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Biomedical subjects

S Abe

Publications and source records attributed to S Abe.

At least 217 records · Page 12Linked to original sources

[The validity and problems of a new staging system for lung cancer from the point of view of surgical results].

The validity and problems of the new staging system for resected lung cancer were assessed. In the new staging system for primary lung cancer, stage I is divided into two groups (A and B) on the basis of the tumor diameter. The boundary is 30 mm in maximum diameter of the tumor. On the other hand, intrapulmonary satellite nodules in the resected lung (PM1) are considered as T4. This means that a patient with PM1 is classified as stage IIIB or IV. The five-year cumulative survival rates of 191 consecutive patients of T1 or T2N0M0 who had undergone complete lung resection were calculated. The patients were divided two groups on the basis of the boundaries of the tumor diameter, such as 15, 20, 25, 30 and 40 mm (The tumor diameter in group A is the boundary and less than boundary and the diameter in group B is more than the boundary), and the cumulative survival rates of the two groups were compared. The 5-year cumulative survival rate (Kaplan-Meier survival rate) of each group and the p-value (logrank test) were 85.0%, and 0.463 in the case of the boundary of 15 mm; 84.8%, 79.9%, and 0.374 in the case of 20 mm, 82.3%, 80.0%, and 0.553 in the case of 25 mm, 79.5, 83.5, 0.524 in the case of 30 mm and 81.0%, 82.2%, and 0.783 in the case of 40 mm. In all cases, there were no significant differences between the rates in the two groups. On the other hand, 15 cases of T4N0M0 lung cancer included 12 cases of pm1, 2 cases of p3 and 1 case of d2. The five-year cumulative survival rate for T4N0M0 patients with pm1 was 71.1%, which was similar to the rate for stage I or II patients, while the two T4N0M0 patients with p3 died of recurrences of lung cancer at 10 and 13 months after the operation, and the T4N0M0 patient with d2 died of local recurrence of lung cancer 60 months postoperatively. We concluded that the sub-classification of stage I on the basis of the boundary of tumor diameter was meaningless, if the boundary was between 15 and 40 mm and that N0M0 patients with PM1 should be classified as stage II or less, or as 1 grade up of T status.

Adolescent↗

Newt prolactin and its involvement in reproduction.

The amino acid sequence of newt (Cynops pyrrhogaster) prolactin deduced from the nucleotide sequence of its cDNA showed a relatively high homology with sequences of chicken and sea turtle prolactins as well as with those of anuran prolactins. Cynops prolactin receptor transcripts were detected in various tissues and organs, suggesting that prolactin plays multiple roles in urodeles. Urodele prolactin was purified from the pituitaries of C. pyrrhogaster. Antiserum against this prolactin was used for radioimmunoassay of plasma prolactin and immunoneutralization experiments. Endogenous prolactin was shown to induce migration to water, courtship behavior, and cessation of spermatocytogenesis in the Cynops newt. The hormone was found to be involved in the development of cloacal glands such as the lateral and abdominal glands, growth of the tail and Mauthner neurons, secretion of oviducal jelly, and enhanced synthesis of a female attracting pheromone (sodefrin), and responsiveness of the olfactory epithelium to sodefrin. In most of these cases, prolactin was found to act synergistically or antagonistically with sex steroids. We also discovered that hypersecretion of prolactin in the newts subjected to cold temperature was induced by hypothalamic stimulation rather than release from hypothalamic inhibition.

Amino Acid Sequence↗

Human connexin 30 (GJB6), a candidate gene for nonsyndromic hearing loss: molecular cloning, tissue-specific expression, and assignment to chromosome 13q12.

Mutations in connexin 26 are responsible for approximately 20% of genetic hearing loss and 10% of all childhood hearing loss. However, only about 75% of the mutations predicted to be in Cx26 are actually observed. While this may be due to mutations in noncoding regulatory regions, an alternative hypothesis is that some cases may be due to mutations in another gene immediately adjacent to Cx26. Another gap junction gene, connexin 30 (HGMW-approved symbol GJB6), is found to lie on the same PAC clone that hybridizes to chromosome 13q12. Human connexin 26 and connexin 30 are expressed in the same cells of the cochlea. Cx26 and Cx30 share 77% identity in amino acid sequence but Cx30 has an additional 37 amino acids at its C-terminus. These considerations led us to hypothesize that mutations in Cx30 might also be responsible for hearing loss. Eight-eight recessive nonsyndromic hearing loss families from both American and Japanese populations were screened for mutations. In addition, 23 dominant hearing loss families and 6 singleton families presumed to be recessive were tested. No significant mutation has been found in the dominant or recessive families.

Amino Acid Sequence↗

Identification of catalytic residues of pepstatin-insensitive carboxyl proteinases from prokaryotes by site-directed mutagenesis.

Pepstatin-insensitive carboxyl proteinases from Pseudomonas sp. (PCP) and Xanthomonas sp. (XCP) have no conserved catalytic residue sequences, -Asp*-Thr-Gly- (Asp is the catalytic residue) for aspartic proteinases. To identify the catalytic residues of PCP and XCP, we selected presumed catalytic residues based on their high sequence similarity, assuming that such significant sites as catalytic residues will be generally conserved. Several Ala mutants of Asp or Glu residues were constructed and analyzed. The D170A, E222A, and D328A mutants for PCP and XD79A, XD169A, and XD348A mutants for XCP were not converted to mature protein after activation, and no catalytic activity could be detected in these mutants. The specificity constants toward chromogenic substrate of the other PCP and XCP mutants, except for the D84A mutant of PCP, were similar to that of wild-type PCP or XCP. Coupled with the result of chemical modification (Ito, M., Narutaki, S., Uchida, K., and Oda, K. (1999) J. Biochem. (Tokyo) 125, 210-216), a pair of Asp residues (170 and 328) for PCP and a pair of Asp residues (169 and 348) for XCP were elucidated to be their catalytic residues, respectively. The Glu(222) residue in PCP or Asp(79) residue in XCP was excluded from the candidates as catalytic residues, since the corresponding mutant retained its original activity.

Amino Acid Sequence↗

Novel missense mutation (Leu466Arg) of the DAX1 gene in a patient with X-linked congenital adrenal hypoplasia.

We identified a DAX1 missense mutation, a substitution of arginine for leucine at codon 466 (Leu466Arg), in an infant with X-linked congenital adrenal hypoplasia (AHC). A heterozygous substitution, Leu466Arg, was also identified in his mother and sister. Since leucine at position 466 is well conserved among other orphan nuclear hormone receptor superfamilies and Leu466Arg was not detected among 50 normal Japanese control individuals, the mutation is most likely responsible for X-linked AHC. It is interesting to note that Leu466Arg among all mutations ever reported is located at the most C-terminal region of the DAX-1 protein. Most mutations identified previously were located in the C-terminal presumptive ligand binding domain. Hence, the C-terminal end of the DAX-1 protein may play an important role in the biological function, such as in normal adrenal embryogenesis.

Adrenal Insufficiency↗

Fluctuating sensorineural hearing loss associated with enlarged vestibular aqueduct maps to 7q31, the region containing the Pendred gene.

The most common form of inner ear abnormality, enlarged vestibular aqueduct (EVA), is of particular interest because it is associated with characteristic clinical findings, including fluctuating and sometimes progressive sensorineural hearing loss and disequilibrium symptoms. Although EVA has been reported to be inherited in a recessive manner, nothing else is known about the genetic basis of this hearing loss. Here we report on the localization of the gene responsible for sensorineural hearing loss associated with EVA to chromosomal region 7q31, with maximum multipoint LOD score of 3.647. The EVA candidate gene region lies in a 1.7-cM interval between the flanking markers D7S501 and D7S2425. Interestingly, this region overlaps the region containing the gene responsible for Pendred syndrome, called PDS, which was identified recently. However, the present subjects did not fulfill the criteria for Pendred syndrome. It is hypothesized that different mutations within the PDS gene may cause different phenotypes ranging from EVA to the Mondini deformity seen in Pendred syndrome.

Chromosome Mapping↗

Ultrasonic assessment of vascular complications in coronary angiography and angioplasty after transradial approach.

The transradial approach has currently been accepted as an alternative entry method for coronary angiography and angioplasty. Vascular complications of this method were evaluated by 2-dimensional echo and color Doppler ultrasonic studies in 162 patients before, early (2+/-2 [mean+/-SD] days), and late (95+/-29 days) after catheterization. Mean age was 64+/-10 years, and 103 were men. Coronary angioplasty was performed in 59 patients (79 lesions) with angiographic success in 92%. Early after the procedure, segmental stenosis was noted in 35 patients (22%) and no flow in 15 patients (9%). Late after the procedure, segmental stenosis was noted in 2, diffuse stenosis in 36 (22%), and no flow in 8 (5%) patients. The cessation of radial artery pulse was unpalpable in only 2% of cases, whereas radial flow by color Doppler was undetectable in 9% early after the procedure. Late after the procedure, recanalization was observed in 60% of these occluded cases. Thirty-three of 86 patients (38%) with no flow or diffuse stenosis had radial artery diameters smaller than the sheath diameter, and 11 of 76 patients (14%) had radial artery diameters larger than the sheath diameter (p <0.01). Multivariate analysis revealed risk factors for vascular complications: (1) Radial artery diameter before the procedure was one of the significant and independent determinants of no flow both early (p = 0.06) and late (p = 0.004) after the procedure. (2) The difference in radial artery diameter and sheath size was related to the occurrence of diffuse stenosis late after the procedure (p = 0.003). (3) Diabetes mellitus was related to no flow (p = 0.05) or diffuse stenosis (p = 0.11) late after the procedure. Thus, ultrasonic evaluation of the radial artery was useful in selecting both an access route and an appropriate size of the sheath to determine early and late vascular complications.

Angioplasty, Balloon, Coronary↗

Serum levels of Clara cell 10-kDa protein are decreased in patients with asthma.

Clara cell 10-kDa protein (CC10), the predominant product from nonciliated cells in the epithelial lining of bronchioles (Clara cells), has been shown to have immunomodulatory and antiinflammatory activity and may play a role in controlling airway inflammation. This study was designed to measure serum CC10 concentrations in healthy and asthmatic nonsmokers. Serum CC10 concentrations in asthmatic nonsmokers were significantly lower than in healthy nonsmokers. Asthmatic patients with a long duration of the disease (>/=10 years) had significantly lower serum CC10 levels than those with a short duration of the disease (<10 years). There was no significant difference in serum CC10 levels in asthmatic patients between the time of the asthmatic attack and the stable condition. Serum CC10 levels may reflect decreased production of CC10 caused by remodeling of the small airways in asthma.

Asthma↗

MRI of the brain in the Kearns-Sayre syndrome: report of four cases and a review.

We report brain MRI findings in four patients with typical Kearns-Sayre syndrome (KSS) and correlate them with clinical manifestations. MRI was interpreted as normal in two patients; cerebral and cerebellar atrophy was seen in the other two. On T2-weighted spin-echo images, two patients had high-signal lesions bilaterally in subcortical white matter, thalamus and brain stem. In one patient, the white matter lesion extended into the deep cerebral white matter and the cerebellum was also affected. The other also had bilateral high-signal lesions in the globus pallidus. There was little correlation between neurological deficits and MRI findings. A review of the literature revealed that 10 of the 13 patients with typical KSS previously studied had bilateral subcortical white-matter lesions on T2-weighted images; at least 7 also had high-signal lesions in the brain stem, globus pallidus, thalamus or cerebellum. Although MRI may be normal or show atrophy, the characteristic finding in KSS is a combination of the high-signal foci in subcortical cerebral white matter and in the brain stem, globus pallidus or thalamus.

Adolescent↗

Non-syndromic hearing loss associated with enlarged vestibular aqueduct is caused by PDS mutations.

Enlarged vestibular aqueduct (EVA), known as the most common form of inner ear abnormality, has recently been of particular genetic interest because this anomaly is inherited in a recessive manner. The locus for non-syndromic sensorineural hearing loss with EVA has been mapped to the same chromosomal region, 7q31, as the Pendred syndrome locus. In the present study, seven mutations in the PDS gene (PDS), the gene responsible for Pendred syndrome, have been found in families of non-syndromic sensorineural hearing loss with EVA. One family is homozygous, three families are compound heterozygotes, and two families are heterozygous but with no other mutation detected. The present results provide evidence that mutations in PDS cause both syndromic and non-syndromic hearing loss.

Carrier Proteins↗

EYA1 nonsense mutation in a Japanese branchio-oto-renal syndrome family.

Advances in molecular genetics have recently revealed that mutations in the EYA1 gene are responsible for branchio-oto-renal (BOR) syndrome in European and other populations. This is the first report confirming that an EYA1 gene mutation is also disease-causing in an Asian population. We have described one Japanese BOR syndrome family showing a novel mutation in exon 7 of the EYA1 gene. There was extensive variation of clinical phenotypes within this family. When the physician is confronted with a BOR family showing a wide variation in clinical expression, molecular genetic testing helps to achieve accurate diagnosis.

Audiometry↗

Rapid mass screening method and counseling for the 1555A-->G mitochondrial mutation.

The 1555A-->G point mutation is associated with a susceptibility to aminoglycoside antibiotics, and is of particular interest, as it may cause hearing loss even without aminoglycoside exposure. There may be a considerably large high-risk population in Japan, and to avoid possible side effects in this group, a rapid mass screening system and careful counseling are recommended. We are currently using the mutant allele specific amplification (MASA) method to detect the 1555A-->G mitochondrial mutation and we distribute a warning card to subjects found to bear this mutation.

Aminoglycosides↗

Low-dose cyclosporin for multiple colonic ulcers associated with mixed connective tissue disease.

This report describes a patient with multiple colonic ulcers and mixed connective tissue disease. The histological findings of the colonic lesions showed vasculitis with T-cell infiltration, and the peripheral T cells were frequently in the activated phase of the cell cycle. In this patient, low-dose cyclosporin treatment (2.5 mg/kg/day) inhibited the T-cell activation in the peripheral lymphocytes and was very effective in the gastrointestinal disorder, which might be related to T-cell activation. This case suggests the possibility that even low-dose cyclosporin can exert a great influence on peripheral T cells and directly inhibit T-cell activation, thereby improving symptoms related to T-cell activation.

Adult↗

Hyperthermic isolated regional perfusion for the treatment of osteosarcoma in the lower extremity.

BACKGROUND: In order to reduce the systemic toxity of cisplatin and to increase the effect on the local tumor, facilitating limb-preserving procedures, we have been using hyperthermic isolated regional perfusion (HIRP) for the treatment of osteosarcoma in addition to preoperative chemotherapy. MATERIALS AND METHODS: Twenty patients with an osteosarcoma in a lower extremity were treated with both preoperative chemotherapy and HIRP. RESULTS: The chemotherapeutic effects of preoperative chemotherapy with HIRP was grade III in 6, and grade IV (no viable cell areas observed) in 7. The surgical margins could be reduced in these 13 cases of good responders showing over 90% necrosis (grade III or grade IV), which mainly involved postnecrotic fibrosis and osteosclerosis. CONCLUSION: HIRP can help to control the tumor locally. A more conservative operation was then possible in cases of good responders to preoperative chemotherapy with HIRP.

Adolescent↗

Semen specific gamma-glutamyltransferase carries ABH antigens: a sandwich ELISA for simultaneous semen detection and its ABO blood typing.

Semen type of gamma-glutamyltransferase (gamma-GTP) is different from the membrane bound type of the enzyme in both biochemical and immunological properties, and consists of two subunits (150 and 95 kDa). We found that anti-ABH antibodies recognize a 150-kDa subunit of seminal gamma-GTP by Western blot and immunoprecipitation analyses. Using SG2, one of anti-semen specific gamma-GTP monoclonal antibodies which we had produced, and anti-ABH antibodies, we established a sandwich ELISA for identifying human seminal gamma-GTP and its ABO type simultaneously. This sandwich ELISA allows ABO typing of highly diluted semen. The dilutions for ABO typing were 10(5) times for A or O, and 10(4) times for B. Furthermore, ABO typing of semen was successfully performed by this ELISA, even in the mixed presence of vaginal fluid, saliva and blood. Thus, seminal gamma-GTP carries ABH antigens and the sandwich ELISA with SG2 and anti-ABH antibodies enables ABO typing of semen. The sandwich ELISA is extremely useful for ABO typing originated from semen in the mixture of biological fluids.

ABO Blood-Group System↗

Sudden pressure elevation can trigger acute muscle cell death of the heart and aorta.

The object of this study was to clarify whether or not the acute muscle cell death of the aortic media observed in normal rabbits treated with Russell's viper venom (RVV) and angiotensin II (Ang) is a result of either acute hypertension or the apoptotic effect of angiotensin II. The incidence and mean % area necrosis of the aorta and left ventricle in the rabbits receiving RVV and Ang (group 1) were compared with those in rabbits receiving Ang and saline (group 2), RVV and saline (group 3), RVV, Ang type 1 receptor blocker (CV 11974) and Ang (group 4), RVV, Ang and nicardipine, dihydropyridine derivative (group 5) and RVV, Ang type 2 receptor blocker (PD 123319) and Ang (group 6). The incidence as well as the mean % area of acute muscle necrosis of the aortic media and left ventricle in groups 3, 4 and 5 were found to be significantly lower than those in either group 1 or group 6. The mean % area of acute spotty myocardial necrosis in group 2 (Ang, saline) was also significantly higher than that in groups 3, 4 and 5. There was no evidence of cells with positive in situ nick end labeling (TUNEL reaction). As a result, the acute muscle necrosis of the aortic media and left ventricle was considered to be due to the sudden elevation in the blood pressure, but not due to apoptosis mediated through Ang type 2 receptor. We thus conclude that a sudden increase in blood pressure may be one of the triggering mechanisms for an acute onset of cardiovascular disorders.

Angiotensin II↗