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Biomedical subjects

T Fujimoto

Publications and source records attributed to T Fujimoto.

At least 487 records · Page 27Linked to original sources

A study of the extracellular matrix protein as the migration pathway of neural crest cells in the gut: analysis in human embryos with special reference to the pathogenesis of Hirschsprung's disease.

Immunocytochemical studies on the human embryo were made using antineuronal cell antibody and a panel of anti-extracellular matrix protein antibodies such as fibronectin, laminine, collagen type IV, and hyaluronic acid. All the enteric ganglia are shown to be from a single, vagal neural crest source, although the recent dual gradient migration theory of neural-crest-derived cells in the gut can be challenged. Neural-crest-derived cells first appear in the mesenchyme of the developing esophagus at 4 weeks, and then migrate down along the gut in a craniocaudal direction. The observed distribution of fibronectin and hyaluronic acid indicates the presence of these matrices providing a migration pathway for neural-crest-derived cells in the developing gut. The appearance of neural-crest-derived cells in the gut is always preceded by the appearance of these matrices. On the other hand, substrate or laminine and collagen type IV appears to promote outgrowth of neurites from settled neural-crest-derived cells and their maturation. The distribution of these matrices within the pathway seems consistent with their role in navigating the neural-crest-derived cells toward their final destination. Enteric neurogenesis is dependent on these matrices, and their alteration in early embryonal stage may be a significant factor in the pathogenesis of Hirschsprung's disease.

Cell Movement↗

An autopsy case of cholesterol embolism following percutaneous transluminal coronary angioplasty and aortography.

A 67-year-old woman with a 6-year history of angina pectoris underwent percutaneous transluminal coronary angioplasty. Just after manipulation of the guiding catheter during a second attempt at angioplasty and aortography, the patient developed intestinal obstruction with peritonitis. Laparotomy was performed, and surgical specimens taken during surgery revealed necrosis and perforation of the small intestine. Microscopical examination proved that this was the result of multiple fresh cholesterol emboli in the arteries. Postoperatively, renal failure and sepsis developed, and the patient died 13 days after surgery. Autopsy revealed multiple cholesterol emboli in arteries of the intestine, spleen, pancreas, liver and kidneys. This case demonstrates that cholesterol embolism can be a serious complication of percutaneous transluminal coronary angioplasty.

Aged↗

Susceptibility of methicillin-resistant Staphylococcus aureus to the selenium-containing compound 2-phenyl-1,2-benzoisoselenazol-3(2H)-one (PZ51).

The growth of Staphylococcus aureus 209P was inhibited by 0.20 micrograms of 2-phenyl-1,2-benzoisoselenazol-3(2H)-one (PZ51) per ml, while strains of the family Enterobacteriaceae were more resistant to the drug. The MIC for 90% of methicillin-resistant S. aureus strains was 1.56 micrograms/ml, and the drug was bactericidal. The selenium in PZ51 was essential, since its sulfur analog (PZ25) lost the antibacterial activity.

Azoles↗

Retrieving vesicles in secretion-induced rat chromaffin cells contain fodrin.

We examined the distribution of fodrin and cytochrome b561 in secretion-induced rat chromaffin cells (epinephrine cells) by immunofluorescence and immunoelectron microscopy. Fasted rats injected with a large dose of insulin were perfusion-fixed and frozen sections of the adrenal medulla were immunolabeled. Fodrin, a peripheral membrane protein, was distributed only in the cell periphery in control cells, but was observed in the cell interior after the insulin treatment; many of the markers were found around small vesicles, 50-200 nm in diameter, and large vacuoles, more than 500 nm in diameter. On the other hand, cytochrome b561, an integral membrane protein, was seen only in the chromaffin granules in control cells, and appeared in small vesicles in the stimulated cells but not in large vacuoles. By double immunolabeling it was shown that cytochrome b561 coexisted with fodrin in the small vesicles. The coexistence of the two proteins was confirmed by the labeling of subcellular particles immunoadsorbed from the insulin-treated adrenal medulla homogenate; vesicles immunoisolated with anti-fodrin antibody on polyacrylamide beads were positively immunolabeled with anti-cytochrome b561 antibody. The present results show that during massive secretion fodrin is taken into the cell interior by vesicles, which may be a mechanism that retrieves the secretory granule membrane from the cell surface.

Animals↗

Immunoelectron microscopy of fodrin in the rat uriniferous and collecting tubular epithelium.

We examined the localization of fodrin in epithelial cells of rat uriniferous and collecting tubules by immunofluorescence and immunoelectron microscopy of frozen sections. In the uriniferous tubule, fodrin was found along the cell membrane and in the well-developed terminal web, as previously reported in other epithelial cells: in the terminal web and along the basolateral cell membrane in the proximal tubule; all around the cell surface in the thin limb of Henle; along the basolateral surface in the thick limb of Henle's thick segment and the distal tubule. In the intercalated cells of the collecting tubule, fodrin was found not only along the basolateral cell membrane but also in the apical cytoplasm. The most peculiar labeling was obtained in the principal cells of the collecting tubule. In addition to labeling in the basolateral cell membrane, fodrin was found diffusely in the cytoplasmic matrix. Association of fodrin with any particular structure could not be identified, but the Golgi area was apparently free of labeling. Cytoplasmic labeling was more conspicuous in the principal cells of the medulla than in those of the cortex. The present results show that fodrin need not always exist in association with the cell membrane or the cytoskeleton but can occur in the cytoplasmic matrix, at least in epithelial cells. We discuss the possible physiological significance of the latter distribution.

Animals↗

Determination of sisomicin in eluate from dried blood spot on filter paper disc for monitoring of blood level in rat, by reversed-phase high-performance liquid chromatography after pre-column fluorimetric derivatization.

About 20 microliters of whole blood obtained by venipuncture from rat tail vein was spotted onto a filter paper and the blood spot was punched out (5 mm diameter). Sisomicin (SISO) in the dried blood spot (DBS) was extracted effectively into 0.5 M Na2HPO4 solution by ultrasonication and determined by reversed-phase high-performance liquid chromatography with pre-column derivatization using o-phthalaldehyde and beta-mercaptopropionic acid. This method could be used for the pre-clinical study of SISO blood levels of a number of mice or rats without killing. The results were identical with those for SISO in serum, if corrected for hematocrit values, and were used for the calculation of pharmacokinetic parameters for individual rats. The detection limit of SISO in DBS (10.1 microliters of whole blood) was 1.0 microgram per ml of whole blood.

Animals↗

[Determination of isepamicin in the eluates from the dried blood spots on filter paper for monitoring of blood levels in a guinea-pig].

In general, collection of serial blood samples from small experimental animals is difficult in terms of sampling site and operation technique. To overcome these problems, a simple reproducible method has been improved by the use of filter papers. Whole blood obtained by venipuncture from the ear vein of guinea-pig was spotted onto a filter paper. Isepamicin in the dried blood spot was extracted with 0.5 M Na2HPO4 buffer by incubation and determined by fluorescence polarization immunoassay. Linearity was established over the range of 5-150 micrograms/ml by using only 100 microliters of whole blood. Consequently its accuracy and precision were good, with mean coefficient of variation of less than 5%. The method described here correlates well with a conventional sampling method and could be used for the pre-clinical study of isepamicin blood levels of individual guinea-pigs. This method is suitable for the simultaneous measurement of aminoglycoside antibiotics or physiological parameters after the administration of aminoglycoside antibiotics for the pharmacokinetics study.

Animals↗

Determinants of late potentials in myocardial infarction.

To clarify factors which have an influence on late potentials (LPs), signal averaged electrocardiogram, echocardiogram, cardiac catheterization and Holter monitoring were studied in 86 patients with previous myocardial infarction (MI). Group 1 consisted of 27 patients with LPs (LP duration greater than or equal to 20 msec) and Group 2 consisted of 59 patients without them. Twelve percent of anterior MI and 35% of inferior MI had LPs. Left ventricular (LV) diastolic dimension was larger and % fractional shortening was lower in group 1 than those in group 2. LV end-diastolic volume index and LV end-systolic volume index were larger and LV ejection fraction was lower in group 1 than those in group 2. Aneurysm was noted in 37% in group 1 and 17% in group 2 (p less than 0.05), and mean number of involved coronary vessels was 2.3 +/- 0.8 in group 1 and 1.7 +/- 0.8 in group 2 (p less than 0.05). No significant difference was found in other clinical and hemodynamic parameters. The incidence of patients with 100 or more ventricular premature contractions per hours and that with ventricular tachycardia (VT) were significantly higher in group 1 than in group 2 (26% vs 7%, p less than 0.05, 33% vs 7%, p less than 0.01, respectively). Multiple regression analysis and the method of quantification demonstrated that ventricular arrhythmia was most strongly associated with LP duration.

Action Potentials↗

The effects of class IA antiarrhythmic drug on the common type of atrial flutter in combination with pacing therapy.

In 11 patients with common type of atrial flutter (common AF), rapid atrial pacing from the high right atrium was performed before and/or after class Ia antiarrhythmic drug administration, confirming transient entrainment by decreasing the pacing cycle length by 10 ms. In 10 patients before the drug administration, common AF was not interrupted although the pacing cycle length was decreased to 200 ms in 5 patients, accelerated atrial flutter or atrial fibrillation was induced in 4 patients, and common AF was converted into sinus rhythm in only 1 patient. After the drug administration common AF was converted into sinus rhythm in 5 out of 6 patients. The class Ia antiarrhythmic drug prolonged the common AF cycle length (255 +/- 12 ms vs. 298 +/- 37 ms, p less than 0.005) and widened the entrainment zone (64 +/- 7 ms vs. 90 +/- 20 ms, p less than 0.05). The widening of the entrainment zone and the prolongation of the common AF cycle length facilitate the successful conversion of common AF at a longer pacing cycle length, which would not precipitate atrial fibrillation or accelerated atrial flutter. The combination therapy of rapid atrial pacing and the class Ia antiarrhythmic drug is thought to be useful in the therapy of common AF.

Adult↗

Disorganizing-fibrosing processes in alveolar walls of interstitial pneumonia, "alveolopneumonitis": a morphopathological study.

Disorganizing-fibrosing processes of alveolar walls in 13 autopsied (including 4 previously biopsied) and 3 biopsied cases of acute and chronic interstitial pneumonia were presented. The processes of alveolar walls were characterized initially by histolysis of the alveolar walls and transformation of the tissue into mesh or reticular structure caused by proliferation of fixed cells probably of endothelial cell origin, subsequently by formation of basement membrane-like structures along the proliferated cells, and ultimately by either fibrosis of the entire thickness of the disorganized tissue or axial fibrosis with accumulation of proliferated cells towards axis and peripheral recanalization. These processes tended to occur in the subpleural regions and extend thereafter to the deeper portions of lungs. In some cases recurrent alveolitis which occurred on the basis of axial fibrosis as aforementioned was noted. Problems concerning genesis and nature of these processes were discussed, and a new nomenclature "alveolopneumonitis" was proposed instead of interstitial pneumonia.

Adult↗

Disorganization process in the development of diabetic nodular glomerulosclerosis.

In order to clarify the mode of development of the diabetic nodular glomerulosclerosis, 38 kidney specimens of autopsied and biopsied diabetic cases were studied light and electron microscopically including serial sections. Disorganization process occurred chiefly at the capillary region of glomeruli. Early change of this process was proliferation of intramembranous cells following histolysis in the glomerular loop and it was characterized by transformation of the glomerular loop into enmeshed or reticular structure, that is, disorganization of the glomerular architecture. In the subsequent stage intercellular matrix production and hyalinization accompanied by axial crowding of proliferated intramembranous cells and peripheral recanalization of blood spaces were clarified. And in the later stage axially crowded intramembranous cells decreased in number and the matrix was increased and hyalinized, resulting in the formation of the axial hyaline nodule. The distribution of this process was focal and segmental, lesions of various stages coexisted, and it was suggested that glomerular lesions may spread all over the kidney by recurrence of this process. This process was quite similar to those seen in disorganization process of glomerulonephritis. But another characteristic changes were the presence of foam cells, intra- and intercellular deposition of lipid droplets, and increased matrix formation.

Biopsy↗

The sites of intra-embryonic haemopoiesis prior to the hepatic haemopoiesis in the chick.

The sites of intra-embryonic haemopoiesis of the chick embryo (stages 15-26) preceding the initiation of hepatic haemopoiesis was investigated by means of serial sections stained with azan liquid. Hitherto undescribed blood islands of large size and clear outline were found in the neck and lateral body fold of the embryo. They consisted of dense aggregations of erythroblasts and thin endothelial cells surrounding them, and could be clearly identified by azan staining. In the neck, the blood islands were located near the branchyal arteries at stages 15-18, while in the lateral fold they were seen mainly at stages 17-19. Examination of serial sections indicated that the blood islands extended in a cephalocaudal direction, assuming a rod shape. The largest blood island was found in the lateral fold, measuring 50 microns in diameter and 900 microns in length. Besides these islands, occasional sites of haemopoiesis were found in the mesonephros, mesentery, dorsal regions of the trunk, head and allantois after stage 18. As the blood islands found in this study alternated their localization sites according to developmental stage, they were considered to be temporary haemopoietic tissues rather than persistent ones.

Animals↗

Chromosome pattern in juvenile chronic myelogenous leukemia, myelodysplastic syndrome, and acute leukemia associated with neurofibromatosis.

We studied chromosomes of BM cells from four neurofibromatosis (NF) patients with leukemia. One patient had a normal diploid karyotype in the chronic phase of juvenile chronic myelogenous leukemia (JCML). When the the leukemia evolved into the accelerated phase, she had cells with 46,XX,-7,+der(7)t(3;7)(q21;p22); the abnormalities resulted in a partial 7p deletion. In another patient with JCML, BM cells in the accelerated phase had 45,XY,-7. The abnormal cells with monosomy 7 disappeared from the BM after chemotherapy but reappeared later in the course. Another patient developed refractory anemia with excess of blasts in transformation (RAEB-T) and had cells with 46,XX,-6,+r(6)(p23?q21?); the abnormalities resulted in partial 6p and 6q deletions. The other patient with ANLL had cells with 45,XX,-7. Our findings and review of data on nine other patients suggest that BM cells of NF patients with JCML in chronic phase have no microscopically detectable chromosome changes and that cells with chromosomal deletion emerge when JCML evolve into the accelerated or blast phase. Thus, deletion of the whole or part of certain chromosomes, such as chromosomes 6, 7, etc., may be an important step towards the evolution of JCML cells or the development of de novo acute leukemias in NF patients.

Child↗

[Preventive hepatic arterial infusion in high risk cases of liver metastasis from gastric cancer].

Preventive hepatic arterial infusion (MMC 20 mg, 5-FU 500 mg; one-shot) was applied to high risk cases of liver metastasis from gastric cancer. Postoperative liver metastases were found in 5 (16.1%) of 31 arterial infusion patients, against 9 (25.7%) of 35 controls. The average interval to recurrence from operation was 6.8 +/- 3.0 (SD) months in arterial infusion, against 5.4 +/- 3.0 months in controls. These results suggest that preventive hepatic arterial infusion will decrease the rate of postoperative liver metastasis from gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical study on clarithromycin granule and tablet in the field of pediatrics].

A newly developed macrolide clarithromycin (TE-031, A-56268), with antibacterial spectrum and antibacterial activity nearly equal to those of erythromycin (EM), shows beneficial characteristics such as a higher blood level, higher recovery rate in urine, and better penetration into each tissue than conventional macrolides (MLs). TE-031 has been studied in adults against various infections and proved to be useful. The present paper describes the results of a study in children to examine the usefulness of TE-031 granules and tablets with a potency of 50 mg. TE-031 granules were administered to 132 children with ages from 6 months to 13 years and 10 months. Excluded from the evaluation were 12 cases in which clinical effects were deemed unevaluable. The evaluable subjects consisted of 1 case with pharyngitis, 3 with tonsillitis, 9 with acute bronchitis, 19 with pneumonia, 19 with mycoplasmal pneumonia, 2 with scarlet fever, 20 with Campylobacter enteritis, 11 with impetigo, 2 with subcutaneous abscess, 18 with primary atypical pneumonia and 16 with acute enteritis of unidentified pathogens; a total of 120 subjects. An average daily dose of TE-031 was 25.9 mg/kg, divided into 3 doses except 1 case with 2 daily doses and lengths of the treatment averaged 7 days. TE-031 tablets each containing 50 mg potency, were administered to 49 subjects with ages from 3 year and a month to 14 years consisting of 8 cases with pharyngitis, 1 with tonsillitis, 1 with acute bronchitis, 4 with pneumonia, 14 with mycoplasmal pneumonia, 4 with scarlet fever, 5 with Campylobacter enteritis, 7 with impetigo, 1 with atypical pneumonia, 1 with Salmonella gastroenteritis and 3 with acute enteritis caused by unidentified pathogens, at an average daily dose of 13.5 mg/kg dived into 2-4 doses (2 doses/day for 12 cases, 3 doses for 32, 4 doses for 5) for 7 days on the average. In addition to examine the clinical and bacteriological effects of the 2 dosage forms of TE-031, minimum inhibitory concentrations (MICs) were determined for 9 antibiotics consisting of 5 MLs including TE-031, EM, josamycin (JM), midecamycin acetate (MDM acetate), and rokitamycin (RKM), 3 penicillins including ampicillin (ABPC), methicillin, cloxacillin and 1 cephem antibiotic, cefaclor (CCL), against 29 strains consisting of 12 strains of Staphylococcus aureus, 7 of Streptococcus pyogenes, 2 of Streptococcus pneumonia 2 of Haemophilus influenzae and 6 of Campylobacter jejuni, out of 71 strains of pathogens or possible pathogens that had been isolated from the cases given TE-031.

Age Factors↗

[Gastrointestinal bleeding in children].

The site and nature of lesions producing gastrointestinal bleeding was evaluated in pediatric patients admitted to Tokai University Hospital. The differential diagnosis was possible based upon the character of the bleeding and the age of the patient. Upper endoscopy is the diagnostic maneuver of choice in evaluating the upper gastrointestinal bleeders. Sigmoidoscopy, colonoscopy, technetium scans, tagged red cell scans and intraoperative angiography were helpful in locating bleeding sites of lower bleeders. Common causes of bleeding were as follows: Hemorrhagic disease, necrotizing enterocolitis, and midgut volvulus in neonates; intussusception and internal hernia in infants; juvenile polyp and infectious diarrhea in children; duodenal ulcer and ulcerative colitis in adolescents. Gastro-duodenal ulcers were found in all age groups. One neonate died of indomethacin induced bleeding, however, bleeding from acute ulcer was usually controlled by conservative treatments. Increasing frequency of variceal bleeding due to portal hypertension after successful Kasai procedure for congenital biliary atresia was emphasized.

Adolescent↗

[Acute childhood leukemia].

The overall event-free survival of childhood acute leukemia has increased to 60-65% in ALL and to 40-60% in ANLL. This progress has resulted from a closely integrated scientific effort, including drug development, pharmacology, preclinical modeling, experimental design with respect to clinical trials, quantitative criteria for response, and a series of clinical trials in which the importance of complete remission, of dose and schedule, of sequencing chemotherapeutic agents, of pharmacological sanctuaries, and particularly of combination chemotherapy was studied. In this paper, recent treatment results of acute childhood leukemia made by the Children's Cancer and Leukemia Study Group of Japan were reviewed, and current challenges and future perspectives are discussed.

Acute Disease↗