Biomedical subjects

T Horio

Publications and source records attributed to T Horio.

At least 37 records · Page 2Linked to original sources

PubMed2001

Photobiologic and photoimmunologic characteristics of XPA gene-deficient mice.

Xeroderma pigmentosum group A (XPA) gene-deficient mice cannot repair UV-induced DNA damage and easily develop skin cancers by UV irradiation. Just like human XP patients, homozygous (-/-) mice developed stronger longer-lasting acute inflammation than did wild-type mice after a single irradiation with UVB. Moreover, the model mice showed more severe UV-induced damage of keratinocytes and Langerhans cells than did the control mice. UVB-induced local and systemic immunosuppression was greatly enhanced in the (-/-) mice. Treatment with indomethacin, an inhibitor of prostaglandin (PG) synthesis, inhibited UV-induced inflammation and abrogated immunosuppression. In XPA-deficient mice, the amount of PGE2 and the expression level of COX-2 mRNA greatly increased after UVB irradiation compared with wild-type mice. These results suggest that the excess DNA photoproducts remaining in XPA-deficient cells after UV radiation induce COX-2 expression and subsequently produce a high amount of PGE2, which causes the enhancement of inflammation and immunosuppression. In XPA-deficient mice, the natural killer cell activity significantly decreased after repeated exposures to UVB. Our experimental data indicate that cancer development in XP patients involves not only mutagenesis due to the defect in DNA repair, but also the enhanced UV-immunosuppression and intensified impairment of natural killer function.

Animals↗

PubMed2001

Heightened ability of monocytes from sarcoidosis patients to form multi-nucleated giant cells in vitro by supernatants of concanavalin A-stimulated mononuclear cells.

The main immunocompetent cells in sarcoidal lesions are epithelioid cells and multi-nucleated giant cells (MGC), both of which are derived from monocyte-macrophage lineage cells. To understand further the relevance of monocytes in sarcoidosis, we examined in vitro MGC formation using monocytes from sarcoidosis patients, patients with other granulomatous diseases (OGD) and healthy control subjects. The supernatant of concanavalin A-stimulated peripheral blood mononuclear cells (conditioned medium) generated Langhans type-MGC and foreign body type-MGC from monocytes. Conditioned medium from any three groups had the same ability to form MGC from normal monocytes. On the other hand, MGC were more highly formed using monocytes from sarcoidosis patients than from other groups. When macrophages induced by treatment of monocytes with macrophage colony-stimulating factor (M-CSF) were used, the rate of MGC formation in sarcoidosis patients was about threefold or fourfold as much as that in OGD patients or healthy controls, respectively. Oxidized ATP inhibited MGC formation in all groups. The susceptibility of monocytes cultured in conditioned medium for 24 h to 2'- and 3'-o-(4-benzoyl-benzoyl)ATP-mediated cytolysis was significantly higher in sarcoidosis patients than other groups. These findings suggest that the ability of monocytes to form MGC through P2x7 receptors is enhanced in sarcoidosis patients.

Adenosine Triphosphate↗

PubMed2001

Development and fate of crescentic and granulomatous lesions in rat Masugi nephritis.

It has been observed that with Masugi nephritis in Wistar rats the initiation of endocapillary proliferative changes with macrophage accumulation is usually followed by glomerular sclerosis without extracapillary extension. In the present study, the provocation of an extracapillary lesion was attempted using accelerated Masugi nephritis in Wistar-Kyoto rats. In order to accelerate the accumulation of monocyte/macrophages, the administration of methylcellulose was added in an additional group. The development and fate of extracapillary lesions were analyzed histopathologically and immunohistochemically. As a result, the formation of extracapillary proliferation of granulomatous lesions could be initiated in this model. Granulomatous lesions were composed of CD4+ T cells and CD8+ T cells and monocyte/macrophages including multinucleated giant cells. These inflammatory cells had seemingly escaped from the capillary lumen through the injured glomerular basement membrane and formed cellular and granulomatous crescents. In addition, tenascin was strongly expressed in cellular crescents and was a unique extracellular matrix at this cellular stage. The cellular crescents then progressed to sclerosis with the formation of increased collagenous extracellular matrix. These results suggest that a delayed-type hypersensitivity plays a role in granulomatous crescent formation, even though the initial glomerular injury was evoked by a humoral antibody.

Animals↗

PubMed2001

Molecular forms of plasma and urinary adrenomedullin in normal, essential hypertension and chronic renal failure.

OBJECTIVES: Human adrenomedullin precursor is converted to glycine-extended adrenomedullin (AM-Gly), an intermediate inactive form of adrenomedullin. Subsequently, AM-Gly is converted to active form of mature adrenomedullin (AM-m). The aim of the present study was to investigate (i) whether sex or age influences plasma and urinary AM-m and AM-Gly levels in normal subjects; (ii) the daytime variability of plasma AM-m and AM-Gly levels in normal subjects; (iii) AM-m and AM-Gly levels and its ratio in plasma and urine in normal subjects, individuals with essential hypertension (HT), and chronic renal failure (CRF); and (iv) the ratio of AM-m and AM-total (T) in plasma of various veins and aorta. METHODS: We measured plasma levels and urinary excretions of AM-m, AM-Gly and AM-T (AM-m + AM-Gly) by recently developed immunoradiometric assay in normal subjects (n = 81), HT (n = 28) and CRF (n = 30). We also determined the molecular forms of plasma adrenomedullin taken from various sites during angiography in patients with suspected renovascular hypertension (n = 9). RESULTS: There were no differences in plasma and urinary excretions of two molecular forms of adrenomedullin among sexes or ages in normal subjects. There was no daytime variation of plasma two molecular forms of adrenomedullin in normal subjects. Plasma AM-m, AM-Gly and AM-T levels were increased in patients with HT and CRF compared with normal subjects, whereas urinary AM-m, AM-Gly and AM-T excretions were decreased in patients with HT and CRF compared with normal subjects. Urinary AM-m: AM-T ratios were significantly higher than plasma AM-m: AM-T ratios. Plasma AM-m and AM-T levels taken from various veins were similar, and they were significantly higher than those of aorta, although there were no differences in plasma AM-Gly levels between aorta and veins. CONCLUSIONS: These results suggest that in normal subjects, and individuals with HT and CRF: (i) plasma and urinary excretions of AM-m and AM-Gly are not affected by age or sex; (ii) AM-m in parallel with AM-Gly is increased; (iii) urine contains a higher percentage of active adrenomedullin than plasma; and (iv) plasma AM-m may be partly metabolized in the lung.

Adrenomedullin↗

PubMed2001

Comprehensive analysis of 28 patients with latex allergy and prevalence of latex sensitization among hospital personnel.

Recently anaphylactic shock caused by latex gloves and medical instruments has been discussed as an important problem in surgical operations. Patients with contact urticaria or anaphylaxis due to natural rubber latex were first reported in Japan in 1993, and the number of cases is gradually increasing. In the present study, we analyzed 28 patients examined in our clinic from 1993 to 1998. The diagnosis of latex allergy was made on the basis of clinical history, latex specific IgE antibody, skin test, and use test. The 3 male and 25 female patients included 20 nurses, 4 doctors, 2 housewives, one animal hospital employee, and one worker in a senile rehabilitation center. The majority were health care workers. Contact urticaria from rubber gloves was the most common clinical symptom. Some of the patients developed severe attacks of anaphylaxis. During the period from 1995 to 1997, we also performed a questionnaire study and a serum examination of latex specific IgE antibody among the personnel of our university hospital. The screening test for the antibody was more reliable than our questionnaire study in detecting latex-sensitive persons. The prevalence of latex allergy was found to be 4.6%. This indicates that not only dermatologists but also all hospital workers should be aware of this type of allergy.

Adult↗

PubMed2001

Role of increased circulating and renal adrenomedullin in rats with malignant hypertension.

Although it has been reported that the circulating adrenomedullin (AM) level is elevated in hypertension and renal failure, the pathophysiological significance of circulating and intrarenal AM in malignant hypertension remains unknown. We investigated the circulating and intrarenal AM system in rats with malignant hypertension by measuring the plasma level, renal tissue level, and mRNA abundance of AM and the mRNA abundance of AM receptor. We also investigated the effects of intravenously infused calcitonin gene-related peptide (CGRP)-(8-37), an antagonist of AM, on the hemodynamics and renal tubular function. We studied the following four groups: control Wistar-Kyoto rats (WKY), control spontaneously hypertensive rats (C-SHR), salt-loaded SHR (S-SHR), and DOCA-salt SHR (D-SHR). After 3 wk of DOCA treatment, D-SHR developed malignant hypertension. D-SHR were characterized by higher blood pressure, kidney weight, urinary protein excretion and blood urea nitrogen, and lower creatinine clearance compared with the other three groups. The plasma AM level and urinary excretion of AM were markedly higher in D-SHR than in the other three groups. In the kidney, the tissue AM level and the expression of AM mRNA in the renal medulla were significantly increased in D-SHR compared with the other three groups, whereas there were no significant differences in these levels in the renal cortex among the four groups. In the renal AM receptor system, the expression of the gene for receptor activity modifying protein 3 was significantly increased in the renal medulla in D-SHR compared with the other three groups. An immunohistochemical study revealed that AM immunostaining in renal collecting duct cells and distal tubules was more intense in D-SHR than in the other three groups. After CGRP-(8-37) infusion, blood pressure increased significantly and urinary sodium excretion and urine flow decreased significantly only in D-SHR. These results suggest that the increased circulating AM and renal AM and the increased expression of the mRNA for AM and its receptor may at least partly compensate for the malignant hypertensive state in certain forms of malignant hypertension via the hypotensive, natriuretic, and diuretic actions of AM.

Adrenomedullin↗

PubMed2001

Alterations of intrarenal adrenomedullin and its receptor system in heart failure rats.

Calcitonin receptor-like receptor/receptor activity-modifying protein 2 (CRLR/RAMP2) and CRLR/RAMP3 complexes have been reported to be specific adrenomedullin (AM) receptors. In the present study, we evaluated the pathophysiological significance of renal AM and its receptor system in aortocaval shunt (ACS) rats. Renal AM levels were measured serially during 5 weeks after the operation. Renal gene expressions of AM, CRLR, RAMP2, and RAMP3 were measured at 2 weeks (decompensated phase) and 5 weeks (compensated phase) after the operation. Immunohistochemical localizations of renal AM were also evaluated. Furthermore, the relations between urinary sodium excretion (UNaV) and renal AM levels were evaluated. Renal AM levels were higher in ACS than in control animals only at 1, 2, and 3 weeks after the operation. At 2 weeks after the operation, renal AM mRNA expression was also higher in ACS than in control animals. CRLR, RAMP2, and RAMP3 mRNAs were expressed in the kidney, but there were no differences between the 2 groups. Immunohistochemistry revealed the positive AM immunostaining within the renal tubular cells, and it was more intense in ACS than in control animals. There were significant correlations between UNaV and renal AM levels. At 5 weeks after the operation, there were no differences in mRNA levels of AM, CRLR, RAMP2, and RAMP3 between the 2 groups. There was a significant correlation between UNaV and medullary AM levels. The present findings suggest that increased renal AM levels in decompensated heart failure, presumably due to increased AM production in renal tubules, in part, are involved in the regulation of sodium excretion.

Adrenomedullin↗

PubMed2001

The active molecular form of plasma adrenomedullin is extracted in the pulmonary circulation in patients with mitral stenosis: possible role of adrenomedullin in pulmonary hypertension.

Adrenomedullin (AM), a novel hypotensive peptide, preferentially dilates pulmonary vessels rather than systemic vessels. This suggests the possibility that AM is a circulating hormone which participates in regulation of the pulmonary circulation. A recent study revealed that two molecular forms of AM, i.e. a mature, active form of AM (AM-m) and an intermediate, inactive, glycine-extended form of AM (AM-Gly), circulate in human plasma. In the present study we investigated the production and clearance sites and pathophysiological significance of the two molecular forms of AM in the pulmonary circulation in patients with mitral stenosis. We measured the plasma levels of AM-m and total AM (AM-T; AM-m+AM-Gly) using a recently developed specific immunoradiometric assay, and thus calculated plasma AM-Gly levels, in blood samples obtained from the femoral vein, pulmonary artery, left atrium and aorta of 28 consecutive patients with mitral stenosis (20 females and eight males; age 53+/-10 years). Patients with mitral stenosis had significantly higher venous concentrations of AM-T, AM-Gly and AM-m than age-matched normal controls (AM-T, 15.9+/-2.5 and 10.6+/-2.1 pmol/l respectively; AM-Gly, 14.0+/-2.1 and 9.8+/-1.9 pmol/l respectively; AM-m, 1.9+/-0.6 and 1.1+/-0.3 pmol/l respectively; each P<0.001). There was a significant decrease in the concentrations of AM-m and AM-T between the pulmonary artery and the left atrium (AM-T, 16.1+/-2.7 and 14.0+/-2.4 pmol/l respectively; AM-m, 2.0+/-0.6 and 0.7+/-0.2 pmol/l respectively; each P<0.001); however, there were no differences in plasma AM-Gly levels between the pulmonary artery and the left atrium (14.1+/-2.3 and 13.5+/-2.3 pmol/l respectively). The venous concentrations of AM-m, AM-Gly and AM-T showed similar correlations with mean pulmonary artery pressure (AM-T, r=0.67; AM-Gly, r=0.63; AM-m, r=0.59; each P<0.001) and total pulmonary vascular resistance (AM-T, r=0.77; AM-Gly, r=0.70; AM-m, r=0.75; each P<0.001). These results suggest that the plasma concentration of AM-m is increased in parallel with those of AM-Gly and AM-T, and that the main site for clearance of AM-m from the plasma is the lung; the extracted AM-m in the lungs may help to attenuate the increased pulmonary arterial resistance in secondary pulmonary hypertension due to mitral stenosis.

Adrenomedullin↗

PubMed2001

Activation of Fc epsilon RI-positive eosinophils in bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune disease frequently occurring in elderly persons. It has been reported that 92-kDa gelatinase released from eosinophils cleaves the extracellular domain of BP180 protein, suggesting a direct role of eosinophils in bulla formation in this disease. The expression of the high-affinity IgE receptor, Fc epsilon RI, on eosinophils was examined in patient with BP. Samples of affected skin obtained from 7 patients with BP were stained immunohistochemically by the alkaline phosphatase anti-alkaline phosphatase (APAAP) method and mirror sections were examined. Eosinophils were present at a rate of 1.0-19.0% in lesions of the dermis, and the number of IgE-positive cells exceeded that of Fc epsilon RI-positive cells in all cases. These cells were not detected in the epidermis, and examination of mirror sections confirmed that the Fc epsilon RI-positive cells corresponded to eosinophils. It has been demonstrated that Fc epsilon RI-positive cells are involved in the dermal lesions of BP. The activation of eosinophils by Fc epsilon RI may participate in the pathogenesis of BP by triggering the degranulation of mast cells.

Biopsy↗

PubMed2001

Muramyl dipeptide and mononuclear cell supernatant induce Langhans-type cells from human monocytes.

Muramyl dipeptide (MDP) in bacterial cell walls reportedly evokes epithelioid cell granulomas. We examined its effects on multinucleated-giant-cell (MGC) formation from monocytes. Supernatant of concanavalin A-stimulated peripheral blood mononuclear cells (conditioned medium) generated MGCs from monocytes. MDP significantly increased the fusion index of Langhans-type MGCs (LGCs) but did not affect total MGCs. N-Acetylmuramyl-L-alanyl-L-isoglutamine, an MDP analogue, had no effect on MGC formation. MGCs were produced by conditioned medium from CD14(++)/CD16(-) monocytes. MDP enhanced the LGC fusion index from CD14(++)/CD16(-) monocytes. MGCs were not produced from CD14(+)/CD16(+) monocytes or immature dendritic cells induced by granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL) 4 and only weakly produced from macrophage (M)-CSF- or GM-CSF-induced macrophages. Added MDP did not generate MGCs from CD14(+)/CD16(+) monocytes or dendritic cells but enhanced LGC formation from macrophages. Because IFN-gamma, IL-3, and GM-CSF reportedly are important in LGC induction, we added anti-IFN-gamma, anti-IL-3, or anti-GM-CSF monoclonal antibody (mAb) concomitantly to the monocyte culture treated with conditioned medium alone or plus MDP. Anti-IFN-gamma mAb completely abrogated MGC generation, whereas anti-GM-CSF and anti-IL-3 mAbs significantly inhibited LGCs. These findings suggest that CD14(++)/CD16(-) monocytes are fused to form LGCs by MDP derived from granulomatous-disease-causing pathogens with inflammatory mediators such as IFN-gamma, IL-3, and GM-CSF.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2000

Protective effects of sunscreening agents on photocarcinogenesis, photoaging, and DNA damage in XPA gene knockout mice.

We investigated the protective effects of commercial sunscreening agents against UVB-induced photoresponses in group A xeroderma pigmentosum (XPA) model mice. XPA gene-deficient mice are defective in nucleotide excision repair and show a high incidence of skin tumors and severe acute inflammation in response to UVB irradiation, in a similar manner to XP patients. SPF 10 and SPF 60 sunscreens protected partially and almost completely, respectively, ear swelling responses produced by UVB up to 200 mJ/cm2 in (-/-) mice. XPA (-/-) mice were irradiated three times a week to a cumulative dose of 2.6 J/cm2 UVB for a period of 24 weeks with or without SPF 10 or SPF 60 sunscreen. UV-induced skin tumors had developed in all unprotected (-/-) mice (13.3 tumors per mouse) at the completion of UVB irradiation. The SPF 60 sunscreen afforded stronger protection against photocarcinogenesis (1.0 tumors per mouse) than the SPF 10 sunscreen (4.4 tumors per mouse). Regarding photoaging, SPF 60 sunscreen also protected against mast cell infiltration (79% inhibition), elastic fiber accumulation, and dermal cyst proliferation in XPA (-/-) mice compared with unprotected (-/-) mice. In (-/-) mice, the SPF 60 sunscreen provided stronger protection against cyclobutane pyrimidine dimer formation shown immunohistologically following irradiation with 200 mJ/cm2 UVB than the SPF 10 sunscreen. The XPA model mouse is a useful animal for the evaluation of the photoprotective ability of sunscreens because photoresponses, even chronic changes, can be easily and quickly induced experimentally.

Aging↗

PubMed2000

Preservation of the right atrial appendage improves reduced plasma atrial natriuretic peptide levels after the maze procedure.

OBJECTIVES: The present study was conducted to determine whether preservation of the right atrial appendage lessens the decrease of plasma atrial natriuretic peptide levels after the maze procedure and whether the increase of plasma atrial natriuretic peptides improves the ability of the kidneys to excrete the fluid load after the operation. METHODS: We evaluated 42 patients who underwent the maze procedure. The right atrial appendage was preserved in 22 patients but not in 20. Blood samples were obtained before and after the operation for measurement of atrial natriuretic peptides. To evaluate the influence of atrial natriuretic peptides on the ability of the kidneys, we also measured body weight, fluid balance, and the doses of furosemide and dopamine administered after the operation. RESULTS: The restoration to sinus rhythm at 1 month after was comparable in the two groups. Plasma atrial natriuretic peptide levels significantly increased after the operation in patients in whom the right atrial appendage was preserved (1 day after: 23.4 +/- 17.8 vs 3 days after: 42.7 +/- 23.6 and 7 days after: 36.3 +/- 23.7 pg/mL, P <.05) but not in patients in whom the right atrial appendage was not preserved (1 day after: 20.0 +/- 19.6, 3 days after: 28.5 +/- 19.3, and 7 days after: 23.0 +/- 16.1 pg/mL). Furthermore, plasma atrial natriuretic peptide levels were significantly lower in patients in whom the right atrial appendage was not preserved than in patients in whom the right atrial appendage was preserved at 3 and 7 days after the operation. The fluid balance during the first 7 days of the postoperative period was comparable in the two groups, although the total dose of dopamine used in the same period was significantly smaller in patients in whom the right atrial appendage was preserved than in patients in whom the right atrial appendage was not preserved (155.3 +/- 119.0 vs 244.9 +/- 129.0 microg/kg, P <.05). CONCLUSIONS: The present study showed that preservation of the right atrial appendage lessens the decrease of plasma atrial natriuretic peptide levels after the maze procedure and that increased plasma atrial natriuretic peptides may improve the ability of the kidneys to excrete the fluid load after the operation.

Atrial Appendage↗

PubMed2000

Differentiation from thymic B cell progenitors to mature B cells in vitro.

The role of the thymic microenvironment in the development of murine thymic B cells has yet to be fully clarified. We therefore investigate the microenvironment that supports the development of mature thymic B cells (sIg+/B220+/CD43-B cells) from thymic B cell progenitors with immunophenotypes of sIg-/B220med/CD43+ cells. As we have previously reported, thymic B cells generated from these progenitors in the thymus are CD5+ B cells. We next study the in vitro condition that supports the differentiation of thymic B cell progenitors. Stromal cells (from the bone marrow or thymus), thymus-derived cell lines with the character of thymic nurse cells (TNCs) or thymic epithelial cells (TECs), or the bone marrow-derived cell line (MS-5) are tested for their ability to support B-lymphopoiesis from thymic B cell progenitors. Interestingly, thymic stromal cells (but neither stromal cells from the bone marrow nor stromal cell lines) support the differentiation of thymic B cell progenitors into thymic B cells in the presence of IL-7. Cortical epithelia (but not medullary epithelia, thymic macrophages or dendritic cells) are found to contribute to thymic B cell differentiation. Surface phenotype and Ig rearrangement analyses reveal that mature B cells generated in this condition are primarily CD5+ B cells, indicating that the thymic microenvironment (particularly cortical epithelia) determines the differentiation of thymic B cells.

Animals↗

PubMed2000

Dynamic changes in microtubule organization during division of the primitive dinoflagellate Oxyrrhis marina.

The marine dinoflagellate Oxyrrhis marina has three major microtubular systems: the flagellar apparatus made of one transverse and one longitudinal flagella and their appendages, cortical microtubules, and intranuclear microtubules. We investigated the dynamic changes of these microtubular systems during cell division by transmission and scanning electron microscopy, and confocal fluorescent laser microscopy. During prophase, basal bodies, both flagella and their appendages were duplicated. In the round nucleus situated in the cell centre, intranuclear microtubules appeared radiating toward the centre of the nucleus from densities located in some nuclear pores. During metaphase, both daughter flagellar apparatus separated and moved apart along the main cell axis. Microtubules of ventral cortex were also duplicated and moved with the flagellar apparatus. The nucleus flattened in the longitudinal direction and became discoid-shaped close to the equatorial plane. Many bundles of microtubules ran parallel to the short axis of the nucleus (cell long axis), between which chromosomes were arranged in the same direction. During ana-telophase, the nucleus elongated along the longitudinal axis and took a dumbbell shape. At this stage a contractile ring containing actin was clearly observed in the equatorial cortex. The cortical microtubule network seemed to be cut into two halves at the position of the actin bundle. Shortly after, the nucleus divided into two nuclei, then the cell body was constricted at its equator and divided into one anterior and one posterior halves which were soon rebuilt to produce two cells with two full sets of cortical microtubules. From our observations, several mechanisms for the duplication of the microtubule networks during mitosis in O. marina are discussed.

Actins↗

PubMed2000

Inhibitory influences of tranilast on multinucleated giant cell formation from monocytes by supernatant of concanavalin A-stimulated mononuclear cells.

Tranilast is an anti-allergic drug that inhibits the release of chemical mediators from mast cells. There have been cases-reports showing that tranilast is effective for the treatment of granulomatous diseases such as granuloma annulare and cutaneous sarcoidosis. Here we examined the in vitro effects of tranilast on the formation of multinucleated giant cells (MGCs) from human peripheral monocytes. Supernatant of concanavalin A (Con A)-stimulated mononuclear cells induced Langhans-type and foreign body-type MGCs and the addition of 10 or 100 microg/ml tranilast inhibited the formation of total MGCs and foreign body-type MGCs. Tranilast decreased the number of MGCs with 16<nuclei and increased that of MGCs with three to five nuclei. Fluorescence-activated cell sorting analysis showed that tranilast-treated monocytes had lower expressions of intercellular adhesion molecule-1 (ICAM-1). These findings suggest that tranilast is effective for cutaneous lesions in some cases of granulomatous disorders partly through a direct effect on monocyte/macrophage-lineage cells.

Anti-Allergic Agents↗

PubMed2000

Indications and action mechanisms of phototherapy.

Recently phototherapy has become one of the most commonly used modalities for the treatment of a variety of skin diseases, although the action mechanisms have not been fully understood. The inhibitory effect of UVR on DNA synthesis may be one of the actions for proliferating skin diseases. However, phototherapy is also used for the treatment of allergic or autoimmune diseases. It has been confirmed that the skin is an important immunologic organ whose constitutive cells are all involved in immunologic reactions. We have investigated the effects of PUVA and UVB radiation on the immunocompetent cells, including Langerhans cells, T lymphocytes, mast cells, endothelial cells and natural killer cells. Exposure to UVR inhibits contact sensitization to haptens applied not only to the irradiated skin area but also to the non-irradiated distant skin when the exposure dose is relatively high and/or the application skin area is large. In addition, hapten-specific tolerance develops by the generation of suppressor T cells. Phototherapy is also useful for immediate type hypersensitivity such as urticaria. Action mode in the case may be the inhibitory effects of UVR on histamine release from mast cells. The results obtained from these experiments suggest that phototherapy exerts its anti-allergic and anti-inflammatory effects through immunosuppression.

Adjuvants, Immunologic↗

PubMed2000

Successful treatment of lichen myxoedematosus with PUVA photochemotherapy.

Lichen myxoedematosus is an unusual disorder of unknown etiology and pathogenesis. Although several treatments have reportedly been tried, therapeutic efficacies are variable and unsatisfactory. A patient with severe skin changes of this disease was successfully treated with PUVA photochemotherapy. PUVA therapy was carried out using 30 mg of 8-methoxypsoralen orally, and subsequent exposure to UVA starting at 4 J/cm2. The eruption disappeared almost completely after 35 treatments at a cumulative dose of 202 J/cm2. Histologically, mucin deposition was greatly diminished after the therapy. The photochemotherapy may exert its effect directly by inhibiting proliferation of fibroblasts and synthesis of mucopolysaccharides, and also indirectly by immunomodulating action.

Humans↗

PubMed2000

Effect of neutral endopeptidase inhibitor on endogenous atrial natriuretic peptide as a paracrine factor in cultured cardiac fibroblasts.

1. Cardiac remodelling is a fundamental response to hypertension, myocardial infarction and chronic heart failure, and involves cardiac fibroblast proliferation and production of extracellular matrix components such as collagen. The present study was performed to examine the role of endogenous atrial natriuretic peptide (ANP) as a possible paracrine factor for cardiac fibroblasts, and to examine the effects of three neutral endopeptidase (NEP) inhibitors, thiorphan, phosphoramidon and ONO-BB-039-02 (ONO-BB) on endogenous ANP-induced changes in collagen synthesis by cultured neonatal rat cardiac fibroblasts. 2. Each NEP inhibitor singly had no significant effect on collagen synthesis by cardiac fibroblasts, except for maximum concentration (10(-3) M) of thiorphan. 3. Exogenous ANP inhibited collagen synthesis in a concentration-dependent manner (10(-8) - 10(-6) M). Thiorphan (10(-4) and 10(-3) M) and phosphoramidon (10(-5) and 10(-4) M) enhanced the ANP (10(-7) M)-induced decrease in collagen synthesis. ONO-BB (10(-5) and 10(-4) M) slightly enhanced the ANP-induced decrease in collagen synthesis. 4. Myocyte-conditioned medium (MC-CM), as well as exogenous ANP, inhibited collagen synthesis dose-dependently. The decrease in collagen synthesis at 100% MC-CM was augmented by thiorphan (10(-3) M), phosphoramidon (10(-4) M) and ONO-BB (10(-4) M). 5. HS-142-1, a natriuretic peptide receptor antagonist, significantly reduced the MC-CM plus thiorphan- and MC-CM plus ONO-BB-induced decrease in collagen synthesis, by 92 and 62%, respectively and showed a tendency to attenuate the MC-CM plus phosphoramidon-induced decrease in collagen synthesis by 40%. 6. Our observations suggested that endogenous ANP released from cardiomyocytes inhibited collagen synthesis as a paracrine factor and that NEP inhibitors enhanced the activity of this peptide in cardiac fibroblasts.

Animals↗