转录调控因子CBF1（RBP—Jκ）对Cbfal和Ose2元件启动子活性的影响

目的：探讨Notch信号转录调控因子CBF1(RBP—Jκ)对核心结合因子Cbfal基因启动子和骨钙素基因启动子区域Ose2元件启动子活性的影响。方法：构建CBF1真核表达载体pCMV—Tag4／CBF1；将梯度浓度pCMV—Tag4／CBF1和荧光素酶报告质粒共转染两成骨前体细胞系Kusa—A1和Kusa-O，用双荧光素酶报告基因方法检测Cbfa1和Ose2元件启动子活性。结果：随CBF1浓度增加，Kusa—A1和Kusa-O细胞中Cbfa1和Ose2元件启动子活性均逐渐提高。统计分析表明：Kusa—A1细胞中1／40μg／μL实验组两启动子活性均与对照组差异显著；Kusa-0细胞中1／40μg／μL实验组Ose2元件启动子活性与对照组差异显著。结论：转录调控因子CBF1可以促进Cbfa1和Ose2元件启动子活性，从而可能对细胞的成骨性分化有正调节作用。     

Acral granulomatous dermatosis

A 17-year-old boy developed an acral granulomatous dermatosis which resembled clinically acrodermatitis continua of Hallopeau. The histology showed dermal and subcutaneous abscess formation with granulomas. The lesions responded to systemic corticosteroid therapy, with residual atrophy and contractures of the fingers.     

Recovery from neuroendocrinological abnormalities and frontal hypoperfusion after remission in a case with rapid cycling bipolar disorder

Abstract  A 51-year-old Japanese woman who had been suffering from a rapid cycling affective disorder (RCAD) for 24 years responded to combined clonazepam and carbamazepine therapy. Before remission, she showed neuroendocrinological and neuroimaging abnormalities such as subclinical hypothyroidism with exaggerated response to thyrotropin releasing hormone (TRH) injection, non-suppression on the dexamethasone suppression test (DST) and hypofrontality in cerebral blood flow. Her symptoms improved remarkably soon after adjunctive clonazepam treatment. After remission, her biological markers gradually returned to normal. First, subclinical hypothyroidism improved 2 months after remission. Next, hypofrontality disappeared 18 months later. Furthermore, non-suppression on the DST normalized 24 months later. The normalization of biologcal markers with apparent recovery from RCAD suggests a decreased risk of relapse into mood disorder. These findings reiterate the importance of following-up on the biological markers in RCAD for years after remission.     

Chemical synthesis of phosphorylated peptides of the carboxy-terminal domain of human p53 by a segment condensation method

A segment condensation method was developed for the chemical synthesis of large (>90 amino acid) phosphopeptides and was used to produce phosphorylated and non-phosphorylated derivatives of the C-terminal tetramerization and regulatory domains of human p53 (residues 303-393). Efficient condensation synthesis of the 91 residue p53 domain was achieved in two steps. The non-phosphorylated N-terminal segment p53(303-334) (1) and its derivative phosphorylated at serine 315 (1P315), and the non-phosphorylated middle segment p53(335-360) (2), were synthesized as partially protected peptide thioesters in the solid phase using Boc chemistry. The C-terminal segment p53(361-393) (3) and its derivative phosphorylated at serine 392 (3P392) were synthesized as partially protected peptides in the solid phase using Fmoc chemistry. Phosphoamino acid was incorporated into the N-terminal segment (1P315) at the residue corresponding to p53 serine 315 as Boc-Ser(PO₃(Bzl)₂)-OH during synthesis. Serine 392 in the C-terminal segment was selectively phosphorylated after synthesis by phosphitylation followed by oxidation. A derivative phosphorylated at serine 378 was synthesized in a one-step condensation of the unphosphorylated N-terminal segment (1) and the phosphorylated long C-terminal segment p53(335-393) (2-3P378). Yields of the ligated peptides after removal of the protecting groups and HPLC purification averaged 60% for the first condensation and 35% for the second condensation. All five p53 peptides exhibited monomer-tetramer association as determined by analytical ultracentrifu-gation. Circular dichroism spectroscopy revealed that phosphorylation at Ser315 increased the α-helical content, which was abolished when Ser392 also was phosphorylated, suggesting an interaction between N-terminal and C-terminal residues of the C-terminal domain of p53. © Munksgaard 1996.     

Immunotherapy Affects the Seasonal Increase in Specific IgE and Interleukin-4 in Serum of Patients with Seasonal Allergic Rhinitis

This study was designed to determine seasonal changes in cytokines, soluble CD23 and specific IgE in the serum of patients with seasonal allergic rhinitis, and the effect of immunotherapy on these seasonal changes. Fifty-four patients with seasonal allergic rhinitis caused by Japanese cedar pollens were divided into a medication group and an immunotherapy group. The patients of the medication group were treated with non-sedating antihistamines alone during the pollen season. The patients of the immunotherapy group had been treated for variable periods (mean, 5.0 ± 3.2 years) with immunotherapy using Japanese cedar pollen antigens. Serum samples were collected before and during the pollen season from each patient, to determine specific IgE, interleukin-4 (IL-4), interferon-γ (IFN-γ) and soluble CD23 levels in serum. A significant increase in specific IgE and IL-4 and a significant decrease in IFN-γ were observed during the pollen season in the medication group. In contrast, in the immunotherapy group, none of specific IgE, IL-4 and IFN-γ was significantly changed following natural exposure to pollens. However, these effects were not significant in patients undergoing immunotherapy for 3 or fewer years. Seasonal rates of increase in specific IgE and IL-4 differed significantly between good responders and poor responders to immunotherapy, but seasonal rates of decrease in IFN-γ did not. A seasonal rate of increase in soluble CD23 was significantly correlated with a seasonal rate of increase in specific IgE, in both the medication and the immunotherapy groups. The seasonal rate of increase in soluble CD23 was significantly smaller in the good responders than in the poor responders to immunotherapy. In conclusion, pollen immunotherapy reduces the seasonal increase in specific IgE, IL-4 and soluble CD23 in serum, and in addition switches the seasonal preferential activation of Th-2 cells to reciprocal activation of Th-1 cells with treatment over several years. It is likely that the mechanisms responsible for the clinically beneficial effects of immunotherapy principally involve the modulation of Th-2 rather than Th-1 cytokines.     

Color Doppler ultrasonography as a routine clinical examination in male infertility

AIM: We assessed the value of scrotal color Doppler ultrasonography as a routine examination in infertile men. METHODS: Color Doppler ultrasonography was performed in 545 infertile men with a mean age of 35.8 years to detect intrascrotal abnormalities. Findings were compared with those of physical examination. RESULTS: Intrascrotal abnormalities were detected by ultrasonography in 65.3% of patients. Of 374 abnormalities, 58.3% were undetected by physical examination. Left varicocele was found in 313 patients (57.4%); testicular microlithiasis in 30 (5.5%); epididymal cyst in 21 (3.9%); right varicocele in 4 (0.8%); and testicular cysts in 3 (0.6%). One occurrence each (0.2%) was found for testicular tumor, intrascrotal hemangioma, and hydrocele of the spermatic cord. Compared to ultrasonography, sensitivity in detecting left varicocele by physical examination was 58.4%; specificity, 79.3%; accuracy, 67.3%; and positive predictive value, 79.3%. Venous diameters in the pampiniform plexus were 3 mm or more in 61.5% of 130 subclinical left varicoceles. Of 30 patients with testicular microlithiasis, 14 had varicocele, 2 had epididymal cyst,s 3 had a history of mumps orchitis, 1 had retractile testis, and 1 had a history of orchiectomy for contralateral testicular tumor. CONCLUSIONS: The routine Color Doppler ultrasonography is valuable for diagnosing scrotal abnormalities in infertile men, frequently detecting non-palpable lesions.     

Up-titration of vardenafil dose from 10 mg to 20 mg improved erectile function in men with spinal cord injury

AIM: Vardenafil is a highly selective phosphodiesterase type-5 inhibitor for the treatment of erectile dysfunction (ED). Efficacy of vardenafil has been demonstrated in various ED populations, but that in Japanese patients with spinal cord injury (SCI) has not been assessed. METHODS: This was an open-label, multicenter, flexible dose, 12-week study in patients with ED due to SCI. Following a 4-week observation period, patients received vardenafil 10 mg for 4 weeks, and based on efficacy, tolerability and patient preference, doses for the remaining 8 weeks were decided by investigators. The primary efficacy parameter was erectile function domain score of the International Index of Erectile Function. RESULTS: Ten patients took 10 mg all through the study, while 22 patients took 20 mg after completing 4 weeks' treatment with 10 mg. The erectile function domain score increased from 12.2 at baseline to 25.0 at Last Observation Carried Forward (LOCF) in the former group and from 10.3 to 22.5 in the latter group, respectively. Importantly, there was a 5.0 point increase in erectile function domain score after up-titration in the latter group. Drug-related adverse events were observed in 22% of patients including hot flushes (9%) and headache (6%), but these were transient and mild in intensity. Serious adverse events and adverse events leading to discontinuation of the study drug were not reported. CONCLUSIONS: Vardenafil 10 and 20 mg was well tolerated and improved erectile function in patients with SCI. Of interest, erectile function was further improved by 20 mg in patients who were not sufficiently treated with 10 mg.