Search PubMed⌕ Search

Biomedical subjects

Y Kubo

Publications and source records attributed to Y Kubo.

At least 217 records · Page 12Linked to original sources

Towards the elucidation of the structural-functional relationship of inward rectifying K+ channel family.

With recent cDNA cloning of members of the inward rectifying K+ channel family, it was revealed that they have only 2 putative transmembrane regions with no voltage-sensor element. Based on the deduced primary structure, possible schematic models to explain their characteristic features are proposed in this article. The features are (1) blocking by intracellular Mg2+, (2) intrinsic gating, (3) the triple barrel structure of the inward rectifier K+ channel and (4) the activation by the direct interaction with G-protein subunits of the muscarinic K+ channel. The recent findings of the mutagenesis study of voltage-gated K+ channels, which provide a clue for the structural-functional study of the inward rectifying K+ channels, are also looked at.

Amino Acid Sequence↗

Molecular cloning and characterization of a murine AIDS virus-related endogenous transcript expressed in C57BL/6 mice.

The murine AIDS (MAIDS) virus has a unique sequence in the gag p12 region, which could be responsible for MAIDS development. RNA preparations from the spleens of normal uninfected C57BL/6 mice contain a transcript hybridizing with this sequence. Levels of the transcript in the kidney of C57BL/6 mice were higher than in the spleen, liver or thymus. Although BALB/c, NFS, DBA/2 and SL murine strains also contained genomic sequences hybridizing with the MAIDS virus-specific probe, no transcript hybridizing with the probe was detected in these strains of mice. The cDNAs carrying the transcript expressed in C57BL/6 mice were molecularly cloned. The complete nucleotide sequence of the clone indicates that the transcript is one of the endogenous murine leukaemia virus-related sequences containing large deletions from the R and U5 regions of the 5' long terminal repeat (LTR) to gag p15, from the C-terminal region of pol p40 (integrase) to the N-terminal region of env p15E, and many short deletions in the 3' LTR U3 region. The nucleotide sequence in the gag p12 region of the transcript was closely similar to that of the MAIDS virus, but the amino acid sequence was less similar because of frameshifting, even when translated. As the MAIDS virus was isolated from C57BL/6 mice with radiation-induced leukaemia, this transcript may be the progenitor of the MAIDS virus. To determine whether the gag p12 region of the transcript contains a functional sequence, a recombinant virus was generated by replacing the gag p12 region of a replication-competent BM5eco virus with that of the endogenous transcript. The recombinant virus was replication-competent, and the p12 region of the transcript retained the functional sequence present in the BM5eco virus.

Amino Acid Sequence↗

p53 gene mutations in human skin cancers and precancerous lesions: comparison with immunohistochemical analysis.

Mutations of exons 3 through 9 of the p53 gene in skin lesions were screened in 23 cases of squamous cell carcinoma (SCC), 25 cases of basal cell carcinoma (BCC), two cases of Bowen's disease, 10 cases of solar keratosis, and five cases of keratoacanthoma by polymerase chain reaction--single strand conformation polymorphism analysis. Mutations of the p53 gene were detected in seven of 23 SCCs (30%), three of 25 BCCs (12%), and none in all cases of Bowen's disease, solar keratosis, or keratoacanthoma. Of 23 cases of SCC, mutations were detected in four of 15 SCCs (27%) that originated in the sunlight-exposed skin region, in two of three SCCs (67%) that originated in the scar tissue, and in one of three SCCs (33%) that originated in radiation dermatitis. Mutations of C-->T transition predominated in SCC and BCC that originated in the sunlight-exposed skin region. Mutations of C-->A or CC-->AT observed in tumors that originated in the predisposed conditions, presumably unrelated to UV light, are different from those found in UV light-related SCC or BCC. Twelve cases of SCC were comparatively analyzed with the immunohistochemical staining with anti-p53 antibody. Two of four cases with positive staining had missense mutations, and three of eight cases with negative staining had nonsense mutations. Based on these findings, immunohistochemical results do not necessarily mean the presence or absence of p53 gene mutations in skin tumors, and sequence analysis is essential for determining whether the gene is mutated.

Aged↗

Gene screening in Japanese families with complete deficiency of thyroxine-binding globulin demonstrates that a nucleotide deletion at codon 352 may be a race specific mutation.

OBJECTIVE: Thyroxine-binding globulin (TBG) is a serum protein that transports 75% of circulating thyroxine. Eleven naturally occurring mutations in the human TBG gene have been identified, ten of which alter the properties of the molecule. Three of these mutations produce complete deficiency of TBG (TBG-CD) and four are associated with a second mutation in codon 283 (TBG-poly) which is polymorphic in some ethnic groups but, when present alone, does not alter the properties of the TBG molecule. In this communication we investigate whether two unrelated Japanese families with TBG-CD harboured the TBG-CDJ mutation in codon 352 associated with TBG-CD in families residing in more distant locations of the Japanese Islands. In addition we examined the possible association with TBG-poly and its incidence in the Japanese population. DESIGN: Mutant alleles were identified by amplification of genomic DNAs by the polymerase chain reaction, using allele-specific oligonucleotide primers. PATIENTS: Eight family members and 25 normal subjects. MEASUREMENTS: Serum free thyroxine and TBG concentration were measured by a conventional radioimmunoassay and a more sensitive enzyme immunoassay. Genomic DNAs were extracted from white blood cells and specific mutations at codons 352 and 283 were identified by allele-specific amplification. RESULTS: Three males and three females, whose serum TBG levels were decreased, had mutations at codon 352 as hemizygous and heterozygous, respectively. This mutation was not present in the DNA of any of the related or unrelated subjects with normal TBG concentration. The presence of TBG-poly was demonstrated in only one heterozygous family member and in six out of 30 alleles (20%) in normal unrelated subjects. The frequency of this TBG polymorphism in the Japanese is similar to that of 16% reported in French Canadians. CONCLUSIONS: We conclude that TBG-CDJ might be a prevalent cause of complete deficiency of thyroxine-binding globulin in the Japanese and that TBG-poly probably appeared before the divergence of human races.

Alleles↗

Inhibition of murine AIDS (MAIDS), development by the transplantation of bone marrow cells carrying the Fv-4 resistance gene to MAIDS virus-infected mice.

To examine whether the resistance allele of the Fv-4 gene (the Fv-4r gene) is a dominant inhibitory-product-encoding gene which an be used to prevent the development of murine AIDS (MAIDS), bone marrow cells from BALB/c-Fv-4wr mice were transplanted into BALB/c mice and C57BL/6 mice infected with MAIDS virus. Almost all of the virus-infected BALB/c and C57BL/6 mice developed MAIDS within 4 months and died 2 or 3 months later. However, when the virus-infected mice were subjected to cobalt irradiation and then given an intravenous injection of 10(7) BALB/c-Fv-4wr mouse bone marrow cells, the recipient mice survived much longer than the untreated mice, which suggests that the Fv-4 gene is a dominant inhibitory gene that is potentially useful in gene therapy of MAIDS.

Animals↗

The p15gag and p12gag regions are both necessary for the pathogenicity of the murine AIDS virus.

The defective murine AIDS (MAIDS) virus has unique sequences in its p15gag and p12gag regions. To clarify whether these sequences are responsible for the development of MAIDS, we constructed recombinant viruses by replacing various regions of the gag gene of the nonpathogenic replication-competent LP-BM5 ecotropic virus with those of the MAIDS virus. Recombinants containing both unique sequences of the MAIDS virus were replication defective and induced MAIDS. However, a recombinant containing either the p15gag or p12gag region of the MAIDS virus was also replication defective but nonpathogenic in mice. A recombinant virus containing only the p30gag region of the MAIDS virus was replication competent and nonpathogenic. These results indicate that the p15gag and p12gag regions of the MAIDS virus do not function like those of replication-competent viruses and that both of the unique sequences in the p15gag and p12gag regions are required to develop MAIDS.

Animals↗

Surgical treatment of ossification of the posterior longitudinal ligament in the thoracic spine.

Thoracic ossification of the posterior longitudinal ligament (OPLL) is a rare entity causing thoracic myelopathy. Its surgical decompression is still challenging. Three patients admitted with progressive myelopathy due to thoracic OPLL are described. A transthoracic anterolateral approach was used in the first and second cases, in which OPLL was located at the T3-T4 and T5-T6 and at the T7-T8 levels, respectively. In the third case, a transsternal approach was adopted for OPLL at the T1-T2 level. The OPLL, including dural ossification, was removed by microsurgical techniques as extensively as possible. Myelopathy in all three cases became relieved or stable postoperatively. Operative procedures are described in detail. From the viewpoint of surgical anatomy, the selection of operative approach depends on the level of the OPLL. The authors emphasize that a transthoracic anterolateral approach is the treatment of choice for extensive anterior pathology such as OPLL involving more than two thoracic bodies below the T4. A transsternal approach can provide excellent access to a lesion at the upper three thoracic bodies.

Aged↗

Microsurgical anatomy of the lower cervical spine and cord.

The authors dissected the cervical spine and its surrounding structures from 40 adult cadavers under a surgical microscope. The anterior part of the spine and spinal cord was examined after vertebrectomy. The posterior longitudinal ligament (PLL) consists of two layers; the anterior one is termed the deep layer, and the posterior one is termed the superficial layer. These two layers adhered together loosely. In the lateral portion of the spinal canal, the superficial layer joined the periradicular sheath at the level of the intervertebral disc spaces and joined the dura mater at the level of the vertebral bodies. After the removal of the deep layer, the anterior internal vertebral venous plexus was seen on top of the lateral part of the superficial layer. The venous plexus was embedded between the double-layered PLLs, was not located in the epidural space, and was not seen in the medial part of the PLL. The PLL without venous channels on top of it was about 10 mm in width at the levels of the intervertebral disc and about 5 mm at the levels of the vertebral body. The anterior root exit zone (AREZ) was an elliptical shape; the transverse length of the AREZ was about 2 mm, and the longitudinal length was 10 to 15 mm. The average number of anterior rootlets on the AREZ was 17 to 25 and tended to decrease in the lower cervical spinal cord. The posterior structures were examined after en bloc laminectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

New chlorine-containing prenylated C6-C3 compounds increasing choline acetyltransferase (ChAT) activity in culture of postnatal rat septal neurons from Illicium tashiroi.

The structures of two new chlorine-containing C6-C3 compounds isolated from the woods of Illicium tashiroi have been established as 2(R)-12-chloro-2,3-dihydroillicinone E (1) and 12-chloroillicinone E (2) by X-ray crystallographic analysis and spectroscopic data, respectively. Compound 1 has been found to significantly increase ChAT activity in culture of P10 rat septal neurons.

Animals↗

[Congenital coronary arterial fistula drained to the coronary sinus--a case report].

We report a very rare case of an infant with coronary arterial fistula in whom the communication between a dilated right coronary artery and the coronary sinus was found. The patient was 1-year-old. She had pulmonary congestion and cardiomegaly due to the left-to-right shunt through the fistula, and underwent ligations of the fistula. Ligations of the fistula was indicated because the patient was too small to undergo a fistula resection and coronary arterial bypass grafting. Although the patient had a successful post-operative course, we are paying attention to the aneurysmal change of the dilated right coronary artery proximal to the site of ligations.

Arteriovenous Fistula↗

[Recent advances and problems in peripheral arterial reconstruction].

Recent advances in the field of peripheral arterial reconstruction have been remarkable. These advances are mainly derived from the development of diagnostic technology such as Doppler ultrasound analysis, further refinement of surgical technique including surgical instruments and materials, and naturally improvement of patient care in the pre-, peri- and postoperative period. During the past 14 years we have performed peripheral arterial reconstruction in 1,200 cases (1,660 limbs) mainly with occlusive lesion due to arteriosclerosis obliterans. In our hand, aorto-iliac occlusive lesion has been routinely bypassed with Dacron prostheses and the secondary patency rate at eleven years reached 96.5%. The main problems encountered in this region were anastomotic aneurysm in the femoral artery (3.9%) and graft infection (1.2%). In the infrainguinal region there are still problems to be solved, although the primary (secondary) 5 year patency rates of reversed vein graft as well as in situ vein graft including femoro-popliteal below knee and femoro-crural bypasses have exceeded 70% (85%). First, there is no graft material comparable to the autogenous vein (AVG). Secondly, many of the AVG should suffer occlusive pathological changes from the environment in the long term following surgery. At the present time, we have no effective method to solve these problems, therefore we should follow up the patients heedfully to maintain the graft patency as well as to improve their quality of life and prognosis.

Anastomosis, Surgical↗

[A case report of innominate and carotid artery aneurysms causing cerebral embolism].

Brachiocephalic aneurysms are relatively rare in Japan. A case with tandem aneurysms of innominate and right carotid artery was experienced and its successful surgical treatment was reported. A 54-year-old female patient had an attack of cerebral infarction with left hemiparesis. Computed tomography and angiogram revealed aneurysms of innominate and right carotid artery causing cerebral embolisms. Aneurysmectomy and replacement with Dacron prosthesis was performed. A temporary shunt was utilized between ascending aorta and common carotid artery during clamping carotid artery. She had no problems after operation, and her postoperative course was uneventful.

Anastomosis, Surgical↗

Dexamethasone inhibits induction of liver tumor necrosis factor-alpha mRNA and liver growth induced by lead nitrate and ethylene dibromide.

We have recently demonstrated that a single injection of the mitogen lead nitrate to rats induced a rapid increase of tumor necrosis factor-alpha (TNF-alpha) mRNA in the liver and suggested that this cytokine may be involved in triggering hepatocyte proliferation in this model of direct hyperplasia. In this study, we examined whether a similar induction of liver TNF-alpha mRNA could be observed preceding the onset of hepatocyte proliferation induced by ethylene dibromide, another hepatocyte mitogen. In addition, we used dexamethasone, a well known inhibitor of TNF-alpha production, to determine whether its administration could suppress hepatocyte proliferation induced by lead nitrate and ethylene dibromide. A single intragastric administration of ethylene dibromide (100 mg/kg) to male Wistar rats enhanced liver TNF-alpha mRNA after 4 and 7 hours, which then returned to control levels by 24 hours. TNF-alpha mRNA was detectable only in a nonparenchymal cell fraction of the liver. Pretreatment of rats with a single dose of dexamethasone (2 mg/kg) 60 minutes before lead nitrate (100 mumol/kg) or ethylene dibromide completely abolished the increased levels of liver TNF-alpha mRNA induced by these agents. Inhibition by dexamethasone of TNF-alpha mRNA was associated with an inhibition of liver cell proliferation induced by these mitogens, as measured by [3H]thymidine incorporation into hepatic DNA, mitotic index, and DNA content. These results further support the hypothesis that TNF-alpha may be involved in triggering hepatocyte proliferation induced by primary mitogens.

Animals↗

[A comparative study on long-term care facilities for the aged in Japan].

Presently in Japan, care for the aged who are bedridden, afflicted with dementia or other conditions, is provided by hospitals, skilled nursing homes (providing a certain amount of medical care) and special nursing homes (for those needing ADL assistance). Facilities for long term care of the aged are insufficient, and there are many problems in matching care needs to the services supplied in these facilities. In October 1990, a survey was conducted to collect data for helping define the optimum services needed for the aged in long term care facilities. The subjects consisted of 1,262 persons in 12 facilities: 314 in three general hospitals (average age: 78.5); 391 in three hospitals for the aged (80.8); 410 in four skilled nursing homes (81.2); 147 in two special nursing homes (81.3). Results of the survey are as follows: 1. The proportion of "seriously demented" and "very seriously demented" subjects, (according to Karasawa's scale.), was 17.5% in general hospitals, 28.7% in hospitals for the aged, 16.4% in skilled nursing homes, and 22.6% in special nursing homes. 2. For ADL, "mobility" with whole assistance was required for 40.5% of the subjects in general hospitals, 58.7% in hospitals for the aged, 22.9% in skilled nursing homes, and 37.5% in special nursing homes. 3. During the month preceding the survey, medical examinations were conducted on 98.4% in general hospitals, 99.5% in hospitals for the aged, 23.0% in skilled nursing homes, and 59.4% in special nursing homes. These examinations consisted mostly of urine and blood analyses. ECGs and x-ray tests were also performed on more than 70% of subjects in the two types of hospitals.

Activities of Daily Living↗

[Postoperative reconstruction of chest wall using polyglycolic acid mesh--a case report].

A 75-year-old male with infected chest wall tumor was treated with en-block resection of the tumor including the second and third ribs, part of the M. pectoralis major, pleura and pulmonary parenchyma. As the wound was infected, the defect of the chest wall was reconstructed leaving a muscle pedicle of the pectoralis major and polyglycolic acid mesh, 9.0 x 8.5 cm in area. The resected tumor was 9.0 x 8.0 x 4.0 cm in size, 170 gr in weight and histopathologically poorly or moderately differentiated adenocarcinoma. The primary lesion of the tumor was unknown in spite of investigations of the whole body. The postoperative course was uneventful, and the wound was completely healed within 3 weeks. This mesh material was therefore considered to be useful for reconstruction of the chest wall especially in the infected region.

Adenocarcinoma↗

Roles of growth factors and of tumor necrosis factor-alpha on liver cell proliferation induced in rats by lead nitrate.

BACKGROUND: A single intravenous injection of lead nitrate to rats induces a synchronized wave of hepatocyte proliferation without accompanying liver cell necrosis. However, the mechanism of the mitogenic effect of lead nitrate is not known, and whether hepatocyte growth factor (HGF), transforming growth factor-alpha (TGF-alpha), and transforming growth factor-beta 1 (TGF-beta 1) play any role in it have not been investigated. These growth factors have indeed been shown to provide either positive or negative stimuli for liver cell regeneration after partial hepatectomy or liver cell necrosis. Moreover, there are reports showing that administration of non-necrogenic doses of tumor necrosis factor-alpha (TNF-alpha) to rats lead to an enhanced proliferation of hepatocytes and liver nonparenchymal cells. Lead is known to sensitize animals to lethal effects of bacterial lipopolysaccharides (LPS), suggesting that lead nitrate may modify the production of TNF-alpha in response to endogenous LPS of intestinal origin. An enhanced production of TNF-alpha could therefore be involved in the mitogenic action of lead nitrate. EXPERIMENTAL DESIGN: We investigated first whether a single intravenous dose of lead nitrate (100 mumole/kg) to rats modifies the production of HGF, TGF-alpha, and TGF-beta 1, by examining the steady-state level of their mRNA in the liver by Northern blot analyses. The response of rats given lead nitrate to various doses of LPS was next evaluated to determine whether lead-treated rats have an enhanced sensitivity to LPS. Finally, the level of TNF-alpha mRNA was examined in the liver of rats at various time periods after a single injection of lead nitrate. RESULTS: No changes were observed in the liver levels of mRNAs for HGF, TGF-alpha, and TGF-beta 1 at various time intervals after a single injection of lead nitrate. All rats given only single injections of LPS up to 100 micrograms survived. However, lead nitrate-treated rats tolerated LPS at dosages of only 6 micrograms. The liver of control rats showed a single 1.6 kb TNF-alpha transcript, whereas 1.8-kb transcripts were seen at 1 hour after lead nitrate injection, and persisted for 12 hours. The 1.8 kb TNF-alpha transcript was also present in the spleen of control rats, and its expression was enhanced in lead nitrate-treated rats. CONCLUSIONS: Stimulation of hepatocyte proliferation induced by lead nitrate was not accompanied by changes in liver levels of HGF, TGF-alpha, or TGF-beta 1 mRNA. Lead nitrate, however, enhanced expression of TNF-alpha at a time preceding the onset of hepatocyte DNA synthesis, indicating that TNF-alpha may trigger the lead nitrate-induced proliferation of hepatocytes.

Animals↗

["Extended aortic arch anastomosis" in Shone's anomaly--a case report].

We report a case of a newborn with Shone's anomaly in whom the parachute mitral valve, mild subaortic stenosis, hypoplastic aortic arch, and severe coarctation of the aorta were found. The patient was 10 days old, who had symptoms of low output syndrome due to the progressive obstruction of patent ductus arteriosus, underwent "extended aortic arch anastomosis" to repair the hypoplastic aortic arch and severe coarctation of the aorta. This surgical procedure, resulting in a successful post-operative course of the patient, might be effective in such anomalies.

Anastomosis, Surgical↗

[Effectiveness of fibrin glue in preventing postoperative pulmonary air leakage].

The authors investigated the effectiveness of fibrin glue in preventing pulmonary air leakage after lung surgery. We first examined 29 patients who underwent pulmonary resection without the use of fibrin glue. On the basis of preoperative spirometry data, these patients were divided into normal respiratory function and poor function groups (%VC < 80% and/or FEV1.0% < 70%), and the duration of postoperative pulmonary air leakage in each group was studied. The duration was 2.2 +/- 1.4 days (mean +/- S.D, n = 18) in the normal group and 5.2 +/- 4.3 days (mean +/- S.D, n = 11) in the poor respiratory function group. The latter values were significantly greater than the former (p < 0.05, unpaired t-test). Then we examined seven patients who underwent lung surgery with the use of fibrin glue. We found that in three patients with normal respiratory function, the air leakage disappeared within one day, and in four patients who had poor respiratory function, the air leakage disappeared in three days. In both respiratory function groups, the air leakage seemed to disappear more quickly with the use of fibrin glue. These results suggest that fibrin glue is effective in preventing pulmonary air leakage.

Adult↗