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Biomedical subjects

M Kitajima

Publications and source records attributed to M Kitajima.

At least 253 records · Page 14Linked to original sources
PubMed1996

Epidermal growth factor receptor-dependent cytotoxic effect by an EGF-ribonuclease conjugate on human cancer cell lines--a trial for less immunogenic chimeric toxin.

Mammalian pancreatic ribonuclease (RNase) was conjugated chemically via a disulfide bond to human or murine epidermal growth factor (EGF). The conjugation between EGF and RNase was ascertained by SDS-PAGE using reduced and nonreduced conjugates. The EGF-RNase conjugate retained potent RNase activity and competed with 125I-EGF for binding to EGFR to the same extent as unconjugated EGF. Both the human and murine EGF-RNase conjugates showed dose-dependent cytotoxicity against EGFR-overexpressing A431 human squamous carcinoma cells with IC50 values of 3 x 10(-7) M and 6 x 10(-7) M, respectively, whereas free RNase had an IC50 of 10(-4) M. Against the EGFR-deficient small-cell lung cancer cell line H69, the EGF-RNase conjugate had no cytotoxic effect. The Human EGF-RNase conjugate showed dose-dependent cytotoxicity against other squamous carcinoma cell lines (TE-5, TE-1) and breast cancer cell lines (BT-20, SK-BR-3, MCF-7) and the cytotoxicity of the conjugate correlated positively with the level of expression of EGFR by each cell line. An unconjugated mixture of EGF and RNase had no greater effect than RNase alone on any cell line. Excess free EGF blocked EGF-RNase conjugate cytotoxicity against A431 cells. These results suggest that the EGF-RNase conjugate may be a more effective anticancer agent with less immunogenicity than coventional chimeric toxins.

Antineoplastic Agents↗
PubMed1996

Epidermal growth factor receptor-dependent cytotoxicity for human squamous carcinoma cell lines of a conjugate composed of human EGF and RNase 1.

Recombinant human ribonuclease 1 (RNase 1) was chemically linked to recombinant human epidermal growth factor (EGF). The EGF-RNase conjugate showed dose-dependent cytotoxicity for EGF receptor-overexpressing A431 and TE-8 human squamous carcinoma cells with an IC50 of 2 x 10(-7)M and 10(-6)M, respectively, whereas the IC50 of RNase alone was almost 10(-4)M. An unconjugated mixture of EGF and RNase had no greater effect than RNase alone. The conjugate showed no detectable cytotoxicity against EGF receptor-deficient small cell lung cancer cells (H69). Addition of excess EGF in the medium protected A431 cells from the EGF-RNase conjugate cytotoxicity. The cytotoxicity of the EGF-RNase conjugate was positively correlated with the EGF receptor numbers of each cell line. The chimeric toxin composed of only human proteins might be a more useful anti-cancer agent with less immunogenicity than the conventional chimeric toxins.

Carcinoma, Squamous Cell↗
PubMed1996

Meanings of c-erbB and int-2 amplification in superficial esophageal squamous cell carcinomas.

BACKGROUND: Accumulation of genetic abnormalities is linked to the development and progression of cancer. We therefore analyzed the correlation between the clinical characteristics of superficial esophageal squamous cell carcinoma patients and oncogene amplifications. METHODS: Between 1980 and 1991, there were 63 cases of superficial esophageal carcinoma (Tis and T1 cancer) at Keio University Hospital. The T1 cases were divided into two groups: T1a cases, in which the tumor had invaded the lamina propria, and T1b cases, in which the tumor had invaded the submucosa. DNA was isolated from paraffin-embedded blocks. Oncogene amplification was determined by slot-blot hybridization. RESULTS: Amplification of int-2 and c-erbB was detected in 14 and 5, respectively, of the 54 cases. Three of 12 T1b patients with int-2 amplification died of distant organ metastasis. The survival rate for the group with int-2 amplification was significantly lower than that without int-2 amplification. All 4 T1b patients with c-erbB amplification had lymph node metastasis at operation. CONCLUSIONS: These findings mean that genetic abnormalities are a useful marker for treating patients with superficial esophageal squamous cell carcinomas.

Carcinoma, Squamous Cell↗
PubMed1996

Motor activity of refashioned colorectoanus in patients with total colonic aganglionosis.

An ano-recto-sigmoid colon pressure study was designed to evaluate the characteristics of the motor activity of refashioned colorectoanus in patients with total colonic aganglionosis (TCA) in comparison to patients with rectosigmoid Hirschsprung's disease (HD) and healthy children (HC), and to elucidate the pathophysiology of the pulled-through ileum, with aganglionic colon as an onlay patch, in coordination with the anal sphincter. The study group consisted of six patients with TCA, six with HD who underwent endorectal colonic pull-through, and six HC. Pressure studies were performed using a triple-lumen catheter; recording sites were 15 and 9 cm from the anal verge, and at the anal canal. The following were measured and compared: (1) anal canal pressure profile, (2) resting pattern of activity at the refashioned colorectum and anal canal, and (3) changes in motor activity after stimulation with cold water and glycerin. The motor activities of the refashioned colorectoanus of TCA and HD patients differed greatly from those of HC. All six HC had no isolated high-amplitude contraction (IHAC) in the colorectum during the 45-minute study period; they complained of a strong urge to defecate after glycerin enema and actually did so. In contrast, IHAC appeared 2.0 +/- 1.3 times per 10 minutes, with maximal amplitude of 60.3 +/- 24.9 cm H2O in TCA, and 5.6 +/- 3.7 per 10 minutes with maximal amplitude of 79.5 +/- 11.7 cm H2O in HD. After glycerin enema, IHAC increased to 0.5 +/- 0.2 per minute and 69.3 +/- 44.6 cm H2O in TCA and to 0.8 +/- 0.4 per minute and 93.0 +/- 12.8 cm H2O in HD. Defecation was postponed for more than 10 minutes in two HD and all TCA patients. The mean motility index per minute was least for TCA patients (76.9 +/- 98.2); it was 406.5 +/- 197.1 (P < .05) for HD patients and 159.2 +/- 84.2 (P < .01) for HC. TCA patients had the lowest amplitude of maximal resting anal pressure, and hypoactivity of the colorectum during rest and after stimulation; this suggests that motor dysfunction involves even the ganglionic ileum, concomitant with suppressed signals to the higher integrating center for defecation.

Adolescent↗
PubMed1996

Therapeutic efficacy of pamidronate in combination with chemotherapy to bone metastasis of breast cancer in a rat model.

Bone metastasis is clinically often recognized in breast cancer patients, and in the progression of bone destruction due to bone metastasis, osteoclastic bone resorption is an important step. Therefore, drugs such as bisphosphonates-which have anti-osteoclastic activity-are expected to inhibit the progression of bone metastasis. However, bisphosphonates demonstrate no cytotoxic effects for cancer cells. In the present study we have evaluated the therapeutic efficacy of pamidronate (3-amino-1-hydroxypropylidene-1,1-bisphosphonic acid) combined with mitomycin C (MMC) on bone metastasis of breast cancer using an animal model. The model for bone metastasis was developed by injecting c-SST-2 (spontaneously developed rat mammary adenocarcinoma in a SHR rat) cells into the thoracic aorta of 45-46 day-old female SHR rats. Three weeks after the tumour cell injection, these 48 animals were divided into four groups: control, n = 16; pamidronate, n = 12; MMC, n = 10; pamidronate with MMC, n = 10). In order to evaluate therapeutic effects on bone metastasis in each animal, the whole spine was harvested for histological examination. The bone metabolic markers used were: pyridinoline/creatinine (Pyd/Cr), deoxypyridinoline/creatinine (Dpd/Cr), bone alkaline phosphatase (BAP), and osteocalcin-measured 1 week after therapy. Histological scores of bone destruction in the treatment groups were lower than those of the control, and there were no differences among treatment groups. Although the values of Pyd/Cr and Dpd/Cr in the treatment groups, including pamidronate, were significantly lower than those in the control (P < 0.05), the other markers did not differ. It was suggested that pamidronate inhibited the progression of bone resorption, mainly by osteoclast activation due to bone metastasis, and Pyd/Cr and Dpd/Cr could be useful in part as a marker which reflects therapeutic effect. However, no additional effects were observed when it was combined with MMC.

Animals↗
PubMed1996

Rapid diagnosis of methicillin-resistant Staphylococcus aureus bacteremia by nested polymerase chain reaction.

OBJECTIVE: The purpose of this study was to establish a rapid and sensitive diagnostic method for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in postoperative patients. SUMMARY BACKGROUND DATA: As a result of diffusion and abuse of third-generation cephalosporin antibiotics in the 1980s in Japan, an outbreak of MRSA infection has been posed. In the field of surgery, severe postoperative infections with MRSA such as MRSA bacteremia, which may lead to multiple organ failure, have emerged with a high mortality. METHODS: Thirty-five patients with high fever (above 38.5 C) or watery diarrhea or both within 2 weeks after gastrointestinal major surgery and 6 healthy volunteers were examined. Nested polymerase chain reaction was used to detect mecA and toxic shock syndrome toxin-1 (TSST-1) genes in blood specimens. RESULTS: The mecA and TSST-1 genes were not detected in the blood samples of any of the six healthy volunteers. In all 12 samples from which MRSA colonies were isolated by blood culture, mecA and TSST-1 genes were detected. Although it took at least 48 hours to identify MRSA by the blood culture method, the presence of mecA and TSST-1 genes was determined by nested polymerase chain reaction method within only 3 to 4 hours after blood sampling. CONCLUSIONS: This method, as a sensitive and rapid monitoring system for MRS bacteremia, would be clinically beneficial for prevention of cross infection and for early determination of appropriate treatment for infected patients.

Bacteremia↗
PubMed1996

Case report: lymphangioma of the oesophagus endoscopically resected.

Lymphangioma of the oesophagus is an extremely rare entity, with only nine cases having been reported worldwide. We report on a 52-year-old woman with oesophageal lymphangioma, diagnosed using endoscopic ultrasonography and endoscopically resected. No case of malignant transformation of the lymphangioma has been reported in the literature. Endoscopic resection seems to be a minimally invasive method that is appropriate both for the removal of the tumour and precise diagnosis.

Endoscopy↗
PubMed1996

The effect of atrial natriuretic peptide on pulmonary acid injury in a pig model.

The effect of exogenous atrial natriuretic peptide (ANP) on pulmonary injury induced by aspiration of hydrochloric acid (0.1 N HCl, 2.0 ml/kg) was examined in anesthetized pigs ventilated with 100% oxygen. Group-specific diuretic treatment was used 60 min after aspiration and followed for a further 120 min. No diuretics were used for Group 1, 0.1 microg/kg/min of ANP was infused intravenously for 60 min in Group 2, and 0.05 mg/kg of furosemide was injected (intravenous bolus) in Group 3. Total urine volume after diuretic treatment did not differ significantly between Groups 2 and 3. However, the increase in PaO2 (to 386.3 +/- 67.5 mm Hg) after infusion of ANP was significantly higher than the increase in PaO2 (to 275.9 +/- 63.3 mm Hg) after furosemide treatment, and in the no treatment control (to 171.1 +/- 31.5 mm Hg). Pulmonary hypertension induced by acid aspiration was significantly reduced (p < 0.01 versus Groups 1 and 3) during ANP infusion. ANP has a beneficial effect on acute lung injury, possibly through its diuretic and/or pulmonary vasodilating action.

Animals↗
PubMed1996

Effects of steroids on the lung accumulation of neutrophil and monocyte in rabbits with endotoxemia.

STUDY OBJECTIVE: To determine the effects of steroids on the lung accumulation of polymorphonuclear leukocytes (PMNs) and monocytes in rabbits with endotoxemia. DESIGN: A prospective, randomized, controlled animal trial. SETTING: Surgical research laboratory, Keio University School of Medicine. SUBJECTS: Twenty-four female Japanese white rabbits. INTERVENTIONS: Rabbits with endotoxemia were pretreated with steroids sufficient to inhibit the production of tumor necrosis factor (TNF) and to prevent the fall of BP. MEASUREMENTS AND RESULTS: The circulating leukocyte counts and the leukocyte accumulation in the lung were evaluated. Endotoxin caused a rapid decrease in circulating PMNs and monocytes followed by an 8-fold greater accumulation of PMNs (p < 0.001) and a 6.5-fold greater accumulation of monocytes (p < 0.05). Steroids failed to inhibit this initial drop of PMNs and monocytes. However, steroids inhibited the PMN accumulation in the lung by 50% (p < 0.05), without inhibiting the monocyte accumulation in the lung. CONCLUSIONS: These findings suggest that the lung accumulation of PMNs is dependent on TNF or other inflammatory mediators that are inhibited by steroids while the lung accumulation of monocyte is not.

Animals↗
PubMed1996

[Modified surgery for early gastric cancer].

Based on the sufficiently accumulated results of early gastric cancer (EGC), particularly the diagnostic accuracy regarding the depth of cancerous involvement in the gastric wall, lymph node metastasis, pattern of recurrence etc., the modified surgery has been induced for the treatment of EGC since late 1970's. The modification is as follows depending on the depth and location of EGC: constriction of size of gastric resection; narrowing of the extent of lymphadenectomy; preserving omentum, pancreas, spleen, pylorus, vagal nerve, lower esophageal sphincter etc; sparing thoracotomy. This kind of surgery has resulted in remarkable reduction of blood loss during surgery, reduced operation time and hospital stay, which have brought improved QOL to the patients as well as satisfactory survival rate after surgery.

Aged↗
PubMed1996

[Laparoscopic surgery for early gastric cancer].

We have successfully treated 40 patients with early gastric cancer by using two different laparoscopic procedures since March 1992, which are laparoscopic wedge resection of the stomach using a lesion-lifting method (n = 25) and laparoscopic intragastric mucosal resection (n = 15). The indication is as follows; 1) mucosal cancer, 2) < 25 mm, if the lesion is protruded type, 3) < 15 mm and U1 (-), if the lesion is depressive type. All patients were discharged within 4-8 days uneventfully. The resected specimens were 66 +/- 16 mm and 48 +/- 8 mm in diameter respectively, and had a sufficient surgical margin horizontally (16 +/- 5 mm, 8 +/- 4 mm) and vertically. Histology revealed they were all curative surgeries except one case in whom an additional gastrectomy with lymph node dissection by laparotomy was required one month after surgery because lymphatic invasion had been revealed by pathology. In conclusion, these laparoscopic procedures are curative and minimally invasive treatment for early gastric cancer.

Adult↗
PubMed1996

The effect of allopurinol on interstitial purine metabolism and tissue damage in skeletal muscle I-R injury.

OBJECTIVE: Many studies show that allopurinol can reduce skeletal muscle I-R (ischemia-reperfusion) injury, but the mechanism of the effect is still unclear and some studies suspect the effect. In this study, we determined whether allopurinol really reaches to reperfused muscle and reduces tissue injury by inhibiting xanthine oxidase or not. EXPERIMENTAL DESIGN: In this study, microdialysis method combined with HPLC (high performance liquid chromatography) were employed and purines, MDA (malondialdehyde), allopurinol in gracilis muscle were measured continuously in I-R injury model of canine gracilis muscle. The effect was compared between Group N (no treatment: n=8), Group P (pre-ischemic treatment: n=8) and Group R (pre-reperfusion treatment: n=8). RESULTS: Allopurinol reduced the increase of xanthine, uric acid, MDA in the muscle and CPK in blood effluent from gracilis muscle after reperfusion. Tissue protecting effect of allopurinol was more effective in group R than in group P. CONCLUSIONS: By continuous measurement of purines, allopurinol and MDA in canine gracilis muscle during 5 hr ischemia and 2 hr reperfusion, it was proved that allopurinol was delivered to reperfused skeletal muscle and reduced I-R injury by inhibiting xanthine oxidase.

Allopurinol↗
PubMed1996

MR signal intensity of the optic radiation.

PURPOSE: To determine whether a hyperintense layer adjacent to the lateral ventricle on T2-weighted MR images represents the optic radiation. METHODS: We reviewed 11 brain specimens from patients with nonneurologic diseases and MR images from 43 healthy volunteers. The MR images in a patient with cerebral infarction involving the lateral geniculate body were also reviewed to evaluate wallerian degeneration of the optic radiation. RESULTS: The external sagittal stratum, composed of the optic radiation, showed a pale layer in specimens stained by Bodian's method. On high-power microscopic views of the specimens, the axons of the external sagittal stratum were large and separated by wide translucent spaces. In the volunteers, the external sagittal stratum appeared hyperintense on T2-weighted MR images and hypointense on T1-weighted images. The MR images in a patient with cerebral infarction showed hyperintensity within the layer corresponding to the external sagittal stratum. CONCLUSIONS: The hyperintense layer on T2-weighted images represents the external sagittal stratum, or optic radiation. The signal intensity of the external sagittal stratum reflects histologic characteristics of low axonal density.

Aged↗
PubMed1996

[Microcirculatory disturbances after surgical insults--important role of inflammatory cytokines].

Microcirculatory disturbances in the gastric mucosa was investigated in rats after thermal injury using intravital video microscopy. Mucosal blood flow decreased significantly 5 hrs after thermal injury and increased neutrophil-endothelial cell interaction was observed at the same time. Zymosan stimulated-free radical production from peripheral blood was also increased and acute gastric mucosal lesion (AGML) appeared 5 hrs after thermal injury. These data suggest that neutrophil-endothelial cell interaction and increased free radical production induce AGML formation and that microcirculatory disturbance is one of the main reasons for organ failure after surgical insults. The role of inflammatory cytokines in hepatic microcirculatory disturbance was also studied in endotoxin-injected rats using IL-1 receptor antagonist (IL-1Ra) or TNF binding protein (TNFbp). Pretreatment with IL-1Ra or TNFbp significantly improved hepatic microcirculatory disturbance and reduced both the number of leukocytes adhered to the sinusoidal wall and the number of injured cells as well. These data suggest that inflammatory cytokines play a crucial role in microcirculatory disturbance after surgical insults by promoting neutrophil-endothelial cell interaction and systemic excessive inflammation.

Animals↗
PubMed1996

[Laparoscopic curative surgery for early gastric cancer].

We have successfully treated 40 patients with early gastric cancer by using two different laparoscopic procedures since March 1992, which are laparoscopic wedge resection of the stomach using a lesion-lifting method (n = 25) and laparoscopic intragastric mucosal resection (n = 15). The indication is as follows; 1) mucosal cancer, 2) < 25 mm, if the lesion is protruded type, 3) < 15 mm and Ul(-), if the lesion is depressive type. All patients were discharged within 4-8 days uneventfully. The resected specimens were 66 +/- 16 mm and 48 +/- 8 mm in diameter respectively, and had a sufficient surgical margin horizontally (16 +/- 5 mm, 8 +/- 4 mm) and vertically. Histology revealed they were all curative surgeries except one case in whom an additional gastrectomy with lymph node dissection by lapalotomy was required one month after surgery because lymphatic invasion had been revealed by pathology. In conclusion, these laparoscopic procedures are curative and minimally invasive treatment for early gastric cancer.

Gastrectomy↗