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Biomedical subjects

H Kojima

Publications and source records attributed to H Kojima.

At least 199 records · Page 11Linked to original sources

Varicella-zoster virus-specific cellular immunity in subjects given acyclovir after household chickenpox exposure.

The time course of primary cell-mediated immune responses to varicella-zoster virus (VZV) among persons receiving acyclovir prophylaxis after exposure to chickenpox has not been well defined. Fifteen children who had household exposure to varicella received prophylactic acyclovir (40 mg/kg/day for 7-14 days after exposure) and were studied for development of both antibody and cell-mediated immunity (CMI) to VZV. Twelve developed antibodies and/or CMI; 10 had no symptoms and 2 manifested mild varicella. Two were already immune to varicella and had booster immune responses. One was not infected and subsequently developed full-blown varicella. Although acyclovir given after exposure to VZV is highly effective and does not appear to attenuate the immune response, it remains necessary to confirm whether, in the absence of clinical varicella, persons acquire specific immunity.

Acyclovir↗

Roles of cytokines and cell cycle regulating substances in proliferation of cholesteatoma epithelium.

OBJECTIVES: It can be surmised that the cell cycle must be involved in cell proliferation of the epithelium of middle ear cholesteatoma. Thus a comparative study was conducted of the levels of expression of cyclin-dependent kinase 2 (cdk2) and cyclin-dependent kinase 4 (cdk4)-substances known to be involved in the cell cycle-in cholesteatoma epithelium and the normal epithelium of the bony region of the external ear canal. In addition, it has been reported that the expression of cytokines in the epithelium is accelerated in response to subepithelial inflammation. This suggests that an interaction between the epithelium and subepithelium, which is subject to paracrine regulation, is deeply involved in epithelial proliferation. Accordingly, attention was focused on interleukin-1alpha (IL-1alpha) and keratinocyte growth factor (KGF), cytokines which are found in the subepithelium, and experiments were conducted to elucidate their effects on the expression of the substances known to be involved in the cell cycle. METHODS: The expressions of cdk2 and cdk4 in the cholesteatoma epithelium and external ear canal epithelium were investigated by an immunohistochemical technique. In addition, cultured human keratinocytes were grown in medium containing IL-1alpha or KGF at concentrations of 0, 20, and 100 ng/mL, and the differences in the expression of cdk2 and cdk4 were investigated and compared by Western blot analysis. RESULTS: In the cholesteatoma epithelium specimens, cdk2 and cdk4 were observed to be expressed in the basal and parabasal layers and in the upper layer (prickle layer and granular layer). Their expression tended to be increased compared with their expression in the normal external ear canal epithelium, and this tendency was marked in subepithelial sites showing severe inflammation. In addition, exposure of cultured human keratinocytes to IL-la or KGF resulted in accelerated expression of both cdk2 and cdk4, and this was especially striking in the case of addition of KGF. CONCLUSION: It can be surmised that, in cholesteatoma, accelerated expression of IL-1alpha and KGF by inflammatory cells at subepithelial sites of inflammation leads to upregulation of cdk2 and cdk4 in epithelial cells and to cell proliferation. It was concluded that this is at least one sequence of events involved in the mechanism causing epithelial proliferation in cholesteatoma.

Adult↗

Terminal differentiation of epithelial cells in middle ear cholesteatoma: investigation of patterns of expression of protein kinase C-delta and protein kinase C-eta.

OBJECTIVES: The objective of this study was to elucidate the differentiation mechanism of keratinocytes in cholesteatoma. STUDY DESIGN: To achieve the objective, we analyzed the expressions of various cellular proteins: the delta and eta isoforms of protein kinase C (PKCdelta and PKCeta), which are thought to play key roles in signal transduction in differentiation; cytokeratin 1 (CK1) and cytokeratin 10 (CK10) (cytoskeletal constitutive proteins); and involucrin (a marker of differentiation). METHODS: The materials used in this study were tissue specimens obtained from cholesteatoma epidermis, normal external ear canal skin, normal inguinal skin, and psoriatic skin. Immunohistochemical staining techniques were applied to compare the expressions of the above proteins (i.e., PKCdelta, PKCeta, CK1, CK10 and involucrin) in those various tissues. RESULTS: No clear differences in the patterns of expression of PKCdelta and PKCeta were found between the cholesteatoma epidermis and the normal external ear canal skin. These proteins were expressed mainly in the stratum spinosum and stratum granulosum, and their patterns of expression were almost the same as those of the CK1, CK10, and involucrin proteins. CONCLUSION: The findings of this study indicate that the terminal differentiation of keratinocytes in the cholesteatoma epidermis is the same as in normal skin tissues. It was concluded that the growth of epidermis which has undergone hyperproliferation of keratinocytes because of increased levels of various cytokines is being regulated by means of normal terminal differentiation.

Adult↗

Proposed classification of nonatherosclerotic cerebral fusiform and dissecting aneurysms.

OBJECTIVE: The aim of this study is to classify nonatherosclerotic aneurysms unrelated to the branching zones (including fusiform aneurysms and dissecting aneurysms). METHODS: Damage to the internal elastic lamina (IEL) is often an associated factor in the pathogenesis of aneurysm formation. In this study, 85 nonatherosclerotic aneurysms arising from an arterial trunk unrelated to the branching zones were classified into four different types, based on the lesional patterns of the IEL and the state of the intima. Type 1 corresponded to classic dissecting aneurysms, the pathogenesis of which was characterized by acute widespread disruption of the IEL without intimal thickening. Patients with Type 1 aneurysms had an ominous clinical course, and many presented with sudden subarachnoid hemorrhage with frequent rebleeding. Type 2 aneurysms were segmental ectasias, which had an extended and/or fragmented IEL with intimal thickening. Weakness of the arterial wall caused by the damaged IEL was assumed to be compensated by the intimal thickening. The luminal surface of the thickened intima was smooth without thrombus formation. The patients with Type 2 aneurysms had a placid clinical course. Type 3 aneurysms were dolichoectatic dissecting aneurysms, pathologically characterized by fragmentation of the IEL, multiple dissections of thickened intima, and organized thrombus in the lumen. Most of them were symptomatic and progressively enlarged over time. Type 4 aneurysms were saccular aneurysms unrelated to the branching zones. They arose in areas with minimally disrupted IEL without intimal thickening, and there was a risk of rupture. CONCLUSION: There was a strong relationship between the pathological features of the aneurysms and their clinical courses. This classification may provide a rationale for modes of treatment.

Adult↗

Prognostic factors in severe alcoholic liver injury. Nara Liver Study Group.

Severe alcoholic liver injury has been relatively rare, but is gradually increasing in Japan. The clinical features and prognostic factors in severe alcoholic liver injury were retrospectively investigated in 105 patients, consisting of 3 with severe alcoholic hepatitis (SAH), 43 with cirrhosis with superimposed alcoholic hepatitis [liver cirrhosis (LC)+alcoholic hepatitis (AH)], 38 with AH, and 21 with alcoholic cirrhosis. Seven of the 105 patients (6.7%, 2 with SAH and 5 with LC+AH) died of hepatic failure. Patients with SAH showed severe hyperbilirubinemia, reduced hepatic biosynthetic capacity, and marked acute inflammatory reactions, and developed multiple organ failure, such as disseminated intravascular coagulation (DIC), renal failure, acute pancreatitis, or pneumonia. Two SAH patients died within 1 month, whereas five with LC+AH died within 77 days during the second episode of AH. In these nonsurvivors, the serum total bilirubin (T.Bil) level was not normalized, and the hepaplastin test (HPT), serum albumin, cholesterol, and platelet count were not markedly improved after the first episode of AH. In the survivors, elevation of AST lasted longer, and the improvement of T.Bil, hepatic biosynthetic capacity, and the platelet count were much less in patients with LC+AH than in those with AH. Multivariate analysis using the Cox proportional hazards model showed serum C-reactive protein (CRP) and DIC as significant independent prognostic factors among SAH, LC+AH, and AH groups. When factors related to multiple organ failure, such as DIC and renal failure, were excluded, T.Bil and CRP were selected as independent prognostic factors. In patients with LC+AH and AH, CRP, and HPT were shown to be significant independent prognostic factors. These results suggest that SAH with multiple organ failure, and another episode of AH in advanced LC with hyperbilirubinemia and reduced hepatic biosynthetic capacity, are indicative of an extremely poor prognosis in chronic alcoholics.

Adult↗

ATP binding cassette transporter retina genotypes and age related macular degeneration: an analysis on exudative non-familial Japanese patients.

AIM: To determine whether mutations in the Stargardt's disease gene, ATP binding cassette transporter retina (ABCR) affect the occurrence of age related macular degeneration (AMD) in Japanese non-familial patients. METHODS: 80 unrelated Japanese patients with AMD (67 males and 13 females; mean age, 67.2 years) diagnosed by indocyanine green angiography and 100 age matched control subjects were studied. Among the AMD patients, 70 (87.5%) had choroidal neovascularisation of exudative type. Genomic DNA was purified from the total blood and 10 exons (exons 11, 23, 29, 32, 34, 37, 41, 43, 44, and 49) that have been reported to contain AMD associated mutations were amplified by polymerase chain reaction (PCR). The amplicons were analysed by the single strand conformation polymorphism (SSCP) method. The nucleotide sequencing of the amplicons was determined when necessary. RESULTS: Of the 10 exons, aberrant patterns of SSCP were detected in three exons-exons 29, 41, and 43. In exon 29, an aberrant pattern was found in seven of 80 patients (8.8%) and eight of 100 controls (8%). Sequencing of the PCR products revealed a heterozygous T1428M mutation which has been previously reported as one of the AMD associated mutations. Statistical analysis showed that there was no significant difference in the occurrence of this mutation between these AMD patients and the control groups (p = 0.86). In exons 23, 41, and 43, polymorphisms and sequence variations were found. CONCLUSION: No data to support the association between the ABCR gene mutations and AMD of Japanese patients, especially that of the exudative type, were obtained in this molecular genetic analysis.

ATP-Binding Cassette Transporters↗

High prevalence of anti-hepatitis B virus serological markers in patients with hepatitis C virus related chronic liver disease in Japan.

BACKGROUND/AIMS: Evidence is accumulating that hepatitis B virus (HBV) is present in patients who are hepatitis B surface antigen negative but have antibody to hepatitis B core antigen (anti-HBc). Furthermore, recent studies have shown that patients with hepatocellular carcinoma who have antibody to hepatitis C virus (HCV) often possess HBV related serological markers. Data on the seroprevalence of HBV infection in patients with HCV related chronic liver disease were collected to evaluate the significance of the presence of antibodies to HBV. METHODS: The prevalence of HBV related serological markers was analysed in a total of 2014 Japanese patients with HCV infection. The control group comprised 352 subjects without liver disorder. RESULTS: A large number of patients (49.9%) with HCV related chronic liver disease including hepatocellular carcinoma were positive for anti-HBc. In addition, the prevalence of anti-HBc closely correlated with the clinical stage of the liver disease. There was no relation between a past history of blood transfusion and the prevalence of anti-HBc. Notably, anti-HBc was the only serological marker for HBV infection in a significant number of patients with HCV related chronic liver disease (24.1%). CONCLUSIONS: Our data provide further evidence for the high prevalence of anti-HBc in patients with HCV related chronic liver disease, particularly those with hepatocellular carcinoma, suggesting that HBV infection, probably including latent infection, may play an important role in carcinogenesis in these patients.

Adult↗

Endothelium-specific activation of NAD(P)H oxidase in aortas of exogenously hyperinsulinemic rats.

To examine the effects of chronic hyperinsulinemia on vascular tissues, we examined the production of superoxide anion (O(-2)) in the aortic tissues of control and exogenously hyperinsulinemic rats performed by the implantation of an insulin pellet for 4 wk. O(-2) production by aortic segments from hyperinsulinemic rats was 2. 4-fold (lucigenin chemiluminescence method) and 1.7-fold (cytochrome c method) of that of control rats without any differences in O(-2) degrading activities in aortic tissues, respectively (P < 0.025). The increment was completely abolished in the presence of either 100 micromol/l apocynin (an inhibitor of NADPH oxidase) or 10 micromol/l diphenyleneiodonium (an inhibitor of flavin-containing enzyme) and was exclusively endothelium dependent. Consistently, NAD(P)H oxidase activities in endothelial homogenate in hyperinsulinemic rats were dose dependently stimulated above the values of control rats, although these activities in nonendothelial homogenate were not significantly stimulated by insulin. Furthermore, an insulin effect was also demonstrated 1 h after exposing aortic tissues to insulin. These results indicate that O(-2) production specifically increases in endothelium of aortic tissues in chronic hyperinsulinemic rats through the activation of NAD(P)H oxidase.

Animals↗

Incidence and risk factors of benign creatine phosphokinase elevations in chronic psychiatric patients.

There have been few studies focusing on the creatine phosphokinase (CPK) elevations in chronic psychiatric patients. The survey was conducted prospectively to investigate the incidence and risk factors of CPK elevations in chronic psychiatric patients during a 2-year follow-up period. Sixteen of 32 (50%) patients had maximums of more than 230 U/l (upper limit of our normal range) and 7 (22%) patients had maximums of more than 500 U/l. Surprisingly, 4 (13%) patients had maximums of more than 1,000 U/l after exercises such as swimming and walking. Nonetheless, none of the 16 patients with the CPK elevations developed severe conditions such as rhabdomyolysis despite an absence of therapeutic intervention, and their CPK elevations were proven to be benign. According to the path analysis, usual physical activity and neuroleptic doses seemed to underlie CPK elevations directly. The present findings suggest that not a few chronic psychiatric inpatients may have at least one CPK elevation per 2 years. Patients engaging in more physical activity or receiving higher neuroleptic doses are at greater risk of developing such CPK elevations. However, most of these increases are benign, and it is not considered necessary to treat them.

Adult↗

Anatomic study for posterior medialization thyroplasty.

To attain posterior medialization by thyroplasty type I, we simulated the surgery using 3 cadaveric larynges. Two approaches were applied to adduct the arytenoid cartilage: one involved compression of the vocal process, and the other, compression of the muscular process inward. The inner perichondrium was incised to reach the arytenoid cartilage from the framework. To compress the vocal process, a large silicone plug was required. In this method, there was some difficulty in compressing the vocal process precisely, and there was the risk of postoperative extrusion of the large plug. In contrast, the muscular process was more superficial relative to the framework, and it could be precisely compressed, resulting in sufficient posterior glottal closure. The silicone plug required for this procedure has a shallow depth that may provide the advantage of preventing postoperative extrusion. In conclusion, the compression of the muscular process is preferable for safely achieving posterior glottal closure.

Arytenoid Cartilage↗

Interaction among the subunits of Golgi membrane mannosyltransferase complexes of the yeast Saccharomyces cerevisiae.

Saccharomyces cerevisiae Mnn9 protein is a type II Golgi membrane protein which concerns in protein mannosylation. When solubilized by Triton X-100, it was recovered in two distinct complexes both having mannosyltransferase activity; one with Van1 protein (V-complex) and the other with Anp1, Hoc1, Mnn10, and Mnn11 proteins (A-complex). Characterization of the null mutants suggested that A-complex is also concerned in protein O-glycosylation. A-complex was more resistant than V-complex to dissociating conditions. Interaction between the lumenal domains of Van1 and Mnn9 was detected by a two-hybrid experiment. The anchor domain of Mnn9 protein could be replaced with other membrane anchors without losing the ability to form complexes similar to V- and A-complexes. Thus the lumenal domains are important to assemble these distinct complexes.

Fungal Proteins↗

Low phagocytic activity of resident peritoneal macrophages in diabetic mice: relevance to the formation of advanced glycation end products.

Formation of advanced glycation end products (AGEs) is accelerated in diabetic subjects along with hyperglycemia. Although several lines of evidence indicate that AGEs stimulate macrophages to secrete several cytokines and growth factors, little is known about the effect of AGEs on the primary function of macrophages, such as phagocytosis. On the other hand, impairment of the phagocytic function of monocytes/macrophages is suggested to contribute to the low resistance to infection in diabetic subjects. In the present study, we examined the effect of AGEs on the phagocytic function of macrophages. Using flow cytometric analysis of mouse resident peritoneal macrophages, we showed that AGEs suppress phagocytosis of fluorescent microspheres by cultured macrophages. In addition, experiments using streptozotocin-induced diabetic mice demonstrated a significant decrease in the phagocytic activity of resident peritoneal macrophages 12 weeks after induction of diabetes compared with age-matched control mice. The phagocytic activity of peritoneal macrophages correlated inversely with AGE content in the adjacent peritoneal tissue. Furthermore, reduced phagocytic activity of macrophages was associated with a reduction in intracellular ATP content. Because phagocytosis is an important component of the defense system, suppression of such activity by AGEs may explain, at least in part, the increased susceptibility of diabetic patients to infection.

Adenosine Triphosphate↗

The 3'-untranslated region polymorphism of the gene for skeletal muscle-specific glycogen-targeting subunit of protein phosphatase 1 in the type 2 diabetic Japanese population.

A newly identified 3'-untranslated region (UTR) polymorphism of the gene for skeletal muscle-specific glycogen-targeting subunit of protein phosphatase 1 (PPP1R3) was associated with insulin resistance and type 2 diabetes in Pima Indians (Xia J, Scherers W, Cohen PTW, Majer M, Xi T, Norman RA, Knowler WC, Bogardus C, Prochazka M: A common variant in PP1R3 associated with insulin resistance and type 2 diabetes. Diabetes 47:1519-1524, 1998). Thus, we investigated the frequency of polymorphism of the adenine- and thymine-rich element (ARE-1 and its variant ARE-2) in 426 Japanese type 2 diabetic and 380 nondiabetic subjects using a polymerase chain reaction (PCR)-restriction enzyme fragment length polymorphism (RFLP) method. The allele frequency of the ARE-2 variant in diabetic subjects was higher than that in nondiabetic subjects (0.34 vs. 0.29; P < 0.05), even though its frequency in Japanese subjects was lower (P < 0.001) than the reported value in Pima Indians (0.56). An aspartate polymorphism at codon 905 was 100% coupled to the ARE-2 allele, and its allele frequency was higher also in diabetic subjects. Although a serine substitution at codon 883 was partially linked with the ARE-2 allele, there was no difference between diabetic and nondiabetic subjects. These results indicate that the frequency of polymorphism of the PPP1R3 gene (ARE-2 and Asp905) is different between two ethnic groups and is increased in Japanese people with type 2 diabetes, suggesting that these variants may be a possible marker for searching for diabetogenic genes.

3' Untranslated Regions↗

High-dose chemotherapy with peripheral blood stem cell rescue in blastoid natural killer cell lymphoma.

A 25-year-old man was referred because of skin rash, lymphadenopathy and anemia. Laboratory examinations revealed severe anemia (Hb, 4.8 g/dl) and elevated levels of GOT, GPT, LDH and soluble interleukin-2 receptor. Work-up studies disclosed the involvement of lymphoma cells in lymph nodes, skin, bilateral kidneys and bone marrow. Lymph node biopsy revealed diffuse proliferation of medium- to large-sized lymphoblastic cells. Bone marrow aspiration showed massive infiltration of large blastic cells with no cytoplasmic granules. The lymphoma cells in bone marrow and lymph node showed surface CD3-, cytoplasmic CD3epsilon+, CD4+, CD8-, CD56+, CD57-, CD16- and CD43 (MT-1)+ phenotype. Analyses of T cell receptor beta and gamma genes showed germ line configurations. EBER-1 was not detectable in the lymphoma cells. He was diagnosed as having blastoid natural killer (NK) cell lymphoma. In spite of several courses of combination chemotherapy, the lymphoma was progressive. He was then treated with high-dose chemotherapy and peripheral blood stem cell rescue, achieving remission which has now lasted for more than 12 months. We consider that blastoid NK cell lymphoma is an extremely aggressive subtype of CD56-positive lymphomas, and high-dose chemotherapy with peripheral blood stem cell rescue should be included for the choice of the treatment.

Adult↗

[Pathophysiology and treatment results of auditory ossicle damage due to earpick-induced trauma].

We examined 10 ears from 10 patients undergoing ossiculoplasty due to a diagnosis of earpick-induced traumatic ossiculodialysis. Surgical findings induced dialysis of the incudostapedial joint in 5 patients, however, dialysis of this articulation was infrequent. Abnormal stapes were observed in 9 patients, including 6 patients with foot plate invagination. Five patients had a concomitant perilymphatic fistula. Perilymphatic fistula was found in 5 of 6 patients with vertigo but not in patients with tinnitus. It is thought to be difficult to diagnose ossiculodialysis from a tympanogram alone; stapedius reflex could possibly be referred to at diagnosis. The auditory ossicle was reconstructed using the stapes head and foot plate in patients with normal foot plates. In patients with ossicular invagination, the position of the auditory ossicle was reduced and the perilymphatic fistula closed, with ossicular reconstruction as needed. The surgical results were satisfactory, and auditory acuity was improved in 90% of the patients.

Adult↗

[Three-dimensional reconstruction of functional brain images].

We consider PET (positron emission tomography) measurement with SPM (Statistical Parametric Mapping) analysis to be one of the most useful methods to identify activated areas of the brain involved in language processing. SPM is an effective analytical method that detects markedly activated areas over the whole brain. However, with the conventional presentations of these functional brain images, such as horizontal slices, three directional projection, or brain surface coloring, makes understanding and interpreting the positional relationships among various brain areas difficult. Therefore, we developed three-dimensionally reconstructed images from these functional brain images to improve the interpretation. The subjects were 12 normal volunteers. The following three types of images were constructed: 1) routine images by SPM, 2) three-dimensional static images, and 3) three-dimensional dynamic images, after PET images were analyzed by SPM during daily dialog listening. The creation of images of both the three-dimensional static and dynamic types employed the volume rendering method by VTK (The Visualization Toolkit). Since the functional brain images did not include original brain images, we synthesized SPM and MRI brain images by self-made C++ programs. The three-dimensional dynamic images were made by sequencing static images with available software. Images of both the three-dimensional static and dynamic types were processed by a personal computer system. Our newly created images showed clearer positional relationships among activated brain areas compared to the conventional method. To date, functional brain images have been employed in fields such as neurology or neurosurgery, however, these images may be useful even in the field of otorhinolaryngology, to assess hearing and speech. Exact three-dimensional images based on functional brain images are important for exact and intuitive interpretation, and may lead to new developments in brain science. Currently, the surface model is the most common method of three-dimensional display. However, the volume rendering method may be more effective for imaging regions such as the brain.

Brain↗

[Chancroid].

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Chancroid↗