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Biomedical subjects

M Fukuda

Publications and source records attributed to M Fukuda.

At least 901 records · Page 50Linked to original sources
PubMed1990

Regional ploidy variations in signet ring cell carcinomas of the stomach.

Regional ploidy variations within individual tumors were analyzed by in-situ cytofluorometry of metaphase cells in Feulgen-stained paraffin sections, using 45 resected stomachs with early and advanced signet ring cell carcinomas. Aneuploid cells were found in one of 30 early cancers and in eight of 15 advanced cancers, and were almost always accompanied by diploid cancer cells in the mucosal part of the cancers. The diploid and the aneuploid cells were generally found to be distributed in different territories in the mucosa, and aneuploid foci were often included in the diploid area. These findings suggest the diploid origin of signet ring cell carcinomas and the occurrence of aneuploidy during the tumor development. Moreover, the aneuploid cells appeared to infiltrate beyond the mucosa more readily than the diploid cells; most of the aneuploid populations already invaded the extramucosal tissue, and the cancer cells infiltrating in the extramucosal tissue were predominantly aneuploid in six of the nine cancers with aneuploidy. Thus, it appears that the occurrence of aneuploid clones may accelerate the progression of signet ring cell carcinomas from early to advanced stages.

Adenocarcinoma, Mucinous↗
PubMed1990

Combination effect of hyperthermia and photodynamic therapy on carcinoma.

We investigated the time course of hematoporphyrin oligomer uptake in squamous cell carcinoma transplanted into C3H mice after intraperitoneal injection by measuring its fluorescence intensity. The intensity peaked 83 hours after the injection. The tumors disappeared after an average of 4.12 days with a single application of photodynamic therapy or microwave hyperthermia 83 hours after hematoporphyrin oligomer injection. However, all the tumors treated with these single modalities regrew within 4 weeks after the treatments. Therefore, we investigated the therapeutic effect of microwave hyperthermia in combination with photodynamic therapy. As a result, the combination effect was strongest when high-dose therapy was used as the first choice, irrespective of the order of the treatments, and no tumor regrowth occurred for 45 days.

Animals↗
PubMed1990

CD43 (leukosialin, sialophorin, large sialoglycoprotein) can be expressed in both normal and Wiskott-Aldrich fibroblasts via transfection of a leukosialin cDNA.

Human leukosialin is among the most abundant sialoglycoproteins found on the surface of cells of the lympho-hematopoietic system. Leukosialin, also known as sialophorin, is involved in T cell proliferation, and its molecular isoform changes upon cellular activation. We show that human leukosialin is identical to the antigens described by the monoclonal antibodies (mAb) G10-2, G19-1 (CD43) and B1B6 (large sialoglycoprotein). This identity was suggested by immunoblot analysis of transformed cell lysates. Further, fibroblasts transfected with the human leukosialin cDNA gain reactivity to these mAb, showing conclusively that molecules recognized by these mAb are determined by the same cDNA. Expression of the leukosialin gene is readily detected on the surface of transfected human and mouse fibroblasts. Immunoblot analysis of the transfectants indicates that processing of the human protein occurs in both species. Alterations of leukosialin expression have been reported in patients with the Wiskott-Aldrich Syndrome (WAS), an X-chromosome-linked immunodeficiency disease. While essentially all of the transfected tumor and primary fibroblasts from normal individuals express the transfected gene on the cell surface, only half of the transfected Wiskott-Aldrich fibroblasts express CD43. Nonetheless, the antigenic pattern by immunoblot analysis of both normal and WAS-transfected fibroblasts appears identical. These results indicate that WAS-derived cells can express leukosialin and that the product of WAS X-chromosome mutation may not be expressed in fibroblasts.

Animals↗
PubMed1990

Intracellular pH regulation of normal rat brain: 31P-MRS study.

Intracellular pH changes in rat brain tissue were investigated during low or high extracellular pH induced by acetazolamide or sodium bicarbonate, respectively. Intracellular pH was measured by 31P-MRS in the brain of spontaneously breathing rats under intraperitoneal sodium pentobarbital anaesthesia. Extracellular pH was calculated from the results of blood gas analysis. After intravenous injection of sodium bicarbonate (280 mg/kg), the extracellular pH rose significantly (p less than 0.05) from 7.47 +/- 0.06 to 7.82 +/- 0.15 (mean +/- SE). After administration of acetazolamide (50 mg/kg), the extracellular pH dropped significantly (p less than 0.05) from 7.45 +/- 0.02 to 7.34 +/- 0.03. Despite the changes in extracellular pH, the intracellular pH of rat brain did not change significantly under either condition. The following four factors are thought to contribute to the maintenance of intracellular pH in the normal brain: 1) production and consumption of H+ by brain metabolism, 2) physicochemical buffering, 3) transmembrane transport of H+ and its equivalent, 4) compensatory adaptation of circulatory factors. These mechanisms are not disturbed in the brain of rats that are breathing spontaneously, because the cerebral circulation and energy metabolism are preserved in the normal range.

Acetazolamide↗
PubMed1990

Evolution of the glycophorin gene family in the hominoid primates.

Analysis of nucleotide sequences of the human glycophorin A (GPA) and glycophorin B (GPB) genes has indicated that the GPA gene most closely resembles the ancestral gene, whereas the GPB gene likely arose from the GPA gene by homologous recombination. To study the evolution of the glycophorin gene family in the hominoid primates, restricted DNA on Southern blots from man, pygmy chimpanzee, common chimpanzee, gorilla, orangutan, and gibbon was probed with cDNA fragments encoding the human GPA and GPB coding and 3'-untranslated regions. This showed the presence in all of the hominoid primates of at least one GPA-like gene. In addition, at least one GPB-like gene was detected in man, both chimpanzee species, and gorilla, strongly suggesting that the event that produced the GPB gene occurred in the common ancestor of man-chimpanzee-gorilla. An unexpected finding in this study was the conservation of EcoRI restriction sites relative to those of the other four enzymes used; the significance of this observation is unclear, but raises the question of nonrandomness of EcoRI restriction sites in noncoding regions. Further analysis of the evolution of this multigene family, including nucleotide sequence analysis, will be useful in clarification of the evolutionary relationships of the hominoid primates, in correlation with the structure and function of the glycophorin molecules, and in assessment of the role of evolution in the autogenicity of glycophorin determinants.

Animals↗
PubMed1990

Multiple restriction fragment length polymorphisms associated with the Vc determinant of the MN blood group-related chimpanzee V-A-B-D system.

Twelve restriction fragment length polymorphisms (RFLPs) were detected in common chimpanzee using two restriction enzymes (HindIII and MspI) and four DNA probes to the coding regions of the human glycophorin A (GPA) and glycophorin B (GPB) genes and their 3'-untranslated regions. Seven RFLPs correlated with red cell expression of the Vc determinant of the MN blood group-related V-A-B-D system and five RFLPs correlated with nonexpression of this antigen. Animals heterozygous for the V allele that encodes the Vc determinant had all 12 polymorphic restriction fragments and appeared to show reduced intensity of probe hybridization to these fragments, consistent with the presence of a V and a non-V allele. No RFLPs were detected with EcoRI, SstI, or BamHI, in spite of the relatively large segment of DNA (at least 20 kb) involved in the polymorphisms. The RFLPs were chimpanzee specific and were not found in man, gorilla, orangutan, or gibbon. Multiple RFLPs distinguishing primate species are rare and may be useful markers for molecular evolution.

Animals↗
PubMed1990

Thrombin stimulates the proliferation of human retinal glial cells.

Retinal glial cells may play a role in most of the proliferative retinopathies. Although glial cell proliferation is a frequent event in retinal pathobiology, no specific mitogens for human retinal glial cells are known. Using cultured retinal glial cells obtained from postmortem adult human eyes, we found that thrombin stimulates glial cell proliferation in a dose-dependent manner with a half-maximal concentration of 100 ng/ml (0.4 U/ml). Thus, thrombin may be a plasma-derived mitogen capable of stimulating retinal glial cells to proliferate when there is a breakdown of the blood-retinal barrier. We also observed that this proliferative response of retinal glia requires more than 6 h of continuous exposure to thrombin. This finding suggests that a thorough wash-out of a thrombin-containing infusate and/or the rapid inactivation of this molecule would prevent thrombin form exacerbating a proliferative disorder of the retina.

Adult↗
PubMed1990

Variation of lysosomal enzyme activity with gestational age in chorionic villi.

The activities of 14 lysosomal enzymes in chorionic villi at gestational ages of 6-12 weeks were assayed. Arylsulphatases A and B, alpha-glucosidase and beta-glucuronidase activities increased with advancing gestational age. When compared with the activity in cultured amniotic fluid cells, arylsulphatase A, beta-galactosidase, alpha-glucosidase, heparan N-sulphatase, alpha-L-iduronidase, alpha-mannosidase, neuraminidase, and sphingomyelinase showed significant differences. All except beta-glucuronidase showed lower activity in chorionic villi than in cultured amniotic fluid cells. Prenatal diagnosis using chorionic villi was possible except for alpha-L-iduronidase. Storage at -20 degrees C up to 42 days did not significantly affect activity. The results emphasize the importance of using fresh or frozen age-matched control tissue for diagnosis.

Amniotic Fluid↗
PubMed1990

Better control of esophageal variceal bleeding by sclerotherapy followed by surgery.

This paper reports the clinical results of a retrospective study comparing endoscopic injection sclerotherapy (EIS) and back-up surgical treatment after EIS in the management of acute variceal bleeding. The 74 patients included in the study were divided into 2 groups. Group I consisted of 41 patients who received EIS over a mean period of 2.2 sessions and Group II consisted of 33 patients who underwent EIS and subsequent surgical intervention, in the form of 19 distal splenorenal shunts and 14 nonshunting procedures. The overall percentage of patients in whom initial control of variceal bleeding was achieved was 91.8 per cent. Four of the Group II patients were saved by emergency nonshunting operations. Rebleeding was experienced by 4 (28.6 per cent) of the 14 patients who underwent nonshunting surgery but by only 1 (5.3 per cent) of the 19 patients who underwent selective shunt surgery. The cumulative survival in Group II was significantly superior to that in Group I with 2 year survival being achieved in 66.7 per cent of the Group II patients but in only 23 per cent of Group I patients. Thus, the combination of initial EIS and back-up surgical intervention may be more beneficial than sclerotherapy alone for patients with acute variceal bleeding, while, the distal splenorenal shunt may be a more suitable surgical technique for patients having previously EIS.

Combined Modality Therapy↗
PubMed1990

Hepatobiliary and gastrointestinal imaging after pancreaticoduodenectomy--a comparative study on Billroth I and Billroth II reconstructions.

This study was conducted to compare the passage of bile and food through the remnant alimentary tract between 2 and 6 months following pancreaticoduodenectomy in patients undergoing Billroth I (Imanaga) and Billroth II (Child) reconstructions, using dual scintigraphy. In the patients who underwent Child's operation (n = 14), hepatobiliary scintigraphy showed a prominent stasis of bile tracer in the proximal jejunal loop and a significant time delay before the bile and food became mixed at the upper jejunum. On the other hand, in the patients who underwent Imanaga's operation (n = 9) no bile stasis in the proximal jejunal loop was found and the time taken before the two agents became mixed was similar to that of healthy controls (n = 7). The time taken for the two agents to mix at the upper jejunum was 65.8 +/- 7.9 min in the patients after Child's operation, 17.3 +/- 2.5 min in those after Imanaga's operation, and 18.5 +/- 2.8 min in the healthy controls, respectively. Continuous stasis of bile in the proximal loop and severe postcibal asynchronism in patients who undergo Child's operation can therefore cause reflux cholangitis and absorptive disturbances in the long postoperative term. The results of this study suggest that Imanaga's reconstruction is a more physiological procedure than Child's reconstruction following pancreaticoduodenectomy.

Anastomosis, Surgical↗
PubMed1990

Phase II study of (glycolate-O,O') diammineplatinum(II), a novel platinum complex, in the treatment of non-small-cell lung cancer.

A total of 68 patients with non-small-cell lung cancer who either had not previously been treated (38) or had undergone prior therapy (30) were treated in a phase II study of (glycolate-O,O') diammineplatinum(II) (NSC 375 101D; 254-S), a new platinum complex. The drug was given as a single intravenous infusion at a dose of 100 mg/m2 every 4 weeks. All 68 patients could be evaluated for response and 62, for toxicity. Objective responses were seen in 10 of 68 cases (14.7%; 95% confidence interval, 7.3%-25.4%), and the median duration of response was 15 weeks (range, 8-23 weeks). The response rates were similar for previously untreated and treated patients (13% and 17%, respectively), including three previously treated with cisplatin. Myelosuppression was the dose-limiting toxicity. Thrombocytopenia (less than 100,000 platelets/mm3) and leukocytopenia (less than 3,000 WBC/mm3) were observed in 22 (35%) and 18 (29%) patients, respectively. Mild to moderate nausea and vomiting occurred in 45 cases (73%). No significant renal or neurotoxicity was observed. We conclude that as a single agent, 254-S is well tolerated but appears to have marginal activity against non-small-cell lung cancer.

Adenocarcinoma↗
PubMed1990

Adult T-cell leukemia/lymphoma of the tongue.

A case of posterior tongue lymphoma associated with adult T-cell leukemia (ATL) that occurred as a lesion in the lingual dorsal portion is reported in a 64-year-old woman. Initially, a diagnosis of Hodgkin's lymphoma was considered as no findings associated with ATL except lymphadenopathy and serum anti-ATLA antibodies were present. Combined radiotherapy and chemotherapy were administered with favorable results; however, 4 months later, Pneumocystis carinii pneumonia developed, and 2 months later, generalized lymphadenopathy and hypercalcemia evolved. At this time, a diagnosis of ATL was made. The patient died of renal dysfunction 6 months after the initial presentation. In suspected cases of ATL and malignant diseases of T-cell lineage, namely, malignant lymphoma and mycosis fungoides, the presence of HTLV-1 infection should be confirmed by testing for anti-ATLA antibodies.

Diagnosis, Differential↗
PubMed1990

Tumor necrosis factor reduces lifespan of human endothelial cells in vitro.

Tumor necrosis factor (TNF) is known to regulate the proliferation and function of vascular endothelial cells (ECs). We have examined the effects of TNF on the growth and aging of human ECs of different origins and compared them with those in human normal diploid fibroblasts. The results obtained were as follows: (1) TNF reduces the growth rate and in vitro life span of ECs in both dose- and treatment length-dependent fashions; (2) ECs are significantly more sensitive to TNF than fibroblasts; and (3) the life span shortening effect of TNF on ECs increases as a function of in vitro cell age. These results suggest that the aging of ECs is modified by TNF exposure.

Cell Division↗
PubMed1990

Nitro reaction in mice injected with pyrene during exposure to nitrogen dioxide.

We have previously reported that the beta-glucuronidase-treated urine of mice injected intraperitoneally with pyrene during exposure to NO2 contained highly mutagenic compounds such as nitropyrene metabolites when tested by the Ames assay using Salmonella typhimurium strain TA98. In the present study, we found that the formation of these mutagens was dose-dependent between 10 and 200 mg of pyrene per kg of body weight at 5 and 10 ppm of NO2. Further, to elucidate the substrate of nitration in vivo, we injected 1-hydroxypyrene, which is the metabolite of pyrene, to mice intraperitoneally during exposure to NO2. Since the results were the same as those obtained by injection with pyrene, we suggest that the pyrene was not nitrated directly but after its hydroxylation.

Animals↗
PubMed1990

Central action of endogenous sugar acid (2-buten-4-olide): comparison with local anesthesia in hypothalamus.

Rats were trained to discriminate cue tone stimuli (CTS) predicting reward (CTS+) [juice or intracranial self-stimulation (ICSS)], or aversion (CTS-) (mild electric shock or tail pinch). Unit activity in the lateal hypothalamus (LHA) and lateral preoptic-anterior hypothalamic area (lPOA-AHA) of the rat was recorded during CTS learning. The effects of local anesthesia of the amygdala (AM), ventral tegmental area (VTA) or LHA by procaine hydrochloride, and the effects of intraperitoneal or intravenous 2-buten-4-olide (2-B4O) on LHA neural activity and licking behavior were compared. LHA neurons differentiated between rewarding and aversive stimuli, and acquired corresponding discrimination of CTS+ and CTS-. In the lPOA-AHA, neurons responded similarly to CTS+, rewarding stimuli, CTS- and aversive stimuli. Procainization of the AM suppressed LHA neural responses to CTS1+ predicting juice, and stopped licking for juice. Procainization of the VTA suppressed LHA neural responses to CTS2+ predicting ICSS, and stopped licking for ICSS. LHA procainization suppressed both licking for juice and ICSS. Both intraperitoneal and intravenous 2-B4O stopped licking for juice and ICSS, but did not influence LHA responses to CTS1+ or CTS2+. The results suggest that dynamic interaction of AM-LHA-VTA are important for CTS+ learning, and 2-B4O acts directly on LHA neurons while maintaining afferent sensory inputs to the LHA.

4-Butyrolactone↗
PubMed1990

Dopamine and ACh involvement in plastic learning by hypothalamic neurons in rats.

Unit activity in the rat lateral hypothalamus (LHA) was recorded during discrimination learning of cue tone stimuli (CTS). CTS+ predicted reward (glucose or intracranial self-stimulation); CTS- predicted aversion (electric shock or tail pinch); and all behavior responses were by the same act, licking. Roles of the LHA dopaminergic and cholinergic systems in CTS learning were investigated by electrophoretic application of dopamine (DA) and acetylcholine (ACh), and their antagonists. The CTS+, the predicted reward and DA, all had similar effects (inhibition) on many LHA neurons; and these were all opposite to the effects (excitation) of CTS-, the predicted aversion, and ACh. Neural responses to CTS+ were blocked by spiperone, and responses to CTS- were blocked by atropine. Sensitivity of LHA neurons to DA was reduced by extinction of CTS+ learning for reward, and sensitivity to ACh was reduced by CTS- learning for aversion. The data suggest that afferent DA and ACh inputs to LHA neurons are essential for plastic CTS+ and CTS- learning.

Acetylcholine↗
PubMed1990

G3M T typing by dot immunobinding with monoclonal anti-G3M T antibody.

Dilutions of 100 serum samples of various GM phenotypes were dotted onto a nitrocellulose membrane. The serum dot-blots were detected with peroxidase-labeled anti-G3M T monoclonal antibody (anti-G3M T MAb). Up to a 1 : 256 dilution could be G3M T-typed correctly. By use of anti-G3M T MAb and peroxidase-labeled anti-mouse IgG or the biotin-avidin system instead of use of labeled anti-G3M T MAb, up to a 1 : 512 or 1 : 1024, respectively, dilution was typable. As with previous work with G3M G MAb, the dot immunobinding (DIB) method for G3M T typing was found very simple and practical.

Antibodies, Monoclonal↗