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Biomedical subjects

K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 145 records · Page 8Linked to original sources
PubMed2000

An air-liquid interface promotes the differentiation of gastric surface mucous cells (GSM06) in culture.

The gastric surface epithelium is situated at an air-liquid interface because the luminal surface of the alimentary tract is in continuity with the air phase. However, the effects of this microenvironment on the gastric epithelium remain unclear. The aim of this study was to clarify the effects of an air-liquid interface on gastric epithelial cell biology. Gastric surface mucous cells (GSM06) were cultured at an air-liquid interface. Cultured cells were examined by histology, histochemistry, and transmission electron microscopy. When the cells were cultured at an air-liquid interface, the surface cells on the collagen gel became tall columnar and secreted periodic acid-Shiff-positive substances at the apical surface. These cells indicated many mucous granules in the apical cytoplasm and organized the basal lamina at the contact side with the gel. In contrast, under immersed condition, the surface cells showed immature features. This is the first report of an air-liquid interface promoting the differentiation of gastric surface mucous cells in a reconstruction culture of the gastric surface epithelial layer, suggesting that an air-liquid interface may function as a crucial luminal factor to maintain the homeostasis of gastric mucosa.

Air↗
PubMed2000

Hypoxia-induced pulmonary blood redistribution in subjects with a history of high-altitude pulmonary edema.

BACKGROUND: Pulmonary hypertension has been suggested to play an important role in development of high-altitude pulmonary edema (HAPE), and individual susceptibility has been suggested to be associated with enhanced pulmonary vascular response to hypoxia. We hypothesized that much greater pulmonary vasoconstriction would be induced by acute alveolar hypoxia in HAPE-susceptible (HAPE-s) subjects and that changes in pulmonary blood flow distribution could be demonstrated by radionuclide study. METHODS AND RESULTS: We performed ventilation-perfusion scintigraphy in 8 HAPE-s subjects and 5 control subjects while each was in the supine position and acquired functional images of pulmonary blood flow and ventilation under separate normoxic and hypoxic (arterial oxygen saturation, 70%) conditions. We also measured acceleration time/right ventricular ejection time (AcT/RVET) with Doppler echocardiography under each condition in both groups. Moreover, we assayed human leukocyte antigen (HLA) alleles serologically in the HAPE-s group. Pulmonary blood flow was significantly shifted from the basal lung region to the apical lung region under hypoxia in HAPE-s subjects, although no significant change in regional ventilation was observed. With Doppler echocardiography, HAPE-s subjects showed increased pulmonary arterial pressure during hypoxia compared with control subjects. The magnitude of cephalad redistribution of lung blood flow was significantly higher in the HLA-DR6-positive than in HLA-DR6-negative HAPE-s subjects. CONCLUSIONS: These findings suggest that acute hypoxia induces much greater cephalad redistribution of pulmonary blood flow that results from exaggerated vasoconstriction in the basal lung in HAPE-s subjects. Furthermore, pulmonary vascular hyperreactivity to hypoxia may be associated with HLA-DR6.

Altitude Sickness↗
PubMed2000

Absolute configuration of scyphostatin

[reaction: see text] The absolute configuration of the side chain of scyphostatin (1) has been established. The chemical degradation of 1 gave 4 and 9, which correspond to the C7'-C12' and C13'-C16' fragments of the natural products, respectively. The spectroscopic data and [alpha]D values of both compounds were compared to those of authentic samples. The results show that the absolute configuration of 1 is 8'R,10'S,14'R.

Journal Article↗
PubMed2000

Distribution and serum concentration of sisomicin released from fibrin glue-sealed dacron graft in the rat and human.

We investigated whether or not fibrin glue (FG) used as a sealant in vascular prostheses to prevent leakage might be useful as a carrier of antibiotics for the prevention of local graft infection. Sisomicin (SISO) was incorporated into fibrin glue (SISO-FG) and evaluated as to its safety and pharmacokinetics. SISO (1.75 mg) -FG Dacron grafts were implanted subcutaneously in the anterior abdominal region of Sprague-Dawley rats, and then the changes in SISO concentrations in the serum and in the tissue around the implantation sites were compared with those same sites in rats that had had intravenous injection of SISO (1.75 mg). The serum SISO concentrations were significantly lower in the SISO-FG Dacron graft group than they were in the intravenous injection group. However, until 4 h after implantation the SISO concentrations in the tissues around the implantation sites were significantly higher in the SISO-FG Dacron group than they were in the iv injection group, and the peak concentrations during that time were 5.8 times higher for the SISO-FG Dacron group than they were for the intravenous injection group. The ratio of the area under the tissue concentration time curve of SISO (AUC tissue) after implantation of the SISO-FG Dacron graft to that after intravenous injection of SISO was 13.08. Therefore, FG was considered to control the release of SISO into the serum and to maintain a high SISO concentration in the tissue around the implantation site. Clinically, SISO (45 mg) -FG was applied directly to the Dacron grafts implanted in 10 patients who underwent prosthetic vascular reconstruction. No graft infection was observed in any of the patients who received SISO-FG Dacron grafts. The mean serum concentration of SISO was 0.65+/-0.17 microg/mL after 1 h and 0.33+/- 0.21 microg/mL after 3 h. The results of these clinical applications are in close correlation with those of the animal experiment and suggest that FG is useful as a carrier of SISO, allowing its controlled release for the prevention of local infection.

Aged↗
PubMed2000

Gene therapy of Parkinson's disease using adeno-associated virus (AAV) vectors.

Parkinson's disease (PD) is characterized by the progressive loss of the dopaminergic neurons in the substantia nigra and a severe decrease in dopamine in the striatum. A promising approach to the gene therapy of PD is intrastriatal expression of dopamine-synthesizing enzymes [tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC)]. The most appropriate gene-delivery vehicles for neurons are adeno-associated virus (AAV) vectors, which are derived from non-pathogenic virus. Therefore, TH and AADC genes were introduced into the striatum in the lesioned side using separate AAV vectors in parkinsonian rats, and the coexpression of TH and AADC resulted in better behavioral recovery compared with TH alone. Another strategy for gene therapy of PD is the protection of dopaminergic neurons in the substantia nigra using an AAV vector containing a glial cell line-derived neurotrophic factor (GDNF) gene. Combination of dopamine-supplement gene therapy and GDNF gene therapy would be a logical approach to the treatment of PD.

Animals↗
PubMed2000

Relationship between cancer cell proliferation and thallium-201 uptake in lung cancer.

UNLABELLED: Although thallium-201 (201Tl) uptake is related to perfusion in many normal tissues, the biologic rationale for 201Tl uptake in tumors is uncertain. To determine if tumor uptake is related to cell proliferation, we correlated the relative retention of 201Tl in lung tumors with expression of Ki-67, an indicator of cell proliferation. METHODS: Sixty patients with lung tumors, included small cell carcinoma (n = 8) and non-small cell carcinoma (n = 52), underwent 201Tl single photon emission computed tomography (SPECT) imaging. The 201Tl lesion uptake was determined on early and delayed images and the radiotracer retention index (RI) was calculated. Tumor specimens were obtained at surgery or bronchoscopy. The cell proliferation ratio was estimated with MIB-1, a monoclonal antibody that recognized the nuclear antigen Ki-67. RESULTS: The average 201Tl index was 2.13+/-0.61 (early) and 2.46+/-0.83 (delayed). The average RI was 17.44+/-35.01. Overall, the 201Tl index (delayed) and the cancer cell proliferation were correlated (r = 0.70, p < 0.0001). Of interest, there was a significant correlation (r = 0.872, p < 0.0005) between the 201Tl index on delayed images and the cell proliferation ratio in patients with small cell but not non-small cell lung carcinoma. The 201Tl index (delayed) was significantly higher (p < 0.0001) in patients with small cell lung carcinoma than in patients with non-small cell lung carcinoma. CONCLUSION: 201Tl imaging appears to be useful for evaluating patients with small cell lung carcinoma but not non-small lung carcinoma, and is correlated with the monoclonal antibody MIB-1, a marker of cell proliferation.

Adult↗
PubMed2000

Basal layer reactivity in hyperplastic and metaplastic lesions of the bronchi as studied by lectin histochemistry.

The relationship between squamous metaplasia and squamous cell carcinoma of the bronchi has been the subject of controversy. We investigated basal cell hyperplasia, stratification, squamous metaplasia, and squamous cell carcinoma by means of lectin histochemistry with peanut agglutinin (PNA), Ulex europeus agglutinin-I, soybean agglutinin, and Dolichos biflorus agglutinin for all normal basal cells that are reactive. A basal layer stained with PNA was observed in basal cell hyperplasia, stratification, and squamous metaplasia, but this layer was not exhibited by squamous cell carcinoma. In hyperplasia and metaplasia, PNA staining was biased toward the lowest (basal) layer, whereas staining for the other lectins was more uniformly distributed across the layers. A PNA-positive basal layer may be important for the morphologic reversibility of the bronchial mucosa in hyperplastic and metaplastic lesions, and destruction of this layer may be associated with a progression from metaplasia to squamous cell carcinoma.

Adenocarcinoma↗
PubMed2000

Double cancer (lung and colon cancer) that showed complete remission with irinotecan and cisplatin combined chemotherapy.

We report a rare case of double (colon and lung) cancer which showed complete remission with chemotherapy with irinotecan (CPT-11) and cisplatin (CDDP). The patient was a 67-year-old man who was diagnosed as having double cancer (stage IIIb pulmonary adenocarcinoma and stage 0 [or 1] well-differentiated adenocarcinoma of the ascending colon). Two courses of chemotherapy (CPT-11, 60 mg/m2, days 1 and 8; CDDP, 30 mg/m2, days 1 and 8) were performed. The combination therapy of CPT-11 and CDDP was very effective. In Japan, there have been few published reports describing the use of CPT-11 for the treatment of gastrointestinal cancer. We think that the use of CPT-11 in gastrointestinal cancer is promising.

Adenocarcinoma↗
PubMed2000

Loss of diurnal variation in ornithine decarboxylase and apoptosis in small intestine of Mongolian gerbils.

The aim of this study was to examine the diurnal variations in ornithine decarboxylase (ODC) activity and apoptosis in the small intestinal mucosa of Mongolian gerbils. First, the feeding, drinking, and ambulatory patterns of the gerbils were recorded. The results indicated that Mongolian gerbils lost diurnal cyclicity in feeding, drinking, and ambulatory patterns. Second, ODC activity and apoptosis in the intestinal mucosa of gerbils were characterized by measurements at four time points (11:00, 17:00, 23:00, and 05:00 h; light period, 08:00-20:00 h). Apoptosis was evaluated in terms of percent fragmented DNA (fragmented DNA/total DNA). Neither ODC activity nor apoptosis showed diurnal variation in the jejunal mucosa of the Mongolian gerbils. In 48-h fasted gerbils, ODC activity in the intestinal mucosa decreased, but this activity increased significantly 2 h after refeeding; percent fragmented DNA increased in the intestinal mucosa, and returned to the control level 2 h after refeeding. These results indicate that postprandial local nutrients are an important factor in regulating diurnal variation in ODC activity and apoptosis in the small intestine of gerbils.

Animals↗
PubMed2000

Stress and coping behavior in patients with diabetes mellitus.

Diabetes mellitus is a disease which must be controlled over the lifetime of a patient. We investigated the issues of stress and coping for diabetes mellitus which may influence self-management. In addition, we examined the association of these factors with blood glucose control, in order to review self-management instructions for diabetes mellitus. The study included 153 patients with diabetes mellitus. The patients were divided into two subgroups: good-control group, comprising patients with glycohemoglobin (HbA1c) values less than 7.0%; and poor-control group, comprising those with HbA1c values of 7.0% or more. All patients responded to a questionnaire regarding stress tolerance, Jalowiec and Power's coping scale and awareness of diabetes mellitus. Stress tolerance was not significantly different between the good-control and poor-control groups. No significant gender differences in coping score were evident for the good-control group. However, in the poor-control group, the coping score in men was significant higher than that in women. The problem-oriented coping score for men in the poor-control group was significantly higher than that for the good-control group (p < 0.01). In a comparison of awareness of diabetes mellitus, the proportion of patients who replied that they were rigidly following diabetes treatment was higher in the poor-control group than the good-control group. Patients with diabetes mellitus may have a knowledge of the disease and a strong will to resolve problems. This is especially true for male patients in that their will appeared to be stronger, but they may not have the resolve to establish appropriate behavior patterns. In the future, methods for evaluating self-management should be included in diabetes education.

Adaptation, Psychological↗
PubMed2000

Changes of serum calcitonin in stress load.

Calcitonin, one of the calcium-regulating hormones, is known to have diverse biological effects including those on the gastrointestinal tract. In this organ, the hormone is reported to inhibit gastric acid secretion, gastric motility, and gastrin secretion and to stimulate release of somatostatin, thereby exerting antiulcer and antilesion effects on stress-induced as well as other types of experimental gastric ulcers or lesions. This fact prompted us to examine changes in serum calcitonin concentration during the development of stress-induced gastric lesions in rats. DA rats were constrained in a stress cage after a 24-h fast and then immersed in 24 degrees C water to the level of the xiphoid process for 2 or 5 h. Serum calcitonin concentrations in stressed rats were significantly lower than those in control rats. To investigate the mechanism of the decline in serum calcitonin level under stress in these rats, we conducted a time-course study of serum calcitonin concentration and ionized calcium level during water-immersion stress, lasting 2 h, and during 4 h following release from the stress. Water immersion caused a remarkable decrease in serum calcitonin concentration as early as at 30 min. After release from stress, serum calcitonin concentration gradually recovered. The ionized calcium level in the blood did not change significantly throughout the experimental period. Furthermore, to examine if the sympathetic nerve system was involved in the stress-induced change of serum calcitonin concentration, alpha- and beta-receptor antagonists were administered intraperitoneally before stress exposure. Administration of alpha-receptor antagonist at a low dose that did not have any effect on serum calcitonin concentration in a preliminary study, restored the decline of serum calcitonin level, whereas beta-receptor antagonist did not. These results suggest that stress-provoked decrease of serum calcitonin concentration may be mediated not by a change of ionized calcium level but by alteration of sympathetic nerve activity (particularly via the alpha-receptor).

Adrenergic alpha-Antagonists↗
PubMed2000

Endoscopic injection sclerotherapy for esophageal varices prolonged survival of patients with hepatocellular carcinoma complicating liver cirrhosis.

BACKGROUND: A prospective controlled study was performed between 1982 and 1991 to evaluate the efficacy of endoscopic injection sclerotherapy (EIS) in patients with esophageal varices complicated by hepatocellular carcinoma and liver cirrhosis. METHODS: The study included 83 patients with esophageal varices, hepatocellular carcinoma, and liver cirrhosis. Forty-three patients (group 1) underwent prophylactic EIS or emergent EIS for bleeding varices. EIS was performed weekly 4 to 6 times until the varices disappeared. The remaining 40 patients (group 2) underwent conservative therapy and did not undergo EIS. Survival rates were compared between the 2 groups. RESULTS: During the 5-year observational period, all patients who did not undergo EIS died. Sixteen in group 2 (40.0%) died of gastrointestinal bleeding including ruptured esophageal varices. In contrast, patients treated with EIS survived significantly longer (p<0.001). Nine patients (20.9%) treated with EIS experienced gastrointestinal bleeding as a result of which 5 (11.6%) died. EIS prolonged survival in patients classified as Child's A or B but did not affect survival in patients with Child's C hepatic function. EIS was effective in prolonging survival in patients with hepatocellular carcinomas smaller than 5 cm. However, EIS had no effect in patients with hepatocellular carcinomas that were larger than 5 cm. EIS prolonged survival only for patients with nodular hepatocellular carcinoma and had no effect in patients with massive and diffuse hepatocellular carcinoma. Further, EIS prolonged survival only for patients who did not have portal vein thrombosis. CONCLUSION: Based on this prospective study, we concluded that EIS was effective in prolonging the survival period of a select subset of patients with hepatocellular carcinoma.

Aged↗
PubMed2000

Pulmonary artery remodeling modifies pulmonary hypertension during exercise in severe emphysema.

To clarify the relation between the vessel remodeling and the physiology of pulmonary circulation in chronic obstructive pulmonary disease (COPD), we studied the pulmonary hemodynamics at rest and during exercise (25W) and the morphology of pulmonary arteries with external diameters of 100-200 microm in ten patients with severe emphysema. The wall thickness (WT) was defined as the intima plus media. The percent WT of the external diameter (% WT) in emphysema (36.0 +/- 4.3%) was significantly increased compared with that (22.6 +/- 3.3%) in five control lungs. The % WT was not related to pulmonary arterial pressure (Ppa) at rest, but was highly correlated with exercise Ppa (r = 0.721, P = 0.02) and with deltaPpa (Ppa during exercise-Ppa at rest) (r = 0.899, P = 0.0004). These findings suggest that pulmonary artery remodeling leads to reduced recruitability and distensibility of pulmonary vessels and is closely related to exercise pulmonary hypertension.

Aged↗
PubMed2000

A preoperative alternating chemotherapy and radiotherapy program for patients with stage IIIA (N2) non-small cell lung cancer.

The objective of the present study was to evaluate the feasibility and toxicity of a preoperative alternating chemotherapy and radiotherapy program followed by surgery in stage IIIA non-small cell lung cancer (NSCLC). The tumor response, resection rate, tumor/lymph node downstaging, and survival were also evaluated. The positive predictive value (PPV) in the diagnosis of mediastinal lymph node metastasis was 81% using conventional magnetic resonance imaging (MRI) with short inversion-time inversion recovery (STIR) technique (STIR-MRI) on our criteria. Eligible patients had clinical N2 lesions (stage IIIA) and a World Health Organization (WHO) performance status of 0-2. The treatment program consisted of two courses of preoperative cisplatin, vindesine, and ifosfamide; alternating with radiotherapy, including two courses of 20 Gy radiation. Surgery was performed within 4 weeks after the treatment. Twenty-two patients with stage IIIA (N2) NSCLC (20 men and two women, age 35-71 years) were enrolled into the study. Hematologic and other toxicities were within an acceptable range. Surgery was not indicated for two patients because of distant metastasis; one patient with renal dysfunction and one with pancytopenia during this treatment underwent surgery subsequently. The clinical response rate was 50% (partial response in 11/22). Definitive surgery was indicated for 18 patients resulting in 17 patients with complete resection and one exploratory thoracotomy. A pathologic complete response of the primary tumor occurred in 41% of the patients (seven of 17; without residual tumor), whereas 58% (ten of 17) were pathologic N0. The median survival was 33 months with an actuarial 4-year survival rate of 33% in 17 patients with complete resection and 30 months with 28% 4-year survival rate in all entered patients. A randomized phase-III study using this approach for stage IIIA (clinical N-2 disease) is warranted.

Adult↗
PubMed2000

Tubular injury as a cardinal pathologic feature in human heme oxygenase-1 deficiency.

Heme oxygenase (HO) catalyzes degradation of heme to biliverdin, iron, and carbon monoxide. It consists of three isoforms: an inducible form (HO-1), a constitutive form (HO-2), and the third isoform (HO-3), with properties similar to HO-2. There is limited evidence to suggest that the induction of HO-1 may have anti-inflammatory effects in an in vivo model of oxidative stress-mediated renal injury. We experienced the first human case of HO-1 deficiency. The patient had persistent proteinuria and hematuria, with biochemical evidence of renal tubular injury. We obtained three consecutive renal specimens: two from renal biopsies at 2 and 5 years of age and the third from autopsy at 6 years of age. The patient had systemic vascular endothelial-cell injury with massive intravascular hemolysis. The serum was loaded with heme and a large amount of heme-conjugated haptoglobin. A high concentration of haptoglobin was also detectable in urine. Mesangial proliferation or change in glomerular capillary-wall thickness was relatively mild to moderate in all specimens. Electron microscopic examination showed widespread endothelial detachment and subendothelial deposits of an unidentifiable material. It was striking that tubulointerstitial injury, with tubular dilatation and/or atrophy, interstitial fibrosis, and inflammatory cell infiltration, advanced progressively. Tubular epithelial cells were injured, and massive deposition of iron and haptoglobin was detectable. Bowman's capsules were dilated significantly, probably secondary to the collapse of atrophic tubuli. This is the first report to show that HO-1 has critical roles in vivo in protecting renal tubuli, in addition to vascular endothelium, from oxidative injury.

Child, Preschool↗
PubMed2000

Control of cell death by the smart polymeric vehicle.

We report a novel drug delivery system for apoptosis induction by a "smart" polymer vehicle possessing thermosensitivity and bioaffinity. The polymer chain was prepared by copolymerization of N-isopropylacrylamide and N-methacryloyloxysuccinimide. Cell-adhesive RGDS peptide was conjugated with the copolymer as a ligand model for bioaffinity. When the temperature was increased, nanoscale aggregates precipitated from a copolymer aqueous solution. Either dolichyl phosphate (dol-p), which is an apoptotic inducer, or dolichol was added to aggregates at around the precipitation temperature (31 degrees C), and the temperature was raised to 37 degrees C for incorporation. Aggregates incorporating dol-p or dolicol were added to a human promonocytic leukemia U937 cell suspension at 37 degrees C. When the temperature was lowered to 25 degrees C, cells underwent apoptosis in the presence of Ca2+. Probably, copolymer vehicles were concentrated on a cell surface through the binding of RGDS and integrin and the release of lipid inducers was caused by the disruption of vehicles in response to temperature.

Acrylamides↗
PubMed2000

Histaminergic effect on apoptosis of rat small intestinal mucosa after ischemia-reperfusion.

This study aimed to examine the relationship between a harmful effect of histamine and apoptosis following ischemia-reperfusion in the rat intestine. The superior mesenteric artery was occluded for 60 min followed by reperfusion for 60 min. Rats were infused with H1-receptor antagonist (chlorpheniramine maleate) or H2-receptor antagonist (cimetidine). Additional rats were pretreated with aminoguanidine (100 mg/kg). Percent apoptosis in the intestinal mucosa increased after reperfusion, but neither H1 nor H2 antagonists had any effect on apoptosis. Aminoguanidine pretreatment inhibited activity of diamine oxidase and increased the plasma histamine concentration. Aminoguanidine attenuated the increase in mucosal apoptosis following reperfusion. Apoptosis induced by an ischemic insult to the intestinal mucosa was not related to an undesirable effect of histamine. Attenuation of increased intestinal apoptosis might be due to increased plasma histamine level and/or other pharmacological action of aminoguanidine, including inhibition of inducible nitric oxide synthase.

Animals↗