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Biomedical subjects

A Masuda

Publications and source records attributed to A Masuda.

At least 55 records · Page 3Linked to original sources
PubMed2000

Histological type-selective, tumor-predominant expression of a novel CHK1 isoform and infrequent in vivo somatic CHK2 mutation in small cell lung cancer.

Inactivation of p53, which represents the most prevalent genetic alteration in lung cancer, has been shown to play a crucial role in the acquisition of genomic instability. We examined 44 lung cancer specimens to search for mutations in the CHK1 and CHK2 genes, which have been suggested to play roles in regulating p53 after DNA damage. We found that the CHK2 gene was somatically mutated in lung cancer in vivo, although at a low frequency, and that a previously undescribed shorter isoform of CHK1 was expressed preferentially in small cell lung cancer in a tumor-predominant manner. Additional studies are warranted to investigate the functional significance of these changes as well as the potential involvement of other components in this important pathway to maintain genomic stability.

Amino Acid Sequence↗
PubMed2000

Absence of interleukin-4 enhances germinal center reaction in secondary immune response.

The germinal center (GC) is a compartment for B cell differentiation and proliferation. Interleukin (IL)-4 has been considered essential for GC functioning. To define the role of IL-4 in GC reaction, immunohistology of draining lymph nodes (LNs) of IL-4 gene-targeted (IL-4(-/-)) mice was performed during secondary immune response. IL-4(-/-) mice were immunized with ovalbumin emulsified in Freund' complete adjuvant. Final antigen challenge was done 4 weeks later. IL-4(-/-) mice had a higher production of IgG2a and IgG2b and a lower production of IgG1 than those in wild-type (WT) mice. In comparison with WT mice, LNs of IL-4(-/-) mice on days 4 and 7 after final antigen challenge were larger and contained a markedly greater number of GCs, which showed marked size variations with a large number of small GCs and a small number of markedly large GCs. By day 14, the number of GCs decreased to the same level as that in WT mice. However, the LN size in IL-4(-/-) mice was still larger than that in WT mice due to the presence of markedly large GCs. Although well-developed complement receptor(+) follicular dendritic cell (FDC) networks were present in GCs of IL-4(-/-) mice, no FDCs of mature phenotype (CD23(+)) were observed in many of the small GCs. In conclusion, the absence of IL-4 enhanced GC reaction and specific antibody response of Th1-type. IL-4 may play an important role in inducing the appropriate magnitude of humoral immune response.

Animals↗
PubMed2000

Measurement of isotopes of light rare earth elements in the form of oxide ions: a new development in thermal ionization mass spectrometry

An isobaric interference free thermal ionization mass spectrometry (TIMS) method is presented here for the precise isotope measurements of light rare earth elements (LREEs). LREE isotopes can be measured in the form of monoxide ion (MO+), but the previous determinations of LREE isotopes in the form of oxide were hindered, notably by the 17O and 18O related isobaric interferences. In the present study, 16O-enriched oxygen was introduced into the ion source chamber via a specially designed gas inlet system. It was observed that the isobaric interferences caused by 17O and 18O were remarkably reduced by up to 6 and 70 times, respectively, compared to those caused by natural oxygen bleeding. Isotopic ratios of La, Ce, and Nd obtained without isobaric interference corrections show the excellent precision and accuracy in the present study. The results also shed some light on the formation mechanism of the measured oxide species in TIMS. Furthermore it promises more precise determination of LREE abundances and La-Ce and Sm-Nd ages in geochemistry and cosmochemistry.

Journal Article↗
PubMed2000

The effects of n-alcohols on evoked synaptic potentials in rat hippocampal slices: Hill coefficients account for the cut-off phenomenon.

The anesthetic potencies of n-alcohols increase progressively with lengthening of the carbon chain and then disappear at a cut-off point of a longer-chain n-alcohol. In order to assess the mechanisms for cut-off in mammalian central nervous system, the effects of a series of n-alcohols (C(2)-C(11)) were examined on the evoked synaptic potentials of the rat hippocampal preparation in vitro. The n-alcohols (C(2)-C(10)) reduced the slope of the excitatory post-synaptic potential in a concentration-dependent manner, and the inhibitory potencies enhanced as a function of carbon chain length. The effect disappeared at n-undecanol (C(11)). The Hill coefficients of the concentration-response curves of the n-alcohols negatively correlated with the number of carbon atoms. The decrease in the Hill coefficient could account for the cut-off phenomenon, indicating that the results can support the anesthetic pocket hypothesis.

Alcohols↗
PubMed2000

Heterogeneities in the biological and biochemical functions of Smad2 and Smad4 mutants naturally occurring in human lung cancers.

Smad family members are essential intracellular signaling components of the transforming growth factor-beta (TGF-beta) superfamily involved in a range of biological activities. The loss of sensitivity to TGF-beta is frequent in human lung cancers and inactivation of Smad family members are thought to play important roles in disruption of TGF-beta signaling. In the study presented here, we characterized the biological and biochemical functions of six Smad2 and Smad4 mutants, which we previously identified in human lung cancers. All mutant Smad2 and Smad4 were in fact found to be defective in transmitting growth inhibitory signals originating from TGF-beta and incapable of activating Smad/hFAST-1-mediated transcription. Transcriptional activation of plasminogen activator inhibitor type 1 (PAI-1) was impaired in four of the six mutants due to the defects in homo- and/or hetero-oligomerization with wild-type Smads. In contrast, the remaining two Smad mutants showed a modest reduction in the PAI-1 transcriptional activation and apparently retained the ability to oligomerize with wild-type Smads. Significant loss of growth inhibition and Smad/hFAST-1-mediated transcriptional activation by all of the six mutants suggested that Smad mutants are indeed functionally impaired Smad mutations and may play a role in lung tumorigenesis. Moreover, the present findings suggest that in addition to the impairment in the homo- and/or hetero-oligomerization, there may be an alternative mechanism producing disruption of TGF-beta signaling, involving hFAST-1-or possibly other transcriptional cofactor(s)-mediated transcriptional activation.

DNA-Binding Proteins↗
PubMed2000

Diversity of opsin immunoreactivities in the extraretinal tissues of four anuran amphibians.

The pineal complex, deep brain, and skin have been known to function as extraretinal photoreceptors in non-mammalian vertebrates. To see the diversity of localization of extraretinal photoreceptors in lower vertebrates having different habitats, we analyzed the opsin-like immunoreactivities in anuran amphibians, Xenopus laevis, Rana catesbeiana, Rana nigromaculata, and Bufo japonicus. An antiserum (toad Rh-AS) was raised against rhodopsin purified from the retinas of Japanese toad, B. japonicus. In the retina of all the anurans examined, the outer segments of rods were immunopositive to toad Rh-AS. The outer segments of most pinealocytes were immunopositive in R. catesbeiana, R. nigromaculata, and B. japonicus. The outer segments of photoreceptor-like cells within the frontal organ of R. nigromaculata were immunostained. Interestingly, toad Rh-AS immunostained many secretory cells of mucous glands in the head skin of B. japonicus, implying the presence of a novel photoreceptive molecule. Within the hypothalamus, toad Rh-AS immunostained many cells in the magnocellular preoptic nucleus of R. catesbeiana and B. japonicus. Toad Rh-AS also labeled cerebrospinal fluid (CSF)-contacting cells in the anterior preoptic nucleus of R. nigromaculata and those adjacent to the lateral ventricle within the septum of R. catesbeiana. Thus the distribution patterns of the rhodopsin-like immunoreactivities among the anurans were highly diverged, and there was no relationship between the distribution patterns and their habitats. J. Exp. Zool. 286:136-142, 2000.

Animals↗
PubMed2000

Cloning and functional expression of a Boophilus microplus cathepsin L-like enzyme.

A cysteine proteinase gene homologous to cathepsins L genes was isolated from a B. microplus cDNA library. The precursor protein deduced from the nucleotide sequence contains 332 amino acid residues consisting of a signal sequence (pre-region), a pro-region and a mature proteinase. The DNA fragment coding for the proenzyme was cloned and expressed using the E. coli expression vector pMAL-p. The recombinant protein (MBP+PROCP) once activated is able to hydrolyze synthetic substrates as well as protein substrates like hemoglobin, vitellin and gelatin. Its optimal enzymatic activity on both fluorogenic and protein substrates was found to occur at an acidic pH. Expression of the proteinase gene was tested by RT-PCR with tick larvae RNA. Detection of amplified sequences indicates that the gene is expressed at this stage of the tick life cycle and the molecule is therefore potentially a target for chemotherapy or an immunogen in a vaccine.

Animals↗
PubMed2000

Automated analysis of digital oximetry in the diagnosis of obstructive sleep apnoea.

BACKGROUND: The gold standard diagnostic test for obstructive sleep apnoea (OSA) is overnight polysomnography (PSG) which is costly in terms of time and money. Consequently, a number of alternatives to PSG have been proposed. Oximetry is appealing because of its widespread availability and ease of application. The diagnostic performance of an automated analysis algorithm based on falls and recovery of digitally recorded oxygen saturation was compared with PSG. METHODS: Two hundred and forty six patients with suspected OSA were randomly selected for PSG and automated off line analysis of the digitally recorded oximeter signal. RESULTS: The PSG derived apnoea hypopnea index (AHI) and oximeter derived respiratory disturbance index (RDI) were highly correlated (R = 0.97). The mean (2SD) of the differences between AHI and RDI was 2.18 (12.34)/h. The sensitivity and specificity of the algorithm depended on the AHI and RDI criteria selected for OSA case designation. Using case designation criteria of 15/h for AHI and RDI, the sensitivity and specificity were 98% and 88%, respectively. If the PSG derived AHI included EEG based arousals as part of the hypopnea definition, the mean (2SD) of the differences between RDI and AHI was -0.12 (15. 62)/h and the sensitivity and specificity profile did not change significantly. CONCLUSIONS: In a population of patients suspected of having OSA, off line automated analysis of the oximetry signal provides a close estimate of AHI as well as excellent diagnostic sensitivity and specificity for OSA.

Adult↗
PubMed2000

Usefulness of HMG-CoA reductase inhibitor in Japanese hyperlipidemic women within seven years of menopause.

OBJECTIVE: To assess the therapeutic value of treatment with an HMG-CoA reductase inhibitor in women with hypoestrogenic hyperlipidemia caused by menopause. DESIGN: Fifty-six women with total cholesterol (TC) levels of 220 mg/dl or more who were within 7 years of menopause were randomly assigned to receive an HMG-CoA reductase inhibitor (pravastatin 10 mg/day; treated group, 26 patients) or no medical treatment (nontreated group, 30 patients) in this 6-month nonblinded prospective trial. RESULTS: In the treated group, the mean (SD) TC levels decreased significantly from 254.5+/-22.3 mg/dl at baseline to 204.7+/-22.2 mg/dl (19.6%), and the mean low-density lipoprotein cholesterol (LDL-C) level decreased significantly from 146.7+/-30.5 to 104.3+/-22.5 mg/dl (28.9%); the mean arteriosclerotic index decreased significantly from 2.98 to 2.08 (30.2%). There were no significant changes in either triglyceride levels or high-density lipoprotein cholesterol (HDL-C) levels. In the nontreated group, there were no significant changes in the TC, HDL-C, LDL-C, or triglyceride levels; there was also no change in the arteriosclerotic index. After 6 months, the TC level, LDL-C level, and arteriosclerotic index were significantly lower in the treated group compared with the nontreated group (p<0.01). CONCLUSIONS: The results indicate that the HMG-CoA reductase inhibitor lowered TC and LDL-C levels and was useful in the treatment of hypoestrogenic hyperlipidemia for periods of at least 6 months.

Arteriosclerosis↗
PubMed2000

Study of lipid in the ear canal in canine otitis externa with Malassezia pachydermatis.

An epidemiological investigation of 120 canine otitis externa cases in 1,370 dogs was done on the incidence rate, ear pinna shapes, breeds and their relationships. Eighty-five cases (12.6%) in 672 dogs with pendulous ears and 35 cases (5.0%) in 698 dogs with erect ears had otitis externa, and the difference between them was significant (P<0.05). Ninety-five auditory cerumen specimens were cultured for Malassezia pachydermatis (M. pachydermatis) and analyzed for concentrations of major fatty acids. Although rates of cases positive for M. pachydermatis in both ear pinna shapes were almost the same, i.e. 55.2% in the pendulous group and 53.6% in the erect group, the average total fatty acid level of the pendulous ear group was significantly (P<0.05) higher than that in the erect ear group after dismissing extraordinary levels in the Siberian husky. Isolated M. pachydermatis strains were examined for the effects of fatty acid supplementation on their growth. The majority of the strains utilized fatty acids and grew faster in fatty acid supplemented broth. These results suggest that M. pachydermatis, the predominant causative agent of canine otitis externa, prefers the auditory canal of dogs with lipid-rich earwax and grows fast, but growth strongly depends upon the canine breed.

Animals↗
PubMed2000

Psychobehavioral and immunological characteristics of HTLV-1 carriers and non-carriers with persistently low natural killer cell activity.

OBJECTIVE: To clarify the differences in immunological and psychobehavioral characteristics of HTLV-1 carriers and non-carriers with persistently low natural killer (NK) cell activity. METHODS: The individuals with persistently low NK cell activity were divided into HTLV-1 carriers and non-carriers. NK cell activity, lymphocytic proliferation, lymphocyte subsets (CD4+, CD8+, CD16+, CD20+, CD56+), and psychobehavioral responses were examined. PATIENTS: Of 296 outpatients with physical complaints, 30 patients with persistently low NK cell activity (10 HTLV-1 carriers and 20 HTLV-1 non-carriers) and 20 healthy controls negative for HTLV-1 antibody and with normal NK cell activity were randomly selected. RESULTS: In HTLV-1 carriers with persistently low NK cell activity, no significant differences were observed in NK cell subsets (CD16+ and CD56+) and psychobehavioral responses compared with the healthy controls. In HTLV-1 non-carriers, NK cell subsets were significantly low, and depression, anxiety and fatigue were significantly greater than in healthy controls. CONCLUSIONS: These findings suggest that persistently e low NK cell activity in HTLV-1 carriers might be reduced due to the HTLV-1 infection. On the other hand, the reduction in the NK cell activity in HTLV-1 non-carriers appears a to be related to depression, anxiety, and fatigue.

Adult↗
PubMed2000

[Infratemporal fossa approach for mid-skull base lesion: its usefulness, surgical anatomy, and intraoperative device].

The usefulness of the infratemporal fossa type C approach is reported through a presentation of a case of clival chordoma, which was successfully treated by this approach. Although it is complicated and includes some demerits, this approach gives a shorter and wider access to mid-skull base pathology than other approaches. Among the demerits, deformity of the temporal region caused by extensive drilling of the bone could be minimized by cosmetic mastoidectomy, which was first applied during this approach by the authors. The surgical anatomy for this approach is demonstrated using a cadaver specimen.

Adult↗
PubMed2000

Cyclooxygenase-2 inhibitor induces apoptosis and enhances cytotoxicity of various anticancer agents in non-small cell lung cancer cell lines.

In recent years, a combination of two demographic phenomena, an increase in the number of older people in the population and an increase in the incidence of lung cancer with age, has made it mandatory to develop therapeutic modalities with less toxicity for the treatment of inoperable elderly patients with lung cancer. Our study shows that a cyclooxygenase (COX)-2 inhibitor, nimesulide, can inhibit proliferation of non-small cell lung cancer cell lines in vitro in a dose-dependent manner, in part by inducing apoptosis even at clinically achievable low concentrations. Our observations also suggest that the responsiveness of non-small cell lung cancer to COX-2 inhibitors does not require the presence of wild-type p53, but may be influenced by the degree of COX-2 expression. In addition, we found that nimesulide, when used in combination at clinically achievable concentrations, reduced the IC50 values of various anticancer agents by up to 77%, although the level of reduction varied considerably. Because our previous studies have indicated a significantly increased COX-2 expression in up to 70% of adenocarcinoma cases, the present findings are of great clinical interest. In conjunction with the recent development of next generation, highly selective COX-2 inhibitors, they can be expected to lead to even greater efficacy of their use as adjuncts to various anticancer agents for the treatment of high-risk patients without compromising their quality of life.

Antineoplastic Agents↗
PubMed2000

Mutation analysis of the p53 tumor suppressor gene using paraffin-embedded specimens of human transitional cell carcinomas by the direct sequencing method.

A very small quantity of DNA was extracted from paraffin sections of 25 bladder and 2 ureteral cancer cases, and exons 5-8 of the p53 gene were amplified by the polymerase chain reaction. Mutations were detected by direct sequencing, and their relationships to clinicopathological factors were assessed. Point mutations of the p53 gene were observed in 2 of 27 specimens of transitional cell carcinoma. One was a novel nonsense mutation. The prognosis of patients with p53 gene mutations was poorer than those of patients without mutations. Analysis of the data showed that assessment of the potential malignancy of bladder cancer, combined with a conventional pathological diagnosis, allows a more precise prognosis. Direct sequencing of tissue specimens enables swift prognostic evaluation and prompt decisions concerning treatment.

Adult↗
PubMed1999

Search for in vivo somatic mutations in the mitotic checkpoint gene, hMAD1, in human lung cancers.

We previously reported the presence of mitotic check-point impairment in about 40% of lung cancer cell lines. To gain an insight into the molecular basis of this impairment, we examined 49 lung cancer specimens for alterations in the hMAD1 mitotic checkpoint gene and identified a somatic, non-conservative missense mutation, which substitutes alanine (GCG) for threonine (ACG) at codon 299, together with a number of amino acid substituting, single nucleotide polymorphisms. This is the first demonstration of hMAD1 mutation in any type of human cancers. The present finding marks hMAD1 as a potential target, although with low frequency, for genetic alterations in lung cancer. Thus, further studies of hMAD1 dysfunction caused by other mechanisms appear to be warranted, as well as potential involvement of other components of the mitotic checkpoint.

Base Sequence↗
PubMed1999

Identification of frequent impairment of the mitotic checkpoint and molecular analysis of the mitotic checkpoint genes, hsMAD2 and p55CDC, in human lung cancers.

The mitotic checkpoint is thought to be essential for ensuring accurate chromosome segregation by implementing mitotic delay in response to a spindle defect. To date, however, very little data has become available on the defects of the mitotic checkpoint in human cancer cells. In the present study, impaired mitotic checkpoint was found in four (44%) of nine human lung cancer cell lines. To our knowledge, this is the first demonstration of frequent impairment of the mitotic checkpoint in this leading cause of cancer deaths. As an initial step towards elucidation of the underlying mechanism, we further undertook a search for mutations in a key component of the mitotic checkpoint, known as hsMAD2, and its immediate downstream molecule, p55CDC. No such mutations were found, however, in either 21 lung cancer cell lines or 25 primary lung cancer cases, although we could identify silent polymorphisms and the transcribed and processed hsMAD2 pseudogene that was subsequently mapped at 14q21-q23. The present observations appear to warrant further investigations, such as search for alterations in other components, to better understand the molecular pathogenesis of this fatal disease, and warn against potential misinterpretation when performing mutational analyses for other cancer types based on cDNA templates.

Antineoplastic Agents↗