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N Aoki

Publications and source records attributed to N Aoki.

At least 109 records · Page 6Linked to original sources

Germline MEN1 mutations in sixteen Japanese families with multiple endocrine neoplasia type 1 (MEN1).

OBJECTIVE: Multiple endocrine neoplasia type 1 (MEN1) is a syndrome of endocrine tumors involving the parathyroids, anterior pituitary and enteropancreatic neuroendocrine tissues, and is inherited in an autosomal dominant manner. Recently, the gene responsible for this syndrome, MEN1, was positionally cloned in 11q13. We aimed to assess the significance of MEN1 gene diagnostics in families with MEN1. DESIGN: Sixteen probands of familial MEN1 and their 40 family members were subjected to the study. METHODS: Full-length sequencing of the open reading frame and exon-intron boundaries in the MEN1 gene was performed with probands of familial MEN1. Family members were examined for the identified mutation in the proband. RESULTS: We identified heterozygous germline mutations of the MEN1 gene in all of 16 Japanese MEN1 families examined, achieving the highest detectability of MEN1 mutations in familial MEN1 among studies that examined more than 10 families. Eleven kinds of the identified MEN1 germline mutations were novel. More than half were nonsense or frameshift mutations resulting in a premature stop codon (9/15; 60%), and no mutation hot spots or no apparent genotype-phenotype relationships were observed, in support of the results of other studies. We identified 40 mutant MEN1 gene carriers and 16 non-carriers in the course of the present study in those families. CONCLUSIONS: Analysis of the germline mutations in the MEN1 gene, providing significantly useful clinical information to probands and family members of MEN1, should be considered as a standard procedure and categorized as belonging to Group 1 cancer predisposition testing by the American Society of Clinical Oncology.

Adult↗

[Murine typhus].

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Animals↗

[Epidemic typhus].

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Anti-Bacterial Agents↗

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1997)].

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and analyzed some characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In these 17 institutions around the entire Japan, 512 strains of presumably etiological bacteria were isolated mainly from the sputa of 440 patients with lower respiratory tract infections during the period from October in 1997 to September in 1998. MICs of various antibacterial agents and antibiotics were determined against 100 strains of Staphylococcus aureus, 81 strains of Streptococcus pneumoniae, 85 strains of Haemophilus influenzae. 71 strains of Pseudomonas aeruginosa (non-mucoid strains), 27 strains of Pseudomonas aeruginosa (mucoid strains), 33 strains of Moraxella subgenus Branhamella catarrhalis, 17 strains of Klebsiella pneumoniae etc., and the susceptibilities of these strains were assessed except for those strains that died during transportation. S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus: MRSA) accounted for 55.0%. The frequency of the drug resistant bacteria decreased comparing to the previous year's 67.3%. Arbekacin (ABK) and vancomycin (VCM) showed the most potent activities against MRSA. Imipenem (IPM) and panipenem (PAPM) of carbapenems showed the most potent activities with MIC80S of 0.063 microgram/ml against S. pneumoniae. The frequency of penicillin (PC)-intermediate S. pneumoniae (PISP)+PC-resistant S. pneumoniae (PRSP) had decreased gradually, that is, in 1995 the frequency of it was 40.3%, but that was 30.9% in 1997. Against H. influenzae and M.(B.) catarrhalis, all the drugs showed good activities. But the sensitive strains of them against ceftazidime (CAZ) had decreased in 1997, compared those in 1995 and 1996. Meropenem (MEPM), IPM and tobramycin (TOB) showed the most potent activity against P. aeruginosa (mucoid strains). And TOB and ciprofloxacin (CPFX) showed the most potent activities against P. aeruginosa (non-mucoid strains). All drugs except ampicillin (ABPC) were more active against K. pneumoniae in 1997 than that in 1996. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. The examination of age distribution indicated that the proportion of patients with ages over 70 years was 45.5% of all the patients showing a slight increase year by year. About the proportion of diagnosed diseases, not so particular changes were recognized as follows: Bacterial pneumonia and chronic bronchitis were the most frequent with 33.6% and 29.1%, respectively. Number of strains isolated from patients before administration of antibiotics were more than those after administration of them in chronic bronchitis, but these had reversed in bacterial pneumonia. The tendency in bacterial pneumonia had been acknowledged since 1995. The increase of S. aureus and P. aeruginosa (both mucoid and non-mucoid strains) isolated after administration of antibiotics, has suggested the decrease of the susceptibility of these strains against antibiotics. Administration of antibiotics has changed the results of the frequency of isolation of bacterial species. Bacterial isolations before administration of antibiotics were as follows: S. pneumoniae 24.5%, H. influenzae 21.4%, S. aureus 18.4% and P. aeruginosa 12.2%. The frequencies of S. aureus decreased after antibiotics administration over 15 days, but the frequencies of P. aeruginosa was not affected. The frequencies of P. aeruginosa was 47.8% after administration over 15 days. From patients administered antibiotics of penicillins and cephems. S. aureus was mainly detected with 31.7-58.3%, and from patients administere

Adult↗

Molecular analysis of a novel protein kinase in maturing rice seed.

Protein kinases play important roles in controlling biological functions. We employed PCR-based cloning technique to isolate a protein kinase gene from rice endosperm and obtained a novel protein kinase (REK) cDNA clone from a cDNA library constructed from maturing rice seed. The deduced amino acid sequence from the cDNA exhibited a high similarity to the wheat abscisic acid inducible protein kinase (PKABA1), including 11 conserved regions of the catalytic domain. REK belongs to the SNF1-related family that possesses abundant acidic amino acid resides in the C-terminal region. RT-PCR analysis showed that the REK gene is expressed in leaf and maturing seed, but not in stem and root. Bacterial recombinant REK showed autophosphorylation activity depending upon Ca2+. In addition, we isolated a REK genomic clone and determined its gene structure.

Amino Acid Sequence↗

Differential effect of alpha-lactalbumin on beta-1,4-galactosyltransferase IV activities.

We isolated a human cDNA clone encoding beta-1,4-galactosyltransferase (beta-1,4-GalT IV) which shares 37% identity with previously characterized mammalian beta-1,4-GalT (beta-1,4-GalT I). By transfection of the full length cDNA into Sf-9 cells and assay of the cell homogenates, higher beta-1,4-GalT activity toward GlcNAc beta-S-pNP was obtained, and its activity was modulated with alpha-lactalbumin, while no lactose synthetase activity was detected in the presence of alpha-lactalbumin. Northern blot analysis using total and poly (A)+ RNA preparations revealed that the expression level of beta-1,4-GalT IV transcript is low and relatively constant while that of beta-1,4-GalT I transcript is dramatically increased in the mouse mammary gland during lactation. These results indicate that beta-1,4-GalT IV can interact with alpha-lactalbumin but has no lactose synthetase activity.

Animals↗

Development of an enzyme-linked immunosorbent assay-based method for measuring galactosyltransferase activity using a synthetic glycopolymer acceptor substrate.

A lectin-assisted enzyme-linked immunosorbent assay (ELISA)-based method using a synthetic glycopolymer as an acceptor substrate was developed for measuring beta 1,4-galactosyltransferase (GalT) activity. A polyacrylamide derivative having a beta-linked N-acetylglucosamine (GlcNAc beta) moiety on each monomeric unit was synthesized chemically and immobilized on a polystyrene microtiter plate as an acceptor substrate for GalT. After the plate was incubated with bovine GalT, the enzyme reaction product, beta-linked Gal residue on the polyacrylamide-bound GlcNAc residue, was detected by using Ricinus communis agglutinin 1 (RCA1), rabbit anti-RCA1 antibody, and a peroxidase-labeled anti-rabbit IgG. The lowest GalT concentration detectable by this method was about 0.5 mU/ml, which is comparable to those by the previously reported ELISA-based assays. The unique property of the glycopolymer, PAP(GlcNAc beta), of binding noncovalently but tightly to the polystyrene microtiter plate allowed the use of this acceptor substrate for the GalT activity measurement even in the presence of 1% Triton CF-54 and X-100. Our system was successfully applied to assess GalT activity in milk of various mammals.

Acetylglucosamine↗

Spontaneous intracranial hypotension associated with subdural hematoma: diagnostic usefulness of percutaneous subdural tapping and magnetic resonance imaging.

A 55-year-old woman presented with headache which was characterized by aggravation in the upright position and relief in recumbency. Although intracranial hypotension syndrome was considered to be the most-likely possible entity, computed tomography (CT) scans demonstrated subdural fluid collections associated with findings reminiscent of transtentorial herniation. Because of these CT features, cerebrospinal fluid pressure measurement by a lumbar puncture was not performed. In stead, as an alternative method, she underwent percutaneous subdural tapping, which failed to obtain spontaneous drainage of liquid haematoma, indicating intracranial hypotension. In addition, gadolinium-enhanced magnetic resonance imaging study performed later supported the diagnosis of spontaneous intracranial hypotension. Thus, the usefulness and safety of percutaneous subdural tapping for the diagnosis of spontaneous intracranial hypotension is stressed.

Female↗

Human platelet activation by thrombolytic agents: effects of tissue-type plasminogen activator and urokinase on platelet surface P-selectin expression.

The mechanisms that underlie reocclusion during thrombolytic therapy have not yet been clarified. The purpose of this study was to investigate the activating effects of tissue-type plasminogen activator and urokinase and the inhibitory effects of acetylsalicylic acid by measuring platelet surface P-selectin as a marker of platelet activation. After addition of urokinase (final concentration 192 U/ml, 1920 U/ml, or 19,200 U/ml) or tissue-type plasminogen activator (final concentration 120 U/ml, 1200 U/ml, or 12,000 U/ml) to platelet-rich plasma from 12 healthy persons, platelet surface P-selectin expression was measured by means of flow cytometry with an anti-CD62 monoclonal antibody. The presence of urokinase and tissue-type plasminogen activator increased platelet surface P-selectin expression in a concentration-dependent manner. In the next step, either 160 mg/day (n = 6) or 660 mg/day (n = 6) acetylsalicylic acid was administered to the 12 healthy persons, and venous blood samples were collected after 7 days of treatment. Platelet surface P-selectin expression was measured with the method used earlier and after addition of tissue-type plasminogen activator or urokinase. Although the effect of acetylsalicylic acid at 160 mg/day on P-selectin expression was minimal, a dose of 660 mg/day suppressed platelet P-selectin expression and inhibited the platelet activating effects of tissue-type plasminogen activator and urokinase in a statistically significant way. Platelets were activated by tissue-type plasminogen activator or urokinase, and this platelet activation was suppressed with administration of acetylsalicylic acid at 660 mg/day.

Aspirin↗

Enzymic method for the determination of nitrite in meat and fish products.

A simple spectrophotometric method for the determination of nitrite is described. Nitrite is measured enzymically through its reaction with nitrite reductase coupled with NADH. The entire enzymic procedure required 15 min to complete. The calibration curve was linear in the range 0.1-10 micrograms cm-3 nitrite with a slope of 6.25. The relative standard deviation at 5 microgram g-1 was 1.7% (n = 5). The method greatly simplifies the procedure of nitrite determination and enables the routine inspection of a number of samples with very little laboratory equipment. A comparison study showed that the method was superior to the GC method for samples containing large amounts of reducing substances while good agreement was achieved between both methods for other foods.

Fish Products↗

A case of myelodysplastic syndrome with an intronic point mutation of the p53 tumour suppressor gene at the splice donor site.

We analysed genomic DNA and mRNA of the p53 gene in a case of myelodysplastic syndrome (MDS) with monosomy of chromosome 17. DNA analysis revealed a mutation at the splice donor site (GT to GC) of intron 5. mRNA analysis revealed the presence of abnormal splicing with 46 nucleotide deletion in exon 5, producing a downstream frame shift and a predicted truncated protein which lacked normal function. The p53 gene mutation at the splice donor site contributes to the inactivation of the p53 gene function and may play an important role in the pathogenesis, progression and therapeutic responsiveness of MDS.

Aged↗

Hair follicle has a novel anagen-specific protein, mKAP13.

To identify the anagen hair follicle-specific proteins, we screened the cDNA library prepared from the murine skins of anagen phase by the differential hybridization technique. Fifty-four cDNA clones expressed specifically in anagen phase were isolated, and most were found to correspond to known proteins in the hair follicles. Alternatively, we isolated a cDNA clone encoding a novel protein that possessed an entire open reading frame of 501 base pairs. This protein with a molecular weight of 17.9 kDa has no specific motifs nor significant homology to proteins already reported, although it contains some direct repeats that are often observed in intermediate filament-associated proteins and has a similar amino acid composition as a member of them. Northern blot analysis demonstrates that the transcript of this protein is skin specific, and that it is present in mid- and late anagen but not in catagen, telogen, and early anagen phases. The transcript appears to be expressed specifically in the keratogenous zone of the cortical cells of hair follicles, as exhibited by in situ hybridization. Furthermore, immunohistochemical study confirms that the protein is distributed in the cytoplasms of the keratinizing cortical cells and is undetected in the completely keratinized ones. These results suggest that this protein can be identified as a new member of intermediate filament-associated proteins and is related to the keratinization of the cortical cell layer in mouse hair. Therefore, we have termed this novel protein mKAP13 according to the unified nomenclature.

Amino Acid Sequence↗

Serial neuroimaging studies in Sotos syndrome (cerebral gigantism syndrome).

To elucidate the mechanism of excessive size of the head in Soto syndrome, serial neuroimaging features from birth were reviewed in two patients. Macrocephaly shortly after birth was attributed to increased volume of the cerebral parenchyma itself (megalencephalon). Subsequent excessive size of the head was related to retention of cerebrospinal fluid in the ventricles and the subarachnoid spaces. Thus, macrocephaly in Sotos syndrome reflects two different mechanisms. The value of serial evaluation of intracranial structures is emphasized.

Brain↗

Changes in hemodynamics in jejunal flaps of rabbits due to ischemia, venous congestion, and reperfusion as measured by means of colored microspheres.

The effect on the jejunal hemodynamics of restoration of blood flow of the jejunal artery or vein in the free jejunal flap has not yet been elucidated. In the present study, a model of ischemia and reperfusion in the jejunal flap of rabbits, and that of venous congestion and reperfusion, were prepared. Jejunal blood flow was measured by means of colored microspheres, and changes in jejunal blood flow were analyzed. Three segmental jejunal flaps were designed on each rabbit (n = 16), with one artery and one vein kept intact. Arterial clamp and venous clamp groups were prepared with a control group in which there was no clamping. After clamping for 5 minutes (n = 7), the jejunal blood flow of the arterial clamp group decreased to 1.6 percent of that of the control group (p = 0.0002), and that of the venous clamp group decreased to 31.2 percent of that of the control group (p = 0.0041). At 5 minutes after release of clamping, the jejunal blood flow of the arterial clamp group recovered to only 74.1 percent of that of the control group, with no consistent tendency; that of the venous clamp group recovered to 45.9 percent of that of the control group (p = 0.0194), with an increase of only 14.7 percent over that of the clamped jejunal blood flow group. Thus, injury of the jejunal hemodynamics in the venous clamp group had already begun in response to clamping for 5 minutes. After clamping for 30 minutes (n = 9), the jejunal blood flow of the arterial clamp group decreased to 4.3 percent of that of the control group (p = 0.0060), and that of venous clamp group decreased to 12.5 percent of that of the control group (p = 0.0106). At 5 minutes after release of clamping, jejunal blood flow of the arterial clamp group recovered to 171.0 percent of that of the control group (p = 0.0295), and that of venous clamp group recovered to 41.7 percent of that of the control group (p = 0.0276). Jejunal blood flow of the arterial clamp group recovered to 409.7 percent of that of the venous clamp group (p < 0.0001). When measurement of jejunal blood flow was repeated twice after changing the color of microspheres, jejunal blood flow of the second measurement was approximately 24 percent greater in mean value than that of the first measurement. The histologic results of the jejunum of the arterial clamp group clamped for 30 minutes showed no injury, which was similar to the results of the control group. The jejunum of the venous clamp group clamped for 5 minutes showed injury with severe hemorrhage in the lamina propria, and irreversible injury 30 minutes thereafter, with massive hemorrhage in all layers of the jejunal wall. In conclusion, as microcirculatory hemodynamics and histologic results of the jejunum demonstrated evidence of injury even by venous congestion for 5 minutes, restoration of blood flow of the free jejunal flap must be started from the jejunal vein.

Animals↗