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When recording with a palm electrode, a premotor potential (PMP) precedes the compound muscle action potential that is evoked from the second lumbrical muscle following median nerve stimulation. The origin of this PMP has been uncertain. We demonstrate that median sensory nerve action potentials (SNAPs) can be recorded orthodromically with the palm electrode and conclude that the origin of the PMP is a median SNAP arising from antidromically activated digital sensory branches.

Rationale, Aims and Objectives: To develop clinical prediction rules for true bacteremia, blood culture positive for gram-negative rods, and in-hospital death using the data at the time of blood withdrawal for culture., Methods: Data on all hospitalized adults who underwent blood cultures at a tertiary care hospital in Japan were collected from an integrated medical computing system. Logistic regression was used for developing prediction rules followed by the jackknife cross validation., Results: Among 739 patients, 144 (19.5%) developed true bacteremia, 66 (8.9) were positive for gram-negative rods, and 203 (27.5%) died during hospitalization. Prediction rule based on the data at the time of blood withdrawal for culture stratified them into five groups with probabilities of true bacteremia 6.5, 9.6, 21.9, 30.1, and 59.6%. For blood culture positive for gram-negative rods, the probabilities were 0.6, 4.7, 8.6, and 31.7%, and for in-hospital death, those were 6.7, 15.5, 26.0, 35.5, and 56.1%. The area of receiver operating characteristic for true bacteremia, blood culture positive for gram-negative rods, and in-hospital death were 0.73, 0.64, and 0.64, respectively, in original cohort and 0.72, 0.64, and 0.64 in validation respectively., Conclusions: The clinical prediction rules are helpful for improved clinical decision making for bacteremia patients.

Adenofibroma is a rare benign biphasic neoplasm that is classified into the mixed epithelial and mesenchymal tumor group. We report the case of a 42-year-old woman with adenofibroma of the endometrium protruding into the vagina. Transvaginal ultrasonography revealed the tumor as an intravaginal mass containing multiple cystic components. Magnetic resonance imaging (MRI) showed a heterogeneous high-intensity mass filling the vaginal cavity on T2-weighted imaging, with a low-contrast enhanced septum identified within the mass on gadolinium-enhanced, T1-weighted imaging. Contrast-enhanced computed tomography (CT) showed a heterogeneous low-attenuating multicystic mass filling the vaginal cavity. Although preoperative diagnosis of this rare tumor is very difficult, the combination of MRI, CT, and ultrasonography offers a useful diagnostic tool.

Inner-shell excitation spectra and fragmentation of small clusters of formic acid have been studied in the oxygen K-edge region by time-of-flight fragment mass spectroscopy. In addition to several fragment cations smaller than the parent molecule, we have identified the production of HCOOH.H+ and H3O+ cations characteristic of proton transfer reactions within the clusters. Cluster-specific excitation spectra have been generated by monitoring the partial ion yields of the product cations. Resonance transitions of O1s(C[double bond]O/OH) electrons into pi(CO)* orbital in the preedge region were found to shift in energy upon clusterization. A blueshift of the O1s(C[double bond]O)-->pi(CO)* transition by approximately 0.2 eV and a redshift of the O1s(OH)-->pi(CO)* by approximately 0.6 eV were observed, indicative of strong hydrogen-bond formation within the clusters. The results have been compared with a recent theoretical calculation, which supports the conclusion that the formic-acid clusters consist of the most stable cyclic dimer andor trimer units. Specifically labeled formic acid-d, HCOOD, was also used to examine the core-excited fragmentation mechanisms. These deuterium-labeled experiments showed that HDO+ was formed via site-specific migration of a formyl hydrogen within an individual molecule, and that HD2O+ was produced via the subsequent transfer of a deuterium atom from the hydroxyl group of a nearest-neighbor molecule within a cationic cluster. Deuteron (proton) transfer from the hydroxyl site of a hydrogen-bond partner was also found to take place, producing deuteronated HCOOD.D+ (protonated HCOOH.H+) cations within the clusters.

Background: Risk stratification for mortality in intracerebral haemorrhage (ICH) helps guide care, but existing clinical prediction rules are too cumbersome for clinical practice because of their complexity., Aim: To develop a simple decision tree model of in-hospital mortality risk stratification for ICH patients., Methods: We collected information on spontaneous ICH patients hospitalized in a teaching hospital in Japan from August, 1998 to December, 2001 (n = 374). All variables were abstracted from data available at the time of initial evaluation. A prediction rule for in-hospital mortality was developed by the Classification and Regression Tree (CART) methodology. The accuracy of the model was evaluated using the area under receiver-operator characteristic curve., Results: Overall in-hospital mortality rate was 20.2%. The CART methodology identified four groups for mortality risk, varying from low (2.1%) to high (58.9%). Level of consciousness (coma) was the best single predictor for mortality, followed by high ICH volume (cut-off 10.4 ml), and then age (cut-off 75 years). The accuracy of our CART model (0.86) exceeded that of a multivariate logistic regression model (0.81)., Discussion: ICH patients can easily be stratified for mortality risk, based on three predictors available on admission. This simple decision tree model provides clinicians with a reliable and practical tool.

Background: Patients with endometrial cancer can present with various complicating illnesses, including obesity, diabetes mellitus, hypertension and advanced aging. These patients are at high risk of severe post-operative complications. Thus, the question of whether or not to perform systemic pelvic and para-aortic lymphadenectomy remains controversial for all patients. It is reported that external iliac lymph nodes are the most commonly involved lymph nodes in endometrial cancer, and para-aortic lymph node (PAN) metastases spread via a route shared by the common iliac lymph nodes. The aim of this study was to evaluate the potential efficacy of omitting PAN dissection when metastasis of the common iliac and external iliac lymph nodes is negative., Methods: Between January 1994 and June 2004, a total of 101 patients at Akita University Hospital who had undergone total hysterectomy and bilateral salpingo-oophorectomy, total pelvic lymphadenectomy and para-aortic lymphadenectomy to the level of the renal vein for endometrial cancer were enrolled in this study., Results: Eleven patients in all were found to have metastasis for PANs. Among 13 patients with common and/or external iliac positive lymph nodes, 10 showed PAN metastasis. Of the 88 patients with negative lymph nodes, 87 showed no PAN metastasis. Based on these data, common and/or external iliac lymph nodes had 90.9% sensitivity (10/11) and 96.7% specificity (87/90) for detecting PAN metastasis., Conclusion: Para-aortic lymphadenectomy might be avoided by the negativity of such lymph nodes, thereby minimizing post-operative complications.

The Raman spectra of alpha form 5-nitro-2,4-dihydro-1,2,4-triazole-3-one (alpha-NTO, space group P) were measured in a high-pressure vessel diamond anvil cell (DAC). The pressure was increased to 27.6 GPa. In general, Raman bands show a blue shift because of the nature of the molecule packing as a high-pressure effect, but some particular bands exhibited a red shift, disappearance, split, or slight shifting in our experiments. Those red-shifting bands concerning hydrogen bonds, i.e., carbonyl and amino groups, are likely to work as a stabilizer against stimuli to the molecule or crystal. This stabilizing nature might characterize the insensitivity of NTO. Molecular dynamic (MD) calculations were performed to reveal the high-pressure effect of the alpha-NTO crystal. The coordinates of individual atoms in the crystal structure were obtained using X-ray diffraction analysis. The pressure dependence of the power spectra of the correlation functions of the C=O bond length in NTO was calculated. A unique high-pressure effect of the alpha-NTO crystal was found on the power spectra. The peak frequency in the power spectrum of the C=O stretching vibration exhibited a red shift with an increase in pressure to 10.0 GPa, while the peak intensity considerably decreased under the same pressure process, because this bond length increased with an increase in pressure to 10.0 GPa. At a pressure of >20.0 GPa, a blue shift appeared. These results of the MD calculations are in good agreement with our experimental data.

Background: The government-led "evidence-based guidelines for cataract treatment" labelled pirenoxine and glutathione eye drops, which have been regarded as the standard care for cataracts in Japan, as lacking evidence of effectiveness, causing great upset among ophthalmologists and professional ophthalmology societies. This study investigated the reasons why such "scientific evidence of treatment effectiveness" is not easily accepted by physicians, and thus, why they do not change their clinical practices to reflect such evidence., Methods: We conducted a qualitative study based on grounded theory to explore physicians' awareness of "scientific evidence" and evidence-supported treatment in relation to pirenoxine and glutathione eye drops, and to identify current barriers to the implementation of evidence-based policies in clinical practice. Interviews were conducted with 35 ophthalmologists and 3 general practitioners on their prescribing behaviours, perceptions of eye drop effectiveness, attitudes toward the eye drop guideline recommendations, and their perceptions of "scientific evidence.", Results: Although few physicians believed that eye drops are remarkably effective, the majority of participants reported that they prescribed eye drops to patients who asked for them, and that such patients accounted for a considerable proportion of those with cataracts. Physicians seldom attempted to explain to patients the limitations of effectiveness or to encourage them to stop taking the eye drops. Physicians also acknowledged the benefits of prescribing such drugs, which ultimately outweighed any uncertainty of their effectiveness. These benefits included economic incentives and a desire to be appreciated by patients. Changes in clinical practice were considered to bring little benefit to physicians or patients. Government approval, rarity of side effects, and low cost of the drops also encouraged prescription., Conclusion: Physicians occasionally provide treatment without expecting remarkable therapeutic effectiveness, as exemplified by the use of eye drops. This finding highlights that scientific evidence alone cannot easily change physicians' clinical practices, unless evidence-based practices are accepted by the general public and supported by health policy.

We hypothesized that the disordered tissue architecture in cancer results from the cells executing the program designed during ontogeny in a spatio-temporally inappropriate manner. HOX genes are known as master regulators of embryonic morphogenesis, and encode transcription factors which regulate the transcription of the downstream genes to realize the program of body plan. In this study, we quantified the expression levels of 39 HOX genes in 41 human non-small cell lung cancer (non-SCLC) and non-cancerous lung tissues by a comprehensive analysis system based on the real-time RT-PCR method. We found that the expression levels of HOXA1, A5, A10 and C6 in squamous cell carcinoma tissues (and HOXA5 and A10 in adenocarcinoma tissues) were significantly higher than those in the non-cancerous tissues. Comparison of HOX gene expressions between adenocarcinoma and squamous cell carcinoma tissues showed higher expressions of HOXA1, D9, D10 and D11 in squamous cell carcinoma tissues than in adenocarcinoma tissues. Immunohistochemical analysis revealed that HOXA5 and A10 proteins were localized in the cytoplasm of tumor cells in both adenocarcinoma and squamous cell carcinoma tissues. These results suggest that the disordered patterns of HOX gene expressions were involved not only in the development of non-SCLC but also in the histologically aberrant diversity such as adenocarcinoma and squamous cell carcinoma.

Male mice and rats were fed a diet containing four bisphenol antioxidants, 2,2'-methylenebis(4-ethyl-6-tert-butylphenol) (ME), 2,2'-methylenebis(4-methyl -6-tert-butylphenol) (MM), 4,4'-butylidenebis(3-methyl-6-tert-butylphenol) (BM), or 4,4'-thiobis(3-methyl-6-tert-butylphenol) (TM) at levels of 0.06-0.25% for 2 months. BM and TM decreased epididymal, seminal vesicular, prostate and preputial weights, and injured seminiferous tubules in mice in a dose-dependent fashion. BM and TM also reduced sex accessory organ weights and sperm production capacity in rats, but MM and ME were more toxic to rats than BM and TM. ME and MM did not bind ERalpha up to 10(-3) M, while BM and TM competitively bound ERalpha against beta-estradiol (E2). Fifty percent inhibitory concentrations (IC50 s) of BM, TM, and bisphenol A (positive control) against E2-binding were 7.3 x 10(-6) M, 1.8 x 10(-5) M, and 1.4 x 10(-5) M, respectively. When ovariectomized (OVX) mice were sc administered TM at doses of 60 and 300 mg/kg/day for 4 days, or when OVX mice were fed BM in the diet at a level of 0.25% for 2 months, uterine weight was significantly increased. These results suggest that BM and TM are weakly toxic, possibly through an estrogenic mechanism to male reproductive organs in mice as well as rats, while MM and ME may be the direct testicular toxins in rats but not mice.

Site-specific chemical reactions following core excitation of poly-(methyl methacrylate) (PMMA) and poly-(isopropenyl acetate) (PiPAc) thin films were investigated. New x-ray absorption spectra of PMMA and PiPAc at the C and O K edges and theoretical spectra within the framework of density functional theory using model molecules were reported, and some new peak assignments were proposed for these spectra. Core-hole excited state molecular dynamics simulations were performed to discuss dissociation dynamics for the target systems, and some specific reaction mechanisms were discussed and explained theoretically; for example, the amount of CH3 ion fragments for PMMA was enhanced at the C and O K edges through the existence of the repulsive sigma*(O-CH3) excited state.

We report a new theoretical procedure for calculating Auger decay transition rates including effects of core-hole excited-state dynamics. Our procedure was applied to the normal and first resonant Auger processes of gas-phase water and compared to high-resolution experiments. In the normal Auger decay, calculated Auger spectra were found to be insensitive to the dynamics, while the repulsive character of the first resonant core-excited state makes the first resonantly excited Auger decay spectra depend strongly on the dynamics. The ultrafast dissociation of water upon O(1s)-->4a(1) excitation was analyzed and found to be very sensitive to initial vibrational distortions in the ground state which furthermore affect the excitation energy. Our calculated spectra reproduce the experimental Auger spectra except for the Franck-Condon vibrational structure which is not included in the procedure. We found that the Auger decay of OH and O fragments contributes to the total intensity, and that the contribution from these fragments increases with increasing excitation energy.

Chemical agents have been used previously in wartime on numerous occasions, from World War I to the Gulf War. In 1994 and 1995, sarin nerve gas was used first in peacetime as a weapon of terrorism in Japan. The Tokyo subway sarin attack was the first large-scale disaster caused by nerve gas. A religious cult released sarin gas into subway commuter trains during morning rush hour. Twelve passengers died and about 5500 people were harmed. Sarin is a highly toxic nerve agent that can be fatal within minutes to hours. It causes the clinical syndrome of cholinergic hyperstimulation by inhibition of the crucial enzyme acetylcholinesterase. Therapy of nerve agent toxicity is divided into three categories, decontamination, respiratory support, and antidotes. All of these therapies may be given simultaneously. This article reviews toxicology and management of this acute chemical emergency. To help minimize the possible catastrophic impact on the public, we make several recommendations based on analysis of the Tokyo subway sarin attack and systematically review the current scientific literature.

Objective: Some endometrial cancer patients without clinical evidence of extrauterine spread die as a result of recurrence even after curative operation. These recurrences may arise from occult tumor cells that are not detected by conventional methods. The goal of this study was to develop a quantitative method for the detection of disseminated tumor cells (DTCs) in the peripheral blood (PB) and lymph nodes (LNs) of patients with endometrial cancer., Methods: Ninety-eight PB samples from 30 patients and 218 LNs from 14 patients were studied. Real-time quantitative analysis was performed using a LightCycler instrument and a TaqMan probe for cytokeratin 19 (CK19) as a marker gene., Results: This method resulted in the reproducible quantitation of 10 to 10(6) MCF-7 cells (CK19-expressing breast cancer cell line) per 10(6) peripheral blood nucleated cells. CK19 mRNA expression was detected in 28 PB samples and in 62 LNs. Only three preoperative PB samples and one postoperative PB sample (from four patients) and 33 LNs (from six patients) were PCR-positive. The PCR-positive rate of LNs was higher in patients with pathologically metastatic (path-positive) LNs than in patients with path-negative but PCR-positive LNs. Furthermore, the CK19 mRNA background expression rate was higher in the LNs of path-negative but PCR-positive patients than in LNs of path-negative and PCR-negative patients., Conclusions: Real-time qRT-PCR with TaqMan probes is a sensitive, specific and rapid method for the detection of DTCs in PB and LNs. Additional studies with larger numbers of patients and adequate follow-up would be of benefit.

Background: The Ankle brachial index (ABI) has been shown to be useful in diagnosing peripheral arterial disease (PAD). Ankle systolic blood pressures are measured by a Doppler device; however, general physicians cannot always use it in daily practice. The ausculutatory method (AUS) is an alternative method and quite easy to perform, but has not yet been validated in diagnosing PAD., Objective: To validate AUS for diagnosing PAD based on ABI, compared with Doppler method as gold standard., Methods: Cross-sectional study. Study subjects were 119 patients aged 50 years and older, who were consecutively admitted to the division of general internal medicine in two community hospitals in Japan. We measured the systolic blood pressures of the brachial and the posterior tibial arteries by two methods. We calculated the ABI from the systolic blood pressure obtained by these two methods. PAD was considered to be present when ABI 0.9., Conclusions: While AUS is not efficient enough to confirm the presence of PAD based on ABI, it could be clinically useful in excluding PAD when ABI >0.90. When measuring ankle blood pressure by AUS in the daily practice, it is important to realise its strengths and weaknesses.

Objectives: To identify the relationship of risk factors for atherosclerosis with venous thromboembolism (VTE) and the utility of transthoracic echocardiography in acute pulmonary thromboembolism (APTE)., Methods: In 75 patients with VTE (VTE group), 101 patients with suspected VTE (N group), and 50 control subjects (control group), the frequency of atherosclerosis risk factors such as hyperlipidemia, obesity, hypertension, smoking, and diabetes mellitus and the number of risk factors were evaluated. Transthoracic echocardiographic findings such as tricuspid regurgitation, right ventricular dilation, pulmonary hypertension, and right ventricular dysfunction were evaluated in 15 patients with APTE (APTE group) and 38 patients in the N group (NC group)., Results: The incidence of hyperlipidemia in the VTE group was statistically higher than that in the control group (odds ratio 2.16, 95% confidence interval 1.43-3.08). Additionally, the incidence of obesity was higher in the VTE and N groups than in the control group (odds ratio was 2.76, 95% confidence interval 1.67-4.37). Risk factors other than obesity and hyperlipidemia and the number of risk factors were not significant. The incidence of tricuspid regurgitation, right ventricular dilation, and pulmonary hypertension in APTE was statistically greater than that in NC group. Right ventricular dilation and right ventricular dilation + tricuspid regurgitation are reliable findings in echocardiography. However, even combining with tricuspid regurgitation, right ventricular dilation is insufficient to identify or screen patients with APTE., Conclusions: Hyperlipidemia and obesity may be risk factors for VTE. However, obese patients can manifest similar findings to VTE. Although transthoracic echocardiograpghy is not recommended as a diagnostic or screening test in APTE, it should be used as an ancillary test.

Objective: The ankle-brachial index, which is calculated by dividing ankle systolic blood pressure by brachial systolic blood pressure, is useful in diagnosing peripheral arterial disease. Consensus has not been reached, however, on a standard method for measuring ankle systolic blood pressure. This study evaluated two cuff-wrapping methods for measuring ankle systolic blood pressure, compared with intra-arterial pressure as a gold standard., Methods: Study participants were 24 consecutive adult patients who underwent surgery under general anesthesia at Kyoto Prefectural University Hospital in Japan between January and March 2002. Indirect ankle systolic blood pressure was measured in the posterior tibial artery using a Doppler device and two cuff-wrapping methods: spiral, and straight. Direct ankle systolic blood pressure was measured in the dorsalis pedis artery., Results: Mean difference in ankle systolic blood pressure between indirect and direct measurements (indirect minus direct) was 1.4 mmHg [standard deviation of the difference (SDd), 17.6 mmHg] with the straight method and -1.4 mmHg (SDd, 22.2 mmHg) with the spiral method. The limit of agreements (mean difference +/-2 SDd) and intraclass correlation coefficient between two observers were -17.6 to 20.1 mmHg and 0.94, respectively, for the straight method and -39.4 to 40.0 mmHg and 0.78, respectively, for the spiral method., Conclusions: The straight method, the same cuff-wrapping method used for measuring brachial blood pressure, appears to represent a more suitable wrapping method because of better interobserver reproducibility. Accuracy and reproducibility of indirect ankle systolic blood pressure measurement, however, were not adequately improved by either of the wrapping methods.

Aim: To evaluate surgical indications for combined partial rectosigmoidectomy in ovarian cancer with direct invasion of the rectum and sigmoid colon or dissemination into the pouch of Douglas., Methods: Subjects comprised 25 patients with ovarian cancer who underwent primary surgery and rectosigmoidectomy between 1990 and 2002 at our hospital. Federation of Obstetrics and Gynecology staging of tumors was II (n = 6), III (n = 17) or IV (n = 2). The histologic type was serous adenocarcinoma (n = 18), clear cell adenocarcinoma (n = 4), and others (n = 3). Bowel resection was performed during primary surgery in 18 patients, and after neoadjuvant chemotherapy (NAC) in seven patients. Cumulative survival rate was compared between NAC and non-NAC groups. Patients were divided into three groups based on extent of surgical resection to compare survival rates: no residual tumor (n = 19); maximum residual tumor diameter <1 cm (n = 5); and maximum residual tumor diameter > or =1 cm (n = 1)., Results: Cumulative 5-year survival was 41.3% for all patients. Cumulative 5-year survival in the 18 patients who underwent bowel resection during primary surgery was 62.2%, compared to 13.9% in the seven patients who underwent bowel resection after NAC. Cumulative 5-year survival based on extent of surgical resection was: no residual tumor, 60.8%; residual <1 cm, 0%; and residual > or =1 cm, 0%. Cumulative 5-year survival for patients with complete tumor resection (no residual tumor), excluding clear cell adenocarcinoma, was 79.5%., Conclusion: In ovarian cancer with direct invasion of the rectum or sigmoid colon or dissemination into the pouch of Douglas, complete tumor resection with rectosigmoidectomy during primary surgery is associated with good clinical outcomes.

Thorough mastication has the potential to affect postprandial plasma glucose concentrations by improving digestibility and absorption of nutrients. To evaluate the effects of mastication on postprandial plasma glucose concentration, we compared usual and thorough mastication in subjects with normal glucose tolerance (NGT group, n = 16) and subjects predisposed to type 2 diabetes (first-degree relatives of type 2 diabetic patients, subjects with impaired glucose tolerance, and type 2 diabetic patients) (predisposed group, n = 10) in a crossover trial of 52 test meals. Plasma glucose and serum insulin concentrations were measured for 3 hours postprandially, and the insulinogenic index (the ratio of incremental serum insulin to plasma glucose concentration during the first 30 minutes after meal) was calculated. In the NGT group, thorough mastication reduced the postprandial plasma glucose concentration at 90 minutes (5.8 +/- 0.3 vs 6.5 +/- 0.4 mmol/L, P < .05) and 120 minutes (5.4 +/- 0.2 vs 6.3 +/- 0.4 mmol/L, P < .05) and the area under the curve (AUC) from -15 to 180 minutes (19.1 +/- 0.6 vs 20.6 +/- 0.8 [mmol . L]/h, P < .05) without an increase in the AUC for insulin. In the predisposed group, thorough mastication significantly augmented plasma glucose and serum insulin concentrations and the AUCs compared with usual mastication. Thorough mastication elicited a significantly higher insulinogenic index than usual mastication in the NGT group (205.0 +/- 27.6 vs 145.6 +/- 17.7 pmol/mmol, P < .05), whereas the predisposed group showed significantly less early-phase insulin secretion than the NGT group. In the NGT group the postprandial plasma glucose concentration upon thorough mastication of meal was significantly lower, most probably because of the potentiation of early-phase insulin secretion. In the subjects predisposed to type 2 diabetes, thorough mastication did not potentiate early-phase insulin secretion and elicited a higher postprandial plasma glucose concentration.

To clarify the functional role of the dorsal column nucleus (DCN) in nociception in rats with advancing age, single neuronal activity and substance P-like immunoreactivity (SP-LI) of the gracile nucleus (GN) were studied in aged rats (29 to 34 mo old) and adult rats (9 to 12 mo old). A total of 122 neurons [aged: 34 wide-dynamic-range (WDR), two nociceptive-specific (NS), and 32 low-threshold mechanical (LTM) neurons; adult: 22 WDR and 32 LTM neurons] were recorded from GN. For WDR neurons, the latency to antidromic activation of the ventral posterior lateral nucleus of the thalamus showed no difference between the aged and adult rats. Sciatic nerve stimulation with C-fiber intensity induced responses of GN with significantly longer latency in aged rats than in adults, whereas there was no difference in the response latency to A-fiber intensity stimulation. Background activity and afterdischarges were significantly higher in the aged rats than those in the adult rats. Responses to noxious mechanical and thermal stimuli were significantly greater in the aged rats during application of graded stimuli. There were no significant differences in responses to nonnoxious mechanical stimulus, mechanical response threshold, and the size of the receptive fields between neurons in the aged and adult rats. The area occupied by SP-LI fibers in the GN and the size of SP-LI dorsal root ganglia neurons were significantly larger in aged rats than in adults. The present findings suggest that the hyperexcitability of GN neurons could be involved in abnormal noxious pain sensations with advancing age.

The thermal decomposition of formic acid was reinvestigated in the gas phase using two types of shock tubes. It was confirmed that the unimolecular decomposition proceeds through a main channel of dehydration (k1) and a minor decarboxylation channel (k2). This result is in good agreement with our previous study (J. Chem. Phys. 1984, 80, 4989). Furthermore, it was confirmed that the dehydration process is in the second-order region and that the decarboxylation is in the falloff region, in the temperature range of 1300-2000 K and over the total density of (0.5-2.5) x 10(-5) mol cm(-3). The experimental ratios between the two channels, k2/k1, are compared with those of theoretical calculations by conventional transition state theory and the Rice-Ramsperger-Kassel-Marcus theory.

Purpose: We examined post-activation depression in 35 stroke patients and 10 healthy subjects, and investigated whether their clinical symptoms were correlated to post-activation depression., Methods: Post-activation depression of the soleus H-reflex evoked by electrical stimulation of the common peroneal nerve with supramaximal intensity of motor response on the tibialis anterior muscle., Results: Post-activation depression was decreased on the affected side of the stroke patients. There was a significant difference between the affected and unaffected sides of the patients with post-activation depression, but no difference between the unaffected sides of the patients and healthy subjects. The presence of ankle clonus and the decrease in post-activation depression were correlated., Conclusion: Decreased post-activation depression in stroke patients suggests that a mechanism other than postsynaptic inhibition, such as reciprocal Ia inhibition and Ib inhibition, and presynaptic inhibition, may contribute to the exaggerated stretch reflexes, in particular, the manifestation of clonus.

A 71-year-old man had been treated as an outpatient for pemphigus vulgaris. Endoscopic examination disclosed an ulcerated lesion in the middle of the esophagus. A biopsy specimen was diagnosed pathologically as squamous cell carcinoma. At surgery, the esophageal mucosa beyond the resection margin appeared edematous and blistered. We carried out anastomosis with sutures rather than staples at the site where the epithelium was least damaged, to minimize likelihood of anastomotic breakdown from poor blood flow. Histopathologic examination of the resected specimen additionally showed blisters and acantholytic cells throughout the esophageal mucosa, so esophageal pemphigus was diagnosed in addition to carcinoma. The patient's general condition deteriorated from worsening of pemphigus. We initiated steroid therapy, making adjustments according to changes in titers of anti-intercellular bridge antibody and antibodies to the cell adhesion molecules (desmoglein 1 and 3). Fever and extensive blistering subsided dramatically, and the patient was discharged in good condition on hospital day 103. When performing esophagectomy in the presence of esophageal pemphigus, the anastomosis must be fashioned cautiously because any mechanical stress can abrade the friable edematous esophageal mucosa. While steroid therapy is known to be effective for pemphigus vulgaris, our findings indicate that in patients with postoperative deterioration of their general condition, marked improvement can be obtained by using antibody titers to guide timing and dose in steroid administration.

We examine in depth the functional dependence of computed core-electron binding and excitation energies based on a total-energy difference approach within Kohn-Sham density functional theory. Twenty-seven functional combinations were studied using a database of reliable experimental data on 18 molecules. The computed core-electron binding energies are largely dependent on the choice of exchange functional. The term value of the first resonant excited state and energy differences between the lowest core-excited states are, however, quite insensitive to the choice of functionals since the errors due to the core-region cancel out. Using these results we define a different exchange functional, which mixes two functionals designed by Perdew and Wang (PD86 and PD91), with the best results for both excitation and binding energies obtained for a mixing ratio 60:40 between these. We also reexamine the relativistic corrections for inner-shell excitations., ((c) 2004 American Institute of Physics.)

Dental crowding is defined as a discrepancy between tooth size and jaw size that results in a misalignment of the tooth row. Proposed reasons for crowding include excessively large teeth, small jaws, and a combination of both. Nevertheless, the parameters that would allow the prediction of crowding have not been identified. This study compared the shape of crowded and uncrowded dental arches, matched for size and sex. The application of elliptical Fourier functions (EFFs) provided an accurate numeric description of the dental arch form. Dental casts from the Nihon University School of Dentistry at Matsudo, Chiba, Japan, were studied. Group I, the control group, consisted of 118 dental cast pairs (49 female, 69 male, aged 20.40 +/- 1.68 years [mean +/- SD]) with little or no crowding. Group II, which exhibited crowding, consisted of 78 dental cast pairs (64 female, 14 male, aged 19.67 +/- 4.95 years). From photographs, a set of 24 homologous points describing the tooth row was identified. These points were then fitted with EFFs. Each maxillary and mandibular outline was subsequently standardized for size by scaling the bounded area to a constant 10,000 mm(2). These "shape only" data were used to assess differences between arches in the 2 groups. By multivariate analysis of variance, statistically significant shape differences between groups I and II were obtained for both arches. Patients with crowding exhibited more variability than did the controls. This variability was illustrated with canonical axes derived from discriminant function analysis.

Background: The aim of this prospective study was to estimate whether adding human papillomavirus 16 (HPV16) testing to abnormal cervical smears is useful in the prediction of cervical intraepithelial neoplasia 3 (CIN3)., Methods: Between October 1994 and May 1996, a total of 207 patients at the Akita University Hospital had abnormal smears. Of these patients, 153 patients with CIN1,2 or atypical squamous cells of undetermined significance (ASCUS) were enrolled in this study and followed until June 2001. At the initial visit, a cervical swab was collected for cytology and for HPV16 testing using nested polymerase chain reaction (PCR). When the HPV16 test was positive, HPV16 testing was performed every 3 to 6 months. We compared the prevalence of progression to CIN3 between the HPV16-positive group (n = 16) and the HPV16-negative group (n = 137). We also investigated the risk of progression to CIN3 associated with persistent HPV16 infection., Results: At the end of the study period, four patients (25%) in the HPV16-positive group developed CIN3, and all of these patients were found to have persistent HPV16 infection during this period. Only three patients (2.2%) in the HPV16-negative group developed CIN3., Conclusions: The prevalence of progression to CIN3 in the HPV16-positive group was significantly higher than that in the negative group (p = 0.0023). The odds ratio of progression to CIN3 was 14.9 [95% confidence interval (CI) 2.98-74.4]. In particular, the risk of progression to CIN3 increased with persistent HPV16 infection. Adding HPV16 testing when abnormal cervical smears are detected promises to be useful for predicting CIN3.

The population size of the sika deer Cervus nippon on Hokkaido Island of Japan had been remarkably reduced because of heavy hunting pressure since the beginning of Meiji Period and effects of heavy snow in 1879 and 1881. After that, the number of sika deer in Hokkaido has increased gradually due to the protection by the Hokkaido government. In the present study, in order to investigate the bottleneck effects, we analyzed ancient mitochondrial DNA (mtDNA) on sika deer bones excavated from archaeological sites just before Meiji Period. On 86 of 113 bones from 13 archaeological sites of Ainu Culture Period (17-19th centuries), 602 base-pair fragments of the mtDNA control region were successfully sequenced. Consequently, we found three new haplotypes (g-, h- and i-types) which had not been identified in modern sika deer. In addition, four haplotypes (a-, b-, c- and d-types) identified from modern sika deer were also found in the archaeological deer. The new haplotypes and previously reported hapoltypes from sika deer of Hokkaido were phylogenetically much closer to each other, compared with those of modern sika deer from Honshu, Kyushu and the Chinese continent. Geographical distribution patterns of haplotypes of the ancient population were different from those of the modern population in Hokkaido. Our findings indicated that their genetic diversity was reduced through the bottleneck and that population structures of sika deer were changed widely in Hokkaido due to genetic drift.

Ancient mitochondrial DNA (mtDNA) mainly from Jomon Period Sus scrofa bone specimens (6,100-1,700 years old) was examined to clarify the genetic relationships between prehistoric and contemporary S. scrofa on Hokkaido, Honshu, Sado, and Izu islands of the Japanese Archipelago. Phylogenetic analysis of the mtDNA control region (574 bp) and analysis of pairwise nucleotide differences between prehistoric and contemporary S. scrofa sequences showed the following relationships between these groups: (1) a group genetically similar to contemporary Japanese wild boars was found mainly on Honshu Island, Hokkaido Island, and the Izu Islands, and (2) a monophyletic group distinct from contemporary Japanese wild boars was found on Sado Island. These results suggest that prehistoric people introduced S. scrofa from Honshu Island to Hokkaido Island and the Izu Islands. The estimated divergence times between the prehistoric Sado group and the other prehistoric S. scrofa is approximately congruent with the geological isolation of Sado Island from Honshu Island. Our results suggest that this extinct S. scrofa population was present on Sado Island as recently as around 2,000 years ago.

The idea of a computer-controlled range-compensating system for heavy charged particle radiotherapy, the multibar compensator, is proposed. By stacking multiple energy-absorbing layers along the beam, each of which has structure and behaviour similar to those of a multileaf collimator, variable range compensation will be achieved. The analysis of the conventional range compensators actually used for treatment concluded that the proposed system would not seriously degrade the treatment quality for the most cases, except for tumours in the head and neck region where 1 mm precision may be required. The system will even be able to coexist with the conventional range compensators to provide either method depending on clinical situations.

Herein, we report a new method for obtaining sensory nerve conduction velocities (SCVs) in the distal segment of the superficial peroneal nerve (SPN). Twenty lower extremities from 10 normal subjects (mean age: 33.4 years) were evaluated. The recording electrodes were placed on the dorsal surfaces of the ankle and foot. We stimulated the SPNs on the anterior edge of subjects' fibulas, and evoked sensory nerve action potentials (SNAPs) antidromically. SCVs were calculated based upon the distances and the latencies. The mean SCV was 41.3 +/- 4.3 m/s in the distal segment, which was slower than in the proximal segment (51.7 +/- 3.9 m/s). We were able to stimulate only the SPN with certainty. In conclusion, the described technique should be of clinical value in diagnosing peripheral neuropathy.

Attention deficit-hyperactivity disorder (ADHD) has been noted for its high rate of comorbidity. The present study is the first report in Japan evaluating the proportion of comorbidity in ADHD cases presenting in the clinical setting, aiming at clarifying the picture of ADHD in Japan. The subjects consisted of 68 child and adolescent cases meeting criteria for ADHD (Diagnostic and Statistical Manual of Mental Disorders, 4th edn) under treatment at a child psychiatry clinic (IQ > 50, mental age >or= 4 years old). Disorders evaluated as comorbid disorders were mood disorders, anxiety disorders, elimination disorders, sleep disorders, tic disorders, oppositional defiant disorder (ODD), conduct disorder (CD), school refusal, and epilepsy. Comorbidity with mood disorders, anxiety disorders, ODD, and CD, were found to be lower than the high rates conventionally reported in North America. The lower age of the present subjects, primarily in infancy and elementary school age with few adolescent cases, and a bias towards milder cases from an outpatient clinic without inpatient facilities are believed to be factors accounting for this disparity. Furthermore, it was a notable fact that mentally delayed cases (IQ: 51-84) amounted to 34% of the cases, indicating the necessity to consider intelligence level when formulating a treatment strategy for ADHD.

Approximate theoretical normal and resonant Auger spectra for a series of methylcyano ketones were calculated. Compared with our previous procedure, a set of initial molecular orbitals (MOs) for Auger decay probability calculations of the normal Auger process was modified by changing from a set of ground state MOs to a set of core-holed MOs. For the resonant Auger process, a set of MOs was also modified in the same manner. Furthermore, the bond dissociation factor, which we introduced in the previous article, was also calculated to estimate the bond strength after Auger decay. The site-selectivity for a series of methylcyano ketones was qualitatively explained, but a significant state-specificity was not observed. Molecular size dependence after Auger decay was also discussed., (Copyright 2003 Wiley Periodicals, Inc.)

Male Crj:Wistar rats, HsdHot:Holtzman SD rats, Crj:CD-1(ICR) mice and C57BL/6CrSlc mice were administered bisphenol A (BPA) in the diet at a level of 0 (control) and 0.25% for 8 weeks. Daily BPA intake was about 200 and 400 mg/kg for rats and mice, respectively. No conspicuous signs of general or reproductive toxicity were observed after administration in any strain of these animals. Serum testosterone concentrations were not decreased in BPA-fed rats and mice. Successive subcutaneous administration of BPA at a dose of 200 mg/kg/day for 4 weeks significantly decreased the testis, epididymis, prostate and seminal vesicle weights, and the testicular daily sperm production in Jcl:Wistar rats. Successive intraperitoneal administration of BPA at a dose of 20 mg/kg/day for 4 weeks decreased the prostate and seminal vesicle weights but not the testis or epididymis weights. An intraperitoneal dose of 2 mg BPA/kg/day did not cause any toxicity. These results indicate that dietarily administered BPA is less toxic to most strains of rats and mice, and the maximum non-toxic dose and/or minimum toxic dose may be about 200 mg/kg/day. Subcutaneous or intraperitoneal BPA is much more toxic on male reproductive and sex accessory organs than dietary.

This paper summarizes Bacillus Calmette-Guerin (BCG) vaccination and revaccination policies in Japan, its cost-effectiveness, side effects, proposed selective vaccination strategy, and present tuberculosis situation in Japanese perspectives based on Medline database and other published reports. Universal BCG vaccination in infants and revaccination among children were not found economically justifiable. Overall tuberculosis incidence in Japan is higher than that of other developed countries. Trend of decline in tuberculosis incidence is similar to that of the countries where universal BCG vaccination has never been implemented. In the recent years, the number of tuberculosis group infection has been escalating. Since BCG revaccination program has already been discontinued, a consensus on universal BCG vaccination is also essential based on social, political, and economical factors. Side by side, more pragmatic strategies such as well-defined tuberculin test, selective vaccination policy based on tuberculosis incidence in each administrative zone, and early vaccination of high risk groups, should be formulated.

Background: Influenza is a major cause of morbidity and mortality in Japan and worldwide, especially for people of >65 years old and those with high-risk medical conditions. Although the influenza vaccine is effective in reducing the morbidity and mortality, the vaccine coverage rate has not increased adequately in Japan, compared with western countries., Objective: Our aim was to assess whether medical and personal characteristics are associated with receiving influenza vaccination in Japanese patients., Methods: Out-patients of a city hospital were recruited for a case-control study between November 1998 and February 1999. Cases were 98 out-patients aged 18 years or older who received influenza vaccination. Controls were 112 non-vaccinated out-patients matched with cases for primary physician and date of clinic visit. The candidates were interviewed by telephone and asked to respond to a 26-item questionnaire. The data were analysed using multiple logistic regression models., Results: The factors associated with the acceptance of influenza vaccination were: (i) recommendation by a family member and/or a close friend [odds ratio (OR) 17.74; 95% confidence interval (CI) 1.95-161.77]; (ii) belief in influenza vaccine efficacy (OR 10.55; 95% CI 3.42-32.49); (iii) having a family member and/or friends who had been vaccinated before (OR 6.44; 95% CI 2.37-17.50); (iv) physician's recommendation (OR 4.03; 95% CI 1.42-11.37); and (v) knowledge about the influenza vaccine (OR 3.06; 95% CI 1.02-9.20). Fear of adverse reactions (OR 0.21; 95% CI 0.07-0.66) was the sole factor associated with non-acceptance of influenza vaccine., Conclusion: Patients in Japan are likely to be greatly influenced by their family members or close friends in their decision of whether to accept influenza vaccination, unlike US patients who make health care decisions on their own. When implementing an influenza vaccination programme, this effect of cultural background observed in Japan should be taken into account in other countries.

Objective: To estimate the cost of treating a tuberculosis (TB) case and to analyse TB-related medical service utilisation, a cost-of-illness study was conducted for all patients with a primary diagnosis of TB admitted to a public hospital in Japan., Methods: Retrospective analysis by abstracting in- and out-patient medical records of 57 paediatric patients diagnosed with TB during 1993-1998 at a public hospital in Osaka prefecture. Costs were estimated based on third party's payer perspectives according to the service utilisation pattern. In addition to cost data, sociodemographic information and service utilisation pattern were also extracted from the medical records. Cost of preventing a case of TB was abstracted from the published literature., Results: The average cost of treatment was 8384 US dollars (95%CI 5667-11,099), while the average length of hospitalisation was 63 days (95%CI 43-84). Based on 20-80% vaccine efficacy, the cost of preventing a case of TB was 35,950-175,862 US dollars. In univariate analysis, site of TB (P = 0.04) was significantly associated with TB treatment cost, while case-finding method (contact tracing, symptoms, etc.) was associated with length of hospitalisation (P = 0.03). Multivariate regression analysis, however, showed none of the factors to be significant predictors of TB treatment cost and length of hospital stay., Conclusion: The cost of treating a case of paediatric TB is much lower than that of preventing one. Japan's universal BCG vaccination policy should be re-examined in the light of economic, social and political issues.

Ab initio MO calculations were carried out to examine the conformational energies of various benzylic compounds C(6)H(5)CH(2)XR (X=O, CH(2), CO, S, SO, SO(2); R=CH(3), C(2)H(5), iC(3)H(7), tC(4)H(9)) at the MP2/6-311G(d,p)//MP2/6-31G(d) level. Rotamers with R/Ph in gauche relationship are generally more stable than the R/Ph anti rotamers. In these stable geometries, the interatomic distance in the interaction of alpha- or beta-CH in the alkyl group and the ipso-carbon atom of the phenyl ring is short. The computational results are consistent with experimental data from supersonic molecular jet spectroscopy on 3-n-propyltoluene and NMR and crystallographic data on structurally related ketones, sulfoxides, and sulfones. In view of this, the alkyl/phenyl-congested conformation of these compounds has been suggested to be a general phenomenon, rather than an exception. The attractive CH/pi interaction has been suggested to be a dominant factor in determining the conformation of simple aralkyl compounds.

CX-659S (1) [(S)-6-amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4-(1H,3H)-pyrimidinedione], has been developed as a new type anti-inflammatory agent for the treatment of dermatitis. The structure of a major metabolite of CX-659S was determined as (S)-6-amino-5-[2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxo-1,4-cyclohexadienyl)butanamide]-3-methyl-1-phenyl-2,4-(1H,3H)-pyrimidinedione (2) by direct comparison with the synthesized authentic compound. The anti-inflammatory activity of 2 was equipotent with that of 1 on the contact hypersensitivity reaction (CHR) induced by picryl chloride (PC) in mice, suggesting that compound 2 contributes, at least in part, to the anti-inflammatory activity of CX-659S.

c-Fos protein is a nuclear protein coded by c-fos proto-oncogene subsequent to synaptic activation of the neurons. We used immunohistochemical methods to visualize the expression of c-Fos protein in myenteric neurons of the guinea pig distal colon and examined the effects of the extrinsic autonomic inputs on the enteric circuits. No c-Fos immunoreactivity was observed in the colonic segments fixed immediately after removal from the animal body. A number of c-Fos-immunoreactive nuclei of myenteric neurons, however, appeared in all preparations that were incubated in Krebs solution in vitro (n=10). Application of tetrodotoxin (0.2 microM) abolished the expression of c-Fos-immunoreactivity (n=6), but hexamethonium (100 microM) failed to decrease the number of c-Fos-positive neurons despite a complete suppression of spontaneous peristaltic movements (n=5). Neither the electrical stimulation (n=8) nor the severing of the pelvic nerves (n=5) changed the number of c-Fos-positive neurons. Application of clonidine, an alpha(2)-agonist, (0.1 microM) abolished the expression of c-Fos protein in all preparations (n=5), while denervation of the sympathetic fibers in the lumbar colonic and hypogastric nerves in vivo increased the number of c-Fos-positive neurons (n=5). The results indicate that the enteric circuit in the distal part of the gastrointestinal tract is under tonic inhibition by the sympathetic nervous system from the lumbar spinal cord. c-Fos immunoreactivity expressed in the colonic preparations in vivo might be the results of enhanced activation of non-nicotinic receptors after removal of the sympathetic inhibition., (Copyright 2002 Elsevier Science B.V.)

We explored the degree of Japan's contribution to research in the field of infectious disease in the last decade. Articles published from 1991-2000 in highly reputed journals on infectious disease were accessed through the MEDLINE database. The number of articles having an affiliation with a Japanese institution was counted in total and for the respective journals. The proportions of randomized controlled trials (RCTs), case-control/cohort studies, and case reports among the articles affiliated with Japan were also calculated, and were compared with the overall proportions of these types of articles for all articles published in these journals. Japan's contribution to research on infectious disease was 3.4% of the total articles and ranked sixth among all countries. The recent trend in contribution was negative, although not statistically significant (P = 0.19). RCTs in total articles published in these journals were 3.9%, which proportion has been increasing significantly over time. On the other hand, only one RCT (0.2%) was reported from Japan in the last decade. In addition, the proportion of case-control/cohort studies (2.2%) was smaller for articles from Japan than those from other countries. Compared with those of other developed countries, Japan's contribution to research on infectious disease has been unsatisfactory in the last decade. An explanation for this phenomenon should be determined and remedial measures should be taken forthwith.

Objectives: Recent advances in medical and surgical treatment have led to the survival of increasing numbers of adults with congenital heart disease (CHD). However, the social status of these patients remains unknown. This survey investigated the social prospects for adults with CHD, and the limiting factors for social independence., Methods: A written questionnaire on patient characteristics, education, employability, marital status and insurability was designed to define the characteristics of social independence in adults with CHD. Randomly selected adults with CHD were enrolled: 13 patients with cyanotic unrepaired CHD (4 males, 9 females, mean age: 29.8 +/- 10 years, range: 18-56 years) and 102 patients with other CHDs (48 males, 54 females, mean age: 29.5 +/- 10 years, range: 18-74 years)., Results: University of California at Los Angeles functional class I-II was found in 94% of patients, medication in 46%, and hospitalization in 51%. Compared with the data from Japanese general population, study patients had a lower ratio of high school graduates (86% vs 94%), life insurability (51% vs 71%), marital status (31% vs 32%) and employability (82% vs 80%). Patients with unrepaired cyanotic CHD had significantly lower ratio than those with other CHDs (marital status 15%, p = 0.19; employability 40%, p = 0.0003; high school graduates 69%, p = 0.06; life insurability 18%, p = 0.02, respectively)., Conclusions: Factors affecting social independence in adults with CHD were severity of disease, continuing medication, lower level of education, lower self-esteem, and unknown natural history of CHD. To improve social independence in these patients, further development of medical and surgical therapy and more detailed knowledge of the patients, caretakers and society in this field are needed.

We investigated the antioxidative activities and the effects on acute inflammation in mice of a novel diaminouracil derivative, CX-659S ((S)-6-amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4(1H,3H)-pyrimidinedione). CX-659S showed potent scavenging activities against the hydroxyl radical and peroxynitrite and inhibited lipid peroxidation in rat brain homogenates in vitro. Topically applied CX-659S dose-dependently inhibited arachidonic acid- and 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema in mice. Consistent with its antioxidative properties in vitro, CX-659S dramatically attenuated the accumulation of lipid peroxides in the mouse ear elicited by repeated application of TPA. Previously, we reported the effectiveness of CX-659S against contact hypersensitivity reactions in both mouse and guinea pig models. These present results further suggest the therapeutic potential of CX-659S for acute skin inflammation that may involve oxidative tissue damage.

The reaction space map (RESMAP) representation is proposed for the comprehensive description of the chlorination and dechlorination reactions of polychlorobenzenes. By using the B3LYP/6-311G energies and by assuming the chemical reactions which govern the chlorination and dechlorination processes of polychlorobenzenes, the relative energies of polychlorobenzenes and polychlorophenyl radicals were defined artificially. They were collected as the RESMAP which has the relative energies of polychlorobenzenes at the diagonal parts and the polychlorophenyl radicals connecting two polychlorobenzenes at the off-diagonal parts. The RESMAPs created for three models for the chlorination/dechlorination processes provided a general view of the thermodynamically controlled isomer distributions and chlorination/dechlorination reaction patterns for benzene and (poly)chlorinated benzenes.

A rare case of rapidly growing osteosarcoma that developed in the uterine corpus of a 62-year-old woman is presented. The tumor occupied almost the entire pelvic cavity and extended into the abdominal cavity, with marked involvement of the intestines. Histopathologically, the tumor was composed of an osteoblastic component, accompanied by conspicuous bone formation, and a fibroblastic component. The tumor cells were positive for vimentin and osteocalcin, as well as desmin, alpha-smooth muscle actin and muscle-specific actin, but negative for h-caldesmon. The results indicated myofibroblastic differentiation in a part of the tumor. A review of 14 reported cases and our case of uterine osteosarcoma revealed that this tumor has a biologically aggressive nature, although its histopathological and immunohistochemical features are similar to those of osteosarcomas in soft tissue and bone. As the prognosis of patients with this tumor is poor, it is of importance to differentiate this tumor from other types of tumors arising from the uterine corpus.

Duchenne/Becker muscular dystrophy (DMD/BMD) are the most common inherited muscular diseases caused by mutations in the dystrophin gene. The identification of novel dystrophins in the brain has recently implicated its absence or malfunction etiologically in mental retardation (MR). We therefore examined the relationship between molecular abnormalities and clinical phenotypes. Deletions of the dystrophin gene were analyzed in a total of 137 DMD/BMD patients (DMD 94, BMD 43) to determine central nervous system (CNS) symptoms. The mental capacity was assessed and patients with IQs below 70 were defined as mentally retarded. Thirty-nine percent of DMD boys and 12% of BMD patients were classified as mentally retarded. Eight DMD and 2 BMD patients were diagnosed as having autism. Forty-four percent of DMD and 79% of BMD patients had deletions in the dystrophin gene. All the DMD/BMD patients with deletions upstream of the 5' end of the gene were mentally normal. All of DMD/BMD patients with MR and/or autism had deletions containing the 3' end, although some patients with similar deletions were mentally normal. Our data suggest that Dp140, Dp71 and/or Dp116, the C-terminal translational products of dystrophin, may be related to MR and/or autism in DMD/BMD. However, there was an exception in our series. Three of eight sibling pairs in our cases had different phenotypes, although they had the same mutations in the dystrophin gene. Thus the CNS phenotypes were not determined by the mutations of dystrophin gene alone, and the interaction of dystrophin with other nuclear genes may play important roles.

Cementum-derived attachment protein (CAP) is a 56 kDa collagenous protein that promotes attachment of mesenchymal cells. Previous studies have shown that the presence of CAP is restricted to cementum in adult human tissues. In this study, we report generation of a monoclonal antibody against CAP and its use for the investigation of CAP in developing bovine tooth germs. Mice were immunized with CAP purified from bovine cementum, and a monoclonal antibody, 3G9, was produced. Immunohistochemical staining of bovine tooth germ at root forming stage using 3G9 antibody showed that the tissue distribution of CAP expression was limited to cementum matrix and cementoblasts during cementogenesis. Alveolar bone did not stain with the 3G9 antibody, whereas anti-type I collagen stained positively. CAP was purified from bovine tooth germs with immunoaffinity purification using the 3G9 antibody. Examination of the immunoaffinity-purified fraction showed that CAP existed in tooth germ as a 65 kDa protein. The protein was susceptible to bacterial collagenase. To investigate the possible biological function of CAP during cementogenesis, we isolated dental follicle cells from the bovine tooth germ, and showed that they adhered to surfaces containing CAP. These data demonstrate that CAP is expressed by bovine cementoblasts as a 65 kDa protein and that the CAP may have a function in cementogenesis.

Male F344/DuCrj (Fischer) rats were given bisphenol A (BPA) in the diet at levels of 0 (control), 0.25, 0.50 and 1.00%, equivalent to 0, 235, 466 and 950 mg/kg per day, respectively, for 44 days. Body weight gains were depressed dose-dependently in BPA-treated rats, and those of 0.50 and 1.00% groups were significant. Testis and epididymis weights were not significantly decreased. Both absolute and relative weights of dorsolateral prostate and preputial glands were reduced in a dose-related fashion. Absolute weights of seminal vesicles and hypophysis were also decreased. Histopathologically, seminiferous tubule degeneration and loss of elongated spermatids were observed, the severity being related to BPA dose. The disorganization, distortion and degeneration of late spermatids, and the atrophy of seminiferous tubules were found even in the 0.25% BPA group. Serum testosterone concentrations were not decreased in BPA-treated groups. These results indicate that BPA even at a level of 0.25% (235 mg/kg per day) is clearly toxic to male reproductive organs.