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Biomedical subjects

M Fukuda

Publications and source records attributed to M Fukuda.

At least 721 records · Page 40Linked to original sources
PubMed1994

[Anticancer agents and apoptosis].

We reviewed recent reports on apoptosis and summarized the presentations at the Shirafu Cancer Symposium, 1993. The study of programmed cell death, apoptosis, has become one of the mainstream in cell biology, particularly in immunology, developmental biology and oncology. To determine whether the apoptotic cell death induced by anti-cancer agents could be inhibited by bcl-2, we established a bcl-2-transfected human small cell lung cancer cell line, SBC-3/Bcl-2. SBC-3/Bcl-2 showed higher resistance to ADM, CPT-11 and MMC compared with the parental line SBC-3. Agarose gel electrophoresis showed typical DNA fragmentation of SBC-3 following treatment with CPT-11 or MMC. In contrast, the same concentration of the drugs did not induce DNA fragmentation in SBC-3/Bcl-2. However, there was no difference in sensitivity to CDDP, VP-16, ACNU, MTX and Taxol between SBC-3 and SBC-3/Bcl-2 (Ohmori, T. et al. Biochem. Biophys. Res. Commun. 1993). These studies indicate that bcl-2 can modulate the cytotoxicity of some anti-cancer agents by inhibiting the process of apoptosis. We speculate that some apoptotic pathways are bcl-2-sensitive and others bcl-2-independent.

Animals↗
PubMed1994

[Evaluation of the exercise capacity recovery process after lung cancer surgery by exercise test and expire gas analysis].

This study was conducted to evaluate the numerical changes and the recovery process in exercise capacity over time, and to establish new criteria that will objectively evaluate the recovery in exercise capacity after lung surgery using an expired gas analysis incorporating an exercise test. The subjects consisted of 47 patients that underwent curative resection (only lobectomy) for lung cancer in the four years from 1989 to 1992 that were able to undergo expired gas analysis incorporating an exercise test before and after surgery. The expired gas analysis were performed within one week prior to surgery and over a period from 14 to 449 days after surgery, maximum oxygen consumption (VO2max) and anaerobic threshold (AT) measured, and the VO2max/m2 and AT/m2 were calculated as an index by dividing by the body surface area (m2). In addition, in order to examine the changes in exercise capacity after surgery, the presurgical values were used as 100, and the rate of change after surgery found. These rate were divided into the following measuring times, and the postsurgical changes over time analyzed. The postsurgical measuring times were divided into five groups from 14-30 days (n = 11), from 31-90 days (n = 25), from 91-180 days (n = 8), from 181-270 days (n = 19), and greater than 271 days (n = 8) after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

[Clinical role of ultrasound and color Doppler ultrasound in diagnosing pancreatic endocrine tumors].

US, EUS, color Doppler US, and color Doppler EUS were performed for five cases of pancreatic endocrine tumors. US was able to detect four cases of five tumors (80%), but could not sufficiently evaluate the internal echo. Color Doppler US was able to reveal the blood flows inside in only one case (25%). EUS was able to detect clearly all five cases (100%), and color Doppler EUS was able to reveal a significant amount of the internal blood flow in all cases. Color Doppler EUS was reflected in hypervascular findings on angiogram and proliferating vascular findings on histology. Therefore, ultrasound, especially EUS was useful for diagnosing the location of the tumor and for evaluating the internal echo, whereas color Doppler EUS was useful for evaluating the vascularity of the tumors.

Adenoma, Islet Cell↗
PubMed1994

[Assessment of tumor extent in extrahepatic bile duct cancers--utility of intraductal ultrasonography].

Intraductal ultrasonography (IDUS) were performed in patients with extrahepatic bile duct cancer and compared to other diagnostic modalities and to resected specimens. Endoscopic ultrasonography (EUS) is a non-invasive diagnostic method useful for screening patients with bile duct cancers and determining whether they are resectable or not. While, EUS was not useful for the differential diagnosis of advanced and early tumors, and less useful in case of bile duct tumors located at the hilus hepatitis. IDUS proved useful without blind spot even in case of bile duct cancers at the hilus hepatis. IDUS was especially useful for the differential diagnosis of advanced and early tumors. IDUS is the very accurate diagnostic modality which make up for EUS and essential to determine the appropriate operation plan.

Aged↗
PubMed1994

[Early phase II study of MST-16 (sobuzoxane) for breast cancer].

An early phase II study of MST-16 for breast cancer was conducted with the participation of 9 hospitals. MST-16 was administered at three doses; 1) 1,600 mg/body for 5 consecutive days repeating every 4 weeks, 2) 1,200 mg/body for 10-14 consecutive days every 5 weeks, and 3) 1,200 mg/body daily for at least 4 weeks. A total of 28 patients were entered, and 27 cases were eligible. Twenty-five cases were evaluated for efficacy and 27 cases for safety. One patient achieved complete response, 2 patients attained partial response, and the response rate thus obtained was 12.0%. Major side effects observed were myelosuppression represented by leukopenia (69.2%) followed by gastrointestinal disorders. These symptoms, however, were reversible by the cessation of administration.

Adult↗
PubMed1994

Distribution of organized sensory nerve endings in the human periodontal ligament.

The purpose of the present study was to clarify the distribution pattern of organized nerve endings in human-periodontal ligament. The materials investigated were obtained from the first premolar teeth. The fresh periodontal ligament of the extracted tooth was stained using the methylene blue vital staining method. Then the whole-mount preparations of the periodontal ligament were observed by light microscope. Three kinds of receptors (encapsulate corpuscles, bush-like endings and free-nerve endings) were located in the ligament. The ratio of total number of encapsulated corpuscles to bush-like endings was one to three. The density of the encapsulated corpuscles ranged from 0.2/mm2 to 1.2/mm2 and the bush-like endings ranged from 1.3/mm2 to 3.2/mm2. The most organized nerve endings were distributed at the middle one third in the ligament. The distribution of bush-like endings, which differed from that of encapsulated corpuscles, might contribute to their response thresholds and static properties.

Adolescent↗
PubMed1994

[Long-term results of the surgical treatment for thymoma].

Long-term results of the surgical treatment for 27 cases of thymoma were studied. The clinical stages according to Masaoka's classification were: 7 cases of stage I, 9 cases of stage II, 8 cases of stage III, 1 case of stage IVa and 2 cases of stage IVb. The histological classifications were: epithelial cell type in 10 cases, lymphocytic type in 9 cases and mixed type in 8 cases. Complications consisted of 18 cases of myasthenia gravis (MG). The long-term survival at 5 and 10 years were as follows: 90.6%, 74.8% in all cases; 100.0%, 50.0% in the non-invasive type; 88.2%, 80.2% in the invasive type; 72.0%, 72.0% in the epithelial cell type; 100.0%, 75.0% in the lymphocytic type; 100.0%, 80.0% in the mixed type; 88.9%, 44.4% in cases not complicated with MG; 92.9%, 84.4% in cases complicated with MG. Complete resection and adjuvant therapy improved prognosis even in cases of invasive thymoma, but one case died due to local recurrence of thymoma at 10 years after operation, so we emphasize it is important to follow up for the long time period more than 10 years.

Adult↗
PubMed1993

Cellular mechanism of glyburide-induced insulin gene expression in isolated rat islets.

The cellular mechanism for the effects of glyburide on the synthesis and release of insulin and insulin gene expression in isolated islets was investigated. On incubation for 1 h, glyburide increased insulin release without affecting either the insulin content or the PPI mRNA level. H-7, an inhibitor of PKC, inhibited the glyburide-induced insulin release, while H-8, an inhibitor of cyclic nucleotide-dependent protein kinases, did not affect the glyburide-induced insulin release. On incubation for 20 h, glyburide increased insulin release and the PPI mRNA level, without affecting the insulin content. H-7 inhibited glyburide-induced insulin release and increased the PPI mRNA level. H-8 significantly inhibited both the glyburide-induced increase in insulin release and increase in PPI mRNA level. In conclusion, glyburide stimulated insulin release via a PKC-mediated pathway and increased the PPI mRNA level via cyclic nucleotide-dependent protein kinase(s).

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1993

Identification of a precursor genomic segment that provided a sequence unique to glycophorin B and E genes.

Human glycophorin A, B, and E (GPA, GPB, and GPE) genes belong to a gene family located at the long arm of chromosome 4. These three genes are homologous from the 5'-flanking sequence to the Alu sequence, which is 1 kb downstream from the exon encoding the transmembrane domain. Analysis of the Alu sequence and flanking direct repeat sequences suggested that the GPA gene most closely resembles the ancestral gene, whereas the GPB and GPE genes arose by homologous recombination within the Alu sequence, acquiring 3' sequences from an unrelated precursor genomic segment. Here we describe the identification of this putative precursor genomic segment. A human genomic library was screened by using the sequence of the 3' region of the GPB gene as a probe. The genomic clones isolated were found to contain an Alu sequence that appeared to be involved in the recombination. Downstream from the Alu sequence, the nucleotide sequence of the precursor genomic segment is almost identical to that of the GPB or GPE gene. In contrast, the upstream sequence of the genomic segment differs entirely from that of the GPA, GPB, and GPE genes. Conservation of the direct repeats flanking the Alu sequence of the genomic segment strongly suggests that the sequence of this genomic segment has been maintained during evolution. This identified genomic segment was found to reside downstream from the GPA gene by both gene mapping and in situ chromosomal localization. The precursor genomic segment was also identified in the orangutan genome, which is known to lack GPB and GPE genes. These results indicate that one of the duplicated ancestral glycophorin genes acquired a unique 3' sequence by unequal crossing-over through its Alu sequence and the further downstream Alu sequence present in the duplicated gene. Further duplication and divergence of this gene yielded the GPB and GPE genes.

Base Sequence↗
PubMed1993

Protective effects of sialylated oligosaccharides in immune complex-induced acute lung injury.

Using sialyl Lewisx (SLX) oligosaccharides derived from fucosyl transferase-expressing cells or generated synthetically, the ability of these compounds to protect against acute lung damage after deposition of immunoglobulin (Ig)G or IgA immune complexes has been determined. The synthetic compounds were tetra- and pentasaccharide derivates of SLX as well as the nonfucosylated forms of SLX as controls. In the IgG immune complex model of lung injury, which is E-selectin dependent, SLX preparations provided dose-dependent protective effects, as assessed by changes in lung vascular permeability and hemorrhage. Protective effects were associated with diminished tissue accumulation of neutrophils in lungs (as assessed by myeloperoxidase). Morphological assessment revealed reduced physical contact of neutrophils with the pulmonary vascular endothelium and reduced tissue accumulation of neutrophils. In the model of IgA immune complex-induced lung injury, which does not involve participation of neutrophils and is independent of the requirement for E-selectin, SLX preparations were not protective. These data suggest that, in neutrophil-mediated and E-selectin-dependent lung injury, SLX preparations provide significant, protective effects against inflammatory vascular injury. The ability to achieve antiinflammatory outcomes in vivo with appropriate oligosaccharides suggests a new approach to the blocking of acute inflammatory responses.

Acute Disease↗
PubMed1993

Amygdala-hypothalamic control of feeding behavior in monkey: single cell responses before and after reversible blockade of temporal cortex or amygdala projections.

Single unit activity in the monkey amygdala and the lateral hypothalamic area was recorded during an operant feeding task. The task required discrimination of food, non-food, rewarding, aversive, novel, and familiar objects. Correct discriminations were rewarded with food or juice. Some amygdala neurons responded to the sight of objects in a graded manner that depended on the degree of affective significance of the object. Some neurons in the lateral hypothalamus responded to reward predicting objects, such as the sight of some non-food item that had been associated with juice reward. Neuronal responses to the sight of objects were influenced by extinction or reversal tests. Responses in the amygdala depended on extent of the affect or value of the reward and responses in the lateral hypothalamus depended on positive reinforcement. Information processing in the inferotemporal cortex--amygdala--lateral hypothalamus axis was identified by reversible changes induced in the temporal cortex or amygdala by cooling. The results suggest that the amygdala contributes to stimulus--affect associations and that the lateral hypothalamus is related directly to the initiation or termination of feeding through learning of stimulus-reinforcement association and/or maintenance of homeostasis. In addition the results suggest that the amygdala does more sensory processing than the lateral hypothalamus.

Amygdala↗
PubMed1993

E-selectin-dependent adhesion efficiency of colonic carcinoma cells is increased by genetic manipulation of their cell surface lysosomal membrane glycoprotein-1 expression levels.

Lysosomal membrane glycoprotein (lamp)-1 and lamp-2 are the most abundant glycoproteins within the lysosomal membrane. A small amount of lamp-1 and lamp-2 molecules, however, can be present on the cell surface. We have shown previously that highly metastatic colonic carcinoma L4 cells express more lamp-1 and lamp-2 on the cell surface than low metastatic SP cells (Saitoh, O., Wang, W.-L., Lotan, R., and Fukuda, M. (1992) J. Biol. Chem. 267, 5700-5711). Since lamp-1 and lamp-2 are the major carriers for poly-N-acetyllactosamines that are able to display sialyl-Le(x) termini, we sought to determine if an increased amount of lamp-1 on the cell surface would lead to increased expression of cell surface sialyl-Le(x) determinants and to the increased adhesion of those cells to E-selectin. Expression of increased amounts of lamp-1 on the cell surface was achieved either by overexpression of lamp-1 or by expressing a mutant lamp-1 molecule preferentially at the plasma membrane, rather than in lysosomes. Cells that express variable amounts of cell surface lamp-1 were tested for their adhesion to activated endothelial cells or E-selectin expressing Chinese hamster ovary cells. The results clearly show that the extent of adhesion to E-selectin and cell surface sialyl-Le(x) determinants is proportional to the amount of cell surface lamp-1. Moreover, it was demonstrated that such adhesion can be inhibited by soluble lamp-1 generated from Chinese hamster ovary cells expressing sialyl-Le(x) structures. These results indicate that lamp-1 can efficiently present ligands for E-selectin and at the same time can be a useful reagent for inhibition of E-selectin (and possibly P-selectin)-mediated interaction.

Animals↗
PubMed1993

Polymorphic hemoglobin from a midge larva (Tokunagayusurika akamusi) can be divided into two different types.

The hemoglobin from the 4th-instar larva of Tokunagayusurika akamusi, a common midge found in eutrophic lakes in Japan, was composed of as many as 11 separable components (IA, IB, II, III, IV, V, VIA, VIB, VII, VIII, IX) on a DEAE-cellulose column. However, we have found that these components can be divided into two groups on the basis of their spectroscopic properties, one being named as the normal type (N-type) and the other being referred to as the low type (L-type). Since the major difference between them seemed to be the presence or absence of the distal (E7) histidine residue, which plays an important role in the stability properties of the bound dioxygen, the complete amino acid sequence was then determined for each typical component, namely, VII (N-type) and V (L-type): the former hemoglobin contained the usual distal histidine residue at position 64, whereas the latter one replaced it by isoleucine at position 66. The homology test for 40 N-terminal amino acid residues of all components also demonstrates that T. akamusi hemoglobin is composed of two different clusters showing a very early separation in the phylogenetic tree.

Amino Acid Sequence↗
PubMed1993

MHC-linked diabetogenic gene of the NOD mouse: molecular mapping of the 3' boundary of the diabetogenic region.

To localize and characterize the MHC-linked diabetogenic gene of the NOD mouse, we studied the class III region of the MHC in the NOD mouse and related strains. Hsp70, Bat5, Tnfa and Tnfb loci were studied by microsatellite polymorphism analysis and/or restriction mapping. The CTS mouse had the same allele as the NOD mouse at the Hsp70 locus, but different alleles at the Bat5, Tnfa and Tnfb loci from those of the NOD mouse. Our previous studies indicated that in the CTS mouse, class II MHC was the same as that of the NOD mouse, but that class I MHC was different at both K and D loci, and that CTS MHC was diabetogenic in the presence of NOD background genes. These data map major genetic susceptibility to type 1 diabetes to the segment flanked by class I K and class III Bat5 loci. Moreover, since the diabetogenic effect of the CTS MHC is weaker than that of the NOD MHC, these data suggest the presence of a second MHC-linked gene or gene complexes that modulate susceptibility to type 1 diabetes outside this segment.

Animals↗
PubMed1993

The genes of major lysosomal membrane glycoproteins, lamp-1 and lamp-2. 5'-flanking sequence of lamp-2 gene and comparison of exon organization in two genes.

Human lysosomal membrane glycoproteins lamp-1 and lamp-2 are the major sialoglycoproteins present in lysosomal membranes. The expression of lamp-2 molecules is uniquely regulated, whereas lamp-1 is constitutively synthesized. In order to investigate the unique expression of lamp-2, and the gene evolution of lamp-1 and lamp-2, we isolated genomic phage clones encoding these glycoproteins. Comparison of the genomic and cDNA sequences revealed that the lamp-2 gene consists of nine exons. The transcriptional start site of the lamp-2 gene was determined by primer extension analysis. In order to locate the transcriptional regulatory region of this gene, various regions of 5'-sequences were tested for promoter activity using chloramphenicol acetyltransferase as a reporter molecule. The results revealed that the 5'-flanking sequence from -172 to -20 base pairs has strong promoter activity. In this sequence, potential SP1 and AP-1 binding sites and CAAT boxes are found. Most notably, the promoter activity is suppressed if the 5' farther upstream KpnI repeat sequence is included in the tested 5'-flanking sequence, thus suggesting that the KpnI repeat sequence may have some regulatory function in the lamp-2 gene expression. Comparison of the exon organization of human lamp-2 and lamp-1 genes, or chicken lamp-1 gene, reveals that these two proteins utilize the same exon phase in corresponding introns. Furthermore, each exon encodes almost identical portions of the proteins. On the other hand, the amino acid sequence of human lamp-1 is more homologous to lamp-1 of other species than it is to human lamp-2. These results indicate that lamp-1 and lamp-2 genes were most likely produced by duplication of a primordial gene, which took place early in evolution.

Amino Acid Sequence↗
PubMed1993

Progression of signet ring cell carcinomas in the human stomach.

BACKGROUND: Stomach cancers show various growth patterns. It remains to be clarified how this variability is related to the genetic changes that occur during tumor progression. METHODS: To estimate the genetic changes from tumor ploidy, maps were made (using DNA cytofluorometry of metaphase cells in histologic sections) of 39 advanced signet ring cell carcinomas of the human stomach and correlated with tumor stage and the size of the primary mucosal lesion. RESULTS: Aneuploid area and multipattern aneuploidy were particularly common in advanced cancers with primary mucosal lesions smaller than 2 cm in diameter, of which a large portion were predominantly aneuploid and already diffusely infiltrating. As the tumor stage advanced, the incidence of aneuploidy in the mucosal lesion increased, whereas predominantly aneuploid tumors were less common as primary mucosal lesions became larger. Purely diploid areas with an incidence of polyploidy as low as in early cancers were common in advanced cancers. In addition, there were diploid-appearing cancer cells that infiltrated diffusely and were accompanied by polyploid as often as aneuploid cells. Some of these were aneuploid at the chromosomal level. CONCLUSIONS: In signet ring cell carcinoma, aneuploid cells show higher invasive activity toward the extramucosal part and may occur incidentally in originally diploid tumors, depending on the degree of genetic instability. An analysis of polyploidy is useful for differentiating cytometrically diploid (but actually, aneuploid) cells from diploid cells with minor genetic abnormalities.

Adenocarcinoma, Mucinous↗