Biomedical subjects

K Kitagawa

Publications and source records attributed to K Kitagawa.

At least 145 records · Page 8Linked to original sources

PubMed1996

Primary cornea guttata in Japanese patients with cataract: specular microscopic observations.

To evaluate the prevalence of primary cornea guttata (the first stage of Fuchs' dystrophy) in Japanese patients, we retrospectively examined specular photomicrographs of patients' cataracts. Primary cornea guttata in subjects without corneal inflammation was defined as dark areas, seen on specular microscopy, and irregular refractile dots, observed with slit-lamp microscopy. In 107 patients with cataract (211 eyes), primary cornea guttata was found in 4 women (7 eyes), aged 56 to 76 years. One eye of patient 4, who had a history of angle-closure glaucoma and laser iridotomy, had bullous keratopathy. We also examined 16 relatives (32 eyes) of these 4 affected patients (probands), and found 2 women (4 eyes) with primary cornea guttata. No hereditary influence was identified. We believe that the incidence of primary cornea guttata (Fuchs' dystrophy) in Japan is lower than that in North America.

Adult↗

PubMed1996

[A comparative study of caregivers of the elderly with dementia between 1982 and 1991].

The purpose of this study is to clarify the changes of the caregivers'status with comparison of two cross-sectional studies. The subjects were 658 (primary, in 1982) and 705 (secondary, in 1991) group members of "The Association of Families Caring for Elderly Persons with Dementia". The summary of results are as follows: 1) The mean life span of a person suffering dementia was found to be longer in 1991 than 1992. 2) In 1991, about 30 percent of the patients in all age groups were hospitalized and about 70 percent of the patients were treated at home. These facts indicated that the medical facilities had expanded their capacities during the 9 year period for receiving the elderly with dementia. 3) Family members who wished to live independently supported the idea that care should be given by a decreased number of individuals within the family. In that sense, the family's power of caregiving was decreased. 4) The range of main caregivers' informal social-support-network was remarkably expanded. 5) The more the service were expanded, the more the service were utilized by the caregivers. However, the quality and the quantity of the services provided are still not sufficient to meet the caregivers' need. 6) In balance, the difficulties caregivers used to face, seemed to be decreased in 1991.

Aged↗

PubMed1995

Isolation and mapping of human homologues of an imprinted mouse gene U2af1-rs1.

We have isolated human homologues of the imprinted mouse gene, U2af1-rs1. Two different types of cDNAs and three distinct genomic DNAs belonging to different groups were isolated. We have identified chromosomal genes corresponding to each cDNA by restriction mapping and sequencing. Using both a panel of rodent/human somatic cell hybrids and fluorescence in situ hybridization, group 1 and group 2 genes were mapped to chromosome 5q22 and chromosome Xp22.1, respectively. We designated group 1 and group 2 genes as human U2AF1-RS1 and U2AF1-RS2, respectively, because these genes corresponded to mouse U2af1-rs1 (chromosome 11) and U2af1-rs2 (chromosome X), which we also isolated and mapped. Amino acid sequences of human U2AF1-RS1 and U2AF-RS2 showed significant homology to U2AF small subunit. The group 3 gene, designated as U2AF1-RS3, of which the cDNA has not yet been isolated, was mapped to chromosome 19p13.2.

Amino Acid Sequence↗

PubMed1995

Cloning and mapping of the U2af1-rs2 gene with a high transmission distortion in interspecific backcross progeny.

We have cloned and analyzed the mouse U2af1-rs2 gene based on its sequence similarity to the imprinted gene U2af1-rs1 (SP2). Sequence analysis of this U2af1-rs2 cDNA revealed that it contained an open reading frame encoding a protein of 462 amino acid residues. The predicted amino acid sequence showed 72.7 and 35.8% identity to the U2af1-rs1 and U2 small nuclear ribonucleoprotein auxiliary factor, respectively. Interspecific backcross analysis showed this gene to map to the distal region of the X chromosome and also indicated that there was significant distortion of transmission ratio of the U2af1-rs2 allele in the backcrossed progeny from (C57BL/6J x Mus spretus)F1 females mated to Mus spretus males.

Amino Acid Sequence↗

PubMed1995

Loss of Apc heterozygosity and abnormal tissue building in nascent intestinal polyps in mice carrying a truncated Apc gene.

Mutations in the APC (adenomatous polyposis coli) gene appear to be responsible for not only familial adenomatous polyposis but also many sporadic cases of gastrointestinal cancers. Using homologous recombination in mouse embryonic stem cells, we constructed mice that contained a mutant gene encoding a product truncated at a 716 (Apc delta 716). Mendelian transmission of the gene caused most homozygous mice to die in utero before day 8 of gestation. The heterozygotes developed multiple polyps throughout the intestinal tract, mostly in the small intestine. The earliest polyps arose multifocally during the third week after birth, and new polyps continued to appear thereafter. Surprisingly, every nascent polyp consisted of a microadenoma covered with a layer of the normal villous epithelium. These microadenomas originated from single crypts by forming abnormal outpockets into the inner (lacteal) side of the neighboring villi. We carefully dissected such microadenomas from nascent polyps by peeling off the normal epithelium and determined their genotype by PCR: all microadenomas had already lost the wild-type Apc allele, whereas the mutant allele remained unchanged. These results indicate that loss of heterozygosity followed by formation of intravillous microadenomas is responsible for polyposis in Apc delta 716 intestinal mucosa. It is therefore unlikely that the truncated product interacts directly with the wild-type protein and causes the microadenomas by a dominant negative mechanism.

Adenoma↗

PubMed1995

Allele-specific methylation and expression of an imprinted U2af1-rs1 (SP2) gene.

The mouse U2af1-rs1(SP2) gene, which was cloned by a two-dimensional genome scanning method, is expressed exclusively from the paternally inherited chromosome. This gene has significant similarity to U2AF and located in chromosome 11, of which maternal duplication/paternal deficiency results in a small body. In this report, we cloned genomic U2af1-rs1(SP2) and found its promoter was methylated in a maternal-allele-specific manner. This allelic methylation was not established in parental gametes, but established between 1.5 d.p.c. and 12.5 d.p.c. on the contrary, the allele-specific expression occurred in the two-cell stage when transcription initiates. Absence of the methylation of the upstream region in this stage indicates that methylation is not necessary for inactivation of the expression.

Alleles↗

PubMed1995

Femoral peak bone mass and osteoclast number in an animal model of age-related spontaneous osteopenia.

BACKGROUND: SAMP6 was developed as a murine model of age-related spontaneous osteopenia characterized by low peak bone mass. A morphometric study of the growing femur in SAMP6 and sex-matched SAMP2 at 10 days to 4 months of age was done to examine the pathogenic process related to osteopenia. METHODS: Age-related changes in cortical bone thickness, femur score, trabecular bone volume, thickness of epiphyseal growth plate, number of osteoclasts, and osteoclast surface were measured with a computerized image analyzer. Osteoclasts were examined cytomorphometrically after TRAP (tartrate resistant acid phosphatase) staining of the femoral sections. RESULTS: Cortical bone thickness and femur score increased significantly with age, while trabecular bone volume decreased significantly. Comparing mean values of cortical bone thickness, femur score and trabecular bone volume, we noted significantly lower mean values in SAMP6 than in SAMP2 mice. These significant inter-stain differences first became evident in 20-40-day-old mice, but there was no significant difference in thickness of the epiphyseal growth plate between the two strains. The mean values of the number of osteoclasts per unit bone surface length and of the osteoclast surface in SAMP6 were significantly greater than in age- and sex-matched SAMP2. Histograms of distribution of size of osteoclasts of 40-day-old male mice revealed that larger ones were more frequently seen in SAMP6. Furthermore, the ratio of osteoclasts/TRAP positive cells free in the bone marrow cavity was significantly higher in SAMP6 than in SAMP2. CONCLUSION: Activated bone resorption may play a role in the osteopenia seen in SAMP6.

Aging↗

PubMed1995

Liquid secondary-ion mass spectrometry of peptides containing multiple tyrosine-O-sulfates.

The behavior of peptides containing multiple tyrosine-O-sulfates in liquid secondary-ion mass spectrometry (LSIMS) has been investigated. In the positive-ion spectra of the peptides containing two tyrosine-O-sulfates, Cionin and CCK-associated C-terminal nonapeptide (CAP-9), the completely desulfated [M+H-2SO3]+ ions formed the base peaks, accompanying the significantly less-intense [M+H]+ and [M+H-SO3]+ ions. In the negative-ion spectra of these peptides, the [M-H]- and [M-H-SO3]- ions gave prominent peaks with significantly weaker [M-H-2SO3]- ions. In the case of a peptide containing three tyrosine-O-sulfates, [Tyr(SO3H).1]CAP-9, the completely desulfated [M+H-3SO3]+ ion again formed the base peak in the positive-ion spectrum. On the other hand, the sulfated tyrosine-containing [M+H]+, [M+H-SO3]+, and [M+H-2SO3]+ ions were of negligible abundance compared to the spectra of peptides containing two tyrosine-O-sulfates. We observed an intriguing 'ladder fragmentation pattern' in the negative-ion spectrum of this triply-sulfated peptide. The ladder consisted of the [M-H]-, [M-H-SO3]-, and [M-H-2SO3]- ions, but without the completely desulfated [M-H-3SO3]- ion. These characteristic fragmentation patterns of sulfated tyrosine-containing peptides were considered to bear a close correlation with the inherent acid-lability of a tyrosine-O-sulfate in solution. A possible mechanism has been proposed to explain the fragmentation patterns in the gaseous phase, in which a proton plays a decisive role.

Amino Acid Sequence↗

PubMed1995

Physical mapping of the retinoid X receptor B gene in mouse and human.

Retinoid X receptors (RXRs) are zinc finger-containing nuclear transcription factors. They belong to the nuclear receptor superfamily that contains retinoid receptors, vitamin D receptors, thyroid hormone receptors, and steroid hormone receptors as well as the so-called orphan receptors. We previously mapped all three RXR genes on mouse chromosomes, using a panel of Mus spretus-Mus musculus interspecific backcross mice: Namely, the RXRA-gene (Rxra) on Chr 2 near the centromere, the RXRB gene (Rxrb) on Chr 17 in the H2 region, and the RXRG gene (Rxrg) on distal Chr 1. Using cosmid clones that cover the major histocompatibility complex (MHC) region, we determined the precise physical map positions of the gene encoding mouse and human RXRB, respectively. The mouse gene (Rxrb) maps between H2-Ke4 and H2-Ke5: namely, immediately telomeric to H2-Ke4 which encodes a histidine-rich transmembrane protein, and 12 kilobases centromeric to H2-Ke5 which is expressed in lymphoid tissues. Rxrb and H2-Ke4 are transcribed into opposite directions from a CpG-rich promoter of about 250 base pairs. This gene organization is well conserved also in the human genome at the HLA-DP subregion of Chr 6p, underscoring the strong conservation of the gene organization in the MHC region between the two mammals.

Animals↗

PubMed1995

Prevalence of dry eye in Japanese eye centers.

BACKGROUND: The purpose of the investigation was to ascertain the prevalence of dry eye in new outpatients. METHODS: A total of 2127 consecutive new outpatients seen in eight Japanese centers from April 1992 to January 1993 underwent comprehensive examinations, including double vital staining and measurement of tear film break-up time, basal tear secretion, and tear clearance. Dry eye was diagnosed if patients had abnormalities of both the tear film and the ocular surface. RESULTS: Three hundred fifty-nine patients (17%) had dry eye. There was no seasonal pattern for dry eye. The condition was significantly more common in Tokyo than in suburban areas (P < 0.01). The prevalence of dry eye in visual display terminal (VDT) users and contact lens (CL) wearers was significantly higher than in non-VDT users and non-CL wearers (P < 0.05 and P < 0.02, respectively). CONCLUSION: Our findings suggest that dry eye is one of the most common ocular disorders encountered by physicians. Furthermore, if patients use VDTs or wear CLs, the likelihood of dry eye occurring is higher.

Adolescent↗

PubMed1995

Therapeutic effect of bifemelane on unilateral cerebral ischemia in gerbils.

To examine the therapeutic effect of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (bifemelane) on neuronal ischemia-reperfusion injury, we evaluated the neurological score in gerbils subjected to unilateral common carotid occlusion. Using the neurological score method, we selected animals which showed stroke symptoms without seizures, because seizure activity can modify the neurological outcome. Just after the clip removal following 30 min of ischemia, 0.2 ml of either vehicle (0.9% saline, n = 10) or bifemelane (25 mg/kg, n = 10) was administered intraperitoneally. Then, the neurological score and the maximum inclination at which the gerbil could maintain its equilibrium were recorded at 5, 10, and 30 min, and 1, 2, 3, 6, and 24 hr after the insult. Animals were then decapitated and their brains were processed for immunohistochemical investigation. Treatment with bifemelane after reperfusion significantly improved the neurological score and motor function. Immunohistochemistry using an antibody for microtubule-associated protein 2 clearly demonstrated preservation of staining especially in the caudate-putamen in the animals treated with bifemelane. The present findings suggest a beneficial effect of bifemelane on neuronal ischemia-reperfusion injury, which may be common after cerebral ischemia.

Animals↗

PubMed1995

Cell cycle regulators in the keratinocyte (cyclin-cdk).

It has recently become clear that cyclin-dependent kinase (cdk) complex regulates the cell cycle by phosphorylating Rb protein, a tumor suppressor protein. It is likely that this complex is a target of various growth factors and anti-growth factors (UV, TGF-beta etc.) in keratinocyte (KC). It has also been suggested that abnormalities in the cell cycle regulating mechanism such as increased activity of cyclin-cdk due to mutation of p53, a tumor suppressor gene, and overexpression of cyclin D may be concerned with carcinogenesis of KC. Thus, recent studies indicate that the cyclin-cdk complex is a common target of proliferation and carcinogenesis in KC.

Animals↗

PubMed1995

Analysis of protein-DNA and protein-protein interactions of centromere protein B (CENP-B) and properties of the DNA-CENP-B complex in the cell cycle.

We previously reported that centromere protein B (CENP-B) forms a stable complex (designated complex A) containing two alphoid DNAs in vitro. Domains in the CENP-B polypeptide involved in the formation of complex A were determined in the present study with truncated derivatives expressed in Escherichia coli and in rabbit reticulocyte lysates. It was revealed by gel mobility shift analyses that polypeptides containing the NH2-terminal DNA-binding domain bind a DNA molecule as a monomer, while dimerizing at a novel hydrophobic domain in the COOH-terminal region of 59 amino acid residues. This polypeptide dimerization activity at the COOH-terminal region was also confirmed with the two-hybrid system in Saccharomyces cerevisiae cells. The results thus proved that CENP-B polypeptides form a homodimer at the COOH-terminal hydrophobic domain, each binding a DNA strand at their NH2-terminal domains. The dimerization and DNA-binding domains fall into two of the three completely conserved sequences found in human and mouse CENP-B, and complex A-forming activity was also detected in nuclear extracts of mouse cells. Metaphase-specific phosphorylation of CENP-B was also detected, but this had no effect on its complex A-forming activity. On the basis of the present results, we propose that CENP-B plays an important role in the assembly of specific centromere structures by forming unique DNA-protein complexes at the sites of CENP-B boxes on the centromeric repetitive DNA both in interphase nuclei and on mitotic chromosomes.

Amino Acid Sequence↗

PubMed1995

Reperfusion induces 5-lipoxygenase translocation and leukotriene C4 production in ischemic brain.

5-Lipoxygenase (5-LO) converts arachidonic acid, released from membrane phospholipids upon external stimulation, to leukotriene C4 (LTC4), which induces various kinds of cellular and molecular responses. We examined the effects of 5 min of ischemia on brain 5-LO and LTC4 during reperfusion using the gerbil model of transient forebrain ischemia that develops neuronal necrosis selectively in the hippocampus. Neurons exhibited dense 5-LO immunoreactivity; 5-LO was partially redistributed from cytosolic to particulate fractions 3 min during reperfusion. LTC4 was generated in neurons and was increased in all forebrain regions during reperfusion. Postischemic increases in LTC4 were inhomogeneous; a greater increase was observed in the hippocampus (13.37 +/- 0.24 pmol/g tissue) than in the other regions (cerebral cortex: 3.29 +/- 1.09 pmol/g). Superoxide dismutase and dimethylthiourea, oxygen radical scavengers, attenuated the production of LTC4 and damage to the neurons in the hippocampus during reperfusion. Our findings indicated that reperfusion, which was associated with translocation of cytosolic 5-LO to membranes and generation of oxygen radicals, induced the production of LTC4 and suggested that excess LTC4 production may mediate irreversible reperfusion injuries in the hippocampal neurons.

Animals↗

PubMed1995

Transdermal delivery of theophylline using an ethanol/panasate 800-ethylcellulose gel preparation.

A novel ethylcellulose gel preparation using an ethanol/panasate 800 (tricaprylin) (40/60) binary lipophilic vehicle was developed and applied to the transdermal delivery of theophylline. The in vitro skin permeability of theophylline across excised hairless mouse skin was improved by the use of this ethanol/panasate 800 (40/60) binary vehicle compared with either ethanol or panasate 800 as a single vehicle, and the addition of lauric acid as a permeation enhancer to the binary vehicle shortened the lag time and increased the permeated amount of theophylline up to 6 h (initial permeation amount). The in vitro permeability of theophylline from the ethanol/panasate 800 (40/60)-ethylcellulose gels decreased with an increase in the content of ethylcellulose in the gels. In the in vivo evaluation using abdominal rat skin, the ethanol/panasate 800 (40/60)-7% (w/w) ethylcellulose gel produced a good feature as a sustained-release preparation, with a relatively high bioavailability (BA) of theophylline, and dose dependency was observed.

Administration, Cutaneous↗

PubMed1995

Neutron generator at Hiroshima University for use in radiobiology study.

A neutron generator (HIRRAC) for use in radiobiology study has been constructed at the Research Institute for Radiation Biology and Medicine, Hiroshima University (RIRBM). Monoenergetic neutrons of which energy is less than 1.3 MeV are generated by the 7Li(p,n)7 Be reaction at proton energies up to 3 MeV. The protons are accelerated by a Schenkel-type-accelerator and are bombared onto the 7Li-target. An apparatus for the irradiation of biological material such as mice, cultured cells and so on, was designed and will be manufactured. Neutron and gamma-ray dose rates were measured by paired (TE-TE and C-CO2) ionization chambers. Contamination of the gamma ray was less than about 6% when using 10-microns-thick 7Li as a target. Maximum dose rates for the tissue equivalent materials was 40 cGy/min at a distance of 10 cm from the target. Energy distributions of the obtained neutrons have been measured by a 3He-gas proportional counter. The monoenergetic neutrons within an energy region from 0.1 to 1.3 MeV produced by thin 7Li or 7LiF targets had a small energy spread of about 50 keV (1 sigma width of gaussian). The energy spread of neutrons was about 10% or less at an incident proton energy of 2.3 MeV. We found that HIRRAC produces small energy spread neutrons and at sufficient dose rates for use in radiobiology studies.

Animals↗

PubMed1995

Mutation in alpha 5(IV) collagen chain gene in nonfamilial hematuria.

Alport syndrome is an inherited disorder characterized by progressive nephritis with ultrastructural basket-weave changes of the glomerular basement membrane and neurosensory deafness. Mutations in the COL4A5 gene encoding the Type IV collagen alpha 5 chain have been reported to occur in patients with X-linked Alport syndrome. A girl with hematuric nephritis, characteristic basket-weave glomerular basement membrane changes, and abnormal expression of the Type IV collagen alpha 5 chain immunohistochemically, but no family history of nephritis, was identified. Mutation detection enhancement gel electrophoresis of the polymerase chain reaction-amplified exons of COL4A5 from this patient revealed a sequence variant in the exon 50 region. Sequence analysis of her polymerase chain reaction product demonstrated a single-base (C; nucleotide 4728 from the 5' end) deletion in exon 50. This novel mutation alters the reading frame and introduces a translation stop codon that would be expected to result in a noncollagenous domain with only 209, instead of the normal 229, amino acid residues. Gene tracking with restriction enzyme AfIIII demonstrated that her mother was normal. These findings represent a new mutation of the X-linked Alport syndrome in this patient and demonstrate that a COL4A5 gene mutation causes the abnormal expression of Type IV collagen alpha 5 chain protein.

Base Sequence↗

PubMed1995

Focal sparing of segment IV in fatty livers shown by sonography and CT: correlation with aberrant gastric venous drainage.

OBJECTIVE: One of the most common sites of focal sparing in fatty livers (focal spared area) shown by sonography or CT is the posterior edge of segment IV. The differentiation of such a focal spared area from tumor has been a diagnostic challenge. The purpose of this study was to determine if a correlation exists between the focal spared area at the posterior edge of segment IV in fatty liver and the decrease of portal perfusion from the main portal vein due to aberrant gastric venous drainage directed into segment IV. SUBJECTS AND METHODS: Seventeen patients with fatty liver diagnosed on the basis of sonographic and CT findings who had hepatic arteriography and/or CT during arterial portography (CTAP) were included in the study. Seven patients had a focal spared area more than 2 cm in the longest diameter at the posterior edge of segment IV, and 10 patients did not have a focal spared area. The frequency of aberrant gastric venous drainage shown by arteriography (17 patients) and/or by CTAP (15 patients) was compared in the two groups of patients. RESULTS: Hepatic arteriography showed aberrant gastric venous drainage in all patients who had a spared area, and CTAP showed a portal perfusion defect at the posterior edge of segment IV in all five patients with a focal spared area who underwent CTAP. On the other hand, no definite aberrant gastric venous drainage and portal perfusion defect were seen in any patient without a spared area. The difference in the frequency of aberrant gastric venous drainage between the two groups of patients was statistically significant (chi-square test, p < .0001). CONCLUSION: Our results show that a strong correlation exists between the focal spared area at the posterior edge of segment IV in fatty liver and aberrant gastric venous drainage directed to segment IV. Focally decreased blood flow from the main portal vein associated with aberrant gastric venous drainage is a likely cause of the focal spared area. This fact is important for the differential diagnosis of hepatic tumors.

Adult↗