Biomedical subjects

T Kakegawa

Publications and source records attributed to T Kakegawa.

At least 19 recordsLinked to original sources

PubMed1999

Total esophagectomy versus proximal esophagectomy for esophageal cancer at the cervicothoracic junction.

To investigate the adequate extent of esophagectomy and lymphadenectomy for an esophageal cancer localized at the cervicothoracic junction, the mortality and morbidity rates, survival rates, and patterns of recurrence were retrospectively analyzed in two groups-14 patients who underwent total esophagectomy with or without laryngectomy and 15 patients who underwent proximal esophagectomy with or without laryngectomy-at Kurume University Hospital from 1981 to 1996. Proximal esophagectomy with or without laryngectomy resulted in a lower hospital mortality rate and better overall survival for patients who underwent curative esophagectomy compared with total esophagectomy with or without laryngectomy. Multivariate analysis indicated that the extent of esophagectomy (total esophagectomy versus proximal esophagectomy) was not a prognostic factor. The incidence of recurrence was not different between the two groups. Lymph node metastasis or recurrence from such esophageal cancers was localized to the neck and upper mediastinum. For an esophageal cancer localized at the cervicothoracic junction, therefore, proximal esophagectomy with or without laryngectomy and with cervical and upper mediastinal lymphadenectomy could be better indicated for preselected patients.

Aged↗

PubMed1999

Enzyme level of enterococcal F1Fo-ATPase is regulated by pH at the step of assembly.

The amount of F1Fo-ATPase in Enterococcus hirae (formerly Streptococcus faecalis) increases when the cytoplasmic pH is lowered below 7.6, and protons are extruded to maintain the cytoplasmic pH at around 7.6. In the present study, we found that the transcriptional activity of the F1Fo-ATPase operon was not regulated by pH. The synthesis of F1 subunits was increased 1.65 +/- 0.12-fold by the acidification of medium from pH 8.0 to pH 5.3. Western-blot analysis showed that there were F1 subunits in the cytoplasm, and the number of alpha plus beta subunits in the cytoplasm was 50% of the total number of the subunits in cells growing at pH 8.0. This decreased to 22% after shifting the medium pH to 5.3, with a concomitant 5.1-fold increase in the level of membrane-bound F1Fo-ATPase. The cytoplasmic F1 subunits were shown to be degraded, and Fo subunits not assembled into the intact F1Fo complex were suggested to be digested. These data suggest that regulation of the enzyme level of F1Fo-ATPase by the intracellular pH takes place mainly at the step of enzyme assembly from its subunits.

Cytoplasm↗

PubMed1998

Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor.

In the search for an endogenous ligand of the orphan G protein-coupled receptor APJ, the presence of the ligand in various tissue extracts was examined by measuring the increase in extracellular acidification rate of the cells expressing the APJ receptor as a specific signal induced by the interaction of the receptor and ligand. By monitoring this activity, we isolated an APJ receptor ligand, designated apelin, from bovine stomach extracts. The structures of bovine and human apelin preproproteins were deduced from the sequences of the corresponding cDNAs. The preproproteins consisted of 77 amino acid residues, and the apelin sequence was encoded in the C-terminal regions. Synthetic peptides derived from the C-terminal amino acid sequence of bovine preproapelin were capable of specifically promoting the acidification rate in the cells expressing the APJ receptor in a range from 10(-7) to 10(-10) M, indicating that apelin is an endogenous ligand for the APJ receptor.

Amino Acid Sequence↗

PubMed1998

pH dependence of the function of sodium ion extrusion systems in Escherichia coli.

Escherichia coli has three systems for sodium ion extrusion, NhaA, NhaB and ChaA. In this study, we examined the effect of pH on the function of these transporters using mutants having one of them, and found that (1) a mutant having NhaB excreted sodium ions at pH 7.5 but not at pH 8.5, (2) the efflux of sodium ions from mutant cells having ChaA was observed at both pH 7.5 and 8.5, but the activity was lower at pH 7.5, and (3) sodium ions were excreted from mutant cells having NhaA at pH 6.5 to 8.5. The extrusion activity of cells having NhaA was higher than that of cells having NhaB or ChaA. These results indicate that NhaB functions at a pH below 8, and ChaA extrudes sodium ions mainly at an alkaline pH above 8. It was also suggested that the activity of NhaB and ChaA is not enough to maintain a low level of internal sodium ions when the external concentration of sodium ions is high, and NhaA is induced within a wide range of medium pH under such conditions.

Escherichia coli↗

PubMed1998

Treatment of superficial cancer of the esophagus: a summary of responses to a questionnaire on superficial cancer of the esophagus in Japan.

BACKGROUND: Histopathologic characteristics and optimal treatment modality for superficial esophageal cancer were reevaluated on the basis of 2418 patients from 143 institutions through a nationwide questionnaire to the members of the Japanese Society for Esophageal Diseases. METHODS: A questionnaire was designed for patients with preoperatively untreated superficial cancer of the esophagus who had undergone either surgical or endoscopic treatment between January 1, 1990, and December 30, 1994. Mucosal cancer and submucosal cancer were divided into three subclasses according to the criteria formulated by the Society. RESULTS: The incidence of positive lymphatic invasion or lymph node metastases tended to increase markedly as cancer infiltrates reached the lamina muscularis mucosa. The majority of the cases with 0-I or 0-III components were submucosal cancer. The indication of endoscopic mucosal resection (EMR) was limited to mucosal 1 and mucosal 2 superficial cancer in 76% of the institutions surveyed. Tumors measuring 2 cm or more in diameter were resected piecemeal in 94% of patients. Complications of EMR, including perforation, stenosis, and hemorrhage, were observed in approximately 6.8% of patients. Almost all patients with mucosal 1 or mucosal 2 cancer are still alive. There was no significant difference in prognosis between mucosal 3 cancer and mucosal 1 or mucosal 2 cancer, but submucosal 1 cancer showed worse prognosis than mucosal cancer. CONCLUSIONS: Local resection of cancer lesions is regarded as the treatment of choice against the superficial esophageal cancers limited to the lamina propria mucosae. Further study is advocated to define the treatment strategy against mucosal 3 or submucosal 1 cancer.

Aged↗

PubMed1997

Growth of an Escherichia coli mutant deficient in respiration.

An Escherichia coli mutant deficient in genes for heme biosynthesis grew in medium of initial pH 8 containing 1% tryptone and glucose under aerobic growth conditions, and its doubling time was approximately 60 min at 37 degrees C. The growth rate was not increased under O2-limiting conditions. When the mutant was grown in medium of initial pH 6, growth stopped at the middle of the exponential growth phase. This could be overcome and the growth yield increased by the addition of 20 mM lysine to the growth medium. Lysine did not prevent the decrease in the medium pH as growth proceeded, making it unlikely that lysine decarboxylation stimulates growth by the alkalinization of the medium. These results indicate that respiration is not obligatory for growth under aerobic conditions, but growth without respiration at low pH requires a large amount of lysine.

Aerobiosis↗

PubMed1997

Dose intensity of uracil and tegafur in postoperative chemotherapy for patients with poorly differentiated gastric cancer.

A retrospective analysis of postoperative chemotherapy had shown the continuous administration of UFT, an oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4, to be effective for poorly differentiated gastric cancer. We therefore sought to determine prospectively the effective dose of postoperative chemotherapy with UFT for patients with poorly differentiated gastric cancer following a curative resection. We determined the effect of the combined intravenous administration of mitomycin C (MMC) and oral treatment with protein-bound polysaccharide Kreha (PSK), extracted from the basidiomycete Coriolus versicolor, and UFT at a dose of either 8 mg/kg or 12 mg/kg daily for 1 year. A total of 224 patients with poorly differentiated stage II-IV gastric cancer were entered into this study after undergoing a curative resection. No differences were observed between the two treatment groups in terms of prognostic factors, the toxicity rate or the doses of the drugs prescribed, other than UFT. The higher dose of UFT in maintenance therapy led to a decrease in the recurrence rate (P < 0.05), and increases in disease-free survival and cause-specific survival (P < 0.05). UFT at 12 mg/kg in postoperative chemotherapy was thus found- to improve the postoperative results with no increase in toxicity for poorly differentiated gastric cancer, and is also cost-effective for outpatients.

Adult↗

PubMed1997

A randomized trial of surgery with and without chemotherapy for localized squamous carcinoma of the thoracic esophagus: the Japan Clinical Oncology Group Study.

OBJECTIVE: To determine whether postoperative adjuvant chemotherapy confers a survival benefit on patients with esophageal squamous cell carcinoma undergoing radical surgery, we undertook a cooperative, prospective randomized controlled trial. METHODS: A total of 205 patients underwent transthoracic esophagectomy with lymphadenectomy at eleven institutions between December 1988 and July 1991. These patients were prospectively randomized into two groups (100 patients underwent surgery alone and 105 patients had additional two courses of combination chemotherapy with cisplatin (70 mg/m2) and vindesine (3 mg/m2). The two groups did not differ with respect to sex, age, location of tumor, and distributions of pT, pN, pM, or p stage. RESULTS: The 5-year survival was 44.9% in the surgery alone group and 48.1% in the surgery plus chemotherapy group. The relative risk was estimated to be 0.89 (95% confidence interval, 0.61 to 1.31) in the surgery plus chemotherapy group compared with the surgery alone group. No significant differences in survival were detected between the two groups, even with lymph node stratification. CONCLUSION: Postoperative adjuvant chemotherapy with cisplatin and vindesine has no additive effect on survival in patients with esophageal cancer compared with surgery alone.

Adult↗

PubMed1996

Postoperative chemotherapy for colorectal cancer by combining 5-fluorouracil infusion and 1-hexylcarbamoyl-5-fluorouracil administration after curative resection.

BACKGROUND: Colorectal cancer is one of the major malignant diseases and, recently, its incidence appears to be increasing. Surgical resectability is an important prognostic determinant; however, recurrent tumors are commonly noted, even after apparently curative surgery. Because such metastatic disease cannot be cured, better adjuvant therapies are urgently called for. METHODS: We studied the effect of postoperative chemotherapy using 5-fluorouracil (5-FU) infusions and 1-hexylcarbamoyl-5-fluorouracil (HCFU) oral administration for curatively resected Stage II to IV colorectal cancer. This study was prospectively randomized and controlled and 251 (93.3%) of 269 patients were determined to be candidates for statistical assessment. The inductive regimen for Group A included a total of 6 5-FU intravenous injections, 10 mg/kg, on postoperative days 0, 1, 2, 7, 8, and 9. For maintenance therapy, Group A also received oral HCFU, 300 mg daily for 52 weeks beginning 2 weeks after surgery. The regimen for Group B included only 5-FU injections of Group A. RESULTS: There were no differences in the prognostic factors or doses of 5-FU between Groups A and B. In addition, no difference was observed in the toxicity rate between the two groups. Group A, with 5-FU infusions plus oral HCFU administration, produced a reduction in the recurrence rate and a prolongation of the survival time for patients with rectal cancer. In a retrospective analysis, this protocol was also effective for patients with Stage III to IV, wall invasion-positive, and lymph node metastasis-positive colorectal cancers. CONCLUSIONS: This study suggests that the combination of 5-FU infusions and the continuous oral administration of HCFU is a reasonable therapeutic approach for patients with surgically resected colorectal cancer and a high risk of recurrence.

Adult↗

PubMed1996

Comparative analysis of imaging modalities in the preoperative assessment of nodal metastasis in esophageal cancer.

Preoperative radiological findings of nodal status in 74 patients, using endoscopic ultrasonography (EUS), computed tomography (CT), ultrasonography (US), and magnetic resonance imaging (MRI), were compared to histopathology reports following transthoracic total esophagectomy with radical lymphadenectomy (TTE), involving complete dissection of the mediastinal and abdominal nodes and lower cervical lymph nodes. Accuracy, sensitivity, and specificity of each radiological investigation were calculated for each anatomic group of nodes. Statistical analysis revealed that EUS is more accurate and significantly more sensitive (P<0.01) for lymph nodes along the right recurrent laryngeal nerve and those in the upper and mid-periesophageal, infracarinal locations. Paratracheal and lower paraesophageal nodes are assessed better using CT whereas MRI is better for mid-paraesophageal and infra-aortic nodes. US is most accurate and sensitive for evaluation of cervical and abdominal nodes (P<0.01).

Abdomen↗

PubMed1996

Total pelvic exenteration for locally advanced colorectal carcinoma.

Twenty-six patients who underwent total pelvic exenteration for locally advanced colorectal cancer were studied retrospectively. The operative mortality rate was 8 per cent (two deaths). In patients with stage II primary disease the recurrence rate after curative surgery was three of seven, although the mean survival time was 58 months and the 5-year survival rate 71 per cent. Patients with stage III primary disease had a shorter mean survival time regardless of supposed curability (curative 14 months versus non-curative 9 months). Patients with stage IV disease had a mean survival time of 5 months. In patients who underwent curative surgery for recurrent disease the mean survival time was 33 months and 5-year survival rate 25 per cent, although in those receiving non-curative surgery the survival time was significantly shorter at 10 months (P < 0.05). Total pelvic exenteration is warranted for patients with stage II locally advanced colorectal carcinoma and is an option for those with recurrent carcinoma when performed with curvative intent.

Adenocarcinoma↗

PubMed1996

Effect of fentanyl citrate analgesia on glucose production following trauma in rats.

The postoperative hormonal milieu enhances glucose production. The objectives of this study were to determine whether fentanyl plus pentobarbital anesthesia reduced the excretion of stress hormones and whether this resulted in decreased glucose production following trauma. Male Sprague-Dawley rats were assigned into control and trauma. The trauma group was further subdivided into three groups according to the methods of anesthesia: T-1, pentobarbital (PB) alone; T-2, pentobarbital plus fentanyl (FE); and T-3, given PB during surgery and FE at the end of surgery. Glucose production was measured by a primed constant infusion of 3-3H-glucose. Fentanyl plus pentobarbital anesthesia prevented an increase in corticosterone levels in the plasma compared with in T-1 and T-3, 0.5 hr after the surgery. Fentanyl plus pentobarbital, anesthesia caused reductions of insulin and glucagon levels in the plasma and a decrease in catecholamines excretion in the urine. Glucose production was lower with FE+PB anesthesia than with PB alone (PB: 4.6 +/- 0.1 mg/kg/min vs PB+FE: 3.6 +/- 0.2 mg/kg/min, P < 0.05). However, fentanyl given at the end of surgery did not alter hormonal milieu and glucose production compared with pentobarbital alone. Blocking afferent neural stimuli from the wound and injury during the surgery is one approach to prevent an enhancement of postoperative glucose production.

Analgesia↗

PubMed1996

Effect of fentanyl citrate anesthesia on protein turnover in patients with esophagectomy.

The objectives of this study were to determine whether high doses of fentanyl anesthesia reduced the surgical stress level and to elucidate the effect of fentanyl anesthesia on protein turnover after esophagectomy. Seventeen male patients with esophageal cancer were divided into two groups, conventional anesthesia (CA) and fentanyl anesthesia (FA). The FA patients received 134.0 +/- 15.3 microg/kg fentanyl citrate and the CA patients 15.7 +/- 7.4 microg/kg fentanyl during the surgery. Protein turnover was measured by the method of bolus infusion of [15N]glycine (1 g). High dose of fentanyl anesthesia reduced cortisol levels during the surgery (CA 38.0 +/- 13.8 pg/ml vs FA 13.5 +/- 2.4, P < 0.05) and interleukin-6 levels in the plasma after the surgery (P < 0.02). The postoperative nitrogen retention was greater with fentanyl anesthesia than with conventional anesthesia. Both protein synthesis and breakdown rates were increased with fentanyl anesthesia, while they were unaltered in CA patients. Postoperative fibrinogen synthesis rate was greater with FA than with CA (CA 51.1 +/- 9.2%/day vs FA 100.9 +/- 14.0, P < 0.01). The protein turnover and fibrinogen synthesis data suggested a shorter duration of shock phase in FA patients than in CA patients. We concluded that a high dose of fentanyl anesthesia reduced surgical stress levels and shortened the postoperative shock phase, resulting in a nitrogen-sparing effect.

Acute-Phase Proteins↗

PubMed1996

Evaluation of the cell kinetics of MNNG-treated rat gastric mucosa based on AgNOR and ODC activity.

To investigate the process of carcinogenesis in gastric cancer, we studied the histological features and cell kinetics in the gastric mucosa of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-treated rats. Samples of gastric mucosa from both MNNG-treated and control rats were histologically examined by staining with nucleolar argylophilic nonhistone (AgNOR) proteins, and their ornithine decarboxylase (ODC) activity was determined every 2 months for 10 months. In 40% of the MNNG-treated rats, atrophy of the gastric mucosa was observed after 2 months, followed by adenomatous proliferation. More AgNOR-positive granules were found in the pyloric glands than in the fundic glands, and the total number of positive granules increased over time. Cancerous and hyperplastic lesions preferentially developed in the pyloric glands and showed significantly more AgNOR-positive granules than the normal mucosa. After 6 months the ODC activity in the MNNG-treated rats was significantly higher than that in the control rats. These results thus suggest that the pyloric glands have a high growth activity, while in addition, adenomatous proliferation is a characteristic pathological feature of precancerous lesions in the stomach in MNNG-treated rats.

Adenocarcinoma↗

PubMed1996

Effect of thyroidectomy on photoreceptor cells in adult rat retina.

To evaluate the effect of thyroid hormone on the retina in the adult male rat, morphometric and autoradiographic studies were made. Four days after an intravenous pulse injection of L-[3H]-leucine into adult male rats, the eyeballs were removed and the autoradiogram made. Two weeks after thyroidectomy, the length of photoreceptor cell inner segments was significantly decreased, but that of the outer segments did not change. Daily supplement of T4 (100 microg/kg sc twice for 2 days) before L-[3H]-leucine injection did not restore the decrease in the length. The silver grains of radioactive material distributed in the outer segment were divided into 3 equal portions. Thyroidectomy significantly increased the number of grains in the basal portion near the inner layer indicating a reduction in the renewal rate of the outer segment, but the T4 supplement did not restore the reduction in the renewal rate. These findings suggest that thyroid hormone is required to maintain the rate of renewal of the photoreceptor cell outer segment but the hormone supplement did not rapidly restore the renewal rate.

Animals↗

PubMed1996

Drug sensitivity testing for clinical samples from oesophageal cancer using adhesive tumour cell culture system.

A total of 83 specimens of surgically resected tumours from 78 patients with oesophageal cancer were assayed for drug sensitivity using an adhesive tumour cell culture system (LifeTrac CSA assay). Seventyone of 83 specimens had a sufficient number of cells to permit growth in culture and 57 of 71 (80%) were evaluable for drug response. Cells (3 x 10(3) ml-1 well-1) were cultured for 14 days and exposed to drugs on days 3-8. Growing cells were confirmed as cancer cells by immunohistochemical staining. IC90 values against several anti-cancer drugs were determined and population distributions of IC90 for each drug served as the basis for judging sensitivity. The 10th percentiles of IC90 (microgram ml-1) for CDDP, 5-FU, DOX, CPM, MTX, VP16, IFOS, VDS, BLM and CDDP + 5-FU were 0.3, 0.16, 0.005, 0.9, 0.006, 0.09, 0.8, 0.006, 0.04 and 0.15 + 0.09 respectively. The population distribution of IC90 against each drug showed a specific pattern that was very similar among histopathological gradings and stages of the disease. This system appeared to be a clinically applicable drug sensitivity test for human oesophageal cancer.

Antineoplastic Agents↗

PubMed1996

[Successful neoadjuvant chemotherapy in a patient with advanced gastric cancer with periaortic lymph node metastasis].

We described a case of advanced gastric cancer accompanied by metastasis to the periaortic lymph node. Two cycles of the neoadjuvant chemotherapy consisting of 5-FU and low-dose CDDP (FP therapy) were given. 5-FU (800mg/body/day) was administered as a continuous intravenous infusion for five days, and CDDP (10mg/body/day) was given as an intravenous infusion for an hour on days 1-5. The FP therapy resulted in a significant effect in the metastatic periaortic lymph node. Then, total gastrectomy with combined resection of spleen was done. Histological examination of the resected specimen revealed the histological effect showing Grade 3 in the primary site and Grade 2 in the periaortic lymph node. The patient is alive with no evidence of recurrence 13 months after operation. Thus, FP therapy is thought to be effective against advanced gastric cancer.

Aged↗

PubMed1996

[Treatment of superficial carcinoma of the esophagus--a review of responses to questionnaire on superficial carcinoma of the esophagus collected at the 49th conference of Japanese Society for Esophageal Diseases].

Histopathological characteristics and optimal treatment modality for superficial esophageal carcinoma were reevaluated by the way of nationwide questionnaires to the members of the Japanese Society for Esophageal Diseases. A questionnaire was designed for patients with preoperatively untreated superficial carcinoma of the esophagus who had undergone either surgical or endoscopic treatment between January 1, 1990 and December 30, 1994. As the results, the incidence of positive lymphatic invasion or lymphnode metastases tended to increase markedly as cancer infiltration reached the lamina muscularis mucosa. The majority of the cases with 0-I or 0-III components were sm. cancer. The indication of endoscopic mucosal resection (EMR) was limited to m1 and m2 superficial carcinoma in 76% of the institutions surveryed. Tumors measuring 2cm or more in diameter were resected piecemeal in 94% of the patients. The complications of EMR were observed in approximately 6.8% of patients, which denoted perforation, stenosis, and hemorrhage on most of the cases. As for the result of the treatment, almost all patients with m1 or m2 cancer survived. There was no significant difference in prognosis between m3 cancer and m1 or m2 cancer, but sm1 cancer showed worse prognosis than mucosal carcinoma. From this review, further study was advocated to refine the treatment strategy against m3 or sm1 cancer in the future.

Endoscopy↗