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Biomedical subjects

T Tsunoda

Publications and source records attributed to T Tsunoda.

At least 55 records · Page 3Linked to original sources
PubMed2001

VEGF, basic-FGF, and TGF-beta in Crohn's disease and ulcerative colitis: a novel mechanism of chronic intestinal inflammation.

OBJECTIVE: Inflammatory bowel disease (IBD), the precise etiology of which remains unknown, is comprised of two forms of chronic intestinal inflammation; ulcerative colitis (UC) and Crohn's disease (CD). Recent evidence increasingly suggests that IBD is the result of dysfunctional immunoregulation manifested by inappropriate production of mucosal cytokines. An abnormal microcirculatory system has also been implicated in its pathogenesis. To elucidate the mechanism of ischemic change in IBD, we assesse serum concentration levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), and plasma level of endothelin-1 (ET-1). We also investigated the expression of VEGF, b-FGF, and transforming growth factor-beta1,2,3 (TGF-beta1,2,3) in tissue by immunostaining. METHODS: Blood samples were obtained from 11 patients with UC, 11 patients with CD, and 10 patients as controls. Paraffin-embedded samples were used for an immunohistochemical study. RESULTS: The concentration levels (in picograms per milliliter) were as follows: for ET-1, UC: 127+/-47.0, CD: 167.3+/-35.1, and controls (asthma: 38.5+/-23.8, p < 0.01; diverticulitis: 40.5+/-25.6, p < 0.01), for b-FGF, UC: 9.2+/-1.9, CD: 9.1+/-1.5, and controls (asthma: 5.0+/-0, p < 0.01; diverticulitis: 5.0+/-0, p < 0.01), for VEGF, UC: 659.8+/-181.0, CD: 740.0+/-182.3, and controls (asthma: 193.7+/-58.7, p < 0.01; diverticulitis: 199.6+/-59.7, p < 0.01). The levels of VEGF and b-FGF were significantly higher in active IBD than those in the controls. There was a significant positive correlation among the serum levels of VEGF and b-FGF and the plasma level of ET-1; that is, elevated VEGF, b-FGF, and ET-1 levels correlated well with each other. Immunohistochemical studies showed increased venula in the submucosa and lamina propria. Overexpression of VEGF and b-FGF in endothelial cells was revealed and TGF-beta2 and TGF-beta3 were found in inflammatory cells of active IBD, but no change was observed around the vessels in the controls. CONCLUSIONS: It is suggested that the reciprocal reaction of these cytokines may contribute to angiogenesis in IBD b inducing intestinal ischemia through vasoconstriction.

Adult↗
PubMed2001

Rapid spontaneous resolution of acute subdural hematoma occurs by redistribution--Two case reports.

Coronal magnetic resonance imaging provided evidence of redistribution during the rapid spontaneous resolution of acute subdural hematoma (ASDH) in two patients. A 79-year-old female was transferred to our hospital after a traffic accident. Computed tomography (CT) on admission demonstrated an ASDH in the right frontal cerebral cortex. CT 12 hours after the accident revealed spontaneous resolution of the ASDH. Coronal magnetic resonance (MR) imaging 3 days after the accident clearly detected a very thin, sharply demarcated layer diffusely covering the cerebral convexity and the middle cranial fossa. A 41-year-old female fell and sustained head trauma with the loss of consciousness. CT on admission demonstrated an ASDH in the left frontal cerebral cortex. CT 12 hours after the accident revealed spontaneous resolution of the ASDH. Coronal MR imaging 3 days after the insult clearly demonstrated the redistribution and dispersal of the hematoma. Although CT showed the disappearance of the hematoma, MR imaging demonstrated redistribution rather than disappearance of the blood in both cases. These cases indicate that spontaneous resolution of ASDH occurs by redistribution and dispersal of the hematoma.

Accidental Falls↗
PubMed2001

[A child case of subarachnoid hemorrhage triggered by head injury: a case report].

We report a case of basal subarachnoid hemorrhage in a child. The etiology of this lesion was difficult to diagnose. The patient was a 9-year-old boy. He sustained minor head injury followed by loss of consciousness and cardiopulmonary arrest. He was brought to our emergency room by ambulance. On arrival, he presented with cardiopulmonary arrest and deep comatose state. Basal subarachnoid hemorrhage was revealed on CAT scan. 3D-CTA documented two bulging portions: one was at the junction between the left vertebral artery and the left posterior inferior cerebellar artery. The other one was shown at the basilar artery. He died on the 7th hospital day. The autopsy revealed a laceration of the left vertebral artery. Microscopically, the wall around the laceration showed a defect in the internal elastic membrane and a decrease of smooth muscle cells with moderate fibrosis in the tunica media. These findings were compatible with the structure of a congenital aneurysm. Hence, the patient was strongly suspected to have had a congenital aneurysm whose rupture was triggered by minor head injury.

Aneurysm, Ruptured↗
PubMed2000

Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-Ras signaling pathway in human colon cancer cells.

To identify the genes located downstream of the activated Ki-Ras signaling pathways in human colon cancer cells, a PCR-based cDNA subtraction library was constructed between HCT116 cells and HCT116-derived activated Ki-ras-disrupted cells (HKe3). One of the genes in HCT116 that was evidently up-regulated was epiregulin, a member of the epidermal growth factor family that is expressed in many kinds of human cancer cells. HKe3-stable transfectants expressing activated Ki-Ras regained over-expression of epiregulin. To further elucidate the biochemical structure and significance of epiregulin expression in tumorigenesis, HKe3-stable transfectants expressing epiregulin (e3-pSE cells) were established. Epiregulin existed as highly glycosylated membrane-bound forms, and TPA rapidly induced ectodomain shedding of epiregulin. Furthermore, the conditioned medium of e3-pSE cells showed more DNA synthesis for 32D cells expressing epidermal growth factor receptor (DER) cells than that of HKe3. Although anchorage-independent growth in soft agar was not observed for e3-pSE cells, tumorigenicity in nude mice was observed evidently, and their growth rate was correlated with each amount of exogenous epiregulin expression. These results suggested that activated Ki-Ras will be one of the factors contributing to the overexpression of epiregulin in human colon cancer cells, and that epiregulin will play a critical role in human tumorigenesis in vivo.

Animals↗
PubMed2000

Identification by cDNA microarray of genes involved in ovarian carcinogenesis.

To identify genes involved in the development or progression of ovarian cancer, we analyzed gene expression profiles of nine ovarian tumors using a DNA microarray consisting of 9121 genes. Comparison of expression patterns between carcinomas and the corresponding normal ovarian tissues enabled us to identify 55 genes that were commonly up-regulated and 48 genes that were down-regulated in the cancer specimens. When the five serous adenocarcinomas were analyzed separately from the four mucinous adenocarcinomas, we identified 115 genes that were expressed differently between the two types of tumor. Investigation of these genes should help to disclose the molecular mechanism(s) of ovarian carcinogenesis and define molecular separation of the two most common histological types of ovarian cancer.

Adenocarcinoma, Mucinous↗
PubMed2000

Statistical analysis of the 5' untranslated region of human mRNA using "Oligo-Capped" cDNA libraries.

We constructed 34 types of human "full-length enriched" and "5'-end enriched" cDNA libraries based on the "Oligo-Capping" method. We randomly picked and sequenced 10,000 clones from these libraries. BLAST analysis showed that about 50% of the cDNAs were identical to known genes. Among them, we selected 954 species of cDNA that should represent the entire sequence from the mRNA start sites. Compared with previously reported sequences, they were on average 45 bp longer in the 5'-end. Using these cDNA data, we statistically analyzed the sequence features of the 5'UTR. The average length of the 5'UTR was 125 bp, and there was little correlation with the corresponding mRNA length (correlation coefficient = 0.26). Of the 954 species of 5'UTR, 459 contained no in-frame terminator codon, which is against the common belief. Two hundred seventy-eight species contained at least one ATG codon upstream of the initiator ATG codon. We identified 569 upstream ATGs, in total, 63% of which adequately satisfied Kozak's criteria. These findings are contrary to the typical translation initiation model, which states that translation is initiated from the "first" ATG codon.

5' Untranslated Regions↗
PubMed2000

In vitro augmentation of antitumor effect in combination with CPT-11 and CDDP for human colorectal cancer.

BACKGROUND AND OBJECTIVES: Irinotecan hydrochloride (CPT-11) is one of the camptothecin analogues that has shown a broad spectrum of strong antitumor effectiveness against various cancers, including colorectal cancer. In order to promote the clinical response of chemotherapy for colorectal cancer using CPT-11, one of the most effective strategies is to use it in combination with other anticancer agents. In the present study, anticancer effects after combining CPT-11 and other antitumor agents were determined by a 3-(4,5-di-methylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay of colorectal cancer cells, especially freshly isolated cancer cells. METHODS: Freshly isolated cancer cells from 20 patients with colorectal cancer and the established colon cancer cell lines were used in this study. The augmentation of the antitumor effectiveness of 7-ethyl-10-hydroxy-CPT (SN-38) was analyzed in combination with other anticancer agents. Furthermore, the antitumor effectiveness using lower concentrations of anticancer agents was measured to understand the mechanism of the augmentation. RESULTS: The percent inhibition of SN-38 in combination with cisplatin (CDDP) and mitomycin revealed a high anticancer effect compared with each anticancer agent alone for freshly isolated rectal cancer. CDDP also had a synergistic effect in combination with SN-38 according to the fractional product concept. At lower than plasma peak concentrations of SN-38, the anticancer effects were augmented in combination with lower concentrations of CDDP for freshly isolated colorectal cancer. This augmentation showed a strong synergistic effect. CONCLUSIONS: These results may be supportive to ongoing clinical studies of chemotherapy by using CPT-11 and CDDP for advanced colorectal cancer.

Adenocarcinoma↗
PubMed2000

Pulmonary sequestration associated with aspergillosis.

Pulmonary sequestration involves an abnormal pulmonary tissue separated from the normal pulmonary parenchyma, not connected to the tracheobronchial tree and supplied by a systemic artery. A case of intralobar pulmonary sequestration is presented. Case; a 49-year-old male was admitted to our hospital complaining of fever, cough and sputum production. Sputum culture resulted in a large growth of Aspergillus niger. Angiography showed an abnormal blood supply from the abdominal aorta to the right lower lobe. Right lower lobectomy was performed. The postoperative courses are uneventful.

Aspergillosis↗
PubMed2000

Coronary flow velocity immediately after primary coronary stenting as a predictor of ventricular wall motion recovery in acute myocardial infarction.

OBJECTIVES: The purpose of this study was to examine the relationship between the pattern of coronary blood flow velocity immediately after successful primary stenting and the recovery of left ventricular (LV) wall motion in patients with acute myocardial infarction (AMI). BACKGROUND: It is difficult to predict the recovery of LV wall motion immediately after direct angioplasty in AMI. Recent reports indicate that dysfunctional coronary microcirculation is an important determinant of prognosis for AMI patients after successful reperfusion. METHODS: We measured left anterior descending coronary flow velocity variables using a Doppler guide wire immediately after successful primary stenting in 31 patients with their first anterior AMI. The patients were divided into two groups: those with and those without early systolic reverse flow (ESRF). Changes in LV regional wall motion (RWM) and ejection fraction (EF) at admission and at discharge were compared between the two groups. Coronary flow velocity variables immediately after primary stenting were compared with changes in left ventriculographic indexes. RESULTS: The change in RWM was significantly greater in the non-ESRF group than it was in the ESRF group (0.9 +/- 0.7 vs. -0.1 +/- 0.3 standard deviation/chord, respectively, p < 0.001). The change in EF was also significantly greater in the non-ESRF group than it was in the ESRF group (10 +/- 10 vs. 1 +/- 6%, respectively, p < 0.05). In the non-ESRF group (diastolic to systolic velocity ratio [DSVR] <3.0), the DSVR correlated positively with the change in RWM (r = 0.60, p < 0.005, n = 24) and the change in EF (r = 0.52, p < 0.01). CONCLUSIONS: The coronary flow velocity pattern measured immediately after successful primary stenting is predictive of the recovery of regional and global LV function in patients with AMI.

Aged↗
PubMed2000

A novel method for assessing assisted female fertility: bioelectric impedance.

Early detection of declining female fertility is important for effective prevention and treatment of infertility. Age, serum concentration of FSH in the early follicular phase (basal FSH), and the clomiphene citrate (CC) challenge test correlate only with large declines in fertility. We serendipitously discovered that by a novel mechanism bioelectric impedance (BEI) sensitively reflects early fertility decrements. BEI was measured between the right and left arms by the tetrapolar method before and during ovarian stimulation for in vitro fertilization (IVF). In a stepwise multiple logistic regression analysis of five factors (BEI on luteal day 4 prior to the IVF cycle [BEI-L4], age, basal FSH, body height, and body mass index), BEI-L4 alone was a significant predictor (P<0.05) of achievement of pregnancy by IVF in 148 women (74 pregnant and 74 nonpregnant). BEI showed a nadir on the day of administration of hCG in the pregnant but not the nonpregnant group. Serum concentrations of VEGF during ovarian stimulation were significantly higher in the pregnant group, but not those of 17beta-estradiol and progesterone. The CC challenge test revealed no significant difference between 11 pregnant and 15 nonpregnant women. The clinical usefulness of BEI was evaluated in 272 consecutive IVF cycles. Rate of pregnancy was significantly higher (P<0.01) in IVF cycles with BEI-L4 > or =600 Ohms than <600 Ohms (44% and 26% in 149 and 123 cycles, respectively). When BEI-L4 was > or =600 Ohms, pregnancy rates were constantly high irrespective of age and basal FSH. In prediction of nonpregnancy, sensitivity of BEI-L4 (0.52) was significantly (P<0.05) higher than those of age and basal FSH (0.39 and 0.046, respectively). BEI, which is easy, noninvasive, and inexpensive, predicts female fertility more sensitively than age and basal FSH, probably reflecting angiogenic capacity of reproductive organs.

Adult↗
PubMed2000

Oral administration of fluoroquinolones in the treatment of typhoid fever and paratyphoid fever in Japan.

OBJECTIVE: To study the adverse reactions and therapeutic effects of fluoroquinolones to investigate whether they can be used for the treatment of patients with typhoid fever and paratyphoid fever. METHODS: The adverse reactions and therapeutic effects of fluoroquinolones were studied retrospectively in patients with typhoid fever and paratyphoid fever. PATIENTS: 58 patients (54 Japanese) with typhoid fever, 42 patients (41 Japanese) with paratyphoid fever, and 1 Japanese patient with both typhoid fever and paratyphoid fever, who were admitted in hospitals in Tokyo, Kawasaki, Yokohama, Kyoto, and Osaka from 1995 to 1998 and treated with fluoroquinolones. RESULTS: Almost 80% of the patients were treated with tosufloxacin (TFLX) and the remaining 20 % were treated with norfloxacin, ciprofloxacin, levofloxacin, or sparofloxacin. Side effects (nausea, urticaria, aphthous stomatitis) and elevation of serum amylase were found in 3.6% and 8.3 % of patients treated with TFLX, respectively, but these adverse reactions disappeared in all of these cases either with or without a change in the drug used. No adverse reactions were found in patients treated with the other fluoroquinolones. The clinical and bacteriological effects of these drugs were adequate. CONCLUSION: Though further studies still need to be performed on the fluoroquinolones other than TFLX, we can preliminarily conclude that fluoroquinolones are safe drugs and they can be recommended for the initial therapy of patients with typhoid fever and paratyphoid fever.

Administration, Oral↗
PubMed2000

[Evaluation of coronary flow reserve in patients with vasospastic angina].

OBJECTIVES: The presence of microvascluar impairment was evaluated in 154 patients with vasospastic angina identified by the acetylcholine provocation test. METHODS: Coronary flow reserve was evaluated with a Doppler flow guidewire in 128 vessels of 72 patients with chest pain, but no significant coronary stenosis(less than 50% stenosis) and no clinical factors that affect coronary flow reserve. Coronary flow reserve was obtained from the ratio of adenosine triphosphate-induced maximum/baseline averaged peak velocity. These vessels were classified into 2 categories according to whether acetylcholine-induced vasospasm was positive or negative. Vasospasm positive was defined as more than 90% stenosis provoked with chest pain and/or ischemic ST change. Positive vessels were subdivided according to focal or diffuse vasospasm. These vessels were also classified into 2 other categories according to whether vasospasm in the distal artery was positive or negative. RESULTS: Coronary flow reserve was significantly lower in vessels with vasospasm than in vessels without vasospasm in patients without vasospasm(2.9 +/- 0.8 vs 3.6 +/- 1.0, p = 0.0005). Coronary flow reserve was significantly lower in vessels without vasospasm in patients with vasospasm than in vessels without vasospasm in patients without vasospasm(3.0 +/- 0.8 vs 3.6 +/- 1.0, p = 0.03). There was no significant difference in coronary flow reserve between vessels with vasospasm and vessels without vasospasm in patients with vasospasm(2.9 +/- 0.8 vs 3.0 +/- 0.8, p = 0.8). There was no significant difference in coronary flow reserve between focal and diffuse vasospasm(3.2 +/- 0.8 vs 2.9 +/- 0.8, p = 0.3). Coronary flow reserve was significantly lower in vessels with vasospasm in the distal artery than in vessels without vasospasm in the distal artery (2.8 +/- 0.8 vs 3.4 +/- 1.0, p = 0.004). CONCLUSIONS: Patients with vasospastic angina have microvascular impairment in both vessels with vasospasm, and vessels without vasospasm. Microvascular impairment is prominent in vessels with vasospasm in the distal artery.

Acetylcholine↗
PubMed2000

[Does quinapril improve coronary vasoconstriction in vasospastic angina?].

OBJECTIVES: Endothelial dysfunction is one of the important mechanisms of coronary spasm. Recently, the angiotensin converting enzyme (ACE) inhibitor quinapril, which has a high affinity for vascular ACE, has improved endothelial dysfunction in coronary artery disease. This study investigated whether quinapril improves coronary vasoconstriction induced by acetylcholine in vasospastic angina. METHODS: Twenty-four patients with vasospastic angina without significant organic stenosis diagnosed by the acetylcholine provocation test (vessel with spasm defined as > or = 90% stenosis provoked with chest pain and/or ischemic ST change) were enrolled in this study. Patients were randomly assigned to 2 groups: the quinapril group (receiving quinapril 20 mg/day, n = 12), and the non-quinapril group (not receiving quinapril, n = 12). All patients received calcium antagonist. Six months later, coronary angiography was repeated and changes in coronary spasm were compared between the groups. Seven patients were withdrawn from this study, so 17 patients were evaluated (the quinapril group: 8 patients, the non-quinapril group: 9). RESULTS: Angina symptoms were completely or almost suppressed in all patients during the study period. Angiographically, the number of patients with improvement of spasm, patients with deterioration of spasm and patients with stability of spasm were 1, 0, 7 in the quinapril group versus 0, 1, 8 in the non-quinapril group, respectively. There was no significant change between the 2 groups. Quantitative angiographic analysis showed that the coronary spasm rate (percentage of minimal lumen diameter at the site of spasm after administration of acetylcholine to minimal lumen diameter after administration of isosorbide dinitrate) at the first and second angiography were 71 +/- 10% and 62 +/- 21% in the quinapril group versus 73 +/- 14% and 67 +/- 15% in the non-quinapril group, respectively. There were no significant interval changes between the 2 groups (p = 0.60). CONCLUSIONS: Our results did not indicate that quinapril had improved coronary vasoconstriction induced by acetylcholine in patients with vasospastic angina.

Acetylcholine↗