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Biomedical subjects

K Kikuchi

Publications and source records attributed to K Kikuchi.

At least 217 records · Page 12Linked to original sources

Broad specificity in binding of NIPP-1, nuclear inhibitor of protein phosphatase-1, to PP1 isoforms in vivo.

Protein phosphatase type-1 (PP1), one of the most abundant Ser/Thr protein phosphatases, plays a central role in the regulation of various cell functions. Almost all the PP1 molecules exist as holoenzymes in vivo consisting of a catalytic subunit (PP1C) and a variable regulatory subunit that regulates substrate specificity and/or subcellular localization. In order to clarify fine regulation of PP1, we overexpressed a nuclear inhibitor of PP1 (NIPP-1) in a Flag-tagged form in mammalian cells. The Flag-tagged NIPP-1 was found to be immunoprecipitated with three isoforms of PP1C, namely, PP1alpha, PP1gamma1, and PP1delta with a similar efficiency, suggesting that NIPP-1 makes a complex with the PP1C through the region conserved among the three isoforms. These results suggested that NIPP-1 can be involved in the regulation of various PP1 holoenzymes in vivo.

Animals↗

Successful treatment of a patient with nephrotic syndrome associated with chronic lymphocytic leukemia.

We report the case of a 62-year-old man with nephrotic syndrome associated with stage B chronic lymphocytic leukemia (CLL). Kappa Bence Jones proteinuria and the glomerular deposition of kappa-light chain were observed. Although treatment with cyclophosphamide and prednisolone tended to reduce the level of proteinuria, the administration of angiotensin-converting enzyme inhibitor, enalapril, resulted in complete remission of nephrotic syndrome.

Angiotensin-Converting Enzyme Inhibitors↗

An adult case of mumps brainstem encephalitis.

We present an adult case of mumps brainstem encephalitis. He was successfully treated with steroid pulse therapy and recovered completely except for persistent dysuria. He had not been vaccinated and had no history of acute mumps infection. We consider that encephalitis in this case was caused by a reversible autoimmune process triggered by mumps infection. We emphasize the usefulness of pulse therapy for the treatment of some cases of mumps brainstem encephalitis in addition to the importance of mumps vaccination to prevent such a severe complication as encephalitis.

Adult↗

Extensively calcified hemangioma of the diaphragm with increased 99mTc-hydroxymethylene diphosphonate uptake.

A 31-year-old woman visited an out-patient clinic, because of low-grade fever and general fatigue. She was referred to our hospital and admitted for examination of an abnormal shadow which had been found on the chest radiograph. She had experienced faint right lateral chest pain several times on the deep inspirations. Chest radiography showed a mass shadow with calcification in the right lower lung field on the mediastinal side. Chest radiographic computed tomography showed a 6x6 cm tumor in the right lung field. There were low-density areas with septae inside the tumor. Bone scintigraphy showed extremely high uptake of (99m)Tc-HMDP in the tumor. After surgical resection and pathological examination, we concluded that the tumor was an extensively calcified benign hemangioma of the diaphragm.

Adult↗

Immunoreactivity to various human cytochrome P450 proteins of sera from patients with autoimmune hepatitis, chronic hepatitis B, and chronic hepatitis C.

Numerous human Cytochrome P450 enzymes (CYPs) associated with 'phase I' drug metabolism have been identified. Among them, CYP2D6 is thought to be the major target autoantigen to anti-liver kidney microsome (LKM)-1 autoantibody, a characteristic feature of autoimmune hepatitis (AIH) type II. In this study, we were able to clone CYP2D6 cDNA from a human liver cDNA library and express the CYP2D6 recombinant protein, and also to prepare four other representative human CYP proteins (CYP1A2, 2C9, 2E1, and 3A4). These preparations were used to assay the immunoreactivity of patients with AIH type I (n=35) and type II (n=9). As comparison groups, sera from patients with chronic hepatitis B (n=15), chronic hepatitis C (n=55; 24 anti-LKM-1-positive, 31 anti-LKM-1-negative), and from normal controls (n=30) were included. The five CYP proteins did not react with sera from normal controls nor from patients with chronic hepatitis B. CYP2D6 reacted with sera from 100% (9/9) of AIH type II patients, 79% (19/24) of patients with anti-LKM-1-positive chronic hepatitis C, and 6.5% (2/31) of patients with anti-LKM-1-negative chronic hepatitis C. In contrast, CYP1A2 reacted with serum from one patient with AIH type I, CYP2E1 reacted with sera from two patients with AIH type I, one patient with anti-LKM-1-positive chronic hepatitis C, and two patients with anti-LKM-1-negative chronic hepatitis C, and CYP3A4 reacted with sera from one patient with AIH type II and one patient with anti-LKM-1-positive chronic hepatitis C. CYP2C9 did not react with any of the sera included in this study. From these results, it is suggested that CYPs other than CYP2D6 can function as immunotargets in certain disease conditions.

Adult↗

Quantitation of macrophage migration inhibitory factor (MIF) using the one-step sandwich enzyme immunosorbent assay: elevated serum MIF concentrations in patients with autoimmune diseases and identification of MIF in erythrocytes.

We raised monoclonal antibodies against human macrophage migration inhibitory factor (MIF), and developed a one-step sandwich enzyme-linked immunosorbent assay (ELISA) method highly specific for human MIF. The ELISA system utilizes a solid phase monoclonal antibody as a capture antibody and a horseradish peroxidase-conjugated monoclonal antibody as a detector antibody. We used this ELISA method to evaluate the serum level of MIF in 240 healthy volunteers (140 males and 100 females). We found no significant difference in MIF concentration with respect to age. A significant difference was found with respect to sex, with the mean value (+/- SD) for male subjects of 5.3+/-2.3, and that for female subjects of 4.6+/-2.3 ng/ml (p<0.05). We next measured the serum MIF contents of patients with autoimmune diseases, and found that MIF levels were significantly elevated in patients with systemic lupus erythematosus and rheumatoid arthritis, 20.0+/-11.0 ng/ml and 21. 7+/-11.2 ng/ml, respectively. Using anti-MIF antibody-immobilized sepharose column chromatography, we discovered for the first time that MIF was present in erythrocytes. Taken together these results suggest that MIF plays a major role in autoimmune diseases and, moreover, potentially induces various patho-logical outcomes in cases of hemolytic disorders.

Adult↗

Increased expression of NIPP-1 mRNA correlates positively with malignant phenotype in rat hepatomas.

In order to elucidate an involvement of protein phosphatase type 1 (PP1) in the malignant transformation, we have isolated rat cDNA for NIPP-1, a nuclear inhibitor for PP1. Rat NIPP-1 protein conserved the PP1 binding domain and the nuclear targeting sequence. The mRNA was ubiquitously expressed with the highest expression in bone marrow and thymus. The rat NIPP1 mRNA levels were slightly, if at all, increased in some primary hepatomas, and significantly increased in rat ascites hepatomas. The levels of NIPP-1 mRNA were closely correlated with malignant phenotype of rat ascites hepatomas, suggesting that NIPP-1 is tightly linked to malignant phenotype in hepatomas.

Amino Acid Sequence↗

Expression in hepatomas and chromosomal localization of rat protein phosphatase 5 gene.

The serine/threonine protein phosphatase type 5 (PP5) gene expression was ubiquitously observed among all the tissues examined, but being at the lowest level in the liver. The levels of PP5 mRNA were markedly elevated in rat highly malignant ascites hepatomas, while those in several rat primary hepatomas were slightly increased and those in the regenerating livers were not elevated at all compared to the control liver. The PP5 gene was mapped to rat chromosome 1q22.1. This region has been identified to have linkage homology among human, mouse and rat, and is known to be associated with several tumor types. Taken together, the present results strongly suggest important roles of PP5 in tumorigenesis.

Animals↗

[Intrascrotal tumors: a clinicopathologic study of 15 cases].

PURPOSE: We reviewed cases of intrascrotal tumors treated at our institution except for germ cell testicular tumors. PATIENTS AND METHODS: From 1977 to 1998 (22 years), 120 cases of intrascrotal tumors treated at the University of Tsukuba. Of these, 15 cases (12.5%) were not germ cell testicular tumors. The patients' ages varied between 2 and 77 years with a mean of 49.6. RESULTS: The most common complaint regarding symptoms was painless testicular enlargement. Tumor weight ranged from 2 to 200 g, with an average of 104.6 g. The histological diagnoses of 15 patients were 8 malignant lymphomas, 2 paratesticular rhabdomyosarcomas, 2 metastatic tumors (origin; stomach and prostate), 1 epidermoid cyst, 1 cyst of tunica testis, and 1 adenomatoid tumor. As for the cases with malignant lymphoma, all of them were non-Hodgkin's lymphoma whose clinical stages were stage I in 2 cases and stage IV in 6 cases. Five 8 patients died in spite of systemic chemotherapy after an orchiectomy, whereas 2 cases with metastatic tumors died of primary cancer, and two cases with paratesticular rhabdomyosarcoma are still alive and have had no evidence of disease. CONCLUSIONS: Intrascrotal tumors except for germ cell testicular tumors are not common, and consist of various diseases. In particular, some kinds of malignant lymphoma mimic anaplastic seminoma histopathologically. Therefore, accurate diagnosis and precise treatment is important in the patient with intrascrotal tumors.

Adolescent↗

[Substance isolated from the kelp rhizoid identified as L-tryptophan shows high inhibition of breast cancer].

In general, the root of a seaweed is poorly developed as compared with its thallus and is called the rhizoid or holdfast. In Laminaria, belonging to Phaeophyceae, although the thallus is used for food, the rhizoid is considered an unuseful natural resource. We attempted to detect anti-breast cancer substances from that resource. As a result, a substance having a weak absorptivity to aluminium oxide and Sephadex G-25 was found. According to analysis of the FAB-MS spectra and 1H NMR spectra, the substance was identified as tryptophan, an amino acid. Finally, it was concluded by a chiral column-HPLC method that the tryptophan was the L-form.

Antineoplastic Agents↗

Circulating levels of soluble CD30 are increased in patients with localized scleroderma and correlated with serological and clinical features of the disease.

OBJECTIVE: To determine serum soluble CD30 (sCD30) levels in patients with localized scleroderma. METHODS: Serum soluble CD30 levels were assayed by a sensitive ELISA in 55 patients with localized scleroderma, in 15 with systemic sclerosis (SSc), and in 20 healthy controls. RESULTS: Serum levels of sCD30 were significantly higher in patients with localized scleroderma than in healthy controls. Serum levels of sCD30 were correlated with the number of sclerotic lesions, the number of involved areas, levels of anti-histone antibody IgM, and levels of interleukin 6. sCD30 levels in sera from patients with SSc were also significantly higher than in healthy controls. CONCLUSION: These results suggest possible involvement of Th2 cells in the immunopathogenesis in localized scleroderma, and serum sCD30 levels may be helpful in following the outcome of the disease.

Adolescent↗

Indirect evidence of TTV replication in bone marrow cells, but not in hepatocytes, of a subacute hepatitis/aplastic anemia patient.

The presence of a new DNA virus (TTV) has been reported in sera from patients with posttransfusion hepatitis of unknown etiology. The precise replication site of TTV, however, has not been established. In this study, the presence of TTV in liver autopsy material, and in bone marrow biopsy and autopsy samples taken from a subacute hepatitis/aplastic anemia patient was determined by PCR and Southern blot analyses. Liver cells were found to contain only TTV DNA and not mRNA. Bone marrow material, especially that taken at biopsy, contained high levels of TTV DNA. It is suggested that the TTV replication site was in the bone marrow rather than in the liver, and that TTV infection was the cause of this patient's aplastic anemia. The precise etiological association of TTV with hepatitis remains to be established.

Adult↗

[MRI of ductal carcinoma in situ of the breast: patterns of findings and evaluation of disease extent].

Ten cases of ductal carcinoma in situ (DCIS) or DCIS with microinvasion were reviewed in order to evaluate the characteristic findings of DCIS and to evaluate the extent of disease on MRI. A 1.5Tesla Signa or Horizon (GE Medical Systems) unit was used with a dedicated receive-only breast coil. The pulse sequence based on RARE was used with the fat suppression technique. After examining both breasts with a large FOV (30 cm), the affected breast alone was examined with a smaller FOV (18 cm) and larger matrix (512 x 384) with and without Gd-enhancement. DCIS showed several types of findings on MRI: linear, spotty enhancement; gathering of linear enhancement; enhanced area or mass without distortion of the surrounding tissue; and well-circumscribed mass mimicking intraductal papilloma. Compared with typical findings of invasive carcinoma, DCIS tended to be enhanced slowly. After performing MR examination in addition to mammography and ultrasonography, a more accurate diagnosis of disease extent was possible in 6 of 10 patients. MRI was useful in providing more precise information on the disease extent of DCIS, and it is considered useful in planning the type of surgery. Further study using larger series and precise pathological correlations are necessary.

Adult↗

Serum levels of KL-6 as a useful marker for evaluating pulmonary fibrosis in patients with systemic sclerosis.

OBJECTIVE: KL-6 is a mucin-like glycoprotein that is strongly expressed on type II pneumocytes in the lung. Circulating KL-6 has been shown to be a sensitive marker of the disease activity of interstitial lung diseases. We determined the serum levels of KL-6 in patients with systemic sclerosis (SSc) and investigated whether these levels would serve as a useful marker of pulmonary fibrosis (PF) in patients with SSc. METHODS: The serum KL-6 levels were determined using a specific ELISA in 91 patients with SSc, and in 38 healthy controls. RESULTS: The serum levels of KL-6 were significantly higher in patients with SSc than in healthy controls (923+/-860 vs. 382+/-55 U/ml; p<0.0001). The serum KL-6 levels of the patients with diffuse cutaneous SSc (dSSc) tended to be higher than those with limited cutaneous SSc (ISSc) (1054+/-1000 vs. 800+/-694 U/ml), but there was no significant difference between these 2 groups. The serum KL-6 levels in the patients with PF were significantly elevated compared to those without PF (1283+/-1056 vs. 520+/-148 U/ml; p<0.0001). Moreover, DLCO and VC were also significantly decreased in the patients with elevated KL-6 levels compared to those with normal levels (62+/-22% vs. 72+/-17%, p<0.05; 87 +/-20% vs. 100+/-18%, p<0.01, respectively). CONCLUSION: Serum KL-6 level may be a useful serum marker for evaluating pulmonary fibrosis in patients with SSc.

Adult↗

[Persistent primitive trigeminal artery presenting with Weber's syndrome: report of a case with three-dimensional CT angiographic evaluations].

We report a rare case of persistent primitive trigeminal artery(PPTA) presenting with brain stem infarction known as Weber's syndrome, and document its unique findings of three-dimensional CT angiography(3 D-CTA). A 69-year-old woman was admitted to our hospital because of gait disturbance and blepharoptosis on the right eye. Neurological examination on admission revealed the right oculomotor nerve palsy, left hemiparesis and dysarthria, all of which indicated the signs and symptoms of Weber's syndrome. Initial CT scan revealed no abnormality, but a subsequent 3 D-CTA demonstrated the PPTA originating from the right internal carotid artery penetrate into the clivus directly to the distal basilar artery, on top of which a small saccular aneurysm was incidentally visualized. Right internal carotid angiograms showed the PPTA run between the cavernous segment of the internal carotid artery and the distal portion of the basilar artery with the filling of both the posterior cerebral and superior cerebellar arteries. However, the proximal portion of the basilar artery was visualized through the right vertebral artery and there was no blood flow to its distal portion. Evidence of infarction was finally confirmed at the right midbrain and thalamus by the MRI performed 5 days after the onset. With a conservative treatment including physical therapy, the patient recovered well from the deficits and could walk by herself with a cane. With regard to the pathogenesis of vertebrobasilar insufficiency in a patient with PPTA, it is generally considered that microembolus from an atherosclerotic carotid artery may be its cause because of the presence of direct communication between the anterior and posterior circulations. In the present case, however, this mechanism may not be applied since there was no evidence of atherosclerotic plaque or stenotic lesions on the carotid arteries. Alternatively, an embolic occlusion may have occurred in the paramedian branches of the posterior cerebral artery since a dilated PPTA itself, which resembled fusiform-aneurysm in appearance, may become the origin of microembolus.

Aged↗

[Two cases of methicillin-resistant Staphylococcus aureus (MRSA) sepsis following craniotomy].

We report here two cases of MRSA sepsis following craniotomy. In case 1, a petroclival meningioma was subtotally removed and lumbar drainage was inserted postoperatively to prevent cerebrospinal fluid leakage. Ventriculo-peritoneal shunt was performed after meningitis was treated with vancomycin and panipenem/betamipron. Two weeks after the procedure, the patient revealed continuous spiking fevers related to MRSA sepsis, which did not improve with vancomycin and arbekacin administration. The focus of infection was found by scintigraphy and CT by 67Ga to be spondylo-diskitis at the level of L2-L3. The lesion was removed and bone from the iliac crest grafted. In case 2, seven days after surgery for multiple meningioma, the patient exhibited spiking fevers and swelling in the left leg. The central venous catheter was removed from the left femoral vein and MRSA was found from blood culture. The patient was treated with arbekacin (200 mg/day). Venous thrombosis diagnosed by CT was treated with heparin. Symptoms related to the infection and laboratory data did not improve because the concentration of arbekacin in the blood did not reach an effective level. The symptoms markedly improved when the dose of arbekacin was doubled (400 mg/day).

Adult↗

[Efficacy of cibenzoline for chest oppression and ventricular arrhythmia during effort and alcohol consumption in a patient with hypertrophic obstructive cardiomyopathy: a case report].

A 67-year-old man presented with chest oppression and palpitation during effort and alcohol consumption. Echocardiography demonstrated asymmetric septal hypertrophy and systolic anterior motion of the anterior mitral leaflet with a pressure gradient of 80 mmHg across the left ventricular outflow tract (LVOT), leading to the diagnosis of hypertrophic obstructive cardiomyopathy. During the treadmill exercise test, blood pressure decreased with electrocardiographic ST-segment depression and subsequent frequent premature ventricular contractions. Holter-electrocardiographic monitoring also showed ST-segment depression with premature ventricular contractions during effort and alcohol consumption. Coronary angiography showed no abnormalities and cardiac catheterization at baseline showed a systolic pressure gradient of only 2 mmHg across the LVOT. However, the gradient increased to 33 mmHg after premature ventricular contraction, 27 mmHg at Valsalva maneuver and 75 mmHg with dobutamine infusion (5 micrograms/kg/min) and disappeared with 70 mg of intravenous cibenzoline. Medication with cibenzoline (300 mg/day) for one month reduced the LVOT gradient at rest to 53 mmHg and strikingly improved symptoms and exercise tolerance and also suppressed premature ventricular contractions during exercise and alcohol consumption. We conclude that cibenzoline was effective for reduction of LVOT gradient both at rest and during exercise and alcohol consumption.

Administration, Oral↗

[Recent advances in surgical treatment for primary lung cancer].

In the last 10 years, the treatment of primary lung cancer have remarkably changed and advanced. Concerning surgical treatment we have seen the introduction of thoracoscopic surgery; intentional limited resection of peripheral small lung cancer; increased number of reoperation cases for recurrence and second primary tumors in resected lung cancer; as well as developments and improvements in new anticancer drugs and their adoption to adjuvant therapy and surgical treatments. Now, we'll report four points of recent changes and advances in surgical treatment for lung cancer.

Adenocarcinoma↗