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Biomedical subjects

H Kubota

Publications and source records attributed to H Kubota.

At least 109 records · Page 6Linked to original sources

Autoantibodies against chaperonin CCT in human sera with rheumatic autoimmune diseases: comparison with antibodies against other Hsp60 family proteins.

Chaperonin CCT containing t-complex polypeptide 1 is a cytosolic molecular chaperone that assists in the folding of actin, tubulin, and other proteins and is a member of the 60-kDa heat shock protein (Hsp60) family. We examined antibody titers against human CCT and other Hsp60 family members in the sera of patients with rheumatic autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematodes, Sjögren syndrome, and mixed connective tissue disease. Autoantibody titers against not only human mitochondrial Hsp60 but also CCT were significantly higher in the sera of patients with rheumatic autoimmune diseases than in healthy control sera. Although immunoglobulin G (IgG) titers against Escherichia coli GroEL were high in all the groups of sera tested, no significant differences in anti-GroEL responses were detected between patients and healthy controls. IgG titers against mycobacterial Hsp65 showed a similar pattern to titers of autoantibodies recognizing GroEL. Immunoabsorption experiments demonstrated that most of the autoantibodies recognizing CCT were cross-reactive with mitochondrial Hsp60, E coli GroEL, and mycobacterial Hsp65. Although most of the anti-Hsp60 IgG recognized CCT, anti-GroEL (or antimycobacterial Hsp65) IgG contained antibodies specific for GroEL (or mycobacterial Hsp65) in addition to antibodies cross-reactive with CCT and Hsp60. Results from immunoblot analyses, together with weak (15% to 20%) amino acid sequence identities between CCT and the other Hsp60 family members, suggested that CCT-reactive autoantibodies recognize conformational epitopes that are conserved among CCT and other Hsp60 family members.

Adult↗

HLA-DR expression of synovium and correlation with clinical features of patients with rheumatoid arthritis.

To investigate whether the expression of human leukocyte antigen-DR (HLA-DR) in synovial tissues obtained at synovectomy contributes to the clinical features of patients with rheumatoid arthritis (RA), immunohistochemical analysis was performed to determine the intensity and pattern of HLA-DR expression in synovial tissue from 96 patients with RA. The clinical features before and 1 year after the synovectomy were investigated. At the time of the surgery, duration of morning stiffness was associated with the degree of HLA-DR expression in synovial lining layer, and this synovial lining expression of HLA-DR was more frequently observed in elbow and wrist joints than in knee joint. In patients who underwent knee synovectomy, erythrocyte sedimentation rate and C-reactive protein level one year after the surgery were significantly higher in the patients with intense expression of HLA-DR in the synovial lining. Our findings showed that the expression of HLA-DR in the synovial lining contributes to several clinical features, and the expression in large joint such as knee may related with disease course of patients with RA.

Adult↗

[Effect of epilepsy surgery based on magnetic resonance imaging (MRI) classification].

We prospectively analyzed the effect of surgical procedures in epilepsy patients, except for those with mesial temporal lobe epilepsy. Twenty patients with a mean age of 26 years (range 3 to 58 years, 10 male and 10 female) underwent the surgical procedures. These patients were divided into 3 groups according to MRI findings, as follows; group A (localized type): localized lesions such as angiomas or benign tumors, group B (widespread type): widespread lesions such as regional encephalitis or stroke, visible on anatomical neuroimaging, and group C (cryptic type): no lesion visible on anatomical neuroimaging. Following surgery, 11 (85%) of the 13 patients in group A were seizure-free, one showed worthwhile improvement, and one, whose lesion was not removed totally, was unchanged. In group B, two patients (50%) were seizure-free and 2 (50%) showed worthwhile improvement. All the patients in group C showed worthwhile improvement. Lesionectomy, cortical excision, multiple subpial transection (MST) or a combination of these procedures were effective in groups A and B. Patients in group C had a chance to obtain worthwhile improvement by corpus callosotomy or cortical excision. Intracranial EEG recording provides useful information for epilepsy surgery in intractable cases.

Adolescent↗

[Simultaneous abdominal aortic replacement and thoracic stent-graft placement for multiple aortic aneurysms: report of a case].

Patients with aneurysmal disease involving both the thoracic and abdominal aorta have historically required simultaneous or sequential conventional operations. Staged operations were generally preferred, but we experienced that a patient had rupture of the second aneurysm after he finished initial treatment for the first aneurysm. We have implemented simultaneous operation using thoracic stent-graft placement. A 78-year-old male who had multiple aortic aneurysm involving both the thoracic and abdominal aorta underwent conventional abdominal aortic replacement with endovascular stent-graft placement into the distal arch of the thoracic aorta under fluoroscopic guidance. The stent-graft was composed of two units of self-expanding stainless-steel Z stent covered with an thin wall woven Dacron graft. Postoperative aortography showed no stent migration and no endoleak. Simultaneous abdominal aortic replacement and deployment of a thoracic stent-graft may be a valuable treatment option for these patients. However, careful long term follow up is necessary to prove the value and the effects of the endovascular treatment.

Aged↗

[Effects of the gene transfer into sperm mediated by liposomes on sperm motility and fertilization in vitro].

To clarify the problems of gene transfer in the fertility clinic, we investigated the safety and effectiveness of the gene transfer of mouse sperm using the lipofection method. We used the pCAGGS-lacZ plasmid connected with cytomegarovirus enhancer/chicken beta-actin promoter as an adventitious gene. After incubation of the DNA-liposome complex and mouse sperm of epididymis in the medium, we investigated the sperm motility after gene transfer, in vitro fertilization rate of the gene transferred sperm, and gene expression of the fertilized ovum and fetus. Sperm motility was lowered significantly with the increase in DNA density. The fertilization rate for in vitro fertilization was lowered significantly with the increase in DNA density. Gene expression was observed in some of the fertilized ova. In the fetus 12.5 days after embryo transfer, gene transfer was confirmed by the PCR method, but we could not find gene expression by X-gal staining. We proved that the sperm with a gene transferred by the lipofection method could fertilize the ovum and transfer adventitious gene to ova. We speculate that sperm motility and fertility rate were lowered because the introduction of DNA and the DNA-liposome complex destroyed parts of the cell. Development of a sperm fractionation method for DNA transfer and establishment of a method for effective and safe DNA transfer are awaited.

Animals↗

Cyclooxygenase-2 expression correlates with tumor neovascularization and prognosis in human colorectal carcinoma patients.

The role of cyclooxygenase-2 (COX-2) in tumor neovascularization of human colorectal carcinoma is yet to be delineated. One hundred colorectal carcinoma specimens were evaluated for COX-2 expression and CD34-stained microvessel density (MVD) by immunohistochemical methods. The relationships between COX-2 expression and clinicopathological feature of the patients, MVD, and survival time were analyzed. Increased COX-2 expression was significantly correlated with pathologically unfavorable findings such as tumor size (> 3.0 cm), tumor differentiation (poor, moderate > well differentiated), number of metastatic lymph nodes (24), and Dukes' stage (Dukes' B, C, and D). Larger number of microvessels congregated around the COX-2-expressing area, and the Spearman rank correlation test showed a strong correlation between COX-2 expression and tumor MVD (P < 0.0001). Patients with COX-2-positive tumors had a significantly (P = 0.037, by log-rank test) shorter survival time than those with negative tumors did. In the multivariate analysis, however, only Dukes' stage and number of metastatic lymph nodes remained as independent prognostic factors. Augmented tumor neovascularization may be one of the several effects of COX-2 responsible for poor prognosis in human colorectal carcinoma patients.

Aged↗

[Total hematological analysis system as a screening test for hematological malignancy].

Measurement of complete blood cell count and white blood cell differentiation is an essential laboratory test and the most important screening test for hematological malignancy. Recently, several automated blood cell analyzers have been developed to improve accuracy and precision. When flag messages generated in the presence of morphological abnormalities of the samples are displayed, manual revision is necessary. In our laboratory, the manual revision rate has been 35-40%. Therefore blood cell analyzers are useful in screening for abnormalities as well as greatly reducing expensive and time-consuming manual differential procedures. In addition, automated blood cell analyzers can provide several types of useful information including the leukocyte distribution scattergram. However, most such information is not utilized in the clinical field. In the future, a total hematological analysis system will be constructed so that all information provided by automated blood cell analyzer and by manual methods are available.

Blood Cell Count↗

Spontaneous apoptosis in advanced esophageal carcinoma: its relation to Fas expression.

The prognostic importance of spontaneous apoptosis and its correlation with clinicopathological characteristics and Fas expression have yet to be delineated in esophageal carcinoma. Specimens from 65 patients with advanced squamous cell carcinoma of the esophagus were used for immunohistochemical evaluation of Fas, proliferating cell nuclear antigen, and apoptosis. The mean apoptotic index (AI) of 65 tumors was 1.38 +/- 0.99% (range, 0.10-4.49%). Thirty-nine (60.0%) patients had a high AI, and 26 (40.0%) patients had a low AI. Low AI was correlated with advanced tumor stage (P = 0.0197) and weak Fas expression (P = 0.0093). Patients with a low AI had significantly (P = 0.0095) worse survival than those with a high AI. However, by multivariate analysis, low AI alone was not an independent prognosticator. When combined with cellular proliferation index, AI became an independent prognostic factor (P = 0.0283) in this group of patients. Our results suggest that enhanced Fas expression is responsible for high AI in squamous cell carcinoma of the esophagus. High AI, combined with the cellular proliferation labeling index, could be an independent prognostic indicator.

Age Factors↗

Atrial ablation using an IRK-151 infrared coagulator in canine model.

BACKGROUND: A method of atrial ablation was developed with the aim of shortening the aortic cross-clamp time during MAZE surgery. The IRK-151 infrared coagulator (Infrarot-Kontaktkoagulator: MBB: Messerschmidt-Bolkow-Blohn, Germany) was employed. Our aim was to electrophysiologically confirm the efficacy of this device. METHODS: The MAZE-III procedure was performed in four mongrel dogs. Instead of a pulmonary vein-encircling incision, IRK-151 was applied several times to create a continuously overlapping circular lesion. After aortic declamping, the potentials of both atria were recorded using 18 bipolar electrodes implanted in the atrial wall. The recording conditions were: 1) sinus rhythm, 2) overdrive pacing from outside the encircling coagulation, and 3) overdrive pacing from inside the encircling coagulation. RESULTS: 1) There was no detectable potential within the pulmonary vein-encircling coagulation. 2) There was no conduction of paced atrial potential inside the encircling coagulation. 3) Only the area within the encircling coagulation was activated by the stimulus. Other parts of the atrium showed sinus rhythm simultaneously. CONCLUSIONS: The left atrium within the pulmonary vein-encircling coagulation was isolated electrophysiologically.

Animals↗

Prognostic factors in node-negative squamous cell carcinoma of the thoracic esophagus.

BACKGROUND: Among several clinicopathological factors influencing the outcome of patients with esophageal carcinoma, the presence or absence of lymph node metastasis is the most important. Prognostic indicators, however, in patients without lymph node involvement have not been fully understood. MATERIALS AND METHODS: Out of 247 patients with primary squamous cell carcinoma of the thoracic esophagus between February 1981 and December 1998, 154 patients (62.3%) underwent esophagectomy with curative intent; 78 patients (50.6%) had no lymph node metastasis. Clinicopathological characteristics of those node-negative 78 patients were investigated. RESULTS: Pathological tumor stages (pT) were pT1 in 44 patients, pT2 in 24 patients, pT3 in 9 patients, and pT4 in one patient. Forty-six patients are alive free of cancer and another one with pT2N0 tumor is alive with recurrence. Four patients died of recurrence; one in pT1 and three in pT3. The remaining 27 patients died of miscellaneous causes other than esophageal cancer. The 1-, 3-, 5-, and 10-year overall survival rates of all 78 patients including in-hospital mortality were 86.3%, 73%, 66.5%, and 34.6%, respectively. The 3- and 5-year survival rates were 75.4% and 67.7% for those with pT1, T2 tumor (n = 68) and 57.1% and 57.1% for those with pT3, T4 tumor (n = 10) (p = 0.0151). The factors influencing overall survival rate were patient age (< 65 vs. > or = 65), depth of invasion (pT1,T2 vs. pT3, T4), time of operation (< or = 420 min vs. > 420 min), and estimated blood loss (< or = 810 ml vs. > 810 ml). More elderly patients died of unrelated causes to esophageal cancer than younger patients. Among those four variables, the patient age (p = 0.0114) and depth of invasion (p = 0.0443) were independent prognosticators for survival determined by multivariate analysis. CONCLUSION: For follow-up of elderly patients with node-negative esophageal cancer, evaluation of medical problems is more important than detection of recurrence. pT2N0 stage tumors should be considered a group with an excellent prognosis like pT1N0 tumors.

Aged↗

Cytosolic chaperonin is up-regulated during cell growth. Preferential expression and binding to tubulin at G(1)/S transition through early S phase.

The chaperonin containing t-complex polypeptide 1 (CCT) is a heterooligomeric molecular chaperone assisting in the folding of actin, tubulin, and other cytosolic proteins. The expression levels of CCT subunits varied among seven mouse cell lines tested but showed a close correlation with growth rate. Both the CCT protein and mRNA levels in the human promyelolytic cell HL60 decreased concomitant with growth arrest during differentiation. More rapid decrease in CCT level occurred when the mouse interleukin (IL)-3-dependent myeloid DA3 cells were starved for IL-3. Readdition of IL-3 caused rapid resumption of CCT synthesis during synchronous growth: the maximum CCT protein and mRNA levels were observed at G(1)/S transition through early S phase. The turnover rate of CCT was nearly constant regardless of growth. Gel filtration and immunoprecipitation analyses indicated that CCT in vivo is associated with tubulin at early S phase, but not at G(0)/G(1) phase. These results demonstrated that CCT expression is strongly up-regulated during cell growth especially from G(1)/S transition to early S phase and is primarily controlled at the mRNA level. CCT appears to play important roles for cell growth by assisting in the folding of tubulin and other proteins.

Animals↗

Transcriptional activation of mouse cytosolic chaperonin CCT subunit genes by heat shock factors HSF1 and HSF2.

The chaperonin containing TCP-1 (CCT) is a eukaryotic molecular chaperone consisting of eight subunit species and assists in the folding of cytosolic proteins. We show here that all eight mouse CCT subunit genes contain sequences called heat shock elements for binding heat shock transcription factors (HSFs) by electrophoretic mobility shift assays and that these genes are transcriptionally activated by HSFs in reporter gene assays using HeLa cells transiently overexpressing HSFs. These results suggest that HSF1 and/or HSF2 play a role in Cct gene expression.

Animals↗

Cytogenetic alterations in pituitary adenomas detected by comparative genomic hybridization.

Pituitary adenomas are benign monoclonal tumors that are either hormonally functional or nonfunctional. Although their histologic and immunocytologic characteristics have been studied extensively, cytogenetic studies are scarce. We have investigated the cytogenetic alterations and DNA ploidy patterns of 12 sporadic pituitary adenomas, including 2 growth-hormone-secreting tumors, 1 prolactinoma, and 9 nonfunctional adenomas, by comparative genomic hybridization (CGH) and laser scanning cytometry (LSC). CGH revealed that the mean number of sites of copy gain was significantly higher in functioning adenomas than in nonfunctioning tumors (P < 0.01). The most frequent change detected was loss of 13q (5 cases), with a minimal common overlapping region at 13q14. These findings suggest that a putative tumor suppressor gene on 13q14 may play an important role in the development of pituitary adenomas. DNA aneuploidy was detected by LSC in 3 of the 12 cases. The DNA aneuploid adenomas showed cytogenetic changes more frequently than did the DNA diploid tumors (P < 0.02).

Adenoma↗

Prognostic factors in T1 and T2 squamous cell carcinoma of the thoracic esophagus.

BACKGROUND: Prognostic indicators in patients with T2 tumor have not been fully understood. OBJECTIVE: To clarify the clinicopathologic characteristics and long-term results of T1 and T2 squamous cell carcinomas of the thoracic esophagus. DESIGN: Consecutive case series. SETTING: Department of surgery in a university hospital. PATIENTS: Of 234 patients with primary squamous cell carcinoma of the thoracic esophagus, 142 patients underwent esophagectomy with curative intent: 97 patients had pT1 and pT2 tumors. INTERVENTIONS: Investigated were clinicopathologic characteristics of 65 of 97 patients with pT1 and pT2 tumors; excluded were 7 patients who died of postoperative complications and another 25 patients who died of causes other than esophageal cancer. MAIN OUTCOME MEASURES: Clinicopathologic characteristics and long-term results. RESULTS: Pathologic tumor stages were pT1 N0 in 23 patients, pT1 N(+) in 7 patients, pT2 N0 in 15 patients, and pT2 N(+) in 20 patients. Fifty patients are alive and free of cancer and 15 patients died of tumor recurrence (1 patient with pT1 N0 tumor, 1 patient with pT1 N[+][+] tumor, 1 patient with pT2 N0 tumor, and 12 patients with pT2 N[+] tumor). The sites of metastatic nodes in 6 survivors with pT1 N(+) tumor were a solitary perigastric node in 4 patients, a solitary mediastinal node in 1 patient, and 2 mediastinal nodes in 1 patient. The 5-year survival rates of patients with pT1 N0, pT1 N(+), and pT2 N0 tumors all exceeded 85%, and the rate of those with pT2 N(+) tumor was 33.9% (pT2 N[+] vs. others: pT1 N0, pT1 N[+], and pT2 N0; P = .003). The factors affecting survival rate by univariate analysis were Borrmann classification (0, 1 vs. 2, 3, 4), tumor size (<4.0 vs. > or =4.0 cm), combined T, N factor (pT2 N[+] vs. others), time of operation (< or =420 vs. >420 minutes), estimated blood loss (<1000 vs. > or =1000 mL), and lymph vessel invasion (marked vs. not marked). Stage pT2 N(+) tumor became a single independent prognostic factor for survival as determined by multivariate analysis (pT2 N[+] vs. others; P = .008). CONCLUSIONS: Stage pT1 N(+) tumors with a few diseased nodes and pT2 N0 tumors are considered to be a group with an excellent prognosis, similar to pT1 N0 tumors. Patients with pT2 N(+) diseases had worse prognoses and thus should have meticulous lymph node dissection and extensive adjuvant therapy.

Aged↗

Prognostic factors after extended esophagectomy for squamous cell carcinoma of the thoracic esophagus.

BACKGROUNDS AND OBJECTIVES: In Japan, extended esophagectomy with extensive lymphadenectomy has become the standard surgical procedure for carcinoma of the thoracic esophagus. Although mortality and morbidity rates after such extensive esophagectomy have been acceptable, the long-term outcomes are not necessarily satisfactory. METHODS: Among 235 patients with primary squamous cell carcinoma of the thoracic esophagus between June 1981 and March 1998, 143 patients (60.9%) underwent extended esophagectomy with extensive lymphadenectomy. To exclude the effects of surgery-related postoperative complications, 14 patients who died within 90 days after operation were excluded. Thus, clinicopathological characteristics and prognostic factors of 129 patients were retrospectively investigated. RESULTS: Sixty-three patients were alive and free of cancer. Sixty-six patients died: 37 of recurrence of the esophageal cancer and 29 of other causes. The 1-, 3-, 5-, and 10-year overall survival rates in the 129 patients were 78.8%, 53.5%, 45.8%, and 30.9%, respectively, and the disease-specific survival rates were 85.7%, 69.1%, 67.9%, and 56.2%, respectively. The factors influencing the disease-specific survival rate were tumor location (upper third vs. non-upper third), Borrmann classification (0, 1 vs. 2, 3), size of tumor (</=3.0 vs. >3.0 cm), depth of invasion (T1, 2 vs. T3, 4), number of lymph node metastases (0 or 1 vs. >/=2), time of operation (</=420 vs. >420 min), amount of blood transfused (</=2 vs. >/=3 U), lymph vessel invasion (marked vs. not marked), and blood vessel invasion (marked vs. not marked). Among those significant variables, independent prognostic factors for survival determined by multivariate analysis were number of lymph node metastases (P < 0.001), amount of blood transfusions (P = 0.0016), and tumor location (P = 0.0382). CONCLUSIONS: Patients with a single metastatic node after extended esophagectomy should be considered to have excellent prognosis, like patients with pN0 tumors. Patients with multiple involved nodes should receive aggressive postoperative adjuvant treatments. Reduced blood loss during extended esophagectomy and minimal blood transfusions might improve the outcome of curative esophageal resections.

Aged↗

Induction of general anesthesia using propofol for cesarean section of a woman with cerebral palsy.

A 45-year-old pregnant woman with cerebral palsy was scheduled for cesarean section at 37 weeks' gestation due to the risk of athetotic reaction. Spinal anesthesia appeared difficult to perform due to maintenance position, and because maternal respiratory depression due to athetotic reaction to mechanical stimulation might cause fetal hypoxia. We therefore selected general anesthesia. Propofol and succinylcholine were intravenously (i.v.) administered for induction, and additional propofol was administered i.v. for hemodynamics stabilization. Neonatal Apgar scores were 8 at one minute and 10 at five minutes. No maternal respiratory depression was observed postoperatively, and a healthy baby was successfully delivered.

Anesthesia, General↗