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Biomedical subjects

M Yamazaki

Publications and source records attributed to M Yamazaki.

At least 181 records · Page 10Linked to original sources

Two regions of homozygous deletion clusters at chromosome band 9p21 in human lung cancer.

We examined 149 lung cancer cell lines for homozygous deletions using 24 DNA markers, which were mapped and ordered in chromosome band 9p21, to define the target regions for 9p21 deletions in human lung cancer. Homozygous deletions were detected in 39 (26%) cell lines and clustered at 2 independent regions. One was the region containing the p16/CDKN2A tumor suppressor gene, and this region was deleted in 32 (21%) cell lines. The other was the region containing D9S171, which is the locus approximately 3 Mb proximal to the CDKN2A locus. This region, designated as the D9S171 region, was deleted in 18 (12%) cell lines. Seven of the 18 cell lines had identical minimum deletions of a 17,036 bp sequence located 20 kb distal to the D9S171 locus. However, such a deletion was also observed in the corresponding B-lymphoblastoid cell line from 1 of the 7 cell lines and in 5 (16%) of 32 noncancerous tissues, suggesting that the deletion was a genetic polymorphism. By considering this polymorphism, 11 (7%) cell lines still had deletions at the D9S171 region. Two NSCLC cell lines showed deletions at the D9S171 region and retentions of the CDKN2A locus. Furthermore, an NSCLC cell line showed discontinuous deletions including either the CDKN2A or D9S171 locus. Therefore, the region surrounding the D9S171 locus was defined as another target region for the 9p21 deletions. It is possible that unknown tumor suppressor gene(s) are present in this chromosomal region. Genes Chromosomes Cancer 27:308-318, 2000.

Carcinoma, Non-Small-Cell Lung↗

[An autopsy case of primary cerebellar-pontine angle epidermoid carcinoma].

A 65-year-old man developed right facial palsy and six months later experienced sudden unconsciousness and right hemiplegia. On admission he had severe nuchal rigidity, decreased visual acuity, and a hearing disturbance. A CT scan and angiography failed to reveal any lesions in the brain, but CSF cytology showed undifferentiated malignant cells with a high level of neuron-specific enolase. A postcontrast CT scan and MRI demonstrated diffuse meningeal enhancement and a faintly rim-enhanced cystic lesion at the cerebellopontine angle. The patient died four months after admission, and postmortem examination revealed meningeal dissemination of squamous cell carcinoma, probably arising from an epidermoid cyst at the cerebellopontine angle. Microscopic examination revealed squamous epithelial debris and a foreign body reaction in portions of the cyst wall and in the surrounding subarachnoid space near the base of the cyst. Rim enhancement of the cyst on MRI and the microscopic findings indicated that the recurrent headaches may have been the result of chemical aseptic meningitis caused by spontaneous leakage of the cyst's contents.

Aged↗

[Supplementary motor area epilepsy associated with ADHD in an abused history].

A 6-year-old girl with attention-deficit hyperactivity disorder (ADHD) who had been abused by her mother in infancy developed supplementary motor area (SMA) epilepsy. The seizure was characterized by bilateral tonic seizure of the upper and lower extremities, speech arrest, preserved consciousness and a lack of postictal confusion. The duration of the seizure was usually 10-60 seconds. The seizures sometimes clustered. She was diagnosed as having SMA epilepsy based on the characteristic clinical symptoms, interictal EEG, ictal video-EEG and ictal SPECT. Though her seizure was initially improved by anti-epileptic drugs, the symptoms appeared again after discharge. Since her clinical course indicated that her seizure was aggravated by her mental state, treatment included both medication with anti-epileptic drugs and the adjustment of her living environment in cooperation with a child guidance clinic. Thereafter both her epileptic seizure and ADHD symptoms improved. These changes may be related to each other, because both conditions are associated with frontal lobe dysfunction. It was interesting that the adjustment of the environment improved frontal lobe epilepsy, which in turn ameliorated ADHD symptoms.

Attention Deficit Disorder with Hyperactivity↗

[Non-Hodgkin's lymphoma in two married couples].

Couple 1: A 74-year-old woman was diagnosed as having diffuse large B-cell lymphoma (DLBL) by left axillary lymph node biopsy. About 6 months later, DLBL was also diagnosed in her 79-year-old husband by right submandibular lymph node biopsy. Although the wife achieved partial remission with chemotherapy, she died due to disease progression. The husband's disease was chemotherapy-resistant, and he died of renal failure. Couple 2: An 86-year-old man was diagnosed as having DLBL by left axillary lymph node biopsy. About 4 years later, DLBL was also diagnosed in his 86-year-old wife by left axillary lymph node biopsy. Both the husband and the wife received chemotherapy. The husband is currently alive in complete remission, and although the wife achieved partial remission, she died due to disease progression. In both of these couples, it was considered unlikely that Epstein-Barr virus or human T-cell lymphotropic virus type I was related to the development of non-Hodgkin's lymphoma, and no environmental factors were confirmed to be involved. It is postulated that other unknown factors or agents may be associated with the development of lymphoma in married couples.

Aged↗

An increase in multi-drug-resistant isolates of Salmonella typhimurium from healty carriers in Aichi, Japan.

To investigate the prevalence of drug-resistant isolates of Salmonella Typhimurium in Aichi, Japan, we performed antimicrobial susceptibility tests for 148 isolates from healthy carriers, and from sporadic and outbreak cases of salmonellosis from 1980 to 1999. We found an increase in drug-resistant isolates from 56% (37/66) in the 1980s to 74% (61/82) in the 1990s due to increasing examples of four-, five-, and six-drug resistances. Of 98 resistant isolates in 1980-1999, 12 were identified as ampicillin (A)-, chloramphenicol (C)-, streptomycin (S)-, sulfonamide (Su)-, and tetracycline (T)-resistant S. Typhimurium (4 in the 1980s, 8 in the 1990s), whose pattern was identical to that of multi-drug-resistant S. Typhimurium definitive phage type 104 (DT104) which has been recently detected in various developed countries. Six-drug-resistance ACSSuTP (piperacillin), in which P was added to the core pattern of the ACSSuT, was also found in four isolates in the 1980s and seven in the 1990s. Another six-drug-resistant pattern, ACSSuTN (nalidixic acid), appeared in five isolates in the 1990s. These multi-drug-resistant isolates were predominately found in healthy carriers (21/28), suggesting that in Aichi the multi- (five- or six-) drug-resistant isolates of S. Typhimurium have existed in healthy carriers as well as in diarrhea patients in 1980 to 1999.

Anti-Bacterial Agents↗

[Bacteria isolated from surgical infections and their susceptibilities to antimicrobial agents. Special references to bacteria isolated between April 1997 and March 1998].

The annual multicenter studies on isolated bacteria from infections in general surgery and their antimicrobial susceptibility have been conducted in 19 facilities in Japan since July 1982. This paper describes the results obtained during the period from April 1997 to March 1998. The number of cases investigated as objectives was 215 for one year. A total of 420 strains (170 strains from primary infections and 250 strains from postoperative infections) were isolated from 174 cases (80.9% of total cases). In primary infections, the isolation rate of anaerobic bacteria was higher than in postoperative infections, while in postoperative infections, those of aerobic Gram-positive bacteria and Pseudomonas aeruginosa were higher than in primary infections. Among aerobic Gram-positive bacteria, the isolation rate of Enterococcus faecalis was the highest, followed by Staphylococcus aureus, which was frequently isolated from postoperative infections. Among anaerobic Gram-positive bacteria, Peptostreptococcus spp. and Streptococcus spp. were commonly isolated from both types of infections. Among aerobic Gram-negative bacteria, Escherichia coli was most predominantly isolated from primary infections, followed by P. aeruginosa, Klebsiella pneumoniae in this order, and from postoperative infections, P. aeruginosa was most predominantly isolated, followed by E. coli and K. pneumoniae. Among anaerobic Gram-negative bacteria, Bacteroides fragilis group was the majority of isolates from both types of infections. We found neither vancomycin nor arbekacin resistant strains of S. aureus, and found no vancomycin resistant strains of Enterococcus spp. The susceptibility of P. aeruginosa against carbapenems did not decline in the year 1997, while resistance of B. fragilis group against cephems advanced increasingly.

Anti-Bacterial Agents↗

[Arterial infusion chemotherapy for liver metastases from colorectal cancer--therapeutic effects of different protocols].

The therapeutic effects of different protocols for arterial infusion chemotherapy were compared in patients with multiple liver metastases from colorectal cancer. A total of 49 patients with colorectal multiple liver metastases treated in our hospital since 1988 were the subjects. In order to compare the therapeutic effects on the regression of cancer and the survival rate, the subjects were assigned into Groups A-D, which were treated using different protocols. Group A received ADR, EPI, CDDP or 5-FU alone at first. If this drug was not effective, it was replaced with another of those mentioned here, and so on. Group B received CDDP 50 mg on day 1, 5-FU 500 mg/day from day 2 to day 7 and 5-FU 500 mg/day for 2 weeks thereafter (FP treatment). Group C received CDDP 50 mg at the time of reservoir insertion and 5-FU 1,000 mg for 5 hours thereafter (WHF treatment). Group D received 5-FU 1,000 mg for 24 hours on day 1, day 3, and day 5 of every week with combination of CDDP 5-10 mg/day from day 1 to day 5 and none on day 6 and day 7 (intermittent F + low-dose P treatment) for 3 weeks. The response rate was 33% for Group A (n = 18), 46% for Group B (n = 13), 25% for Group C (n = 8) and 80% for Group D (n = 10), showing significant differences between Group D and other groups. The 1-year survival rate was 50% for Group A, 46% for Group B, 29% for Group C and 89% for Group D. Significant differences in survival rate were found between Group B and D, and Group C and D.

Antineoplastic Agents↗

Effects of the 5-HT(3) receptor antagonist ondansetron on the ketamine- and dizocilpine-induced place preferences in mice.

The effects of the 5-HT(3) receptor antagonist ondansetron on the ketamine- and dizocilpine-induced place preferences in mice were examined. The non-competitive NMDA receptor antagonists ketamine (1. 0-10 mg/kg, i.p.) and dizocilpine (0.1 and 0.2 mg/kg, i.p.) each produced a place preference in a dose-dependent manner. The ketamine (10 mg/kg)- and dizocilpine (0.2 mg/kg)-induced place preferences were dose-dependently blocked by pretreatment with ondansetron (0. 03-0.1 mg/kg, s.c.). These results suggest that 5-HT(3) receptor may be involved in the development of the place preferences produced by ketamine and dizocilpine.

Animals↗

Effect of anti-B7-1 and anti-B7-2 mAb on Theiler's murine encephalomyelitis virus-induced demyelinating disease.

We examined the role of B7-1 and B7-2, costimulatory molecules critical to full activation of T cells, in the development of Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Treatment with mAbs to B7-1 resulted in significant suppression of the development of this disease both clinically and histologically. In mice treated with these mAbs, the production of TNF-alpha and IFN-gamma in the spleen cells was decreased. The delayed-type hypersensitivity and T cell proliferative response specific for TMEV were decreased by this treatment. In contrast, treatment with Abs to B7-2, resulted in no effect on TMEV-IDD. These data suggest that B7-1 is critically involved in the pathogenesis of TMEV-IDD and that Abs to B7-1 could be a novel therapeutic approach in the clinical treatment of demyelinating diseases such as human multiple sclerosis.

Animals↗

Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation.

Synthesis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], a signaling phospholipid, is primarily carried out by phosphatidylinositol 4-phosphate 5-kinase [PI(4)P5K], which has been reported to be regulated by RhoA and Rac1. Unexpectedly, we find that the GTPgammaS-dependent activator of PI(4)P5Kalpha is the small G protein ADP-ribosylation factor (ARF) and that the activation strictly requires phosphatidic acid, the product of phospholipase D (PLD). In vivo, ARF6, but not ARF1 or ARF5, spatially coincides with PI(4)P5Kalpha. This colocalization occurs in ruffling membranes formed upon AIF4 and EGF stimulation and is blocked by dominant-negative ARF6. PLD2 similarly translocates to the ruffles, as does the PH domain of phospholipase Cdelta1, indicating locally elevated PI(4,5)P2. Thus, PI(4)P5Kalpha is a downstream effector of ARF6 and when ARF6 is activated by agonist stimulation, it triggers recruitment of a diverse but interactive set of signaling molecules into sites of active cytoskeletal and membrane rearrangement.

ADP-Ribosylation Factor 1↗

Identification of amino acid sequence in the hinge region of human vitamin D receptor that transfers a cytosolic protein to the nucleus.

The localization of human vitamin D receptor (VDR) in the absence of its ligand 1,25-dihydroxyvitamin D(3) was investigated using chimera proteins fused to green fluorescent protein (GFP) at either the N or C terminus, and the nuclear localization signal (NLS) was identified. Plasmids carrying the fusion proteins were transiently or stably introduced into COS7 cells, and the subcellular distribution of the fusion proteins was examined. GFP-tagged wild-type VDRs were located predominantly in nuclei but with a significant cytoplasmic presence, while GFP alone was equally distributed throughout the cells. 10(-8) M 1,25-dihydroxyvitamin D(3) promoted the nuclear import of VDR in a few hours. To identify the NLS, we constructed several mutated VDRs fused to GFP. Mutant VDRs that did not bind to DNA were also localized predominantly in nuclei, while the deletion of the hinge region resulted in the loss of preference for nucleus. A short segment of 20 amino acids in the hinge region enabled cytoplasmic GFP-tagged alkaline phosphatase to translocate to nuclei. These results indicate that 1) VDR is located predominantly in nuclei with a significant presence in cytoplasm without the ligand and 2) an NLS consisting of 20 amino acids in the hinge region facilitates the transfer of VDR to the nucleus.

Amino Acid Sequence↗

Recurrent steroid-responsive trismus and painful ophthalmoplegia.

A 63-year-old woman experienced two episodes of trismus and painful ophthalmoplegia at an interval of six years. She suffered left visual loss, and enhanced CT scan and MR imaging revealed heterogeneous enlargement of the left extraocular muscles extending to the orbital apex. In addition, the left pterygopalatine fossa was filled with a mass isointense with muscle without evidence of surrounding tissue invasion; 67Ga scintigraphy showed high uptake in this lesion. Steroid administration dramatically resolved the trismus, and the mass in the orbit and extraorbit vanished completely. Orbital pseudotumor is characterized by self-limited, relapsing, steroid-responsive painful ophthalmoplegia, and this case could be a variant of this entity with inflammation extending into the extraorbital area.

Anti-Inflammatory Agents↗

Effects of electrostatic interaction on the phase stability and structures of cubic phases of monoolein/oleic acid mixture membranes.

To elucidate effects of electrostatic interactions due to the surface charges on structures and phase stability of cubic phases of lipids, the mixture membranes of monoolein (MO) and oleic acid (OA) (OA/MO membrane) have been investigated by small-angle X-ray scattering method. As increasing OA concentration in the OA/MO membrane, a phase transition from Q(224) to Q(229) phase occurred, and above 1.0 mol% OA, OA/MO membranes were in the Q(229) phase. However, when NaCl concentration in the bulk phase is large, the Q(224) phase is more stable than the Q(229) phase in the OA/MO membranes containing high concentrations of OA. These results indicate that the electrostatic repulsion between the headgroups of these membranes makes the Q(229) phase more stable than the Q(224) phase. We have also found that lowering pH induces a phase transition from Q(229) to Q(224), and at lower pH a phase transition from Q(224) to H(II). These results are discussed in terms of the spontaneous curvature of the monolayer membrane and a lipid packing parameter of the membrane.

Glycerides↗

Molecular dynamics of MHC genesis unraveled by sequence analysis of the 1,796,938-bp HLA class I region.

The intensely studied MHC has become the paradigm for understanding the architectural evolution of vertebrate multigene families. The 4-Mb human MHC (also known as the HLA complex) encodes genes critically involved in the immune response, graft rejection, and disease susceptibility. Here we report the continuous 1,796,938-bp genomic sequence of the HLA class I region, linking genes between MICB and HLA-F. A total of 127 genes or potentially coding sequences were recognized within the analyzed sequence, establishing a high gene density of one per every 14.1 kb. The identification of 758 microsatellite provides tools for high-resolution mapping of HLA class I-associated disease genes. Most importantly, we establish that the repeated duplication and subsequent diversification of a minimal building block, MIC-HCGIX-3.8-1-P5-HCGIV-HLA class I-HCGII, engendered the present-day MHC. That the currently nonessential HLA-F and MICE genes have acted as progenitors to today's immune-competent HLA-ABC and MICA/B genes provides experimental evidence for evolution by "birth and death," which has general relevance to our understanding of the evolutionary forces driving vertebrate multigene families.

Base Pairing↗

Effects of solvents interacting favorably with hydrophilic segments of the membrane surface of phosphatidylcholine on their gel-phase membranes in water.

We have investigated the effects of two kinds of solvents forming the lamellar liquid-crystalline (L(alpha)) phase in phosphatidylcholine (PC) membranes in neat condition, such as formamide and 1,3-propanediol, on phase behaviors of multilamellar vesicle (MLV) of DPPC (DPPC-MLV). These solvents induced the interdigitated gel (L(beta)I) phase in DPPC-MLV in excess water above their critical concentrations. Solubility measurement indicates that these solvents interact favorably with the hydrophilic segment of the PC membrane but interact unfavorably with the alkyl chains. Based on these results, we propose the mechanism of the induction of the L(beta)I phase by these solvents.

Journal Article↗