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Hiroshi Izumi

Publications and source records attributed to Hiroshi Izumi.

At least 19 recordsLinked to original sources

Fliplike motion in the thalidomide dimer: Conformational analysis of (R)-thalidomide using vibrational circular dichroism spectroscopy.

The dynamic fliplike motion in the (R)-thalidomide dimer has been reported for the first time. The vibrational circular dichroism (VCD) spectrum of (R)-thalidomide in DMSO-d6 indicates the characteristic nu(CO) bands with opposite signs and reflects the structural property of the equatorial configuration of the phthalimide ring. On the other hand, the VCD spectrum of (R)-thalidomide in CDCl3 exhibits a different pattern of nu(CO) bands and suggests the fliplike motion in dimer forms. This novel insight for the dimer forms would be helpful for the understanding of the structure-activity relationship for thalidomide.

Circular Dichroism↗

Prognostic significance of a histologic subtype in small adenocarcinoma of the lung: the impact of nonbronchioloalveolar carcinoma components.

BACKGROUND: We tried to clarify whether the histologic subtypes and the size of the solid component of an adenocarcinoma are more important predictive factors for invasiveness or prognosis than is total tumor size, even in lung adenocarcinomas that were 2 cm or smaller. METHODS: Between 1996 and December 2005, after standard surgical treatment, 82 patients were diagnosed as having adenocarcinoma with a maximum diameter of 2 cm or less. The group comprised 37 females and 45 males, with ages ranging from 41 to 80 years (median, 64). The clinicopathologic records of the patients were examined with regard to age, sex, nodal status, tumor size (largest diameter of the total tumor as well as the largest diameter without the bronchioloalveolar carcinoma [BAC] component [solid component]), serum carcinoembryonic antigen level, and histologic type. These variables were analyzed as risk factors for vascular or lymphatic invasion, lymph node metastasis, and prognosis. Histologic subtype was classified into two groups: mixed BAC (mixed adenocarcinoma with BAC) and minimal or non-BAC (tumors with little or no BAC component). RESULTS: Histologic subtype was a significant predictive factor both for invasiveness (vascular or lymph vessels) and lymph node metastasis, in both univariate and multivariate analysis. Tumor diameter was not a significant factor in either univariate or multivariate analysis (p = 0.28, 0.15, respectively). However, diameter excluding the BAC component was a significant factor for invasiveness in mixed BAC type (p = 0.035), whereas total diameter was not significant (p = 0.28). Finally, histologic subtype and lymph node metastasis were significant prognostic factors for survival in both univariate (p = 0.03, 0.05, respectively) and multivariate (p = 0.04, 0.05, respectively) analyses. The 5-year survival rate was 94.4% (94.1% for pN0) for the mixed BAC type and 71.4% (78.7% for pN0) for the minimal or non-BAC type (p = 0.009; p = 0.04 for pN0 nodes). CONCLUSIONS: Small adenocarcinomas can be classified into two categories. The first category is a minimal or non-BAC adenocarcinoma that shows aggressive biological behavior. The second category is a mixed BAC, which demonstrates less invasive or aggressive biological behavior than the minimal or non-BAC type, with the degree of invasiveness being associated with the size of the non-BAC component.

Adenocarcinoma↗

Absolute configuration determination of donor-acceptor [2.2]paracyclophanes by comparison of theoretical and experimental vibrational circular dichroism spectra.

Vibrational circular dichroism (VCD) spectra were obtained for the assignments of the absolute configurations of diastereomeric 4,7-bis(methoxycarbonyl)-12,15-dimethoxy-[2.2]paracyclophanes (1 and 2), and density functional theory (DFT) calculations were performed at the B3LYP/6-31G(d) level for all possible conformations of both 1 and 2 to give the theoretical VCD spectra. Comparisons of the experimental and theoretical VCD spectra obtained unambiguously established the absolute configurations of the dextrorotatory (+)-enantiomers as (4S(p);12S(p))-1 and (4S(p);12R(p))-2, respectively.

Journal Article↗

[Efficacy of the combined use of taurine for hyperbilirubinemia caused by UFT therapy after surgery for colonic cancer].

For postoperative adjuvant chemotherapy, UFT was administered to 69 cases of stage II and III colonic cancer following surgery with a radical curability of A. Among these patients, 8 developed hyperbilirubinemia. UFT administration was discontinued for those who developed overt jaundice or dermatological symptoms, experienced a relapse of an earlier asthmatic respiratory difficulty, or for those who were found with multiple hepatic metastases. For the 4 who had developed subclinical jaundice with a total bilirubin level of 1.6 to 2.2 mg/dl, UFT was combined with taurine. The combination successfully eliminated hyperbilirubinemia. All 4 are currently alive with no recurrence at this writing. Taurine ameliorates one's capacity to excrete bile, blood flow, and augments the actions of hepatocytes. It is effective in treating the hyperbilirubinemia that develops during UFT therapy.

Adult↗

Evidence for parasympathetic vasodilator fibres in the rat masseter muscle.

The present study was designed to examine (1) whether there are vasodilator fibres in the masseter muscle, and (2) if there are, to establish the neural pathways mediating these responses in urethane-anaesthetized rats. Electrical stimulation of the central cut end of the lingual nerve (LN) elicited intensity- and frequency-dependent increases of the blood flow in the masseter muscle (MBF) and lower lip (LBF). Increases in both the MBF and LBF evoked by the LN stimulation were reduced by hexamethonium in a dose-dependent manner (1-10 mg kg(-1)). Pretreatment with phentolamine or propranolol at a dose of 100 microg kg(-1) had no effect on the increases in either MBF or LBF evoked by LN stimulation. Pretreatment with atropine (100 microg kg(-1)) significantly reduced the MBF increase induced by LN stimulation, but not that in the LBF. The sectioning of the superior cervical sympathetic trunk did not affect the responses. MBF increases occurred with electrical stimulation of the trigeminal ganglion, and these increases were significantly reduced by the administration of hexamethonium and atropine. Lidocaine microinjection into the trigeminal spinal nucleus or salivatory nuclei caused a significant attenuation of the LN-induced MBF increases. When wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected into the masseter muscle, labelled neurones were abundantly observed in the otic ganglion. The present study indicates that there are parasympathetic cholinergic and noncholinergic vasodilator fibres originating from cell bodies in the otic ganglion in the rat masseter muscle. The MBF increase evoked by activation of the parasympathetic fibres occurred via the trigeminal mediated reflex, suggesting that the novel parasympathetic vasodilator response may play an important role in the regulation of the haemodynamics of jaw muscles.

Animals↗

Relationship of coffee consumption with risk factors of atherosclerosis in rats.

AIMS: In experimental animals we investigated the relationship of coffee consumption with risk factors of atherosclerosis such as cholesterol, homocysteine, oxidative stress and inflammatory cytokines. METHODS: Forty-eight male Wistar rats were assigned to 3 treatment groups (a control diet group, 0.62% coffee diet group, and 1.36% coffee diet group), and animals were maintained on the experimental diets for 140 days. RESULTS: Coffee diets led to an increase in the caffeine concentration to 0.53 +/- 0.11 and 1.77 +/- 0.22 microg/ml, respectively, although caffeine in serum was not detected in rats fed the control diet. It also led to slightly increased total serum levels of homocysteine and cholesterol, but no significant differences were found between the control and coffee diet groups. Coffee intake did not affect the production of IL-6 and TNF-alpha induced by LPS, which contributes to the atheroma-promoting effect of recurrent bacterial infection. Regarding the biomarkers of oxidative stress, the serum level of 15-isoprostane F(2t), which was significantly increased by LPS injection, was not altered by coffee intake. In contrast, urinary 8-hydroxy-2-deoxyguanosine was significantly increased in the coffee diet groups (p < 0.05). On the other hand, serum glutathione peroxidase (GPx) activity tended to decrease in the coffee groups compared with the control group, but no significant difference was found between the control and coffee diet groups. Interestingly, a significant negative correlation was observed between GPx activity and homocysteine levels in the sera from control and coffee diet groups (r = -0.403, p < 0.05). CONCLUSIONS: This report is the first animal study on the relationship of coffee consumption with risk factors for atherosclerosis. From these results, we conclude that moderate coffee intake is not a risk factor for atherogenesis.

8-Hydroxy-2'-Deoxyguanosine↗

Prognostic value of CD44 isoform expression in thymic epithelial neoplasms.

BACKGROUND: Many histologic classifications of thymic epithelial tumors have been reported to date, but to the authors' knowledge, none of them closely reflect the clinical behavior or prognosis of the tumor. Therefore, it is necessary to establish a biologic marker for thymic epithelial tumors. Variants of CD44 may be important in promoting tumor progression and metastasis. Accordingly, the expression of CD44 isoforms in thymic epithelial neoplasms was investigated using immunohistochemistry to assess their possible value as prognostic indicators. METHODS: Expression of CD44v6 in thymic epithelial tumors was investigated with immunohistochemistry using consecutive surgical specimens resected from 108 patients between 1983 and 2002 at Juntendo University Hospital in Tokyo, Japan. RESULTS: Among the 108 thymic epithelial tumors, 70 were negative for CD44v6, 20 were weakly positive, and 18 were strongly positive. The status of CD44v6 expression (negative vs. weakly plus strongly positive) was found to be correlated with the tumor stage according to the Masaoka staging system (noninvasive vs. invasive tumors) (P = 0.0214). When patients with tumors that were negative and weakly positive for CD44v6 expression were combined, the 5-year, 10-year, and 15-year recurrence-free survival rates were 98.2%, 95.9%, and 86.1%, respectively, whereas the corresponding rates for patients with strongly positive tumors were 73.5%, 73.5%, and 55.1%, respectively. Therefore, these two groups demonstrated a significant difference with regard to recurrence-free survival (P = 0.0172). CONCLUSIONS: CD44v6 expression in thymic epithelial neoplasms demonstrated a significant difference based on the World Health Organization classification, the Masaoka stage (invasive vs. noninvasive tumors), and recurrence, if an appropriate cutoff value was chosen in each case. This suggests that CD44v6 can be used as a marker that reflects the stage of thymic tumors.

Adult↗

Homocysteine attenuates the expression of osteocalcin but enhances osteopontin in MC3T3-E1 preosteoblastic cells.

It has been pointed out that very high plasma levels of homocysteine are characteristic of homocystinuria, a rare autosomal recessive disease accompanied by the early onset of generalized osteoporosis. However, it is unclear by which mechanism hyperhomocysteine induces osteoporosis, although it is known to interfere with the formation of cross-links in collagen, an essential process in bone formation. Therefore, we investigated the effect of homcysteine on expression of osteocalcin and osteopontin in MC3T3-E1 preosteoblastic cells. Confluent cells were grown in RPMI 1640 containing 10% fetal calf serum with or without homocysteine in an atmosphere of 95% humidified air, 5% CO2 at 37 degrees C. The secretion of osteocalcin from the cells increased time-dependently until the end of culture (day 34), but 500 microM homocysteine led to an approximately 61% decrease for osteocalcin after 19 days of culture as compared with the control. On the other hand, osteopontin was not inhibited by 500 microM homocysteine but rather activated, and ranged from 134%-209% of the control level in the period from 10 days until the end of culture. From analysis of RT-PCR for mRNA of osteocalcin and osteopontin at the end of the culture, homocysteine levels of 100 and 500 microM significantly increased the expression of osteopontin mRNA with the control (p < 0.05). In contrast, the expression of osteopontin mRNA was suppressed in a dose-dependent manner, showing a mirror image of the effect on osteopontin mRNA. These findings suggest that hyperhomocystenemia appears to be an independent risk factor for osteoporosis by disturbing osteoblast function.

Animals↗

Risk of recurrence after surgical resection of small-sized invasive lung adenocarcinoma: analysis based on apoptotic index.

OBJECTIVE: It has been reported that small-sized invasive lung adenocarcinomas, i.e., those classified as type C through type F according to Noguchi's classification, may also recur even after complete resection. We evaluated the prognostic value of molecular biologic markers (apoptosis, Ki-67, p53, epidermal growth factor) and clinicopathological factors in patients with small-sized invasive lung adenocarcinomas. METHODS: The clinical records of all patients who had had a peripheral adenocarcinoma surgically resected between 1996 and 2002, and histologically diagnosed as type C through type F according to Noguchi's classification were retrospectively reviewed. The apoptotic index (AI) was determined by the triphosphate biotin nick end-labeling method and the expression of Ki-67, aberrant p53 protein and epidermal growth factor receptor was determined by immunohistochemical staining. RESULTS: Data from 28 patients who had been followed up for a mean period of 41.8 months (range: 16 to 89 months) were evaluated. During the follow-up period, recurrence was seen in 6 patients. The log-rank test showed that AI was a significant predictor of cancer recurrence. The 5-year disease-free survival rate of the 10 patients in the high AI group (AI > 0.3%) was 100%; while that of the 18 patients in the low AI group (AI < or = 0.3%) was 50.5% (p = 0.036). None of the other molecular biologic markers or clinicopathological factors were found to be a significant predictor of cancer recurrence. CONCLUSION: Peripheral small-sized invasive lung adenocarcinomas with a low AI carry an increased risk of distant metastases, indicating that adjuvant chemotherapy after complete resection might be needed.

Adenocarcinoma↗

Adenocarcinoma of the thymus: mucinous subtype.

Primary thymic adenocarcinoma, mucinous subtype, is extremely rare with only one case reported to date. We describe herein a case of thymic mucinous adenocarcinoma. A 59-year-old man was identified to have an anterior mediastinal tumor and was diagnosed as mucinous adenocarcinoma. Clinical and radiographic examinations disclosed no evidence of tumor elsewhere. The patient received radiotherapy, but the general condition deteriorated and died 11 months after tumor detection. Thoracic autopsy revealed an anterior mediastinal tumor measuring greater than 10 cm, uncapsulated, and white. The tumor had clear margins and was clearly isolated from the lung. Histologically, the tumor demonstrated papillary, acinar, and cribriform structure and produced abundant extracellular mucin. Immunohistochemically, most tumor cells were positive for cytokeratin 7, were partially positive for CD5, and were negative for TTF-1, Sp-A, CDX-2, MUC2, napsin A, and cytokeratin 20. Collectively, the diagnosis of the tumor was primary mucinous adenocarcinoma of the thymus. We propose that the mucinous subtype should be recognized as one of the histopathological entities of thymic adenocarcinoma.

Adenocarcinoma, Mucinous↗

Multilocular thymic cyst associated with follicular hyperplasia: clinicopathologic study of 4 resected cases.

We report here 4 cases of multilocular thymic cysts (MTCs) with reactive lymphoid follicular hyperplasia. They were admitted to our hospital to examine anterior mediastinal masses demonstrated on chest computed tomographic scans. Three patients presented high-grade intermittent fever, and 2 patients were associated with Sjogren syndrome with elevated serum antinuclear antibody levels. All patients were subjected to extended thymectomy. Interestingly, their fever disappeared immediately after surgery. Histologically, the lesions were characterized by several cystic spaces separated by various thick walls with dense lymphoid tissue containing large reactive germinal centers. The inner cyst walls were lined by flattened cuboidal epithelia in some portions. Columnar epithelia with focal cilia were partially observed in 2 cases. These pathological findings led to a diagnosis of MTCs that were thought to result from cystic transformation of medullary duct derivatives by acquired inflammatory processes. The pathological findings, together with clinical courses of our cases, suggest that inflammation accompanied by autoimmune diseases may play, in part, an important role in the development of MTCs.

Adult↗

Parasympathetic mediated pupillary dilation elicited by lingual nerve stimulation in cats.

PURPOSE: To determine the autonomic efferent nerve pathways for the reflex pupillary dilation elicited by somatic stimulation in cats. METHODS: Cats anesthetized with a mixture of alpha-chloralose (50 mg/kg) and urethane (100 mg/kg) were intubated and paralyzed by intravenous injection of pancuronium bromide. The central cut end of the lingual nerve (LN) was stimulated electrically to simulate somatic stimulation, and 1 microL of lidocaine (2%) was microinjected into the Vsp or the EW nucleus to determine its effect on the pupillary dilation induced by LN stimulation. The effect of electrically stimulating the Vsp or sectioning the superior cervical sympathetic nerve (CSN) on the pupillary response was also examined. RESULTS: Stimulation of the LN or the trigeminal spinal nucleus (Vsp) evoked pupillary dilation in a frequency- and intensity-dependent manner. These responses were not affected by sectioning the ipsilateral or both CSNs. The pupillary responses were markedly suppressed by microinjecting lidocaine into the ipsilateral Vsp or the Edinger-Westphal (EW) nucleus, but not by injection into the contralateral Vsp. CONCLUSIONS: These results indicate that the Vsp and EW nucleus act as bulbar relay centers for pupillary dilation elicited by LN stimulation and suggest that the efferent arc of the response is a parasympathetic pathway. The contralateral pupillary dilation appears to be mediated, at least in part, by fibers projecting from the Vsp to the contralateral EW nucleus.

Animals↗

[Correlation between human papilloma virus infection in cervical lesions and expression of p53, p21 proteins and Ki-67].

BACKGROUND: Human papilloma virus (HPV) is the most important factor in the oncogenic mechanism of cervical tumor. Furthermore, in a separate multi-stage process, abnormality in cell cycle kinetics has been demonstrated. In order to elucidate the oncogenic mechanism, we examined the relationship between cervical carcinoma and HPV infection, and also investigated the expression of p53 and p21 proteins as well as the cell proliferation capability by detecting Ki-67, and analyzed the correlations of these factors. MATERIALS AND METHODS: We studied the biopsy specimens from 107 patients of chronic cervicitis, cervical intraepithelial neoplasia and squamous cell carcinoma (SCC). HPV DNA was detected by the hybrid capture method. Immunostaining by LSAB procedures were performed using antibodies to p53 protein, p21 and MIB-1. The PCR-denaturing gradient gel electrophoresis (DGGE) method was used to search for mutation in exons 5, 6, 7 and 8 of p53. RESULTS: Of 107 cases studied, high-oncogenic HPV was detected in 80 cases (74.8%) with a particularly high prevalence in SCC. No correlation was observed between HPV infection and expression of p53, p21 or Ki-67. The degree of positivity of Ki-67 expression tended to be higher with disease progression. Cases strongly positive (2+) for p53 and p21 proteins were weakly positive for Ki-67, and cases positive (1+) or negative for p53 and p21 were strongly positive for Ki-67. CONCLUSION: In oncogenesis of cervical carcinoma, p53 protein, p21 protein and HPV may act separately as independent factors in some cases, and there is a strong possibility that other factors are involved.

Carcinoma, Squamous Cell↗

A case of diffuse pleural mesothelioma in which contralateral exploratory thoracoscopy assisted the selection of therapy.

Diffuse pleural mesothelioma is a rare condition with a poor prognosis. Recent reports have indicated that extensive surgery combined with chemotherapy and radiotherapy prolongs the survival of selected patients with early disease. Thoracoscopy allows complete visualization of the pleural cavity and provides high-quality biopsy samples. We present a case of successful diagnosis of bilateral pleural mesothelioma by thoracoscopy. It is important to observe the contralateral pleural cavity by thoracoscopy to confirm the presence or absence of a tumor before considering extrapleural pneumonectomy for mesothelioma.

Aged↗

Clinical usefulness of the WHO histological classification of thymoma.

PURPOSE: Rosai et al. published the World Health Organization (WHO) classification of thymic epithelial tumors in 1999, and its clinical usefulness seems to be established. It is our purpose to find the clinically relevant diagnostic points in the WHO Histological Classification of Thymoma. METHODS: Thymomas surgically removed from 100 consecutive patients at Juntendo University Hospital between October 1983 and February 2002 were classified according to the WHO histological classification. We assessed overall survival and recurrence-free rate calculated for each tumor type in the WHO classification compared with those of tumors classified by the Masaoka system. RESULTS: The thymic epithelial tumors in this series comprised 10 type A, 15 type AB, 18 type B1, 21 type B2, 33 type B3, and 3 type C tumors according to the WHO classification. Based on the Masaoka system, the disease was stage I in 53 patients, stage II in 30, stage III in 15, and stage IV in 2. The 15-year recurrence-free rate was 100% for type A, AB and B1, while the rates for types B2 and B3 were 66.7% and 54.5%, respectively. The 10-year recurrence-free rate was 66.7% for type C. The 15-year recurrence-free rate of the 64 patients with type A, AB, B1, and B2 thymomas was significantly higher from that of the 33 patients with type B3 thymoma (p=0.0026). CONCLUSION: When using the WHO classification, it is critical to distinguish type B3 thymoma from other tumor types.

Adult↗

An early case of pulmonary lymphangioleiomyomatosis diagnosed by video-assisted thoracoscopic surgery.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare and progressive disease of young women that usually causes death from respiratory failure. Here we report an early case that was diagnosed by thoracoscopy. A 28-year-old woman presented to a local clinic with chest pain and her chest X-ray film showed left pneumothorax. After placement of a chest tube, the lung re-expanded fully. Following the recurrence of left pneumothorax, she was referred to our hospital and underwent video-assisted thoracoscopic surgery (VATS). However, left pneumothorax recurred again one month later. She underwent a second thoracoscopic operation, during which a bulla was recognized in the lingular segment of the left lung and was resected. On histological examination of the surgical specimen findings consistent with LAM were obtained. Taking the preoperative imaging findings and the thoracoscopic findings into consideration, a diagnosis of early lymphangioleiomyomatosis was made. Thoracoscopic management of pneumothorax in young women can facilitate the early diagnosis of this condition.

Adult↗

Bulbar pathway for contralateral lingual nerve-evoked reflex vasodilatation in cat palate.

We investigated the brain-stem pathway(s) by which electrical stimulation of the central cut end of the lingual nerve (LN) evokes parasympathetic reflex vasodilatation in the palate contralateral to the stimulated side. This occurs in artificially ventilated, cervically vagosympathectomized cats deeply anesthetized with alpha-chloralose and urethane. For this purpose, we made microinjections within the brain stem to produce nonselective, reversible local anesthesia (lidocaine) or soma-selective, irreversible neurotoxic damage (kainic acid). Local anesthesia of the trigeminal spinal nucleus (Vsp) ipsilateral to the stimulated side produced by microinjection of lidocaine (2%; 1 microl/site) reversibly and significantly reduced the LN stimulus-evoked palatal blood flow (PBF) increases. PBF increases ipsilateral and contralateral to the stimulated nerve were equally affected. In contrast, microinjection of lidocaine into the Vsp contralateral to the stimulated side did not affect these responses. Microinjection of kainic acid (10 mM/site; 1 microl) into the Vsp ipsilateral to the stimulated side led to a bilateral irreversible reduction in reflex vasodilatation in the palate. Microinjection of lidocaine into either superior salivatory nucleus (SSN) attenuated the PBF increase only on the side ipsilateral to the microinjection site. Hexamethonium (1.0 mg/kg iv) significantly reduced the vasodilator responses to electrical stimulation of Vsp by blocking ganglionic transmission on both sides. The simplest interpretation of these results is that the LN-evoked parasympathetic reflex vasodilatation in the contralateral palate depends on activation of a pathway originating from the Vsp ipsilateral to the stimulated nerve and crossing to the contralateral SSN.

Animals↗

Bone metabolism and oxidative stress in postmenopausal rats with iron overload.

Osteoporosis is associated with many etiological causes such as nutrition, cytokines, hormones, and aging. Recently, reactive oxygen species (ROS) are considered to be responsible for the aging process and osteoporosis. We investigated the relationship between ROS and bone metabolism in young female and postmenopausal rats, by using dietary iron overload and several indices including bone metabolic markers, oxidative stress and antioxidant markers, and cytokines. Postmenopausal rats exhibited significant decreases in serum alkaline phosphatase activity and the level of osteocalcin as bone formation markers compared with young female rats; however, urinary excretion of deoxypyridinoline, a bone resorption marker, did not change. On the other hand, a 5% iron lactate diet for 4 weeks in postmenopausal rats led to significantly increased excretion of urinary deoxypyridinoline and 8-hydroxy-2'-deoxyguanosine (8-OHdG) but not serum alkaline phosphatase activity. Interestingly, the diet induced significant increases of serum osteopontin and TGF-beta1, augumenting osteoclast-mediated bone resorption through the RANK/RANKL pathway [J. Clin. Invest. 112 (2003) 181]. TGF-beta1 showed a negative correlation with serum glutathione peroxidase (GPx) activity (r = -0.674, P < 0.003), but a positive correlation with the serum iron level (r = 0.836, P < 0.0001). Taken together, these results suggest for the first time that oxidative stress could be involved in the pathogenesis of metabolic bone diseases such as osteoporosis as demonstrated by analysis of the relationship between bone metabolism and oxidative stress.

Animals↗