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Biomedical subjects

H Murai

Publications and source records attributed to H Murai.

At least 91 records · Page 5Linked to original sources

High incidence of ultraviolet-B-or chemical-carcinogen-induced skin tumours in mice lacking the xeroderma pigmentosum group A gene.

Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by a high frequency of skin cancer on sun-exposed areas, and neurological complications. XP has a defect in the early step(s) of nucleotide-excision repair (NER) and consists of eight different genetic complementation groups (groups A-G and a variant). We established XPA (group-A XP) gene-deficient mice by gene targeting of mouse embryonic stem (ES) cells. The XPA-deficient mice showed neither obvious physical abnormalities nor pathological alterations, but were defective in NER and highly susceptible to ultraviolet-B- or 9,10-dimethyl-1,2-benz[a]anthracene-induced skin carcinogenesis. These findings provide in vivo evidence that the XPA protein protects mice from carcinogenesis initiated by ultraviolet or chemical carcinogen. The XPA-deficient mice may provide a good in vivo model to study the high incidence of skin carcinogenesis in group A XP patients.

9,10-Dimethyl-1,2-benzanthracene↗

Serum-soluble interleukin-2 receptor levels before and after surgical treatment for Graves' disease.

Serum-soluble interleukin-2 receptor (ssIL-2R) is released from its specific affinity membrane receptor on activated T lymphocytes and is detected as a form of the alpha-chain of IL-2R in the peripheral blood. We measured the ssIL-2R levels by enzyme-linked immunosorbent assay in 29 healthy subjects and 39 patients with Graves' disease who were given antithyroid drugs to prepare them for surgical treatment. The preoperative ssIL-2R levels in Graves' patients were significantly higher than those in the healthy controls (681 +/- 387 vs 369 +/- 149 U/ml); in particular, the preoperative levels in hyperthyroid patients were significantly higher than those in euthyroid patients. On the 5th day after thyroid resection, their ssIL-2R levels (560 +/- 296 U/ml) were significantly lower than the preoperative levels. There were no correlations between the preoperative ssIL-2R levels and the immunological parameters such as thyroglobulin antibody, microsomal antibody, and thyroid-stimulating hormone receptor antibody. Thus, we conclude that ssIL-2R levels can be decreased by surgical resection of goiter in Graves' patients whose hyperthyroid status does not respond to the administration of antithyroid drugs, and this may be a useful indicator of immunological status after surgical treatment of Graves' disease.

Adult↗

Hepatitis C virus associated cryoglobulinemic neuropathy successfully treated with plasma exchange.

A 28-year-old Japanese woman who suffered from mononeuritis multiplex was admitted to our hospital. Serological study revealed cryoglobulinemia (type III), hypocomplementemia, high titers of rheumatoid factor (RF), and positive antihepatitis C virus (HCV) antibody. Nerve conduction velocities were slower in sensory nerves than in motor nerves. Biopsied sural nerve showed a marked decrease of myelinated fibers but no evidence of angitis. She received plasma exchange and cryoglobulinpheresis over a period of 2 months with approximately 2.0 L (40 ml/kg) of plasma replaced in each procedure. Both plasma exchange and cryoglobulinpheresis alleviated clinical symptoms, and nerve conduction velocities were improved in several nerves. The serum cryoglobulin level was markedly reduced after the treatment together with the recovery of the C4 level. Thus, complements appeared to be consumed in large quantities in the presence of cryoglobulinemia in this patient. Efficacy of cryoglobulinpheresis indicates the possibility that cryoglobulins produced in association with HCV infection played a role in damaging the nerve directly through the activation of the complement system.

Adult↗

Serum-soluble interleukin-2 receptor concentrations in patients with gastric cancer.

BACKGROUND: Serum concentrations of soluble interleukin-2 receptor (IL-2R) were found to be high in patients with autoimmune diseases, lung cancer, malignant lymphoma, tuberculosis, and other diseases. Serum-soluble IL-2R was evaluated as a tumor maker in patients with gastric cancer. METHODS: Preoperative concentrations of serum-soluble IL-2R were examined in 40 patients with gastric cancer. The authors investigated the correlations of serum-soluble IL-2R concentrations with various characteristics of this cancer (disease stage, gross appearance, depth of the tumor, lymph node metastasis, liver metastasis, peritoneal metastasis, histopathologic grade, serum carcinoembryonic antigen (CEA), alpha-fetoprotein (alpha-FTP), carbohydrate antigen 19-9 (CA19-9), and immunosuppressive acidic protein (IAP). Serum soluble IL-2R concentrations were measured with an enzyme-linked immunosorbent assay. RESULTS: Levels of serum-soluble IL-2R in patients with gastric cancer were significantly higher than those of normal control subjects. Serum concentrations of IL-2R in patients with lymph node metastasis were also significantly higher than those of patients without lymph node metastasis. There were no significant differences in histopathologic findings (grade, lymphatic invasion, venous invasion). Moreover, serum concentrations of soluble IL-2R in patients who were IAP positive were significantly higher than those who were IAP negative. CONCLUSIONS: Preoperative serum-soluble IL-2R concentrations in patients with gastric cancer reflect the occurrence of regional lymph node metastases. Preoperative evaluation of serum soluble IL-2R concentrations may be a valuable parameter of indicating the probability of lymph node metastasis preoperatively.

Aged↗

Serum soluble interleukin-2 receptor in colorectal cancer.

Preoperative serum soluble interleukin-2 receptor (IL-2R) levels were measured in patients with colorectal cancer, and correlated with various factors as stage, lymph node metastasis, liver metastasis, grade, serum CEA and IAP (immunosuppressive acidic protein). The levels of serum soluble IL-2R in Dukes stage C were significantly higher than in normal control and in Dukes stage A. Serum levels were also significantly higher in patients with lymph node metastasis than in patients without such metastasis, and in IAP positive patients compared to IAP negative patients. Preoperative serum IL-2R levels thus seem to reflect the stage of the disease.

Adult↗

A hospital-based case-control study of breast-cancer risk factors by estrogen and progesterone receptor status.

It has been proposed that breast cancers may differ in their pathogenesis and etiology according to their estrogen receptor (ER) and progesterone receptor (PR) status. This hospital-based case-control study in Japan assessed the relationship between known and suspected breast-cancer risk factors and ER and PR status. Information on risk factors was collected from histologically confirmed breast-cancer cases (n = 519) and from cancer-free controls (n = 9,506). Of 160 cases with known ER status, 58 percent were ER-positive; 38 percent of 157 cases with known PR status were PR-positive. No statistically significant differences were found between ER-positive cf ER-negative cases. However, statistically significant differences between PR-positive cf PR-negative cases were observed for number of full-term pregnancies (P = 0.01), menstrual regularity as a teenager (P = 0.024), and occupation as housewife (P = 0.036). Borderline differences were observed for age at menopause (P = 0.074), and age at menarche (P = 0.083). This study provides some evidence that etiologic distinctions may be greater between PR-positive and PR-negative breast cancers than between ER-positive and ER-negative breast cancers.

Adult↗

Stability of transpedicle screwing for the osteoporotic spine. An in vitro study of the mechanical stability.

The influence of bone mineral density on the stability of transpedicle screwing was studied in the human cadaveric lumbar vertebrae. The pull-out force correlated with bone mineral density. The tilting moment (load needed to tilt the screw 4 degrees cranially at the screw-plate junction) and the cut-up force (load needed to tip the end plate up by the screw) correlated with bone mineral density. A correlation was also found between the maximum insertion torque of the screw and bone mineral density. The maximum insertion torque correlated with the pull-out force, the tilting moment, and the cut-up force. In the cyclic tilting test (200 cycles), the mean value of the tilting moment at the 200th cycle was 67.4 +/- 6.1%, compared with the first cycle. The results suggest that preoperative measurement of BMD is necessary for transpedicle screwing in osteoporotic cases, and that the cyclic tilting motion decrease its mechanical stability. The authors have also concluded that the maximum insertion torque could predict the mechanical stability.

Aged↗

Hypertrophic cranial pachymeningitis associated with mixed connective tissue disease; a comparison with idiopathic and infectious pachymeningitis.

This is the first report describing hypertrophic cranial pachymeningitis which developed in association with mixed connective tissue disease (MCTD). A 56-year-old man with a two-year history of MCTD gradually developed symptoms of headache and blurred vision. Bilateral papilledema and increased opening pressure and mild pleocytosis of the cerebrospinal fluid were noted. Magnetic resonance imaging of the brain revealed a diffuse thickening and a gadolinium-enhancement of the cranial dura mater. While five previous patients, diagnosed as idiopathic or infectious hypertrophic cranial pachymeningitis in our department, had either otitis media or sinusitis and showed multiple cranial nerve involvement, the present patient had neither otitis media nor sinusitis and did not show any cranial nerve involvement other than papilledema.

Adult↗

FR901277, a novel inhibitor of human leukocyte elastase from Streptomyces resistomycificus. Producing organism, fermentation, isolation, physico-chemical and biological properties.

A novel human leukocyte elastase inhibitor, FR901277 was discovered in the fermentation broth of Streptomyces resistomycificus No. 7622. FR901277 has a molecular weight of 961 and a molecular formula of C47H63N9O13. The mode of inhibition is competitive, with a Ki of 1.2 x 10(-8) M. Oral administration of FR901277 at doses from 32 to 320 mg/kg significantly prevented human leukocyte elastase-induced foot edema in mice.

Animals↗

[Systemic adjuvant chemo-endocrine therapy after breast conservation treatment for breast cancer].

The majority of patients who have undergone breast conserving surgery proved to be node-negative. Node-negative breast cancer has a fairly good prognosis, achieving a 10 year disease-free survival rate of 88%. Patterns of recurrence and relapse in node-negative cases are characterized by a higher ratio of hematogenous metastases after relatively longer disease-free intervals. Such cases have been considered the best indications of systemic adjuvant therapy. Postoperative adjuvant trials using cyclophosphamide (CPA) and/or tamoxifen (TAM) were conducted at the Aichi Cancer Center Hospital, and the following results were obtained concerning adjuvant treatment for early-stage (node-negative or stage I) breast cancer; (1) In the post-menopausal group, CPA and/or TAM administration was recommended as the treatment of choice. (2) In the postmenopausal group, TAM was evaluated as the key drug. After TAM alone or TAM plus CPA administration, an improvement in the disease-free survival rate was expected. (3) After administration of CPA alone in the postmenopausal group, there were no demonstrable benefits. On the contrary, adverse effects were suspected. (4) The risk of contralateral breast cancer was reduced to two-thirds when TAM was administered as an adjuvant therapy.

Breast Neoplasms↗

[A case of severe bronchial asthma following first use of timolol ophthalmic solution].

A 65-year-old woman with stable atopic bronchial asthma received a prescription for timolol maleate eye drops (0.25% solution, one drop twice a day to both eyes) for glaucoma. On that evening, ten minutes after administration of the first application of timolol, the patient experienced wheeze and slight difficulty in breathing. Within the next ten minutes, her respiration became obviously asthmatic. Her symptoms progressed rapidly. When she arrived at our hospital, reduced respiratory sounds, cyanosis and disturbance of consciousness were observed. After treatment with aminophylline, hydrocortisone, epinephrine and oxygen inhalation, her symptoms completely recovered. In a provocation test, fifteen minutes after application of timolol, wheeze and dyspnea were induced following an increase in respiratory resistance. After the asthma attack, transient hypoxemia, bradycardia and decrease in blood pressure were also observed.

Aged↗

A new type of mitogenic factor produced by Streptococcus pyogenes.

A new type of mitogenic factor (protein) was purified from the culture supernatant of a strain of Streptococcus pyogenes by SP-Sephadex C-25 column chromatography, preparative isoelectric focusing and reversed-phase high-performance liquid chromatography. The purified factor, showing marked mitogenic activity in rabbit peripheral blood lymphocytes, gave a single-band staining for protein on SDS-PAGE. The molecular weight of the purified mitogenic factor was determined to be 25,370, which was different from those calculated from reported amino acid sequences deduced from 4 different nucleotide sequences of 3 kinds of streptococcal pyrogenic exotoxins (two SPEAs, SPEB and SPEC). The amino acid sequence of the N-terminal region of the purified mitogenic factor was determined to be Gln-Thr-Gln-Val-Ser-Asn-Asp-Val-Val-Leu-Asn-Asp-Gly-Ala-Ser-Lys-Tyr-Leu- Asn-Glu - Ala-, which was also different from the reported N-terminal sequences deduced from the 4 different nucleotide sequences. These data indicate that this mitogenic factor is distinct from the already described streptococcal pyrogenic exotoxins.

Amino Acid Sequence↗

Proteolytic processing of amyloid beta protein precursor (APP) by thrombin.

Search for proteases responsible for an altered processing of APP which generates intermediates containing beta/A4 peptide is preceding to understand the formation of beta amyloid deposits characteristic of Alzheimer's disease, since many studies reveal that APP is ordinarily processed so as not to generate beta amyloid. Here, we have examined the action of thrombin, a serine protease in the blood clotting, in APP processing. Thrombin cleaved the mouse recombinant APP695 in vitro, resulting in the accumulation of 28 kDa fragment. The immunoblot analysis showed that the fragment is derived from the carboxy-terminal side of the recombinant APP695. Further, amino acid sequencing exhibited that the fragment is generated by the cleavage at Arg 510-Ile 511 and therefore includes entire beta/A4 peptide. We consider that the 28 kDa fragment is a possible intermediate for beta/A4 peptide. Thus thrombin may be involved in the altered processing of APP.

Amino Acid Sequence↗

Independent protective effect of lactation against breast cancer: a case-control study in Japan.

A case-control study was carried out to assess the risk of breast cancer associated with breast feeding in Japan. The data were obtained in a hospital-based case-control study of 521 women with breast cancer and 521 controls from January 1988 to December 1989. Statistical adjustment for potential confounders as well as a likelihood ratio test for linear trend was done by unconditional logistic regression. Compared with parous women who had never breast-fed, women with a positive history of breast feeding had an odds ratio of breast cancer of 0.62 (95% confidence interval 0.37-1.04). The trend of decreasing risk with increasing average months of breast feeding was statistically significant (chi 2 trend = 4.5, p less than 0.05), while it was was nonsignificant for the number of breast-fed children borne. Among premenopausal women, a significant linear relation with a log-transformed term of average months of breast feeding was noted, regardless of the age of the woman at first full-term pregnancy and parity (chi 2 trend = 5.3, p less than 0.05). The risk was the lowest among premenopausal women who had ever lactated for 7-9 months (adjusted odds ratio = 0.39, 95% confidence interval 0.15-0.97). These findings suggest that lactation has an independent protective effect against breast cancer in Japanese women.

Adult↗

Hypertrophic cranial pachymeningitis due to Aspergillus flavus.

A 59-year-old woman suffered from occipital headache and bilateral cranial nerve VII, VIII, IX, X, XI and right XII deficit after developing otitis media. Magnetic resonance imaging (MRI) showed a thickening of the dura mater which was enhanced by gadolinium-DTPA (Gd). Aspergillus flavus was identified from the culture of otorrhea. She was treated with miconazole, flucytosin and fluconazole, which resulted in an improvement of the clinical symptoms and a thinning of the Gd-enhanced lesions on MRI. This is the first case of hypertrophic cranial pachymeningitis caused by Asp. flavus infection.

Aspergillosis↗

Target epitope in the Tax protein of human T-cell leukemia virus type I recognized by class I major histocompatibility complex-restricted cytotoxic T cells.

A trans-acting regulatory gene product p40tax (Tax) of human T-cell leukemia virus type I (HTLV-I) is one of the main target antigens recognized by cytotoxic T lymphocytes (CTL) specific for HTLV-I. A CTL epitope within the Tax protein was identified in this report. HTLV-I-specific CD8+ CTL lines established from two HTLV-I carriers with HTLV-I-associated myelopathy or Sjögren syndrome were previously demonstrated to kill predominantly the target cells expressing HTLV-I Tax. The CTL from two patients showed significant levels of cytotoxicity to autologous target cells pulsed with a synthetic peptide of 24 amino acids corresponding to the amino-terminal sequences of the Tax protein. Allogeneic target cells were also sensitized for CTL by this peptide when the target cells have HLA-A2. Tax-specific cytotoxicity, detected as cytolysis of the target cells infected with vaccinia virus-HTLV-I recombinant expressing Tax protein, was almost completely inhibited by competitor cells pulsed with the synthetic peptide. This indicates that a major CTL epitope is present in this peptide. Further analysis using shorter peptides revealed that the core sequence of the CTL epitope was LLFGYPVYV at positions 11 through 19. This sequence can be aligned with the HLA-A2-specific motifs reported recently.

Amino Acid Sequence↗