Increase of Bone Mass and Mechanical Strength in Rats after Treatment with a Novel Bisphosphonate,YM175, for Two Years

Abstract: We have evaluated the relationship between bone mass and mechanical properties of bone from male and female rats treated with YM175, a novel bisphosphonate, for 104 weeks. YM175 [disodium (cycloheptylamino) methylenediphosphonate monohydrate] was given via the drinking water at a concentration of 0, 0.005, 0.015, 0.05, or 0.15%. Since the mortality in the male 0.15% group exceeded the exclusion criteria (75%) at week 88, this group was omitted from the study. Mean daily intake of YM175 was 2.2-22.1 mg/kg for males and 3.6-104 mg/kg for females. After the treatment, mechanical properties and ash weight of the humerus were determined. In males, 0.015 and 0.05% of YM175 (6.6–22.1 mg/kg) significantly increased failure load of the midshaft. In females, failure load and stiffness of the midshaft tended to be increased by YM175 (up to 104 mg/kg). Furthermore, ultimate compressive load at the humeral metaphysis treated with the highest dose of YM175 was 2- or 3.5-fold greater than that of untreated male or female control. Ash weight of the humerus was increased dose-dependently and was positively correlated with failure load of the midshaft. These findings indicate that treatment for 2 years with YM175 increased bone mass and mechanical strength without blocking bone mineralization.     

Hyperthermo-chemo-radiotherapy as a definitive treatment for patients with early esophageal carcinoma.

Ten patients with early stage esophageal carcinoma were treated with hyperthermo-chemo-radiotherapy (HCR) without surgery. The reasons for the inoperability of these patients included medically inoperable unresectable cancers, advanced age, and/or refusal to undergo surgery. The diagnosis of early esophageal carcinoma was determined by esophagograms, endoscopy, and ultrasonography. Squamous cell carcinoma was histopathologically confirmed in each case. Each patient underwent four to nine sessions of hyperthermic treatment combined with external irradiation and chemotherapy using bleomycin; eight of these patients received additional radiation, and two terminated treatment after the HCR therapy. The tumors in all patients showed either a complete response (CR) or a partial response (PR) after HCR therapy; in two patients viable cancer cells remained, but later disappeared after additional radiation. Five patients experienced no local recurrence for 12 to 70 months and are now alive and doing well, three died of other medical conditions without any evidence of esophageal cancer, and two died of recurrent esophageal cancer 20 to 27 months after initial admission. All ten patients tolerated the HCR well without any systemic side effects. However, in two patients, esophageal erosion was recognized endoscopically. HCR therapy therefore deserves serious consideration when treating patients with small malignant lesions of the esophagus who, for various reasons, are unable to undergo surgery.     

The small airway inflammation of asthmatic patients who have used dry powder type inhaled steroid for moderate-long term evaluated by induced sputum and the efficacy of HFA-BDP (QVAR) inhalation]

Although the dry powder type inhaled steroids, such as Fluticasone Propionate Diskhaler (FP-DH), FP Diskus (FP-DK), Budesonide Turbuhaler (BUD-TH), are widely distributed in daily clinical fields, we clinicians are required to evaluate whether it is effectively inhibiting inflammation of distal airway or not. We also investigated the effect of Hydrofluoroalukan-beclomethasone dipropionate (HFA-BDP), a new type of inhaled steroid which forms super micro aerosol particles, in the distal small airway. METHOD: 85 patients with moderate asthma, who daily used dry powder type inhaled steroid for at least more than 6 months with stable asthmatic condition, were the subject of this study. All subjects underwent sputum induction with the inhalation of 10% of hypertonic saline solution for 15 min and eosinophil counts and eosinophil cationic protein (ECP) in individual induced sputum were measured. Then, patients who had eosinophils detected in their induced sputum changed their previously inhaled steroid to HFA-BDP inhalation (400 i.g./day). Their eosinophil counts and the values of eosinophil cationic protein (ECP), Eotaxin, RANTES and neutrophil elastase (PMN-E) in their induced sputum were also examined before and 4weeks after changing HFA-BDP inhalation. RESULT: Increased eosinophils were found in the induced sputum of 40.5% patients of the FP-DK group, 36.3% of the FP-DH group and 32.4% of the BUD-TH group, respectively. Compared with group of patients in which no sputum eosinophil were detected, the sputum ECP values, in which sputum eosinophils were detected, were significantly high. 4 weeks after changing to HFA-BDP inhalation, eosinophil counts, ECP, Eotaxin, RANTES and PMN-E in their induced sputum were decreased in every group. CONCLUSION: Compared with the ordinary dry powder type inhaled steroids, HFA-BDP can effectively diminish distal airway inflammation, suggesting the possibility that HFA-BDP can effectively reach to the distal small airway by forming super micro aerosol particles.     

Expression of TGF-α, EGF and their common receptor in human fetal kidney

Summary: Transforming growth factor-α (TGF-α) and epidermal growth factor (EGF) are structurally related mitogenic polypeptides. They share the same receptor; EGF receptor. the EGF receptor is widely expressed in human fetal tissues including the kidney, but little is known about the role of TGF-α/EGF/EGF receptor system in human fetal kidney. the expression of TGF-α, EGF and their common receptor was investigated immunohistochemically in the human fetal kidneys. In the cortex, immunoreactivity for TGF-α was found in the differentiating proximal tubules. In contrast, immunoreactivity for EGF was present in the thick ascending limbs of the Henle's loop (TAL) and medullary collecting duct cells (CD). Immunoreactivity for their common receptor was present mainly in the TAL and medullary CD. These data support the assumption that the system of TGF-α, EGF and its receptor has an important role in the proliferation and differentiation of the TAL and medullary CD. the different localization of TGF-α and its receptor may indicate that TGF-α acts through a paracrine mechanism. the co-localization of EGF and its receptor in the TAL and medullary CD suggests that EGF may act as an autocrine growth factor.     

A case of brachial amyotrophic diplegia accompanied with Sj?gren's syndrome presenting good response to immunotherapies in the early course of the disease]

A 74-year-old woman suffered from progressive muscle atrophy and weakness of her arms since she was seventy two years old. Before referral to our department, she was diagnosed as having cervical spondylotic myeloradiculopathy and received spinal fusion. Though spinal decompression was successful, muscle weakness of her upper limbs were progressive even after the surgery. On admission, neurological examinations revealed marked atrophy and weakness of her bilateral upper limbs with absent deep tendon reflexes showing man-in-the-barrel syndrome. Her lower extremities had normal muscle strength, but fasciculations were seen in her all four limbs. Electrophysiologically, motor nerve conduction velocity was almost normal but the amplitude was remarkably decreased, conduction block was not detected, and electromyography showed neurogenic patterns on her all extremities. Spinal progressive musclar atrophy (SPMA) accompanied with Sj?gren's syndrome was the likely diagnosis. Because 50 kDa anti-neuronal antibodies were found in her serum, we assumed that anterior horn cells were impaired by an autoimmune mechanism. Thus we treated her with corticosteroid pulse therapy, plasma exchange (PE) and intravenous immunoglobulin infusion therapy (IVIG). Although steroid pulse therapy only had a minimal effect, PE and IVIG promoted a remarkable improvement on her weakness, and the effect lasted for about three months. This is the first case of SPMA with Sj?gren's syndrome which showed good response to PE and IVIG in the early course of the disease. We considered that some SPMA-like motor neuron syndrome accompanied with autoimmune features may require immunomodulating therapies.     

Scoliosis in cat cry syndrome

Background Cat cry syndrome is an autosomal disease accompanying abnormal deletion of chromosome 5 and occurs in only 1 of 50,000 neonates. Scoliosis has been reported as a skeletal complication in cat cry syndrome. The characteristics and causes of scoliosis in this rare syndrome are unknown. The purpose of this study was to present the characteristics of scoliosis in cat cry syndrome and to speculate on its causative mechanisms. Methods We report on 11 cases (5 boys and 6 girls) of cat cry syndrome. Detailed investigations of scoliosis, as well as physical and imaging examinations, were performed to characterize scoliosis and its causes. Average age at initial diagnosis of scoliosis was 4.3 years, and average age at final examination was 11.8 years. Results The incidence of scoliosis was as high as 73% (8/11). Most cases show a single right thoracic curve. Of the 8 patients with scoliosis, 3 patients who had increased muscular tone showed marked progression of scoliosis with growth. Conclusions Muscular hypertonia may play a key role in the progression of scoliosis in cat cry syndrome.     

Rationale and design for a study using intravascular ultrasound to evaluate effects of rosuvastatin on coronary artery atheroma in Japanese subjects: COSMOS study (Coronary Atherosclerosis Study Measuring Effects of Rosuvastatin Using Intravascular Ultrasound in Japanese Subjects).

BACKGROUND: There have been few multicenter studies using intravascular ultrasound (IVUS) to assess the process of atherosclerosis in a Japanese population with hypercholesterolemia that is being treated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors for control of low-density lipoprotein-cholesterol. METHODS AND RESULTS: An open-label multicenter study is planned to evaluate with IVUS whether treatment with rosuvastatin for 76 weeks results in regression of coronary artery atheroma volume in patients who have coronary heart disease (CHD) and hypercholesterolemia. Sample size is 200 subjects with CHD who are to undergo percutaneous coronary intervention. The planned duration is between October 2005 and October 2008. CONCLUSIONS: The COSMOS study will be the first multicenter cardiovascular study in a Japanese population and may provide new evidence on the effects of rosuvastatin on the progression of coronary atherosclerotic lesions.     

Neglected fracture dislocation of the second and third carpometacarpal joints: a case report.

We report a rare case of neglected fracture dislocation of the second and third carpometacarpal joints, which was treated by arthrodesis of the involved joints.     

Kinetics and specificity at the clonal level of the cytotoxic T lymphocyte response to influenza pneumonia

We have studied the kinetics and specificity of the cytotoxic T lymphocyte (CTL) response to influenza A/PR/8 (H1N1) virus pulmonary infection in the mouse detected using spleen cells from infected mice which were stimulated in bulk and limiting dilution cultures. A hybrid protein designated D-peptide, which contains the terminal 157 amino acids of the HA2 subunit of A/PR/8 virus, was used to stimulate influenza virus subtype-specific secondary CTL in vitro. Infection induced two specificities of precursor CTL, cross-reactive and subtype-specific. The kinetics of the subtype-specific CTL response detected by the D-peptide were similar to the cross-reactive CTL response detected by stimulation with live virus. The majority of the precursor CTL (CTL-p) are able to lyse virus-infected target cells in a cross-reactive fashion. The number of memory subtype-specific and cross-reactive CTL increased by approximately 2.5 logs10 during the first 3 weeks after infection.