the biological activities of pure recombinant human BDNF, and the tissue distribution of rat BDNF. BDNF mRNA can be found in some peripheral tissues as well as in the CNS, and recombinant human BDNF is a potent neurotrophic factor for primary peripheral sensory neurons.     

Relationships between American Urological Association symptom index, prostate volume, and disease-specific quality of life question in patients with benign prostatic hyperplasia

The American Urological Association (AUA) symptom index is both valid and reliable in identifying the need to treat patients with benign prostatic hyperplasia (BPH) and in monitoring their response to therapy. We evaluated the relationships between AUA symptom index, disease-specific quality of life question, and prostate volume in patients with BPH. A total of 100 patients who came to Kaohsiung Medical University Hospital, Taiwan, for help due to lower urinary tract symptoms (LUTS) and who were diagnosed with BPH between October 2002 and June 2003 were included in the study. All patients were evaluated using transrectal ultrasonography, AUA symptom index, and disease-specific quality of life question. The disease-specific quality of life question showed good correlation with AUA symptom score (r = 0.815, p < 0.01), but weak correlation with prostate volume (r = 0.225, p < 0.05) and age (r = 0.274, p < 0.05). Prostate volume had weak correlation with AUA symptom score (r = 0.251, p < 0.05) and age (r = 0.472, p < 0.01), but good correlation with prostate specific antigen (r = 0.638, p < 0.01). In addition to AUA symptom index, we suggest using the disease-specific quality of life question to evaluate the influence on quality of life and response to treatment in clinical practice. Moreover, we should assess the impact of BPH symptoms rather than the increase in prostate volume during the management of BPH.     

Prognostic significance of in vitro marrow culture growth pattern in untreated acute nonlymphocytic leukemia

The growth pattern of marrow cells in agar culture was studied in 90 adult patients with acute nonlymphocytic leukemia (ANLL) at diagnosis. We classified the abnormal growth patterns into 4 groups, A: no growth, B: decreased growth, C: excessive microcluster formation and D: excessive cluster growth with more than 20 colonies. There was a good correlation between growth pattern and FAB subtype. A predominance of group A growth was observed in M1, while group B growth was found in 50% of patients with M2 and M5. No relationships between the growth patterns and other clinical parameters were detected. Sixty-six patients were evaluable for treatment outcome. The growth pattern significantly correlated with complete remission rate. The remission rates were 52, 87, 80, and 25% for patients with group A, B, C and D growth, respectively. Analyses of remission duration and survival curves showed significant differences among the different growth patterns. Patients with D growth experienced a shorter remission duration and a lower survival rate than other groups. These results indicate that the in vitro culture growth pattern in untreated ANLL is of prognostic significance in predicting the response to therapy.     

In-vivo evaluation of dopamine receptor-mediated inhibition of gonadotrophin secretion from the pituitary gland of the goldfish, Carassius auratus

Dopamine acts directly on the pituitary to modulate gonadotrophin (GtH) secretion in goldfish (Carassius auratus). In the light of this important role for dopamine in the regulation of goldfish reproduction, this investigation was designed to evaluate the receptor specificity of this dopamine inhibition and to describe the use of domperidone, a specific dopamine D2-receptor antagonist, in the manipulation of pituitary function in goldfish. To investigate the specificity of dopamine inhibition of GtH secretion, selected dopamine receptor antagonists were injected i.p. to block dopamine receptors thereby increasing GtH secretion as reflected by increased serum concentrations of GtH. Serum GtH levels were significantly increased by the active stereoisomer (-)-sulpiride in a dose-related fashion; (+)-sulpiride had no effect. Comparison of dopamine antagonists at low doses indicated that only domperidone and pimozide caused significant increases in serum concentrations of GtH. Dopamine antagonists potentiated the action of a gonadotrophin-releasing hormone analogue (GnRH-A) with an order of potency of domperidone = pimozide greater than metoclopramide = fluphenazine. [3H]Domperidone, injected i.p. with unlabelled domperidone, entered the blood and achieved maximum concentrations 12 h after injection, but did not accumulate in the brain in appreciable amounts. Gonadal 3H radioactivity was usually equal to or in excess of blood radioactivity, while [3H]domperidone was highly concentrated in the pituitary in a time-dependent fashion, with maximal accumulation occurring 24 h after injection. The time-course of pituitary accumulation of [3H]domperidone correlated well with the temporal increase in serum GtH levels in response to i.p. injected domperidone or domperidone plus an analogue of LHRH. Domperidone increased serum concentrations of GtH in a dose-related fashion; an analogue of salmon GnRH (sGnRH-A) increased the sensitivity and magnitude of the serum GtH response to domperidone. Serum concentrations of GtH were increased by sGnRH-A in a dose-related fashion; a low dose of domperidone substantially increased the sensitivity of the serum GtH response to sGnRH-A. These results indicate that dopamine inhibits GtH secretion from the goldfish pituitary by acting through a specific mechanism mediated by a dopamine D2 receptor. Domperidone increased serum concentrations of GtH, potentiated the action of gonadotrophin-releasing hormones and did not pass into the brain after i.p. injection into goldfish. The data also suggest that dopamine and GnRH, although acting through different receptors, influence the effect of each other on GtH release.     

Immunopathogenesis of inflammatory bowel disease

Crohn＇s disease and ulcerative colitis are chronic relapsing immune mediated disorders that results from an aberrant response to gut luminal antigen in genetically susceptible host. The adaptive immune response that is then triggered was widely considered to be a T-helper-1 mediated condition in Crohn＇s disease and T-helpero2 mediated condition in ulcerative colitis. Recent studies in animal models, genome wide association, and basic science has provided important insights in in the immunopathogenesis of inflammatory bowel disease, one of which was the characterization of the interleukin-23/Th-17 axis.     

Clinical and angiographic variables affecting the progression of coronary artery disease as determined by quantitative angiography

To assess by serial quantitative angiography, the significance of clinical and angiographic variables that affect the progression of coronary artery disease (CAD). Progression of disease by sequential angiography is unpredictable and the role of clinical risk factors controversial. Various intervention trials have demonstrated less progression and even regression in hyperlipidemic patients. Correlates of progression have included a younger age, unstable angina, and greater involvement of the coronary arteries, with few studies looking at angiographic features of individual lesions. Serial angiograms on 74 patients were analyzed by computer assisted quantitative angiography using absolute measurements. A total of 99 diseased segments were analyzed for progression defined as an absolute reduction of 20% in luminal cross-sectional area. A preliminary correlation coefficient was calculated for each of the clinical and angiographic variables to detect any association with progression, and the odds ratio determined.The presence of any of the clinical risk factors-diabetes, hypertension, serum cholesterol, smoking, and a family history of coronary disease could not predict progression. The use of beta blockers was three times less likely to be associated with progression (odds ratio 0.33). While the presence of distal disease was associated with progression of a more proximal lesion (odds ratio 2.4), eccentricity, branch point location, lesion length, calcification, thrombus, or the presence of collaterals did not influence progression of disease in an individual segment. In conclusion, the presence of any of the clinical risk factors could not predict progression of disease in an individual coronary segment as determined by serial quantitative angiography, and the use of beta blockers and the absence of coexistent distal disease was associated with less progression of disease in an individual coronary segment. This may be related to changes in wall stress, reduced platelet interactions, and the integrity and permeability of the vascular endothelium to lipids.     

Chemotherapy for non-small cell lung cancer in elderly patients

STUDY OBJECTIVE: To determine the appropriate chemotherapy regimen for inoperable, chemotherapy-na?ve non-small cell lung cancer (NSCLC) in elderly patients. SETTING: National teaching hospital in Taiwan. DESIGN: We retrospectively analyzed data from our clinical trials for a total of 270 patients and compared them with the data from other studies, addressing the elderly in particular or providing subgroup information on age, to analyze the feasibility of current chemotherapy options for elderly patients and possible alternative approaches. RESULTS: The response rates and median survival times of fit elderly patients with NSCLC who were receiving appropriate new anticancer drugs for chemotherapy, including single-agent or combination treatment, were no worse than those of younger patients, and the response rates may have been even higher in the elderly patients, while survival time was slightly poorer in this group. The risk of adverse side effects, such as myelosuppression and peripheral neuropathy, may be higher in elderly patients, who also visit the hospital more frequently. Some items on the lung cancer symptom scale for elderly patients were rated as being slightly worse than those for younger patients after chemotherapy. CONCLUSION: Advanced age alone should not preclude chemotherapy. New single-agent drugs, and non-platinum-based or platinum-based doublets, can all be considered as appropriate treatment for selected fit elderly patients with advanced NSCLC.     

Genetic variation in C-reactive protein (CRP) gene may be associated with risk of systemic lupus erythematosus and CRP concentrations

OBJECTIVE: The gene coding for C-reactive protein (CRP) is located on chromosome 1q23.2, which falls within a linkage region thought to harbor a systemic lupus erythematosus (SLE) susceptibility gene. Recently, 2 single-nucleotide polymorphisms (SNP) in the CRP gene (+838, +2043) have been shown to be associated with CRP concentrations and/or SLE risk in a British family-based cohort. Our study was done to confirm the reported association in an independent population-based case-control cohort, and also to investigate the influence of 3 additional CRP tagSNP (-861, -390, +90) on SLE risk and serum CRP concentrations. METHODS: DNA from 337 Caucasian women who met the American College of Rheumatology criteria for definite (n = 324) or probable (n = 13) SLE and 448 Caucasian healthy female controls was genotyped for 5 CRP tagSNP (-861, -390, +90, +838, +2043). Genotyping was performed using restriction fragment length polymorphism-polymerase chain reaction, pyrosequencing, or TaqMan assays. Serum CRP levels were measured using ELISA. Association studies were performed using the chi-squared distribution, Z-test, Fisher's exact test, and analysis of variance. Haplotype analysis was performed using EH software and the haplo.stats package in R 2.1.2. RESULTS: While none of the SNP were found to be associated with SLE risk individually, there was an association with the 5 SNP haplotypes (p < 0.001). Three SNP (-861, -390, +90) were found to significantly influence serum CRP level in SLE cases, both independently and as haplotypes. CONCLUSION: Our data suggest that unique haplotype combinations in the CRP gene may modify the risk of developing SLE and influence circulating CRP levels.