Biomedical subjects

M Okamoto

Publications and source records attributed to M Okamoto.

At least 217 records · Page 12Linked to original sources

PubMed2000

Autoimmune pancreatitis detected as a mass in the tail of the pancreas.

A mass in the tail of the pancreas was detected in a 62-year-old male patient who had hypergammaglobulinaemia, and was positive for antinuclear antigen and anti-SS-A antibody. Endoscopic retrograde pancreatography revealed focal irregular narrowing of the main pancreatic duct in the tail of the pancreas. Dynamic computed tomography showed swelling of the pancreatic tail, which was enhanced on delayed phase. Autoimmune pancreatitis was suspected and corticosteroid therapy was commenced. This led to significant resolution of the pancreatic stricture. It is important to recognize this clinical entity as corticosteroid therapy may avoid unnecessary surgery.

Autoantibodies↗

PubMed2000

Ultrastructural localization of mint1 at synapses in mouse hippocampus.

Mint1 and mint2 were isolated in the course of seeking the protein ligands to munc18-1, a neuronal protein essential for synaptic vesicle exocytosis. The mint family of proteins has been highly conserved in the course of evolution, being retained from C. elegans to mammals. Several lines of biochemical and genetic evidence have suggested that mint1 and LIN-10, its homologue in C. elegans, function at synapses in the brain. Because the precise subcellular location of mint1 is incompletely known, we used immunostaining to examine the distribution of mint1 in the mouse brain including ultrastructural localization in synapses. Strong, finely punctate mint1 immunolabeling was detected throughout the brain, including cerebral cortex, striatum, hippocampus, thalamus, basal ganglia and cerebellum. At the most synapses in the molecular layer, mint1 was particularly abundant at the active zone and to a lesser extent in association with synaptic vesicles in the presynaptic terminals. In contrast, a very few synapses showed mint1 immunoreactivity in the postsynaptic density and there was no synapse double-positive in presynaptic and postsynaptic terminals. Mint1 distribution within presynaptic terminals overlapped that of munc18-1. These localization results are consistent with previously demonstrated biochemical interactions and strongly support functions of mint1 in synaptic vesicle exocytosis and synaptic organization in the central nervous system.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Interleukin 18 is a potent proliferative factor for intestinal mucosal lymphocytes in Crohn's disease.

BACKGROUND & AIMS: Crohn's disease (CD) is characterized by a marked accumulation of activated Th1 type CD4(+) T cells and macrophages in inflamed intestinal mucosa. Interleukin (IL)-18 is a recently described cytokine that mainly exists in activated macrophages and shares biological activities with IL-12 in driving the development of Th1 type CD4(+) T cells by inducing interferon gamma. To clarify the role of IL-18 in intestinal inflammation in CD, we assessed the functional role of IL-18 in regulating intestinal mucosal lymphocytes. METHODS: Serum IL-18 concentration was measured by enzyme-linked immunosorbent assay. Expression of IL-18 and IL-18 receptor in human intestinal mucosa was determined using immunohistochemistry and flow cytometry. The functional activity of IL-18 was assessed by the use of recombinant IL-18 to stimulate both the growth of intestinal mucosal lymphocytes and IL-2 receptor induction activity. RESULTS: The serum IL-18 concentration was significantly higher in patients with CD than normal controls. In the inflamed colonic mucosa of CD, many IL-18(+)CD68(+) macrophages had infiltrated the lamina propria. Intestinal mucosal lymphocytes from CD expressed functional IL-18 receptors. Recombinant IL-18 induced significant proliferative responses in freshly isolated mucosal lymphocytes from CD patients, but not from normal controls. IL-18 up-regulated IL-2 receptor expression in mucosal lymphocytes from patients with CD, but not from normal controls. CONCLUSIONS: These findings suggest that infiltrated macrophages in the inflamed intestinal mucosa in CD produce IL-18, and that macrophage-derived IL-18 may serve as a potent regulatory factor for intestinal mucosal lymphocytes, thereby contributing to chronic intestinal inflammation in CD.

Cell Division↗

PubMed2000

Outcome of arthroscopic surgery for internal derangement of the temporomandibular joint: long-term results covering 10 years.

OBJECTIVES: To investigate the long-term success (10-year results) of arthroscopic surgery of the temporomandibular joint. PATIENTS AND METHOD: A survey was undertaken of 37 patients who had been treated with arthroscopic surgery for TMJ internal derangement from 1986 to 1990. Thirty-three patients responded, of whom 30 were women and three men, whose age at surgery ranged from 14 to 77 years (mean: 35.1 years). The mean follow-up period was 10 years and 2 months. All patients rated their pain level on a visual analogue scale (VAS), and also recorded pain, jaw dysfunction, and activities of daily living (ADL) before surgery, and at the time of the survey. Interincisal opening was self-assessed (mm). Pre- and postoperative pain, dysfunction and ADL scores were compared for outcome and statistically analyzed with the Student's t-test. RESULTS: Intensity of pain as rated on the VAS was significantly reduced from 5.15 to 0.34 (p<0.01). Pain, dysfunction and ADL scores also decreased from 8.25 to 1.09, 6.5 to 1.93, and 9.1 to 1.32, respectively (p<0.01). At the preoperative examination, 36 of the 37 patients showed limited jaw opening of less than 38 mm, reduced to only three postoperatively. For the success rate of TMJ surgery, the responding 33 plus data of one re-operated patient were assessed. Of these, 27 were rated as excellent, four as good, and three (including two re-operated patients) as poor. The success rate was 83.8% when three patients who did not respond were included in the data. CONCLUSION: The long-term, 10 year outcome of TMJ arthroscopic surgery was considered to be acceptable and stable when compared with other surgical procedures and with the results of previously published middle to long-term treatment outcome studies.

Activities of Daily Living↗

PubMed2000

Morphology and dynamics of the ulnar nerve in the cubital tunnel. Observation by ultrasonography.

We examined 200 normal elbows to assess the usefulness of ultrasonography in examining the ulnar nerve in the cubital tunnel. On longitudinal images in elbow extension, the nerve changed its course at the fibrous band region 11.5 (SD 2.8) mm distal to the medial epicondyle. On axial images, the diameter of the major axis of the nerve was 3.1 (0.5) mm and that of the minor axis was 1.9 (0.4) mm in men. The respective values were 2.7 (0.4) mm and 1.8 (0.4) mm in women. Dynamic studies showed that in 53 elbows (27%), the nerve moved on to the tip of the epicondyle with the elbow flexed and in 39 elbows (20%), the nerve dislocated anteriorly. The diameters of the hypermobile nerves were significantly larger than nerves that did not displace.

Adult↗

PubMed2000

Diagnostic ultrasonography of the ulnar nerve in cubital tunnel syndrome.

Thirty-two elbows in 31 patients diagnosed as having cubital tunnel syndrome underwent ultrasonographic examination to assess morphological changes in the ulnar nerve and its surrounding tissues. On longitudinal images, the site of constriction due to the fibrous band and proximal swelling of the nerve were observed by ultrasonography and were confirmed intraoperatively. On axial images, the lengths of the major axis [7.2 (SD 1.6) mm] and the minor axis [3.7 (0.9) mm] of the nerve at the medial epicondyle were greater than those in normal subjects. There was a correlation between the stage of ulnar nerve palsy and the diameter of the major axis. Preoperatively, ganglia were detected by ultrasonography in the cubital tunnel in three cases and an anconeus epitrochlearis muscle in two.

Cubital Tunnel Syndrome↗

PubMed2000

Primary non-Hodgkin's lymphoma of the mandible treated with radiotherapy, chemotherapy, and autologous peripheral blood stem cell transplantation.

Extranodal presentation in non-Hodgkin's lymphoma (NHL) is uncommon, and the mandible is very rarely involved. Primary NHL of the mandible, for the most part, has intermediate or high malignancy and has a much greater incidence of local recurrence compared with other sites of involvement. A 48-year-old Japanese man with NHL of the mandible received radiotherapy, followed by high-dose chemotherapy supported with peripheral blood stem cell transplantation (PBSCT). High-dose cyclophosphamide, Adriamycin, and vincristine were used for pretransplant conditioning. He achieved complete remission and has survived in continuous complete remission for more than 72 months to date. Marrow-ablative chemotherapy facilitated by PBSCT is thought to be useful as part of the primary therapy for patients with NHL who have poorer prognoses.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

IgE-mediated and age-related bronchial hyperresponsiveness in patients with asthma. relationship to family history of the disease.

OBJECTIVE: to uncover any differences in the age-related and IgE-mediated pathophysiology of the airways in asthmatics. METHODS: we examined the relationship of both IgE-mediated bronchial hyperresponsiveness and the cell content of bronchoalveolar lavage fluid with a family history of asthma in 263 patients with asthma classified according to age at onset. RESULTS: bronchial hyperresponsiveness decreased significantly as age at onset increased in those without a family history. Responsiveness was significantly higher in patients who were > or = 60 years of age at onset who had a family history than in those who did not (P < 0.05). The proportion of lymphocytes in bronchoalveolar lavage fluid was significantly higher in patients between 50 and 59 years old at onset who had a family history than those who did not (P < 0.05). These results suggest that bronchial hyperresponsiveness and the proportion of bronchoalveolar lavage lymphocytes differ according to the presence or absence of a family history, a finding which is closely related to IgE-mediated allergy in elderly patients at onset. CONCLUSIONS: our findings suggest (i) the possibility of asthma induced by non-IgE-mediated allergy in elderly patients and (ii) that bronchial responsiveness is also influenced by IgE-mediated allergy and age at onset.

Adult↗

PubMed2000

Norepinephrine facilitates inhibitory transmission in substantia gelatinosa of adult rat spinal cord (part 2): effects on somatodendritic sites of GABAergic neurons.

BACKGROUND: It has been reported previously that norepinephrine, when applied to the spinal cord dorsal horn, excites a subpopulation of dorsal horn neurons, presumably inhibitory interneurons. In the current study, the authors tested whether norepinephrine could activate inhibitory interneurons, specifically those that are "GABAergic." METHODS: A transverse slice was obtained from a segment of the lumbar spinal cord isolated from adult male Sprague-Dawley rats. Whole-cell patch-clamp recordings were made from substantia gelatinosa neurons using the blind patch-clamp technique. The effects of norepinephrine on spontaneous GABAergic inhibitory postsynaptic currents were studied. RESULTS: In the majority of substantia gelatinosa neurons tested, norepinephrine (10-60 microM) significantly increased both the frequency and the amplitude of GABAergic inhibitory postsynaptic currents. These increases were blocked by tetrodotoxin (1 microM). The effects of norepinephrine were mimicked by the alpha1-receptor agonist phenylephrine (10-80 microM) and inhibited by the alpha1-receptor-antagonist WB-4101 (0.5 microM). Primary-afferent-evoked polysynaptic excitatory postsynaptic potentials or excitatory postsynaptic currents in wide-dynamic-range neurons of the deep dorsal horn were also attenuated by phenylephrine (40 microM). CONCLUSION: The observations suggest that GABAergic interneurons possess somatodendritic alpha1 receptors, and activation of these receptors excites inhibitory interneurons. The alpha1 actions reported herein may contribute to the analgesic action of intrathecally administered phenylephrine.

Adrenergic alpha-1 Receptor Agonists↗

PubMed2000

Actions of midazolam on GABAergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices.

BACKGROUND: Although intrathecal administration of midazolam has been found to produce analgesia, how midazolam exerts this effect is not understood fully at the neuronal level in the spinal cord. METHODS: The effects of midazolam on either electrically evoked or spontaneous inhibitory transmission and on a response to exogenous gamma-aminobutyric acid (GABA), a GABA(A)-receptor agonist, muscimol, or glycine were evaluated in substantia gelatinosa neurons of adult rat spinal cord slices by using the whole-cell patch-clamp technique. RESULTS: Bath-applied midazolam (1 microM) prolonged the decay phase of evoked and miniature inhibitory postsynaptic currents (IPSCs), mediated by GABA(A) receptors, without a change in amplitudes, while not affecting glycine receptor-mediated miniature inhibitory postsynaptic currents in both the decay phase and the amplitude. Either GABA- or muscimol-induced currents were enhanced in amplitude by midazolam (0.1 microM) in a manner sensitive to a benzodiazepine receptor antagonist, flumazenil (1 microM); glycine currents were, however, unaltered by midazolam. CONCLUSIONS: Midazolam augmented both the duration of GABA-mediated synaptic current and the amplitude of GABA-induced current by acting on the GABA(A)-benzodiazepine receptor in substantia gelatinosa neurons; this would increase the inhibitory GABAergic transmission. This may be a possible mechanism for antinociception by midazolam.

2-Amino-5-phosphonovalerate↗

PubMed2000

Induction of cytokines and killer cell activities by cisplatin and 5-fluorouracil in head and neck cancer patients.

It has been suggested that certain antitumor agents stimulate antitumor immunity. In the present study, we examined whether cisplatin and 5-fluorouracil (5-FU) accelerate the antitumor host responses in head and neck cancer patients. Two groups of patients were studied, i.e. an untreated (UT) group and a treated, disease-free (TDF) group that received chemo-immunotherapy in combination with radiotherapy and operation. When peripheral blood mononuclear cells (PBMC) derived from head and neck cancer patients were treated with cisplatin or with 5-FU, interferon-gamma, tumor necrosis factor (TNF)-alpha, TNF-beta, interleukin (IL)-1beta, IL-6, IL-12 and IL-18 as well as killer cell activities were significantly induced in both groups. In this case, these activities induced by cisplatin in UT showed lower levels than those in TDF, whereas the activities induced by 5-FU in the UT group demonstrated almost similar levels to those in TDF. These activities were significantly inhibited by anti-asialo-GM1 antibody. Furthermore, cytokine levels in sera and killer activities of PBMC derived from the cancer patients were significantly increased after cisplatin administration. These findings suggest that cisplatin and 5-FU increase anticancer immunity mediated by induction of cytokines and killer cell activities in patients with head and neck cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Cytokine-inducing activity and antitumor effect of a liposome-incorporated interferon-gamma-inducing molecule derived from OK-432, a streptococcal preparation.

An interferon-gamma (IFN-gamma)-inducing molecule (OK-PSA) has been purified from OK-432 by an affinity chromatographic technique performed on cyanogen bromide-activated Sepharose 4B-bound TS-2 monoclonal antibody, which neutralizes IFN-gamma-inducing activity of OK-432. OK-PSA has striking anti-tumor activity in vivo and in vitro. In the current study, the liposomes were used to improve the delivery of the agent (OK-PSA) to effector cells and to increase the therapeutic effect. Significantly less OK-PSA encapsulated into liposomes (Lipo-OK-PSA) than OK-PSA alone (1/100 or less of OK-PSA alone) was required to induce IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), TNF-beta, interleukin-1 beta (IL-1 beta), natural killer, and lymphokine-activated killer activities by human peripheral blood mononuclear cells and mouse spleen cells. Furthermore, higher levels of these activities were detected in peripheral blood mononuclear cells and mouse spleen cells treated with Lipo-OK-PSA than in those treated with OK-PSA. All of these activities induced by Lipo-OK-PSA were almost completely neutralized by anti-asialo-GM1 antibody and complement (p < 0.001). In in vivo experiments, Lipo-OK-PSA elicited striking anti-tumor activity on syngeneic Meth-A tumor-bearing and colon 26-bearing BALB/c mice and on salivary gland tumor-bearing nude mice far better than did OK-PSA. Furthermore, high levels of natural killer and lymphokine-activated killer activities and a significant increase in the number of cells positive for asialo-GM1, IFN-gamma, TNF-alpha, or IL-1 beta were detected in the spleen cells derived from the animals given Lipo-OK-PSA compared with those given saline. These findings clearly indicate that OK-PSA plays an important role in the anti-tumor efficiency of OK-432, and that, for the most part, liposome encapsulation of this molecule markedly accelerates its effect mediated by asialo-GM1-positive cells (mainly natural killer cells).

Adenocarcinoma↗

PubMed2000

Changes in mint1, a novel synaptic protein, after transient global ischemia in mouse hippocampus.

Mints (munc18-interacting proteins) are novel multimodular adapter proteins in membrane transport and organization. Mint1, a neuronal isoform, is involved in synaptic vesicle exocytosis. Its potential effects on development of ischemic damage to neurons have not yet been evaluated. The authors examined changes in mint1 and other synaptic proteins by immunohistochemistry after transient global ischemia in mouse hippocampus. In sham-ischemic mice, immunoreactivity for mint1 was rich in fibers projecting from the entorhinal cortex to the hippocampus and in the mossy fibers linking the granule cells of the dentate gyrus to CA3 pyramidal neurons. Munc18-1, a binding partner of mint1, was distributed uniformly throughout the hippocampus, and synaptophysin 2, a synaptic vesicle protein, was localized mainly in mossy fibers. After transient global ischemia, mint1 immunoreactivity in mossy fibers was dramatically decreased at 1 day of reperfusion but actually showed enhancement at 3 days. However, munc18-1 and synaptophysin 2 were substantially expressed in the same region throughout the reperfusion period. These findings suggest that mint1 participates in neuronal transmission along the excitatory pathway linking the entorhinal cortex to CA3 in the hippocampus. Because mint1 was transiently decreased in the mossy fiber projection after ischemia, functional impairment of neuronal transmission in the projection from the dentate gyrus to CA3 pyramidal neurons might be involved in delayed neuronal death.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Cigarette smoking and risk for hearing impairment: a longitudinal study in Japanese male office workers.

The association of cigarette smoking with development of hearing impairment (loss of 30 dB at 1000 Hz and 40 dB at 4000 Hz) over a 5-year follow-up was studied in 1554 non-hearing-impaired Japanese male office workers who ranged in age from 30 to 59 years. After controlling for potential predictors of hearing impairment, the relative risk for low-frequency hearing impairment compared with never smokers was 1.12 (95% confidence interval [CI], 0.57 to 2.17) for ever-smokers, 1.21 (95% CI, 0.65 to 2.25) for current smokers of 1 to 20 cigarettes/day, 1.35 (95% CI, 0.70 to 2.61) for current smokers of 21 to 30 cigarettes/day, and 1.82 (95% CI, 0.98 to 3.38) for current smokers of 31 or more cigarettes/day (P for trend = 0.063). The respective multivariate-adjusted relative risks for high-frequency hearing impairment compared with never smokers were 1.70 (95% CI, 0.85 to 3.40), 1.82 (95% CI, 0.92 to 3.59), 2.00 (95% CI, 0.98 to 4.08), and 2.20 (95% CI, 1.09 to 4.42) (P for trend = 0.025). As the number of pack-years of exposure increased, the risk for high-frequency hearing impairment increased in a dose-dependent manner (P for trend = 0.011), but the risk for low-frequency hearing impairment did not (P for trend = 0.172). Our results indicate that cigarette smoking is highly associated with development of high-frequency hearing impairment in Japanese male office workers.

Adult↗

PubMed2000

Reduced levels of chloroplast FtsH protein in tobacco mosaic virus-infected tobacco leaves accelerate the hypersensitive reaction.

In tobacco cultivars resistant to tobacco mosaic virus (TMV), infection results in the death of the infected cells accompanying the formation of necrotic lesions. To identify the genes involved in this hypersensitive reaction, we isolated the cDNA of tobacco DS9, the transcript of which decreases before the appearance of necrotic lesions. The DS9 gene encodes a chloroplastic homolog of bacterial FtsH protein, which serves to maintain quality control of some cytoplasmic and membrane proteins. A large quantity of DS9 protein was found in healthy leaves, whereas the quantity of DS9 protein in infected leaves decreased before the lesions appeared. In transgenic tobacco plants containing less and more DS9 protein than wild-type plants, the necrotic lesions induced by TMV were smaller and larger, respectively, than those on wild-type plants. These results suggest that a decrease in the level of DS9 protein in TMV-infected cells, resulting in a subsequent loss of function of the chloroplasts, accelerates the hypersensitive reaction.

Amino Acid Sequence↗

PubMed2000

A novel bacterial ATP-binding cassette transporter system that allows uptake of macromolecules.

A gram-negative bacterium, Sphingomonas sp. strain A1, isolated as a producer of alginate lyase, has a characteristic cell envelope structure and forms a mouth-like pit on its surface. The pit is produced only when the cells have to incorporate and assimilate alginate. An alginate uptake-deficient mutant was derived from cells of strain A1. One open reading frame, algS (1,089 bp), exhibiting homology to the bacterial ATP-binding domain of an ABC transporter, was cloned as a fragment complementing the mutation. algS was followed by two open reading frames, algM1 (972 bp) and algM2 (879 bp), which exhibit homology with the transmembrane permeases of ABC transporters. Disruption of algS of strain A1 resulted in the failure to incorporate alginate and to form a pit. Hexahistidine-tagged AlgS protein (AlgS(His6)) overexpressed in Escherichia coli and purified by Ni(2+) affinity column chromatography showed ATPase activity. Based on these results, we propose the occurrence of a novel pit-dependent ABC transporter system that allows the uptake of macromolecules.

ATP-Binding Cassette Transporters↗

PubMed2000

Effects of perilla seed oil supplementation on leukotriene generation by leucocytes in patients with asthma associated with lipometabolism.

BACKGROUND: Dietary sources of alpha-linolenic acid, such as perilla seed oil, may have the capacity to inhibit the generation of leukotrienes (LTs) by leucocytes in patients with asthma, as has been reported with the consumption of other long-chain n-3 fatty acids. METHODS: The factors affecting the suppression of leukotriene (LT) C4 generation by leucocytes were examined by comparing the clinical features of patients with asthma who had been given dietary perilla seed oil (n-3 fatty acids). Group A consisted of patients in whom the leucocyte generation of LTC4 was suppressed by dietary perilla seed oil. Group B consisted of those in whom LTC4 generation was not suppressed. RESULTS: LTC4 generation by leucocytes decreased significantly in group A after 2 (p < 0.05) and 4 weeks (p < 0.05); conversely, it increased significantly in group B after 4 weeks (p < 0.05). The two study groups differed significantly in terms of LTC4 generation by leucocytes after 4 weeks of dietary supplementation (p < 0.05). Ventilatory parameters such as peak expiratory flow (PEF), forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) increased significantly after 4 weeks of dietary supplementation in group A (p < 0.05). Values of PEF, FVC, FEV(1) and maximum expiratory flow at 25% of the forced vital capacity (V(25)) differed significantly between groups A and B prior to dietary supplementation. Serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol and phospholipid were significantly decreased by dietary supplementation in group A after 4 weeks. Serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, LDL cholesterol and phospholipid differed significantly between the two study groups prior to dietary supplementation. Serum levels of triglyceride and LDL cholesterol differed significantly between the two study groups after 4 weeks of dietary supplementation. CONCLUSIONS: Dietary supplementation with perilla seed oil in selected patients with asthma suppresses the generation of LTC4 and is associated with clinical features such as respiratory function and lipometabolism.

Adult↗

PubMed2000

Evolution in the hypervariable region of hepatitis C virus in infants after vertical transmission.

To elucidate the clonal evolution of hepatitis C virus (HCV) during mother-to-infant transmission, we prospectively analyzed HCV clones of the hypervariable region in four HCV RNA-positive infants and compared them with those of the mother. Cord blood samples from three of the four infants were positive for the HCV RNA (< or =10(3) copies/mL), and all of the four infants had the HCV RNA titer of >10(6) copies/mL within 2 mo after birth. The hypervariable region clones detected in the infants were closely related to those in the respective mothers. The results suggest the perinatal transmission of HCV. The hypervariable region clones transmitted to infants were not a single selected clone or minor clones in the mother. None of the clones specific to the low-density fraction in the mother was transmitted to the infants. Moreover, the proportion of HCV in the low-density fraction was minimal in the first few months of life, but increased several months after birth in association with the elevation of alanine aminotransferase. These results suggest that the increase of HCV in the low-density fraction reflect the evolution of immune response in infants. We also demonstrated that the emergence of quasispecies in infants precedes the infantile antibody response.

Aging↗