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Biomedical subjects

N Kataoka

Publications and source records attributed to N Kataoka.

At least 19 recordsLinked to original sources
PubMed2001

Magoh, a human homolog of Drosophila mago nashi protein, is a component of the splicing-dependent exon-exon junction complex.

The RNA-binding protein Y14 binds preferentially to mRNAs produced by splicing and is a component of a multiprotein complex that assembles approximately 20 nucleotides upstream of exon-exon junctions. This complex probably has important functions in post-splicing events including nuclear export and nonsense-mediated decay of mRNA. We show that Y14 binds to two previously reported components, Aly/REF and RNPS1, and to the mRNA export factor TAP. Moreover, we identified magoh, a human homolog of the Drosophila mago nashi gene product, as a novel component of the complex. Magoh binds avidly and directly to Y14 and TAP, but not to other known components of the complex, and is found in Y14-containing mRNPs in vivo. Importantly, magoh also binds to mRNAs produced by splicing upstream (approximately 20 nucleotides) of exon- exon junctions and its binding to mRNA persists after export. These experiments thus reveal specific protein-protein interactions among the proteins of the splicing-dependent mRNP complex and suggest an important role for the highly evolutionarily conserved magoh protein in this complex.

Animals↗
PubMed2001

SMN interacts with a novel family of hnRNP and spliceosomal proteins.

Spinal muscular atrophy (SMA) is a common neurodegenerative disease caused by deletion or loss-of-function mutations of the survival of motor neurons (SMN) protein. SMN is in a complex with several proteins, including Gemin2, Gemin3 and Gemin4, and it plays important roles in small nuclear ribonucleoprotein (snRNP) biogenesis and in pre-mRNA splicing. Here, we characterize three new hnRNP proteins, collectively referred to as hnRNP Qs, which are derived from alternative splicing of a single gene. The hnRNP Q proteins interact with SMN, and the most common SMN mutant found in SMA patients is defective in its interactions with them. We further demonstrate that hnRNP Qs are required for efficient pre-mRNA splicing in vitro. The hnRNP Q proteins may provide a molecular link between the SMN complex and splicing.

Amino Acid Sequence↗
PubMed2001

Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex.

Nonsense-mediated messenger RNA (mRNA) decay, or NMD, is a critical process of selective degradation of mRNAs that contain premature stop codons. NMD depends on both pre-mRNA splicing and translation, and it requires recognition of the position of stop codons relative to exon-exon junctions. A key factor in NMD is hUpf3, a mostly nuclear protein that shuttles between the nucleus and cytoplasm and interacts specifically with spliced mRNAs. We found that hUpf3 interacts with Y14, a component of post-splicing mRNA-protein (mRNP) complexes, and that hUpf3 is enriched in Y14-containing mRNP complexes. The mRNA export factors Aly/REF and TAP are also associated with nuclear hUpf3, indicating that hUpf3 is in mRNP complexes that are poised for nuclear export. Like Y14 and Aly/REF, hUpf3 binds to spliced mRNAs specifically ( approximately 20 nucleotides) upstream of exon-exon junctions. The splicing-dependent binding of hUpf3 to mRNAs before export, as part of the complex that assembles near exon-exon junctions, allows it to serve as a link between splicing and NMD in the cytoplasm.

3' Untranslated Regions↗
PubMed2001

The Y14 protein communicates to the cytoplasm the position of exon-exon junctions.

We recently described an RNA-binding protein, Y14, that binds preferentially to spliced mRNAs and persists in the cytoplasm. Y14 is part of a multi-protein complex that also contains the mRNA export factor TAP. This suggests that splicing imprints the mRNA with a unique set of proteins that communicate the history of the transcript to the cytoplasm. Here, using microinjection of pre-mRNAs into Xenopus oocyte nuclei followed by immunoprecipitation of RNase-fragmented mRNAs from the cytoplasm, we show that Y14 is stably bound to sequences immediately upstream of exon-exon junctions. This feature appears to be unique to Y14. Using monoclonal antibodies that we produced against Aly/REF, another component recently reported to be an mRNA export factor, we show that Aly/REF is associated with spliced mRNAs in the nucleus but is not detectable on mRNAs in the cytoplasm. Thus, we propose that the splicing- dependent binding of Y14 provides a position-specific molecular memory that communicates to the cytoplasm the location of exon and intron boundaries. This novel mechanism may play an important role in post-splicing events.

Active Transport, Cell Nucleus↗
PubMed2001

Gastric pneumatosis associated with duodenal stenosis and malrotation.

Pneumatosis intestinalis, which is linear or cystic gas within the bowel wall, is usually found in premature babies in association with necrotizing enterocolitis. Gastric pneumatosis defined as intramural gas of the stomach is a rare sign during infancy. We report an infant with Down's syndrome and a duodenal web with obvious gastric pneumatosis.

Down Syndrome↗
PubMed2001

[Outbreak of measles in a hospital and measures taken against hospital infection--evidence of cost and benefits].

In Japan, an isolated vaccine of measles is used because MMR vaccines have been suspended due to the frequent occurrence of aseptic meningitis after their use. It is administered only once with the cover rate having been approximately 70%. An outbreak of measles was experienced in eight of our health care workers (three doctors, three nurses and two clerks of our hospital) and in seven of our medical students, accompanying local outbreaks. Their condition was severe enough to require admission to our school hospital. One of medical students developed encephalitis, but he has recovered completely. The social cost including medical cost per worker was approximately yen 500,000 (about $4,500). We measured antibodies against measles, rubella, chickenpox and mumps using the ELISA assay in 1048 health care workers less than 40 years of age and 99 medical students before their clinical practice two or three months after the outbreak. The cost including the measuring of antibodies and vaccination for these workers and students was approximately yen 2,800,000 and it will be yen 700,000 for new workers each year. The negative rates for workers were 1.2% for measles, 8.8% for rubella, 10.0% for mumps and 2.0% for chickenpox and those for the medical students were 1.0%, 22.0%, 9.0% and 5.0%, respectively. Of the workers, 9.6% who had more than the defined very high tiaer were thought to have subclinical reinfection because they were non-symptomatic. The rates were 1.2% for rubella, 0.5% for chickenpox and 0.0% for mumps for more than the defined high titers among the workers, suggesting a risk of outbreaks in the future. Therefore, the antibodies of health care workers and medical students should be measured at the hospital and the antibody-negative person should be vaccinated to prevent infection not only from their patients but also prevent other patients from becoming infected by contracted health care workers or students.

Adult↗
PubMed2000

Local mechanical properties measured by atomic force microscopy for cultured bovine endothelial cells exposed to shear stress.

Morphology and mechanical properties of cultured endothelial cells were measured, using a novel atomic force microscope (AFM) system, developed in our laboratory, in conjunction with an inverted confocal laser scanning microscope. We used this system to examine endothelial cell both in static cultures and exposed to a shear stress of 2 Pa. Initially, the three-dimensional topography of a cell was measured by the AFM and a location was selected for the subsequent measurement of the mechanical response of the cell. The surface of statically cultured cell was smooth. The cell height was not altered by the exposed duration of shear stress. A relationship between external force, F, and the indentation depth, delta, was obtained for several different locations on a cell. This force-indentation response was modelled using a quadratic equation, F = adelta2 + bdelta, indicating that two parameters, a and b, will be constants which are representative of the mechanical response. Endothelial cells cultured at static conditions demonstrated a polygonal shape and less stiff mechanical characteristics around the nucleus compared to those at peripheral regions. The stiffness of the endothelial cells exposed to shear stress increased with the duration time of exposure. At 6-h exposures, the stiffness was higher at upstream side of the cell than the downstream side. However, after 24-h exposure, the stiffness was similar on both sides of the cell. These changes in the stiffness of endothelial cells when exposed to shear stress were suggested to correspond with the distribution of stress fibers in the cell.

Animals↗
PubMed2000

Natural language from function dynamics.

A new approach to syntax and semantics of language is presented as a form of function dynamics, which is studied both analytically and numerically. The iteration of the function dynamics leads to articulation and formation of rules, which depend on each other. A hierarchy of meta-rules as rules of rules also emerges through the iteration when the initial function is suitably embedded. Iteration of a model with dialogue between two function dynamics is shown to generate a higher level structure.

Humans↗
PubMed2000

Pre-mRNA splicing imprints mRNA in the nucleus with a novel RNA-binding protein that persists in the cytoplasm.

We describe a novel RNA binding protein, Y14, a predominantly nuclear nucleocytoplasmic shuttling protein. Interestingly, Y14 associates preferentially with mRNAs produced by splicing but not with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Y14 associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. Splicing of a single intron is sufficient for Y14 association. Y14-containing nuclear complexes are different from general hnRNP complexes. They contain hnRNP proteins and several unique proteins including the mRNA export factor TAP. Thus, Y14 defines novel intermediates in the pathway of gene expression, postsplicing nuclear preexport mRNPs, and newly exported cytoplasmic mRNPs, whose composition is established by splicing. These findings suggest that pre-mRNA splicing imprints mRNA with a unique set of proteins that persists in the cytoplasm and thereby communicates the history of the transcript.

Animals↗
PubMed2000

A case of hemolytic uremic syndrome improved with nitric oxide.

Hemolytic uremic syndrome (HUS) after transplantation is difficult to treat, and there is no consensus regarding optimal mode of treatment. We attached transdermal isosorbide tape as a nitric oxide (NO) donor to patients with HUS after bone marrow transplantation (BMT). This was very effective in ameliorating the hemolysis and increasing platelet numbers. We report here the successful use of an isosorbide in a patient with HUS after transplantation. Bone Marrow Transplantation (2000) 25, 109-110.

Bone Marrow Transplantation↗
PubMed2000

Protection of hematopoietic progenitor cells by nitric oxide.

The free radical gas nitric oxide (NO) has been reported to trigger apoptosis of a variety of cell types, but there have also been contradictory reports of an inhibitory effect of NO on this form of programmed cell death. We hypothesized that NO may inhibit apoptosis of hematopoietic cells. In this study, therefore, hematopoietic cells obtained from umbilical cord blood (CB) were incubated with NO, and NO inhibited apoptosis of hematopoietic cells in umbilical CB, although it did not affect the number of mononuclear cells (MNC). Inhibition of apoptosis of hematopoietic cells is important for their use in transplantation. Our results suggest that it might be possible to prevent the loss of hematopoietic cells using NO.

Apoptosis↗
PubMed2000

Testing for rubella-specific IgG antibody in urine.

BACKGROUND: In Japan rubella vaccination is generally done once during a lifetime, and the vaccination rate decreased after a revised vaccination law in 1995. History of rubella or vaccination may still be unreliable. Testing for rubella antibody is significant to prevent the occurrence of congenital rubella syndrome. However, the collection of blood samples to detect antibodies from young children is invasive and difficult. METHODS: For this study we obtained 853 matched serum and urine samples from 904 healthy students 10 or 14 years of age in the Ibara and Yoshii districts of Okayama, Japan, for a comparison of antibodies for rubella in the matched samples. The serum and urine antibodies were measured with hemagglutination-inhibition and enzyme-linked immunosorbent assays, respectively, and with our urine-based antibody test. RESULTS: The sensitivity, specificity and concordance rates of this urine-based antibody test were 96, 99 and 97% based on the serum antibody results of both assays. The coefficiency was 0.627 between the titers of the urinary and serum antibodies by the enzyme-linked immunosorbent assay. The urinary antibodies were stable for at least 5 months at 4 degrees C and 25 degrees C. CONCLUSIONS: Urine-based assay methods are helpful not only because they avoid the invasive approach of venipuncture but also because unprocessed urine specimens can be used and urinary antibody is stable for a long period. Therefore this test is suitable for screening. In addition protective amounts of rubella antibody in blood can be reliably assessed by means of urine samples.

Adolescent↗
PubMed2000

[Comparison of cost and benefits of each model for rubella immunization in Japan].

MMR (measles-mumps-rubella) immunization in Japan was suspended in 1993 due to the high incidence of mumps meningitis as a complication. As a result, immunization coverage for rubella still remains at the 50-60% level in Japan. One way to increase the coverage rate is to increase the frequency of immunization. We calculated the predicted positivity rate of the antibody and cost and the benefits is three models of double vaccination, i.e., vaccination twice. The first model consists of simply two identical vaccinations. The second model consists of two vaccinations with mass vaccination at school for the second immunization. The third model consists of two vaccinations with screening of the urinary antibody for rubella in the second immunization. To calculate the predicted values we used coefficients from Ibara City. The predicted positivity rates and cost increases ranged from 60% to 90% and from 7.3 billion to 12.8 billion yen from the first to third models, respectively. Screening for the urinary antibody should be much cheaper than the presumed price because more than a million subjects will be screened. Since it would cost less than half the price, the third model should be best for the positivity rate of the antibody and cost and benefits. Therefore, we think that third model is the best correction until MMR immunization can be reintroduced.

Antibodies, Viral↗
PubMed2000

[Measures against hospital infection for students in medical schools in Japan--a survey by questionnaires].

We sent questionnaires to 80 medical schools in Japan to know what the problems in hospital infection for students in medical schools are. Seventy-one % were sent back to us. There have been hospital infection from patients to students in 12% of the medical schools, included 3 cases each of measles, chickenpox and mumps, 2 cases each of rubella, hepatitis B and tuberculosis. Fourteen % of the medical schools had reports about the past history of infection and vaccination from students, 70% of the schools determined their antibodies and the 28% did nothing. Ninety-three%, 25%, 23%, 18%, and 15%, of the schools determined antibodies for hepatitis B, rubella, measles, chickenpox and mumps, respectively. Some assays of the measurement were low in sensitivity. The cost for the determination was fully paid in 48% of the schools, but only partially supported in 35%. Tuberculin reaction was performed in 40% of the schools and then BCG was done in 57%. Vaccination was recommended in 40% of the schools. The cost of vaccination was all paid in 38% of them, which was only for hepatitis B, and partially supported in 15% of them.

Cross Infection↗
PubMed2000

[Comparison of positivity rates for antibodies against measles, rubella, chickenpox and mumps by assays].

Our previous study found mistakes by some doctors in the choice of an assay for determining antibodies in Japan. To compare the positivity rates for antibodies by assays, we measured the antibodies of measles, rubella, chickenpox and mumps from the same sera using such methods as the EIA, HI and CF assays. The subjects were 175 nursing students. The positivity rates for measles, chickenpox and mumps by the EIA assay were 96.6%, 93.7%, and 83.3%, respectively. Those for rubella by the HI and CF assays were 92.0% and 10.1%. The sensitivity rates for measles, chickenpox and mumps by the HI and CF assays, based on the results of the EIA assay, were 75.1%, 102.4% and 69.2% in the HI assay, and 20.6%, 38.7% and 8.0% in the CF assay, respectively. Our previous study showed that the sensitivity of the HI assay for rubella antibody is same as that of the EIA assay in Japan. Currently an EIA assay should be chosen for these antibodies and the HI assay or IAHA assay should be possible selections for rubella and chickenpox. However, international comparison of the cutoff titers for these antibodies should be considered.

Antibodies, Viral↗
PubMed2000

Low induction of varicella-zoster virus-specific secretory IgA antibody after vaccination.

Breakthrough after varicella vaccination occurs in approximately 2. 6% approximately 18.6% of immunocompetent children, but the reason has not been demonstrated clearly. As a first defense, specific secretory IgA antibody on the mucosa plays an important role in preventing invasion of microorganisms. To examine induction of varicella-zoster virus (VZV) specific secretory IgA after natural infection and vaccination and its booster mechanisms, 143 salivary samples were tested by ELISA. The VZV-secretory IgA values were significantly higher in the matched children after natural chickenpox than in those after vaccination, although the total secretory IgA did not differ between them. Two (7%) of the vaccinees lacked the sIgA antibody. In the elderly and in immunocompromised children, the VZV-secretory IgA values were no lower than those in healthy children, and they did not lack VZV-secretory IgA. The doctors and nurses taking care of patients with chickenpox had higher values than the other groups as did individuals who had had herpes zoster recently. VZV-secretory IgA was thought to be stimulated by exogenous and reactivated endogenous VZV to neutralize VZV with weak activity. These results suggest that low or no induction of VZV-secretory IgA antibody after vaccination may be one of the possible explanations for a breakthrough.

Aged↗
PubMed2000

[Genetic analysis of two patients with adenosine deaminase (ADA)-deficiency: detection of three novel mutations and characterization of two paradoxical carriers].

Genetic basis of two patients (AT, MT) with ADA deficiency was studied. We identified three novel mutations (119 Q-->Stop, 235 R-->Q, one base deletion in Exon 4) from the patients. 119 Q-->Stop was detected in AT and her father. Deletion of one base in Exon 4 which would change the reading frame after codon 105 H, was detected in MT, her father and brother. There was no relation between the two families, however, 235 R-->Q was also detected in both the patients and their mothers. Extremely low ADA activity of PBMCs was revealed in healthy MT's mother and brother just as MT, although their dAXP levels of RBCs showed significantly lower than that of MT. We defined that they shared an additional mutation (310 M-->T) together with the mutation described above, respectively. EBV-transformed B-cell line (EBV-B) were established from the carriers. To our surprise, ADA activity of their lines was 1/10-1/5 of normal. The result of heat treatment studies using the EBV-B showed that the mutant ADA rapidly lose its enzyme activity without degradation of the protein. It suggests that 310 M-->T mutant ADA rapidly lost its enzyme activity due to conformational change of the catalytic site of ADA.

Adenosine Deaminase↗