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Biomedical subjects

M Mori

Publications and source records attributed to M Mori.

At least 73 records · Page 4Linked to original sources

Expression of apoptosis inhibitor protein Mcl1 linked to neuroprotection in CNS neurons.

Mcl1 is a Bcl2-related antiapoptotic protein originally isolated from human myeloid leukemia cells. Unlike Bcl2, expression has not been reported in CNS neurons. We isolated Mcl1 in a direct screen for candidate modifier genes of neuronal vulnerability by differential display of mRNAs upregulated following prolonged seizures in two mouse strains with contrasting levels of hippocampal cell death. Mcl1 is widely expressed in neurons, and transcription is rapidly induced in both strains. In resistant C57Bl/6J mice, Mcl1 protein levels remain persistently elevated in hippocampal pyramidal neurons after seizures, but fall rapidly in C3H/HeJ hippocampus, coinciding with extensive neuronal apoptosis. DNA damage and caspase-mediated cell death were strikingly increased in Mcl1-deficient mice when compared to +/+ littermates after similar seizures. We identify Mcl1 as a neuronal gene responsive to excitotoxic insult in the brain, and link relative levels of Mcl1 expression to inherited differences in neuronal thresholds for apoptosis.

Animals↗

Clinical evaluation of the measurement of serum procalcitonin: comparative study of procalcitonin and serum amyloid A protein in patients with high and low concentrations of serum C-reactive protein.

Levels of C-reactive protein (CRP) and serum amyloid A protein (SAA) in blood are increased as acute phase proteins in patients with inflammatory conditions. Most of the currently used inflammatory markers, such as erythrocyte sedimentation rate and CRP or SAA levels, are non-specific parameters. By contrast, procalcitonin (PCT) has been reported to be selectively induced by severe infection in systemic inflammatory response syndrome (SIRS) and also in sepsis or multiorgan dysfunction syndrome. PCT expression is induced only slightly, if at all, by viral infections, autoimmune disorders, neoplastic disorders and trauma arising from surgical intervention. Serum PCT and SAA levels were compared in 93 patients with a CRP concentration higher than 100 mg/L and in 26 patients with a CRP concentration lower than 1.5 mg/L. In patients with high levels of CRP, all patients with sepsis and severe bacterial infection showed a significantly increased PCT concentration of more than 1.0 microg/L and it was possible to differentiate between the patients with neoplastic disorders and those with other inflammatory diseases. In patients with low levels of CRP, the PCT concentration was less than 0.3 microg/L and an increased PCT level was not seen in patients with autoimmune disorders or viral and fungal infections. These results suggest that determining the serum PCT level may be useful in the differential diagnosis of severe infection.

Bacterial Infections↗

Clinical significance of the overexpression of the candidate oncogene CYP24 in esophageal cancer.

BACKGROUND: By using array comparative genomic hybridization (CGH), the increased copy number of CYP24 (which encodes vitamin D 24-hydroxylase) at 20q13.2 was previously reported, leading to the identification of CYP24 as a candidate oncogene in breast cancer. CYP24 leads to abrogate growth control mediated by vitamin D. MATERIALS AND METHODS: We examined CYP24 expression as well as VDR (vitamin D receptor) gene expression in 42 esophageal cancer cases using semi-quantitative RT-PCR assay. We induced CYP24 in seven esophageal cancer cell lines using 25-hydroxyvitamin D3 [25(OH)D3] and compared cell growth rate, measured using the 3-(4, 5-dimethylthiazol-2-y)-2, 5-diphenyltetrazolium bromide (MTT) assay system. RESULTS: The overall survival rate was significantly higher in 25 cases of lower CYP24 expression than 17 cases of higher CYP24 expression (P <0.05); on the other hand, 23 cases of low VDR expression had a poorer prognosis than 19 cases of high VDR expression. Moreover, we disclosed that the inverse correlation between CYP24 and VDR expression is significant in esophageal cancer cases (P <0.05). Furthermore, the cell growth evaluated by MTT assay was greatly increased in CYP24-induced and VDR-diminished cells than non-responding cells by 25(OH)D3 activity (P <0.01). CONCLUSIONS: Overexpression of the candidate oncogene CYP24 is inversely correlated to vitamin D receptor expression, and may play an important role in determination of the malignant potential of esophageal cancer.

Adult↗

Expression of enamel proteins and LEF1 in adamantinomatous craniopharyngioma: evidence for its odontogenic epithelial differentiation.

AIMS: Adamantinomatous craniopharyngioma (ACP) resembles histologically some odontogenic tumours, such as ameloblastoma and calcifying odontogenic cyst. However, there has been no evidence that ACP differentiates also functionally as odontogenic epithelium. The aim of this study was to gain evidence of odontogenic epithelial differentiation in ACP by means of immunohistochemistry. Among normal human tissues, enamel proteins are expressed exclusively in teeth, and lymphoid enhancer factor 1 (LEF1), in co-operation with beta-catenin, play an important role in tooth development. The expression of these proteins is therefore indicative of odontogenic epithelial differentiation. METHODS AND RESULTS: The expression of enamel proteins and LEF1 was examined in 10 adamantinomatous and six papillary craniopharyngiomas. All the ACPs showed a variable degree of enamel protein expression, including amelogenin, enamelin and enamelysin, mainly in ghost cells. LEF1 was also heterogeneously expressed in ACPs; remarkably, its expression pattern was identical to that of nuclear beta-catenin accumulation. In contrast, none of the papillary craniopharyngiomas expressed enamel proteins or LEF1. CONCLUSIONS: These results suggest that ACP consistently shows odontogenic epithelial differentiation. Since ACPs harbour beta-catenin mutation, the inappropriate activation of beta-catenin/LEF1 complex-dependent transcription may play a critical role in ACP tumorigenesis.

Adult↗

Delayed therapy with curative intent in a contemporary prostate cancer watchful-waiting cohort.

OBJECTIVE: To identify predictors of delayed therapy with curative intent, an increasingly common option in contemporary patients with prostate cancer who initially choose watchful waiting. PATIENTS AND METHODS: The characteristics of all patients at one institution and diagnosed with T1-4NXM0 prostate cancer between 1993 and 2000 were prospectively recorded. Factors recorded included: age, tumour stage, histological type, Gleason score, serum prostate specific antigen (PSA) level, prostate volume, PSA density (PSAD), percentage of positive biopsy cores, and the initial treatment selection. Outcomes, including all cancer-directed interventions, all serum PSA values, and initial outcomes of all interventions with curative intent, were determined by review of all medical records and cancer registry data. RESULTS: Of 187 patients on watchful waiting, 175 had stage T1 or T2 cancer and were analysed primarily. Thirty-eight (22%) of these patients received delayed intervention with curative intent (15 radical prostatectomy, 17 external beam radiotherapy, six brachytherapy). Age (P < 0.001) and percentage of positive biopsy cores (P = 0.042) were significant independent predictors of intervention with curative intent. When the PSA doubling time was added to the model it became a significant predictor (P = 0.018), with percentage positive biopsy cores (P = 0.022) and age (P < 0.001). CONCLUSIONS: Therapy with curative intent is common in contemporary patients with prostate cancer who initially choose watchful waiting. Age and percentage positive biopsy cores are independent predictors of such intervention, with PSA doubling time also an independent predictor.

Adenocarcinoma↗

Airway problems related to laryngeal mask airway use associated with an undiagnosed epiglottic cyst.

This report describes airway management difficulties in a patient with an asymptomatic and undiagnosed epiglottic cyst. Mask ventilation after induction of general anesthesia was uneventful. Insertion of an LMA resulted in inadequate ventilation. Fiberoptic intubation through an intubating LMA was impossible because the LMA pushed the cyst into the laryngeal inlet. Fibreoptic intubation, assisted by the use of a direct laryngoscope without the LMA was uneventful. Preoperative craniocervical scans performed for assessment of other conditions may reveal asymptomatic pathology in the airway.

Airway Obstruction↗

Diagnostic utility of waveform analysis of compound muscle action potentials for carpal tunnel syndrome.

PURPOSE: To determine the diagnostic utility of waveform analysis of compound muscle action potentials (CMAP) for carpal tunnel syndrome (CTS). METHODS: A total of 131 hands in 71 patients diagnosed with CTS (grouped according to severity) and 80 hands in 44 normal subjects were evaluated using nerve conduction test through the carpal tunnel combined with waveform analysis of CMAP. RESULTS: Compared to normal subjects, the sensory nerve conduction velocity and mean frequency of the CMAP waveform were significantly reduced in patients with CTS. Compared with distal motor latency and sensory nerve conduction velocity, the mean frequency of the CMAP decreased significantly with increasing clinical severity. CONCLUSION: This study suggests that waveform analysis of CMAP is of diagnostic value in CTS, and is also of value in objective evaluation of postoperative recovery of carpal median nerve dysfunction.

Action Potentials↗

Squamous cell carcinoma of the eyelid treated with photodynamic therapy.

The ocular tissues can be the site of a number of malignant tumors in adults. Approximately 5% to 10% of all skin tumors occur in the eyelid. Incidence studies indicate that basal cell carcinoma is the most frequent malignant eyelid tumor (90%) followed by squamous cell carcinoma (9%). A 55-year-old man presented a squamous cell carcinoma (SCC) of 8 mm diameter, localized in the middle third of the lower eyelid, 3 mm under the eyelid margin on the eyelids. The histopathologic examination of a biopsy specimen showed the typical features of squamous cell carcinoma. Photodynamic therapy (PDT) with topical 5-aminolevulic acid (ALA) after Frost suture was employed. Very good results were obtained with rapid healing, without invasiveness, and without anesthesia. There was no evidence of scar formation and no signs of recurrence at 6 months follow-up. Many therapeutic methods have been suggested for squamous cell carcinoma of the eyelid. We consider photodynamic treatment of eyelid skin malignancies to be of great interest and it may represent an interesting future perspective for their management especially when surgical intervention cannot be tolerated by the patient.

Aminolevulinic Acid↗

New proposal for the treatment of nodular basal cell carcinoma with intralesional 5-aminolevulinic acid.

Photodynamic therapy (PDT) is a treatment modality using a photosensitizer, light and oxygen to cause photochemically-induced selective cell death. Topical PDT is most suitable for thin lesions such as superficial basal cell carcinoma and actinic keratoses in dermatology. Results with PDT as treatment of thicker lesions such as nodular basal cell carcinoma appear to have a limited role because the photosensitizer or the light cannot penetrate deeply enough into the thicker tumor volume. In this preliminary study we use intralesional administration of 5-aminolevulinic acid to enhance the efficacy of the photosensitivity of nodular basal cell carcinomas, thus improving clinical cure.

Adult↗

Differences in patterns of progression in demyelinating and axonal Guillain-Barré syndromes.

BACKGROUND: Immune treatments are recommended for patients with Guillain-Barré syndrome (GBS) who cannot walk independently, but a considerable number of GBS patients are in the progressive phase at the first examination. OBJECTIVE: To investigate whether progression patterns differ in demyelinating and axonal subtypes of GBS. METHODS: Clinical, laboratory, and electrophysiologic data on 131 consecutive patients with GBS were reviewed. Patients were classified as having acute inflammatory demyelinating polyneuropathy (AIDP) or acute motor axonal neuropathy (AMAN) based on electrodiagnostic criteria. RESULTS: Forty-one patients had AIDP, 62 AMAN, and 28 were unclassified. Age, sex, and Hughes Functional Grading Scale score at the first medical examination did not differ for the AIDP and AMAN patients. Mean periods between neurologic onset and first examination (5.3 vs 4.2 days; p = 0.01) and neurologic onset and nadir (18.0 vs 11.5 days; p = 0.001) were longer for the AIDP group. In the subgroup of those with mild disability (able to walk independently at the first neurologic examination), 88% of the AMAN patients had reached the nadir, whereas 65% of the AIDP patients had reached it. The remaining 35% progressed to it over the next 1 to 2 weeks and were unable to walk at nadir. CONCLUSIONS: The patterns and speeds of progression differ in AMAN and AIDP, AMAN having a rapid progression and an early nadir. AIDP patients frequently have a significantly long progression after the first examination; therefore, they need to be carefully monitored.

Acute Disease↗

Anti-GM1 antibody IgG subclass: a clinical recovery predictor in Guillain-Barré syndrome.

OBJECTIVE: To determine whether the anti-GM1 antibody IgG subclass (IgG1 to 4) is associated with clinical profiles and patterns of recovery in Guillain-Barré syndrome (GBS). METHODS: The IgG subclassification of anti-GM1 antibody was examined and compared with clinical data on 42 GBS patients positive for the antibody. RESULTS: Frequent anti-GM1 antibody subclasses were IgG1 (76%) and IgG3 (31%). IgG1 antibody was associated with preceding gastroenteritis and Campylobacter jejuni serology, whereas IgG3 antibody was associated with preceding respiratory infection. Although the severity at nadir was similar for IgG1- and IgG3-positive patients, the percentage of patients who could not walk independently was greater for the IgG1-positive group 1 month (42 vs 0%; p = 0.02), 3 months (28 vs 0%), and 6 months (25 vs 0%) after onset. Rapid recovery within 1 month occurred frequently in the patients with the IgG3 antibody but rarely in those with the IgG1 antibody (67 vs 11%; p = 0.003). CONCLUSIONS: The IgG1 subclass of anti-GM1 antibody is a major subtype indicative of slow recovery, whereas isolated elevation of IgG3 subclass antibody titer suggests rapid recovery. Variation in subclass patterns may depend on which pathogen precipitates GBS.

Adult↗

Mapping QTLs for seed dormancy and the Vp1 homologue on chromosome 3A in wheat.

A major component of the observed genetic variation for pre-harvest sprouting in wheat ( Triticum aestivum L.) appears to be the level of seed dormancy. Group 3 chromosomes have received attention as carrying the R genes for seed-coat color and the taVp1 genes that are orthologous to the maize Vp1 gene which encode a dormancy-related transcription factor. The objectives of the present study were to map quantitative trait loci (QTLs) for seed dormancy on chromosome 3A and to investigate an association between taVp1 or R-A1 and the QTLs detected. A mapping population in the form of recombinant inbred lines developed from the cross between the highly dormant Zenkoujikomugi (Zen) and Chinese Spring (CS) was utilized. Nineteen marker loci, including taVp1, were mapped on chromosome 3A. The taVp1 locus was located in the middle of the long arm, about 85 cM from the centromere. The population was evaluated in duplicate by growing them under controlled environment conditions. Two QTLs for seed dormancy, designated as QPhs.ocs-3A.1 and QPhs.ocs-3A.2, were identified on the short and long arms, respectively. QPhs.ocs-1 explained 23-38% of the phenotypic variation and the Zen allele had a striking effect on maintaining dormancy. QPhs.ocs-2, with a minor effect, was detectable only at the dormancy-breaking stage. Although QPhs.ocs-2 was loosely linked to taVp1 by around 50 cM, they are clearly distinct genes. Zen and CS carry the white R-A1a allele, and no QTL effect was detected in the vicinity region of R-A1. Hence it was concluded that the high dormancy associated with chromosome 3A of Zen is ascribable to QPhs.ocs-1 on the short arm but is not due to the direct contribution of either the taVp1 or R-A1 locus.

Chromosomes, Plant↗

Is high-grade adenomatous hyperplasia an early bronchioloalveolar adenocarcinoma?

Atypical adenomatous hyperplasia (AAH) is a probable forerunner of bronchioloalveolar carcinoma (BAC) and pulmonary adenocarcinoma (AC) of mixed type. The present study analysed four low-grade AAHs, 13 high-grade AAHs, two BACs, nine mixed ACs, and one squamous cell carcinoma derived from 13 patients using comparative genomic hybridization. The average number of chromosomal aberrations was 1.2 in low-grade AAH, 9.6 in high-grade AAH, and 12.5 in AC. A high degree of overlap of genetic changes was found in high-grade AAH, BAC, and AC within individual patients. The high number of aberrations and the degree of shared aberrations found in high-grade AAH and AC raises questions about the separation of these two entities. In addition, in view of the monoclonal origin of multiple foci within the same patient, AAH may not be a precursor of AC in some cases, but rather may represent intraepithelial spread.

Adenocarcinoma, Bronchiolo-Alveolar↗

The movement protein gene is involved in the virus-specific requirement of the coat protein in cell-to-cell movement of bromoviruses.

Brome mosaic virus (BMV) requires the coat protein (CP) for cell-to-cell movement whereas Cowpea chlorotic mottle virus (CCMV), from the same genus, does not. Chimeric viruses created by exchanging the movement protein (MP) gene between the viruses can move from cell to cell. We show that interference in CP expression impaired the movement of the chimeric CCMV with the BMV MP gene but not of the chimeric BMV with the CCMV MP gene. We thus conclude that the MP gene plays a crucial role in determination of the virus-specific CP requirement in bromovirus cell-to-cell movement.

Amino Acid Sequence↗

BCA-1, A B-cell chemoattractant signal, is constantly expressed in cutaneous lymphoproliferative B-cell disorders.

We analysed the immunophenotypic and molecular expression of BCA-1 (B-cell-specific chemokine) and CXCR5 (BCA-1 receptor) in normal skin and different cutaneous lymphoproliferative disorders (cutaneous T-cell lymphoma (CTCL); cutaneous B-cell lymphoma (CBCL); cutaneous B-cell pseudolymphoma (PCBCL)), with the aim of investigating their possible involvement in the pathogenesis of cutaneous B-cell disorders. BCA-1 and CXCR5 were constantly expressed in CBCL and PCBCL, but not in normal skin and CTCL. BCA-1 and CXCR5 were constantly coexpressed by CD22+ B-cells, while CD35+ follicular dendritic cells coexpressed BCA-1 in PCBCL cells only. In low grade CBCL, as compared with high grade CBCL, the intensity of CXCR5 expression on neoplastic CD22+ cells was lower than that of BCA-1. The image analysis of reverse transcriptase-polymerase chain reaction (RT-PCR) products showed a significant quantitative difference between PCBCL/low grade CBCL and high grade CBCL. The above findings, although only observed in a small series of patients, are in keeping with findings in MALT gastric and gastric MALT lymphomas, adding further evidence of the close similarities between CBCL and MALT lymphomas.

Base Sequence↗

Antigen selectivity characteristic of polyclonal antibodies against omega-conotoxin GVIA and N-type voltage-dependent calcium channels.

The antibodies against omega-conotoxin GVIA (omega-CTX GVIA; N-type voltage-dependent calcium channel [VDCC] blocker) and B1Nt (N-terminal segment [residues 1-13] of BI alpha1 subunits of VDCCs) were prepared, and the selectivity for each antigen omega-CTX GVIA and B1Nt was investigated. For the antigen selectivity of anti-omega-CTX GVIA antibody against omega-CTX GVIA, ELISA, and immunoprecipitation were used. The reactions for ELISA and immunoprecipitation were observed except when antibody IgG purified by Protein A-Sepharose CL-4B from nonimmunized serum (purified NI-Ab) was used. The specific reactions were inhibited by 10 nM omega-CTX GVIA, but not by omega-CTX SVIB (N-type VDCC blocker), omega-CTX MVIIC (N- and P-type VDCC blocker), or omega-Aga IVA (P-type VDCC blocker). For the antigen selectivity of the anti-B1Nt antibody, analyses by ELISA, immunoprecipitation, and Western blotting were conducted. The reactions were observed except when NI-Ab was used. The ELISA and immunoprecipitation reactions were inhibited by the antigen peptide B1Nt, and the IC50 values were about 1.2 x 10(-8) and 1.3 x 10(-8) M, respectively. The bands of 210 and 190 kD by Western blotting of crude membranes from chick brain were also inhibited by 1 microM B1Nt. These results suggest that the antibodies prepared against omega-CTX GVIA and B1Nt in this work have high selectivity for their antigen. Therefore we assume that the antibodies against omega-CTX GVIA and B1Nt are useful tools for the analyses of the function and distribution of N-type VDCCs. The anti omega-CTX GVIA antibody must also be useful for the radioimmunoassay of omega-CTX GVIA.

Animals↗

Selective insufficiency of IFN-gamma secretion in patients with hyper-IgE syndrome.

BACKGROUND: Hyper-immunoglobulin E (IgE) syndrome is a complex immune deficiency characterized by chronic eczematous dermatitis, recurrent staphylococcal infections, pneumatoceles, reduced neutrophil chemotaxis, and variably impaired T cell function. Although decreased interferon-gamma (IFN-gamma) production in patients with hyper-IgE syndrome is pointed out and known as a cause of reduced neutrophil chemotaxis, precise mechanism of their inadequate production of IFN-gamma remains unknown. To elucidate the pathogenesis of the defective production of IFN-gamma in patients with hyper-IgE syndrome, we assessed the in vitro production and secretion of IFN-gamma by peripheral blood mononuclear cells (PBMCs) from patients with hyper-IgE syndrome. METHODS: Chemotaxis of neutrophils, mRNA levels of several cytokines, intracellular production and extracellular secretion of IFN-gamma, interleukin-2 (IL-2), and IL-4 by PBMCs from three patients with hyper-IgE syndrome were determined. RESULTS: The transcription of IFN-gamma mRNA and the production of its protein molecules progressed normally. However, selective insufficiency in the secretion of IFN-gamma molecules was found in patients with hyper-IgE syndrome. Confocal laser scanning microscopy clearly demonstrated the accumulation of IFN-gamma in patients with hyper-IgE syndrome. CONCLUSION: We demonstrated that there was a selective insufficiency in the secretion of IFN-gamma in patients with hyper-IgE syndrome. We hope that this fact would offer a new paradigm for understanding this disease.

Adult↗