Tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) stimulate osteoclastic bone resorption

As both tissue inhibitor of metalloproteinases-1 (TIMP-1) and TIMP-2 have been reported to inhibit bone resorption, we examined whether TIMP-1 or TIMP-2 in fetal calf serum (FCS), with which culture media were supplemented, affected osteoclastic bone resorption in vitro. Contrary to our expectation, almost complete suppression of osteoclastic bone resorption was observed when both TIMP-1 and TIMP-2 were removed from the FCS. Bone resorption was, however, almost fully restored by the addition of recombinant TIMPs. TIMPs stimulate bone resorption at significantly lower concentrations (∼ng/ml) than those (∼μg/ml) required to inhibit bone resorption. To understand the mechanism of TIMP-dependent bone resorption, we counted and compared the number of tartrate-resistant acid phosphatase-(TRAP-) positive and multinuclear cells in cultures containing either 10% FCS or TIMP-1-free and/or TIMP-2-free FCS. There was essentially no difference in number among these, suggesting that the TIMP role seems to be related to the functional expression of osteoclasts. Metallo-proteinase inhibitors, either BE16627B[l-N-(N-hydroxy-2-isobutylsuccinynamoyl)-seryl-l-valine] or R94138 {N-methyl-(3S)-2-[(2R)-2-hydroxycarbamoylmethylundecanoyl] hexahydropyridazine-3-carboxamide}, could not replace TIMPs, suggesting that the osteoclast-stimulating activity of TIMPs cannot be ascribed to merely their inhibitory effect on matrix metalloproteinases. Received: Oct. 15, 1998 / Accepted: April 5, 1999     

Endosalpingiosis of nonmetastatic lymph nodes along the stomach in a patient with early gastric cancer: Report of a case

We report herein the case of a 32-year-old woman who underwent distal gastrectomy with D2 lymph node dissection for gastric cancer. Microscopic examination of the resected specimen revealed signet-ring cell carcinoma of the stomach with lymph node metastases, and endosalpingiosis in the normal lymph nodes. There was no evidence of malignancy in the peritoneal cavity. To our knowledge, no other case of endosalpingiosis in the lymph nodes along the stomach has ever been reported. The possible significance of endosalpingiosis is discussed following this case report.     

Individualizing Hearing Preservation in Acoustic Neuroma Surgery

Surgical series of hearing preservation in acoustic neuroma usually emphasize a team's results with one particular technique. This report reviews acoustic neuroma outcomes of individualizing the surgical approach to patient and tumor characteristics. This study reviews 60 consecutive hearing preservation acoustic neuroma surgeries in a total series of 330 acoustic neuromas. Tumor sizes ranged from 0.3 to 4 cm in patients ranging from 23 to 74 years of age. Middle fossa surgery was performed in 57%, retrosigmoid in 43%. Overall, measurable hearing was preserved in 77%, and useful hearing in 67%. Among middle fossa cases, 85% had measurable and 74% had useful hearing. Among retrosigmoid surgeries, 65% had measurable hearing and 58% had useful hearing. Overall, long-term facial nerve function was excellent (grade I or II) in 90% and poor (grade V or VI) in 2%. There was one case of bacterial meningitis(2%), and cerebrospinal fluid leaks requiring surgery occurred in four patients (7%). The hearing preservation and other outcome parameters in this series compare favorably with other reports. We believe that individualizing the surgical approach to the patient's tumor characteristics and clinical features contributed to the high rate of hearing preservation.     

Survey on visual and musculoskeletal symptoms in VDT workers]

With the spread of visual display terminals (VDT) in offices, the numbers of workers using VDT and the working hours at such equipment have increased rapidly in recent years. Also, preventive measures for fatigue have been proposed and the office-working environment has been improved. To examine the effects of the rapid changes in working conditions and environment on the health of VDT workers, we conducted a questionnaire survey in 2002. A self-reported questionnaire was distributed to 3,927 office workers; 2,374 (60.5%) responded. Subjects whose questionnaires had missing data were excluded from analysis. As a result, 1,406 (male: 1,069, female: 337) workers aged 20 to 59 were subjected to analysis. By a logistic regression model, we examined the association between VDT use and visual and musculoskeletal symptoms. Prevalence of eye strain and/or pain (72.1%) was the highest, followed by neck stiffness and/or pain (59.3%), low back stiffness and/or pain (30.0%) and hand or arm strain and/or pain (13.9%). Women consistently reported more discomfort than men. As a result of the logistic regression model, eye strain and/or pain was associated with dissatisfaction with airflow, but not with factors affecting visual symptoms as reported in previous studies, for example, reflection of light and blurred characters on the screen. It was thought that airflow appeared as a risk factor because the lighting environment had been improved in offices to prevent reflection of light on the screen. Neck stiffness and/or pain was associated with raising the shoulders during VDT work, the unsuitable shape of the computer mouse for a hand, and the inconvenient arrangement of the mouse in relation to the body. Hand or arm strain and/or pain were associated with the arrangement of the mouse and inappropriate height of the desk. Low back stiffness and/or pain were associated with dissatisfaction with the chair and using the keyboard without a wrist rest. Although measures to prevent fatigue had been implemented for VDT workers, risk factors for musculoskeletal symptoms would be the same as in previous studies.     

Galectin-9 as a prognostic factor with antimetastatic potential in breast cancer.

PURPOSE: Galectin-9, a member of the beta-galactoside-binding galectin family, induces aggregation of certain cell types. We assessed the contribution of galectin-9 to the aggregation of breast cancer cells as well as the relation between galectin-9 expression in tumor tissue and distant metastasis in patients with breast cancer. EXPERIMENTAL DESIGN: Subclones of MCF-7 breast cancer cells with high or low levels of galectin-9 expression were established and either cultured on plastic dishes or transplanted into nude mice. The tumors of 84 patients with breast cancer were tested for galectin-9 expression by immunohistochemistry. The patients were followed up for 14 years. RESULTS: MCF-7 subclones with a high level of galectin-9 expression formed tight clusters during proliferation in vitro, whereas a subclone (K10) with the lowest level of galectin-9 expression did not. However, K10 cells stably transfected with a galectin-9 expression vector aggregated in culture and in nude mice. Ectopic expression of galectin-9 also reduced MCF-7 cell adhesion to extracellular matrix proteins. Tumors of 42 of the 84 patients were galectin-9 positive, and those of 19 of the 21 patients with distant metastasis were galectin-9 negative. None of the 13 patients with galectin-9-positive tumors and lymph node metastasis up to level II manifested distant metastasis. The cumulative disease-free survival ratio for galectin-9-positive patients was more favorable than that for the galectin-9-negative group (P < 0.0001). Multivariate analysis revealed that galectin-9 status influenced distant metastasis independently of and to a greater extent than lymph node metastasis. CONCLUSIONS: Galectin-9 is a possible prognostic factor with antimetastatic potential in breast cancer.     

Effect of sarpogrelate on cardiovascular disorders

The present article, dedicated to Dr NS Dhalla on the occasion of the jubilee of his life’s work, is a brief review of articles based on the authors’ studies of sarpogrelate conducted in collaboration with Dr NS Dhalla. These studies on the effects of sarpogrelate on cardiovascular disorders have been ongoing for more than 10 years, and 10 articles have been published to date.     

Pemphigus with thymoma improved by thymectomy: report of a case

A 53-year-old female with pemphigus vulgaris received treatment with prednisolone for 3 years. On chest computed tomography performed at follow-up, an anterior–mediastinal tumor (4 cm × 3 cm) was detected and diagnosed as a thymoma. Although amyosthenia was absent, the patient’s anti-acetylcholine-receptor antibody level was high, and she was positive for anti-desmoglein 3 antibodies. She underwent extended thymectomy in the same year, following which both the anti-acetylcholine receptor antibody and the anti-desmoglein 3 antibody levels were normalized. The patient’s skin symptoms improved, and the steroid dose was gradually lowered and finally discontinued 4 years postoperatively. Extended thymectomy may be an effective therapy for treating patients with pemphigus.     

A successful antimicrobial therapeutic strategy for the discitis caused by Aggregatibacter actinomycetemcomitans under unknown drug susceptibility: A case report

Aggregatibacter actinomycetemcomitans is well-known as the pathogen of gingivitis or periodontitis, and discitis or vertebral osteomyelitis cases caused by this organism have rarely been reported. Ampicillin or amoxicillin has been used in the previously reported discitis cases; however, no cases have been reported that is treated with levofloxacin. We report the first published case we chose levofloxacin to treat. We failed to perform the susceptibility testing because of the poor growth and fastidious nature of the organism, and the result of susceptibility of amoxicillin was unclear. Levofloxacin, which A. actinomycetemcomitans is usually susceptible to, can be an effective alternative oral antimicrobial agent in such cases.