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Biomedical subjects

M Fukuda

Publications and source records attributed to M Fukuda.

At least 469 records · Page 26Linked to original sources
PubMed1997

Fibronectin concentration in tears of contact lens wearers.

The tears of soft contact lens wearers (wearing lenses on an extended were schedule) were analysed for the amount of fibronectin, albumin and total protein. Tears were collected during the day without stimulation and the levels were then compared to levels in non-contact lens wearers tears. The level of fibronectin in the tears of contact lens wearers (120 ng ml-1) was significantly higher than in the tears of non-contact lens wearers (21 ng ml-1; P < 0.01). There were no differences in the amount of albumin or total protein. When contact lens wearers were divided into those subjects who carried significant levels of bacteria on their contact lenses and non-carriers, the amount of fibronectin and albumin was found to be higher in the tears of bacterial carriers (P < 0.03), whereas the amount of total protein remained the same. The fibronectin in the tears and on the contact lens may predispose subjects to contamination by bacteria and thus increase the risk of inflammatory or infectious diseases associated with bacterial contamination of contact lenses.

Adult↗
PubMed1997

Neuronal responses at the sight of objects in monkey basal forebrain subregions during operant visual tasks.

The basal forebrain appears to be important in cognitive function. It has been suggested that this region is composed of several cholinergic cell groups, mainly the medial septum, the diagonal band of Broca, and the nucleus basalis of Meynert. To elucidate the functional differences between these subregions, we have recorded single-unit activity from the periventricular areas involving the medial septum, the diagonal band of Broca (ms/dbB), and the substantia innominata (SI), including the nucleus basalis of Meynert, of an object-discriminating monkey. Of 226 ms/dbB and 439 SI neurons analyzed, 36 (15.9%) and 115 (26.2%), respectively, responded to the sight of some complex object. Thirteen (5.8%) ms/dbB and 80 (18.2%) SI neurons responded to virtually all objects and the ratio of these neurons in the SI was higher than that in the ms/dbB. The other 23 (10.2%) ms/dbB and 35 (8.0%) SI neurons responded preferentially to one or two of three categories (rewarding, aversive, or meaningless) of familiar or to unfamiliar objects, and response selectivity to one category of the ms/dbB neurons (15; 6.6%) was higher than that to the SI neurons (14; 3.2%). The results suggest that the SI, including the nucleus basalis of Meynert, may encode visual information about objects more broadly and participate more fully in visual attention than the ms/dbB region, which may be more closely related to learning.

Animals↗
PubMed1997

A novel quinoline derivative, MS-209, overcomes drug resistance of human lung cancer cells expressing the multidrug resistance-associated protein (MRP) gene.

PURPOSE AND METHODS: MS-209 is a newly synthesized quinoline compound used orally to overcome human P-glycoprotein (Pgp)-mediated multidrug resistance (MDR). The multidrug resistance-associated protein (MRP) gene is thought to play an important role in MDR in lung cancer. To investigate whether MS-209 could also overcome MRP-mediated MDR, we examined the effect of the compound using a cytotoxicity assay on MDR1 gene-negative drug-selected MDR and wildtype lung cancer cells with various levels of MRP gene expression. The effects of MS-209 were compared with those of verapamil (VER) and cyclosporin A (CsA). The level of MRP gene expression in the cells was evaluated semiquantitatively by RT-PCR. For vincristine (VCR), intracellular accumulation of [3H]-VCR was measured with or without MS-209. RESULTS: In MDR UMCC-1/VP small-cell lung carcinoma cell line, 5 microM of MS-209 and VER enhanced the cytotoxicity of etoposide, doxorubicin (DOX) and VCR more than twofold, and completely reversed the resistance to VCR. The mean reversing effects of MS-209 on DOX and VCR were significantly stronger than those of VER and CsA. In wildtype non-small-cell lung carcinoma cells, the effects of MS-209 were almost equal to those of VER and CsA. The effect of these three agents correlated with the level of MRP gene expression. The MS-209-induced increase in intracellular accumulation of VCR was proportional to the level of MRP gene expression in these cells. CONCLUSION: Our results indicate that MS-209 is a potentially useful drug that can overcome MRP-mediated intrinsic and acquired MDR in human lung cancer.

Antineoplastic Agents↗
PubMed1997

Oxidative stress on mitochondria and cell membrane of cultured rat hepatocytes and perfused liver exposed to ethanol.

BACKGROUND & AIMS: The precise pathogenic significance of oxidative injury in the evolution of alcohol-induced liver disease is still obscure. The present report was designed to investigate whether ethanol alters the production of active oxidants and biological activities of hepatocytes. METHODS: The following parameters in rat hepatocytes were investigated by using fluorescence probes in vitro and ex vivo: (1) mitochondrial membrane potential and membrane permeability transition, (2) oxygen radicals generation, (3) membrane barrier function, and (4) glutathione level. RESULTS: Ethanol (50 mmol/L) increased oxidative stress in hepatocytes and subsequently induced an increased mitochondrial permeability transition and a decreased membrane potential. These ethanol-induced alterations were attenuated by an inhibitor of alcohol dehydrogenase and an intracellular oxidant scavenger, whereas they were enhanced by diethyl maleic acid, a glutathione depletor. Ethanol plus diethyl maleic acid but not ethanol alone increased the number of hepatocytes with membrane barrier dysfunction. A continuous infusion of ethanol (50 mmol/L) increased oxidative stress and decreased mitochondrial membrane potential in the pericentral area of isolated perfused rat liver. CONCLUSIONS: Active oxidants generated during ethanol metabolism increase mitochondrial permeability transition and modulate mitochondrial energy synthesis in hepatocytes. Reduction of glutathione level enhances mitochondrial dysfunction and impairs membrane barrier function of hepatocytes.

Alcohol Dehydrogenase↗
PubMed1997

Effects of repeated cold stress on feeding, avoidance behavior, and pain-related nerve fiber activity.

The specific alternation of rhythm in temperature (SART), which is defined as rapid and frequent changes in the environmental temperature several times within the course of a day, produces abnormalities in behavior such as hyperphagia and in sensory sensation such as hyperalgesia. As the first step toward understanding the mechanisms of these abnormalities, we studied the effects or SART stress on ingestive behavior. During the light and dark phases, the animals' food intake increased, but their body weight gain decreased. In addition, diurnal variation in body weight also decreased. Next, we examined the behavioral and electrophysiological effects of SART stress on avoidance behavior by studying the rat's avoidance of a noxious stimulus in the form of a footshock. The rats demonstrated hyperreactivity; the delay in escaping the footshock was decreased by SART stress. The excitability of C-fiber activity, which responds to mechanical and thermal stimuli to a single saphenous nerve, was not changed by SART stress. This suggests that the hyperreactivity in footshock avoidance and the hyperalgesia in pain response induced by SART stress are based on excessive emotionality.

Animals↗
PubMed1997

Use of endosseous implants for dental reconstruction of patients with grafted alveolar clefts.

PURPOSE: The purpose of this study was to investigate the clinical application of endosseous implants placed into grafted alveolar clefts and to evaluate the short-term outcome. PATIENTS AND METHODS: Nineteen patients (6 males and 13 females; mean age, 17.9 years; range, 9.7 to 33.6 years at first implant surgery), including 11 with unilateral cleft lip and palate, and eight with unilateral cleft lip and alveolus, were studied. All patients except for one who underwent periosteoplasty received grafts of autogenous particulate cancellous bone and marrow (PCBM) obtained from the llium. After bone bridge formation, orthodontic treatment and preparation for implant placement were performed. RESULTS: A total of 21 implants were placed in the bone-grafted alveoli of the 19 patients. The most frequently used length was 15 mm. In five patients with insufficient alveolar bone height, a chin bone onlay graft was combined with simultaneous implant insertion. The follow-up period ranged from 1 year to almost 3 years after implant placement, and the clinical outcome was excellent in all except one patient. In this short-term study, the overall survival rate was 90.5%. CONCLUSION: The grafted alveoli were well suited to the placement of endosseous implants, and this treatment was shown to be a viable option for the dental reconstruction of alveolar clefts. However, the interdental alveolar bone height was insufficient for implant installation in a few patients. Further longitudinal studies are required to determine the optimal timing between secondary bone grafting and implant placement.

Adolescent↗
PubMed1997

Roles of synaptotagmin C2 domains in neurotransmitter secretion and inositol high-polyphosphate binding at mammalian cholinergic synapses.

To determine the functional role of synaptotagmin (Syt) regulatory domains, affinity-purified antibodies specific for C2A or C2B domains were injected into presynaptic neurons of cholinergic synapses formed between rat sympathetic neurons in culture. Following injection of anti-C2A antibody, postsynaptic responses evoked by presynaptic action potentials at a frequency of 0.05 Hz decreased rapidly, while anti-C2B antibody slowly decreased synaptic transmitter release. The inhibitory effect of anti-C2B antibody depended on the amount of synaptic activity. Asynchronous release induced by hypertonic solution was also affected by the antibodies. Anti-C2A antibody showed a dual action on miniature excitatory postsynaptic potentials, a decrease and following increase in the frequency, while synapses loaded with anti-C2B antibody showed a decrease in the frequency after long repetitive stimulation (0.05 Hz for more than 60 min). Anti-C2B antibody prevented the inhibition of acetylcholine release induced by injection of inositol 1,3,4,5-tetrakisphosphate (IP4), indicating that C2B domain may down-regulate transmitter release by IP4 binding. These results confirm similar experiments in the glutamatergic squid giant synapses and suggest a model in which Syt C2A and C2B domains differentially control synaptic vesicle trafficking in mammalian cholinergic terminals; C2A domain may act on the fusion step as a calcium sensor in synaptic vesicle exocytosis evoked by action potentials in addition to controlling spontaneous transmitter release, while C2B domain is involved in exo- and endocytosis.

Acetylcholine↗
PubMed1997

Clinical study of epilepsy with severe febrile seizures and seizures induced by hot water bath.

We followed five cases with severe febrile seizures (FS) with early onset and seizures induced by hot water bath, indicating severe myoclonic epilepsy in infancy (SME) or the peripheral form of SME. These cases, however, had far better clinical courses than that of SME or the peripheral form of SME. These cases were characterized by: (a) severe FS with early onset and seizures induced by hot water bath; (b) a lack of myoclonic seizures; (c) no psychomotor deterioration; (d) no underlying disorders or signs of brain insult on neurologic and laboratory examination; (e) relatively successful seizure control; (f) none of the severe EEG abnormalities seen in SME and the peripheral form of SME; and (g) a positive family history of convulsive disorders.

Adolescent↗
PubMed1997

Predictive value of serum medroxyprogesterone acetate concentration for response in advanced or recurrent breast cancer.

Medroxyprogesterone acetate (MPA) is one of the most commonly prescribed drugs for endocrine therapy of metastatic breast cancer. In this study, the serum MPA concentration was measured by high-performance liquid chromatography (HPLC) and evaluated for its usefulness in predicting the response in 79 cases of advanced or recurrent breast cancers. Overall, 29 patients (37%) achieved an objective response. The response rate correlated significantly with the oestrogen receptor (ER) status (P = 0.03), proliferative activity determined by DNA polymerase alpha (P = 0.04), the disease-free interval (DFI) (P = 0.05) and the serum MPA concentration (P < 0.001). Patients with ER-positive tumours, lower proliferative activity, a longer (DFI) or a higher serum MPA concentration responded more frequently. The mean serum MPA concentration in the responders with ER-positive tumours (P = 0.01) or tumours with a lower proliferative activity (P = 0.008) were significantly lower than in cases with ER-negative tumours or tumours with a higher proliferative activity, respectively. Cases with soft tissue metastases showed responses at significantly lower MPA concentrations (P = 0.003) than those with bone or visceral metastases. Furthermore, there was a dramatic decrease in the MPA concentration when a responder with a high concentration became unresponsive to the therapy. Thus, the serum MPA concentration is a determining factor for the response to treatment.

Adult↗
PubMed1997

Anti-tumour activities of a new benzo[c]phenanthridine agent, 2,3-(methylenedioxy)-5-methyl-7-hydroxy-8-methoxybenzo[c]phena nthridini um hydrogensulphate dihydrate (NK109), against several drug-resistant human tumour cell lines.

Drug resistance is one of the problems severely limiting chemotherapy in cancer patients. Thus, it is very important to develop new drugs that are effective against drug-resistant tumour cells. The novel anti-tumour agent NK109 has been developed from benzo[c]phenanthridine derivatives by Nippon Kayaku (Tokyo, Japan). We have confirmed that NK109 shows anti-tumour effects against a number of human tumour cell lines by inhibiting DNA topoisomerase II activity through the stabilization of the cleavable complex. Further, its efficacy against several drug-resistant tumour cell lines was also shown. NK109 showed potent anti-tumour activity against doxorubicin-resistant human tumour cell lines that have a typical multidrug resistance phenotype caused by P-glycoprotein. NK109 was not pumped extracellularly by P-glycoprotein and, consequently, NK109 accumulated in resistant cells. Cisplatin-resistant human tumour cell lines, which demonstrated decreased cisplatin accumulation, were sensitive to NK109. NK109 non-cross-resistance was confirmed using xenografts of tumour cells that were resistant to cisplatin in SCID mice. Furthermore, etoposide-resistant cells, with decreased topoisomerase II activity, were markedly sensitive to NK109 when compared with their parent cells, suggesting the possibility that the cytotoxic mechanism of NK109 differs from that of etoposide. In conclusion, NK109 is a very promising new anti-tumour drug for clinical use, because the efficacy of NK109 is not susceptible to several known molecular alterations that are associated with drug resistance. A clinical study of this compound is now in progress in Japan.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Identification of nicotinic acetylcholine receptors on lymphocytes in the periphery as well as thymus in mice.

The existence of nicotinic acetylcholine receptors (nAChR) on lymphocytes remains controversial. We attempted to show the existence of nAChR on murine lymphocytes. The intraperitoneal injection of nicotine induced the lymphocytosis in the spleen on day 3. Although freshly isolated lymphocytes bound small quantities of fluorescein isothiocyanate (FITC)-conjugated alpha-bungarotoxin (alpha BuTx), they began to bind alpha BuTx after incubation in medium. In contrast to granulocytes, various lymphocyte subsets obtained from various lymphoid organs were found to bind alpha BuTx. Affinity purification of alpha BuTx-binding protein revealed that lymphocytes expressed the same nAChR molecules as those of muscle. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that lymphocytes expressed the alpha-subunit mRNA of nAChR. These results suggest that lymphocytes carry nAChR on the surface and are stimulated directly via their nAChR by parasympathetic nerve stimuli.

Animals↗
PubMed1997

The Neisseria type 2 IgA1 protease cleaves LAMP1 and promotes survival of bacteria within epithelial cells.

Infection of human epithelial cells by Neisseria meningitidis (MC) and Neisseria gonorrhoeae (GC) increases the rate of degradation of LAMP1, a major integral membrane glycoprotein of late endosomes and lysosomes. Several lines of evidence indicate that the neisserial IgA1 protease is directly responsible for this LAMP1 degradation. LAMP1 contains an IgA1-like hinge region with potential cleavage sites for the neisserial type 1 and type 2 IgA1 proteases. Neisserial type 2 IgA1 protease cleaves purified LAMP1 in vitro. Unlike its wild-type isogenic parent, an iga mutant of N. gonorrhoeae cannot affect LAMP1 turnover and its growth in epithelial cells is dramatically reduced. Thus, IgA1 protease cleavage of LAMP1 promotes intracellular survival of pathogenic Neisseria spp.

Animals↗
PubMed1997

Infection with hepatitis G virus and its strain variant, the GB agent (GBV-C), among blood donors in Japan.

BACKGROUND: The purpose of the study was to survey the epidemiology of recently reported non-A through -E hepatitis virus designated hepatitis G virus (HGV) and its strain variant, the GB agent (GBV-C). STUDY DESIGN AND METHODS: Pilot samples from 2461 blood donors in Japan, randomly selected to form cohorts with different levels of alanine aminotransferase (ALT) and markers of hepatitis B virus or hepatitis C virus (HCV) infection, were tested for RNA of HGV/GBV-C by reverse transcription-polymerase chain reaction with nested primers deduced from the 5'-noncoding region. RESULTS: HGV/GBV-C RNA was detected in 23 (7.4%) of the 361 donors with anti-HCV and HCV RNA. This detection is more frequent than that in donors without elevated ALT levels (< or = 45 U/L) or markers of HCV or hepatitis B virus infection (15/1303; 1.2%) (p < 0.001), donors with ALT values between 46 and 99 U per L (0/108) (p < 0.002), donors with ALT values > or = 100 U per L (5/361; 1.4%), and donors with anti-HCV but without detectable HCV RNA (1/93; 1.1%) (p < 0.05). CONCLUSION: More than 1 percent of Japanese blood donors were infected with HGV/GBV-C, and the prevalence was much higher in those with HCV RNA. Should persistent infection with HGV/GBV-C induce any hepatotoxic sequelae, either alone or in concert with the other hepatitis viruses, screening of blood units for HGV/GBV-C would deserve consideration.

Adult↗
PubMed1997

Expression of the large I antigen forming beta-1,6-N-acetylglucosaminyltransferase in various tissues of adult mice.

Large I antigen is specifically formed by a beta-1,6-N-acetylglucosaminyltransferase (IGnT), which is a Golgi enzyme. IGnT converts a linear carbohydrate structure, the i antigen, to a branched structure, the I antigen in N-acetyllactosamines. This conversion has been shown to be developmentally regulated in human erythrocytes. In mouse embryonic development, it has been shown that poly-N-acetyllactosamine plays a critical role in the compaction process (Rastan,S., Thorpe,S.J., Scudder,P., Brown,S., Gooi,H.C., and Feizi,T. (1985) J. Embryol. Exp. Morphol., 87, 115-128.). In order to understand the regulation of IGnT expression during mouse development, the IGnT transcripts were studied using in situ hybridization. The cDNA encoding IGnT was isolated from a murine PCC4 teratocarcinoma cDNA library by nucleic acid hybridization using probes generated from the human IGnT cDNA. The IGnT cDNA was used to produce a fusion protein, which was then used as an immunogen to produce polyclonal antibodies against the enzyme. Nucleotide sequence data was used to design oligonucleotide primers and cDNA probes. The primers and probes, antibodies specific to the fusion protein, and previously obtained human anti-I or i sera, were used to analyze adult and embryonic mouse tissues for expression of IGnT and I antigen. To detect IGnT mRNA, in situ reverse-transcription and polymerase chain reaction were performed on tissue sections using the oligonucleotide primers. Amplified DNA products were detected by in situ hybridization using the cDNA probes. IGnT protein was detected by immunohistochemistry using the IGnT fusion-protein antibody. Expression of the carbohydrate structures was detected using human anti-I or i sera. The results presented demonstrate that IGnT and the I antigen appear in epithelial cells and dividing cells. The antigen also appears to be expressed on cells exposed to the lumenal surface of tissues. These results support the conclusions obtained by the previous studies that IGnT and the resultant I antigen may play critical roles during development and in adult organisms.

Amino Acid Sequence↗
PubMed1997

Does corpus luteum locally affect follicular growth negatively?

In this study bilateral ovarian follicular growth during the luteal phase was investigated in relation to the ovary where ovulation occurred. The diameter of the largest follicle in the contralateral ovary without corpus luteum and in the ipsilateral ovary with corpus luteum was measured using vaginosonography in a total of 66 natural cycles of 27 normally cycling women undergoing treatment with intrauterine insemination (IUI). None of the women received ovarian stimulation or luteal support. Follicles from 2 to 11 mm in diameter were measured in early luteal phase (day +1 to +4), mid-luteal phase (day +5 to +9) and late luteal phase (day +10 onwards). The mean diameters of the largest follicle in the contralateral ovary without corpus luteum during the early, mid- and late luteal phases were 6.81 +/- 1.33 (mean +/- SD), 6.14 +/- 1.29 and 5.71 +/- 1.17 mm respectively, while those of the ipsilateral ovary with corpus luteum were 6.48 +/- 1.40, 5.65 +/- 1.47 and 4.98 +/- 1.19 mm respectively. While there was no significant difference during the early luteal phase, the mean diameter of the largest follicle in the ipsilateral ovary with corpus luteum was significantly smaller than that of the contralateral ovary without corpus luteum during the mid-luteal phase (P < 0.004) and the late luteal phase (P < 0.0005). These results indicate that the corpus luteum locally affects neighbouring follicular growth negatively during the luteal phase of the menstrual cycle, with the most pronounced effect expressed in the mid- and late luteal phases.

Adult↗
PubMed1997

Increased cell proliferation of urothelium in rat bladder following unilateral nephrectomy.

PURPOSE: The aim of this study is to investigate the effect of unilateral nephrectomy on cell proliferation of normal urinary bladder epithelium in adult rats. MATERIALS AND METHODS: Following unilateral nephrectomy or sham operation 5 rats for each time point were sacrificed and their bladders were removed at 6 and 12 hours and also on 1, 2, 4, 7, 14, 28, and 56 days. Another 5 rats were not operated and served as the control. The percent number of proliferating cell nuclear antigen (PCNA) positive cells and the number of argyrophilic nucleolar organizer regions (AgNORs) were determined for each bladder. RESULTS: In the nephrectomized groups, a significant increase of PCNA expression in urothelial cells of the bladder was found at each sacrifice time with the exception of 28 and 56 days when compared with that of the control and corresponding sham-operated groups. Percent PCNA labeling index (PCNA-LI) reached a peak value of approximately 9.1% on day 2 post operation. From day 4 post nephrectomy, however, PCNA-LI decreased gradually reaching control levels by day 28. No significant difference was found between the control and sham-operated groups. The mean number of AgNOR dots in nephrectomized rats sacrificed on day 1, 2, 4, 7 and 14 post operation was significantly larger than that of the control and corresponding sham-operated groups. CONCLUSION: The results suggest that unilateral nephrectomy temporarily enhances normal urothelial cell proliferation in adult rat bladder.

Animals↗
PubMed1997

The entire nucleotide sequences of two GB virus C/hepatitis G virus isolates of distinct genotypes from Japan.

Recently, putative viral agents responsible for human non-A to E hepatitis have been independently reported by two groups of investigators and designated GB virus C (GBV-C) and hepatitis G virus (HGV), respectively. The entire nucleotide sequences were determined for two viral genomes isolated from Japanese blood donors with GBV-C RNA. One of them (GT230) had a total genomic length of 9390 nucleotides (nt) with 5' and 3' untranslated regions of 551 and 313 nt, while the other (GT110) had genomic lengths of 9395, 281 and 315 nt, respectively. They both had a single long open reading frame, encoding 2842 amino acids (aa) in GT230 and 2933 aa in GT110. Surprisingly, they both lacked a clearly identifiable core gene, and possessed the E1/E2 gene with only four potential N-linked glycosylation sites. Pairwise comparison and phylogenetic analysis of the entire sequence indicated that the prototype GBV-C and two HGV isolates reported, as well as GT230 and GT110, are the same virus possibly of different genotypes. The five GBV-C/HGV isolates were variable up to 13.8% in the genomic nucleotide sequence, and contained deletions and insertions within the 5'-terminal 518-593 nt, which resulted in four different sizes of predicted polyproteins encoded by genomes of individual isolates. By contrast, the 3' untranslated region was well conserved. The high degree of sequence conservation within this region would favour it as a target for sensitive detection of GBV-C/HGV RNA.

Amino Acid Sequence↗