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Biomedical subjects

A Kaneko

Publications and source records attributed to A Kaneko.

At least 145 records · Page 8Linked to original sources

[Comparison of life habits and health examination data between smokers and ex-smokers].

Health practice and health examination data were compared between smokers and ex-smokers in 6,076 male subjects, whose ages ranged from 40 to 59 years, who participated in health examinations in 1993 in 17 towns of Gunma Prefecture. A total of 4,629 (76.2%) subjects replied to the interview on health practice and also had health examination data that could be used. The numbers of smokers and ex-smokers were 2,681 and 245, respectively for a total of 2,926 target population. The percentage for those having breakfast daily was significantly higher in ex-smokers than in smokers in the age 40's group (p < 0.01). The percentage for those doing exercise more than one day a week was significantly higher in ex-smokers than in smokers in the age 50's group (p < 0.05). Mean body mass index (BMI) was significantly higher in ex-smokers than in smokers in the age 40's and 50's groups, with p < 0.05 and p < 0.01, respectively. Mean high-density lipoprotein cholesterol (HDLC) was significantly higher in ex-smokers than in smokers in the age 40's group (p < 0.05). The two way analysis of variance on BMI and HDLC was conducted by smoking and drinking factors. BMI was related to only smoking in the age 40's and 50's groups. Smoking and drinking habit related to HDLC in the age 40's group and the latter habit had a relatively large association to HDLC. From the association between BMI and smoking habit, we speculate that exercise was practiced by ex-smokers due to the obesity potential of the ex-smoking status.

Adult↗

[A case of familial amyotrophic lateral sclerosis with markedly decreased accumulation on 123I-MIBG myocardiac scintigraphy and atonic bladder].

A 63-year-old Japanese woman with familial amyotrophic lateral sclerosis (ALS) showed cardiac hypofunction and neurogenic bladder. Her autonomic function was evaluated by means of 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy and urodynamic study. (1) MIBG scintigraphy: Both early and late imagings showed severe defects of myocardial 123I-MIBG accumulation despite the normal accumulation of 201thallium. (2) Urodynamic study: Atonic bladder was observed on cystometry. These data indicate that both sympathetic and parasympathetic nerve functions were disturbed, suggesting the possibility that autonomic disturbance in familial ALS may differ from those in sporadic ALS, in which increased sympathetic nervous function has been reported.

3-Iodobenzylguanidine↗

Genomic imprinting of the human serotonin-receptor (HTR2) gene involved in development of retinoblastoma.

Epidemiological and genetic studies of retinoblastoma (RB) suggested that imprinted genes might be genetically linked to the RB gene. In this study, we found that the human serotonin-receptor, HTR2, gene, which had been mapped nearby the RB gene on chromosome 13, was expressed only in human fibroblasts with a maternal allele and not in cells without a maternal allele. The 5' genomic region of the human HTR2 gene was cloned by PCR-mediated method. Only the 5' region of the gene was methylated in cells with the maternal gene, and it was not methylated in cells without the maternal gene. A polymorphism of PvuII site of the gene was also found and useful for the segregation analysis in a family of a RB patient and for analysis of loss of heterozygosity on chromosome 13 in tumor and its parental origin. These results suggest that the human HTR2 gene might be affected by genomic imprinting and that exclusive expression of the maternal HTR2 gene may be associated with the delayed occurrence of RB, which had lost the maternal chromosome 13.

Alleles↗

Delayed development of retinoblastoma associated with loss of a maternal allele on chromosome 13.

Loss of heterozygosity (LOH) on chromosome 13, which is associated with the functional inactivation of the retinoblastoma (RB) gene, is critical for the development of RB. To date, we have found that LOH-negative tumors develop earlier than LOH-positive tumors in hereditary cases of RB, an observation which suggests that loss of one allele on chromosome 13 may be disadvantageous with respect to growth of RB tumors. In this study, the parental origin of the lost allele on chromosome 13 and the age at operation of 13 patients with non-hereditary RB tumors that had been enucleated at the same stage were studied, in an attempt to determine whether there are any differences between tumors with loss of a maternal allele on chromosome 13 and tumors with loss of a paternal allele. Six tumors had lost the maternal allele and 7 tumors had lost the paternal allele on chromosome 13. The age (average 694 days) of patients at operation in the case of tumors with loss of the paternal allele was significantly lower than the age (average 1,079 days) of patients at operation for removal of tumors with loss of the maternal allele. RB tumors that had lost the maternal allele on chromosome 13 developed later than tumors that had lost the paternal allele. The possibility is discussed that loss of the maternal allele on chromosome 13 might be disadvantageous for growth of RB tumors.

Age Factors↗

Induction of apoptosis in cultured retinoblastoma cells by the protein phosphatase inhibitor, okadaic acid.

The induction of apoptosis in cultured retinoblastoma cells by diverse drugs was examined by analyzing DNA fragmentation, a hallmark of apoptosis. First, the ability of six retinoblastoma cell lines to undergo apoptosis was surveyed using etoposide (30 micrograms/ml, 20 h exposure). The NCC-RbC-60 cell line, established in this laboratory showed DNA fragmentation clearly, whereas the other cell lines tested, including the representative retinoblastoma cell line, Y-79, did not show distinct DNA fragmentation. Biochemical modulators, such as A23187, forskolin, retinoic acid, phorbol 12-myristate 13-acetate and okadaic acid, were examined to ascertain whether they could induce apoptosis in NCC-RbC-60 and Y-79 cells after exposure for 20 h. Only okadaic acid induced DNA fragmentation in all the retinoblastoma cell lines tested and it induced DNA fragmentation in Y-79 cells in a time- and concentration-dependent manner. Flow-cytometric analysis and microscopic examination revealed that Y-79 cells treated with okadaic acid for 24-48 h accumulated at the G2/M, especially M, phases, before undergoing DNA fragmentation. Other mitotic poisons, nocodazole, colcemid and taxol, also induced apoptosis in Y-79 cells. In the K1034 cell line, established from non-malignant retinal pigmented epithelium, okadaic acid failed to induce both G2/M arrest and DNA fragmentation. These findings suggest that okadaic-acid-induced apoptosis occurs as a result of metaphase arrest.

Apoptosis↗

Expression and phosphorylation of rat c-met/hepatocyte growth factor receptor during rat liver regeneration.

Hepatocyte growth factor receptor is identified as a heterodimeric tyrosine kinase encoded by the c-met gene. This study was designed to determine how the c-met/hepatocyte growth factor receptor participates in the intracellular events involved in rat liver regeneration induced by administration of carbon tetrachloride. Expression of the rat c-met mRNA increased, peaking 24 h after carbon tetrachloride administration almost in parallel with MET protein expression. Histochemical studies demonstrated that expression of the rat c-met was enhanced in cells surrounding the damaged areas, and also that the distribution of cells expressing MET was almost in accordance with that of cells expressing proliferating cells nuclear antigen. The MET protein underwent intense tyrosine phosphorylation peaking at 12 h after carbon tetrachloride administration, and prior to DNA synthesis. Phospholipase C gamma and phosphatidylinositol 3-kinase, intracellular signal transducing molecules containing Src homology 2 domain, were associated with the MET protein following tyrosine phosphorylation in vivo. These observations suggest that expression and tyrosine phosphorylation of MET protein associated with signal transducing molecules may provide a mechanism whereby hepatocyte growth factor exerts its action on hepatocyte growth during rat liver regeneration induced by carbon tetrachloride administration.

Animals↗

Accumulation of lauric acid in skin as an enhancer for the percutaneous absorption of thiamine disulfide.

The permeation and accumulation of lauric acid (12:0) in rat skin as an enhancer for the percutaneous absorption of thiamine disulfide (TDS), using propylene glycol as a vehicle, were determined in vitro. 12:0 barely permeated through skin, and accumulated in skin. The accumulated amount increased increasing concentrations in the vehicle (1-20%). The proportion of the accumulation to total dose was highest at a dose of 5%. A positive relationship was found between the accumulated amount of TDS and 12:0. It was suggested that the penetration of 12:0 into skin contributes to the enhanced partition of TDS to skin.

Animals↗

Cell dissociation with papain reduces the density of cGMP-activated channels of the retinal rod.

A proteolytic enzyme, papain, is the enzyme commonly used for dissociation of retinal neurons. To ask whether papain modifies the activity of ion channels, cGMP-activated channels were recorded in inside-out membrane patches excised from the bullfrog rod outer segment, and the activity was compared between cells dissociated using papain and cells dissociated mechanically. While the affinity to cGMP, I-V relation, channel kinetics, and single-channel current amplitude were almost the same in both papain-treated and the control preparations, the total current flowing through the patch membrane of the papain-treated cells was reduced to about 20% of the control, suggesting that papain reduced the density of cGMP-activated channels.

Animals↗

GABA-induced chloride current in catfish horizontal cells mediated by non-GABAA receptor channels.

GABA-induced currents were recorded in cone-driven horizontal cells dissociated from the catfish, using the patch clamp technique in the whole-cell configuration. GABA-induced current consisted of two components; approximately 80% of the current was blocked by 100 microM picrotoxin (PTX), and the remaining 20% of the current was blocked when extracellular Na+ was replaced with Li+ or choline. The PTX-sensitive current was carried by Cl-. When methanesulfonate was substituted for the intrapipette Cl-, the reversal potentials of the PTX-sensitive current shifted to a more negative potential close to the Cl- equilibrium potential. The PTX-sensitive current was unaffected either by bicuculline (up to 500 microM), pentobarbital (100 microM), or diazepam (100 microM). These observations suggest that the PTX-sensitive current is not mediated via GABAA receptors. Baclofen, a GABAB receptor agonist, had no effect, suggesting the absence of GABAB receptors. Cis- or trans-4-aminocrotonic acid (CACA and TACA), GABAC receptor agonists, evoked currents in a dose-dependent manner. The potency sequence was TACA > GABA > muscimol > CACA. These observations suggest that the PTX-sensitive current of cone-driven horizontal cells is carried via the GABAC receptor channel. The Cl- equilibrium potential in intact cells was estimated to be approximately -30 mV by recording the GABA-induced voltage response of dissociated cells with a conventional intracellular microelectrode. The intracellular Cl- concentration seemed to be approximately 40 mM. From these results, it is suggested that GABAC receptor channels shape the kinetics of light-induced responses of horizontal cells, and mediate a chemical coupling between neighboring horizontal cells.

Animals↗

Actions of nipecotic acid and SKF89976A on GABA transporter in cone-driven horizontal cells dissociated from the catfish retina.

Whole-cell voltage-clamp recordings were made from dissociated horizontal cells of the catfish retina. In the presence of picrotoxin (PTX, 100 microM), GABA evoked a sustained inward current at negative holding potentials. Dose-response measurements were well fitted by a logistic curve with a Hill coefficient of 1.11 and EC50 of 9.76 microM. When external Na+ was replaced with Li+, this GABA-induced current was eliminated. The substitution of methanesulfonate for Cl- also suppressed the current. This current was blocked by either nipecotic acid or SKF89976A. However, the mechanisms by which these drugs suppress the GABA-induced current differ. Intracellularly applied SKF89976A blocked the GABA-induced current, while nipecotic acid intracellularly had no effect. beta-Alanine at concentrations greater than 1 mM exerted a slight inhibitory effect. Extracellularly applied SKF89976A produced no current by itself but suppressed GABA-induced currents. Dose-response curves showed that SKF89976A has an IC50 of 0.93 microM and a Hill coefficient of 2.68. Nipecotic acid evoked a current response, like GABA. A Hill coefficient was 1.64 and an EC50 was 7.69 microM. This nipecotic acid-induced current was blocked by substituting Li+ for Na+ or by the addition of SKF89976A. This result is consistent with other studies indicating that nipecotic acid is transported in place of GABA. Extracellular Na+ was required for the prolonged suppression by extracellularly applied SKF89976A, while the extracellular Cl- depletion has no influence on the suppression. The pharmacological profile of this GABA transporter fits the neuronal rather than the glial type of cloned transporters.

Animals↗

Neuronal nicotinic acetylcholine receptors of ganglion cells in the cat retina.

Ganglion cells, retrogradely labeled with DiI, were dissociated from the cat retina. Under the whole-cell clamp mode using a patch pipette, ACh induced a transient current (IACh) in all cells tested. The soma diameter of ACh-responsive cells distributed from 11 to 23 microns, indicating that the preparation included Y, X, and W cells. IACh was inward rectifying. The reversal potential of IACh was close to the zero-current potential predicted from the intra- and extracellular monovalent cation concentrations by the Goldman-Hodgkin-Katz equation. The concentration-response curve gave a Hill coefficient of 0.89 and an EC50 of 3.2 x 10(-5) M. Nicotine (10(-4) M) induced a transient current, while muscarine (10(-4) M) was ineffective. The nicotinic antagonist, hexamethonium, reduced the amplitude of IACh in a concentration-dependent manner with an IC50 of 1.3 x 10(-6) M. The muscarinic antagonist, atropine, showed a concentration-dependent reduction in the amplitude of IACh with an IC50 of 4.4 x 10(-6) M. The amplitude of IACh was dependent on the extracellular Ca2+ concentration ([Ca2+]O); small at low [Ca2+]O and large at high [CA2+]O. The time course of desensitization was also dependent on [Ca2+]O; fast at low [Ca2+]O and slow at high [Ca2+]O. The replacement of extracellular Ca2+ to Sr2+ increased the amplitude of IACh, but replacement to other divalent cations reduced it. The results indicate the presence of functional neuronal nicotinic ACh receptors in Y, X, and W cells.

Acetylcholine↗

[Comparative clinical study of azithromycin with tosufloxacin tosilate in the treatment of acute odontogenic infection].

To objectively assess azithromycin (AZM) for its clinical efficacy, safety and usefulness in the treatment of acute odontogenic infections (periodontitis, pericoronitis and osteitis of the jaw), a double-blind, randomized, multi-center trial was conducted in which tosufloxacin tosilate (TFLX) was used as the control drug. AZM was administered to 90 patients at a once-daily 500 mg dose for 3 days, while TFLX was given to 90 patients at a 150 mg t.i.d. dose for 7 days. 1. The clinical efficacy rates calculated according to evaluation at an endpoint set on the 3rd day of treatment by a committee of experts were 85.9% (73/85) in the AZM group and 78.9% (71/90) in the TFLX group. No statistically significant difference between the treatment groups was detected, and clinical equivalence was verified (p = 0.002). 2. The clinical efficacy rates according to evaluations made by investigators at the end-of-tail point was 87.1% (74/85) in the AZM group and 73.3% (66/90) in the TFLX group. The efficacy rate in the AZM group was higher than that in the TFLX group, and the difference was statistically significant (p = 0.006). 3. The bacteriological elimination rate in the AZM group was 97.5% (39/40) and that in the TFLX group was 85.7% (30/35), but the difference was deemed statistically not significant. 4. Adverse reactions were observed in 11 of 88 cases (12.5%) in the AZM group and 5 of 90 cases (5.6%) in the TFLX group. Six of 85 cases (7.1%) in the AZM group and 5 of 85 cases (5.9%) in the TFLX group showed laboratory abnormalities. However, neither adverse reactions nor laboratory abnormalities showed any differences in statistical significance between the treatment groups. 5. The safety rates, expressed as percentages of cases with no adverse events and no laboratory abnormalities, was 84.1% (74/88) in the AZM group and 90.0% (81/90) in the TFLX group. The difference between the two groups was found to be statistically insignificant. 6. The usefulness rates, the ratio of cases rated as either "Very useful" or "Useful", was 83.9% (73/87) in the AZM group, and it was statistically higher (p = 0.025) than 72.2% (65/90) obtained for TFLX group. Judging from the above results, it has been concluded that AZM is as useful as TFLX in the treatment of acute dental infections.

Adolescent↗

L-glutamate-induced responses and cGMP-activated channels in three subtypes of retinal bipolar cells dissociated from the cat.

Effects of L-glutamate (Glu), the neurotransmitter released by photoreceptors, on isolated cat bipolar cells were examined. Membrane currents of bipolar cells were recorded by the patch-clamp technique in a conventional whole-cell recording configuration using pipettes containing 1 mM cGMP, which has been known to activate a cationic current sensitive to Glu in ON-type bipolar cells. ON-type bipolar cells (depolarized by light in in situ) and OFF-type bipolar cells (hyperpolarized by light) were identified by their response polarity to Glu. When the whole-cell configuration was established, ON-type bipolar cells showed a steady inward current which was suppressed by Glu, consistent with the response polarity observed in in situ recordings. In contrast, OFF-type cells did not show a steady current during the recordings. However, they responded to Glu with an increase in cationic conductance. Among recorded cells, rod-driven bipolar cells were identified by their immunoreactivity to anti-protein kinase C (PKC-IR) antibody. Examination of PKC-IR revealed that ON-type bipolar cells included both rod- and cone-driven bipolar cells, while OFF-type cells were all cone-driven bipolar cells. The cGMP-activated current observed in ON-type cells was accompanied by a change in the current fluctuation due to the opening and closing of underlying channels. Fluctuation analysis gave a unitary conductance value of 13 pS. In half of the cells examined, maximum open probability reached almost 100%. The cGMP-activated channel in bipolar cells seems novel, fundamentally different from those found in photoreceptor cells or olfactory receptor cells.

Animals↗

[Antineuronal autoantibody to a 40-kDa protein in a patient with cerebellar ataxia and breast cancer].

A 49-year-old woman was admitted to Utsunomiya Saiseikai hospital complaining of right breast swelling. There was half a year history of difficulty in walking. A diagnosis of breast cancer was made by biopsy. Neurological examination revealed scanning speech, nystagmus, intention tremor and ataxic gait, but brain CT scan and MRI showed neither metastatic, invasive lesions nor atrophy in the brain. Lumpectomy for breast cancer was performed. For immunocytochemical studies, the cytoplasm of neurons in sections of normal human cerebral cortex, cerebellum, spinal cord and dorsal root ganglia were stained by the patient's serum, but glial cells were not. Upon Western blot, the patient's serum reacted with a 40-kDa protein in extracts of both cerebrum and cerebellum obtained from normal rats. A diagnosis of paraneoplastic cerebellar degeneration (PCD) was made on the basis of clinical manifestations and detection of the antineuronal antibody. The antibody accompanying the breast cancer which stained neuronal cytoplasm and bound to a 40-kDa protein may be a subtype of antibody causing PCD.

Autoantibodies↗

Activation of Na+/H+ exchanger by hepatocyte growth factor in hepatocytes.

The effect of the hepatocyte growth factor (HGF) on the Na+/H+ exchanger was studied using primary cultured hepatocytes. HGF induced intracellular pH (pHi) elevation of 0.10 pH units in hepatocytes cultured for 4 to 7 hours; the response was lower after other culture periods. Even with the same culture period, intercellular heterogeneity was found in the responsiveness to HGF. This heterogeneity may be partially accounted for by the weak but significant correlation observed between the basal pHi level and the degree of pHi elevation caused by HGF in hepatocytes. The pHi elevation caused by HGF was blocked on pretreatment of the hepatocytes with amiloride, suggesting that HGF activates the Na+/H+ exchanger. This hypothesis was confirmed by the fact that HGF increased the initial rapid rate of cell alkalization of acid-loaded hepatocytes. The tyrosine kinase inhibitor, genistein, also blocked the elevation, consistent with the fact that HGF receptor/c-met has a tyrosine kinase domain. To clarify the signal transduction pathway from tyrosine kinase to the Na+/H+ exchanger, we examined the effects of inhibitors of other kinases (H-7, H-8, and W-7) on the HGF-induced pHi elevation and found that only W-7 blocked it. This pHi elevation was also prevented on preincubation of the hepatocytes with thapsigargin, which blocks the calcium response caused by HGF. These results suggest that HGF activates the Na+/H+ exchanger in hepatocytes through a tyrosine kinase-calcium/calmodulin-dependent pathway.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Multiple glucose 6-phosphate dehydrogenase-deficient variants correlate with malaria endemicity in the Vanuatu archipelago (southwestern Pacific).

In studying the relationship between genetic abnormalities of red blood cells and malaria endemicity in the Vanuatu archipelago in the southwestern Pacific, we have found that of 1,442 males tested, 98 (6.8%) were G6PD deficient. The prevalence of GdPD deficiency varied widely (0%-39%), both from one island to another and in different parts of the same island, and generally correlated positively with the degree of malaria transmission. The properties of G6PD from GdPD-deficient subjects were analyzed in a subset of 53 samples. In all cases the residual red-blood-cell activity was < 10%. There were three phenotypic patterns. PCR amplification and sequencing of the entire coding region of the G6PD gene showed that the first of these patterns corresponded to G6PD Union (nucleotide 1360C-->T; amino acid 454Arg-->Cys), previously encountered elsewhere. Analysis of samples exhibiting the second pattern revealed two new mutants: G6PD Vanua Lava (nucleotide 383T-->C; amino acid 128Leu-->Pro) and G6PD Namoru (nucleotide 208T-->C; amino acid 70Tyr-->His); in three samples, the underlying mutation has not yet been identified. Analysis of the sample exhibiting the third pattern revealed another new mutant: G6PD Naone (nucleotide 497G-->A; amino acid 166Arg-->His). Of the four mutations, G6PD Union and G6PD Vanua Lava have a polymorphic frequency in more than one island; and G6PD Vanua Lava has also been detected in a sample from Papua New Guinea. G6PD deficiency is of clinical importance in Vanuatu because it is a cause of neonatal jaundice and is responsible for numerous episodes of drug-induced acute hemolytic anemia.

Adolescent↗

Eyelid metastasis from breast cancer showing marked response to chemotherapy.

A patient with recurrent breast cancer, who was diagnosed with eyelid metastasis as a part of systemic metastases and in whom systemic chemotherapy was markedly effective, is reported. A 50-year-old woman underwent a radical mastectomy for stage II breast cancer in October, 1988. Histologically, the tumor was invasive lobular carcinoma. In October, 1993, the patient consulted our hospital complaining primarily of swelling of the left eyelid and restriction of movement in the left eye. Metastasis from breast cancer was diagnosed on eyelid biopsy. On further examination, metastases were detected in the liver, bone, orbit, peritoneum and pleura. Systemic combined chemotherapy consisting of cyclophosphamide, adriamycin and 5-fluorouracil was administered intravenously at intervals of three weeks. Complete responses were obtained in the eyelid and peritoneal metastases after three courses, and in the liver metastasis after five courses. Partial responses were also observed in the bone and pleural metastases. The incidence of eyelid metastasis from breast cancer is very low, one case only having been previously reported in Japan and 34 cases abroad. Most of these cases were treated locally by surgical resection or radiotherapy, but the mean survival period was only 14 months, ranging from two months to four years. Eyelid metastasis from breast cancer should be regarded as a manifestation of systemic spread of the tumor and, in principle, treated by systemic therapy.

Antineoplastic Combined Chemotherapy Protocols↗