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Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 469 records · Page 26Linked to original sources

[Farmer's lung complicated by bilateral pneumothorax and mediastinal emphysema].

A 35-year-old woman was admitted to the hospital because of severe coughing and right-sided chest pain. She had worked on a farm for 13 years. For the preceding 2 years, she noticed a productive cough, a mild fever, and dyspnea after working in a barn for longer than 6 hours. Chest radiological examinations revealed low lung volumes, especially in the right upper lobe, and diffuse small granular shadows in both lung fields. Pathological examinations of lung specimens, which were obtained by transbronchial lung biopsy, showed alveolitis and granulomas in the interstitium. Micropolyspora faeni organisms were detected in hay from the barn. A M. faeni serum precipitation test revealed that her serum had antibodies against that organism. From these findings, we gave her a diagnosis of chronic farmer's lung. Prednisolone was given because her dyspnea and hypoxemia had increased. During the steroid treatment, bilateral pneumothorax and mediastinal emphysema developed. Bullae were removed surgically because she did not respond well to medical treatment. Although steroid administration may have caused these complications, bilateral pneumothorax and mediastinal emphysema are rare in patients with chronic farmer's lung.

Adult↗

[Ki-1-positive anaplastic large-cell lymphoma with mediastinal involvement].

A 30-year-old woman was admitted to our hospital because of an abnormal mass shadow in the right side of the mediastinum on a a chest X-ray film. The chest X-ray film and computed tomogram revealed a mass approximately 4.8 cm in diameter in the right side of the mediastinum. The mass had invaded the right supraclavicular fossa. Lymph-node biopsy was done. Microscopical examination of an HE-stained specimen of a supraclavicular lymph nodes showed prediferation of large atypical lymphocytes. These atypical lymphocytes were stained immunohistochemically with anti-Ki-1 antibody. No T cell or B cell markers were found on these cells. No other tumors were detected by radiological examination. Therefore, our diagnosis was anaplastic large-cell lymphoma, which is identical to Ki-1 lymphoma of the mediastinum.

Adult↗

[Chest wall reconstruction with pasteurized autogenous bone grafts after resection of desmoid tumor--a case report].

We reported a case of twenty-two years old woman who underwent seventh operation for recurrent desmoid tumor of posterior area of the lower zone of the left chest wall. For complete resection of the tumor, wide resection of the chest wall including 6th to 12th ribs was done. We used autobone grafts at the tumor site to reconstruct her bony thorax. The sixth, seventh, and ninth ribs were used as pasteurized autogenous bone grafts; they were heated in water at 60 degrees C for 30 minutes then cool, and replaced to the bony thoracic area. Her postoperative state was good and no complication was observed. Pasteurization process makes tumor tissue necrotic, and pasteurized bone has osteoinductive activity and have mechanical strength similar as that of fresh bone graft. So, we concluded that pasteurized autogenous bone grafting may be a useful method for chest wall reconstruction.

Adult↗

[Congenital antithrombin III deficiency associated with pulmonary thromboembolism].

A 42-year-old man was admitted to the hospital because of sudden left-lateral chest pain and dyspnea. The chest roentgenogram on admission showed a string-like shadow and pleural effusion, and analysis of arterial blood gases revealed hypoxemia. Many bilateral segmental defects were seen on a radioisotope perfusion scan of the lungs, and the chest CT scan showed a low-density area in the trunk of the pulmonary artery. From these findings, pulmonary thromboembolism was diagnosed. The serum antithrombin III (ATIII) activity and the antigen value were low, and the patient's son's serum ATIII level was also low. Both the patient and his son were given the diagnosis of congenital ATIII deficiency. Gene analysis revealed two point mutations in exon 6 of the ATIII gene, so we classified this case as type IIc. The patient was treated with intravenous urokinase and heparin, and was then given warfarin. The arterial blood gas tensions improved, and the low-density area of the pulmonary artery on the CT scan disappeared, as did the pulmonary perfusion defect on the radioisotope scan. The clinical manifestations of members of 28 families with congenital ATIII deficiency reported in Japan were reviewed. Patients in whom many point mutations were detected in the ATIII gene were rare.

Adult↗

[Prospective controlled study on the usefulness of Carmofur as a postoperative adjuvant chemotherapy for colorectal cancer].

A prospective controlled study, the 7th cooperative study of the Japanese Foundation for Multidisciplinary Treatment, was conducted to evaluate the usefulness of concomitant therapy with MMC + HCFU as a postoperative adjuvant therapy in patients with colorectal cancer who had undergone curative resection for a period of 2 years and 11 months from February, 1986. The Dukes B and C patients with colorectal cancer classified by macroscopic examination who had an intravenous MMC 6 mg/m2 on the day of operation and followed by oral HCFU for 12 months from 2 weeks after operation (Group X) were compared with patients who had operation only (Group Y). Some 978 patients with colon cancer and 713 patients with rectal cancer were enrolled in the study, 85 (5.0%) of whom were not eligible. The 5-year survival rate of Group X in colon cancer was 79.3% and that of Group Y was 76.4%: thus the survival rate of Group X was slightly better than that of Group Y, but no significant difference was found between the two groups. Subset analysis revealed that the survival rate of Group X in advanced cancer of stage III b + IV, according to the General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus in Japan, was 62.4% and that of Group Y was 46.2%. Thus, the survival rate of Group X was significantly better than that of Group Y (logrank test: p = 0.035, generalized Wilcoxon test: p = 0.025). The disease-free survival rate was not significantly different between the groups with colon cancer and rectal cancer. The above results suggest that HCFU is useful for patients with a high risk of recurrence who had advanced colon cancer (stage III b + IV). However, additional prospective studies are required to verify them.

Antineoplastic Combined Chemotherapy Protocols↗

[Development of thymic tumor in HTLV-I transgenic rats under control of a lymphoid tissue specific promoter].

The p40tax protein of Human T lymphocyte virus type I (HTLV-I) is known to be a transactivator not only for the own viral gene but also for the various cellular genes (host genes), including a number of cytokine genes and genes for cell proliferation. Its tumorigenicity was also reported in vivo, such as developments of mesenchymal tumor, neurofibroma, mammary carcinoma and large granular lymphocytic leukemia, using the transgenic technique. To investigate the tumorigenicity in lymphoid tissues, a series of HTLV-I pX transgenic rats (lck-pX rats) which expressed the pX gene under control of lymphocyte specific protein tyrosine kinase (p56 lck) gene type 1 promoter was produced. In some lines of lck-pX rats, pX mRNA was expressed selectively in the thymus, lymph nodes and spleen as expected. However, pX mRNA expression was also detected in other tissues from other lines of lck-pX rats. Thymic tumor with epithelial markers developed in lck-pX rats as early as 8 weeks of age and high expression of pX mRNA was detected in the tumor tissue. This is the demonstration that HTLV-I pX gene causes thymic tumor in the transgenic rat and an lck-pX rat may be a suitable animal model for elucidating pathogenetic role of HTLV-I pX gene in lymphoid tissue neoplasia.

Animals↗

[Clinical significance of 123I-MIBG myocardial scintigraphy in patients with hypertrophic cardiomyopathy].

We studied the abnormality of myocardial sympathetic nervous system in patients with hypertrophic cardiomyopathy using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in comparison with the parameters of other clinical examinations. In 50 patients with HCM, the heart to mediastinum 123I-MIBG uptake ratio (H/M) was significantly low and washout rate (WR) of 123I-MIBG was significantly high respectively compared with normal subjects (n = 8). H/M was negatively correlated with serum norepinephrine level, wall thickness of left ventricle, left ventricular mass index, left ventricular end diastolic pressure respectively, and WR was positively correlated with those parameters respectively. On the other hand, LF/HF calculated by spectral analysis in holter electrocardiogram was positively correlated with H/M, and negatively correlated with WR. In HCM, H/M in patients with subjective symptoms was significantly lower than that without subjective symptoms, and WR in patients with paroxysmal atrial fibrillation was significantly higher than that without paroxysmal atrial fibrillation. This study revealed that H/M and WR reflected the severity and the difference of disease type in HCM. In conclusion, 123I-MIBG contributes to evaluating more details in diagnosis and pathophysiology of HCM.

3-Iodobenzylguanidine↗

[Western blot analysis of anti-M2 antibodies in anti-mitochondrial antibody-negative primary biliary cirrhosis].

One variety of anti-mitochondrial antibody(AMA) is characteristically found in sera from patients with primary biliary cirrhosis(PBC). The major target antigens of this type of AMA are M2s. It is well known, however, that AMA-negative PBC also exists. An alternative disease concept, called autoimmune cholangiopathy, recently has been advocated. This new concept is defined by the following criteria: 1)the failure to detect AMA and anti-M2, 2)the detection of a diffuse type of anti-nuclear antibody and anti-smooth muscle antibody, 3)pathological findings compatible with PBC, and 4)the effectiveness of prednisolone. However, the difference between AMA-negative PBC and autoimmune cholangiopathy is controversial. Therefore, we analyzed antibodies to four major M2 proteins with Western blotting in 34 cases of immunofluorescent AMA-negative PBC. In 31(91.2%) of these 34 AMA-negative sera, antibodies to at least one of these four major M2 proteins was detected. In serum samples from 34 control patients with AMA-positive PBC, antibodies to at least one of these four proteins were detected in all cases. In addition, we studied the frequency of cases which satisfied the serological criteria of autoimmune cholangiopathy. In only one(0.7%) of 141 cases was the serological criteria met. We conclude that to clarify the serological differences between autoimmune cholangiopathy and AMA-negative PBC, the analysis of M2 proteins by Western blotting is essential.

Adult↗

Distribution of anti-p80-coilin autoantibody in collagen diseases and various skin diseases.

Anti-p80-coilin antibody produces a unique pattern of immunofluorescence staining called nuclear dots characterized by the presence of up to six discrete nuclear bodies in interphase cell nuclei. The distribution of this antibody and its clinical relevance have not been established. We studied the prevalence of anti-p80-coilin antibody in the sera from 810 patients with collagen diseases and various skin diseases. Five sera showed the nuclear dot pattern by indirect immunofluorescence on an HEp-2 cell substrate, and reacted by immunoblotting with 80-kDa protein in a nuclear extract from HeLa cells. Four of these sera were from patients with localized scleroderma, and the other was from a patient with primary Raynaud's phenomenon. The patients with localized scleroderma who were positive for anti-p80-coilin antibody had all been classified as having linear scleroderma. They had only one or two lesions, and were negative for antihistone and anti-single-stranded DNA antibodies. Our data indicate that anti-p80-coilin antibody is uncommon in skin diseases: however, this antibody is present in patients with a milder form of linear scleroderma, although the incidence of positivity may not be high.

Autoantibodies↗

[Effect of dopamine receptor on hypoxic ventilatory response].

We studied the effect of intravenous administration of a dopamine (DA) agonist and antagonist on the hypoxic response of phrenic nerve activity in anesthetized, vagotomized and mechanically ventilated rabbits. The experiments were performed in both intact and carotid sinus denervated animals. In the intact animals, hypoxic challenge (FIO2 = 0.10) increased the amplitude of integrated phrenic nerve activity (iPNA) without any alteration in respiratory frequency. In the carotid sinus denervated animals, the hypoxia progressively depressed iPNA. Neither the DA antagonist, haloperidol (0.5mg/kg i.v.), nor the DA agonist, apomorphine (0.3mg/kg, i.v.) changed the iPNA during normoxia in either the intact or denervated group. Administration of haloperidol enhanced iPNA response to hypoxia in the intact group. Apomorphine decreased the hypoxic response to iPNA. Although apomorphine did not change the control hypoxic response to iPNA in the denervated group, haloperidol augmented hypoxic respiratory depression in the carotid sinus denervated group. Therefore, we concluded that the effect of DA on peripheral chemoreceptors inhibits the hypoxic ventilatory response, but stimulates the hypoxic ventilatory response in the central nervous system.

Animals↗

Molecular cloning and analysis of the 5'-flanking region of the rat PP1 alpha gene.

We have cloned an 8 kbp genomic fragment of 5'-flanking region of the gene encoding the catalytic subunit of rat protein phosphatase 1 alpha. Neither CAAT box nor TATA box was detected but a 300 bp high GC region containing nine Sp1 transcription factor binding sites is present immediately upstream of the translation start site, demonstrating that PP1 alpha is a housekeeping gene. Luciferase reporter assay showed that transcription of PP1 alpha is controlled at the high GC region.

3T3 Cells↗

Block of Na+ channel by bepridil in isolated guinea-pig ventricular myocytes.

The effects of bepridil, a potent antiarrhythmic agent, on the Na+ current (INa) of single guinea-pig ventricular myocytes were studied using the whole-cell patch-clamp technique. Bepridil inhibited INa in a dose-dependent manner without causing any change in the I-V. relationship for INa. Bepridil suppressed INa with Kd values of 342 and 40 microM when cells were clamped to holding potentials of -140 and -90 mV, respectively. 10 microM bepridil shifted the steady-state inactivation curve for INa toward more negative potentials by 7.7 mV (n = 6). Bepridil also produced marked use-dependent block with a rapid onset. Recovery of INa from inactivation was retarded (time constant 290 ms) at a holding potential of -140 mV in the presence of 10 microM bepridil. When the onset of INa block was studied in experiments using a double-pulse protocol, bepridil blocked INa by 11.5% after a 4-ms pre-pulse, but significantly blocked it after pre-pulses longer than 16 ms. These results suggest that: (1) bepridil has a higher affinity for the inactivated state than the resting state of Na+ channel; (2) the drug also produces an open channel block; and (3) the drug shows a lidocaine-like fast kinetic block of Na+ current.

Animals↗

Involvement of peptide antigens in the cytotoxicity between 70-kDa heat shock cognate protein-like molecule and CD3+, CD4-, CD8-, TCR-alpha beta- killer T cells.

We previously reported that the 70-kDa heat shock cognate protein-like molecule (hsc70) is expressed on the cell surface along with the neoplastic transformation of rat fibroblast and that this molecule is recognized by CD3+, CD4-, CD8-, NKR-P1-, and TCR-alphabeta- T (DNT) killer cells in an MHC class I-unrestricted fashion. We investigated the mechanism of interaction between hsc70 and DNT cells. H-ras oncogene-transformed rat fibrosarcoma W31 cells expressed hsc70 on the cell surface in almost the same density when the cells were growing in a conventional 5% FCS (5% W31) as when the cell growth was inhibited in the cultivation with 1% FCS (1% W31). However, DNT cells lysed only 5% W31, but not 1% W31. Since these observations suggest that certain peptide Ags of the fast growing W31 cells may play a role in the interaction between hsc70 and DNT cells, we pulsed 1% W31 cells with trifluoroacetic acid (TFA)-extracted fast growing W31 tumor Ags of less than 3000 Da in molecular size. We also pulsed 1% W31 with TFA-extracted Ags from moderate growing W14 tumors and whole fetus tissues. Our data indicated that DNT cells were clearly cytotoxic to 1% W31 pulsed only with TFA-extracted Ags from W31 tumors. Anti-rat hsc70 mAb completely blocked this cytotoxicity. In addition, pronase K treatment of Ags clearly inhibited the cytotoxicity by DNT cells. Taken together, these data suggest that the complex of peptide Ag and hsc70 is involved in the cytotoxic mechanism between hsc70 and DNT cells.

Animals↗

Telomerase activity in normal human epithelial cells.

Telomerase activity is found in most cancer tissues and many immortalized cell lines as well as in germ line cells but it is generally undetected in normal human somatic tissues. There is weak telomerase activity in some cell types of hematopoietic lineage in which a stem cell-like subpopulation may exist. Likewise, physiologically regenerating somatic tissues and organs such as skin, small intestine, and most other epithelia of the human body are supposed to contain similar cell lineages to maintain their renewal throughout the life span of individuals. It is therefore of interest whether telomerase activity is present in physiologically regenerating epithelial cells. Telomerase activity was detected, though very weakly, in cultured normal epidermal keratinocytes and at higher levels in a subpopulation that adhere rapidly on collagen IV-coated culture dishes. No telomerase activity was detected in a subpopulation that was less adherent on the coated dishes. The rapidly adherent subpopulation of keratinocytes was enriched in small proliferating cells with macrocolony forming potential. It was also passaged through more generations in culture, and expressed integrin beta 1 at higher levels than the less adherent subpopulation. Telomerase activity was similarly found in ectocervical keratinocytes as well as in simple endocervical epithelial cells. These findings provide the evidence of a telomerase-positive population among physiologically regenerating normal human epithelial cells. The identity of the telomerase-positive cells remains to be defined.

Base Sequence↗

Renin-angiotensin system in stretch-induced hypertrophy of cultured neonatal rat heart cells.

Although it is well known that mechanical load to cardiac muscles causes cardiac hypertrophy, little is known about how mechanical load is transduced into the activation of intracellular signals which are linked to cell growth. We investigated whether the cardiac renin-angiotensin system was involved in stretch-induced hypertrophy of cultured neonatal rat heart myocytes. Myocytes were cultured with serum-free medium in a deformable silicon dish. Stretch of cardiac myocytes significantly increased the protein/DNA ratio at culture days 6 and 7, and the RNA/DNA ratio at culture days 4 and 5. Stretch significantly accelerated rates of protein synthesis by 15%. c-fos mRNA expression was significantly increased after stretch. The stimulatory effects of cell stretch on these parameters were significantly inhibited by the angiotensin converting enzyme inhibitor, captopril, or the type 1 angiotensin II receptor antagonist, losartan. The concentrations of angiotensin I and angiotensin II in culture media were significantly increased by stretch. Stretch did not change the angiotensin converting enzyme activity. These studies demonstrate that mechanical stretch activates the cardiac renin-angiotensin system in a autocrine and paracrine system which acts as an initial mediator of the stretch-induced hypertrophic growth.

Angiotensin I↗