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Biomedical subjects

S Shimizu

Publications and source records attributed to S Shimizu.

At least 199 records · Page 11Linked to original sources
PubMed2000

[Midterm results of total aortic root replacement with pulmonary autograft (Ross operation)].

Between February 1995 and December 1999, 18 patients underwent Ross operation. Age at the operation ranged from 2 to 31 years. Diagnosis includes congenital aortic stenosis and/or regurgitation in 15, and adult aortic regurgitation in 3. In all cases autograft was implanted by the method of total aortic root replacement, associated with annuloplasty for the dilated aortic annulus in 2 and aortoventriculotomy by the Konno procedure in 3 (Ross-Konno). Right ventricular outflow tract was reconstructed by a pulmonary homograft in 12, a xenopericardial conduit in 3, or the other reconstructive procedures with autologous tissue and outflow patch in 3. There was no operative and late death. Reoperation was needed in 1 patient due to stenosis of pericardial conduit 4 years after the initial operation. Pressure gradient across implanted autograft valve was negligible (4.8 +/- 0.5 mmHg), and echocardiography revealed no aortic regurgitation in 12 cases and trivial to mild in 6, over a mean follow-up period of 23 +/- 18 months (range 2 to 60 months), signifying excellent durability of implanted autograft. Right ventricular outflow tract reconstruction with the homograft resulted in excellent mid-term performance as showing pressure gradient of 9.0 +/- 4.6 mmHg and no regurgitation in 11 of 12 cases, whereas pressure gradient was 17.9 +/- 13.1 mmHg in the patients underwent the other reconstructive procedures. We conclude that Ross procedure associated with the concomitant procedures to adjust the size discrepancy between the native aortic annulus and autograft has provided good midterm results with excellent autograft durability. And this procedure was thought to be a preferable method for children as well as young adults with congenital aortic stenosis.

Adolescent↗
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

[Children with disabilities, families with a disabled child and social policy].

In this article the author described three social movements by families with a disabled child: (1) respite services which refresh family members by a short-term relief care in a local region, (2) after-school activities in which children with disabilities participate in recreation activities and built up a friendship with non-disabled people in neighborhood, and (3) schooling of children with special health care which enables the children to attend unaccompanied by mothers until after-school hours. The author's analysis indicated that a social policy for the people with disabilities and their families should consider other dimensions which may be influenced by the social policy. This is because different social settings (e.g. home, school, family) are interdependent and that events and changes in one unit have an effect on other social settings.

Child↗
PubMed2000

[Factors influencing visual acuity following vitrectomy for exudative age-related macular degeneration].

PURPOSE: We investigated the influence of various factors on visual results in patients undergoing surgical removal of choroidal neovascular membranes (CNVM) caused by age-related macular degeneration (AMD). SUBJECTS AND METHODS: This study was performed in 55 eyes of 55 patients who underwent surgical removal of CNVM for AMD and followed them for 6 months or more. The criterion for surgical eligibility was active subfoveal choroidal neovascular membrane of 0.5 or more disc diameter above the retinal pigment epithelium with visual acuity of 0.3 or worse. We investigated the influence of various factors on the logarithm of the minimum angle of resolution (log MAR) final visual acuity. The factors were age, symptom duration, preoperative log MAR visual acuity, CNVM diameter, mean deviation with visual field analyzer, previous laser treatment, posterior vitreous detachment, findings of indocyanine green angiography, operative complications, and recurrence of CNVM. RESULTS: Better preoperative visual acuity, shorter symptom duration, and smaller CNVM diameter were correlated with better postoperative final visual acuity. CONCLUSIONS: Surgical excision of subfoveal CNVM may be the better therapeutic choice in selected cases with AMD.

Aged↗
PubMed2000

High frequency of clonally related tumors in cases of multiple synchronous lung cancers as revealed by molecular diagnosis.

In patients with multiple synchronous lung tumors, discrimination of multicentric lung cancers from intrapulmonary metastasis is important for treatment decision, but this is sometimes difficult. The aim of this study was to retrospectively distinguish multicentric lung cancers from intrapulmonary metastases in 14 such cases by loss of heterozygosity (LOH) and p53 mutational status. DNA was extracted from microdissected tumor cells in paraffin-embedded archival tissue, and 3p14.2, 3p21, 3p25, 9p21, and 18q21.1 were investigated for LOH. Exons 5-8 of the p53 gene were examined for mutations by the PCR, followed by single-strand conformation polymorphism analysis and DNA sequencing. For cases with the same LOH pattern, we calculated a clonality index, the probability of the given LOH pattern when these tumors were hypothesized to be independent in origin. Eleven of 14 cases (79%) were thus diagnosed as having pulmonary metastasis and only one case as having genuinely multicentric lung cancers. Two cases presented difficulty in diagnosis. In several cases, the LOH patterns conflicted with p53 mutation patterns, suggesting that clonal evolution is directly affected by certain genetic changes. The combination of p53 with LOH helped increase both the sensitivity and specificity of the assay.

Adult↗
PubMed2000

[Hepatic arterial infusion chemotherapy for unresectable liver metastasis of gastrointestinal cancers].

Thirty-two patients with colorectal cancer, eleven with gastric cancer and two with pancreatic cancer were treated by hepatic arterial infusion chemotherapy from March 1988 to December 1999. A single administration of 5-FU, MMC and epirubicin (FAM group), or intermittent continuous infusion of 5-FU 500 mg/2 h (5-FU continuous group) was used for each patient once a week. Overall survival rates were not significantly different between the gastric and colorectal cancer patients. In patients with colorectal cancer, there was a significant prolongation in overall survival for the response group. With gastric cancer, however, there was no significant difference. For both of the two patients with pancreatic cancer, although they were responsive to the therapy, there was no prolongation of survival. In conclusion, intermittent continuous infusion was more effective for the patients with colorectal cancer. In patients with gastric and pancreatic cancer, hepatic intra-arterial infusion could control the progression of liver metastasis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Different pathological findings in each of four parathyroid glands in a long-standing hemodialysis patient.

A 51-year-old male patient with chronic renal failure, who had required dialysis for 22 years, presented with a cervical mass. Laboratory data were consistent with secondary hyperparathyroidism due to chronic renal failure. Cervical exploration was performed with excision of four parathyroid glands and autotransplantation of the normal gland into the forearm. The cervical tumor of the right inferior gland demonstrated parathyroid carcinoma histologically. Adenoma of the right superior gland and hyperplasia of the left superior gland were also recognized. The left inferior gland was normal. A few cases of parathyroid carcinoma in patients on maintenance hemodialysis have been previously reported. However, this is the first report in which all four parathyroid glands revealed different pathological findings: carcinoma, adenoma, hyperplasia and normal gland. Chronic stimulation of the parathyroid glands to release parathyroid hormone might have caused the variety of findings in the four parathyroid glands.

Adenoma↗
PubMed2000

[Consciousness of drug abuse problems and motivational intention for primary community intervention among the community residents].

PROBLEM: An influence of the community factor has a tremendous significance over the policy taken for the social rehabilitation of drug addicts as well as for the prevention of the drug problems. This study focuses, from a sociological viewpoint, on attitudes and consciousness of the community residents on drug abuse problems, particularly addressing their motivational intention of primary intervention in the community settings. METHOD: A social investigation with a random sampling of the adult male population of a ward community in Osaka was conducted by combining the self-administered schedule method and the individual interview method at the door. RESULTS: 1) More than 90% of the respondents recognized the drug abuse problem in Japan as one of the most severe social problems; 2) as for countermeasures against the drug problems, crack-down by police and severe legal punishments were much more preferred overwhelmingly to the soft measures such as education, therapy and social services; 3) ex-patients of drug abuse and dependence discharged from mental hospitals would be supposed to be faced with harsh, rejective interactions in their community life; 4) 15.4% of the respondents reported their recognition of the illegal drug users in the last three years prior to the survey and those reporting the recognition in their life time were found by 26.5%; 5) the active motivation for primary intervention with drug users on the community basis was widely shared among the community residents. DISCUSSION: It was implied that this motivational asset excavated in the community should be activated in one way or another by community programs for the primary prevention against drug abuse.

Adult↗
PubMed2000

[Central necrosis of the lumbo-sacral segment of the spinal cord associated with multiple cholesterin emboli, clinically presenting as acute paraplegia].

A seventy-six-year-old man suddenly suffered from paraplegia and pain in both legs. He had been maintained on hemodialysis and committed a suicide attempt by cutting the shunt at the paraplegic attack. He was brought to the emergency ward for the treatment of hemorrhagic preshock. Neurological examination demonstrated flaccid paraplegia, loss of tendon reflex in the lower extremities, dissociated sensory loss below the fourth lumbar level; and incontinence in defecation. MRI showed T2 shortening in the ventral spinal cord caudal below the level of the eleventh thoracic cord. Postmortem examination confirmed ischemic infarct in the central area of the spinal cord, associated with disseminated cholesterin emboli in the small arteries. This case was the first MRI demonstration of central necrosis caused by cholesterin emboli, and may emphasize the significance of cholesterin emboli in the spinal arterial disorders in the aged.

Acute Disease↗
PubMed2000

[Recurrent episodes of fever of unknown origin as temporal lobe epilepsy].

A 67-year-old woman was admitted to our department for the recurrent fever of unknown origin that occurred once approximately every 1 month for the last 3 years. No clinical and laboratory abnormality were found, except an interictal EEG showing fronto-temporal spike discharges. During hospitalization a characteristic febrile episode was accompanied by automatism, thereby, it became clear that the undetermined periodic febrile episodes were due to temporal lobe epilepsy. In this case, the thermoregulatory center of the hypothalamus might be symptomatic zone of temporal lobe epilepsy.

Aged↗
PubMed1999

Novel bacterial peroxidase without catalase activity from Flavobacterium meningosepticum: purification and characterization.

A novel bacterial peroxidase co-produced intracellularly with H(2)O(2)-forming nucleoside oxidase, was purified from the cell-free extract of Flavobacterium meningosepticum to homogeneity with 10.3% overall recovery through simple purification procedures including successive DEAE-Sephacel, phenyl-Sepharose CL-4B and Sephacryl S-300 chromatography. The relative molecular mass of the native enzyme was 220¿ omitted¿000 Da, and that of its subunit was 54¿ omitted¿000 Da. In contrast to other major intercellular peroxidases of bacterial origin, the enzyme did not show any catalase activity. The amino acid sequences of the 92 NH(2)-terminal amino acids and three internal peptides showed no significant homology with known peroxidases. The enzyme was not sensitive to the typical peroxidase inhibitors NaCN, NaF and NaN(3), while mercuric ion strongly inhibited the enzyme activity, and some carbonyl reagents were also found to have inhibitory effects. The enzyme showed a small K(m) value for H(2)O(2) (9.5 microM) compared to other peroxidases. On the basis of its visible absorption spectrum, the enzyme contained about 1.3 mol of heme per molecule.

Amino Acid Sequence↗
PubMed1999

Apoptotic cytosol facilitates Bax translocation to mitochondria that involves cytosolic factor regulated by Bcl-2.

Proapoptotic members of the Bcl-2 family, including Bax, Bak, and Bid, directly trigger the mitochondrial release of apoptogenic cytochrome c and apoptosis-inducing factor into the cytoplasm. One of the crucial steps before Bax can exert its proapoptotic activity is translocation from the cytoplasm to the mitochondria, but the molecular mechanism of this translocation is not understood. To investigate the mechanism of apoptosis-associated Bax translocation, we used an in vitro system comprising isolated mitochondria and cytosol. We found that both endogenous and exogenous added recombinant Bax translocated to the mitochondria more efficiently in the presence of cytosol from cells with VP16-induced apoptosis than with cytoplasm from normal cells. This apoptosis-dependent promotion of Bax translocation was not seen with cytosol that was prepared from VP16-treated cells expressing Bcl-2. Cytosol from cells with VP16-induced apoptosis, but not that from normal cells or Bcl-2-expressing cells, induced cytochrome c release from isolated mitochondria, which, as assessed by immunodepletion experiments, was mainly mediated by Bax. These results suggest that Bcl-2 exerts its antiapoptotic activity partly by inhibiting the translocation of Bax through the modification of cytosolic factors that are involved in such translocation during apoptosis.

Apoptosis↗
PubMed1999

Delta6-fatty acid desaturase from an arachidonic acid-producing Mortierella fungus. Gene cloning and its heterologous expression in a fungus, Aspergillus.

A DNA fragment was cloned from the fungal strain, Mortierella alpina 1S-4 (which is used industrially to produce arachidonic acid), after PCR amplification with oligonucleotide primers designed based on the sequence information for delta6-desaturase genes (from borage and Caenorhabditis elegans), which are involved in the desaturation of linoleic acid (delta9, delta12-18:2) to gamma-linolenic acid (delta6, delta9, delta12-18:3). This fragment was used as a probe to isolate a cDNA clone with an open reading frame encoding 457 amino acids from a M. calpina 1S-4 library. The predicted amino-acid sequence showed similarity to those of the above delta6-desaturases, and contained a cytochrome b5-like domain at the N-terminus, being different from the yeast delta9-desaturase which has the corresponding domain at the C-terminus. The full-length cDNA clone was expressed under the control of the amyB promoter in a filamentous fungus, Aspergillus oryzae, resulting in the accumulation of gamma-linolenic acid (which was not detected in the control Aspergillus) to the level of 25.2% of the total fatty acids. These findings revealed that the recombinant product has delta6-desaturase activity. The Mortierella delta6-desaturase is the first to be reported in fungi.

Amino Acid Sequence↗
PubMed1999

Purification and characterization of a novel enzyme, L-threo-3-hydroxyaspartate dehydratase, from Pseudomonas sp. T62.

L-threo-3-Hydroxyaspartate dehydratase (L-threo-3-hydroxyaspartate hydro-lyase), which exhibited specificity for L-threo-3-hydroxyaspartate (K(m)=0.74 mM, V(max)=37.5 micromol min(-1) (mg protein)(-1)) but not for D-threo or D, L-erythro-3-hydroxyaspartate, was purified from a cell-free extract of Pseudomonas sp. T62. The activity of the enzyme was inhibited by hydroxylamine and EDTA, which suggests that pyridoxal 5'-phosphate and divalent cations participate in the enzyme reaction. The NH(2)-terminal amino acid sequence showed significant similarity to the Saccharomyces cerevisiae YKL218c gene product, a hypothetical threonine dehydratase. However, the purified enzyme showed no threonine dehydratase activity.

Amino Acid Sequence↗
PubMed1999

Molecular and functional characterization of a novel mouse transient receptor potential protein homologue TRP7. Ca(2+)-permeable cation channel that is constitutively activated and enhanced by stimulation of G protein-coupled receptor.

Characterization of mammalian homologues of Drosophila transient receptor potential protein (TRP) is an important clue to understand molecular mechanisms underlying Ca(2+) influx activated in response to stimulation of G(q) protein-coupled receptors in vertebrate cells. Here we have isolated cDNA encoding a novel seventh mammalian TRP homologue, TRP7, from mouse brain. TRP7 showed abundant RNA expression in the heart, lung, and eye and moderate expression in the brain, spleen, and testis. TRP7 recombinantly expressed in human embryonic kidney cells exhibited distinctive functional features, compared with other TRP homologues. Basal influx activity accompanied by reduction in Ca(2+) release from internal stores was characteristic of TRP7-expressing cells but was by far less significant in cells expressing TRP3, which is structurally the closest to TRP7 in the TRP family. TRP7 induced Ca(2+) influx in response to ATP receptor stimulation at ATP concentrations lower than those necessary for activation of TRP3 and for Ca(2+) release from the intracellular store, which suggests that the TRP7 channel is activated independently of Ca(2+) release. In fact, TRP7 expression did not affect capacitative Ca(2+) entry induced by thapsigargin, whereas TRP7 greatly potentiated Mn(2+) influx induced by diacylglycerols without involvement of protein kinase C. Nystatin-perforated and conventional whole-cell patch clamp recordings from TRP7-expressing cells demonstrated the constitutively activated and ATP-enhanced inward cation currents, both of which were initially blocked and then subsequently facilitated by extracellular Ca(2+) at a physiological concentration. Impairment of TRP7 currents by internal perfusion of the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid revealed an essential role of intracellular Ca(2+) in activation of TRP7, and their potent activation by the diacylglycerol analogue suggests that the TRP7 channel is a new member of diacylglycerol-activated cation channels. Relative permeabilities indicate that TRP7 is slightly selective to divalent cations. Thus, our findings reveal an interesting correspondence of TRP7 to the background and receptor stimulation-induced cation currents in various native systems.

Amino Acid Sequence↗
PubMed1999

Bcl-2/E1B 19 kDa-interacting protein 3-like protein (Bnip3L) interacts with bcl-2/Bcl-xL and induces apoptosis by altering mitochondrial membrane permeability.

We have previously reported on cloning of the human gene encoding Bcl-2/adenovirus E1B 19 kDa-interacting protein 3-like protein (Bnip3L) and its growth inhibitory effect on cancer cells. Here we show that Bnip3L contains a motif similar to the BH3 domain which is conserved in Bcl-2 family proteins as well as containing a membrane-anchoring domain, and that Bnip3L interacts with Bcl-2 and Bcl-xL. Immunofluorescence microscopy revealed that Bnip3L was localized in the mitochondria, when in the presence of the membrane-anchoring domain. Transient expression of Bnip3L induced apoptosis of Rat-1 and HeLa cells and mutational analysis revealed that the BH3 domain and the membrane-anchoring domain were required for Bnip3L to induce cell death. Addition of recombinant Bnip3L to isolated mitochondria induced membrane potential loss and cytochrome c release both of which have been suggested to be prerequisite for apoptotic cell death. These results suggest that Bnip3L is one of the BH3-containing pro-apoptotic proteins and that it targets the mitochondria when inducing apoptosis.

Adenovirus E1B Proteins↗