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Biomedical subjects

S Murakami

Publications and source records attributed to S Murakami.

At least 199 records · Page 11Linked to original sources

Regeneration of periodontal tissues by basic fibroblast growth factor.

Several growth factors (or cytokines) have recently received attention because of their ability to actively regulate various cellular functions of periodontal ligament (PDL) cells and the effects of topical application of such factor(s) on periodontal tissue regeneration has been evaluated. In this study, we examined the role of basic fibroblast growth factor (bFGF) in the wound healing and regeneration of periodontal tissues. Alveolar bone defects (such as 2-wall, 3-wall and furcation class II bone defects) were created surgically in beagle dogs and primates. Recombinant bFGF was topically applied to the artificial bony defects. Six or 8 wk after application, the periodontal regeneration was morphologically and histomorphometrically analyzed. In all sites where bFGF was applied, significant periodontal ligament formation with new cementum deposits and new bone formation was observed in amounts greater than in the control sites. We found it noteworthy that no instances of epithelial down growth, ankylosis or root resorption were observed in the bFGF sites. In vitro studies demonstrated that bFGF enhances the proliferative responses of human PDL cells, which express FGF receptor-1 and -2, but inhibits the induction of alkaline phosphatase activity and mineralized nodule formation by PDL cells. Interestingly, we observed that the mRNA level of laminin in PDL cells, which plays an important role in angiogenesis, was specifically upregulated by bFGF stimulation, but that of type I collagen was downregulated. The present study demonstrates that bFGF can be applied as one of the therapeutic modalities which actively induce periodontal tissue regeneration. The results of in vitro studies suggest that by suppressing the cytodifferentiation of PDL cells into mineralized tissue forming cells, bFGF may play important roles in wound healing by promoting angiogenesis and inducing the growth of immature PDL cells, and may in turn accelerate periodontal regeneration.

Administration, Topical↗

Surgical orthodontic treatment of skeletal Class III malocclusion with anterior disc displacement without reduction (ADNR): a case report.

A female patient with skeletal problems and left temporomandibular joint (TMJ) derangement was treated with an occlusal splint, arthroscopic irrigation, and orthodontic surgery. The left side disc was displaced anteriorly without reduction; and mobility of the left condylar head was restricted. With arthroscopic irrigation, the jaw functions were recovered, but the disc position remained the same. After TMJ therapy, orthodontic and orthognatic surgery treatments were performed to correct the dentofacial deformity. Stable facial esthetics and occlusion devoid of temporomandibular joint disorder (TMD) symptoms were obtained and the patient's progress was monitored over a 5-year period.

Adolescent↗

A phosphonate-induced gene which promotes Penicillium-mediated bioconversion of cis-propenylphosphonic acid to fosfomycin.

Penicillium decumbens is able to epoxidize cis-propenylphosphonic acid (cPA) to produce the antibiotic fosfomycin [FOM; also referred to as phosphonomycin and (-)-cis-1,2-epoxypropylphosphonic acid], a bioconversion of considerable commercial significance. We sought to improve the efficiency of the process by overexpression of the genes involved. A conventional approach of isolating the presumed epoxidase and its corresponding gene was not possible since cPA epoxidation could not be achieved with protein extracts. As an alternative approach, proteins induced by cPA were detected by two-dimensional gel electrophoresis. The observation that a 31-kDa protein (EpoA) was both cPA induced and overaccumulated in a strain which more efficiently converted cPA suggested that it might take part in the bioconversion. EpoA was purified, its amino acid sequence was partially determined, and the corresponding gene was isolated from cosmid and cDNA libraries with oligonucleotide probes. The DNA sequence for this gene (epoA) contained two introns and an open reading frame encoding a peptide of 277 amino acids having some similarity to oxygenases. When the gene was subcloned into P. decumbens, a fourfold increase in epoxidation activity was achieved. epoA-disruption mutants which were obtained by homologous recombination could not convert cPA to FOM. To investigate the regulation of the epoA promoter, the bialaphos resistance gene (bar, encoding phosphinothricin acetyltransferase) was used to replace the epoA-coding region. In P. decumbens, expression of the bar reporter gene was induced by cPA, FOM, and phosphorous acid but not by phosphoric acid.

Amino Acid Sequence↗

Hepatitis B virus X protein: structure, function and biology.

The X gene is conserved among mammalian hepadnaviruses and the X protein, pX, is essential for viral propagation at least in the woodchuck. During the last decade, efforts have centered on elucidating the oncogenic role of pX in hepatitis B virus infection. The accumulating knowledge on pX indicates that it is a multifunctional regulatory protein which modulates many host functions by communicating directly or indirectly with a variety of host targets as is the case for many viral regulatory proteins, such as T antigens, E1A, and human T cell lymphotropic virus tax. pX, which modulates the transcription machinery and/or modulation protein kinase signaling cascades, transactivates many host genes involved in cell proliferation, cytokine networks, acute immune response, and house-keeping functions. Distinct from the transactivation, pX also modulates DNA repair processes by interacting with p53 and/or repair enzymes which may accumulate mutations and sensitize cells to genotoxic stimuli. Several X-interaction host proteins remain to be characterized as targets of pX. The biological roles of pX have been addressed in various systems in addition to the role of pX on viral reproduction. pX may affect cell cycle progress, response to apoptotic stimuli, cell transformation, and carcinogenesis in the presence or absence of additional oncogenic factors. These biological roles of pX have not been described in terms of pX functions and targets and remain subjects of future research using improved experimental systems and technologies. Such efforts will identify important function(s) of pX for hepatocarcinogenesis.

Amino Acid Sequence↗

Direct interaction between gingival fibroblasts and lymphoid cells induces inflammatory cytokine mRNA expression in gingival fibroblasts.

In inflamed periodontal lesions, dense infiltration of lymphocytes is usually observed in the extravascular periodontal connective tissue, adjacent to gingival fibroblasts. Our previous study revealed that activated lymphocytes can adhesively interact with gingival fibroblasts in vitro. In the present study, we investigated whether gingival fibroblasts are activated through direct interaction with lymphoid cells by monitoring the expression of inflammatory cytokine mRNA in human gingival fibroblasts (HGF). Co-culture with various human lymphoid cells in vitro resulted in a marked increase in the expression of IL-1alpha, IL-1beta, and IL-6 mRNA by the HGF. In addition, expression of the mRNA of the IL-1beta-converting enzyme (ICE), which is essential to produce the mature form of IL-1beta, was constitutively observed in the HGF, suggesting that mature IL-1beta is produced by these cells. When HGF were cultured with the culture supernatant of the lymphoid cells, the increase in the inflammatory cytokine mRNA expression was not observed. Similarly, when HGF and lymphoid cells were cultured in the same well but separated by a membrane which prevented direct contact between the cells, no increase in inflammatory cytokine mRNA expression was observed. These results strongly indicate that direct interaction between these heterotypic cell types transduces activation signals into HGF that induce an increase in inflammatory cytokine mRNA expression. Furthermore, IL-1beta mRNA expression in the HGF was synergistically increased when HGF directly interacted with lymphoid cells in the presence of exogeneous IL-1beta. The present study demonstrates that direct interaction between HGF and lymphoid cells stimulates HGF to increase inflammatory cytokine mRNA expression, and raises the possibility that heterotypic cell-cell interaction may facilitate local inflammatory reactions.

Caspase 1↗

High frequency of antibody activity against ribosomal protein S10 in anti-Sm sera from patients with systemic lupus erythematosus.

This study was carried out to clarify the frequency of detection of antibody activity to ribosomal protein S10 (anti-S10) in patients with systemic lupus erythematosus (SLE) with anti-Sm antibodies (anti-Sm), and clinical differences between anti-Sm-positive SLE patients with and without anti-S10. Twenty-seven of 31 serum samples containing anti-Sm reacted with ribosomal protein S10 along with Sm core proteins B/B' and D (87.1%). Four serum samples containing anti-Sm against only B/B' but not D did not react with S10 (12.9%). Patients who had both anti-Sm and anti-S10 showed lower serum complements levels, high frequency of skin lesion and anti-double-stranded DNA antibody. Many anti-Sm antibodies may recognize B/B', D, and S10 simultaneously, and such antibodies may appear in active disease.

Antibody Specificity↗

Cloning of a gene encoding hydroxyquinol 1,2-dioxygenase that catalyzes both intradiol and extradiol ring cleavage of catechol.

Two Escherichia coli transformants with catechol 1,2-dioxygenase activity were selected from a gene library of the benzamide-assimilating bacterium Arthrobacter species strain BA-5-17, which produces four catechol 1,2-dioxygenase isozymes. A DNA fragment isolated from one transformant contained a complete open reading frame (ORF). The deduced amino acid sequence of the ORF shared high identity with hydroxyquinol 1,2-dioxygenase. An enzyme expressed by the ORF was purified to homogeneity and characterized. When hydroxyquinol was used as a substrate, the purified enzyme showed 6.8-fold activity of that for catechol. On the basis of the sequence identity and substrate specificity of the enzyme, we concluded that the ORF encoded hydroxyquinol 1,2-dioxygenase. When catechol was used as a substrate, cis,cis-muconic acid and 2-hydroxymuconic 6-semialdehyde, which were products by the intradiol and extradiol ring cleavage activities, respectively, were produced. These results showed that the hydroxyquinol 1,2-dioxygenase reported here was a novel dioxygenase that catalyzed both the intradiol and extradiol cleavage of catechol.

Amino Acid Sequence↗

The absolute configuration of belactin A, a beta-lactone-containing serine carboxypeptidase inhibitor: importance of the beta-lactone structure for serine carboxypeptidase inhibition.

The absolute configuration of belactin A, a beta-lactone-containing serine carboxypeptidase inhibitor was studied by a crystal X-ray diffraction analysis and its absolute structure was determined to be (2R,3S)-2-¿(3S)-3-[(2-amino-5-chlorophenyl)carboxamido]-1,1-dimethyl-2-o xobutyl¿-3-methyl-4-oxooxetane. The importance of the beta-lactone structure for inhibitory activity was found by preparing several derivatives of belactin A.

Benzamides↗

Inhibition of gastric H+, K(+)-ATPase by flavonoids: a structure-activity study.

Gastric H+, K(+)-ATPase plays a pivotal role in the final step of gastric acid secretion. Over 80 flavonoids, including flavones, flavanones, isoflavones and anthocyanidins were examined for their in vitro effect on gastric H+, K(+)-ATPase and some were found to be inhibitors of this enzyme. Kinetic studies showed that the inhibition of H+, K(+)-ATPase by flavonoids was competitive with respect to ATP, and non-competitive with respect to K+. Structure-activity analysis revealed the following: (1) The inhibitory potency of flavonoids depends on the number of hydroxyl groups up to four per molecule and that above this, no marked enhancement is seen; (2) The hydroxylation pattern is an important determinant of inhibitory potency. Two adjacent hydroxyl groups (catechol-type), three adjacent hydroxyl groups (pyrogallol-type) or hydroxyl groups at C-3, C-5 and C-7 are a minimum requirement for high potency inhibition; (3) Protection of the hydroxyl group(s) by glycosylation or methylation decreases potency; (4) Saturation of the C-2-C-3 double bond results in a decrease in potency; and (5) A ketone at C-4 is not essential for inhibition.

Animals↗

Prognostic impact of second cancer on the survival of early breast cancer patients.

Although numerous reports have been published on the incidence of second cancers after adjuvant therapy for early breast cancer, there have been few studies on the effect of the development of second cancer on overall survival (OS) of the patients. 1857 female patients younger than 80 years of age with operable breast cancer with UICC Stages I, II, and III who entered 3 trials of adjuvant therapy were studied for the detection of recurrence and second cancer. The median follow-up period for surviving patients was 12 years (range, 5-25 years). 384 of recurrence and 119 of second cancers occurred. 465 deaths were recorded, the causes of which were designated to be due to recurrence of breast cancer in 326 patients, second cancers in 57, and due to other causes in 82. Many background factors that were significantly related to recurrence did not influence the incidence of and death by second cancers after mastectomy: age and menopausal status alone were related. The difference in the Kaplan-Meier curves between the event (recurrence and second cancers)-free and relapse-free survivals indicates the incidence of second cancers is a significant event in post-operation course of early breast cancer patients (P=0.0001). The survival curve of patients who were free from recurrence- and second cancer-death is shown to be significantly lower than that of those free from breast cancer-specific death (P=0.0355), suggesting that death by second cancers is significantly influential to the overall survival. According to the Cox regression model using a recurrence or second cancers as time-dependent variables, the diagnosis of a recurrence or second cancer is shown to be highly significant to OS of the patients (hazard ratio: 49.3, and 6.3, respectively). Second cancers are shown to be not statistically significantly influential to the breast cancer specific survival (P=0.0637), nor a recurrence to second cancer specific survival (P=0.2285). In spite of heterogeneous distribution of sites of second primary cancers and their different natural histories, the incidence of second cancer has a significant effect on the postoperative survival of early breast cancer patients. In the survival analysis of early breast cancer patients, we have to estimate the contribution of second cancers to properly evaluate the effect of treatment.

Adult↗

[Effectiveness of Nd: YAG laser therapy on Japanese cedar pollinosis].

Many have reported on the effectiveness of laser surgery therapy for perennial allergic rhinitis. However, the suppressive effects of laser irradiation on allergic rhinitis and its symptoms have not been reported in patients with pollinosis. This is because therapeutic effects on pollinosis are difficult to evaluate. The amount of pollen in the air varies during the year, and from year to year. Also, allergic symptoms develop due to exposure to the amount of pollen which is markedly influenced by the weather. In this study, the severity of allergic symptoms in the pollen season was compared between patients treated with early medication, non-treated patients and patients treated with preseasonal contact Nd: YAG laser surgery. Results suggests that laser surgery was effective in reducing the severity of symptoms in patients with cedar pollinosis. Symptoms were milder in the laser group than in the medication group and non-treated group for 3-4 weeks after the start of seasonal pollinosis, although no differences were noted in the early weeks. This may be explained by the fact that laser irradiation reduces the lamina propria of the nasal mucosa, the site of allergic reactions. This also suggests that allergic pollen can't penetrate the mucosal surface which shows squamous epithelization after laser irradiation.

Adult↗

[Extended resection of the great vessels for primary lung cancer and mediastinal tumor].

From 1973 to 1998, we resected and reconstructed the great vessels in 44 patients with primary lung cancer or mediastinal tumor. Among them, 39 patients (28 with lung cancer and 11 with mediastinal tumor) and 5 patients (all with lung cancer) underwent reconstruction of the superior vena cava (SVC) and aorta, respectively. The SVC was repaired by expanded polytetrafluoroethylene (EPTFE) graft (n = 8), prosthetic patch (n = 5) or direct suture (n = 26). The aorta was repaired with temporary subclavian artery-descending aorta (n = 3), or left atrium-femoral artery bypass (n = 2). No complication or operative death occurred after surgery. The survival rate of the patients with lung cancer who underwent SVC reconstruction at 3 year and 5 year were 26.2% and 11.2%, respectively. Five of 11 (45.5%) patients with mediastinal tumor are alive at 5 years. We concluded that extended resection for primary lung cancer or mediastinal tumor invading the SVC is acceptable operation method for some patients.

Adult↗

[Multiple myeloma in siblings].

We encountered 2 patients with multiple myeloma in a family with 11 siblings, suggesting that the occurrence of the disease may be associated with genetic factors. Patient 1: The second daughter (age 79) was given a diagnosis of multiple myeloma and admitted to our hospital in December 1997 for treatment. IgG-lambda type M protein was detected by serum immunoelectrophoresis, punched out lesions (+) by X ray examination, and atypical plasma cells (14% of total) by bone marrow examination. Patient 2: The fifth daughter (age 68) received a diagnosis of multiple myeloma and was admitted to our hospital in May 1997 for treatment. Bence Jones-kappa type and IgA-kappa type M protein were detected by serum immunoelectrophoresis, punched out lesions (+) by X ray examination, and atypical plasma cells (90% of total) by bone marrow examination. It was noted that the sixth daughter had leukemia; hence, 3 of the 11 siblings had blood disorders. For this reason, HLA studies were performed and detected A31, B39, B51, and Cw7 in patient 1 and A31, B51, B62, and Cw4 in patient 2. Further case studies will hopefully reveal more details concerning the relationship between myeloma and HLA.

Aged↗

[A randomized study of adjuvant treatments for operable breast cancer patients stratified by estrogen receptor and menopausal status].

According to estrogen receptor (ER) and menopausal status, operable breast cancer patients were randomized for adjuvant endocrine therapy with tamoxifen (TAM) in premenopausal patients, after oophorectomy (OVEX), chemotherapy, CHEM (mitomycin C+ oral cyclophosphamide), or chemo-endocrine therapy (TAM + CHEM). Some 1579 patients were entered in the trial between 9, 1978 and 12, 1991, with a median follow-up of 10 years. In ER-positive, premenopausal patients there were no significant differences in relapse-free (RFS) or overall survival (OS) among the OVEX + TAM, CHEM, and CHEM + TAM arms. On the contrary, in ER-positive, post-menopausal patients, the chemoendocrine therapy showed a significantly better OS (p = 0.0254) with a trend of better RFS (p = 0.0674), as compared with TAM or CHEM groups. ER-negative, premenopausal patients showed no significant differences in RFS or OS between CHEM and CHEM + TAM arms. In ER-negative, postmenopausal patients, there was a non-significantly better RFS (p = 0.0888) and a significantly better OS (p = 0.0332) in CHEM + TAM group than in the CHEM alone group. These results suggest that ER and menopausal status are important criteria to select early breast cancer patients for adjuvant treatments.

Adult↗

[Discrimination of leukoencephalopathy from leukemic cell invasion by MR spectroscopy in a patient with acute lymphoblastic leukemia].

A 58-year-old man was admitted to our hospital in November 1992 because of fever and arthralgia. He was given a diagnosis of acute lymphoblastic leukemia and treated with an Ad-VP regimen, which resulted in complete remission. After two courses of consolidation therapy and intrathecal (IT) injections of methotrexate, Ara-C, and prednisolone the patient received high-dose Ara-C plus VP-16 followed by recombinant human G-CSF for the collection of peripheral blood stem cells. However, he relapsed with the appearance of leukemic cells in cerebrospinal fluid (CSF), and was accordingly given IT injections 8 more times. After the disappearance of leukemic cells from CSF, the patient received a peripheral blood stem cell transplant (PBSCT) and achieved rapid hematopoietic recovery. However, he suffered mental aberrations and loss of consciousness 9 days after PBSCT. Proton magnetic resonance spectroscopy (1H-MRS) disclosed severe necrosis due to leukoencephalopathy in the frontal lobe and invasion of leukemic cells around the lateral ventricles. The patient did not receive any therapy for neurological symptoms because of severe necrosis in the frontal lobe, and died of bone marrow relapse in April 1995. MRS is useful for the discrimination of leukoencephalopathy from leukemic cell invasion.

Antineoplastic Agents↗

Up-regulated expression of matrilysin and neutrophil collagenase in human herniated discs.

Spontaneous resorption of herniated nucleus pulposus (HNP) is commonly observed when there is substantial contact of the disc with the spinal canal. We already demonstrated the expression of matrix metalloproteinase (MMP)-3 (stromelysin-1) in the granulation tissues of HNP, suggesting its role in the resorption process of HNP. Recent studies of osteoarthritic cartilages reported an up-regulated expression of metalloproteinases including MMP-7 (matrilysin) and MMP-8 (neutrophil collagenase), suggesting their roles in the matrix degradation. To clarify the expression of MMP-7 and MMP-8 in HNP, immunohistological analysis of various types of HNP was performed. We found MMP-7 was expressed in infiltrated mononuclear cells and chondrocytes, whereas MMP-8 was specifically expressed in chondrocytes. The positive rate for both MMP-7 and MMP-8 significantly increased when HNP was exposed to the epidural space (p < 0.01). Our data suggest that not only MMP-3 but also MMP-7 and MMP-8 may play a role in the resorption process of HNP.

Adolescent↗

[Progress of the stroke registry system by public health centers, and factors associated with its advancement].

In Japan, a community-based stroke registry was started in 1992 based on the policy of the central government. There are mainly two objectives in this registry system. One is to analyze factors related to the incidence of stroke, and the other is to support home care of stroke patients after leaving the hospital. This system has experienced many difficulties, such as obtaining appropriate information smoothly from the hospitals. Therefore, we investigated all 895 public health centers in Japan through a questionnaire sent by mail, in February 1996. We obtained valid replies from 612 (68%) of the public health centers by March 1996. Results showed that 75% of health centers have established a stroke registry system. Some health centers have promoted the system since 1984. In these systems, the flows of information are mainly of two types: ones which flow to the health centers from the hospitals and the ones which flow to the municipalities. In the former, the number of registered cases were significantly higher and the registry was functioning better than the latter. It has become clear that the health center plays a key role in the successful development of a stroke registry system.

Cerebrovascular Disorders↗

[Brain 3 D-CT angiography was a useful tool for diagnosis of internal carotid-posterior communicating artery aneurysm: a case of false negative 3 D-MRA].

A 75-year-old woman with hypertension suddenly developed ptosis in the left eyelid. Neurological examination revealed left oculomotor nerve palsy. Brain T 2-weighted imaging showed abnormal flow void sign in the proximal portion of left middle cerebral artery. Other MRIs, including gadolinium enhancement, were normal. However, brain 3 D-MRA, using time-of-flight sequence, did not disclose any intracranial aneurysms. 3 D-CT angiography revealed left internal carotid-posterior communicating artery (IC-PC) aneurysm. Maximum intensity projection display of CT angiography demonstrated the neck and head portions of IC-PC aneurysm (size = 8 mm). Furthermore, 3 D-CT angiography was beneficial for anatomical evaluation of the aneurysm and the surrounding bony structures. The false negative 3 D-MRA of our patient was thought to result from flow-related artifacts, slow blood flow in the aneurysm, the surrounding noise and the localization of aneurysm. False negative findings of cerebral aneurysms occasionally occur on 3 D-MRA or 3 D-CT angiography, in comparison with digital subtraction angiography. Thus, we should pay more attention to assessment of 3 D-MRA and 3 D-CT angiography in patients who have high risks of cerebral aneurysms.

Aged↗