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Biomedical subjects

S Imamura

Publications and source records attributed to S Imamura.

At least 163 records · Page 9Linked to original sources
PubMed1994

Formation of 8-hydroxy-2'-deoxyguanosine in epidermis of hairless mice exposed to near-UV.

Six-week-old male albino hairless mice (Hos: Hr-1) were exposed to a near-ultraviolet (UV) fluorescent sun lamp (33.5 kJ/m2/hr; wave length > 270 nm with a peak at 312.5 nm) to investigate the induction of oxidative DNA damage in epidermal cells. Significantly higher levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) were detected in a dose-dependent manner in epidermis of mice exposed to near-UV than in those of control animals. The ratio of 8-OHdG in near-UV-exposed/unexposed control was 2.08 +/- 0.19 after 168 kJ/m2 exposure, P < 0.01; 3.49 +/- 0.36 after 335 kJ/m2 exposure, P < 0.01 (means +/- SE). The levels of 8-OHdG decreased with time after near-UV exposure, suggesting the presence of removal and/or repair mechanisms. This is the first report that oxidative DNA base modification is induced in vivo in epidermal cells by near-UV exposure. Oxidative DNA base modification may be one of the causes of sunlight-induced skin carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

[A case of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with acute bilateral optic neuritis with normal findings on pattern-reversal visual evoked potential study].

A 35-year-old man with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) associated with acute bilateral optic neuritis is described. At age 33, he noticed a tingling sensation in his toes followed by weakness in the lower limbs. He was admitted to our hospital because he became unable to walk without support. His motor and sensory symptoms gradually resolved during 7 months admission only with physical rehabilitation. At age 35, in July 1988, he noticed a tingling sensation in his toes and fingers, which reached to the knees and elbows in October 1988, when he developed weakness in the lower limbs. Motor and sensory symptoms were almost stationary thereafter and in March 1989, he experienced bilateral blurred vision of acute onset without ocular pain. He was readmitted to our hospital in April 1989. The neurological examination revealed decreased visual acuity of both eyes without any abnormality of the optic disks, mild weakness on flexion and extension of toes, an absence of Achilles reflex, and distal impairment of pain and touch sensations in the upper limbs, and of pain, touch and vibration sensations in the lower limbs. After laboratory examinations, CSF protein was elevated (122 mg/dl), and sensory nerve conduction velocity of the right median nerve was decreased (37.1 m/sec). The sural nerve action potential was not elicited on electrical stimulation. Central scotoma was found in both eyes by the visual field examination. P100 latency was seen to be normal by repeated pattern-reversal visual evoked potential (VEP) studies. CT and MRI of the brain were unremarkable.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Photodynamic therapy and/or external beam radiation therapy for roentgenologically occult lung cancer.

BACKGROUND AND METHODS: Thirty-nine roentgenologically occult lung cancers in 29 patients were treated using photodynamic therapy (PDT) and/or thoracic radiotherapy (TRT) from January 1986 to March 1992. With the exception of one mixed-tumor case, all were squamous cell carcinomas. RESULTS: Initial PDT achieved complete responses in 25 of 39 (64%) of the cancers. Of the remaining 14 cancers that showed less than complete response (CR), 10 of the 14 (71.4%) showed a CR when subsequently treated with TRT, yielding an overall CR rate of 89.7% for cancers treated. Although nine patients experienced recurrences, six of these had CR when treated with PDT and/or TRT. To date, 22 patients are alive. Causes of death in the patients enrolled in this study are as follows: pyothorax (2); heart failure due to pulmonary hypertension (1); chronic respiratory insufficiency (1); subsequent primary brain cancer (1); and subsequent primary lung cancer (1). Only one died of primary lung cancer. CONCLUSIONS: These findings suggest that PDT and/or TRT may be used as an alternative to surgery in the treatment of selected patients with roentgenologically occult lung cancer.

Adult↗
PubMed1994

Two collagen-binding proteins, osteonectin and HSP47, are coordinately induced in transformed keratinocytes by heat and other stresses.

pSE48 was one of six clones selected by differential colony hybridization as a cDNA coding for mRNA expressed in parietal endoderm-like F9 cells and not in primitive endoderm-like F9 cells. It was sequenced and identified as a segment of mouse osteonectin (SPARC) cDNA. We found osteonectin to be heat-inducible in some cells. Expression and secretion of osteonectin were then investigated using mouse (Pam 212) and human (HSC-1) keratinocyte cell lines. Both the mRNA levels and the secretion of osteonectin increased concurrently when Pam and HSC-1 cells cultured in low calcium medium were exposed to various stresses including heat shock and treatment with sodium arsenite or L-azetidine-2-carboxylic acid. Another collagen-binding stress protein, HSP47, was also found to be expressed, synthesized, and stress-inducible in the keratinocyte cell line. The degree of HSP47 induction by various stresses was not so prominent as that of HSP70 but greater than that of osteonectin. The time courses of osteonectin and HSP47 induction by heat shock were similar to each other and distinct from HSP70; they were slower and more persistent than HSP70. We identified a heat shock element-like sequence in the promoter region of the mouse and bovine osteonectin genes. This sequence might participate in the stress induction of osteonectin. Thus, osteonectin and HSP47 share another common feature, stress-inducibility, as well as collagen-binding capacity and inducibility through differentiation, although they are quite distinct in their amino acid sequence and distribution.

Animals↗
PubMed1994

Immunological characterization of tumor-rejection antigens on ultraviolet-light-induced tumors originating in the CB6F1 mouse.

Six ultraviolet-light(UV)-induced tumors of (BALB/c x C57BL/6)F1 (H-2d/b) mouse origin were analyzed for the effector T cell subsets involved in tumor rejection, the MHC class I to which cytolytic T lymphocytes (CTL) are restricted, and the effect of UV radiation on tumor rejection, to characterize their tumor-rejection antigens (TRA) recognized by CTL. All tumors were rejected in syngeneic normal mice but grew progressively in nude mice. CD8+ T cells mediated the antitumor responses for all tumors and CD4+ T cells could also do so for one tumor 6.1B. Each tumor induced potent CTL that recognized the specific TRA in preferential association with MHC class I haplotypes not from H-2b but from H-2d; that is, Kd, Dd or Ld. Profiles of TRA expression on two tumors were obtained by the analyses of their antigen-loss variants. Female 1A codominantly expressed at least four distinct TRA associated with Kd, all of which induced CTL. On the other hand, UV male 1 had at least two distinct TRA, one of which, associated with Kd, exclusively induced CTL. However, in the absence of the dominant TRA, another TRA associated with Ld on R95C, a variant of UV male, 1, induced CTL. Unlike other tumors, R95C grew progressively in short-term-UV-irradiated syngeneic mice. Nude mice reconstituted with a combination of CD4+ T cells from short-term-UV-irradiated mice and CD8+ T cells from normal mice did not reject R95C. An increase in the former T cell population led the reconstituted mice to reject the tumor. These findings suggest some functional defects of CD4+ T cells rather than the generation of suppressor cells in short-term-UV-irradiated mice. The UV-induced tumors used in the present study provide a unique system for analyzing the preferential sorting of TRA as well as for elucidation of the TRA itself.

Animals↗
PubMed1994

Construction of plasmids useful for production of the B subunit of cholera toxin from Vibrio cholerae or a heat-labile enterotoxin from enterotoxigenic Escherichia coli.

A simple method to construct the plasmids producing the B subunit of porcine or human heatlabile enterotoxin or cholera toxin was developed, and the B subunits produced by the resulting plasmids were purified. The gene of LTp from pEWD 299 was ligated to pHSG 396 or pBluescript SK(+)-1 and the vector carrying one Xbal and EcoR1 site in the LTp-A gene was constructed. The Xbal-EcoR1 fragment of LTp-A gene was exchanged for the multicloning site of pHSG 396 containing Xbal, BamH1, Cla 1, Kpn1, Sac1 and EcoR1 sites. This plasmid (pTSU28) produced the LTp-B subunit. Moreover, the fragment of the LTp-B gene of pTSU 28 was exchanged by the EcoR1-HindIII fragment of LTh-B from E. coli H10407 strain (pTSU 35) or by the Cla 1-Hind III fragment of CT-B gene amplified by the PCR procedure with the chromosomal DNA of V. cholerae 86KT25 (pTSU 32). The DNA sequence of the CT-B subunit amplified by PCR procedure was compared and found identical to that cited in the literature [11]. After these plasmids were transformed into E. coli MV 1184 strain, the toxins produced by them were purified using a Bio-Gel A 5m affinity column for both LT-Bs and an immunobilized D-galactose affinity column for CT-B. Though both columns absorbed only the B subunit, the eluates contained a single protein corresponding to the B subunit, suggesting that each mutant produces only the B subunit.

Animals↗
PubMed1994

The role of CD4+ and CD8+ cells in normal F1 hybrid host in the resistance to lethal graft-versus-host disease induction by transfer of parent spleen cells.

Transfer of a certain number of C57BL/6 (B6) spleen cells into (BALB/cxB6)F1 (CB6F1) nu/nu mice, which are deficient in T cells, causes lethal graft-versus-host disease (GVHD) in the recipients. However, when normal CB6F1 mice are used as recipients, lethal GVHD does not occur. Using this lethal GVHD system, we investigated which roles CD4+ and CD8+ T cells play in the resistance to lethal GVHD induction by parent cell transfer in the normal F1 hybrid host. Lethal GVHD induction by B6 spleen cells in CB6F1 nu/nu mice was blocked by prior reconstitution of the recipients with normal syngeneic spleen cells. In addition, all nu/nu mice reconstituted with syngeneic CD8+ spleen cells developed lethal GVHD, whereas none of the nu/nu mice reconstituted with CD4+ cells did. Both spleen weight and number of spleen cells in the former prominently decreased in contrast to the slight increase (peak at 15 weeks) seen in the latter after transfer of donor spleen cells. H-2Dd- Thy1.2+ cells, which are considered to derive from donor B6 T cells, existed in the spleen from the CD4+ spleen cell-reconstituted GVHD mice, peaking at 5 weeks then gradually decreasing after transfer of donor cells. However, they disappeared in the normal spleen cell-reconstituted GVHD mice 5 weeks later. These findings suggest that CD4+ cells in the normal F1 hybrid host play a critical role in the resistance to lethal GVHD induction by parent spleen cell transfer, although CD8+ cells are required for the prompt elimination of donor cells.

Animals↗
PubMed1994

Effect of botulinum C3 exoenzyme on cell growth and cytoskeleton organization in transformed human epidermal cells in culture: a possible role for rho protein in epidermal cells.

We examined the role of rho gene products (rho proteins) on cell growth and cytoskeleton organization in transformed human epidermal cells in culture (HSC-1), using recombinant botulinum C3 exoenzyme which specifically ADP-ribosylates rho proteins. Incubation of HSC-1 cell lysates with C3 exoenzyme revealed a single [32P]ADP-ribosylated protein with a molecular weight of 23,000. This protein was identified as rhoA protein by isoelectric focusing (pI 6.0). Addition of C3 exoenzyme to the culture medium of HSC-1 cells changed the shape of HSC-1 cells to a round form with beaded processes in a time- and dose-dependent manner. Moreover, C3 treatment reduced the cell growth rate; 72-h treatment with C3 exoenzyme at 1, 3, 10, 30 and 60 micrograms/ml culture medium resulted in 9.0 +/- 1.8%, 20 +/- 2.9%, 26 +/- 2.3%, 50 +/- 1.4% and 40 +/- 2.0% inhibition of the growth rate relative to controls, respectively. Under this condition, actin stress fibers were disassembled, as revealed using fluorescent-labeled phallacidin, whereas keratin intermediate filaments were not affected, visualized by immunofluorescence using anti-keratin antibody. These results suggest that rho proteins are closely related to cell growth and that these proteins regulate, at least in part, the assembly of actin stress fibers in transformed human epidermal cells.

ADP Ribose Transferases↗
PubMed1994

Quantitative evaluations of male pattern baldness.

Several methods for the evaluation of hair growth have been reported; however, none of the hitherto reported methods are satisfactory as unbiased double blind studies to evaluate the efficacy of hair growth agents. In the present paper, we describe quantitative evaluation methods for hair growth by measuring the anagen ratio and hair diameters in 56 Japanese subjects aged 23-56 for 3 years. The average anagen ratio decreased by 3.8% in 3 years. The average hair diameters showed a statistically significant decrease each year totalling 3.4 microns. Subjects were sorted according to their anagen ratio into 4 groups. Each group showed different distribution patterns of hair diameters. The higher anagen ratio group has a high frequency peak at thicker hair diameters and the lower anagen ratio group has a high frequency peak at thinner hair diameters. The number of thicker hairs decreased and the high frequency peak shifted to thinner hair diameters in 3 years. These methods are useful to evaluate both the progression of male pattern baldness and the effects of hair growth agents with double blind studies in an unbiased quantitative fashion.

Adult↗
PubMed1994

Elevated serum levels of IgE-binding factor/soluble CD23 in bullous pemphigoid.

IgE-related abnormalities and impaired B cell function have been reported in patients with bullous pemphigoid (BP). CD23 is a low affinity Fc epsilon RII on haematopoietic cells and its soluble form (sCD23) is involved in B cell growth and differentiation. In order to determine the role of CD23 in the pathomechanisms of BP, the present study assayed the level of sCD23 in sera of BP patients using an ELISA method. Levels of sCD23 were elevated in BP patients compared with mean levels in the sera of normal control. Furthermore, the increase in sCD23 levels correlated with the degree of disease activity. A significant correlation was found between sCD23 and serum IgE levels in BP sera, but not in normal control sera. These results suggest that sCD23 is an important index for monitoring BP with respect to IgE-related abnormalities and impaired B cell function.

Animals↗
PubMed1994

Effects of volatile anesthetics, enflurane, isoflurane, and halothane on ventricular delayed activation in a canine myocardial infarction model.

The authors examined the effects of volatile anesthetics (enflurane, isoflurane, and halothane) on ventricular activation in a canine myocardial infarction model. Enflurane at 1 minimum aveolar concentration further delayed or blocked delayed activation in the infarcted zones with only slight effects on activation of the normal zones. Halothane showed similar and comparable effects on ventricular activation to those of enflurane. Although isoflurane also showed similar effects, they were of a lesser extent. Enflurane and halothane, but not isoflurane, inhibited ventricular stimulation-induced arrhythmias. Thus, enflurane and halothane produced marked depression of delayed activation in myocardial infarction, which may affect, that is, inhibit or provoke, ventricular arrhythmias in myocardial infarction.

Animals↗
PubMed1994

Epitope mapping for epidermolysis bullosa acquisita autoantibody by molecularly cloned cDNA for type VII collagen.

Epidermolysis bullosa acquisita is a subepidermal blistering disease in which patients have autoantibodies against the non-collagenous domain of type VII collagen. Starting with previously isolated 1-kilobase pair (Kb) cDNA for this autoantigen, we isolated overlapping cDNAs with a combined open reading frame of approximately 3.2 Kb, encoding most (approximately 115 kilodaltons [KDa]) of the N-terminal non-collagenous domain of type VII collagen. To localize immunogenic domains, we produced maltose-binding fusion proteins with cDNA encoding different portions of this autoantigen. These cDNA fragments scan from 5' to 3' of this non-collagenous domain and overlap each other. An immunoblot analysis of these fusion proteins with eight epidermolysis bullosa acquisita patient sera demonstrated that each patient serum binds to different regions of this molecule and that epitopes for these patient sera locate throughout this autoantigen. These data suggest that multiple epitopes on the N-terminal non-collagenous domain of type VII collagen are recognized by circulating autoantibodies in patients with epidermolysis bullosa acquisita.

Autoantibodies↗
PubMed1994

Giant metastatic malignant melanoma with an unknown primary site.

We report a case of malignant melanoma of unknown primary origin which presented with a giant metastatic tumor in his right inguinal region. A 94-year-old man noticed a small subcutaneous tumor in the right inguinal region 3 years earlier, which eventually became as larger as 9 cm in diameter without treatment. Although a histological examination of the lesion showed malignant melanoma, extensive examination did not reveal its primary lesion or any metastasis other than that to the right inguinal area. Our case took an interesting course in that this well-growing metastatic tumor was localized in only one region and supported a previous report indicating that malignant melanoma with unknown primary origin has a low tendency to metastasize and a relatively good prognosis.

Aged↗
PubMed1994

Cadherins in cutaneous biology.

The role of cadherins in cutaneous biology has focused mainly on the classical cadherins, E- and P-cadherin. In this review, roles for cadherins in skin morphogenesis, keratinocyte differentiation, and cancer metastasis are discussed. E-cadherin is expressed on the surfaces of whole epidermal layer cells, and P-cadherin is expressed only on the surfaces of basal cells. Ultrastructural studies have shown that E-cadherin is distributed on the cytoplasmic membranes of keratinocytes with a condensation in the intercellular space of the desmosomes. During human skin development, P-cadherin expression is spatiotemporally controlled and closely related to the segregation of basal layers as well as to the arrangement of epidermal cells into eccrine ducts. In human skin diseases, E-cadherin expression is markedly reduced on the acantholytic cells of tissues in pemphigus and also in Darier's disease. Keratinocytes cultured in high calcium produce a much more intense immunofluorescence of intercellular E- and P-cadherin than do cells grown in low calcium. Ultrastructural studies show that E-cadherin on the cytoplasmic membrane of the keratinocytes is shifted to desmosomes under physiological conditions and therein expresses an adhesion function is association with other desmosomal cadherins. Cell adhesion molecules are now considered to play significant roles in the cellular connections of cancers and metastatic cells. Reduced expression of E-cadherin on invasive neoplastic cells has been demonstrated for cancers of the stomach, liver, breast, and several other organs. This reduced expression of E-cadherin is observed in squamous cell carcinoma and Paget's disease. Soluble E-cadherins in sera are elevated in various skin diseases, including bullous pemphigoid, pemphigus vulgaris and psoriasis, but not in patients with burns. Markedly high levels in soluble E-cadherin are demonstrated in patients with metastatic cancers.

Cadherins↗
PubMed1994

Evaluation of the Japanese-Chinese herbal medicine, kampo, for the treatment of lupus dermatoses in autoimmune prone MRL/Mp-lpr/lpr mice.

Kampo, a Japanese-Chinese traditional herbal medicine, has been used for the treatment of various diseases for about 3,000 years in China. Among herbal medicines, Sairei-to is well known for improving the symptoms of rheumatoid arthritis (RA) and other collagen diseases. However, its immunosuppressive effects on autoimmune cutaneous phenomena are not completely understood. We investigated the effects of Sairei-to on the development of lupus dermatoses in autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mice, an animal model which spontaneously develops skin lesions similar to those seen in human lupus erythematosus. Virgin female MRL/lpr mice at 1 month of age, which were treated orally with Sairei-to, had reduced amounts of IgG deposition at the dermoepidermal junction, titers of anti-DNA antibodies and rheumatoid factor, and lymphoproliferation. These results support the use of traditional herbal medicines in patients with human RA and systemic lupus erythematosus.

Animals↗
PubMed1994

The epitope for anti-type VII collagen monoclonal antibody (LH7:2) locates at the central region of the N-terminal non-collagenous domain of type VII collagen.

The monoclonal antibody LH7:2, which recognizes type VII collagen, is now used in the diagnosis and prenatal diagnosis of epidermolysis bullosa dystrophica. We constructed the expression vector which contains the cDNA fragment of type VII collagen. Western blot with LH7:2 was carried out with the resultant fusion proteins which overlap each other, and we found that reactivity is located in the central region of the N-terminal non-collagenous domain of type VII collagen, at a position 81 kDa upstream from the collagenous domain. This epitope mapping for LH7:2 may be useful in studying the role of type VII collagen in epidermolysis bullosa dystrophica.

Antibodies, Monoclonal↗