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Biomedical subjects

T Kubota

Publications and source records attributed to T Kubota.

At least 235 records · Page 13Linked to original sources

[The validity of the sentinel node concept in gastrointestinal cancers].

Although the sentinel node concept has been validated and clinically applied to breast cancer and malignant melanoma, its clinical significance in other solid tumors has not been thoroughly investigated. With regard to gastrointestinal (GI) cancers in particular, our surgeons have been cautious because of the high frequency of skip metastasis and the complicated lymphatic system in the GI tract. We would like to emphasize that so-called skip metastasis has been defined according to anatomic classification of regional lymph nodes and that the lymphatic drainage route must be patient or lesion specific. To test the validity and feasibility of this concept in GI cancers, we have established a radio-guided intraoperative sentinel node navigation system using preoperative endoscopic submucosal injection of radioactive tracer followed by intra-operative gamma-probing. In 131 patients with GI cancers (esophagus: 22, stomach: 71, colorectum: 38), the detection rate of sentinel nades was 91% and overall diagnostic accuracy of lymph node metastasis by sentinel node status was 97%. Initial results suggest further investigation of this procedure as an accurate staging and a minimally invasive approach to early GI cancers.

Gastrointestinal Neoplasms↗

Laparoscopic wedge resection of gastric submucosal tumors.

Minimally invasive surgery has revolutionized the treatment of gastrointestinal tumors. Submucosal tumors (SMTs) of the stomach can be resected using laparoscopic techniques. Between 1993 and 1997, laparoscopic wedge resection was performed in 34 patients with an SMT of the stomach. The tumors ranged from 8 to 60 mm in diameter. All surgical margins were clear. The average operative time was 131 minutes. Most of the patients began eating on the first postoperative day and were discharged within 5 to 7 days. Histopathologic examination of the tumors showed gastrointestinal stromal tumor (n = 14), ectopic pancreas (n = 7), leiomyosarcoma (n = 4), schwannoma (n = 3), carcinoid (n = 2), leiomyoma (n = 2), an inflammatory lesion caused by parasites (n = 1), and cyst (n = 1). No recurrences were observed over the 5-year follow-up period. A solid SMT of the stomach larger than 20 mm in diameter can be treated using laparoscopic wedge resection.

Adult↗

[Acute surgical and endovascular therapy for stroke: especially patients with brain infarction].

From January 1994 to December 1997, 845 patients with stroke were admitted to Hakodate Municipal Hospital. They consisted of 514 patients with brain infarction, 206 with brain hemorrhage, 121 with subarachnoid hemorrhage and 4 with intracranial hemorrhage from arteriovenous malformation. The clinical categories of brain infarction were as follows; atherothrombotic recognized in 158 patients, cardioembolic in 114, lacunar in 217 and other categories in 25. With regard to the cures of brain infarction in the acute phase, direct percutaneous transluminal angioplasty (direct PTA) was carried out on three patients with atherothrombotic infarction, immediate PTA on two, superselective fibrinolytic therapy on two, and STA-MCA anastomosis on three. In all, ten atherothrombotic patients (6.3%) were treated by acute surgical or endovascular therapy. On the other hand, superselective fibrinolytic therapy was carried out on 35 patients (30.7%) with cardioembolic infarction. There were no patients in the lacunar infarction group who were given acute surgical treatment. Neurological improvement after 24 hours was recognized in 4 patients (40%) of 10 with atherothrombotic infarction, and in 9 patients (25.7%) of 35 with cardioembolic infarction. However, symptomatic intracerebral hematoma was recognized in 4 patients (11.4%) with cardioembolic infarction. Indication for acute surgical or endovascular treatment for brain infarction was very limited because of the time factor from the onset to admission. It is suggested that neurosurgeons might enlighten citizens about the necessity for acute surgical or endovascular therapy for stroke.

Angioplasty, Balloon, Coronary↗

[Sensitivity of UCN-01 lies in the balance of CDK 2 kinase and p21].

Five human cancer cell lines (MKN 45, HT-29, WiDr, PAN-3-JCK, and CRL 1420) were used to evaluate the antitumor spectrum of UCN-01, which suppressed the growth of these digestive cancer cell lines. A human pancreatic cancer xenograft (CRL 1420) and breast cancer xenograft (MX-1) were used to determine their sensitivity to UCN-01, in nude mice. UCN-01 significantly suppressed the tumor growth of CRL 1420 at a dose of 10 mg/kg in a schedule of (qd x 5) x 2, but was ineffective for MX-1. While p21 protein expression was induced by UCN-01 in both CRL 1420 and MX-1, an accumulation of dephosphorylated ppRb was observed only in CRL 1420, resulting in G1 block as detected by flow cytometric analysis. The CDK 2 activity of MX-1 was almost 6 times higher than that of CRL 1420, which might account for the resistance of MX-1 to UCN-01 in spite of the induction of p21 in this strain. We conclude that the determinant of sensitivity to UCN-01 lies in the balance of CDK 2 kinase activity and p21 protein induction.

Alkaloids↗

[Curative laparoscopic surgery for early gastric cancer: eight years experience].

We have applied two different laparoscopic surgical techniques for early gastric cancer and have successfully treated 111 patients since March 1992. The indications are: 1) preoperative diagnosis of mucosal cancer; 2) lesion size of < 25 mm if the protruding type; and 3) lesion size < 15 mm and UI (-) if the depressed type. The first technique is laparoscopic wedge resection of the stomach using a lesion-lifting method (n = 93). The gastric wall around the cancerous lesion is exposed laparoscopically. The abdominal wall and gastric wall in the vicinity of the lesion are pierced using a 12-G sheathed needle. A small metal rod with a fine wire is introduced into the stomach through the outer sheath. By retracting the metal rod, the lesion can be lifted precisely (i.e., lesion-lifting method). Wedge resection at a sufficient distance from the metal rod is carried out using an endoscopic stapler. The second technique is referred to as laparoscopic intragastric mucosal resection (n = 18). Three balloon trocars are placed in the stomach laparoscopically. The stomach is then insufflated with CO2, and surgical instruments are introduced. The mucosal and submucosal layers around the lesion are resected with sufficient surgical margins. The selection of the laparoscopic technique depends on the site of the cancerous lesion. In our series of 111 patients, sufficient horizontal (mean 15 +/- 5 mm and 8 +/- 4 mm, respectively, using the first and second technique) and vertical surgical margins were achieved. There was no mortality and no major complications in patients undergoing either surgical technique. There have been two recurrences, both mucosal lesions found 2 years after the initial surgery, which were successfully treated with gastrectomy and laser irradiation. All patients have survived for 3 to 96 months, and there has been no trocar site recurrence. In conclusion, these laparoscopic procedures are curative and minimally invasive treatments for early gastric cancer.

Gastric Mucosa↗

[Proteus syndrome].

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Diagnosis, Differential↗

[Recent advance in gastric cancer chemotherapy].

Because of the low chemosensitivity of gastric cancer to conventionally available agents, several approaches were investigated to design "order made" treatments using chemosensitivity tests, including the histoculture drug response assay (HDRA) which was useful in evaluating the appropriate cancer chemotherapy for the patients with Stage III/IV gastric cancer. A recent investigation using a molecular biological method was introduced to predict the sensitivity of gastric cancer specimens to 5-fluorouracil (5-FU) by dihydropyrimidine dehydrogenase (DPD) activity and its mRNA. The low activity of DPD and DPD mRNA resulted in the low sensitivity to 5-FU, although thymidylate synthetase activity was not related to the sensitivity to 5-FU. This method is promising, since a small amount of material obtained through gastrofiberscopy will be adequate to assess DPD mRNA to predict the sensitivity to 5-FU. On the other hand, some randomized control trials with a huge cohort have indicated the usefulness of a "docetaxel + cisplatin + 5-FU" regimen for advanced and recurrent gastric cancer, and "5-FU + LV + radiation" as an adjuvant therapy for advanced gastric cancer. Furthermore, the efficacy of adjuvant chemotherapy after curative resection for gastric cancer was warranted by a meta-analysis of 19 published randomized trials. The "order made" and "standard" therapies will be complementary in the further development of chemotherapy against gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[Common carotid artery dissection propagated from acute aortic dissection: a case successfully treated by PTA].

We reported a rare case, which was successfully treated by PTA, of right common carotid artery dissection propagated from acute aortic dissection (AAD) type A. A 45-year-old male with a past history of hypertension and an artificial graft replacement of the abdominal aorta due to AAD type B, 7 years ago, was brought into our hospital by ambulance 30 minutes after an attack of fainting and left hemiparesis. On admission, the patient complained not of chest pain or left hemiparesis, but nausea. At that time his consciousness level was JCS 1. During examinations, he had the same attack twice and his consciousness level deteriorated to JCS 2. Brain MRI showed no abnormality, but cervical MRA did not visualize the right carotid artery and thoracic CT depicted acute aortic dissection including branches of the aorta. Emergent angiography disclosed that the dissecting 99% stenosis of the right common carotid artery had developed from AAD type A with poor collateral blood flow. PTA was carried out 8 times and reduced the residual stenosis to about 50% with shortened circulation time. The patient's consciousness disturbance improved. After the replacement of the whole aortic arch in an artificial graft, the residual stenosis disappeared. The patient recovered without neurological deficit but right frontal silent embolic infarction caused by the artificial graft replacement was detected. AAD is a catastrophic illness and sometimes accompanied by devastating ischemic cerebral disease (ICD) because of propagation of dissecting to extracranial vessels. This is the first report that shows the efficacy of PTA for treatment of ICD associated with AAD.

Acute Disease↗

Haemodynamic comparison of propofol-fentanyl anaesthesia with midazolam-fentanyl anaesthesia in CABG patients without preoperative heart failure.

This study was designed to compare prebypass haemodynamics under total intravenous anaesthesia (TIVA) using midazolam-fentanyl (group M) and propofol-fentanyl (group P) combinations. Sixteen adult patients undergoing CABG were studied with patients in group M and P (n = 8 each) given intravenous midazolam 0.1 mg.kg-1.h-1 and propofol 4 mg.kg-1.h-1 with fentanyl 25 micrograms.kg-1 until sternotomy, respectively. Following induction of anaesthesia, cardiac index and heart rate decreased significantly (30% and 20% in both groups, p < 0.05) these variables returned to baseline on completion of sternotomy. In addition, in group P mean arterial pressure decreased significantly (about 15%) following induction and there were no ischaemic signs. Overall for MAP there was no significant difference between the two groups. LVSWI and RVSWI were reduced by around 25% in both groups. Only the change in LVSWI reached statistical significance (p < 0.05). This reduction may have exert a caridioprotectant action by decreasing myocardial oxygen consumption. We conclude that both TIVA techniques represent an acceptable anaesthetic regimen for use in cardiac anaesthesia.

Aged↗

Neonatal repair of anomalous origin of the right pulmonary artery from the ascending aorta. A case report and review in the literature.

A seven-day-old neonate presented with respiratory distress and an early diagnosis was achieved through the echocardiographic studies which successfully visualized an anomalous origin of the right pulmonary artery arising from the ascending aorta. Subsequently a surgical correction with direct anastomosis of the right pulmonary artery to the main pulmonary trunk was accomplished in the neonatal period. The English literature in the last two decades is reviewed to discuss the characteristics, the diagnosis and treatment of neonatal cases with anomalous origin of the right pulmonary artery arising from the ascending aorta.

Angiography↗

Börjeson-Forssman-Lehmann syndrome in a woman with skewed X-chromosome inactivation.

Börjeson-Forssman-Lehmann (BFL) syndrome is an X-linked recessive disorder characterized by minor facial anomalies, obesity, epilepsy, and severe mental retardation. The phenotype of male patients is usually severe, whereas that of carriers is less severe, suggesting X-linked incompletely recessive inheritance. A recent linkage study mapped the BFL syndrome gene to Xq26-q27. The etiology of the condition in female patients with full manifestations is not known, although nonrandom X-chromosome inactivation has been considered. We recently developed an assay for X-inactivation studies based on the methylation-specific polymerase chain reaction (PCR) technique. Using the methylation-specific PCR assay, a woman with typical findings of this syndrome was shown to have an extremely skewed X-inactivation pattern. This finding suggests that the full manifestations of the BFL syndrome in carriers may be caused by skewed X inactivation with a high proportion of cells in which the X chromosome with a normal gene be inactivated, leaving the X chromosome with a mutant gene active.

Adult↗

Characterization of an avian (Gallus gallus domesticus) TCR alpha delta gene locus.

Mammalian TCR delta genes are located in the midst of the TCR alpha gene locus. In the chicken, one large V delta gene family, two D delta gene segments, two J delta gene segments, and one C delta gene have been identified. The TCR delta genes were deleted on both alleles in alpha beta T cell lines, thereby indicating conservation of the combined TCR alpha delta locus in birds. V alpha and V delta gene segments were found to rearrange with one, both or neither of the D delta segments and either of the two J delta segments. Exonuclease activity, P-addition, and N-addition during VDJ delta rearrangement contributed to TCR delta repertoire diversification in the first embryonic wave of T cells. An unbiased V delta 1 repertoire was observed at all ages, but an acquired J delta 1 usage bias occurred in the TCR delta repertoire. The unrestricted combinatorial diversity of relatively complex TCR gamma and delta loci may contribute to the remarkable abundance of gamma delta T cells in this avian representative.

Amino Acid Sequence↗

Physostigmine antagonizes ketamine-induced noradrenaline release from the medial prefrontal cortex in rats.

Physostigmine is known to antagonize ketamine anesthesia. In this study, effects of physostigmine (0.1 mg kg(-1) i.p.) on ketamine (100 mg kg(-1) i.p.)-induced anesthesia time and noradrenaline release from the medial prefrontal cortex in rats were examined. Ketamine produced anesthesia for 27+/-1 min and increased noradrenaline release to 405% of the basal. Physostigmine significantly reduced anesthesia time to 23+/-1 min (p<0.05), and noradrenaline to 248% (p<0.05). Therefore, noradrenaline release may play an important role in ketamine anesthesia.

Anesthesia↗

5,6-trans-16-ene-vitamin D3: a new class of potent inhibitors of proliferation of prostate, breast, and myeloid leukemic cells.

The 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] is the physiologically active form of vitamin D3 that inhibits proliferation and induces differentiation of a variety of malignant cells. We evaluated a newly synthesized vitamin D3 analogue [1,25(OH)2-16-ene-5,6-trans-D3 (Ro 25-4020)] that has a novel 5,6-trans motif. Dose-response studies showed that 1,25(OH)2-16-ene-5,6-trans-D3 had 10-100-fold greater antiproliferative activities than 1,25(OH)2D3 when measuring clonal growth of breast (MCF-7) and prostate (LNCaP) cancer cell lines as well as a myeloid leukemia cell line (HL-60). Because the chief toxicity of vitamin D3 is hypercalcemia, we examined the calcemic activity of 1,25(OH)2-16-ene-5,6-trans-D3 in mice. Remarkably, 1,25(OH)2-16-ene-5,6-trans-D3 was at least 40-fold less calcemic as compared with 1,25(OH)2D3 and 1,25(OH)2-16-ene-D3 (Ro 24-2637). To explore the mechanism by which the 1,25(OH)2-16-ene-5,6-trans-D3 analogue mediated its antiproliferative activity, several studies were performed. Pulse-exposure studies showed that a 4-day pulse exposure to 1,25(OH)2-16-ene-5,6-trans-D3 (10(-7) M) in liquid culture was adequate to achieve a 40% inhibition of MCF-7 clonal growth in the absence of the analogue, suggesting that the growth inhibition mediated by 1,25(OH)2-16-ene-5,6-trans-D3 was at least in part irreversible. Cell cycle studies showed that 1,25(OH)2-16-ene-5,6-trans-D3 increased the proportion of MCF-7 cells in the G0-G1 phase and decreased those in the S phase. Furthermore, 1,25(OH)2-16-ene-5,6-trans-D3 induced an elevated expression of the cyclin-dependent kinase inhibitors, p21waf1 and p27kip1. In addition, 1,25(OH)2-16-ene-5,6-trans-D3 almost completely inhibited telomerase activity, as measured by telomeric repeat amplification protocol assay and human telomerase reverse transcriptase mRNA. For each of the growth-related parameters that were examined, the vitamin D3 analogue was more active than 1,25(OH)2D3. In contrast, 1,25(OH)2D3 was more calcemic than 1,25(OH)2-16-ene-5,6-trans-D3. In summary, 1,25(OH)2-16-ene-5,6-trans-D3, having a novel 5,6-trans motif, strongly inhibited clonal proliferation and reduced telomerase activity with low calcemic activity, suggesting further testing in in vivo cancer models. This analogue may gain a therapeutic niche for selected malignancies.

Animals↗

An interaction between human colon carcinoma cells and hepatocytes activates transforming growth factor-beta1 in vitro.

We established in vitro heterotypic co-cultures of a human colon carcinoma cell line, HT-29, and a human hepatocyte line, tPH5CH, using transwells to investigate possible interactions between colon carcinoma cells and hepatocytes during the metastatic process. Co-culture, but not HT-29 conditioned medium, inhibited tPH5CH cell proliferation, and this inhibition was blocked by an anti-TGF-beta1 antibody. Significantly more activated TGF-beta1 was released by co-culture than by each cell line cultured alone, whereas there were no significant differences between the total TGF-beta1 released by the individual cultured cell lines and that released by co-culture. These data indicate that an interaction between human colon carcinoma cells and hepatocytes activates TGF-beta1 in vitro.

Carcinoma↗

IFN-gamma- and cell-to-cell contact-dependent cytotoxicity of allograft-induced macrophages against syngeneic tumor cells and cell lines: an application of allografting to cancer treatment.

In allogeneic tumor or skin transplantation, the rejection process that destroys the allogeneic cells leaves syngeneic cells intact by discrimination between self and nonself. Here, we examined whether the cells infiltrating into the allografts could be cytotoxic against syngeneic immortal cells in vitro and in vivo. The leukocytes (i.e., macrophages (Mphi; 55-65% of bulk infiltrates), granulocytes (20-25%), and lymphocytes (15-20%)) infiltrating into allografts, but not into autografts, in C57BL/6 mice were cytotoxic against syngeneic tumor cells and cell lines, whereas the cytotoxic activity was hardly induced in allografted, IFN-gamma-/- C57BL/6 mice. Among the leukocytes, Mphi were the major population of cytotoxic cells; and the cytotoxic activity appeared to be cell-to-cell contact dependent. When syngeneic tumor cells were s.c. injected into normal C57BL/6 mice simultaneously with the Mphi-rich population or allogeneic, but not syngeneic, fibroblastic cells, tumor growth was suppressed in a cell number-dependent manner, and tumor cells were rejected either with a Mphi:tumor ratio of about 30 or with an allograft:tumor ratio of approximately 200. In the case of IFN-gamma-/- C57BL/6 mice, however, the s.c. injection of the allograft simultaneously with tumor cells had no effect on the tumor growth. These results suggest that allograft or allograft-induced Mphi may be applicable for use in cancer treatment and that IFN-gamma induction by the allograft may be crucial for the treatment.

3T3 Cells↗