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A Kaneko

Publications and source records attributed to A Kaneko.

At least 91 records · Page 5Linked to original sources
PubMed1999

Histology according to the Revised European-American Lymphoma Classification significantly predicts the prognosis of ocular adnexal lymphoma.

Lymphoid infiltrates in the ocular adnexa are mostly low-grade B-cell lymphoma, but their clinicopathologic characteristics and prognostic factors have not been extensively analyzed according to the Revised European-American Lymphoma (REAL) Classification. We reviewed histopathologic sections from 77 patients with primary ocular adnexal lymphoid infiltrates, and conducted univariate and multivariate analyses of possible prognostic factors. Fifty-seven of the 77 patients were confirmed to have malignant lymphoma. Histopathologic sections from 44 of the 57 patients were reclassified into the following categories; marginal zone lymphoma (MZL) in 35, mantle cell lymphoma (MCL) in two, diffuse large cell lymphoma (DLCL) in six, and lymphoplasmacytoid lymphoma (LPL) in one. In the remaining 13 patients, biopsied specimens were inadequate for further subclassification. The cause-specific survival rates of the 57 patients with primary ocular adnexal lymphoma at 5, 10, and 15 years were 90.1%, 84.8% and 84.8%, respectively. The univariate analysis showed that the clinical stage, serum lactate dehydrogenase (LDH) value and histopathologic subtype were significant. The 5-year cause-specific survival rate of the 35 patients with MZL was 100%, whereas that of the eight patients with non-MZL (DLCL and MCL) was 25% (p<0.0001). The multivariate analysis revealed that the histologic subtype (p=0.010) and serum LDH value (p=0.015) were independent significant predictors of survival. We conclude that malignant lymphomas occurring in the ocular adnexa histologically consist mostly of MZL. The histologic subtype according to the REAL Classification significantly predicts the prognosis of ocular adnexal lymphoma.

Adult↗
PubMed1999

Proguanil disposition and toxicity in malaria patients from Vanuatu with high frequencies of CYP2C19 mutations.

The increasing resistance of falciparum malaria to common antimalarial drugs has renewed interest in the compound proguanil normally metabolized to cycloguanil, a strong dihydrofolate reductase inhibitor, via the cytochrome P450 isozyme CYP2C19. The relationship between CYP2C19 genotypes and proguanil metabolism was therefore studied in 100 uncomplicated malaria patients on Malakula island in Vanuatu, where a CYP2C19-related poor metabolizer genotype status was known to be frequent. The patients (median age, 7 years) with Plasmodium falciparum or P. vivax infections, received proguanil treatment for 3 days in daily doses corresponding to adult doses of 300-500 mg. Capillary blood samples were collected on filter paper for determining both human CYP2C19 mutations by polymerase chain reaction and mutation-specific restriction enzyme digestion and blood concentrations of proguanil and its metabolites by high-performance liquid chromatography. The frequencies of the defective alleles, CYP2C19*2 and CYP2C19*3, were 0.57 and 0.25, respectively. The patients were genotyped as 68 CYP2C19-related poor metabolizers and 32 extensive metabolizers. Proguanil concentrations were higher and cycloguanil and 4-chlorophenylbiguanide concentrations were lower in poor compared to extensive metabolizers. Among the extensive metabolizers, 27 were heterozygous and five were homozygous for unmutated alleles. The tendency of an intermediate degree of proguanil metabolism in heterozygous extensive metabolizers as compared to homozygous extensive metabolizers and poor metabolizers suggests the trend towards the existence of a gene dose effect. Mild adverse events (mainly gastro-intestinal symptoms) were often reported and positively correlated with proguanil concentrations. The incidence was, however, similar in poor and extensive metabolizers. In conclusion, our data demonstrate an association between CYP2C19 mutations and poor metabolism of proguanil.

Antimalarials↗
PubMed1999

[In vitro bactericidal activities of new oral penem, faropenem against the various clinical isolates].

The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of faropenem (FRPM) more compared with those of various oral beta-lactams against 15 isolates each of 6 species of microorganism. FRPM possessed potent in vitro antibacterial activity against both aerobic and anaerobic Gram-positive bacteria tested. FRPM showed the same activity as new oral cephems such as cefdinir, cefditoren and cefcapene against all Gram-negative bacteria, but K. pneumoniae strains were less susceptible. The MBC of FRPM against S. pneumoniae and the other strains tested equal and were within 1 dilution the MIC of that, respectively. These results suggest that FRPM has excellent in vitro bactericidal activity against clinical isolates and is a clinically useful for the chemotherapy of bacterial infections.

Anti-Bacterial Agents↗
PubMed1999

Prolactin locally produced by synovium infiltrating T lymphocytes induces excessive synovial cell functions in patients with rheumatoid arthritis.

OBJECTIVE: To elucidate the role of prolactin (PRL) produced in joints as part of the pathological response of rheumatoid arthritis (RA), we studied PRL production and prolactin receptor (PRLR) expression in RA synovium and its effects on RA synovial cell functions. METHODS: Proinflammatory cytokine and matrix metalloproteinase (MMP) production by RA synovial cells was estimated by ELISA, Western blotting analysis, and zymography. Expression of PRLR by RA synovial cells and local production of PRL were estimated by reverse transcription polymerase chain reaction and immunohistochemical staining. RESULTS: PRL enhanced RA synovial cell proliferation. Production of proinflammatory cytokine and MMP was augmented and production of tissue inhibitor of metalloproteinases (TIMP)-1 was inhibited by PRL treatment of RA synovial cells, suggesting that PRL enhances total collagenase activity in the joints. PRLR was exclusively expressed on fibroblast-like synovial cells and lymphocytes infiltrating into the synovium in patients with RA. Both synovium infiltrating T lymphocytes and, to a lesser extent, fibroblast-like synovial cells synthesized PRL, suggesting that PRL acts as a paracrine as well as autocrine activator of RA synovial cell functions. Stimulation of synovial cells by PRL induced rapid translocation of STAT-5 from cytoplasm into nuclei of RA synovial cells, suggesting that transcriptional regulation of RA synovial cell functions by PRL affects STAT-5. Inhibitors of PRL release, such as bromocriptine, inhibited proliferation of proinflammatory cytokines and collagenases by RA synovial cells. CONCLUSION: Our findings emphasize the importance of PRL, locally produced by infiltrating T lymphocytes, for aberrant synovial cell functions in RA, and suggest possible clinical application of PRL inhibitors.

Aged↗
PubMed1999

[A case of Creutzfeldt-Jakob disease exhibiting athetosis in the early stage].

A 68-year-old man was hospitalized on 24 June, 1998 because of visual and gait disturbance. A month before admission, he had been aware of blurred or double vision while watching TV. A few days later, he developed dysphagia and clumsiness in the fingers. His gait became unstable and he exhibited restless finger movements. His shoulders and trunk showed torsion while walking. On admission, he became disoriented and showed rigidity in the legs and athetosis in the bilateral fingers. Routine laboratory findings, thyroid function data, and the serum levels of vitamin B1, B12, Cu, and ceruloplasmin were within the normal ranges. Periodic synchronous discharges (PSD) were observed on electroencephalography. MRI showed T2-high intensity and atrophy of the bilateral caudate nucleus and putamen in addition to the cerebral cortex. 99mTc-ECD-SPECT showed a decrease of local blood flow in the bilateral frontal, right temporal, and bilateral parietal lobes and bilateral thalami. Athetosis became exacerbated and was observed for a month, overlapping with myoclonus. We diagnosed the patient as having CJD because of progressive dementia, myoclonus and PSD. Analysis of the prion protein revealed that codon 129 was Met/Met and codon 219 Glu/Glu by DNA sequences. The patient developed akinetic mutism and rigid contracture, and died of pneumonia on 5 September, 1998. Because athetosis is thought to involve the bilateral caudate nucleus, putamen and thalamus, the findings of diagnostic imaging in this patient might be relative to the clinical symptoms.

Aged↗
PubMed1999

High and variable frequencies of CYP2C19 mutations: medical consequences of poor drug metabolism in Vanuatu and other Pacific islands.

Cytochrome P450 (CYP) 2C19 is polymorphic with poor metabolizers representing 3-6% of Europeans and Africans, and 13-23% of Asians. Greater than 99% of the poor metabolizer alleles in Asian populations are defined by two single base pair mutations (CYP2C19*2 and CYP2C19*3). We have recently reported an unprecedentedly high prevalence (71%) of CYP2C19-related poor metabolizer genotype individuals and poor metabolism of proguanil on two malarious islands of Vanuatu in eastern Melanesia. To elucidate this further, a total of 5538 individuals from 24 populations on 16 different islands of Vanuatu were genotyped. Of these, 61% had a poor metabolizer genotype (*2/*2, *2/*3 or *3/*3) with substantial variation among the populations (38-79%). The overall frequencies of CYP2C19*1 (wild-type), CYP2C19*2, and CYP2C19*3 were 0.223, 0.633, and 0.144, respectively. A significant linear correlation was observed between heterozygosity and South latitude (r = 0.552, P < 0.05). The genotype frequencies of 21 of the 24 populations were consistent with Hardy-Weinberg expectations (P > 0.05). Comparisons of genetic, linguistic and geographical patterns among populations suggest that short range gene flow is largely responsible for the current distribution of CYP2C19 alleles in Vanuatu. Taken together with previous studies of nuclear genetic loci of Pacific island populations, these data predict that the poor metabolizer genotype is common throughout Polynesia and Micronesia and may be even more prevalent in western Melanesia than in Vanuatu. This suggests that the majority of Pacific Islanders metabolize a wide variety of clinically important drugs to a significantly lower degree than the average European.

Antimalarials↗
PubMed1999

[In vitro activities of levofloxacin and other antibiotics against fresh clinical isolates].

In this study, the in vitro activity of levofloxacin (LVFX) against 1,020 fresh bacterial clinical isolates was compared with the activities of a range of ofloxacin, ciprofloxacin (CPFX), ampicillin (ABPC), cefaclor, cefpodoxime, methicillin and benzylpenicillin. The clinical isolates except Vibrio cholerae were collected in Japan during 1998 from patients with infectious diseases. MICs were determined using the agar dilution method according to the recommendations by the Japan Society of Chemotherapy. Some isolates of methicillin resistant Staphylococcus aureus (MRSA) and coagulase negative Staphylococcus were resistant to fluoroquinolones, but the MIC50 of LVFX against MRSA was 6.25 micrograms/ml. LVFX was the most active against MRSA among the antibiotics tested. Most of Staphylococcus epidermidis strains were susceptible to the fluoroquinolones. LVFX showed greater activity against all streptococci strains compared with fluoroquinolones tested. In particular, all Streptococcus pneumoniae strains including PRSP were susceptible to LVFX at < or = 1.56 micrograms/ml. Among Enterococcus, ABPC showed superior activity against Enterococcus faecalis but many isolates of Enterococcus species were resistant to ABPC. LVFX was more active against to these Enterococcus species compared with other fluoroquinolones. On the other hand, LVFX and CPFX showed similar activity against isolates of Enterobacteriaceae. CPFX had an MIC50/90 of 0.20, 0.39 microgram/ml and LVFX showed an MIC50/90 of 0.78, 1.56 micrograms/ml against Pseudomonas aeruginosa. LVFX (MIC50/90 0.10, 0.20 microgram/ml) was more active against Acinetobacter species than CPFX (MIC50/90 0.10, 0.39 microgram/ml). Haemophilus influenzae, Branhamella (Moraxella) catarrhalis and V. cholerae were inhibited by low concentration of the fluoroquinolones tested. The MIC90 of LVFX and CPFX were < or = 0.10 microgram/ml against above three species. Some isolates of Neisseria gonorrhoeae and Campylobacter species were moderately resistant to the fluoroquinolones tested but the MIC50 of LVFX and CPFX were < or = 0.39 microgram/ml. Among anaerobes, Propionibacterium acnes was more susceptible than Peptostreptococcus species, and the MIC90 of beta-lactams and fluoroquinolones tested were < or = 0.78 microgram/ml. In conclusion, this study, performed on large number of strains, confirmed an excellent and wide spectrum antibacterial activity of LVFX compared with the fluoroquinolones and beta-lactams tested. And our results suggest that LVFX may be useful in the treatment of various bacterial infections.

Ampicillin↗
PubMed1999

Laparoscopic low anterior resection using a triple stapling technique.

Laparoscopic low anterior resections using a triple stapling technique in five patients with rectal cancers (four Dukes A and one Dukes C) were performed. The location of the tumors was between 5 and 18 cm from the anal verge. For easy maneuverability, a 33-mm suprapubic port was used. In this technique, the Endo TA (the first stapler) is applied at the distal margin of the rectum to occlude the bowel. The bowel is irrigated with povidone-iodine solution and transected by an endolinear (the second) stapler. Anastomosis is completed by firing the circular (the third) stapler. The operative time was 177 +/- 28.0 minutes, estimated blood loss was 41.7 +/- 28.6 g, and flatus appeared 1.8 +/- 0.8 days after surgery. Follow-up studies have showed no local recurrence or distant metastasis. This procedure is safe and useful for performing laparoscopic low anterior resection.

Adenocarcinoma↗
PubMed1999

Effects of actarit on synovial cell functions in patients with rheumatoid arthritis.

OBJECTIVE: Actarit (4-acetylaminophenylacetic acid), developed in Japan, has been shown to be effective for suppressing disease activity of rheumatoid arthritis (RA). We analyzed effects of actarit on synovial cell functions in patients with RA for insight into the clinical application of this medication. METHODS: RA primary synovial cells were co-cultured with actarit at 10(-4)-10(-7) M. Their subsequent proliferative responses and proinflammatory cytokine and matrix metalloproteinase (MMP) production at the mRNA and protein levels were measured. Effects of actarit on adhesion molecule expression were analyzed by immunofluorescence flow cytometry and cell-cell binding assay. RESULTS: Spontaneous tumor necrosis factor-alpha and interleukin 1beta secretion by primary synovial cells of patients with RA was reduced by actarit at therapeutic concentrations (10(-5)-10(-6) M). In contrast, actarit also suppressed MMP-1 production by the primary synovial cells. In addition, actarit down-regulates CD44 and intercellular adhesion molecule 1 expression on fibroblast-like synovial cell lines, and very late antigen 4 expression on CD14+ macrophage-like synovial cells resulted in the inhibition of lymphocyte adhesion to RA synovial cells. CONCLUSION: The results suggest that actarit acts on RA synovial cells to reduce cell-cell interactions with autologous synovium infiltrating lymphocytes and to inhibit proinflammatory cytokine and MMP production, leading to amelioration of symptoms of RA.

Antirheumatic Agents↗
PubMed1998

Human granulocyte colony-stimulating factor (G-CSF) stimulates the in vitro and in vivo development but not commitment of primitive multipotential progenitors from transgenic mice expressing the human G-CSF receptor.

Granulocyte colony-stimulating factor (G-CSF) stimulates the proliferation and restricted differentiation of hematopoietic progenitors into neutrophils. To clarify the effects of G-CSF on hematopoietic progenitors, we generated transgenic (Tg) mice that had ubiquitous expression of the human G-CSF receptor (hG-CSFR). In clonal cultures of bone marrow and spleen cells obtained from these mice, hG-CSF supported the growth of myelocytic as well as megakaryocytic, mast cell, mixed, and blast cell colonies. Single-cell cultures of lineage-negative (Lin-)c-Kit+Sca-1(+) or Sca-1(-) cells obtained from the Tg mice confirmed the direct effects of hG-CSF on the proliferation and differentiation of various progenitors. hG-CSF also had stimulatory effects on the formation of blast cell colonies in cultures using 5-fluorouracil-resistant hematopoietic progenitors and clone-sorted Lin-c-Kit+Sca-1(+) primitive hematopoietic cells. These colonies contained different progenitors in proportions similar to those obtained when mouse interleukin-3 was used in place of hG-CSF. Administration of hG-CSF to Tg mice led to significant increases in spleen colony-forming and mixed/blast cell colony-forming cells in bone marrow and spleen, but did not alter the proportion of myeloid progenitors in total clonogenic cells. These results show that, when functional G-CSFR is present on the cell surface, hG-CSF stimulates the development of primitive multipotential progenitors both in vitro and in vivo, but does not induce exclusive commitment to the myeloid lineage.

Animals↗
PubMed1998

Noise analysis of the quinine-induced current in frog taste receptor cells.

It has been shown that quinine, a bitter tasting substance, induces a cationic membrane current in frog taste receptor cells. We analyzed the quinine-induced current fluctuation to further characterize the cationic channel conducting the current. Taste cells were enzymatically isolated from fungiform papillae of the bullfrog tongue. Membrane currents were recorded under voltage-clamp by using the whole-cell patch clamp technique. A Cs(+)-containing pipette solution was used to block K+ currents. When quinine was bath applied, it induced a steady inward current in cells held at -60 mV. The current data were digitized at a sampling frequency of 2 kHz after having been low-pass filtered (cut-off frequency, 1 kHz). The spectral density distribution was calculated by 1024 points fast Fourier transform (FFT), and was fitted by a sum of two Lorentzian functions, with corner frequencies at 10-20 Hz and at 90-120 Hz. The single-channel conductance calculated from the variance versus mean current plot was 5 pS in a normal saline solution containing 1.8 mM Ca2+. In a nominally Ca(2+)-free solution, the single-channel current was doubled. Our previous study has shown that the quinine-induced current is enhanced in low extracellular [Ca2+]. This enhancement could be partly attributable to the Ca2+ suppression of the single-channel conductance.

Analgesics, Non-Narcotic↗
PubMed1998

Improved method for the simultaneous determination of proguanil and its metabolites by high-performance liquid chromatography and solid-phase extraction of 100-microl capillary blood samples dried on sampling paper.

An improved method is presented for the determination of proguanil, cycloguanil and 4-chlorophenylbiguanide in 100-microl capillary blood samples applied to sampling paper. This method also utilises a solid-phase extraction technique and high-performance liquid chromatography. Different kinds of sampling paper, such as ion-exchange and cellulose sampling paper were tested. The best elution recovery (70-80%) was obtained after treatment of cellulose sampling paper with a quaternary ammonium compound. The limit of determination was 50 nmol/l for cycloguanil and 4-chlorophenylbiguanide and 125 nmol/l for proguanil using 100 microl capillary blood. The stability of the analytes and elution performance from sampling paper was validated at different temperature and storage time. Venous blood and capillary blood concentrations of proguanil and metabolites were found to be similar.

Antimalarials↗
PubMed1998

Malaria epidemiology, glucose 6-phosphate dehydrogenase deficiency and human settlement in the Vanuatu Archipelago.

Vanuatu is located at the southeast margin of the malarious band extending from southeast Asia to eastern Melanesia. We analysed the malaria situation on different islands of Vanuatu, using passive case detection and malariometric survey data from 1985 to 1992, i.e. after the DDT residual programme ceased and before the impregnated bed-nets programme started on a larger scale. Malaria was mainly hypo-mesoendemic but with hyperendemic spots in certain years and on some islands. The transmission was generally more intense in the northern islands than in the south. In the late 1980s, annual parasite incidence per one thousand population (API) was around 180. The overall parasite rate was 11.9% with Plasmodium falciparum, P. vivax and P. malariae rate of 5.2, 6.7, and 0.1%, respectively. There was a seasonal fluctuation of P. falciparum incidence, whereas the P. vivax incidence was rather stable. Vivax malaria was confined to children less than 10 years old, while the intense in the northern islands than in the south. In the late 1980s, annual parasite incidence per one thousand population (API) was around 180. The overall parasite rate was 11.9% with Plasmodium falciparum, P. vivax and P. malariae rate of 5.2, 6.7, and 0.1%, respectively. There was a seasonal fluctuation of P. falciparum incidence, whereas the P. vivax incidence prevalence of P. falciparum only changed moderately with age. The mean rate of glucose 6-phosphate dehydrogenase (G6PD) deficiency among male subjects was in 7.4% but with a wide variation of 0-14.3% on different islands. A positive rank-order correlation was found between malaria incidence and G6PD deficiency rate on the different islands. A reasonable hypothesis is that malaria was introduced to the islands with the first human settlement 4000 years ago, with a geographical malaria distribution similar to the present situation. Different malaria endemicities possibly then selected different prevalences of G6PD deficiency over many generations.

Adolescent↗
PubMed1998

L-type calcium channels in the axon terminal of mouse bipolar cells.

Two types of calcium current (I(Ca)) have been identified in the bipolar cell of the mouse retina: a transient (T-) type current and a long lasting (L-) type current. It has been suggested that the former is present in the soma and the latter in the axon terminal. To establish the cellular localization of the two types of I(Ca), bipolar cells of the mouse retina was studied electrophysiologically in a slice preparation, and immunocytochemically by staining specific calcium channels in isolated cells. The dihydropyridine-sensitive L-type I(Ca) was recorded in the axon terminal, and the T-type current was recorded in the somatic region. Strong immunoreactivity to a polyclonal antibody against the L-type calcium channel was found in the axon terminal. These observations suggest that the L-type I(Ca) is generated at the axon terminal and contributes to the transmission of sustained depolarization.

Animals↗
PubMed1998

Thrombotic thrombocytopenic purpura developed suddenly during interferon treatment for chronic hepatitis C.

A 57-year-old man had abnormal hepatic function identified in April 1994. In October 1994, chronic hepatitis C was diagnosed. Based on the findings of a liver biopsy, administration of recombinant interferon (rIFN)-alpha2b was begun. In the 16th week of treatment, the patient experienced headache and fever and developed a markedly decreased, platelet count and hemolytic anemia. He was admitted on May 19, 1995 and thrombotic thrombocytopenic purpura (TTP) was diagnosed. He died on the 3rd hospital day. The causes of TTP have yet to be elucidated, but in this patient the occurrence of TTP appeared to be related to the IFN treatment for chronic hepatitis C.

Antiviral Agents↗