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Biomedical subjects

S Fujimoto

Publications and source records attributed to S Fujimoto.

At least 559 records · Page 31Linked to original sources
PubMed1993

Cytochemical and immunocytochemical demonstration of acetylcholinesterase of the prenatal rat lower limb.

Acetylcholinesterase (AChE) activities in the prenatal rat lower limb were investigated by both cytochemistry and immunocytochemistry. Results indicate that the epidermal cells show immunoreactions of AChE at a limited stage at prenatal day 15, and mesenchymal cells which are occasionally in contact with the basal lamina or with the adjacent myotubes begin to show AChE activities at prenatal day 17. Such AChE-positive mesenchymal cells, involved in the formation of the muscular tissues, have almost disappeared in the subepidermis by prenatal day 19. This suggests that AChE independent of the neuromuscular system may be involved in the mesenchymal cell differentiation especially in the inductive process during myogenesis.

Acetylcholinesterase↗
PubMed1993

[A study of changes in distribution pattern of proliferating cells associated with progression of human colorectal benign and malignant tumor using PCNA immunohistochemistry].

We studied cell kinetics of colo-rectal neoplasms using PCNA (the auxiliary protein of DNA polymerase-delta) immunohistochemistry. We analyzed the distribution pattern of PCNA positive cells on normal colon mucosa, adenoma (6 cases) and cancer (early: 33 cases, advanced: 6 cases). PCNA positive index (PI) was calculated as the percentage of PCNA positive tumor cells in relation to the total number (about 1000) of the tumor cells. PCNA positive indices were 30% in normal colon mucosa, 49% in adenoma and 72% in cancer, respectively. There were statistically significant differences between three mean values (p < 0.01). In normal colon mucosa PCNA positive cells are localized at the lower part of mucosa, but, in adenoma, they are found at the more upper part of mucosa too. In cancer, PCNA positive cells were localized diffusely and their immunoreactivity is higher than those of the normal mucosa and adenoma. In conclusion, our results suggests that the ratio of PCNA positive cells almost equivalents to growth fraction, and is correlated with the histological grading of colo-rectal tumor, but not correlated with depth of carcinoma. It is presumed that carcinoma has a higher ratio of PCNA positive cells than adenoma, and therefore carcinoma has higher proliferating cell density than adenoma.

Adenoma↗
PubMed1993

Relationship between exercise capacity and the severity of emphysema as determined by high resolution CT.

We investigated the relationship between exercise capacity or exercise-induced hypoxaemia and the severity of pulmonary emphysema in 20 patients with pulmonary emphysema. The patients underwent pulmonary function tests, high resolution computed tomography and incremental treadmill exercise testing. Computed tomography scans were obtained at four levels in the lungs, and emphysema scores were determined by the visual assessment of low attenuation areas as a measure of the severity of parenchymal destruction. The emphysema score correlated significantly with diffusing capacity (r = -0.69) in the pulmonary function tests. Among the exercise test parameters, the emphysema score correlated significantly with the total distance walked (r = -0.74), with maximal oxygen consumption (VO2max) (r = -0.77), with arterial oxygen tension (PaO2) at rest (r = -0.50) and at the maximum workload (r = -0.58), and with the decrement of arterial oxygen tension per litre of oxygen consumed (r = -0.64). These results suggest that exercise capacity and exercise-induced hypoxaemia are related to the extent of destruction of lung parenchyma in patients with pulmonary emphysema.

Aged↗
PubMed1993

[Immunoelectron microscopic localization of human chorionic gonadotropin in the syncytiotrophoblast of hydatidiform moles].

The immunocytochemical localization of hCG in the syncytiotrophoblast of hydatidiform moles was observed by means of the immunoglobulin gold technique with rabbit anti-human hCG serum. Immunoreactive gold particles of hCG are preferentially localized in the distal portion of the Golgi complexes, Golgi-derived secretory granules 200-300 nm in diameter, and large electron dense bodies 500-1,000 nm in diameter. The secretory granules exist throughout the cytoplasm above the nuclear region and are occasionally released by exocytosis from the syncytiotrophoblast. On the other hand, the large electron dense granules seem to be cytolysosomes in nature and are involved in uptake and storage of hCG.

Chorionic Gonadotropin↗
PubMed1993

Specific immunosuppression of human anti-murine antibody responses in hu-PBL-SCID mice.

Severe combined immunodeficient (SCID) mice were reconstituted with normal human peripheral blood leukocytes (PBLs) and were shown to produce a human anti-mouse immunoglobulin antibody response on immunization with heat-treated murine monoclonal IgG1 antibody to ovalbumin, referred to as ha-Mab-2. The human anti-mouse antibody response was proportional tot the number of B cells and mononuclear cells transferred from a given batch of PBL. However, pretreatment of hu-PBL-SCID mice with a tolerogenic covalent conjugate of monomethoxypolyethylene glycol (mPEG) and Mab-2 suppressed this response on subsequent injections of ha-Mab-2, and this suppression was shown to be antigen-specific, i.e., it did not suppress the antibody response to ovalbumin and did not affect the level of production of human immunoglobulin of hu-PBL-SCID mice. The suppression was due to the generation of human suppressor CD8+ T (Ts) cells, which down regulated CD4+ helper T cells in an antigen and HLA class I specific manner, i.e., these findings were in accord with the previously shown immunosuppressive effect of tolerogenic mPEG conjugates in normal mice.

Animals↗
PubMed1992

Cytohistologic assessment of antitumor effects of intraperitoneal hyperthermic perfusion with mitomycin C for patients with gastric cancer with peritoneal metastasis.

For 15 patients with refractory gastric cancer and peritoneal metastasis, intraperitoneal hyperthermic perfusion (IPHP) using mitomycin C combined with extensive surgery was prescribed. The antitumor effects were assessed cytohistologically in pre-IPHP and post-IPHP specimens of the abdominal effusion and peritoneal tissue. Gastric cancer cells in the abdominal effusion and/or lavage vanished from post-IPHP peritoneal exudate obtained from the pouch of Douglas. Peritoneal tissues from nine patients were harvested just after the IPHP treatment. All the nuclei of cancer cells were pyknotic in three of nine patients, and two of these three patients are alive with no local recurrence; one patient died of hepatic metastasis. In the remaining six patients, four with preoperative ascitic effusion and positive post-IPHP histologic findings died of peritoneal, intraabdominal, and pericardial metastases. The other two had some residual microscopic foci in the subperitoneal deep layer; one patient died of pleural recurrence, and the other is alive with no evidence of recurrence 42 months after the IPHP. Among the other six patients, whose post-IPHP peritoneal tissues were not available because of disappearance of disseminating foci as a result of the IPHP, two are living with no recurrence and, of the remaining four patients, three died of hepatic and intraabdominal metastases and the other one died of other causes. The histologic findings are suggestive of the following: (1) uniform heat and drug distribution in the abdominal cavity with IPHP treatment, except for an area adjacent to the inflow point of the perfusate; and (2) limited penetration of heat and drug through the subperitoneal layer. Thus, IPHP treatment results in complete destruction of cancer cells in the abdominal effusion and on and just beneath the peritoneum.

Adult↗
PubMed1992

Mutations in the Pit-1 gene in children with combined pituitary hormone deficiency.

Pit-1 is a pituitary-specific transcription factor that binds to and transactivates promoters of growth hormone and prolactin genes. In three unrelated Japanese children with combined pituitary hormone deficiency, we identified three point mutations in the Pit-1 gene, Pro24Leu, Arg143Gln, and Arg271Trp, located on the major transactivation region, POU-specific domain, and POU-homeodomain, respectively.

Amino Acid Sequence↗
PubMed1992

Particular types of tumor cells have the capacity to convert transforming growth factor beta from a latent to an active form.

We investigated the capacities of various tumor types to generate an active versus latent form of transforming growth factor beta (TGF-beta) in its culture supernatants (SNs). Tumor cell lines were divided into three types depending on the form and magnitude of TGF-beta detected in their culture SNs: some (2 of 7 lines) generated mostly an active form (Type A); others (4 of 7) generated exclusively a latent form (Type B); and the remaining line (1 of 7) produced only marginal levels of active/latent TGF-beta (Type C). When Type A tumor cells were cultured at lower numbers, cultures failed to generate active TGF-beta. However, the addition of Type B tumor cell culture SNs containing only a latent form of TGF-beta resulted in the generation of the potent activity of active TGF-beta. This capacity was observed for another Type A tumor but not for other types (Type B and Type C). An active form of TGF-beta was detected in culture SNs of Type A tumor cells as early as 3-6 h after the addition of Type B tumor culture SNs. The emergence of an active form of TGF-beta was also observed in cultures of Type A tumor cells, the protein synthesis of which was almost completely inhibited by pretreatment with cycloheximide. Moreover, the Type B tumor SN used for the induction of active TGF-beta activity was found to contain latent TGF-beta with an apparent molecular weight of about 200,000. Type A tumor cells were also capable of generating active TGF-beta by the addition of recombinant TGF-beta of latent form with a small molecular weight (about 60,000), although the generation of active TGF-beta was much weaker after the addition of small latent TGF-beta than after the addition of large latent TGF-beta. Taken collectively, these results indicate that particular types of tumor cells have the capacity to generate an active form of TGF-beta and that such capacity can be attributed to their potential to convert TGF-beta from a latent (mainly large type) to an active form.

Animals↗
PubMed1992

Phosphatidylinositol-specific phospholipase C activity in the postmortem human brain: no alteration in Alzheimer's disease.

The activity of phospholipase C (PLC) which hydrolyzes exogenous phosphatidylinositol (PI), was investigated in samples prepared from postmortem normal human brains and Alzheimer disease brains. The enzyme activity did not change significantly after rat brains were left for 24 h at room temperature. The PI-specific PLC activity in the Alzheimer cytosolic and particulate fractions was not significantly different from that in the control fractions. The PI-specific PLC activity as a function of the free Ca2+ concentration was also similar between control and Alzheimer brains. These results suggest that the PI-specific PLC activity is not altered in Alzheimer's disease.

Aged↗
PubMed1992

Genomic organization of human fetal specific P-450IIIA7 (cytochrome P-450HFLa)-related gene(s) and interaction of transcriptional regulatory factor with its DNA element in the 5' flanking region.

P-450IIIA7 is a form of cytochrome P-450 which was isolated from human fetal livers and termed P-450HFLa. This form has been clarified to be expressed during fetal life specifically (Komori, M., Nishio, K., Kitada, M., Shiramatsu, K., Muroya, K., Soma, M., Nagashima, K. and Kamataki, T. (1990) Biochemistry 29, 4430-4433). In the present study, we isolated five independent clones which probably corresponded to the human P-450IIIA7 gene. These clones were completely sequenced, all exons, exon-intron junctions and the 5' flanking region from the cap site to-869. Although the sequences in the coding region were completely identical to P-450IIIA7, it is possible that genomic fragments sequenced in this study encode portions of other P-450IIIA7-related genes since we could not obtain a complete overlapping set of genomic clones. Within its 5' flanking sequence, the putative binding sites of several transcriptional regulatory factors existed. Among them, it was shown that a basic transcription element binding factor (BTEB) actually interacted with the 5' flanking region of this gene.

Adult↗
PubMed1992

Simultaneous localization of histamine and factor VIII-related antigen in the endothelium of the human umbilical vein.

Simultaneous immunoelectron microscopic localization of histamine and factor VIII-related antigen was examined on the same ultrathin section of the endothelium of the human umbilical vein from full-term deliveries by means of the double-immunolabeling technique. Small gold particles demonstrating antibody reaction with histamine are preferentially located in the cytoplasmic matrix and organelles, especially in mitochondria and on the luminal membrane surface of the endothelial cells. The gold particles representing histamine immunoreactivity also located on some of Weibel-Palade (WP) bodies. In contrast, large gold particles demonstrating factor VIII-related antigen are concentrated preferentially on most WP bodies. Single labeling of either histamine or factor VIII-related antigen shows similar results to those of the double labeling. The present study indicates that some WP bodies are involved in storage of both factor VIII-related antigen and histamine, but others store factor VIII-related antigen only. This difference in contents of WP bodies may be induced during the development and maturation process of this inclusion. At any rate, it is reasonable to consider that WP bodies have important roles in both vascular tonus and hemostasis during the vascular obliteration.

Cytoplasm↗
PubMed1992

A novel anticancer treatment for xenoplanted human gastric cancer using polyamine antimetabolites in a low polyamine diet.

The aim of the present study was to evaluate a new anticancer treatment for gastrointestinal cancer, using a combination of polyamine antimetabolites, an anticancer agent and a low-polyamine state. Two polyamine antimetabolites, given as either 40 mg/kg of methylglyoxal-bis-guanylhydrazone (MGBG) or ethylglyoxal-bis-guanylhydrazone (EGBG) and a normal diet (ND), or 20 mg/kg of each drug and a low polyamine diet (LPD), together with 1,000 mg/kg of alphadifluoromethylornithine (DFMO) were administered ip to nude mice for six consecutive days. Mitomycin C (MMC) at 2 mg/kg was then given ip for 3 alternate days. The combination of MGBG or EGBG with DFMO plus MMC resulted in an enhanced antitumor efficacy on LPD. However, the combination which included EGBG was much more enhanced than that which included MGBG and there was no evidence of any tumor regrowth. Weight loss was minimal or nil in the mice given the combination with EGBG, but was evident in those given the combination with MGBG. These results led to the conclusion that in mice, the combined therapy of EGBG with DFMO plus MMC and LPD is a safe and effective regimen for the treatment of gastric cancer.

Adenosylmethionine Decarboxylase↗
PubMed1992

Two-color flow cytometric analysis of splenic lymphocyte subpopulations in patients with gastric cancer.

Lymphocyte subpopulations of the spleen were assayed in 26 patients with gastric cancer and 5 patients with benign disease using two-color flow cytometric analysis. The ratio of Leu 2a+.Leu 15+ cells, or suppressor T cells, in the gastric cancer patients was about 6 per cent, being higher than that in the patients with benign disease (p less than 0.05). There were fewer Leu 7+.Leu 11- cells, or natural killer-NK-cells, in the gastric cancer patients in stage III or IV than in those with stages I or II (p less than 0.05). The ratio of Leu 3a+.Leu 8- cells, or helper T cells, in the stage IV patients accounted for about 15 per cent of the splenic lymphocytes, which was less than that seen in the patients in stages I or II (p less than 0.05). The ratio of Leu 2a+.Leu 15- cells, or cytotoxic T cells, was approximately twice that of suppressor T cells. The pre-operative administration of lentinan plus OK-432 increased the ratio of Leu 4+.HLA-DR+ cells, or activated T cells, and cytotoxic T cells (p less than 0.05 and p less than 0.01, respectively). The above results suggest that lymphocyte subpopulations in the spleen may have more immunosuppressive potential in proportion with the stage of gastric cancer, but that this reduced immune state may be altered when lentinan and OK-432 are given to these patients.

Adult↗
PubMed1992

Postnatal changes in sublobular distribution of NADPH-cytochrome P-450 reductase in rat liver.

Immunohistochemical distribution of NADPH-cytochrome P-450 reductase (NADPH-ferrihaemoprotein reductase; EC 1.6.2.4.) in the liver lobule was examined during development of the rat. From the 19th day of gestation to 4 days after birth, the enzyme was distributed uniformly throughout the lobule. The immunostaining for the enzyme was weak before birth, and became slightly stronger after birth. A slightly uneven distribution of immunoreactivity, stronger in perivenular zones, appeared at 5 days after birth. Then, the staining intensity in perivenular zones became progressively stronger with age, except for a slight increase between 10 and 20 days of age. The intensity in periportal zones also increased gradually, although it remained weaker than that in perivenular zones. Around 30 days of age, the distribution of the immunostaining, stronger in perivenular than in periportal zones, was similar to that seen in the lobules of adult animals. Thus, heterogeneity among hepatocytes with respect to the enzyme content is not present in fetal and newborn rats but develops gradually during postnatal development; the postnatal growth of the liver is accompanied by a change in the pattern of the distribution of this enzyme within the lobule.

Age Factors↗
PubMed1992

Studies on the hepatotoxicity induced by bis (tributyltin) oxide.

The toxic effects of bis (tributyltin) oxide (TBTO) on the rat liver were studied with an electron microscope and the accumulation sites of tin were determined with an X-ray microanalyzer. The activities of serum enzymes and the concentration of serum bilirubin were also analyzed. Male Wistar rats received an intramuscular injection of 0.5 ml/kg of TBTO. Marked swelling of the mitochondria appeared in the hepatocytes 4 h after injection of TBTO. Cytoplasmic vacuoles, which contained degenerated mitochondria, gradually increased in number in these hepatocytes. This in turn may have caused a decrease in the volume of hepatic cell cords and an enlargement of sinusoids in the entire hepatic lobule. However, fine structures of intrahepatic bile ducts were not altered. By X-ray microanalysis, tin peaks were preferentially obtained from swollen mitochondria of the hepatocytes. By polarographic analysis of the respiratory responses of mitochondria, it was demonstrated that rates of state 4 respiration and respiratory control ratio were significantly disturbed in TBTO-treated rats in comparison with those of controls. The activities of AST (aspartate aminotransferase) and ALT (alanine aminotransferase) were significantly increased after TBTO treatment, but those of ALP (alkaline phosphatase), LAP (leucine aminopeptidase) and total bilirubin were not changed. These results indicated that parenterally administered TBTO accumulated in the liver cell mitochondria and disturbed oxidative phosphorylation. Mitochondrial dysfunction might induce severe damage of the hepatocytes. Four days after injection of TBTO, hepatic structures and chemical indices were almost restored by the regeneration of hepatocytes.

Alanine Transaminase↗