Biomedical subjects
Publications and source records attributed to T Doi.
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A 63-year-old woman underwent modified radical mastectomy with 3 cycles of adjuvant chemotherapy (cyclophosphamide, epirubicin, 5-fluorouracil) and MPA endocrine therapy for breast cancer. Because of nausea and general fatigue, she refused to continue this therapy and did not visit the hospital. When she came our hospital and 16 months later, she had developed multiple bone metastases. At the same time, she was suffering from lung tuberculosis. She was treated with toremifene at a dose of 120 mg/day without any side effects. After 3 months administration of toremifene, pain disappeared and her high serum CA15-3 and BCA225 dropped to within the normal range. On bone scintigrams, abnormal accumulation almost disappeared after 9 months of administration of toremifene. In this case, the patient was suffering from lung tuberculosis and did not desire intensive chemotherapy. Administration of high-dose toremifene was effective for multiple bone metastases without any side effects.
A 61-year-old man was admitted to our hospital in December 1994 for a suspected retroperitoneal tumor. Systemic imaging investigations demonstrated retroperitoneal solid tumor, which was diagnosed as malignant fibrous histiocytoma (MFH) by immunohistochemistry for alpha 1-antitrypsin. In March 1995, he was treated with 3 courses of systemic chemotherapy with cisplatin, ifosfamide and doxorubicin followed by the same therapy in March 1996, without serious side effects. MFH is known to be resistant to ordinary chemotherapy. However, the CT showed a marked decrease in the size of the tumor, and the tumor disappeared within 2 months after the first treatment. The patient also recovered rapidly from abdominal pain, for which complete remission has been achieved for more than 5 years. The present chemotherapy may be an effective treatment for retroperitoneal MFH.
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Thirty-one patients with advanced pancreatic carcinoma and liver metastases were treated by hepatic and splenic arterial infusion chemotherapy after transcatheter peripancreatic arterial embolization. The response rate for these 31 patients was 61.3%, with a mean survival period of 17.8 +/- 3.2 months and a 50% survival period of 12 months. By site of the primary tumor, the response rate for pancreatic head and body carcinoma was 81%, with a mean survival period of 21.6 +/- 4.0 months and a 50% survival period of 17 months, whereas the response rate for pancreatic caudal carcinoma was 20%, with a mean survival period of 6.1 +/- 0.5 months and a 50% survival period of 6 months. We believe that the current chemotherapy is an effective treatment for advanced pancreatic cancer with liver metastases.
Dual chambers ports were implanted in 7 patients with advanced pancreatic carcinoma and metastatic liver tumors to connect a 3.3 Fr catheter as an indwelling catheter. In comparison with the implantation of a pair of Single chamber ports, implanting a Dual chambers port entails some technical difficulties, but has some benefits in terms of stabler placement, a smaller incision, reduction of medical fees, and improved QOL of patients.
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BACKGROUND: Connective tissue growth factor (CTGF) predominantly is expressed in hypertrophic chondrocytes and its specific receptors are demonstrated on chondrocytic cells. Therefore, CTGF may be involved in the proliferation and/or differentiation of cartilage cells. In the current study, CTGF expression was examined both in chondrosarcoma and enchondroma to clarify the relation between the expression of CTGF and the grade of malignancy. METHODS: The expression of CTGF and proliferating cell nuclear antigen (PCNA) were analyzed immunohistochemically in 34 cartilaginous tumor specimens. Eighteen tumors were determined to be chondrosarcoma including 8 Grade 1 tumors, 6 Grade 2 tumors, and 4 Grade 3 tumors. The percentage of CTGF positive and PCNA positive cells was quantified using at least 500 cells. RESULTS: CTGF was expressed in 70.1% of enchondroma cells, 84.0% of Grade 1 chondrosarcoma cells, 53.7% of Grade 2 tumor cells, and 26.8% of Grade 3 tumor cells (rho = -0.501; P = 0.0053). In chondrosarcoma cases, CTGF expression was correlated closely with tumor grade (rho = -0.920; P = 0.0001). There was a strong correlation between PCNA expression and tumor grade (rho = 0.907; P < 0.0001) and a strong negative correlation between CTGF and PCNA expression (rho = -0.493; P = 0.0061). In chondrosarcoma cases, patients with high expression of CTGF (>/= 30%) showed higher overall survival compared with those with low expression (< 30%) (P = 0.004). CONCLUSIONS: The current study revealed a correlation between the histologic grade of chondrosarcoma and prognosis, and the concomitant association between CTGF immunostaining and tumor grade and prognosis. Therefore, immunohistochemical staining with CTGF is a useful procedure for assessing the tumor grade and clinical course in patients with chondrosarcoma.
We used optical imaging to investigate the mouse cochlear and vestibular nucleus in brainstem slices using a voltage-sensitive dye, RH 155. As a result, the spatiotemporal patterns of excitatory propagation were shown. These optical signals consisted of two components consisting of a spike-like fast signal and a long-lasting slow signal. All responses were abolished by tetrodotoxin. The slow signals were eliminated under a Ca(2+)-free solution. In addition, synaptic fatigue was also observed. The present study indicated the feasibility of optical recording for visually revealing the synaptic transmission in both the vestibular and cochlear nucleus.
TAK-637((aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10, 11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g] [1,7]naphthyridine-6,13-dione) is a novel tachykinin NK(1) receptor antagonist that has been shown to inhibit the micturition reflex in guinea pigs. The aim of this study was to clarify its mechanism of action in guinea pigs. TAK-637 inhibited the spinal vesico-vesical reflex induced by electrical stimulation of the proximal cut end of the pelvic nerve in spinal animals, but not bladder contractions induced by electrical stimulation of the distal cut end of the nerve. Furthermore, TAK-637 had no effect on carbachol- or electrical field stimulation-induced contractions of isolated bladder muscle strips in an organ bath, whereas drugs used for abnormally frequent micturition inhibited both contractions. These results suggest that TAK-637 inhibits the micturition reflex by acting, at least in part, on the spinal cord, and its mechanism of action clearly differs from those of antimuscarinics or spasmolytics.
BACKGROUND: Patients with American Joint Committee on Cancer Stage IV advanced pancreatic carcinoma have been treated by systemic chemotherapy, intraarterial chemotherapy, radiation therapy, and multidisciplinary treatment using a combination of these. However, the outcome has not always been satisfactory. In the current study the authors describe the method and results of a new chemotherapy for advanced pancreatic carcinoma. METHODS: To restrict the blood flow into the pancreas (mainly to the great pancreatic artery and the caudal pancreatic artery), the peripancreatic blood vessels were embolized superselectively with microcoils. In 31 patients with advanced pancreatic carcinoma, the catheter tip for the arterial infusion chemotherapy was placed in the splenic artery just proximal to the branching of the great pancreatic artery when the treatment was given for primary tumors, and in the common hepatic artery when the treatment was given for a metastatic liver lesion. The other end of the catheter was connected to an implanted injection port embedded in the femoral region, and 5-fluorouracil and cisplatin were administered by continuous arterial infusion. RESULTS: Of the 31 patients with advanced pancreatic carcinoma, 23 (74%) underwent hemodynamic change and arterial infusion chemotherapy, with a response rate of 73.9% (complete response rate of 8.7% and a partial response rate of 65.2%) and a mean survival period of 18.26 +/- 10.06 months. The 1-year, 2-year, and 3-year survival rates were 90.9%, 42. 8%, and 18.3%, respectively, with a mean survival period of 19.0 months. Of these 23 patients, the 16 patients with liver metastases had a response rate of 68.8% and a mean survival period of 16.25 +/- 8.35 months, whereas the 7 patients without liver metastases had a response rate of 87.5% and a mean survival period of 22.86 +/- 12.69 months. CONCLUSIONS: In patients with Stage IV advanced pancreatic carcinoma, arterial infusion chemotherapy after hemodynamic change was found to be effective against both primary tumors and metastatic liver lesions. The authors believe that the treatment presented in the current study should be attempted, even in patients with advanced pancreatic carcinoma, as long as the blood vessels for vascular supply distribution exist.
A novel inhibitor for the adhesion of monocytes to cytokine-stimulated endothelial cells, K-7174, was selected by an assay system using the cultured human monocytic cells and human endothelial cells. K-7174 inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1) induced by either tumor necrosis factor alpha or interleukin-1beta, without affecting the induction of intercellular adhesion molecule-1 or E-selectin. K-7174 had no effect on the stability of VCAM-1 mRNA. Electrophoretic mobility shift assay revealed that its inhibitory effect on VCAM-1 induction was mediated by an effect on the binding to the GATA motifs in the VCAM-1 gene promoter region. K-7174 did not influence the binding to any of the following binding motifs: octamer binding protein, AP-1, SP-1, ets, NFkappaB, or interferon regulatory factor. These results suggest that the regulation of GATA binding may become a new target for anti-inflammatory drug development, acting through a mechanism independent from NFkappaB activity.
The effects of a new tachykinin NK(1) receptor antagonist, (aR, 9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10, 11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g] [1, 7]naphthyridine-6,13-dione (TAK-637), on the micturition reflex were compared with those of drugs used for abnormally frequent micturition or incontinence. TAK-637 showed a characteristic effect on the distension-induced rhythmic bladder contractions in guinea pigs. The systemic administration of TAK-637 decreased the number but not the amplitude of the distension-induced rhythmic bladder contractions. A similar effect was observed in animals in which the spinal cord had been severed. TAK-637 also inhibited the micturition reflex induced by topical application of capsaicin onto the surface of bladder dome. From these results, it is concluded that TAK-637 inhibits sensory transmissions from the bladder evoked by both physiological and nociceptive stimuli by blocking tachykinin NK(1) receptors, possibly at the level of the spinal cord. On the other hand, the other drugs such as oxybutynin, tolterodine, propiverine, and inaperisone showed no effects on the frequency of the distension-induced rhythmic bladder contractions but decreased the contraction amplitude. Therefore, TAK-637 may represent a new class of drugs, which would be effective for abnormally frequent micturition without causing voiding difficulties due to decreased voiding pressure.
The mutation of W276 to cysteine within the human endothelin receptor subtype B (ET(B)R) is associated with Hirschsprung's disease, a congenital intestinal disease. The sequence surrounding W276 is highly conserved between the endothelin receptor subtypes A and B. We have introduced sets of mutations into W275 and W276 of the ET(B)R gene, and the corresponding W257 and W258 of the ET(A)R gene, and studied their coupling properties with G(i), G(o), and G(q) in reconstituted phospholipid vesicles. The prepared mutants all showed a similar affinity for endothelin-1. The W276C/ET(B)R and W276A/ET(B)R mutants had reduced activities in G(q) coupling but not in G(i)/G(o) coupling, while the W275A/ET(B)R displayed reduced activities in G(i)/G(q) coupling, with normal G(o) coupling. On the other hand, W257A/ET(A)R and W258A/ET(A)R exhibited wild-type activities in all examined G protein couplings. These results suggest that the defects in the G(q) signaling pathway by the ET(B)R are connected with Hirschsprung's disease and that the two conserved tryptophans play distinct roles in signal transduction by the two receptor subtypes. In addition, W275 and W276, which are thought to be located near the extracellular side of the transmembrane helix 5, play important roles in forming the active structure of ET(B)R.
Severe head injury in humans can cause recurrent seizures; this form of epilepsy appears to correlate with the occurrence of parenchymal hemorrhage. The injection of ferric cations, one component of hemoglobin, into rat amygdala, causes lipid peroxidation, and recurrent spontaneous seizures. We wondered whether the regulation of glutamate might be perturbed as a result of severe head injury, which might then act as a mechanism of chronic epileptogenesis. Levels of glutamate transporter glutamate-aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), and excitatory amino-acid carrier (EAAC-1) mRNA were measured in ipsilateral and contralateral hippocampi and cerebral cortex removed from rats at 60 min, 24 h, and 5, 15 and 30 days after FeCl(3) injection into the amygdaloid body. While the neuronal transporter EAAC-1 mRNA was elevated bilaterally for up to 30 days following the microinjection that initiated seizures, GLT-1 mRNA, derived from glial cells, returned to basal levels. At 15 and 30 days after injection, however, when the experimental animals were experiencing spontaneous limbic behavioral seizures, GLAST mRNA was down-regulated. Epileptogenesis may correlate with the impairment of glial glutamate transport, leading to an excitation and imbalance of transmitter influences within the hippocampi and cerebral cortex.
Spontaneous dehiscence of the aortic wall at the aortic commissure is not recognized as one of the usual pathological causes of aortic regurgitation. We describe the case of a 56-year-old man with hypertension, who experienced acutely progressive congestive heart failure due to massive aortic regurgitation. Local layer dehiscence around the commissure was noted with partial detachment of the commissure resulting in the loss of commissural support with secondary rupture of a non-coronary cusp, which led to massive aortic regurgitation.
UNLABELLED: We investigated the clinical and biochemical characteristics of a 6-year-old Japanese boy with very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. He had hypoketotic hypoglycaemia, exercise- and fasting-induced lethargy, hepatomegaly and cardiomegaly. Significant laboratory findings included elevated plasma levels of creatine phosphokinase and acyl-carnitine and a fatty liver at biopsy suggesting a diagnosis of VLCAD deficiency. CONCLUSION: The diagnosis of very long-chain acyl-CoA dehydrogenase deficiency was supported by the results of acyl-CoA dehydrogenase activity for C8 and C16 fatty acids in skin fibroblasts from the patient. Treatment with medium chain triglycerides and L-carnitine in the diet improved his hepatomegaly and cardiomegaly.