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Biomedical subjects

M Kitajima

Publications and source records attributed to M Kitajima.

At least 289 records · Page 16Linked to original sources
PubMed1995

Active oxygen species in formation of acute gastric mucosal lesions induced by thermal injury in rats.

Active oxygen species generated by circulating leukocytes and released from the gastric mucosa were measured in the process of acute gastric mucosal lesion formation after thermal injury in rats. Alterations of luminol-dependent chemiluminescence activities generated by leukocytes obtained from the gastric vein and the inferior vena cava were approximately same. A decrease in chemiluminescence activity 15 min after thermal injury and a significant increase in chemiluminescence activity 5 hr after thermal injury were observed in leukocytes from both veins. From 15 min to 12 hr after thermal injury, luciferin-dependent chemiluminescence activities were significantly higher than that of the control group. Oral administration of rebamipide resulted in decreased mucosal lesion formation. Rebamipide, an antiulcer agent that protects the mucosa from damage in various animal models decreased chemiluminescence activities only released from the gastric mucosa but not from circulating leukocytes. These results suggest that two different pathways of active oxygen species formation may exist in the pathogenesis of acute gastric mucosal lesions after thermal injury.

Acute Disease↗
PubMed1995

Effect of basic fibroblast growth factor on reinnervation of gastric microvessels. Possible relevance to ulcer recurrence.

Basic fibroblast growth factor (bFGF) has well-established angiogenic and ulcer healing actions. bFGF has also been found to induce neural regeneration in the central nervous system. Thus, the present study was undertaken to clarify the effect of basic fibroblast growth factor on the regeneration of autonomic nerves in the granulation tissues following the induction of experimental gastric ulcer induced by acetic acid in rats. Rats were divided into control, acetic acid alone, and acetic acid plus acid-stable human recombinant basic fibroblast growth factor (CS23, 1 microgram/100 g body wt., every 12 hr for three days, or one or two weeks, through oral gastric intubation) groups. As a result, few autonomic nerves were recognized surrounding the newly formed arterioles and venules in the acetic acid alone group. In the CS23-treated group, the cholinergic, calcitonin gene-related peptide and vasoactive intestinal peptide-immunoreactive nerves were clearly recognized near the microvessels, but few adrenergic nerves were seen even after CS23 treatment. From these observations, basic fibroblast growth factor was suggested to promote the reinnervation of the newly formed microvessels.

Animals↗
PubMed1995

Calculation of biliary atresia prognostic index using a multivariate linear model.

The purpose of this study was to determine the relative value of liver function markers in predicting the magnitude of morbidity and to develop a quantitative estimate of the prognostic risk using a multivariate regression model in patients who have been operated on for biliary atresia. The study sample consisted of 37 patients who had undergone a Kasai portoenterostomy; the jaundice disappeared in 32 and persisted in five. A computer-based stepwise regression procedure produced the linear predictive models by the equation: biliary atresia prognostic index (BAPI) = 9.2 Cu:Zn + 1.0 ZTT + 3.2 TB - 0.05 ChE + 9.9 for infants under 1 year of age, and BAPI = 10.3 Cu:Zn + 0.8 ZTT + 0.03 GGTP - 0.12 ChE + 25.6 for children over 1 year of age. In validation of these models, the indexes fluctuated from -17 to 122, and the degree of morbidity increased linearly with the increase in BAPI. Postoperatively the patients were classified into four categories according to the dynamics of their postoperative course: A (BAPI < 25), successful cases that should not require liver transplantation (40.5%); B (25 < or = BAPI < or = 50), improved cases that have extended survival with their native liver (29.7%); C (50 < BAPI < or = 75), cases that improved in terms of disappearance of jaundice but ultimately will require liver transplantation (8.1%); and D (BAPI > 75), cases that require early referral for transplantation (21.6%). (The percentages indicate the distribution rate of patients at the time of final follow-up evaluation.) These models allow quantification of the risk of morbidity from progressive liver cirrhosis in the individual patient, permitting the clinician to consider whether such patients should be considered for liver transplantation.

Biliary Atresia↗
PubMed1995

Outcomes of ileocolic conduit for biliary drainage in infants with biliary atresia; comparison with Roux-en-Y type reconstruction.

This study was undertaken to define the role of an ileocolic conduit that was devised as anti-reflux procedure in comparative study with Roux-en-Y type reconstruction in infants with biliary atresia treated at a single institution. The ileocolic conduit (IC) consisted of 30 cm of distal ileum anastomosed to the portahepatis and a 10-cm segment of ascending colon vented through the abdominal wall, which was later anastomosed to the second portion of the duodenum. In the Roux-en-Y type reconstruction (RY), 40 to 60 cm of jejunum was used for the hepatic limb. Twenty-three infants in group IC and 16 infants in group RY were entered in this study. Mean ages at definitive surgery were 65.3 +/- 23.1 days for group IC and 65.0 +/- 19.5 days for group RY. The two groups were compared for the postoperative outcomes in terms of bile excretion, incidence of cholangitis, esophageal varices, survival rate, and the effects on physical development. The follow-up ranged from 4 to 15 years. Bile excretion was obtained in all infants in both groups. Twenty infants (87.0%) in group IC and 10 infants (62.5%) in group RY became anicteric. Cholangitis occurred in 60.9% of group IC, compared with 83.3% for group RY, in which 6 infants required revision to complete diversion of Roux-en-Y limb (Suruga II). There was the same occurrence rate of esophageal varices for both groups. However, the varices tended to develop later in group IC (53.0 +/- 18.4 months) than in group RY (12.7 +/- 6.0 months) (P < .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Biliary Atresia↗
PubMed1995

Effect of endogenous and exogenous EGF on the growth of EGF receptor-hyperproducing human squamous cell carcinoma implanted in nude mice.

The effect of epidermal growth factor (EGF) on the biological behaviour of human tumours in vivo is still controversial. We investigated the effect of EGF on the growth of an EGF receptor-hyperproducing human epidermoid carcinoma, A431 tumour, and on a human small-cell lung carcinoma, H69 tumour, without detectable EGF receptor by using sialoadenectomised (sialex) mice as an endogenous EGF-suppressed animal model. The plasma EGF concentration in the sialex athymic mice was significantly lower than that in the sham-operated mice (P < 0.05). After exogenous EGF replacement with an implanted minipump, the plasma EGF concentration was significantly increased in both groups (P < 0.05). There was no significant difference between the body weight growth curves of sialex and sham-operated mice with and without EGF treatment. The tumour weight of A431, both estimated and measured in sialex mice, was significantly lower than that in sham-operated control mice (P < 0.05), and the growth of A431 tumour was significantly increased by exogenous EGF treatment (P < 0.05). Mitotic activity of these tumours detected by immunohistochemical staining for incorporated bromodeoxyuridine indicated a mitosis-stimulatory effect of endogenous and exogenous EGF on A431 tumours. In contrast to these findings on A431 tumours, a growth-stimulatory effect of endogenous and exogenous EGF was not observed in the H69 tumour. These results suggest a growth-promoting effect of physiological levels of endogenous EGF on EGF receptor-hyperproducing human tumours in vivo.

Animals↗
PubMed1995

Dual modulation by l-leucovorin and recombinant human interferon alpha 2a of 5-fluorouracil antitumor activity against the human colon carcinoma xenograft Co-4.

We investigated the dual modulation by l-leucovorin (LV) and recombinant human interferon-alpha 2a (IFN-alpha 2a) of 5-fluorouracil (5-FU) antitumor activity against human colon carcinoma cells (Co-4) using a nude mouse system. 5-FU was administered intraperitoneally (IP) at 10 or 90 mg/kg. 5-FU (10 mg/kg) was administered daily for 10 days, and 90 mg/kg was administered once. LV was administered IP 1 and 0 h before 5-FU treatment at 200 mg/kg. IFN-alpha 2a was administered subcutaneously (SC) daily for 14 days at 60,000 IU/mouse. When 5-FU was administered at 10 or 90 mg/kg with these two modulators, the antitumor effect was increased significantly, with T/C ratios of 18.1 and 6.1, respectively. These modulatory effects were assessed as synergistic, without associated severe side effects or death during the experimental period. LV augmented the antitumor activity of 5-FU through increment of thymidylate synthetase (TS) inhibition, and IFN-alpha 2a showed a modulatory effect in elevating the intratumoral concentration of fluorouridine without change in TS inhibition. These results suggest that 5-FU antitumor activity against human colon carcinoma could be significantly potentiated without severe side effects by these two modulators, which possess different modes of action.

Animals↗
PubMed1995

Circulating concentrations and physiologic role of atrial natriuretic peptide during endotoxic shock in the rat.

OBJECTIVES: To determine if there are changes in circulating concentrations of endogenous atrial natriuretic peptide and the physiologic role of this peptide in endotoxic shock. DESIGN: A prospective, randomized, controlled animal trial. SETTING: University research laboratory. SUBJECTS: Anesthetized male Wistar rats, weighing 250 to 350 g. INTERVENTIONS: Six rats received 1.5 mg/kg body weight of lipopolysaccharide alone. Five rats received 1.5 mg/kg of lipopolysaccharide and 200 microL/100 g body weight of rabbit anti-atrial natriuretic peptide serum. Another five rats received 1.5 mg/kg of lipopolysaccharide and normal rabbit serum in the same volume as the antiserum. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of atrial natriuretic peptide, arginine vasopressin, and aldosterone were measured, and changes in hemodynamic parameters and renal function were monitored in rats with endotoxic shock after catheterization of the right jugular vein. Urine volume, urine sodium excretion, urinary potassium excretion, and urine 3', 5'-cyclic guanosine monophosphate (cGMP) excretion were measured at 12-hr intervals. The plasma atrial natriuretic peptide concentration was slightly but significantly lower 30 mins after the lipopolysaccharide injection (114.8 +/- 9.0 pg/mL at 0 hr, 75.6 +/- 6.2 pg/mL at 30 mins, p < .01) and then began to increase, peaking at 6 hrs (752.8 +/- 104.5 pg/mL, p < .01 vs. 0 time) and remaining at higher concentrations than before the preinjection value, up to 24 hrs. In contrast, acute spike-like increases of arginine vasopressin and aldosterone concentrations were observed 30 mins after the lipopolysaccharide injection, preceding the increase of the plasma atrial natriuretic peptide concentration. Measurements of urine volume and urine sodium excretion showed oliguria during the initial 12 hrs after the lipopolysaccharide injection, followed by diuresis and natriuresis during the subsequent 12 hrs. In addition, injection with anti-atrial natriuretic peptide serum in the diuretic phase 12 hrs after the lipopolysaccharide injection significantly inhibited the diuresis, natriuresis, and urine cGMP excretion in this model. Furthermore, the plasma aldosterone concentration 24 hrs after the lipopolysaccharide injection was significantly increased by the administration of the antisera. CONCLUSIONS: These findings suggest that endogenous atrial natriuretic peptide increases in the acute phase of endotoxic shock and plays an important role in water and electrolyte balance by regulating diuresis.

Aldosterone↗
PubMed1995

Inhibitory effects of intravenous lansoprazole on gastric acid hypersecretion in patients with postoperative stress.

The inhibitory effects of intravenous lansoprazole on gastric acid hypersecretion caused by stress after surgical invasion were studied in patients who underwent surgery under general anesthesia for gastrointestinal diseases. Patients in this study received either 15 mg or 30 mg of lansoprazole by slow intravenous injection twice daily for 3 days (six injections). The total number of patients studied was 82, with 41 patients in each group. Intragastric pH was measured every 8 h after the start of administration, and the inhibitory effects of intravenous lansoprazole on postoperative gastric acid secretion were evaluated using four grades: excellent, good, fair, and poor. In the 15-mg group, 65.8% (25 of 38 patients) were classified as good or excellent, and in the 30-mg group, 75.7% (28 of 37 patients) were good or excellent. No adverse effects directly attributable to the administration of lansoprazole were observed.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1995

In vivo antitumor activity of hexamethylmelamine against human breast, stomach and colon carcinoma xenografts.

We have evaluated the antitumor activity of Altretamine (hexamethylmelamine, HMM) on human carcinoma xenografts serially transplanted in nude mice. Five human breast carcinoma xenografts, MX-1, T-61, MCF-7, R-27 and Br-10, were inoculated subcutaneously into female nude mice. Two human stomach carcinoma xenografts, SC-1-NU and St-4, and three human colon carcinoma xenografts, Co-3, Co-4 and Co-6, were inoculated subcutaneously into male nude mice. One pellet of 17 beta-estradiol (0.1 mg/mouse) was inoculated subcutaneously in the mice transplanted with MCF-7 when the tumors were inoculated. HMM was administered per os daily for 4 weeks. MX-1 and T-61 tumors regressed completely after treatment with HMM at a dose of 75 mg/kg (the maximum tolerated dose: MTD) for MX-1 and 25 mg/kg for T-61. Br-10 was sensitive, whereas MCF-7 and R-27 were resistant to HMM at its MTD. HMM exerted the most potent antitumor effect against T-61. Against MX-1, it exerted an antitumor effect equivalent to that of cisplatin or cyclophosphamide. In addition, this agent was effective against all stomach and colon carcinoma xenografts, in particular St-4 (T/C% = 10.7: the mean tumor weight of treated group/the mean tumor weight of control group) and Co-3 (T/C% = 31.5%) which are insensitive to presently available agents. HMM seems worthy of further clinical investigation as a candidate agent to treat breast, stomach, colon and other carcinomas.

Altretamine↗
PubMed1995

[Prior enrichment of HIV-DNA with probe-DNA particles for an efficient PCR diagnosis].

PCR mediated detection of HIV-DNA has been widely used. However, compared with traditional immunological diagnoses, the extraction of DNA is a laborious and time consuming step. We have developed a procedure for the efficient isolation and concentration of HIV-DNA from cell lysates. We report here a novel method by one can recover HIV-DNA in a small volume (approximately 50 microliters) of solution from a large volume of crude cell lysate which contains as few as several copies. The method uses the specific hybridization of HIV-DNA to HIV probe-DNA particles. This prior enrichment augmented the sensitivity in the detection of HIV-DNA by PCR, and allows us to make a diagnosis even if the specimen contained an extremely low copy number of HIV-DNA molecules in a large volume, which would have otherwise resulted in false-negative data with the conventional extraction method. The method also enables the examination of 100 individual blood specimens in a combined form. Thus, the application of the present enrichment procedure with HIV probe-DNA particles should reduce the labor and cost of HIV diagnosis, since the HIV positive samples represent a very minor group of people among specimens subjected to clinical laboratory tests, and particularly, among blood samples voluntarily donated to be used for transfusions.

Base Sequence↗
PubMed1995

[Neoadjuvant chemotherapy and chemoradiotherapy in the treatment of esophageal cancer].

Adjuvant therapy following surgery has been mainstream in surgical adjuvant therapy for the patients with esophageal cancer in Japan. In western countries, neoadjuvant therapy has become popular in which surgery is performed depending on the effects of preoperative treatment. Neoadjuvant chemotherapy offers the advantage of downstaging the primary tumor and enhancing resectability and the potential advantage of assessing the response to preoperative chemotherapy directly in the primary tumor. Disadvantages include possible emergence of chemotherapy-resistant tumor cells, as well as the delay in achieving effective local tumor control and postoperative morbidity. In the phase II studies, most regimens have included CDDP/5-FU. Pathological CR rates have been less than 10% and median survival terms from eight to 28 months. The rationale for the concurrent use of chemotherapy and radiotherapy is to combine an agent that has an effect upon systemic micrometastases with a modality that enhances local tumor control. In addition, a number of chemotherapeutic agents have radiosensitizing effects. The majority of trials have employed CDDP/5-FU combined with RT for a total dose of 30 Gy. Pathological CR rates were from 20 to 40% and median survival terms from 12 to 29 months. Neither neoadjuvant chemotherapy nor chemoradiotherapy increased operative morbidity mortality, and there was a statistically significant increase in survival in complete responders. However, though the early and median survival was improved, the cure rate was not. Both therapies remain investigational.

Aged↗
PubMed1995

[Chemotherapy and multimodality therapy in the treatment of esophageal cancer].

Many single-agent phase II studies for patients with esophageal cancer had been performed, and at least five agents with modest activity have been indentified, BLM, MMC, CDDP, VDS and MTX, that revealed no CR. Even in the phase II study of 254-S, a new anticancer platinum complex, with a response rate of 43%, CR could not be recognized. Only two regimens of combination chemotherapy have been studied extensively, CDDP/BLM/VDS and CDDP/5-FU. The combination of CDDP/5-FU has gained popularity and JEOG phase II study revealed a response rate of 36%. As surgical adjuvant therapy, postoperative adjuvant therapy has been common in Japan. The 4th JEOG phase III clinical trial, comparing surgery alone and postoperative chemotherapy of CDDP/VDS, showed no additive effect to surgery by postoperative chemotherapy with such a regimen. In western countries, neoadjuvant chemotherapy is frequent and most of the regimens include CDDP/5-FU. Pathological CR rates were less than 10%, and median survival terms were from eight to 28 months. The rationale for the concurrent use of chemotherapy and radiotherapy is to combine an agent that has an effect upon systemic micrometastases with a modality that enhances local tumor control. In addition, a number of chemotherapeutic agents have radiosensitizing effects. In western countries, more than 35 trials studying over 1400 patients have been reported. The majority of trials have employed CDDP/5-FU combined with RT to a total dose of 30Gy. Pathological CR rates were from 20 to 40% and median survival terms were from 12 to 29 months. Both neoadjuvant chemotherapy and chemoradiotherapy did not change operative morbidity or mortality, and there was a statistically significant increase in survival in complete responders. However, early and median survival seems improved but cure rates are not. Both therapies require further investigation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Active oxygen species generation by circulating leukocytes and gastric submucosal microcirculatory disturbances in the early period after thermal injury.

The purpose of the present study was to determine the pattern of microcirculatory disturbance to investigate the causes of gastric mucosal blood flow depression in the early period after thermal injury. Male Wistar rats were anesthetized and a 30% full skin-thickness dorsal burn was inflicted. Active oxygen species (AOS) generated by circulating leukocytes were measured by chemiluminescence. Contraction of arterioles and venules was observed by intravital microscopy, and rolling or sticking of leukocytes in venules was counted using fluorescence microscopy. AOS generation by circulating leukocytes was diminished and arteriolar contraction and increases in rolling or sticking leukocytes in venules were observed 15 min after thermal injury. Decreased AOS generation by circulating leukocytes, contractions of arterioles, and increased rolling or sticking of leukocytes in venules was observed in the early period after thermal injury. Arteriolar contraction may explain decreases in mucosal blood flow. Moreover, decreased AOS generation by circulating leukocytes does not obviate the potential participation of leukocytes in microcirculatory disturbances, because rolling or sticking leukocytes were increased significantly 15 min after thermal injury.

Animals↗
PubMed1994

A genetic linkage map of the mouse using an expanded production system of restriction landmark genomic scanning (RLGS Ver.1.8).

We have developed an expanded system (RLGS Ver.1.8) for producing RLGS patterns that result in a 16-fold increase in the number of gels produced and a 10-fold reduction in the total cost per gel. The major modifications include: 1) performing the blocking and labeling step without phenol extraction or ethanol precipitation; 2) minimizing the reaction volume and the enzyme units in each step; 3) developing a long vertical agarose disc gel electrophoresis for the 1st-dimension; and 4) developing a new apparatus for multiplex vertical 2nd-dimensional electrophoresis. RLGS Ver.1.8 was used with a new combination of restriction enzymes to identify variation for 209 loci between C57BL/6J and DBA/2J. Twenty-six BXD RI strains were analyzed and 195/209 loci were genetically mapped. These loci were mapped in one week of laboratory work by two people. This system provides an important tool for the genetic analysis of new loci in similar genetic resources.

Animals↗
PubMed1994

Dose intensity of mitomycin C in adjuvant cancer chemotherapy for patients with gastric cancer.

Using a cohort of macroscopic curative resections of gastric cancer at stages II, III, and IV, a randomized controlled trial was performed to elucidate the dose efficacy of intensive adjuvant cancer chemotherapy with mitomycin C. Between June 1983 and December 1986, 336 patients with gastric cancer from 31 institutes were enrolled in the study. The cohort was stratified randomly by the telephone method into two arms. Group A received 20 mg and 10 mg of mitomycin C per body intravenously (IV) on postoperative days 0 and 1, respectively, and then tegafur at 600 mg/body daily perorally (PO) from postoperative week 2 for 1 year. Group B also received 0.2 mg of mitomycin C per kg IV at 3, 6, 9, and 12 months after surgery. The background factors in groups A and B were essentially identical, and the adverse effects were tolerable in both groups. The total administered doses of mitomycin C were significantly higher in group B than in group A, according to the protocol. Although no significant differences were observed in the actuarial overall survival rates between groups A and B at stages II, III, and IV, favorable survival was observed in group B, which received histologically absolute curative resection. This dose-intensive adjuvant cancer chemotherapy would be useful for gastric cancer patients treated by histologically curative surgery.

Chemotherapy, Adjuvant↗
PubMed1994

Combination chemotherapy with mitomycin C and cisplatin for advanced gastric cancer with multiple liver metastases.

A patient with advanced gastric cancer with multiple liver metastases was treated by reduction surgery at the primary site as well as by the intraarterial administration of mitomycin C (MMC) and cisplatin (CDDP) through a reservoir catheter inserted into the proper hepatic artery. After a palliative subtotal gastrectomy, MMC 8 mg/m2 was administered intraarterially (i.a.) followed by the administration of CDDP 80 or 40 mg/m2 i.a. with an interval of less than 1 week. After the completion of five courses of this regimen, a complete reduction of the hepatic tumors was achieved, while the level of serum carcinoembryonic antigen decreased to the normal range. The patient is currently alive with signs of disease recurrence at 17 months after initial diagnosis, while additional therapy with MMC + CDDP was continuously undergone until 17 months' after initial diagnosis with various interval. Although thrombocytopenia occurred during the treatment, it resolved within a few weeks after completing the combination chemotherapy without any specific treatment. The present case showed a better prognosis than we had expected, which suggested that combination chemotherapy with MMC and CDDP might thus be clinically useful because of its excellent antitumor activity and low toxicity.

Adenocarcinoma↗