Biomedical subjects

H Miyazaki

Publications and source records attributed to H Miyazaki.

At least 145 records · Page 8Linked to original sources

PubMed1999

Atomic force microscopic measurement of the mechanical properties of intact endothelial cells in fresh arteries.

Mechanical properties of living endothelial cells in the abdominal aortas and in the medial and lateral wall of aortic bifurcations obtained from rabbits were determined by means of an atomic force microscope (AFM), focusing on the locational differences. Force (F)-indentation (delta) curves of the cells were expressed by an exponential function: F = a(exp(b delta)-1), where a and b are constants. The parameters b and c(= ab) represent the rate of modulus change and initial modulus, respectively. The slope of F-delta curves a and the parameter c were higher in the medial wall than in the other sites, which is attributable to abundant stress fibres in endothelial cells in the medial wall. There were no differences in the parameter b among the three locations. These results indicate that endothelial cells are stiffer in the medial wall of aortic bifurcation than in the other regions.

Animals↗

PubMed1999

Transcutaneous PCO2 monitoring in the evaluation of hyperventilation of patients with recurrent nerve paralysis.

Hyperventilation during phonation is one of the causes of fatigue in patients with vocal cord disorders. Transcutaneous (TC) PCO2 and PO2 were analyzed during phonation in patients with known recurrent nerve paralyses (RNP). There was no significant change in TCPCO2 in eight normal subjects. In cases with unilateral RNP and incomplete glottic closure, TCPCO2 decreased during phonation. This decrease in TCPCO2 resulted from hyperventilation during phonation. The TCPCO2 did not decrease in one case with RNP and complete glottic closure. In one case with incomplete glottic closure, the decrease in TCPCO2 and fatigue disappeared after treatment. These results suggest that hyperventilation is one of the causes for easy fatiguability during phonation in patients with RNP, Findings also show that measurements of TCPCO2 during phonation are useful for evaluating the cause of fatigue in patients with vocal disorders.

Adult↗

PubMed1999

MELAS with prominent white matter gliosis and atrophy of the cerebellar granular layer: a clinical, genetic, and pathological study.

This report concerns an autopsy case of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) with unusual neuropathological findings. The patient was a Japanese woman who was 21 years old at the time of death. Her mother is a patient with genetically confirmed MELAS. Her clinical manifestations included convulsions and lactic acidosis in the latter half of the first decade of life, followed by deafness, dementia, muscle weakness in the lower extremities, slight ataxia in the upper and lower extremities, and diabetes mellitus. Muscle biopsy revealed ragged-red fibers, and genetic study showed a point mutation at nucleotide pair 3243 in mitochondrial DNA. She died of lactic acidosis. In the clinical course, she did not develop stroke-like episodes. The neuropathological examination revealed not only minute to small necrotic foci in the cerebral cortex, amygdala, hippocampus, and cerebellum, but also prominent white matter gliosis in the central nervous system and cerebellar cortical degeneration of granular cell type. Our neuropathological findings, including prominent white matter gliosis of the central nervous system and cerebellar cortical degeneration of granular cell type, may indicate morphologically widespread cellular dysfunction, not restricted to either neuronal or vascular derangement, in the brain pathology of MELAS.

Adult↗

PubMed1999

Ischemia induces metallothionein III expression in neurons of rat brain.

Metallothionein III (MT-III) is a brain-specific member of the metallothionein family and binds zinc in vivo. In order to confirm the precise localization of MT-III in normal rat brain and the change of MT-III expression after transient whole brain ischemia, we raised a high affinity phagemid-antibody specific for rat MT-III. Immunohistochemical analysis revealed that MT-III in normal brain is localized abundantly in neuronal cell bodies in CA1-3 regions of hippocampus, dentate gyrus, cerebral cortex, olfactory bulb and Purkinje cells in cerebellum. This expression pattern of MT-III was similar to that of MT-III mRNA observed by in situ hybridization studies. ELISA and Northern blot analysis revealed that MT-III protein as well as mRNA levels were up-regulated in cerebrum soon after ischemic stress. Immunohistochemical analysis also demonstrated intense staining in neurons in injured brain after ischemia, which distributed in the same regions as in normal brain. These results suggest that MT-III plays an important role in protecting neurons from ischemic insult by reducing neurotoxic zinc levels and inhibits uncontrolled growth of neurites after ischemia.

Animals↗

PubMed1999

Neuroprotective effects of a dihydropyridine derivative, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarbox ylic acid methyl 6-(5-phenyl-3-pyrazolyloxy)hexyl ester (CV-159), on rat ischemic brain injury.

CV-159, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic++ + acid methyl 6-(5-phenyl-3-pyrazolyloxy)hexyl ester, is a dihydropyridine derivative that blocks the L-type Ca2+ channel and inhibits the calmodulin (CaM)-dependent pathway. In this study, we examined the effects of CV-159 on rat ischemic brain injury. CV-159 (5 and 10 mg/kg, p.o.) gave significant protection against delayed neuronal death in the hippocampal CA1 region after 15-min transient forebrain ischemia. In contrast, the Ca2+ antagonists nicardipine (1 and 10 mg/kg, p.o.) and nifedipine (1 mg/kg, i.p.) and the CaM antagonist N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7, 500 ng, i.c.v.) had no effect on this hippocampal neuronal death. CV-159 also diminished the size of the brain infarct after permanent middle cerebral artery (MCA) occlusion, although physiological variables, including regional cerebral blood flow, were not affected. The increase in the water content of the infarcted cortex induced by MCA occlusion was significantly reduced by CV-159. On the other hand, neither nicardipine nor nifedipine affected the brain infarct size, volume or increased water content induced by MCA occlusion, as previously reported (A. Sauter and M. Rudin, Am. J. Hypertens. 4 121S-127S, 1991). These findings indicate that Ca2+ antagonists, such as nicardipine and nifedipine, and W-7 have no effect on rat ischemic brain injury. The results suggest that CV-159 protects against ischemic brain injury. This might be mediated by both blocking the L-type Ca2+ channel and inhibiting CaM-dependent function via Ca2+/CaM binding at a different binding site from that of W-7 to CaM (H. Umekawa, K. Yamakawa, K. Nunoki, N. Taira, T. Tanaka, and H. Hidaka, Biochem. Pharmacol. 37 3377-3381, 1988).

Animals↗

PubMed1999

Effects of T-588, a novel cognitive enhancer, on ADP-ribosylation of G(s alpha) by cholera toxin and cyclic AMP accumulation in rat cerebral cortex.

We investigated the effects of R(-)-1-(benzo[b]thiophen-5-yl)-2-[2-(N,N-diethylamino)ethoxy]ethan ol hydrochloride (T-588), a novel cognitive enhancer, on trimeric GTP-binding proteins (G proteins) and cyclic AMP accumulation in rat cerebral cortex. T-588 (0.1-1.0 mM) inhibited the ADP-ribosylation of alpha subunit of Gs in a concentration-dependent manner. Auto-ADP-ribosylation of CTX was not inhibited by T-588. The stimulatory effect of guanosine 5'-(3-O-thio)triphosphate (GTPgammaS) on CTX-catalyzed ADP-ribosylation was attenuated by adding T-588 in assay mixture. ADP-ribosylation of Gi/Go by pertussis toxin was slightly inhibited by T-588. Isoproterenol-stimulated cyclic AMP accumulation was inhibited by adding 3 mM T-588 to rat cerebral cortical slices. Next, we investigated the effects of isoproterenol and T-588 on GTPgammaS binding. Membranes were first incubated with or without isoproterenol and T-588 in the presence of 0.2mM GTPgammaS, then cholate extract preparations were prepared from the washed membranes. Interestingly, the [32P]ADP-ribosylation of G(s alpha) was enhanced not only by isoproterenol but also by T-588. Although the obtained results are apparently inconsistent, T-588 seems to interact with G proteins, specifically Gs.

Adenosine Diphosphate Ribose↗

PubMed1999

Glial cell line-derived neurotrophic factor protects against delayed neuronal death after transient forebrain ischemia in rats.

Glial cell line-derived neurotrophic factor, a member of the transforming growth factor-beta superfamily, is a potent neurotrophic factor, which has a variety of biological activities that affect several types of neurons in both the central and peripheral nervous systems. In this study, we examined the effects of glial cell line-derived neurotrophic factor on delayed neuronal death in the hippocampal CA1 region of rats after transient forebrain ischemia. In the control rats pretreated with the vehicle, transient forebrain ischemia-induced delayed neuronal death in the hippocampal CA1 region was observed seven days after reperfusion. Pretreatment with glial cell line-derived neurotrophic factor (1.0 microg), which was directly microinjected into the right hippocampal CA1 region, gave significant protection against the delayed hippocampal neuronal death. On the contralateral side of the hippocampus, which was not injected with glial cell line-derived neurotrophic factor, delayed neuronal death similar to that seen in vehicle-treated control animals was observed. Intracerebroventricular glial cell line-derived neurotrophic factor (2.5 microg) injection also protected against delayed neuronal death. In addition, pretreatment with glial cell line-derived neurotrophic factor gave significant protection against apoptotic cell death induced by brain ischemia in the hippocampal CA1 region, as determined by in situ staining for DNA fragmentation. These findings suggest that glial cell line-derived neurotrophic factor plays an important role in delayed neuronal death induced by brain ischemia.

Animals↗

PubMed1999

An ACTH-producing pituitary carcinoma developing Cushing's disease.

An autopsy case of an ACTH-producing pituitary carcinoma in a 59-year-old man who developed Cushing's disease is reported. The surgically removed pituitary tumor was diagnosed as chromophobe adenoma, however, pulmonary metastases appeared 2 years after the operation. Autopsy revealed a residual pituitary tumor in the sella turcica with systemic metastases to the lungs, liver, pulmonary lymph nodes, hypothalamus, dura mater, and the subarachnoid space of the midbrain and spinal cord. Immunohistochemistry revealed ACTH positivity in the tumor cells. Further immunohistochemical study showed positive high expression of Ki-67 in the tumor removed at surgery as well as in the autopsied tumor. Ki-67 labeling index provided valuable information about the invasive and proliferative potential compared to noninvasive benign pituitary adenoma.

Adrenocorticotropic Hormone↗

PubMed1999

An autopsy case of malignant mesothelioma with osseous and cartilaginous differentiation: bone morphogenetic protein-2 in mesothelial cells and its tumor.

An autopsy case of biphasic malignant mesothelioma with osseous and cartilaginous differentiation diffusely involving the peritoneal cavity was confirmed by light microscopic histochemistry, immunohistochemistry, and electron microscopy. A reverse transcription-polymerase chain reaction using specific primers for bone morphogenetic protein-2 (BMP-2) revealed weak positive transcript in normal mesothelial cells and up-regulated expression around bone-forming malignant mesothelioma tissue. However, BMP-2 protein expression was detected only in the marginal zone of bone trabeculae and spindle-shaped mesothelioma cells distributed around bone trabeculae in tumor tissue. The distribution of type IV collagen in tumor tissue was in accordance with the BMP-2 expression. Normal mesothelial cells and tumor cells expressed BMP-2 mRNA, but the BMP-2 protein expression was restricted to the bone-forming area in the malignant mesothelioma.

Abdominal Neoplasms↗

PubMed1999

Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel.

CLC-K1 is a kidney-specific chloride channel that mediates transepithelial chloride transport in the thin ascending limb of Henle's loop (tAL) in the inner medulla. Transport of NaCl in the tAL is thought to be a component of urinary concentration in a passive model of the countercurrent multiplication system, but there has been no direct evidence that CLC-K1 is involved in urine concentration. To analyse the physiological function of CLC-K1 in vivo, we generated mice lacking CLC-K1 by targeted gene disruption. Clcnk1-/- mice were physically normal appearance, but produced approximately five times more urine than Clcnk1+/- and Clcnk1+/+ mice. After 24 hours of water deprivation, Clcnk1-/- mice were severely dehydrated and lethargic, with a decrease of approximately 27% in body weight. Intraperitoneal injection of the V2 agonist 1-deamino-8-D-arginine vasopressin (dDAVP) induced a threefold increase in urine osmolarity in Clcnk1+/- and Clcnk1+/+ mice, whereas only a minimal increase was seen in Clcnk1-/- mice, indicating nephrogenic diabetes insipidus. After in vitro perfusion of the tAL, the lumen-to-bath chloride gradient did not produce a diffusion potential in Clcnk1-/- mice in contrast to Clcnk1+/+ and Clcnk1+/- mice. These results establish that CLC-K1 has a role in urine concentration, and that the countercurrent system in the inner medulla is involved in the generation and maintenance of hypertonic medullary interstitium.

Animals↗

PubMed1999

The effects of two antiinflammatory pretreatments on bacterial-induced lung injury.

BACKGROUND: Two antiinflammatory therapies that have been effective in preventing acid-induced lung injury were evaluated. Specifically, their effects on a subsequent bacterial-airspace challenge were compared. Bacteria were instilled 24 h after acid-induced lung injury. Pseudomonas aeruginosa PAO-1 was used as the bacteria, because its effects in healthy lungs was documented previously. METHODS: New Zealand white rabbits were anesthetized and three pretreatments were administered: (1) pentoxifylline pretreatment (a 20-mg/kg bolus dose and then 6 mg x kg(-1) x h(-1) given intravenously), (2) 1 ml anti-tumor necrosis factor alpha antiserum given intravenously, or (3) normal saline given intravenously. The pretreatment doses were shown previously to prevent acid-induced lung injury. Then 1.2 ml/kg hydrochloric acid (HCl), pH 1.25, was instilled into the rabbits' right lungs. All the animals underwent mechanical ventilation for 8 h. Twenty-four hours after the acid instillation, the rabbits were anesthetized again and 2 ml/kg (10(9) colony forming units/ml) PAO-1 was instilled into their left lungs. The rabbits' breathing was aided by mechanical ventilation for another 8 h, and then they were killed and exsanguinated. RESULTS: Both pretreatments attenuated the acid-induced lung injury of the noninstilled left lungs. Arterial oxygen tension and the lung edema of pretreated, acid-exposed animals were significantly and almost equally improved (compared with no pretreatments) by either of the pretreatments. However, when the bacteria were instilled into the left lungs 24 h after the acid injury, the pentoxifylline pretreatment but not the anti-tumor necrosis factor alpha pretreatment prevented much of the bacteria-induced lung injury. Pentoxifylline pretreatment significantly improved the measurements of left lung edema and epithelial and endothelial permeability. There was also a trend for improved oxygenation in the pentoxifylline-pretreated and infected animals. In contrast, the anti-tumor necrosis factor alpha pretreatment did not prevent the bacteria-induced lung injury and increased some of the measurements of lung injury. CONCLUSIONS: Two antiinflammatory therapies that prevented acid-induced lung injury to the noninstilled left lungs had significantly different effects on a subsequent bacteria-induced lung injury to the left lungs. The therapies differed in their mechanism of tumor necrosis factor alpha blockade, and this may have affected the bacteria-induced injury to the lungs.

Animals↗

PubMed1999

Roles of cytokines and cell cycle regulating substances in proliferation of cholesteatoma epithelium.

OBJECTIVES: It can be surmised that the cell cycle must be involved in cell proliferation of the epithelium of middle ear cholesteatoma. Thus a comparative study was conducted of the levels of expression of cyclin-dependent kinase 2 (cdk2) and cyclin-dependent kinase 4 (cdk4)-substances known to be involved in the cell cycle-in cholesteatoma epithelium and the normal epithelium of the bony region of the external ear canal. In addition, it has been reported that the expression of cytokines in the epithelium is accelerated in response to subepithelial inflammation. This suggests that an interaction between the epithelium and subepithelium, which is subject to paracrine regulation, is deeply involved in epithelial proliferation. Accordingly, attention was focused on interleukin-1alpha (IL-1alpha) and keratinocyte growth factor (KGF), cytokines which are found in the subepithelium, and experiments were conducted to elucidate their effects on the expression of the substances known to be involved in the cell cycle. METHODS: The expressions of cdk2 and cdk4 in the cholesteatoma epithelium and external ear canal epithelium were investigated by an immunohistochemical technique. In addition, cultured human keratinocytes were grown in medium containing IL-1alpha or KGF at concentrations of 0, 20, and 100 ng/mL, and the differences in the expression of cdk2 and cdk4 were investigated and compared by Western blot analysis. RESULTS: In the cholesteatoma epithelium specimens, cdk2 and cdk4 were observed to be expressed in the basal and parabasal layers and in the upper layer (prickle layer and granular layer). Their expression tended to be increased compared with their expression in the normal external ear canal epithelium, and this tendency was marked in subepithelial sites showing severe inflammation. In addition, exposure of cultured human keratinocytes to IL-la or KGF resulted in accelerated expression of both cdk2 and cdk4, and this was especially striking in the case of addition of KGF. CONCLUSION: It can be surmised that, in cholesteatoma, accelerated expression of IL-1alpha and KGF by inflammatory cells at subepithelial sites of inflammation leads to upregulation of cdk2 and cdk4 in epithelial cells and to cell proliferation. It was concluded that this is at least one sequence of events involved in the mechanism causing epithelial proliferation in cholesteatoma.

Adult↗

PubMed1999

Terminal differentiation of epithelial cells in middle ear cholesteatoma: investigation of patterns of expression of protein kinase C-delta and protein kinase C-eta.

OBJECTIVES: The objective of this study was to elucidate the differentiation mechanism of keratinocytes in cholesteatoma. STUDY DESIGN: To achieve the objective, we analyzed the expressions of various cellular proteins: the delta and eta isoforms of protein kinase C (PKCdelta and PKCeta), which are thought to play key roles in signal transduction in differentiation; cytokeratin 1 (CK1) and cytokeratin 10 (CK10) (cytoskeletal constitutive proteins); and involucrin (a marker of differentiation). METHODS: The materials used in this study were tissue specimens obtained from cholesteatoma epidermis, normal external ear canal skin, normal inguinal skin, and psoriatic skin. Immunohistochemical staining techniques were applied to compare the expressions of the above proteins (i.e., PKCdelta, PKCeta, CK1, CK10 and involucrin) in those various tissues. RESULTS: No clear differences in the patterns of expression of PKCdelta and PKCeta were found between the cholesteatoma epidermis and the normal external ear canal skin. These proteins were expressed mainly in the stratum spinosum and stratum granulosum, and their patterns of expression were almost the same as those of the CK1, CK10, and involucrin proteins. CONCLUSION: The findings of this study indicate that the terminal differentiation of keratinocytes in the cholesteatoma epidermis is the same as in normal skin tissues. It was concluded that the growth of epidermis which has undergone hyperproliferation of keratinocytes because of increased levels of various cytokines is being regulated by means of normal terminal differentiation.

Adult↗

PubMed1999

Isolation and purification of a protective protein antigen of Erysipelothrix rhusiopathiae.

The rapid growth and high survival rate of Erysipelothrix rhusiopathiae was determined using a culture of the bacterium in tryptic soy broth supplemented with 0.3% Tris-hydroxymethyl aminomethane and 0.1% Tween 80 (TT-TS broth). High concentrations of 64, 66 and 43 kDa proteins, which are associated with protection against E. rhusiopathiae infection in mice, were obtained by alkaline treatment of whole cells using 0.05-1 N NaOH. The supernatant of alkaline treated cells (alkaline extract; AE) was stable at alkaline or neutral pH. However, aggregates appeared at neutral pH in the absence of sodium dodecyl sulphate (SDS). A high yield of 64, 66 and 43 kDa proteins was obtained from strain Agata (serovar 5). The proteins were eluted from gel bands following SDS-polyacrylamide gel electrophoresis (SDS-PAGE) of the AE from strain Agata and designated P64 and P43. The amounts of P64 and P43 isolated were 0.7 and 0.3 mg/16 g of wet bacteria, respectively. In a mouse protection test, 50% protective doses (PD50) of P64 and P43 were 0.58 and 0.63 microgram, respectively. Upon Western blotting of the AE, both anti-P64 and anti-P43 antibodies reacted with the 64 and 43 kDa proteins. From these results, it is suggested that P64 is the most effective protective antigen and that P43 (43 kDa protein) is a degradation product of P64. Therefore, the 64 kDa structural proteins are associated with the induction of a protective activity against E. rhusiopathiae infection in mice.

Animals↗

PubMed1999

Biological roles of angiotensin II via its type 2 receptor during rat follicle atresia.

Type 1 angiotensin II (ANG II) receptors play crucial roles in the regulation of blood pressure and fluid osmolarity, whereas the physiological roles of type 2 ANG II receptors (AT2) remain unclear. Because AT2 is expressed in atretic follicles where granulosa cells undergo apoptosis, we examined the space and time relationship between AT2 expression and follicle atresia in vivo and the effect of AT2 on follicle-stimulating hormone (FSH) actions in vitro. Binding studies, autoradiography, and RT-PCR of AT2 revealed that the AT2 content in granulosa cells was time dependently increased at both protein and mRNA levels in equine chorionic gonadotropin-treated immature female rats. This increase paralleled the progression of atresia. ANG II suppressed FSH-caused prevention of DNA fragmentation, increases in luteinizing hormone receptor content, and estrogen production through AT2 in cultured granulosa cells. Moreover, FSH-induced stimulation of extracellular signal-regulated kinase activity, critical for cell survival, was inhibited by AT2 stimulation. These results suggest that AT2 mediates the progression of follicle atresia through granulosa cell apoptosis by inhibiting FSH actions.

Angiotensin II↗

PubMed1999

Expression of B7-1, B7-2, and interleukin-12 in anti-Fas antibody-induced pulmonary fibrosis in mice.

BACKGROUND: We have previously reported that the inhalation of anti-Fas antibody induced pulmonary fibrosis in mice. To induce an effective immune response, antigen-presenting cells have to not only present antigenic peptide with MHC molecules to T lymphocytes, but also express B7 costimulating molecules. The purpose of this study is to investigate whether B7 family costimulating molecules and interleukin-12 (IL-12), which primarily promote cellular immunity, are associated with anti-Fas antibody-induced pulmonary fibrosis. METHODS: We examined the expression of B7-1, B7-2, and IL-12 using the revese transcription-polymerase chain reaction (RT-PCR), RT-in situ PCR, and immunohistochemistry. RESULTS: We observed the upregulation of B7-1, B7-2, and IL-12 p40 mRNA after anti-Fas antibody inhalation. B7-2 and IL-12 p40 mRNA appeared to be expressed in mononuclear cells, while B7-1 mRNA and protein were expressed in bronchiolar epithelial cells as well as macrophages. CONCLUSION: These findings indicate that the T-cell-mediated immune response in this model involved the upregulation of B7-1, B7-2, and IL-12, and that the aberrant expression of B7-1 in bronchiolar epithelial cells may induce autoreactive T cell proliferation against themselves.

Administration, Inhalation↗

PubMed1999

Immunohistochemical localization of B7 costimulating molecules and major histocompatibility complex class II antigen in pulmonary sarcoidosis.

BACKGROUND: Alveolar macrophages (AM) of sarcoidosis have an enhanced capacity to mediate antigen-induced T lymphocyte proliferation. To induce an effective immune response, antigen-presenting cells have to not only present antigenic peptide with MHC molecules to T lymphocytes, but also express B7 costimulating molecules. OBJECTIVE: The purpose of this study was to investigate the expression of B7 and MHC molecules in lung tissues from patients with sarcoidosis. METHODS: We performed immunohistochemistry for B7-1, B7-2 and MHC class II antigens using transbronchial lung biopsy specimens obtained from patients with sarcoidosis and normal lung parenchyma obtained by lobectomy for solitary pulmonary nodule as controls. RESULTS: B7-1, B7-2 and MHC class II antigen were expressed in epithelioid cells in granulomas in 14 (93.3%), 2 (13.3%) and 9 (60.0%) of 15 patients with sarcoidosis, respectively. These were also expressed in AM in 14 (93. 3%), 5 (33.3%) and 12 (80.0%) of 15 patients with sarcoidosis, respectively. The positivity of B7-1 was significantly higher than that of B7-2 in both epithelioid cells and AM in sarcoidosis (p < 0. 01). Positive signals for B7-1, B7-2 and MHC class II antigen were also found in AM in 9 (90%), 8 (80%) and 8 (80%) of 15 of controls, respectively. However, the intensity of positive signals for B7-1, but not B7-2 or MHC class II antigen in AM was significantly increased in sarcoidosis compared to controls (p < 0.05). CONCLUSIONS: These results suggested that epithelioid cells in granulomas and AM from patients with sarcoidosis had the capability to act as accessory cells and that the accessory function of these cells was shifted to B7-1 rather than B7-2 in sarcoidosis.

B7-1 Antigen↗

PubMed1999

The involvement of Fas-Fas ligand pathway in fibrosing lung diseases.

Pulmonary fibrosis begins with alveolitis, which progresses to destruction of lung tissue and excess collagen deposition. This process could be the result of DNA damage and a form of apoptosis. Therefore, we hypothesized that Fas ligand (FasL), which induces apoptosis in cells expressing Fas antigen (Fas), is associated with pulmonary fibrosis. We examined frozen lung tissues from seven patients with idiopathic pulmonary fibrosis (IPF), and bronchoalveolar lavage fluid (BALF) cells from 19 patients with IPF and from 17 patients with interstitial pneumonia associated with collagen vascular diseases (CVD-IP). We used five frozen lungs with normal lung parenchyma and BALF cells from 10 patients with solitary pulmonary nodule as controls. Reverse transcription-polymerase chain reaction (RT-PCR) showed that FasL messenger RNA (mRNA) was expressed in BALF cells from all patients with IPF and from 15 of 16 patients with CVD-IP. FasL mRNA was not detected in BALF cells except in one of 10 controls. RT in situ PCR detected FasL mRNA in inflammatory cells in BALF from patients with IPF. Immunohistochemistry detected FasL protein in infiltrating lymphocytes and granulocytes in all of seven frozen lung tissues of IPF, but in none of five control lung tissues. Additionally, the expression of Fas appeared to be upregulated in bronchiolar and alveolar epithelial cells in IPF compared with normal lung parenchyma by immunohistochemistry. We conclude that Fas and FasL were upregulated in fibrosing lung diseases and may associate with DNA damage or apoptosis of bronchiolar and alveolar epithelial cells in this disorder.

Adult↗