Biomedical subjects
K Yano
Publications and source records attributed to K Yano.
A case of tuberous sclerosis with a giant angiofibroma.
This is a case study of tuberous sclerosis with unusually large facial angiofibromas. The patient had other intense skin manifestations. Histological findings in the angiofibroma included large and glial-appearing cells specific for this disease. Karyotype analysis revealed a translocation of chromosome (12q-, 15q+).
The induction of cytotoxic T lymphocytes against HLA-A locus-matched lung adenocarcinoma in patients with non-small cell lung cancer.
To induce cytotoxic T lymphocytes (CTL) against non-small cell lung cancer (NSCLC) efficiently, the induction of CTL was attempted using HLA-A locus-shared allogeneic NSCLC cells. T cells derived from either tumor tissue specimens or the regional lymph nodes of patients with NSCLC were stimulated twice or three times with an HLA-A2/A24-positive NSCLC cell line (PC-9), and thereafter the cytotoxic activity was examined by 51Cr-release assay. In patients with HLA-A24/ adenocarcinoma, anti-PC-9 cytotoxicity was induced in all 6 patients tested. Anti-PC-9 cytotoxicity was induced in 2 out of 5 patients with HLA-A2 (A24-)/adenocarcinoma, in 2 out of 4 patients with HLA-A24/squamous cell carcinoma, and 1 of 2 patients with HLA-A2/squamous cell carcinoma. The cytotoxic activity was observed to kill PC-9 selectively, not other NSCLC lines, and the activity was substantially blocked by anti-MHC class I antibody, but not by anti-MHC class II antibody. The PC-9-specific CTL produced gamma-interferon in response to autologous tumor cells. These results indicated that the anti-PC-9 cytotoxicity was mediated by cytotoxic T lymphocytes that may recognize the T cell epitope(s) shared and presented by HLA-A2 and/or HLA-A24-positive NSCLC.
Frequent occurrence of hepatocytic apoptosis in acute rejection of the grafted rat liver.
The present study was conducted to examine the histopathological changes of rat liver grafts in the early post-transplantation period. A total of 44 orthotopic liver transplantations were performed using cuff techniques without anastomosis of the hepatic artery. They were divided into four groups: (i) group 1 (syngeneic, Lewis-->Lewis; n = 10); (ii) group 2 (allogeneic, ACI-->Lewis; n = 20); (iii) group 3 (allogeneic with immunosuppression, ACI-->Lewis; n = 12); and (iv) long-surviving grafts (PVG-->Lewis; n = 2). The histological findings were classified into four categories: (i) mild dilatation of Disse's spaces due to ischemia; (ii) bile duct proliferation; (iii) acute rejection; and (iv) zonal necrosis. Bile duct proliferation occurred on day 6 in all three groups and in one of the two long-surviving grafts (120 days). Acute rejection occurred on day 3 and progressed in groups 2 and 3. Zonal necrosis developed in group 2 after day 6, while acute rejection subsided after day 4 in group 3 receiving 15-deoxyspergualin. A few single cell deaths or acidophilic bodies were variably noted. Most of these cells showed signals by in situ nick end-labeling in their nuclei, implying the cells were undergoing apoptosis. The number of apoptotic hepatocytes increased as the progress and decreased with the regression of acute rejection in group 3. Thus, the extent of hepatocytic apoptosis may reflect the magnitude of acute rejection. More frequent distribution of apoptotic hepatocytes in periportal areas suggests that apoptosis may be induced by a variety of pathological stimuli, including the direct cytotoxic effects of lymphocytes, various cytokines and local circulatory disturbances.
Purification and cloning of a proline 3-hydroxylase, a novel enzyme which hydroxylates free L-proline to cis-3-hydroxy-L-proline.
Proline 3-hydroxylase was purified from Streptomyces sp. strain TH1, and its structural gene was cloned. The purified enzyme hydroxylated free L-proline to cis-3-hydroxy-L-proline and showed properties of a 2-oxoglutarate-dependent dioxygenase (H. Mori, T. Shibasaki, Y. Uosaki, K. Ochiai, and A. Ozaki, Appl. Environ. Microbiol, 62:1903-1907, 1996). The molecular mass of the purified enzyme was 35 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The isoelectric point of the enzyme was 4.3. The optimal pH and temperature were 7.0 and 35 degrees C, respectively. The K(m) values were 0.56 and 0.11 mM for L-proline and 2-oxoglutarate, respectively. The Kcat value of hydroxylation was 3.2 s-1. Determined N-terminal and internal amino acid sequences of the purified protein were not found in the SwissProt protein database. A DNA fragment of 74 bp was amplified by PCR with degenerate primers based on the determined N-terminal amino acid sequence. With this fragment as a template, a digoxigenin-labeled N-terminal probe was synthesized by PCR. A 6.5-kbp chromosome fragment was cloned by colony hybridization with the labeled probe. The determined DNA sequence of the cloned fragment revealed a 870-bp open reading frame (ORF 3), encoding a protein of 290 amino acids with a calculated molecular weight of 33,158. No sequence homolog was found in EMBL, GenBank, and DDBJ databases. ORF 3 was expressed in Escherichia coli DH1. Recombinants showed hydroxylating activity five times higher than that of the original bacterium, Streptomyces sp. strain TH1. It was concluded that the ORF 3 encodes functional proline 3-hydroxylase.
Phe576 plays an important role in the secondary structure and intracellular signaling of the human luteinizing hormone/chorionic gonadotropin receptor.
Recent studies have identified multiple activating mutations in the sixth transmembrane domain of LH/chorionic gonadotropin receptor (LH/CGR) in patients with male-limited precocious puberty. Computer analysis suggested that these mutations had an effect on the secondary structure of the third cytoplasmic loop and sixth transmembrane domain, and that Phe576 was a critical conformational bridging residue between these regions that might be important for receptor activity. We made four amino acid substitutions of the Phe576 (F576I, F576G, F576Y, F576E) in the LH/CG receptor to analyze its functional role. Computer analysis of secondary structure predicted that the F576E mutant changed the secondary structure to a totally helical conformation in the region of the third intracellular and sixth transmembrane domain. In contrast, the F576G, F576I, and F576Y mutants were predicted to change the helical conformation in the region to an extended conformation. In expression studies, mutations of Phe576 produced functional changes in cAMP and inositol phosphate (IP) signaling, and human CG (hCG) binding. Mutations predicted to cause an extended conformation exhibited two functional patterns: first, constitutively activating in cAMP signaling without changes in IP signaling or hCG binding (F576I and F576G), and second, constitutively activating in cAMP signaling with decreased hCG-induced cAMP and IP signaling and with both higher affinity and lower capacity of hCG binding (F576Y). The mutation predicted to cause a totally helical conformation resulted in no cAMP response and a minimal IP response to hCG stimulation, with negligible hCG binding (F576E). These data suggest that the common change induced by the F576I, F576G, and F576Y mutations to an extended conformation on the third cytoplasmic loop and sixth transmembrane domain of the LH/CGR results in increased Gs coupling and activation of adenylyl cyclase. The F576Y mutation appears to have an additional effect, beyond a modification in receptor conformation, that leads to higher affinity and lower capacity of hCG binding, as well as altered Gq coupling and phospholipase C activation. The F576E mutation has a distinct and different impact on receptor conformation, which leads to negligible hCG binding and minimal function; however, the F576E mutation may provide a clue to understanding the receptor mutations that result in loss of function and pseudohermaphroditism. We conclude that Phe576 plays an important role in the human LH/CGR with respect to receptor conformation, Gs coupling, and cAMP signaling consistent with predictions from mutations associated with male-limited precocious puberty.
Direct detection of Campylobacter jejuni in chicken cecal contents by PCR.
Campylobacter jejuni in chicken feces was detected by PCR and Southern blot hybridization (SBH). The detection limits of C. jejuni in chicken feces were 34,000 cells by PCR and 340 cells by SBH. Some cecal contents of chickens up to 3 weeks old were C. jejuni positive by SBH whereas all of them were negative by PCR. Two of 51 cecal contents of 18-day-old chicken embryos were C. jejuni positive by PCR and SBH; but, C. jejuni were not isolated from the samples by conventional culture with selective enrichment.
Calculation of mitral valve area in mitral stenosis using the proximal isovelocity surface area method. Comparison with two-dimensional planimetry and Doppler pressure half time method.
Two-dimensional echocardiographic (2-D) planimetry and the Doppler pressure half-time (PHT) method have been used to estimate mitral valve area (MVA) in patients with mitral stenosis (MS). Recently, the proximal isovelocity surface area (PISA) method has been shown to be accurate for calculating MVA. The purpose of this study was to compare the PISA method with previous methods. Thirty patients with MS were studied; 17 had pure MS, 4 combined mild MR, 6 combined mild AR, and 3 combined MR and AR. Color Doppler flow mapping was performed at an aliasing (blue-red interface) velocity of 14 cm/sec using the zero-baseline shift. MVA was calculated as 2 x 3.14 x R2 x 14 x (theta/180) / PFV, where R is the distance from aliasing to orifice, 14 is the aliasing velocity, theta is the internal angle of the mitral valve, and PFV is the peak flow velocity at the mitral orifice. MVA was also calculated using the 2-D and PHT methods, and compared with the PISA method. MVA calculated using the PISA method correlated well with the 2-D (r=0.90, p < 0.01, SEE = 0.18 cm2) and PHT methods (r=0.82, p < 0.01, SEE = 0.24 cm2). Compared with the 2-D method, the standard error of the estimate of the PISA method was - 0.14+/-0.18 cm2 and the percent error was -10.4+/-18.9%. Compared with the PHT method, the standard error of the estimate of the PISA method was + 0.01+/-0.24 cm2 and the percent error was +3.4+/-34.6%. MVA calculated using the PISA method correlated well with the 2-D and PHT methods in patients with pure MS or with MS combined mild regurgitation. The PISA method may be useful for calculating MVA as an alternative method.
Relationship between serum antibody levels and subgingival colonization of Porphyromonas gingivalis in patients with various types of periodontitis.
Porphyromonas gingivalis is considered to be an important pathogen in periodontitis. The present study investigates the relationship between serum anti-P. gingivalis IgG antibody levels and the subgingival distribution of P. gingivalis in patients with periodontitis. We examined subgingival plaque samples from 15 patients with adult periodontitis (AP), 8 patients with early-onset periodontitis (EOP), and 6 clinically healthy individuals. The samples were collected from periodontal pockets or gingival crevices of all remaining teeth in each subject. The total number of samples was 3,024, ranging from 76 to 120 per subject. Probing depth and bleeding at each sample site were recorded. P. gingivalis was detected using a non-radioactive whole genomic DNA probe. Serum samples were taken from the subjects, and the serum anti-P. gingivalis IgG antibody titer was determined by enzyme-linked immunosorbent assay (ELISA). P. gingivalis was recovered from all AP and EOP patients, and from 3 of the 6 healthy subjects. Two significant positive correlations were observed among the subjects. The serum anti-P. gingivalis IgG antibody titer correlated with detection frequency of P. gingivalis, and the antibody titer correlated with the amount of P. gingivalis detected. Higher levels of P. gingivalis were detected in the EOP group than in the AP group. However, no significant difference was found in the serum IgG titer levels between EOP and AP patients. These findings suggest a direct relationship between the serum anti-P. gingivalis IgG levels and subgingival P. gingivalis colonization; however, the functional capabilities of IgG antibodies may vary among the various types of periodontitis patients.
Three-dimensional computed tomography imaging of a frontal skull base fracture.
A 7-year-old boy presented with recurrent meningitis after head trauma. Coronal computed tomography (CT) revealed prolapse of the intracranial soft tissue into the right ethmoidal sinus, leading to the diagnosis of right frontal skull base fracture. Three-dimensional CT with bone windows provided a lifelike image of the fracture lateral to the right olfactory groove. This image was most useful in the preoperative planning of the repair surgery.
[Bilateral leg ulcers with pathologic evidence of small vessel vasculitis by skin biopsy during hydroxyurea therapy of chronic myelogenous leukemia].
We report a 45-year-old male with chronic myelogenous leukemia (CML) who experienced skin ulcers of the left lateral malleolus and dorsum of both feet. He had been treated with hydroxyurea (HU) for 2 years. His leg ulcers improved after HU was discontinued. Skin biopsy of the ulcerated lesion revealed that the lesion is compatible with small vessel vasculitis, but circulating immune complexes (C1q, anti-C3d antibody) were negative. Although the precise mechanism of the skin ulcer is unknown, we must take into consideration the skin changes were secondary to hydroxyurea therapy in myeloproliferative disorders.
[The functional analysis of LH receptor].
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Prevention of venous air embolism by jugular venous compression under superior sagittal sinus pressure monitoring in a brachycephalic patient during craniofacial reconstruction.
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An aneurysm of the right gastroepiploic artery.
A palpable mass was unexpectedly found in the upper abdomen of a 67-year-old woman. Computed tomography (CT) and abdominal angiography both indicated an aneurysm of the right gastroepiploic artery. An aneurysmectomy was performed, and the aneurysm was found to be spherical with a diameter of 7.5 x 7.7 cm. The patient was eventually discharged in good condition. The histological findings of the aneurysmal wall revealed medial fibrosis and atherosclerosis. Gastroepiploic artery aneurysms are rare among splanchnic artery aneurysms and most such aneurysms are found to be ruptured. The present report described a quite rare case of an asymptomatic giant gastroepiploic artery aneurysm and also includes a review of the 10 reported cases of gastroepiploic artery aneurysms in the English literature to date. Since gastroepiploic artery aneurysms have a high risk of rupture it is essential that appropriate surgical measures be taken immediately.
Production of macrophage inflammatory protein-1alpha by human mast cells: increased anti-IgE-dependent secretion after IgE-dependent enhancement of mast cell IgE-binding ability.
The contributions of mast cells to the pathology of allergic diseases, as well as to the expression of immunoglobulin E (IgE)-dependent host responses to parasites, reflect both the amounts and types of cytokines and other mediators that are released by these cells in such settings. Whereas mast cells cannot intrinsically express immunologically specific functions, the binding of IgE to high-affinity IgE receptors (Fc epsilonRI) on the surface of mast cells primes these cells to secrete cytokines and other biologically active products upon subsequent exposure to specific antigens. We now report that both HMC-1, a growth factor-independent human mast cell leukemia cell line, and growth factor-dependent human umbilical cord blood-derived mast cells can secrete the multifunctional C-C chemokine, macrophage inflammatory protein-1alpha (MIP-1alpha). In addition, we found that in vitro exposure of human umbilical cord blood-derived mast cells to concentrations of IgE within the range observed in the serum of subjects with allergic diseases or parasite infections, which markedly up-regulates the ability of these cells to bind IgE to their surface, also significantly enhances the ability of the cells to secrete MIP-1alpha upon subsequent passive sensitization with IgE and challenge with anti-IgE. Thus, IgE-dependent enhancement of human mast cell IgE-binding ability permits these cells to respond to Fc epsilonRI-dependent challenge with significantly increased secretion of MIP-1alpha, a chemokine that can have diverse functions in inflammation, allergic reactions, and host responses to infection.
[Coronary microvascular dysfunction in coronary artery disease associated with glucose intolerance].
Coronary flow reserve is used as an indicator to assess coronary microvascular function in the absence of obstructive coronary atherosclerosis. Diabetic patients, even with angiographically normal coronary arteries, show significantly reduced coronary flow reserve. This study evaluated coronary microcirculation in coronary artery disease complicated by glucose intolerance. Thirty-three patients with coronary artery disease were divided into three groups: Fourteen patients without glucose intolerance (control group), 8 with impaired glucose tolerance (IGT group), and 11 with noninsulin dependent diabetes mellitus (DM group). A Doppler guide wire was used to measure phasic coronary blood flow velocity in the left anterior descending artery without significant stenosis (> or = 40% diameter narrowing). Coronary flow reserve was determined by intracoronary 10 mg papaverine hydrochloride administration which induced maximal hyperemia. Coronary flow reserve was decreased in the DM group compared with the control group (2.1 +/- 0.6 vs. 3.1 +/- 0.9, p = 0.004), and that in the IGT group (2.5 +/- 0.9) did not show a significant difference compared with the other two groups. Vessel characteristics, such as infarct- or noninfarct-related artery and previous coronary angioplasty, did not have an influence on the results. Other coronary risk factors, left ventricular function, and hemodynamic findings were comparable in the three groups. This study demonstrates that diabetes mellitus may cause functional microvascular abnormalities in coronary artery disease.
[Estimation of 123I-metaiodobenzylguanidine lung uptake in heart and lung diseases--with reference to lung uptake ratio and decrease of lung uptake].
123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was performed in 64 patients with heart and lung diseases. Distribution of MIBG in the chest was evaluated by planar images, using counts ratios of the heart to the mediastinum (H/M) and the unilateral lung to the mediastinum (Lu/M). Most of patients with heart diseases showed obvious lung uptake of MIBG. The ratios of H/M were 1.75 +/- 0.20 in the group without heart failure and 1.55 +/- 0.19 in the group with heart failure. The ratios of Lu/M in the right and left lung were 1.56 +/- 0.16 and 1.28 +/- 0.16 in the group without heart failure. And those were 1.45 +/- 0.16 and 1.19 +/- 0.15 in the group with heart failure. But 3 patients complicated with chronic pulmonary emphysema and one patient with interstitial pneumonia due to dermatomyositis showed markedly decreased lung uptake. The ratios of Lu/M in the right and left lung of these patients were 1.20, 1.17; 1.17, 1.13; 1.01, 0.97 and 1.27, 0.94, respectively. These results suggest that the lung uptake of MIBG may reflect the state of pulmonary endothelial cell function in clinical situations, considering that it has been demonstrated that MIBG may be useful as a marker of pulmonary endothelial cell function in the isolated rat lung.
[Myocardial scintigraphic studies with 123I-MIBG, 201Tl and 99mTc-PYP in patients with cardiac amyloidosis].
Myocardial scintigraphic studies, using 123I-metaiodobenzylguanidine (MIBG), 99mTc-pyrophosphate (PYP) and 201Tl were performed in 4 patients with cardiac amyloidosis. In MIBG myocardial images, 2 patients with familial amyloid polyneuropathy (FAP) showed complete or partial defect and the other 2 with primary amyloidosis had normal myocardial uptake of MIBG. In PYP myocardial images, diffuse myocardial uptake of PYP was mild in 2 patients with FAP and moderate in the other 2. 201Tl myocardial images revealed normal myocardial uptake of 201Tl in 2 patients with FAP and 1 with primary amyloidosis, and intense myocardial uptake in the other one with primary amyloidosis. These results suggest that myocardial scintigraphies with PYP and 201Tl may be useful for the detection of cardiac amyloidosis and estimation of its pathophysiology. And MIBG myocardial scintigraphy may provide useful information about sympathetic nerve abnormalities which vary with type of the fibril protein, clinical syndromes and disease process of cardiac amyloidosis.