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To establish the actual serial changes in body weight in Japanese people and to elucidate the influence of changes in BMI on morbidity, we conducted a historical cohort study of university graduates from 1955 to 1990 using questionnaires and BMI data. The subjects of this study were 3,675 university graduates aged 26-62 years in whom BMI was determined at the time of enrollment in the university (Pre-BMI), 5 to 40 years earlier. Morbidity (one or more system diseases or obesity-related system diseases) was analyzed according to current age, sex, current BMI, deltaBMI (difference between current BMI and pre-BMI), and various lifestyle variables. The proportion of overweight subjects at enrollment to university was higher in recent male students compared to old students, but not in female graduates, and the BMI in both genders increased progressively after graduation, especially in recent male graduates. Pre-BMI correlated negatively and significantly with deltaBMI. The percentages of obese (BMI > or = 30 kg/m2) males and females were 1.6% and 0.5%, respectively, and high morbidity was observed in 56.1% and 42.2% of males and females, respectively. Stepwise regression analysis showed that in subjects with normal BMI at enrollment, prospective morbidity was dependent on ABMI in addition to age. Our results indicate that in subjects with normal body weight, prospective morbidity is determined by increment of ABMI, and suggest that maintenance of BMI at the late adolescence level is an important factor in preventing future disease.

Different bone allografts (pasteurized, autoclaved, and frozen) were compared based on their osteoinductive properties. Our primary purpose was to examine the biologic qualities of pasteurized allografts, as pasteurization inactivates most viruses transmitted by transplantation. Frozen, pasteurized, and autoclaved allografts were packed into a standard defect of rabbit ulna. The animals were sacrificed at 2 and 4 weeks after surgery. The parts of bones with experimental defects were explored en bloc, and a roentgenogram was carried out. Ulna bone samples were then embedded in methyl-methacrylate. Roentgenograms showed that after 2 weeks, calluses were well-formed, but irregular in shape in all 3 types of allografts. After 4 weeks, the calluses were regular in shape in all but the autoclaved grafts. After 2 weeks, the healing processes had begun in the frozen and pasteurized grafts, with the reaching approximately the same stage, while in the autoclaved grafts these processes were not seen and the bone particles were surrounded by connective tissue without any changes. After 4 weeks, osteoinductive processes were very strong, with the first signs of complete bone remodeling at the bone edges of the defect in pasteurized and frozen allografts. The osteoinductive values of these 2 types were very high and similar. Autoclaved allografts, on the other hand, had very low osteoinductive values, as they were still at the very beginning of the healing process. Histomorphometric analysis revealed a significant difference in both newly formed osteoid thickness and osteoblast number per microm of bone surface in all experimental groups (P < 0.005). Values of osteoid thickness and osteoblast number were significantly higher in both frozen and pasteurized grafts when compared with the autoclaved ones (P < 0.005). Osteogenic properties of pasteurized bone allografts were preserved, and the allografts have been gradually replaced with newly formed bone. As such, pasteurized bone grafts from a bone bank have approximately the same biologic validity as frozen grafts, while autoclaved grafts impair bone healing.

We have shown that highly proofreading DNA polymerase is required for the polymerase chain reaction in the genetic analysis of hepatitis C virus (HCV). To clarify the status of HCV quasispecies in hepatic tissue using proofreading DNA polymerase, we performed a genetic analysis of the HCV core protein-encoding region in cancerous and noncancerous lesions derived from 4 patients with hepatocellular carcinoma. In contrast to the previously published data, we observed neither deletions nor stop codons in the analyzed region and no significant difference in the complexity of HCV quasispecies between cancerous and noncancerous lesions. This result suggests that the HCV core gene is never structurally defective in hepatic tissues, including cancerous lesions. However, in 3 of the patients, the consensus HCV species differed between cancerous and noncancerous lesions, suggesting that the predominant replicating HCV species differs between these 2 types of lesions. Moreover, during the course of the study, we obtained several interesting variants possessing a substitution at codon 9 of the core gene, whose substitution has been shown to induce the production of the F protein synthesized by a - 2/+1 ribosomal frameshift.

Anti-idiotype antibodies (Ab2) play an important role in the homeostasis of immune responses and are related to the development and the disease activity of certain autoimmune diseases. The asialoglycoprotein receptor (ASGPR) is considered one of the target antigens in the pathogenesis of autoimmune chronic active hepatitis (AIH). We previously developed a mouse monoclonal antibody (clone 8D7) which recognizes rat and human ASGPR. In this study, to help investigate the anti-ASGPR antibody-anti-idiotype antibody network in patients with AIH, we developed a syngeneic mouse monoclonal Ab2 to the 8D7 anti-ASGPR antibody (Ab1). One clone, designated as 3C8, tested positive for specific reactivity to 8D7-Ab1 and did not bind to other irrelevant immunoglobulins. By competitive inhibition assays, the binding of 8D7-Ab1 to liver membrane extracts, i.e., the crude antigen preparation, was inhibited by 3C8-Ab2 in a dose-dependent manner, and the binding of 8D7-Ab1 to 3C8-Ab2 was inhibited by the liver membrane extracts. In the immunohistochemical analysis, 3C8-Ab2 blocked the specific staining of sinusoidal margins of rat hepatocytes by 8D7-Ab1. These results suggest that 3C8 anti-idiotype antibody recognizes the specific idiotypic determinants within the antigen-binding site of 8D7-Ab1.

When the development of chemotherapeutic agents reaches the clinical trial stage, it is necessary to perform drug sensitivity tests quickly in order to select the most promising agents for the treatment of cancer. In order to assess the possibility of using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay as a substitute for the human tumor clonogenic assay (HTCA), we evaluated the correlation between the results obtained by these 2 assays in 5 human lung cancer cell lines. The correlation coefficient between the results of the HTCA and the MTT assay was 0.673, indicating a relatively good correlation. The correlation was most prominent in platinum analogues (r = 0.939) and good in anthracyclines/anthracenedione (r = 0.611). However, no significant correlation was observed in vinca alkaloids, etoposide, irinotecan, SN-38 (an active metabolite of irinotecan), and rhizoxin. The results of the MTT assay showed a high degree of correlation with those of the HTCA in predicting the sensitivity of cancer cell lines to platinum analogues, and anthracyclines/anthracenedione. These results suggest that the MTT assay may be more convenient and quickly performed than the HTCA and can replace HTCA in evaluating the effects of anticancer agents, especially the platinum analogues and anthracyclines/anthracenedione.

In this paper we describe a patient with polycythemia vera (PV), who presented with hypercalcemia due to a parathyroid adenoma. In November 1999, the patient was admitted to our hospital with meteorism and constipation. Her physical examination revealed plethora and hepatosplenomegaly. Laboratory data revealed hyperparathyroidism in addition to PV: Rbc 8 x 10(6)/mm3, Hct 63.7%, serum calcium 13.4 mg/dl, serum phosphorus 1.2 mg/dl, albumin 4.25 mg/dl, and alkaline phophatase activity 433 U/l. Intact Parathyroid Hormone level (iPTH) was 376 pg/ml (n.v.12-72 pg/ml). Twenty-four hour urinary calcium excretion was higher than normal (900 mg). A parathyroid adenoma was detected with Tc-99m sesta-MIBI scanning under the left lobe of the thyroid gland and an ultrasonographic examination of the neck also supported the diagnosis. The patient was recommended for surgery. The histopathological examination confirmed the diagnosis. Postoperatively, iPTH dropped to 53.4 pg/ml at the 15 th minute and to 33.5 pg/ml at the first hour. The calcium level was 7.5 mg/dl one hour after the operation. Five days later, Hct was 40.8%. This case represents a rare association between PV and primary hyperparathyroidism, and may provide evidence for a causal link between PTH and polycythemia vera in our patient. In conclusion, this case indicates that the differential diagnosis of hypercalcemia and polycythemia vera should also include the possibility of a parathyroid tumor in addition to malignancy.

Postoperative hip alignment was studied on radiographs in cases of total hip arthroplasty (THA) and of Bipolar Head Prosthesis(BHP), both with MX-1. Postoperative anteroposterior-view radiographs of hip joints of patients with a normal hip joint on the unoperated side and without pelvic tilt were used. Thirty-nine THA patients (femoral neck fracture), 26 THA patients (osteonecrosis of the femoral head and osteoarthritis of the hip joint), and 34 BHP patients were selected for this study. Lines and points for measurement of 9 parameters were established on radiographs. The position of the greater trochanter upper edge is 6.5 mm (mean) superior to the femoral head center in the normal hip joint of Japanese, unlike in Caucasians. A femoral head prosthesis should be inserted so that its center and the greater trochanter upper edge are level in order to equalize leg lengths. In BHP cases, the insertion is made so that the greater trochanter upper edge is approximately 4-mm superior to the center of the prosthesis. For further securing of the stem and to equalize leg lengths, stems should be available in 11 diameters from 5-15 mm in 1-mm increments. Postoperative hip alignment in MX-1 THA cases was found to be satisfactory.

The celiac and mesenteric arterial system including the left gastric, splenic, common hepatic, and superior mesenteric arteries shows various types of origins, courses, ramifications and anastomoses. In order to explain the various expressions of this system, we have proposed a typological model, in which celiacomesenteric arteries develop as paired or bilaterally symmetrical primordial vessels originated from the anterior aspect of the aorta, and these vessels anastomose each other with longitudinal and horizontal pathways. Here, we report 3 unusual cases characterized by arterial rings, formed by the left gastric, left accessory hepatic, proper hepatic, anterior pancreaticoduodenal, and dorsal pancreatic arteries. The dorsal pancreatic and anterior pancreaticoduodenal arteries are located to the right and left of the embryonic pancreas developing in the dorsal mesentery, respectively. Such hepatopancreatic arterial rings simultaneously containing right and left elements can only be explained using our typological model, in which the concept of paired arteries or bilateral symmetry is introduced.

Two previously unknown anomalies of the anterior intercostobrachial nerve were described. In one case, the anterior intercostobrachial nerve penetrated the pectoralis minor muscle. In the other case, it penetrated the pectoralis major muscle. In both cases, the anomalous nerve supplied the skin of the upper arm.

We studied parasite detectability in thick films by an acridine orange fluorescence technique (AO) to test its applicability and the use of a Malaria Diagnosis Microscope (MDM)-ESL in the detection of parasites, compared to the conventional Giemsa staining method. This study was conducted on 1,390 clinically suspected malaria cases of Thaton township, Myanmar. We found sensitivities of 82.8% for Plasmodium falciparum (P. falciparum) and 100% for Plasmodium vivax (P. vivax) and specificities of 97.1% for P. falciparum and 98.6% for P. vivax. AO had a higher sensitivity than Giemsa-stained films at low levels of parasitemia (< 1,000/microl). AO showed lower sensitivity and higher specificity than the Giemsa method at parasite levels of more than 1,000/microl. The results of using the AO method, achieved by both novice and experienced observers, showed no significant difference and required less practice to perform the test as well as to identify the parasite. The acridine orange fluorescence technique using a malaria diagnosis microscope MDM-ESL series is simple, rapid and cost effective. The microscope is conveniently operable using standard AC power or a 12-V DC car battery, and it is easily convertible to a conventional biological microscope. With the exception of species differentiation, which is not possible with this method, this method would be appropriate for both clinical and epidemiological studies.

Gastroparesis is a frequent and sometimes life-threatening complication of diabetes mellitus. Autonomic neuropathy seems to be one of the most important mechanisms underlying this entity, together with the other probable pathologies. The present study was performed in order to identify an alternative to gastric scintigraphy as a screening test. The gastric emptying times of 60 subjects (Group 1: 20 insulin-dependent patients, Group 2: 20 non-insulin-dependent diabetes mellitus patients, and Group 3: 20 healthy volunteers) were monitored by gastric scintigraphy. Perception thresholds for cold, heat, and vibration were tested by a quantitative sensory test, and QTc dispersions were calculated from standard electrocardiography recordings. In addition, fasting blood glucose, hemoglobin A1c and urine beta2-microglobulin and microalbumin concentrations were determined for the patient groups. Funduscopic examination was performed by an independent ophthalmologist. Gastroparesis was determined in both patient groups, regardless of fasting blood glucose and hemoglobin A1c concentrations. A strong correlation was observed between nephropathy, retinopathy, and cardiac autonomic denervation (QTc) and gastroparesis. In conclusion, retinal and renal microvasculopathy parameters and cardiac autonomic function tests may be useful for screening diabetic patients for gastroparesis.

We describe a modified method for typing a polymorphic microsatellite D12S391 locus by PCR using a newly designed primer pair. This primer pair produces shorter D12S391 amplified fragments (104-156 bp) than the primer pair originally described by Lareu et al. (209-261 bp). The detection system for the D12S391 locus using the new primer pair and capillary electrophoresis (CE) analysis was evaluated using various forensic samples. The typing results from 70 DNA samples using the new primer pair and the original primer pair were completely identical. One hundred twenty-five amplified fragments from D12S391 alleles were sized correctly within +/- 0.25 bp of the D12S391 allelic ladder. A rare allele, 19.3, previously found only in Caucasians, was found for the first time in a Japanese subject, and it was clearly distinguished from allele 20 by the CE analysis. This detection system was sensitive and could detect D12S391 types from 16 pg of genomic DNA, and from a minor component at a ratio of 1:10 in mixed samples. This system was more useful for the analysis of degraded DNA than was the method using the original primer pair, and could detect D12S391 types from bloodstains that had been stored for 26 years. In addition, the specificity of the method was demonstrated using nonhuman DNA.

We previously reported that anthracyclines, which could generate reactive oxygen species (ROS), could induce the urokinase-type plasminogen activator (uPA) gene expression in human RC-K8 malignant lymphoma cells and in H69 small cell lung cancer (SCLC) cells. In screening other uPA-inducible anti-cancer agents, we found that camptothecin (CPT) and its derivative, SN38, could induce uPA in RC-K8 and H69 cells. CPT and SN38, which are also used for the treatment of lymphoma and SCLC, significantly increased the uPA accumulation in the conditioned media of both cells in a dose-dependent manner. The maximum induction of uPA mRNA levels was observed 24 h after stimulation. Pretreatment with pyrrolidine dithiocarbamate (PDTC), an anti-oxidant, inhibited the CPT-induced uPA mRNA expression. Thus, CPT induces uPA through gene expression, and, therefore, CPT may influence the tumor-cell biology by up-regulating the uPA/plasmin system.

A pilot study was conducted to assess the efficacy and feasibility of daily low-dose cisplatin with concurrent thoracic irradiation for clinically unresectable non-small-cell lung cancer (NSCLC). Patients with inoperable NSCLC who had poor risk factors such as advanced age, poor performance status, poor lung function, or concomitant active malignancy were entered into the study. Low-dose cisplatin (6 mg/m2) was administered daily before concurrent thoracic irradiation (2 Gy/day; total dose of 60 Gy) was given. Twenty-five patients were registered. The majority of the patients had either stage IIIA (24.0%) or stage IIIB (60.0%) disease. Fifteen patients (60.0%) completed the planned treatment. Both chemotherapy and radiotherapy were stopped in 3 patients (12.0%) due to poor response, and 7 patients (28.0%) partly received radiotherapy alone as a result of their toxicity response. The proportion of total administered dose to planned dose was 90.9% for chemotherapy and 99.3% for radiotherapy, which were comparable to those in previous studies for LA-NSCLC patients without poor risk factors. Grade 3 leukopenia and neutropenia developed in 14 patients (56.0%) and 10 patients (40.0%), respectively, but grade 4 toxicity was not encountered. Grade 3 pneumonitis and esophagitis were observed in 4 patients (16.0%) and 2 patients (8.0%), respectively. The overall response rate was 60.0%. The median survival time was 22 months, and the 2-year survival rate was 50.3%. Daily low-dose cisplatin and concurrent thoracic irradiation were well tolerated even by poor-risk patients with NSCLC, and showed a therapeutic efficacy similar to that for good-risk patients.

The morbidity of diabetes mellitus is increasing gradually in Japanese populations. It is important to clarify the risk factors of diabetes in Japanese populations in order to take adequate measures against the increasing morbidity of diabetes. In order to evaluate the link between past and concurrent obesity and diabetes in middle-aged Japanese men, we conducted a worksite-based historical cohort study in Okayama, Japan in 1999. Annual health examination data of middle-aged male workers in a worksite were collected. The relative risks of past and concurrent obesity for developing diabetes were calculated. Subjects with a past history of obesity at between 40 and 50 years of age had a significantly higher risk of developing diabetes by age 55 than did subjects in the normal weight group. These results suggest that, in order to prevent diabetes in middle-aged Japanese men, health guidance for normal weight maintenance should be provided not only for middle-aged men, but also for men under age 40.

Two-directional arthrographic findings made during conservative treatment of developmental dislocation of the hip were compared with the femoral-head configurations and radiological results obtained from long-term follow-up examinations in this retrospective study. Sixty hips were followed until at least age 14. Arthrography was carried out according to Terazawa's method. The shape of the superior, anterior, and posterior limbus was evaluated based on a modified Fujii's classification. The femoral-head configuration was classified into 4 groups, and the radiological results were evaluated using Severin's classification at the final observation. There was a statistically significant relationship between the shape of the anterior limbus, the number of portions of deformed limbus (superior, anterior, posterior), and the femoral-head configuration. Also, a statistically significant relationship between the shape of the limbus and Severin's classification was observed. These results suggest that the deformed limbus seems to play an important role in triggering femoral-head deformities, possibly via mechanical compression, and negatively affects development of the hip joint.

Pathologic features of Mycoplasma pneumoniae infection (M. pneumonia) are generally non-specific, and the literature regarding the pathologic features of M. pneumonia with intraalveolar exudates is limited. Clinical and histopathological studies were performed in 3 patients with M. pneumonia which did not respond to erythromycin and minocycline, but all rapidly recovered after corticosteroid therapy. In pathologic findings, we observed intraalveolar exudates and focal organization in M. pneumonia, and its intraalveolar lesions were compared between M. pneumonia and bronchiolitis obliterans organizing pneumonia containing fibrin (BOOP). Immunohistochemical studies were performed using the streptavidin biotin peroxidase complex method with anti-alpha-smooth muscle actin antibody and anti-pancytokeratin AE1/AE3 antibody. In pathologic findings, more fibrin deposits in intaalveolar lesions were observed in M. pneumonia than in BOOP. In intaalveolar lesions of M. pneumonia, a larger amount of nuclear debris, more neutrophils, and more erythrocytes were noted. Myofibroblasts were observed in the organization of BOOP, while in the intaalveolar lesions of M. pneumonia, myofibroblasts were not observed. These results suggest that M. pneumonia with intraalveolar exudates responds well to corticosteroid and its intraalveolar lesions apparently differed from those in BOOP.

Genetic and molecular biological methodologies are being applied to the study of patients with epilepsy at an ever-increasing pace. Accurate classification of epilepsy within large families has allowed identification of genes through linkage analysis and then isolation of gene products. Mutations causing ion channel abnormalities coupled with clinical patterns of focal epilepsy syndromes are beginning to change our thinking about the etiology of recurrent seizures in all patients. Molecular methodology is beginning to have impact on understanding of the mechanisms of actions of drugs used to treat epilepsy and will have an impact on how future treatments are designed.

Leu-7 positive lymphocytes, including natural killer cells, play an important role in the immune system's surveillance function to prevent the development of cancer. The incidence of lung cancer is significantly high in patients with end-stage pulmonary fibrosis. We hypothesized that the number of Leu-7 positive cells may be decreased in areas of severe pulmonary fibrosis. To demonstrate this, Leu-7 positive cells were immunohistochemically stained in 41 lung specimens obtained from patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with collagen vascular disorders. The number of Leu-7 positive cells was evaluated according to the pathological findings. In pathologically normal lung, Leu-7 positive cells were mostly found within the capillaries of the septa and rarely in the alveolar space or the stroma. The number of Leu-7 positive cells was 0.69 +/- 0.15 in areas of advanced fibrosis (n = 41), 2.39 +/- 0.60 in areas that had newly developeing fibrosis (n = 41), 1.14 +/- 0.57 in bronchiolitis obliterans organizing pneumonia (n = 9), and 1.35 +/- 0.87 in diffuse alveolar damage (DAD) (n = 11). The number of Leu-7 positive cells in areas of newly developing fibrosis (2.39 +/- 0.60) was significantly higher than that in areas of established fibrosis (0.69 +/- 0.15, P < 0.05). Our present study demonstrates a significant decrease in the number of Leu-7 positive cells in areas of advanced fibrosis. This evidence may partly explain the high incidence of lung cancer associated with pulmonary fibrosis.

We studied the pressure exerted by hands during push-ups in 21 paraplegic and 2 tetraplegic patients employing 4 different hand positions. In the fingers-spread position, the initial force exerted was a vertical force (Fz), followed by a medio-lateral force (Fy) and then an antero-posterior force (Fx). In the other 3 positions, the order of force type exertion was Fz, Fx, and then Fy. All subjects with neurological injury levels above T4 and subjects between T5 and T10 without spinal instrumentation could not push themselves up in the fingers-spread position. The fact that Fy is initiated before Fx in the fingers-spread position indicates that lateral balancing of the trunk is critical in this position, thus explaining why subjects without spinal instrumentation with neurological injury at a level higher than T10 could not control their spinal columns while performing push-ups. In contrast, antero-posterior balancing takes priority in the other hand positions. We believe that spinal instrumentation helps balance the trunk in the lateral direction, converting the thoracic spine into a rigid body in subjects with neurological injury at levels above T10.