[Development of diagnostic imagings for prostatic cancer and their detection rates].
Explore the source record for details and available documents.
Diagnostic Imaging↗
Biomedical subjects
M Saitoh
Publications and source records attributed to M Saitoh.
Cerebral artery selective inhibition of protein kinase c-mediated contraction by hns-32, a novel azulene-1-carboxamidine derivative.
The vasorelaxant actions of a novel azulene-1-carboxamidine derivative, HNS-32, were investigated on the tension development evoked by phorbol 12, 13 dibutyrate (PDBu) in cerebral and femoral arteries isolated from the dogs. In basilar artery, HNS-32 inhibited almost completely PDBu-induced contraction in a concentration-dependent manner with potency about 10 times stronger than that of fasudil, a protein kinase inhibitor. In contrast, in femoral artery, HNS-32 failed to suppress the tension development in response to PDBu whereas fasudil inhibited it with a similar potency as in basilar artery. These findings indicate that HNS-32 selectively suppresses cerebral artery contraction mediated via an activation of protein kinase C.
Animals↗
Correlation of glutamate-induced apoptosis with caspase activities in cultured rat cerebral cortical neurons.
In cultured rat cortical neurons lactate dehydrogenase (LDH) activity in the medium, a cell-death marker, increased gradually after exposure to glutamate (100 microM to 1 mM) for 60 min and reached a plateau at 24 to 30 h. Neuronal death was mainly apoptotic as suggested by typical electron microscopic findings, fluorescent double staining with membrane-permeating and nonpermeating chromatin dyes, nick end labeling, and assessment of DNA fragmentation by agarose gel electrophoresis. After 1 mM glutamate exposure, a rise of interleukin-1beta converting enzyme (ICE)-like protease activity in neurons was parallel to cysteine protease p32 (CPP32)-like protease activity and declined before CPP32-like protease activity reached the peak (at 6 h). LDH activity in the medium of glutamate-exposed neurons was decreased by specific ICE and/or CPP32 inhibitors, acetyl-L-tyrosyl-L-valyl-L-alanyl-L-aspart-1-al (Ac-YVAD-CHO) and acetyl-L-aspartyl-L-glutamyl-L-valyl-L-aspart-1-al (Ac-DEVD-CHO), respectively, in a dose-dependent manner. Fluorescent double staining of nuclei also demonstrated that at 100 microM each inhibitor prevented neuronal apoptosis and that this effect was additive. Among agonists corresponding to various glutamate receptor subtypes, N-methyl-D-aspartate (NMDA) and kainate induced apoptosis in cortical neuronal cultures while alpha-amino-3-hydroxy-5-methylisoxazole-4-propinate (AMPA) did not. The metabotropic glutamate receptor agonist, 1-aminocyclopentane-1S, 3R-dicarboxylate (ACPD) prevented apoptosis. Interestingly, apoptosis at 24 h after agonist or antagonist exposure correlated closely with caspase activity 6 h after exposure.
Animals↗
Tissue inhibitor of matrix metalloproteinase-1 in the plasma of patients with gastric carcinoma. A possible marker for serosal invasion and metastasis.
BACKGROUND: Expression of the tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in tumor tissue from patients with gastric carcinoma has been reported to be related to disease progression. However, to the authors' knowledge the clinical significance of plasma TIMP-1 concentrations in these patients has not been clarified. METHODS: Concentrations of TIMP-1 protein were examined by enzyme-linked immunoadsorbent assay in plasma samples from 149 patients who underwent resection of their primary tumors and from 18 patients with nonresected or recurrent disease. RESULTS: In the 149 patients whose primary tumors were resected, plasma TIMP-1 concentration was associated significantly with a variety of pathologic factors including macroscopic type, depth of invasion, lymph node and peritoneal metastases, vessel invasion, pattern of tumor infiltration into surround ing tissue, and disease stage. Plasma TIMP-1 concentration was significantly higher in patients with serosal invasion, lymph node metastasis, peritoneal dissemination, or liver metastasis than in those without these factors. Neither carcinoembryonic antigen (CEA) nor CA 19-9 concentrations appeared to be related to these measures of disease progression. In the 18 patients with nonresected or recurrent disease, TIMP-1, CEA, and CA 19-9 were similarly sensitive in predicting peritoneal, liver, and lymph node metastases. The combination of these three factors was able to detect 73.3% of patients with peritoneal metastasis, 83.3% of patients with liver metastasis, and 88.9% of patients with disease recurrence. CONCLUSIONS: In patients with gastric carcinoma, plasma concentration of TIMP-1 appears to correlate with both serosal invasion and metastasis.
CA-19-9 Antigen↗
Characterization of the Ca2+-dependent binding of annexin IV to surfactant protein A.
We have shown previously that surfactant protein A (SP-A) binds to annexin IV in a Ca2+-dependent manner [Sohma, Matsushima, Watanabe, Hattori, Kuroki and Akino (1995) Biochem. J. 312, 175-181]. Annexin IV is a member of the annexin family having four consensus repeats of about 70 amino acids and a unique N-terminal tail. In the present study, the functional site of both annexin IV and SP-A for the Ca2+-dependent binding was investigated using mutant proteins. SP-A bound in a Ca2+-dependent manner to an annexin-IV truncation mutant consisting of the N-terminal domain and the first three domains (T(N-1-2-3)). SP-A also bound to T3-4, but this interaction was not Ca2+-dependent. SP-A bound weakly to the other truncation mutants (T(N-1-2), T(2-3) and T(2-3-4)). Each consensus repeat of annexin IV possesses a conserved acidic amino acid residue (Glu70, Asp142, Glu226 and Asp301) that putatively ligates Ca2+. Using annexin-IV DE mutants in which one, two or three residues out of the four Asp/Glu were altered to Ala by site-directed mutagenesis [Nelson and Creutz (1995) Biochemistry 34, 3121-3132], it was revealed that Ca2+ binding in the third domain is more important than in the other Ca2+-binding sites. SP-A is a member of the animal lectin group homologous with mannose-binding protein A. The substitution of Arg197 of rat SP-A with Asp or Asn eliminated binding to annexin IV, whereas the substitution of Glu195 with Gln was silent. These results suggest that the Ca2+ binding to domain 3 of annexin IV is required for the Ca2+-dependent binding by SP-A and that Arg197 of SP-A is important in this binding.
Animals↗
Introduction of mannose binding protein-type phosphatidylinositol recognition into pulmonary surfactant protein A.
Pulmonary surfactant protein A (SP-A) and mannose-binding protein A (MBP-A) are collectins in the C-type lectin superfamily. These collectins exhibit unique lipid binding properties. SP-A binds to dipalmitoyl phosphatidylcholine (DPPC) and galactosylceramide (GalCer) and MBP-A binds to phosphatidylinositol (PI). SP-A also interacts with alveolar type II cells. Monoclonal antibodies (mAbs PE10 and PC6) that recognize human SP-A inhibit the interactions of SP-A with lipids and alveolar type II cells. We mapped the epitopes for anti-human SP-A mAbs by a phage display peptide library. Phage selected by mAbs displayed the consensus peptide sequences that are nearly identical to 184TPVNYTNWYRG194 of human SP-A. The synthetic peptide GTPVNYTNWYRG completely blocked the binding of mAbs to human SP-A. Chimeric proteins were generated in which the rat SP-A region Thr174-Gly194 or the human SP-A region Ser174-Gly194 was replaced with the MBP-A region Thr164-Asp184 (rat ama4 or hu ama4, respectively). The mAbs failed to bind hu ama4. Rat ama4 bound to an affinity matrix on mannose-sepharose but lost all of the SP-A functions except carbohydrate binding and Ca2+-independent GalCer binding. Strikingly, the rat ama4 chimera acquired the PI binding property that MBP-A exhibits. This study demonstrates that the amino acid residues 174-194 of SP-A and the corresponding region of MBP-A are critical for SP-A-type II cell interaction and Ca2+-dependent lipid binding of collectins.
Animals↗
Microtubule dysfunction induced by paclitaxel initiates apoptosis through both c-Jun N-terminal kinase (JNK)-dependent and -independent pathways in ovarian cancer cells.
The antineoplastic agent paclitaxel (TaxolTM), a microtubule stabilizing agent, is known to arrest cells at the G2/M phase of the cell cycle and induce apoptosis. We and others have recently demonstrated that paclitaxel also activates the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) signal transduction pathway in various human cell types, however, no clear role has been established for JNK/SAPK in paclitaxel-induced apoptosis. To further examine the role of JNK/SAPK signaling cascades in apoptosis resulting from microtubular dysfunction induced by paclitaxel, we have coexpressed dominant negative (dn) mutants of signaling proteins of the JNK/SAPK pathway (Ras, ASK1, Rac, JNKK, and JNK) in human ovarian cancer cells with a selectable marker to analyze the apoptotic characteristics of cells expressing dn vectors following exposure to paclitaxel. Expression of these dn signaling proteins had no effect on Bcl-2 phosphorylation, yet inhibited apoptotic changes induced by paclitaxel up to 16 h after treatment. Coexpression of these dn signaling proteins had no protective effect after 48 h of paclitaxel treatment. Our data indicate that: (i) activated JNK/SAPK acts upstream of membrane changes and caspase-3 activation in paclitaxel-initiated apoptotic pathways, independently of cell cycle stage, (ii) activated JNK/SAPK is not responsible for paclitaxel-induced phosphorylation of Bcl-2, and (iii) apoptosis resulting from microtubule damage may comprise multiple mechanisms, including a JNK/SAPK-dependent early phase and a JNK/SAPK-independent late phase.
Antineoplastic Agents, Phytogenic↗
Toxicity study of a rubber antioxidant, mixture of 2-mercaptomethylbenzimidazoles, by repeated oral administration to rats.
2-Mercaptobenzimidazole (2-MBI), a rubber antioxidant, is known to exhibit potent antithyroid toxicity in rats and is a candidate as an environmental endocrine disrupter. 2-Mercaptomethylbenzimidazoles (a 1:1 mixture of 4-methyl and 5-methyl isomers, MMBIs), are also employed industrially as rubber antioxidants and are suspected to exert antithyroid toxicity such as 2-MBI. In this investigation, acute and subacute oral toxicity studies of MMBIs in Wistar rats were conducted. The clinical signs of acute oral toxicity were observed including decreased spontaneous movement, a paralytic gait, salivation and lacrimation, and adoption of prone and lateral positions. The LD50 was estimated to be 330 mg/kg. In the subacute oral toxicity study, male and female rats were treated with MMBIs by gavage at doses of 0 (corn oil), 4, 20 and 100 mg/kg for 28 consecutive days followed by a 2-week recovery period for the control and highest dose groups. Body weight and food consumption, clinical signs, organ weights, clinical biochemistry and haematological parameters including clotting times and micronuclei induction in bone marrow erythropoeitic cells, and histopathology were examined. Relative organ weights of lung, liver and kidney, and serum cholesterol and phospholipid significantly increased in male rats treated with MMBIs at doses of 20 and 100 mg/kg. Male rats administered 100 mg/kg MMBIs exhibited a 1.8-fold increase in thyroid weight associated with histopathological changes but not altered serum thyroid hormone levels. Female rats administered 100 mg MMBIs/kg exhibited significant increases of liver and kidney but not thyroid weights, and serum cholesterol level. The antithyroid toxicity of MMBIs in rats was estimated to be one-tenth that of 2-MBI. No-observed-effect levels for male and female rats were found to be 4 and 20 mg/kg, respectively, in this subacute oral toxicity study.
Animals↗
Magnetic resonance imaging of experimentally-induced sialadenitis in rat submandibular glands.
OBJECTIVES: To correlate the features of magnetic resonance (MR) images of experimentally induced obstructive sialadenitis in rat submandibular glands with the histopathological changes. METHODS: Changes in MR images of ligated and non-ligated rat submandibular glands were compared with the histopathological changes and wet weight ratios. Spin echo T1 weighted images (SE T1WI), fast spin echo T2 weighted images (FSE T2WI), and gradient echo T2 weighted images (GE T2WI) were obtained at 1, 2, 3, 4, 5, 7 and 21 days after duct ligation with a 0.3 T MR imaging system. RESULTS: There was a significant difference (P<0.05) between the signal intensity ratios of both ligated and non-ligated glands on each day, except at 21 days on GE T2WI. On SE T1WI, small interval changes of signal intensity ratios were observed on both glands, whereas there were large interval changes at 1 - 2 days, 4 - 7 days and 21 days after duct ligation with FSE T2WI. These three periods correlated highly with three phases of histopathological changes, swelling of acinar cells at 1 - 2 days, atrophy of acinar cells and increase of duct-like structures at 3 - 7 days, and proliferation of connective tissue at 21 days, and the changes in wet weight ratios. A similar tendency was observed on GE T2WI to FSE T2WI. CONCLUSIONS: As FSE T2WI showed large changes in signal intensity that correlated highly with histopathological three phases, it is recommended as the MR sequence of choice for diagnosing the degree of damage in obstructive sialadenitis.
Animals↗
New technique of leukocytapheresis by the use of nonwoven polyester fiber filter for inflammatory bowel disease.
Leukocytapheresis (LCAP) is widely used for the treatment of immunological diseases. We studied a new treatment of LCAP using a nonwoven polyester fiber filter. In a basic study, 30-70% of leukocytes were removed. Also, 30-68% of the leukocyte subsets were removed. Sixteen inflammatory bowel disease (IBD) patients, mainly with ulcerative colitis (UC), were treated by this method. Their cytokine activity was normalized in the filter and in the peripheral blood. Eleven of 12 patients with UC were induced to remission. Four patients with Crohn's disease (CD) exhibited improvement. The LCAP using a nonwoven polyester fiber filter was very efficient for treating the patients with IBD. Also, it will be a very useful treatment for immunological diseases and extracorporeal immunomodulation.
Adult↗
The location of positive nodes partly influences the prognostic value of the number of positive nodes in breast cancer patients.
BACKGROUND: The aim was to determine whether the number of positive lymph nodes or the location of lymph node metastasis (location number) would permit a more accurate prediction of prognoses. METHODS: We compared the survival rates of 3922 patients with primary breast cancer in relation to the location number and the number of positive lymph nodes. Survival rates were calculated by the Kaplan-Meier method and analyzed using the log rank test. RESULTS: Within the n1 alpha group, the presence of one or two positive nodes was associated with significantly better survival than the presence of three positive nodes. These groups should therefore be distinguished. Within the n1 beta group, there was no significant difference in survival between patients with four and those with seven or more positive nodes. Comparisons of n1 beta and n2 patients after subgrouping by the number of positive nodes (4-9 and 10 or more) revealed a significantly poorer prognosis in the n2 group. CONCLUSIONS: When the prognosis of breast cancer is considered from the viewpoint of lymph node metastasis, the location number as described in the General Rules is an excellent classification. However, we should be aware of possible differences in the prognosis depending on the number of positive nodes, as this is masked by the location number.
Adult↗
Autosomal dominant muscle cramp syndrome in a Japanese family.
OBJECTIVES: To identify the clinical, electrophysiological, histological, and genetic characteristics of a Japanese family with a muscle cramp syndrome. METHODS: Fourteen patients (eight men, six women) were studied in four generations of a single family. Electrophysiological examinations were performed in four cases and muscle and nerve biopsies were performed on the propositus. RESULTS: The mode of inheritance seemed to be autosomal dominant. The cramps occurred during both exertion and at rest, and during sleep. Electromyographic examination indicated a neurogenic aetiology. There was a decreased number of large myelinated fibres in the sural nerve, and fibre type grouping in the quadriceps femoris muscle biopsy. CONCLUSIONS: The autosomal dominant muscle cramp syndrome in this family is probably caused by a polyneuropathy.
Aged↗
Characterization of a phosphorylation event resulting in upregulation of the salivary Na(+)-K(+)-2Cl(-) cotransporter.
Previous studies from our laboratory have shown a close correlation between increased Na(+)-K(+)-2Cl(-) cotransporter activity and increased cotransporter phosphorylation after beta-adrenergic stimulation of rat parotid acinar cells. We demonstrate here that these effects are paralleled by an increase in the number of high-affinity binding sites for the cotransporter inhibitor bumetanide in membranes prepared from stimulated acini. We also show that the sensitivity of cotransporter fluxes to inhibition by bumetanide is the same in both resting and isoproterenol-stimulated cells, consistent with the hypothesis that beta-adrenergic stimulation and the accompanying phosphorylation result in the activation of previously quiescent transporters rather than in a change in the properties of already active proteins. In addition, we demonstrate that the increased phosphorylation on the cotransporter resulting from beta-adrenergic stimulation is localized to a 30-kDa phosphopeptide obtained by cyanogen bromide digestion. Immunoprecipitation and Western blotting experiments demonstrate that this peptide is derived from the NH(2)-terminal cytosolic tail of the cotransporter, which surprisingly does not contain the sole protein kinase A consensus site on the molecule.
Adrenergic beta-Agonists↗
Biological roles of angiotensin II via its type 2 receptor during rat follicle atresia.
Type 1 angiotensin II (ANG II) receptors play crucial roles in the regulation of blood pressure and fluid osmolarity, whereas the physiological roles of type 2 ANG II receptors (AT2) remain unclear. Because AT2 is expressed in atretic follicles where granulosa cells undergo apoptosis, we examined the space and time relationship between AT2 expression and follicle atresia in vivo and the effect of AT2 on follicle-stimulating hormone (FSH) actions in vitro. Binding studies, autoradiography, and RT-PCR of AT2 revealed that the AT2 content in granulosa cells was time dependently increased at both protein and mRNA levels in equine chorionic gonadotropin-treated immature female rats. This increase paralleled the progression of atresia. ANG II suppressed FSH-caused prevention of DNA fragmentation, increases in luteinizing hormone receptor content, and estrogen production through AT2 in cultured granulosa cells. Moreover, FSH-induced stimulation of extracellular signal-regulated kinase activity, critical for cell survival, was inhibited by AT2 stimulation. These results suggest that AT2 mediates the progression of follicle atresia through granulosa cell apoptosis by inhibiting FSH actions.
Angiotensin II↗
Is the growth of brown adipocytes necessary for cold acclimation in mice?
Chronic exposure to cold increases the growth of brown adipose tissue and the resistance to more severe cold, thus improving thermogenesis. The present study examined the possibility that dietary compounds can modify cold acclimation. Adenosine (ADO) or adenine (ADE) were administered in drinking water (0.05%, w/v) for 5 weeks to male ddY strain mice from 4 weeks of age. At 5 weeks of age, the mice were exposed to 4 degrees C for 4 weeks. After termination of this period, the interscapular brown adipose tissue (IBAT) and rectal temperature on acute exposure to severe cold (-20 degrees C) for 60 min were measured. Chronic exposure to cold increased the weight of IBAT and made mice resistant to a fall in rectal temperature on exposure to severe cold. The growth of IBAT and improvement in thermogenesis can be used as a cold acclimation profile in ddY mice. The growth of IBAT was selectively prevented by ingestion of ADO. The improvement in thermogenesis was reduced, but only a little, by the ingestion of either ADO or ADE. Thus, growth of brown adipocytes might not be necessary for cold acclimation in mice.
Acclimatization↗
Pineoblastoma showing unusual ventricular extension in a young adult--case report.
A 19-year-old male presented with a 4-week history of headache. Neurological examination showed bilateral papilledema. Computed tomography revealed a pineal region mass with remarkable obstructive hydrocephalus. Magnetic resonance imaging showed a pineal region tumor continuously invading through the tectum into the cerebral aqueduct and the fourth ventricle with the preservation of the adjacent structures. The tumor appeared an iso- to hypointense mass on T1-weighted images, a heterogeneous iso- to hyperintense mass on T2-weighted images, and a heterogeneously enhanced mass after administration of contrast medium. Histological examination after endoscopic biopsy confirmed that the tumor was a pineoblastoma. Radiotherapy was given to the whole brain and the spinal cord, and magnetic resonance imaging showed complete remission of the tumor. Pineoblastomas are highly malignant tumors with seeding potential through the neighboring ventricle or along the meninges, and this type of tumor becomes larger with local extension. We found no previous reports of the continuous extension into the fourth ventricle. The present case showed ventricular extension with minimal mass effect to adjacent structures, and did not disturb ventricular configuration. According to the unusual finding of ventricular extension, this rare case of pineoblastoma requires adjuvant chemotherapy.
Adult↗
[Atypical chronic myeloid leukemia presenting with trilineage dysplasia and IgG (lambda) type monoclonal gammopathy].
A 78-year-old man was diagnosed as leukocytosis in February 1994. Physical examination revealed marked hepatosplenomegaly. A peripheral blood examination disclosed 95,090/microliter leukocytes without hiatus leukemicus, 6.5 g/dl Hb, and 15.0 x 10(4)/microliter platelets. The neutrophil alkaline phosphatase score was 27, and serum VB12 was above 1,600pg/ml. IgG was identified as monoclonal immunoglobulin of type lambda. Bone marrow specimens demonstrated marked granulocytic hyperplasia. Neither the Philadelphia chromosome (Ph1) nor BCR gene rearrangement was detected; hence, the diagnosis of Ph1 (-) chronic myeloid leukemia (CML) was made. The patient was treated with hydroxyurea and low-dose VP-16 with no improvement, and died of pneumonia and sepsis in June 1995. This case was considered to be consistent with atypical CML (aCML) according to the FAB classification because monocytosis was not observed. It seems likely and interesting that the coexistent monoclonal gammopathy and aCML might have arisen from common abnormal hematopoietic stem cells.
Aged↗
Frigen II improves the reliability of measurement of interleukin-1 related substances in amniotic fluid.
BACKGROUND: To investigate the role of interleukin-1 related substances in amniotic fluid in normal term labor without intrauterine infection. METHODS: Amniotic fluid samples were collected from forty-one patients with various backgrounds. A novel pre-assay treatment using Frigen II was introduced to improve the recovery rates of cytokines, i.e., interleukin-1alpha, interleukin-1beta and interleukin-1 receptor antagonist, prior to ELISA assay. Urine samples from newborn infants were also tested. RESULTS: The concentrations of interleukin-1alpha, interleukin-1beta and interleukin-1ra were significantly higher in samples from normal vaginal delivery. The higher levels of interleukin-1alpha were also observed in samples from preterm labor without infection. Preterm infants produced more of interleukin-1 receptor antagonist in urine compared with term infants. CONCLUSIONS: This study provides evidence of the possible involvement of interleukin-1 related substances in labor without signs of infection. The data from newborn urine suggests that amniotic interleukin-1ra originates from the fetus. However, amniotic fluid interleukin-1alpha and interleukin-1beta may be derived from maternal tissue, such as decidua.
Amniotic Fluid↗