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Biomedical subjects

K Katayama

Publications and source records attributed to K Katayama.

At least 73 records · Page 4Linked to original sources

APC protein is required for initiation of neuronal differentiation in rat pheochromocytoma PC12 cells.

The adenomatous polyposis (APC) gene product is highly expressed in the central nervous system. To elucidate the contribution of the APC protein to neuronal differentiation, we used an inducible antisense mRNA vector to suppress APC protein expression and examined neuronal differentiation of PC12 cells induced by nerve growth factor (NGF). When antisense mRNA was induced, APC protein expression was suppressed to 20% of the noninduced level. In those cells, neurite extension induced by NGF and expression of microtubule-associated protein 2 (MAP2) was completely inhibited. However, once cells had differentiated, antisense APC mRNA expression and subsequent suppression of APC protein expression had no effect on either cell morphology or MAP2 protein expression. These results suggest that the wild type APC is critically involved only in the initiation of neuronal differentiation, but not in the maintenance of the differentiated phenotype, or that the neuronal phenotype could be maintained at lower level of APC protein.

Adenomatous Polyposis Coli Protein↗

Increased peripheral blood interferon gamma-producing T cells in acute disseminated encephalomyelitis.

There have been few reports on immunological studies in patients with acute disseminated encephalomyelitis (ADEM). We investigated the immunological features of ADEM using flow cytometry to examine interferon gamma (IFN-gamma)-and interleukin 4 (IL-4)-producing peripheral blood CD3+T cells from four patients with ADEM, three other neurological disorders (Fisher syndrome, epilepsy and aseptic meningitis) and 10 healthy children. IFN-gamma-producing CD3+T cells were increased in ADEM during the acute stage. In a relapsing case of ADEM, the percentages of IFN-gamma-producing CD3+T cells correlated with disease activity. There were no significant changes of IL-4-producing CD3+T cells in ADEM during the acute and convalescent stages. In conclusion, peripheral blood IFN-gamma-producing T cells are related to the pathogenesis at the early phase of the acute ADEM.

CD3 Complex↗

Ion pair skin transport of a zwitterionic drug, cephalexin.

The ion pair skin transport of cephalexin was investigated using various counter ions and solvents. The permeability of cephalexin was enhanced by 1-alkylsulfonates (ASs) at pH 3.0 and by tetraalkylammoniums (AAs) at pH 7.0; the enhancing ratio increased with the number of carbon atoms in their alkyl chains. The corresponding effects of these additives were observed on the partitioning of cephalexin. Most of the additives did not affect the skin transport of D-mannitol and cortisone. These results suggest that the enhanced transport of cephalexin results from the ion pair formation with additives. Although ASs increased the partitioning of cephalexin above that of AAs, the transport enhancement effect of ASs was lower than AAs having the same number of carbon atoms in their alkyl chains, indicating higher diffusivity of the ion pairs with AAs in skin. Moreover, the transport enhancement by AAs increased even more when ethanol-buffer solutions were used as solvents. The conductivity measurement of dissolving solutes in donor solvents showed that the further enhancement might be caused by the increasing ion pair formation in solvents with low dielectric constants. To obtain the maximum enhancement of skin transport of zwitterionic drugs via ion pair concept, one should select a counter ion having high lipophilicity and small volume, and a solvent with suitable pH and low dielectric constant.

Animals↗

Ventilatory and circulatory responses at the onset of voluntary exercise and passive movement in children.

The purpose of this study was to investigate whether or not the ventilatory and circulatory responses at the onset of voluntary exercise and passive movement, especially at the initial stage (phase I), in children are the same as in adults. Ten pre-teenage male children and ten adult men participated in this study. Voluntary exercise and passive movement were performed in a sitting position for about 20 s. Both the exercise and the movement consisted of flexion-extensions of the lower leg from a vertical to horizontal position, either voluntarily or passively, with a frequency of about 60 x min(-1). Inspiratory minute ventilation (V1), tidal volume (VT), respiratory frequency, partial pressure of end-tidal CO2 and O2, heart rate (fc) and mean blood pressure (BP) before, during and after exercise or movement were measured using breath-by-breath and beat-to-beat techniques. Cardiorespiratory responses at the onset of voluntary exercise and passive movement were compared with the relative change (delta), which was estimated from the value at rest (100%). In the present study, it was found that: (1) the V1 during voluntary exercise were significantly lower in the children, mainly due to lower deltaVT; (2) the delta(f)c during voluntary exercise was almost the same in both groups, while deltaf(c) was significantly lower in the children during the last part of passive movement; (3) in the voluntary exercise and passive movement, the BP in the children was increased a little or remained close to the value at rest, while it was significantly decreased in the adults. As a result, there were significant differences in deltaBP between the two groups during voluntary exercise. These results suggest that the cardiorespiratory responses at the onset of voluntary exercise and passive movement may be modified during the growth process.

Adult↗

Heterogeneity found in the cagA gene of Helicobacter pylori from Japanese and non-Japanese isolates.

We analyzed cagA genes from Helicobacter pylori strains isolated from Japanese and non-Japanese individuals for differences that could be associated with variations in virulence. The cagA genes from Japanese isolates (n = 12) and non-Japanese American Type Culture Collection (ATCC) strains (n = 4) were sequenced and compared with three published sequences. Phylogenetic analysis resolved two distinct clusters with a genetic distance of 0.1602. Similarity plot analysis of the amino acid sequences identified two highly variable regions of which each was unique to the Japanese and non-Japanese isolates, respectively. Furthermore, nucleic acid sequence analysis revealed that the multiple repeated sequences present in cagA may have been generated by homologous recombination and/or misaligned replication to promote variation in the cagA gene products. Our data indicate that alleic variations in the H. pylori genome exist between isolates from Japanese and non-Japanese subjects and that distinct H. pylori populations may be circulating in different geographical regions. Phylogenetic analysis did not reveal any association of a specific CagA type with a particular disease. Although extensive alterations were found in the cagA gene, none of the isolates contained a prematurely terminated CagA protein. The cagA gene may be advantageous to H. pylori, possibly by aiding its escape from host immune recognition by antigen modulation. Thus, this ability to elude the host immune system may contribute to an increased risk for gastric disease.

Algorithms↗

Distribution, metabolism and excretion of butylidenephthalide of Ligustici chuanxiong rhizoma in hairless mouse after dermal application.

The absorption, distribution and excretion of butylidenephthalide after dermal application to hairless mouse have been examined with [8-14C]butylidenephthalide. By the investigation of the whole body autoradiogram and liquid scintillation analysis, it was indicated that the transdermally applied butylidenephthalide quickly permeate into peripheral circulation system without accumulation in the skin and then distribute into lung, liver, bile and kidney. The total radioactivity, however, was decreased due to excretion into urine, and in the case of i.v.-administration, 80% of the administered butylidenephthalide was excreted into urine within 24 h, while only 5% was excreted into feces within 24 h. Then, the metabolite in urine was determined to be a cysteine conjugate by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. Thus, it has been concluded that after dermal application butylidenephthalide quickly permeates through skin into peripheral circulation system; distributes to lung, liver, bile and kidney; and then excreted into urine as a cysteine adduct.

Administration, Cutaneous↗

The promoter of rbcS in a C3 plant (rice) directs organ-specific, light-dependent expression in a C4 plant (maize), but does not confer bundle sheath cell-specific expression.

The small subunit of ribulose-bisphosphate carboxylase (Rubisco), encoded by rbcS, is essential for photosynthesis in both C3 and C4 plants, even though the cell specificity of rbcS expression is different between C3 and C4 plants. The C3 rbcS is specifically expressed in mesophyll cells, while the C4 rbcS is expressed in bundle sheath cells, and not mesophyll cells. Two chimeric genes were constructed consisting of the structural gene encoding beta-glucuronidase (GUS) controlled by the two promoters from maize (C4) and rice (C3) rbcS genes. These constructs were introduced into a C4 plant, maize. Both chimeric genes were specifically expressed in photosynthetic organs, such as leaf blade, but not in non-photosynthetic organs. The expressions of the genes were also regulated by light. However, the rice promoter drove the GUS activity mainly in mesophyll cells and relatively low in bundle sheath cells, while the maize rbcS promoter induced the activity specifically in bundle sheath cells. These results suggest that the rice promoter contains some cis-acting elements responding in an organ-specific and light-inducible regulation manner in maize but does not contain element(s) for bundle sheath cell-specific expression, while the maize promoter does contain such element(s). Based on this result, we discuss the similarities and differences between the rice (C3) and maize (C4) rbcS promoter in terms of the evolution of the C4 photosynthetic gene.

Base Sequence↗

CD14+CD16+ monocyte subpopulation in Kawasaki disease.

Kawasaki disease (KD) is an acute febrile illness caused by vasculitis, occurring in early childhood. We have demonstrated that the activation of monocytes/macrophages plays a central role during acute KD. Recently, it has been reported that the CD14+CD16+ monocyte subpopulation plays a more important role in inflammation. In this study, we investigated the peripheral blood CD14+CD16+ monocyte subpopulation by flow cytometry, and serum levels of IL-10 and IL-12 using a sandwich ELISA in 28 KD patients. We also investigated this subpopulation in patients with bacterial infections, mononucleosis and anaphylactoid purpura, since the cause of KD remains unknown. We observed an increase in the number of CD14+CD16+ monocytes with acute KD, which was a positive correlation with C-reactive protein levels, and we observed only the patients with severe bacterial infections had increased this subpopulation during the acute stage among control diseases. In addition, we found that the serum levels of IL-10, but not IL-12, were higher during acute KD. These data suggest that increased peripheral blood CD14+CD16+ monocytes are part of the regulatory system of monocyte function during acute KD.

Acute Disease↗

Probability of hepatocellular carcinoma of small hepatocellular nodules undetectable by computed tomography during arterial portography.

Recent advances in imaging modalities enable the identification of small hepatocellular nodules. Among the imaging techniques currently used for detecting hepatocellular carcinomas (HCC), computed tomography (CT) during arterial portography (CTAP) is one of the most sensitive techniques available for detecting hemodynamic change. Even so, well-differentiated HCCs that display only limited hemodynamic change, a feature shared with nonmalignant hepatocellular nodules, are not always detectable by CTAP. To improve our ability to distinguish well-differentiated HCCs from nonmalignant hepatocellular nodules, we have attempted to clarify how the characteristics of the nodules are shown by each imaging technique. We studied the imaging and pathological characteristics of 31 nodules (in 22 patients) detected by ultrasonography (US), but not by CTAP. Histological diagnoses were as follows: HCC, 17 of 31 nodules (55%); high-grade dysplastic nodules, 1 of 31 (3%); and nonmalignant nodules, 13 of 31 (42%). Neither digital substraction angiography (DSA) nor CT arteriography (CTA) were able to detect any of the nodules. Detection rates for plain CT were: 5 of 17 (29%) HCC, 1 of 1 (100%) high-grade dysplastic nodules, and 1 of 13 (8%) nonmalignant nodules. Detection rates for T1/T2-weighted magnetic resonance imaging (MRI) were: 4 of 17 (24%) HCC, 1 of 1 (100%) high-grade dysplastic nodules, and 3 of 13 (23%) nonmalignant nodules. Dynamic CT and dynamic MRI provided no additional information. In conclusion, there is some probability that hepatocellular nodules detected by US, but not by CTAP, are HCC. Presently, it is difficult to distinguish between benign nodules and malignant ones with these imaging techniques, and our findings indicate that biopsy may be advisable for nodules detected under these conditions.

Adult↗

Mononuclear cells and cytokines in the cerebrospinal fluid of echovirus 30 meningitis patients.

The local immune response to echovirus 30 meningitis in children was investigated in 2 ways: using flow cytometry to examine the mononuclear cell and lymphocyte subsets and enzyme-linked immunosorbent assays to examine the cerebrospinal fluid (CSF) levels of cytokines, including monocyte chemoattractant protein-1 (MCP-1), interferon gamma (IFN-gamma) and interleukin-12 (IL-12). The numbers of macrophages in the CSF were increased, in particular during the early part of the acute stage. The levels of MCP-1, which is responsible for the accumulation of macrophages, as well as those of IFN-gamma and IL-12, which play important roles in the activation of macrophages and T helper (Th) 1 cells, respectively, were increased in the CSF of patients compared with the levels found in the controls. Likewise, numbers of activated CD4 + and CD8 + T lymphocytes were increased in the CSF. Since the ratio of CD4/CD8 correlated with the age of the patients, CD8 + T lymphocytes in the CSF might play a more important role in younger children.

Cerebrospinal Fluid↗

Different expression of ICAM-1 and LFA-1 alpha by peripheral leukocytes during respiratory syncytial virus and influenza virus infection in young children.

We compared the expression of intercellular adhesion molecule (ICAM)-1 and lymphocyte function-associated antigen (LFA)-1 alpha (alpha) on the surfaces of peripheral immunocompetent cells of young children infected with respiratory syncytial virus (RSV) and influenza virus. Flow cytometric analysis revealed a significantly higher percentage of CD14 + monocytes/macrophages that were strongly ICAM-1-positive in the influenza group than in age-matched controls, whereas the ICAM-1 expression levels of the RSV and control groups did not differ significantly. Analysis of LFA-1alpha expression by CD3 + T lymphocytes showed a significantly higher percentage of strongly positive cells in the influenza group than in the age-matched controls. By contrast, the percentage of cells that were strongly LFA-1alpha-positive was significantly lower in the RSV group than in the age-matched controls. These results suggest that no increase of adhesion molecule expression occurs in vivo in patients with RSV infection, and also that there is little activation of peripheral blood monocytes/macrophages and T lymphocytes in young children with RSV infection.

CD3 Complex↗

Cardiovascular response to hypoxia after endurance training at altitude and sea level and after detraining.

The purpose of this study was to elucidate 1) the effects of endurance exercise training during hypoxia or normoxia and of detraining on ventilatory and cardiovascular responses to progressive isocapnic hypoxia and 2) whether the change in the cardiovascular response to hypoxia is correlated to changes in the hypoxic ventilatory response (HVR) after training and detraining. Seven men (altitude group) performed endurance training using a cycle ergometer in a hypobaric chamber of simulated 4,500 m, whereas the other seven men (sea-level group) trained at sea level (K. Katayama, Y. Sato, Y. Morotome, N. Shima, K. Ishida, S. Mori, and M. Miyamura. J. Appl. Physiol. 86: 1805-1811, 1999). The HVR, systolic and diastolic blood pressure responses (DeltaSBP/DeltaSa(O(2)), DeltaDBP/DeltaSa(O(2))), and heart rate response (DeltaHR/DeltaSa(O(2)); Sa(O(2)) is arterial oxygen saturation) to progressive isocapnic hypoxia were measured before and after training and during detraining. DeltaSBP/DeltaSa(O(2)) increased significantly in the altitude group and decreased significantly in the sea-level group after training. The changed DeltaSBP/DeltaSa(O(2)) in both groups was restored during 2 wk of detraining, as were the changes in HVR, whereas there were no changes in the DeltaDBP/DeltaSa(O(2)) and DeltaHR/DeltaSa(O(2)) throughout the experimental period. The changes in DeltaSBP/DeltaSa(O(2)) after training and detraining were significantly correlated with those in HVR. These results suggest that DeltaSBP/DeltaSa(O(2)) to progressive isocapnic hypoxia is variable after endurance training during hypoxia and normoxia and after detraining, as is HVR, but DeltaDBP/DeltaSa(O(2)) and DeltaHR/DeltaSa(O(2)) are not. It also suggests that there is an interaction between the changes in DeltaSBP/DeltaSa(O(2)) and HVR after endurance training or detraining.

Altitude↗

Initial ventilatory and circulatory responses to dynamic exercise are slowed in the elderly.

To elucidate the characteristics of ventilatory and circulatory responses at the onset of brief and light exercise in the elderly, 13 healthy, elderly men, aged 66.8 yr (mean), exerted bilateral leg extension-flexion movements for only 20 s with a weight around each ankle, with each weight being approximately 2.5% of their body mass. Similar movements were passively performed on the subjects by the experimenters. These results were compared with those of 13 healthy, young men (22.9 yr). Minute ventilation increased at the onset of voluntary exercise and passive movements in both groups but showed a slower increase in the elderly. Heart rate also increased in both groups but showed less change in the elderly. Mean blood pressure temporarily decreased in both groups but less in the elderly. The magnitude of relative change (gain) of heart rate in the elderly was significantly smaller than that in the young, whereas the increasing rate to reach one-half of the gain (response time) of ventilation in the elderly was significantly slower than that in the young. Similar tendencies were observed in the passive movements. It is concluded that the elderly show slower ventilatory response and attenuated circulatory response at the onset of dynamic voluntary exercise and passive movements.

Adolescent↗

Drug targeting efficacy to underlying muscle following topical application. I. Evaluation based on a physiological pharmacokinetic model.

A physiological pharmacokinetic model describing the absorption and disposition of topically applied drugs was proposed, and the effect of various pharmacokinetic and physiological parameters on the drug delivery into the targeted muscle was simulated. The proposed model consists of vehicle, and stratum corneum, viable epidermis and muscle below the application and reference sites, and plasma, each joined with transfer clearance and plasma flow. Indomethacin concentrations in tissues and plasma after topical application to rats could be explained by the model. Most indomethacin delivered into the underlying muscle was via direct penetration. The model simulation showed that the increase in plasma clearance and clearance between viable skin and muscle, and the decrease in application area and plasma flow rate into viable skin and muscle would promote the targeting efficacy of topically applied drugs to the underlying muscle.

Administration, Topical↗

Retrospective analysis showing less cardiac events in post-myocardial infarction patients treated with metoprolol. Secondary Prevention Group.

This analysis was carried out to clarify the capacity of metoprolol to prevent cardiac events in Japanese post-myocardial infarction patients during a follow-up period of 16.3 months. Cardiac events occurred in 44 of 650 patients treated without beta-blockers (6.8%) and in 13 of 432 patients treated with metoprolol (3.0%), which represents a significant decline in the incidence of cardiac events among patients receiving metoprolol (p<0.01, odds ratio 0.43, 95% confidence interval 0.23-0.80). Because this was a retrospective analysis, there were unavoidable differences in the backgrounds of the patients in the 2 groups. Subgroup analyses, each focusing on a specific patient characteristic, were therefore performed. These showed that metoprolol effectively reduced cardiac events in many subgroups. Furthermore, multivariate analysis carried out to exclude any modification based on the differences in patient background confirmed metoprolol to be effective in reducing subsequent cardiac events in post-myocardial infarction patients. A large, randomized, placebo-controlled clinical trial needs to be performed in the Japanese population to confirm the present result.

Adrenergic beta-Antagonists↗

Ethylnitrosourea (ENU)-induced apoptosis in the rat fetal tissues.

Ethylnitrosourea (ENU), a well known DNA alkylating agent, induces anomalies in the central nervous system (CNS), craniofacial tissues and male reproductive organs. In this study, pregnant rats were treated with 60 mg/kg ENU at day 13 of gestation, and their fetuses were examined from 1 to 48 hours after treatment (HAT) to find a clue for clarifying the mechanisms of the ENU fetotoxicity and teratogenicity. From 3 to 12 HAT, the moderate to marked increase in the number of pyknotic cells was detected in the fetal CNS, craniofacial mesenchymal tissues, gonads and so on. These pyknotic cells had nuclei positively stained by the TUNEL method, which is widely used for the detection of apoptotic nuclei, and they also showed electron microscopic characteristics identical to those of apoptotic cells. The present results strongly suggest that excess cell death by apoptosis in the fetal CNS, craniofacial tissues and gonads may have a close relation to the later occurrence of anomalies reported in these tissues following ENU-administration.

Alkylating Agents↗