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Biomedical subjects

M Fukuda

Publications and source records attributed to M Fukuda.

At least 739 records · Page 41Linked to original sources
PubMed1993

Glycophorin B and glycophorin E genes arose from the glycophorin A ancestral gene via two duplications during primate evolution.

Human glycophorin A, B, and E genes are homologous from the 5'-flanking region to 1 kilobase downstream from the exon encoding the transmembrane region. Analysis of human Alu sequences at the transition site from the homologous to nonhomologous region suggested that the GPA gene most closely resembles the ancestral gene, whereas GPB and GPE genes arose by homologous recombination within the Alu repetitive sequence, and acquired 3' sequences from an unrelated gene (Kudo, S., and Fukuda, M. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 4619-4623; Kudo, S., and Fukuda, M. (1990) J. Biol. Chem. 265, 1102-1110). To understand glycophorin gene evolution in primate phylogeny, transmembrane and Alu regions of several primate genomes were amplified by the polymerase chain reaction and their sequences were analyzed. These studies revealed that the GPA gene was present in all primates studied, and the GPB gene was present in pygmy chimpanzee, chimpanzee, and gorilla, but absent from orangutan and gibbon. GPE gene was present in all species with a GPB gene, but was detected in only 7 out of 16 gorillas. The 24-base pair insertion sequence found in the transmembrane exon of the human GPE gene was shown to be derived from the ancestral GPB gene and was inserted into the ancestral GPE gene prior to gorilla divergence. The recombination site in the GPA gene was confirmed to be within an Alu repetitive sequence. We conclude that GPB and GPE genes arose from an ancestral GPA gene via two gene duplications occurring during primate evolution, prior to gorilla divergence.

Amino Acid Sequence↗
PubMed1993

Assignment of O-glycan attachment sites to the hinge-like regions of human lysosomal membrane glycoproteins lamp-1 and lamp-2.

The lysosomal membrane glycoproteins lamp-1 and lamp-2 are extensively glycosylated with a variety of different carbohydrate structures of both N-linked and O-linked type. In the present paper, we report the localization of O-linked oligosaccharides exclusively to the hinge-like regions of lamp-1 and lamp-2 isolated from human chronic myelogenous leukemia cells. In both glycoproteins, the O-glycans appear in clusters. In lamp-1, Thr-171, Thr-172, Ser-179, Ser-181, and Ser-183 were fully glycosylated, whereas Ser-169 was partially glycosylated. In lamp-2, complete glycosylation was found at Ser-167, Thr-168, Thr-172, Thr-175, Thr-176, Thr-182, and Thr-183, and partial glycosylation at Ser-179 and Thr-181, and possibly also at Thr-185. The amino acid sequences of these O-glycosylation sites are consistent with the previous reports that residues at positions -1 and +3 may influence the glycosylation reaction. Circular dichroism and nuclear magnetic resonance spectroscopy was used for the structural characterization of a synthetic peptide corresponding to residues 167 to 190 of lamp-1. The results indicated that the proline-rich O-glycan acceptor region does not adopt any typical periodic structure but differs from random-coil structure. The circular dichroism spectrum of the peptide is, however, similar to that of porcine submaxillary apomucin. A significant conformational variability was observed in this region, presumably due to a slow (on the nuclear magnetic resonance time scale) cis-trans isomerization of several proline residues. These results, taken together, strongly suggest that a hinge region does not display any typical ordered structure. The presence of O-glycans thus likely protects this region from intralumenal lysosomal proteases.

Amino Acid Sequence↗
PubMed1993

Cell surface expression of lysosome-associated membrane proteins (LAMPs) in scleroderma: relationship of lamp2 to disease duration, anti-Sc170 antibodies, serum interleukin-8, and soluble interleukin-2 receptor levels.

Lysosome-associated membrane proteins (LAMPs) are integral transmembrane proteins densely expressed on lysosomes which can be shuttled to the plasma membrane during cell activation. The objective of this study was to examine the expression of LAMPs on the cell surface of peripheral blood mononuclear cells (PBMCs) derived from patients with scleroderma. Heparinized blood was obtained from 23 patients with scleroderma and 15 healthy controls and PBMCs were isolated via a Ficoll gradient. Cells were stained with monoclonal antibodies directed against two of the major LAMPs, lamp1 and lamp2, and after subsequent staining with a fluorescent second antibody, were analyzed by flow cytometry. Two -and three-color immunofluorescence was utilized to define the phenotype of LAMP+ cells. The proportion of PBMCs expressing lamp2 on the cell surface was significantly elevated in patients with scleroderma (2.21 +/- 0.38%) compared to controls (1.14 +/- 0.27%; P < 0.05). Multivariate analysis of patient subgroups indicated that the significant factors contributing to higher levels in patients were shorter duration of disease (P < 0.01) and greater functional disability related to disease manifestations (P < 0.01). Patients with anti-Scl70 antibodies had the highest levels of cell surface lamp2 expression (4.19 +/- 0.90%; P < 0.0005). The degree of cell surface lamp2 expression correlated with the level of sIL2R in 19 scleroderma patients (r = 0.48; P < 0.05). Serum IL4 and IL6 did not correlate with cell surface LAMPs or sIL2R. Five of 19 patients had detectable serum levels of interleukin-8 (IL8). These patients had significantly higher cell surface lamp2 expression than those with no detectable IL8 (3.76 +/- 0.48% vs 1.44 +/- 0.39%; P < 0.01). Extended phenotyping revealed that > 85% of lamp2+ cells expressed the B-cell antigen CD19. Cell surface lamp2 expression correlates with clinical and laboratory parameters in scleroderma patients and may reflect immune system activation. Additionally, this is the first report describing an elevation of serum IL8 in an autoimmune or collagen-vascular disease.

Adolescent↗
PubMed1993

SART stress effects on lymphocytes in the thymus and spleen of normal, adrenalectomized, and sympathectomized mice.

The effects of stress due to specific alteration of rhythm of temperature (SART) on lymphocyte subpopulations of the thymus and spleen were examined in C3H/He mice. Thymic and splenic involution were evident in SART-stressed mice, and lymphocyte subpopulations were significantly changed. In the thymus, CD4+ CD8+ and CD3- or CD3low lymphocytes were decreased by SART stress more than other lymphocytes, and CD4- and CD8-single-positive lymphocytes and B lymphocytes in the spleen were decreased equally. Immunoregulation via the adrenal glands and sympathetic nervous system was studied in chemically sympathectomized and adrenalectomized SART-stressed mice. Neither chemical sympathectomy nor adrenalectomy alone influenced the thymus or spleen in nonstressed mice, but chemical sympathectomy enhanced SART stress-induced thymic changes and further decreased the number of B lymphocytes in the spleen of SART-stressed mice; adrenalectomy blocked SART stress-induced thymic changes and increased the number of B lymphocytes in the spleen. These findings indicate that the genesis of thymic changes induced by SART stress is in the adrenal glands, and malfunction of sympathetic nerves and insufficient excretion of adrenal hormones could alter the balance of lymphocytes in the spleen during stress. It was also clear that thymic changes induced by SART stress could be immediately reversed to pretest conditions by alleviating the stress.

Adrenal Glands↗
PubMed1993

Urinary 1-hydroxypyrene as a marker of exposure to polycyclic aromatic hydrocarbons in environment.

The concentrations of pollutants, especially polycyclic aromatic hydrocarbons (PAHs), originating from automobile emissions are high in areas around urban arterial roads. To investigate the possibility of using urinary 1-hydroxypyrene (1-POH) a metabolite of pyrene, as a marker for estimating the amount of human exposure to PAHs, both an animal experiment and an ecological correlation study were conducted. Rats were exposed to one of two sources of PAH: diesel engine emissions containing particulate matter and NO2 at average concentrations of 4.20 mg/m3 and 2.90 ppm, respectively, or, for the control group, air having the respective average concentrations of 0.01 mg/m3 and 0.02 ppm. The concentration of pyrene was 36 ng/mg in the particulate matter in the diluted diesel engine exhaust and 9.0 ng/g in the feed to the rats. Urinary 1-POH levels in the rats of the exposure group increased remarkably over those of the control group, 2.4 times as much by the 2nd week of exposure and 5.6 times by the 4th and 8th weeks. The ecological correlation study was conducted in 1988 and 1989 in two area of Tokyo along arterial roads (Meguro and Itabashi Wards) and in one suburban area (Higashiyamato City) to measure urinary 1-POH levels in elementary school children who lived in those areas. Urinary samples were collected in October in 1988, as well as in January, May, and July in 1989. Throughout the period of investigation, the schoolchildren in the highly NOx-polluted Meguro and Itabashi Wards showed significantly higher urinary 1-POH levels than the children in the less-polluted Higashiyamato City by a factor of 1.1-1.6. These results suggest that the urinary 1-POH level could be used as a good marker for estimating the amount of exposure of residents to PAHs.

Air Pollutants↗
PubMed1993

A case of bilateral obturator hernias: image diagnosis and description of a retropubic operative approach.

A case of bilateral obturator hernias which was diagnosed by ultrasonography (US) and computed tomography (CT), and repaired by a retropubic extraperitoneal operative approach under spinal anesthesia is reported herein. A 91-year-old woman presented with lower abdominal and left groin pain consistent with a Howship-Romberg sign. US demonstrated an image of the bowel projecting from the small pelvic space to the left thigh with a to-and-fro movement of the bowel contents. The definitive diagnosis of an incarcerated left obturator hernia was made by CT which also revealed a mass in the right obturator foramen. Surgery was performed through a retropubic extraperitoneal approach under spinal anesthesia. No necrosis was observed in the incarcerated bowel and resection was not necessary. A simple hernial sac was found in the right obturator canal. The operation using the retropubic extraperitoneal approach was successful and we believe it to be the most effective procedure for obturator hernias which have been diagnosed early.

Aged↗
PubMed1993

A microsatellite polymorphism in the human insulin receptor gene: a highly informative marker for linkage analysis.

To study genetic susceptibility to non-insulin dependent diabetes mellitus (NIDDM), association of insulin receptor gene, a candidate gene for NIDDM, with NIDDM was studied. A microsatellite polymorphism located in intron 2 of the human insulin receptor gene was detected by the polymerase chain reaction and used as a genetic marker. Eight different alleles were observed, indicating highly polymorphic nature of this marker. Although no association of this marker with NIDDM was observed in Japanese subjects, this marker will be useful for linkage studies of insulin receptor gene and genes located close to this gene on chromosome 19.

Alleles↗
PubMed1993

Rat amygdaloid neuron responses during auditory discrimination.

To investigate amygdaloid contribution to stimulus-affect association and to emotional behavior, single neuron activity was recorded in the basolateral and corticomedial amygdala of the rat amygdala during discrimination of conditioned cue tones associated with positive (glucose and intracranial self-stimulation) and negative (weak electric footshock) unconditioned stimuli. Amygdaloid neurons that responded to two rewarding unconditioned stimuli responded in the same manner to both. Responses to conditioned cue tones and those to rewards were also significantly related, suggesting that amygdaloid neuronal responses to conditioned stimuli are closely related to the affective nature of the corresponding unconditioned stimulation. These might be neuronal functions that underlie stimulus-affect association in the amygdala. In random repeated trials, including acquisition to conditioned cue tones and extinction after acquisition, response plasticity was more evident in basolateral than in corticomedial neurons. Furthermore, more basolateral than corticomedial neurons differentiated glucose and its cue from intracranial self-stimulation and its cue by responding to one but not the other. More basolateral than corticomedial neurons were excited by intracranial self-stimulation and its cue and inhibited by footshock and its cue. The differences between the two nuclear groups suggest that basolateral neurons are more plastic and discriminative, and corticomedial neurons respond indiscriminately to positive and negative unconditioned or conditioned stimuli. The results indicate amygdaloid neuron involvement in stimulus-affect association. Basolateral neurons may be more involved than corticomedial neurons in discriminating and learning conditioned stimuli.

Acoustic Stimulation↗
PubMed1993

Neuronal responses in monkey anterior putamen during operant bar-press behavior.

Single neuron activity was recorded in the monkey anterior putamen to compare visuomotor-related responses during operant bar-press behavior with visual discrimination of objects. Of 615 neurons recorded, 9.8% (60/615) responded to the presentation of food during forced delay of access to the bar. Of these 60 neurons, 38 were also tested with nonfood, and 19 of these responded to the nonfood objects regardless of the following movement. The amplitude of the visual-related responses of some differential neurons was graded for different objects to reflect the relative degree of preference for the food presented. However, these responses disappeared in reaction time tasks in which the bar could be accessed for pressing immediately upon presentation of an object. The visual response latency of differential neurons ranged from 50 to 700 ms (mean +/- SD, 386 +/- 211 ms), which was longer than that of the nondifferential responses (207 +/- 204 ms). These results suggest that anterior putamen neurons might participate in estimation of visual information that could be related to forecasting movement.

Animals↗
PubMed1993

Compensatory function of central dopaminergic system for suppressing psychic seizures--repeated plasma homovanillic acid measurement in refractory temporal lobe epilepsy.

Repeatedly measured plasma homovanillic acid concentration, as a clinically available index of central dopaminergic activity in a patient with temporal lobe epilepsy during a drug-free period, was significantly correlated with seizure frequency in the week immediately following, but not preceding, blood sampling days. This result suggests a compensatory function of the dopaminergic system in suppressing refractory psychic seizures.

Adult↗
PubMed1993

Expression of the developmental I antigen by a cloned human cDNA encoding a member of a beta-1,6-N-acetylglucosaminyltransferase gene family.

The blood group i/I antigens were the first identified alloantigens that display a dramatic change during human development. The i and I antigens are determined by linear and branched poly-N-acetyllactosaminoglycans, respectively. In human erythrocytes during embryonic development, the fetal (i) antigen is replaced by the adult (I) antigen as a result of the appearance of a beta-1,6-N-acetylglucosaminyltransferase, the I-branching enzyme. Here, we report the cDNA cloning and expression of this branching enzyme that converts linear into branched poly-N-acetyllactosaminoglycans, thus introducing the I antigen in transfected cells. The cDNA sequence predicts a protein with type II membrane topology as has been found for all other mammalian glycosyltransferases cloned to date. The Chinese hamster ovary cells that stably express the isolated cDNA acquire I-branched structures as evidenced by the structural analysis of glycopeptides from these cells. Comparison of the amino acid sequence with those of other glycosyltransferases revealed that this I-branching enzyme and another beta-1,6-N-acetylglucosaminyltransferase that forms a branch in O-glycans are strongly homologous in the center of their putative catalytic domains. Moreover, the genes encoding these two beta-1,6-N-acetylglucosaminyltransferases were found to be located at the same locus on chromosome 9, band q21. These results indicate that the I-branching enzyme represents a member of a beta-1,6-N-acetylglucosaminyltransferase gene family of which expression is controlled by developmental programs.

Adult↗
PubMed1993

Acquired dermal melanocytosis of the hand: a new clinical type of dermal melanocytosis.

We report a 22-year-old man with acquired dermal melanocytosis on the hand which developed without any history of previous inflammation. He had no history of contact with or oral administration of any drugs or metals which might have caused pigmentation. Histopathologically, spindle-shaped dermal melanocytes were observed running parallel to the collagen bundles and scattered in all portions of the dermis. The dopa reaction of these cells was positive. Ultrastructurally, dermal melanocytes containing numerous melanosomes (stages II to IV) which were surrounded by the extracellular sheath were observed. Differential diagnosis of other dermal melanocytosis was discussed.

Adult↗
PubMed1993

Effects of ultraviolet-B and PUVA on ornithine decarboxylase activity, DNA synthesis, and protein kinase C activity in mouse skin.

Ultraviolet-B and PUVA share several biological events with phorbol ester tumor promoters. The effects of ultraviolet-B irradiation and topical PUVA treatment on ornithine decarboxylase activity, DNA synthesis, and protein kinase C activity, which are known to be induced or activated by phorbol ester tumor promoter, were investigated in hairless mouse skin. Ornithine decarboxylase activity was remarkably enhanced by ultraviolet-B and PUVA. Although PUVA did not affect DNA synthesis significantly, ultraviolet-B stimulated epidermal DNA synthesis approximately 5-fold over control values at 48 h. However, unexpectedly, neither cytosolic nor membrane-bound protein kinase C activity showed any change during the 2 h after either treatment. These results suggest that the protein kinase C system is not involved in the initial signal transduction system of ultraviolet-B or PUVA, unlike the case with phorbol ester tumor promoter.

Animals↗