Clinicopathological Significance of Nuclear Accumulation of Tumor Suppressor Gene p53 Product in Primary Lung Cancer

Since the nuclear accumulation of p53 protein is known to correspond well with mutation of the p53 tumor suppressor gene, the authors examined 88 primary lung cancer specimens immunohistochemically using anti-p53 mouse monoclonal antibody, pAb1801, and analyzed the relationship between the immunohistochemical results and clinicopathological features. Nuclear localization of p53 protein was found in 43/88 (49%) tumor specimens, but not in the corresponding normal lung tissues. The percentage of cases showing nuclear p53 localization varied according to the histological type. In squamous cell carcinoma, nuclear p53 localization was found in 15/26 (57%), appearing more frequently than in other histologic types. However, no obvious correlation was observed between nuclear p53 localization and patients' age, sex, history of smoking, TNM factor, degree of differentiation, or any other clinicopathological features analyzed. In adenocarcinoma, nuclear p53 localization was found in 20/46 (43%). Incidence of positive cases was significantly correlated with regional lymph node metastasis, distant metastasis, and pathological stage ( P < 0.05). These results indicate that mutation of the p53 tumor suppressor gene plays an important role in the development of primary lung cancer, and that nuclear accumulation of p53 protein is a potential prognostic factor in adenocarcinoma of the lung.     

Effect of protocatechualdehyde,a metabolite of the novel antirheumatic agent ACP,on chondrocyte metabolism

We investigated PAL (protocatechualdehyde), one of the metabolites of ACP (3,4-diacetoxy benzylidene diacetate) which is a candidate novel antirheumatic agent. Specifically, we studied the effect and mechanism of action of PAL on chondrocyte metabolism using a primary culture of chondrocytes from rabbit articular cartilage. Proteoglycan (PG) depletion in the chondrocyte matrix was induced by the addition of human recombinant interleukin-1α (hrlL-1α) or phorbol myristate acetate (PMA). PAL (10–100 μM) significantly reduced the induced PG depletion and [³⁵S]-PG release in the chondrocyte matrix. The matrix metalloproteinase (MMPs) inhibitor, 1,10-phenanthroline, and protein kinase C (PKC) inhibitor, H-7, also blocked PG depletion and [³⁵S]-PG release. Furthermore, H-7 reduced the production of MMPs induced by hrlL-1α in the culture media of chondrocytes. These results indicate that hrlL-1α causes MMPs production by the activation of PKC, which is followed by [³⁵S]-PG release in the chondrocyte matrix. While PAL also resulted in significant inhibition of MMPs production, which might be mediated by PKC activation, it had no direct influence on PKC activity. These results suggest that PAL affects chondrocyte metabolism by the inhibition of MMPs production. ©1993 Wiley-Liss, Inc.     

A newly improved sliding tube for colonoscopy for keeping the sigmoid colon in a straight condition.

Although a sliding tube made of plastics is very effective to keep the sigmoid colon in a straight position, there is some difficulty in handling the colonoscope, being restricted by the length of the scope. For the purpose of covering the demerits of the conventional sliding tube, a new slit sliding tube which is made up of three parts was devised by us. After straightening the sigmoidal loop, the three parts of the apparatus are joined together. Then the slit sliding tube is inserted into the descending colon with safety and ease. By using the slit sliding tube, handling of the colonoscope is scarcely restricted and becomes easy. Moreover, the slit sliding tube can be used even for the shorter scopes, by which the distal parts of the colon can be more easily examined in comparison with conventional techniques.     

Exploration of a new type of antimalarial compounds based on febrifugine

Febrifugine (1), a quinazoline alkaloid, isolated from Dichroa febrifuga roots, shows powerful antimalarial activity against Plasmodium falciparum. The use of 1 as an antimalarial drug has been precluded because of side effects, such as diarrhea, vomiting, and liver toxicity. However, the potent antimalarial activity of 1 has stimulated medicinal chemists to pursue compounds derived from 1, which may be valuable leads for novel drugs. In this study, we synthesized a new series of febrifugine derivatives formed by structural modifications at (i) the quinazoline ring, (ii) the linker, or (iii) the piperidine ring. Then, we evaluated their antimalarial activities. Thienopyrimidine analogue 15 exhibited a potent antimalarial activity and a high therapeutic selectivity both in vitro and in vivo, suggesting that 15 is a good antimalarial candidate.     

Clinical evaluation of cefmenoxime (CMX) for complicated urinary tract infection

Cefmenoxime (CMX), a new semisynthetic antibiotic, was administrated in 29 cases diagnosed as complicated urinary tract infection. All patients received drip injection of 2 g (twice a day) for 5 days. Clinical results were excellent in 1 patient (3.4%), good in 15 patients (51.8%) and poor in 13 patients (44.8%). Effectiveness rate was 55.2%. In bacteriological response, out of 35 strains 27 (77.1%) strains were eradicated and 8 (22.9%) strains persisted. As for side effects, except one case of transient diarrhea after administration, no noteworthy reactions were observed. Laboratory abnormalities attributed to CMX treatment consisted of 4 cases of elevated serum transaminase and 2 cases of elevated serum creatinine.     

Effect of oral health care program on the oral function of the elderly

In order to prepare a new prevention program under the long term care insurance from the fiscal year 2006, we have organized an oral health care program for the elderly in a town of Kagoshima prefecture. We conducted a series of oral health education, i.e., instruction on brushing and flossing, and oral function exercises. Before and after the three months program, we evaluated the unstimulated and stimulated salivary flow rate, the counts of S. mutans, the counts of repetitive saliva swallowing test (RSST), bilateral bite force and the number of permanent teeth and artificial teeth. According to the results, a statistically significant improvement was observed in RSST and the unstimulated and stimulated salivary flow rate, but not in the S. mutans level and bite force. The present research suggests the effectiveness of the oral health care program for the aged. A larger sized and longer period intervention will be necessary in order to validate our findings.     

Usefulness of insulin detemir in Japanese children with type 1 diabetes

Background: This multicenter observational study was conducted to investigate the efficacy and safety of insulin detemir (detemir) for diabetes management in Japanese children and adolescents. Methods: Data from the Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes database were analyzed. Ninety children (32 boys, 58 girls; mean age, 11.9 ± 3.8 years) who transferred from a neutral protamine Hagedorn insulin or insulin glargine basal‐bolus regimen to detemir basal‐bolus therapy and who were observed for at least 12 months were identified. Clinical data obtained at 0, 3, 6, and 12 months were analyzed to determine the type of bolus insulin used, number and timing of detemir injections, detemir dose as a proportion of the total insulin dose, hemoglobin A1c (HbA1c), fasting blood glucose (FBG) and frequency of severe hypoglycemia. Results: Twelve months after switching to detemir, the detemir dose represented 39.8% of the total insulin dose, and 37.8% of patients were being treated with twice‐daily injections. HbA1c and FBG were significantly reduced from baseline at 3 and 6 months but not at 12 months. Considering the seasonal HbA1c variation in the Japanese population, a separate analysis was performed using data for 65 children (21 boys, 44 girls; mean age, 11.6 ± 2.9 years) who switched to detemir during the winter. Subset analysis showed significant HbA1c reductions from baseline at all specified times. The incidence of severe hypoglycemia during detemir treatment was 4.4 episodes per 100 patient‐years. Conclusions: Detemir is an effective and safe basal insulin for diabetes management in Japanese children and adolescents.