Transient cold preservation alone stimulates tumor necrosis factor-alpha gene expression in a model of rat syngeneic lung transplantation.
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Animals↗
Biomedical subjects
M Toyoda
Publications and source records attributed to M Toyoda.
Sebaceous glands in acne patients express high levels of neutral endopeptidase.
Acne is a complex, chronic and common skin disorder of pilosebaceous units. Although it is known that exacerbation of acne results from emotional stress, the nature of the association between stress and acne remains unclear. This is due in part to the lack of substantial evidence regarding the participation of cutaneous neurogenic factors in the pathogenesis of acne. To examine the possible involvement of neurogenic factors in the etiology of acne, we used immunohistochemistry to compare the distribution of SP-containing nerve fibers around sebaceous glands and the expression of neutral endopeptidase in sebaceous acini of the facial skin of acne patients and of healthy subjects. More numerous substance P immunoreactive nerve fibers in close apposition to the sebaceous glands and an increase in expression of neutral endopeptidase in sebaceous acini were observed in acne patients compared with the controls. Immunoelectron microscopy revealed that the subcellular localization of neutral endopeptidase was restricted to the Golgi apparatus and the endoplasmic reticulum within sebaceous germinative cells. In addition, in vitro experiments using an organ culture system demonstrated that substance P induced expression of neutral endopeptidase in sebaceous glands in a dose dependent manner. This study reveals that substance P and its degrading enzymes are involved in the pathogenesis of acne, which in turn might partially explain the pathologic significance of neurogenic and psychogenic aspects in the disease process.
Acne Vulgaris↗
Nerve growth factor and substance P are useful plasma markers of disease activity in atopic dermatitis.
BACKGROUND: Neurogenic components, such as neurotrophic factors and neuropeptides, are probably involved in the pathogenesis of atopic dermatitis (AD) via the neuroimmunocutaneous system. Numerous in vitro and in vivo studies have shown that nerve growth factor (NGF), the best-characterized member of the neurotrophin family, modulates the synthesis of the neuropeptide substance P (SP), both of which may be associated with the pathogenesis of human allergic diseases. OBJECTIVES: To evaluate the levels of NGF and SP in the plasma of patients with AD and to examine their possible correlation with disease activity. METHODS: We measured plasma levels of NGF by an immunoenzymatic assay and of SP by aradioimmunoassay in 52 patients with AD, and compared them with 35 normal non-atopic controls. The severity of the disease in AD patients was evaluated using validated clinical scoring systems. RESULTS: Patients with AD had significant increases in plasma levels of NGF and SP compared with controls (P < 0.0005 and P < 0.0001, respectively). A positive correlation between the plasma levels of NGF and SP was found in AD patients (correlation coefficient, Cc = 0.920, P < 0.0001). There was a significant correlation of plasma NGF and SP levels with disease activity evaluated using three different scoring systems: the grading system of Rajka and Langeland (P < 0.001 and P < 0.01, respectively), the objective Severity Scoring of AD (Cc = 0.656, P < 0.005 and Cc = 0.752, P < 0.0005, respectively) and the Eczema Area and Severity Index (Cc = 0.740, P < 0.001 and Cc = 0.765, P < 0.005, respectively). CONCLUSIONS: These data represent the first reported evidence of increased plasma levels of NGF and SP in an allergic human skin disease. They suggest that these neurogenic factors systemically modulate the allergic response in AD, probably through interactions with cells of the immune-inflammatory component. In addition, NGF and SP may be useful markers of disease activity in patients with AD.
Adolescent↗
Correlation between elevator muscle activity and direction of sagittal closing pathway during unilateral chewing.
The closing pathway of masticatory movement in the vicinity of the intercuspal position (ICP) is considered as a functional movement in reconstructing the occlusal guidance. The purpose of this study was to examine a correlation between elevator muscle activity and direction of the closing pathway in the vicinity of the ICP during mastication. Fifty subjects (18 male and 32 female subjects aged from 21 to 34 years) were selected randomly from the students of the Kanagawa Dental College. The measurements of jaw movement during mastication were recorded using a Sirognathograph instrument and surface electromyography (EMG) of the anterior temporalis and masseter muscles simultaneously. The muscle activity and the direction of the closing pathway were calculated on the working and non-working sides during unilateral chewing and analysed at the sections of ICP-2 mm and 2-4 mm in sagittal view. The direction of the closing pathway was expressed by the angle to a vertical reference axis. The direction of the closing pathway correlated significantly with the activity of the anterior temporalis muscles on the non-working side and the masseter muscles on the working side at ICP-2 mm. From the results of this study, it was suggested that the elevator muscle activity may be associated with the direction of the closing pathway during mastication.
Adult↗
A ligand for peroxisome proliferator activated receptor gamma inhibits cell growth and induces apoptosis in human liver cancer cells.
BACKGROUND AND AIMS: Induction of apoptosis of cancer cells through ligands of nuclear hormone receptors (NHRs) is a new approach in cancer therapy. Recently, one of the NHRs, peroxisome proliferator activated receptor gamma (PPARgamma), has been shown to influence cell growth in certain cancer cells although its effect on hepatocellular carcinoma (HCC) has not been analysed. METHODS: Experiments were conducted using three human liver cancer cell lines, PLC/PRF/5, Hep G2 and HuH-7, in vitro. These cells were exposed to troglitazone, a synthetic ligand for PPARgamma, and the effects on cell growth were analysed. RESULTS: Expression of PPARgamma mRNA was detected in all three liver cancer cell lines. Activation of PPARgamma by troglitazone caused a marked growth inhibition in a dose dependent manner in three hepatoma cell lines. The DNA fragmentation ELISA assay and Hoechst 33258 staining revealed that the growth inhibitory effect by adding troglitazone was due to apoptosis of PLC/PRF/5, which strongly expressed PPARgamma. Troglitazone also induced activation of the cell death protease, caspase 3, but not caspase 8, in PLC/PRF/5 cells. However, expression levels of antiapoptotic factor bcl-2 and apoptosis inducing factor bax were not affected. CONCLUSION: Our study showed that PPARgamma was expressed in human liver cancer cells and that the ligand for PPARgamma, troglitazone, inhibited the growth of these cells by inducing apoptosis through caspase 3 activation, indicating that troglitazone could be potentially useful as an apoptosis inducer for the treatment of HCC.
Antineoplastic Agents↗
Overexpression of hepatocyte growth factor/scatter factor promotes vascularization and granulation tissue formation in vivo.
The effect of hepatocyte growth factor/scatter factor (HGF/SF) during wound healing in the skin was investigated, using HGF/SF-overexpressing transgenic mouse model. Histological analysis of HGF/SF transgenic mouse excisional wound sites revealed increased granulation tissue with marked vascularization. Northern blot analysis demonstrated that, relative to control, vascular endothelial growth factor (VEGF) expression in transgenic skin was significantly higher at baseline and was robustly up-regulated during wound healing. Elevated levels of VEGF protein were detected immunohistochemically, predominantly in endothelial cells and fibroblasts within the granulation tissue of HGF/SF transgenic skin. Serum levels of VEGF were also elevated in HGF/SF transgenic mice. Thus, results from our study suggest that HGF/SF has a significant effect on vascularization and granulation tissue formation during wound healing in vivo, involving with induction of VEGF.
Animals↗
Determination of aflatoxins B1, B2, G1 and G2 in spices using a multifunctional column clean-up.
A rapid and simple method using a multifunctional column, which contains lipophilic and charged active sites, was developed to analyse aflatoxins B1, B2, G1 and G2 in various spices, such as red pepper and nutmeg. After extraction by acetonitrile:water (9:1) and clean-up using MultiSep #228 column, the aflatoxins and aflatoxin-TFA derivatives are determined using LC with fluorescence detection. Recoveries of each aflatoxin B1, B2, G1 and G2 spiked to red pepper, white pepper, black pepper, nutmeg and tear grass at the level of 10 ng/g were over 80-85% in all instances. The minimum detectable concentration for aflatoxins in red pepper was 0.5 ng/g.
Aflatoxins↗
Specific tissue distribution of megsin, a novel serpin, in the glomerulus and its up-regulation in IgA nephropathy.
Mesangial cells play critical roles in maintaining a structure and function of the glomerulus. We previously cloned a novel mesangium-predominant gene, megsin, a new serine protease inhibitor. To clarify localization and roles of megsin protein, we raised polyclonal antibodies to megsin. By immunohistochemistry, megsin protein was specifically identified in the mesangial area. The amount of megsin protein was increased in glomeruli of patients with IgA nephropathy than in those of normal individuals and of patients with minimal change nephrotic syndrome or membranous nephropathy, suggesting a pathophysiological role of megsin as a functional modulator of mesangial functions in situ.
Amino Acid Sequence↗
Examination of oral sensitization with ovalbumin in Brown Norway rats and three strains of mice.
We studied the conditions needed to sensitize animals to the oral feeding of food allergens, without induction of tolerance, in order to investigate the allergenicity of orally ingested food proteins. Brown Norway (BN) rats were sensitized by daily OVA (ovalbumin)-gavage or by drinking OVA containing water ad libitum and the ASA (active systemic anaphylaxis) response, as the immediate hypersensitivity response to antigen stimulation after oral sensitization, was examined. The oral administration of OVA by gavage produced a higher OVA-specific IgE response and an increase in serum histamine after antigen challenge, as compared to those produced by drinking water. Next, we examined the effect of murine age, the oral feeding technique and the oral feeding dose on sensitization using BALB/c, B10A and ASK mice. Twenty-week-old mice showed the strongest OVA-specific IgE and IgG1 responses and ASA-associated serum histamine contents increased with gavage in the three different age groups of BALB/c mice. Administering 0.1 mg of OVA by gavage daily for 9 weeks appeared to induce a higher response than administering 1 mg of OVA, in terms of OVA-specific IgE and IgG1 antibody responses and ASA responses. Among the three strains of mice, B10A mice exhibited the highest response in terms of OVA-specific IgE and IgG1 antibody and ASA responses. These findings suggested BN rats and B10A mice were suitable models for oral sensitization with antigen protein and that oral sensitization in mice requires low dose, intermittent antigen intakes.
Administration, Oral↗
Expression of survivin correlates with apoptosis, proliferation, and angiogenesis during human colorectal tumorigenesis.
BACKGROUND: To identify the role of survivin, a novel inhibitor of apoptosis (IAP) in colorectal tumorigenesis, the authors investigated tissue expression of survivin in human colorectal tumors including 43 hyperplastic polyps, 171 adenomas with low dysplasia, 42 adenomas with high dysplasia, and 60 carcinomas in adenoma, and examined whether the expression of survivin correlated with tumor cell apoptosis, proliferation, and angiogenesis, which is known to initiate the imbalance between cell proliferation and apoptosis. METHODS: Immunohistochemical staining for the paraffin sections by using the monoclonal antibodies, survivin, p53, bcl-2, Ki-67, and CD34, was performed by the standard avidin-biotin-peroxidase technique. The apoptotic cells were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method, using an Apop Tag in situ detection kit. RESULTS: The immunoreactivity of survivin significantly increased in the transition from adenoma with low dysplasia to high dysplasia/carcinoma (P < 0.001). Similar changes in protein expression were observed for p53 but not for bcl-2, which was expressed throughout the colorectal tumorigenesis. This transition was associated with a significant decrease in the apoptotic index (AI) and significant increases in the Ki-67 labeling index (LI) and microvessel density (MVD; P < 0.001 for both). The expression of survivin inversely correlated with AI and was positively correlated with Ki-67 LI and MVD (P < 0.001 for both). CONCLUSIONS: These results suggest that, like p53, survivin plays an important role in transition from adenoma with low dysplasia to high dysplasia during human colorectal tumorigenesis.
Adenoma↗
Prolongation of allograft survival with viral IL-10 transfection in a highly histoincompatible model of rat heart allograft rejection.
BACKGROUND: The ability to express genes with potential immunoregulatory capacity could reduce the immunogenicity of allografts and result in long-term graft survival. In this study, we examine the feasibility of transferring viral interleukin-10 (vIL-10) gene into rat hearts using adenovirus by intracoronary administration. The subsequent effects of delivered vIL-10 alone or with subtherapeutic doses of cyclosporine A (CsA) on parameters of allograft rejection (AR) were also examined. METHODS: Recombinant adenovirus vectors containing vIL-10 (Ad-vIL-10) or beta-galactosidase (Ad-beta-gal) were derived from adenovirus type 5. vIL-10 expression in supernatants of transfected COS7 cell cultures and in transfected heart allografts were examined by enzyme immunoassay (EIA) and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. Rat heart transplants (LEWS->ACI) were performed in five groups [group 1: no treatment, group 2: Ad-beta-gal, group 3: AdvIL-10, group 4: CsA (10 mg/kg), and group 5: Ad-vIL10+CsA (10 mg/kg)]. Allograft survival was determined by palpating heartbeats. Allograft tissues were also submitted for histological study. RESULTS: vIL-10 expression was shown in both transfected COS7 cells and heart isografts. Animals transfected with vIL-10 showed prolongation of graft survival (19.6 vs. 12 days, P<0.001) when compared to beta-gal transfected controls. Animals treated with a single low dose injection of CsA showed no significant prolongation of graft survival compared to controls (11.7 vs. 10.5 days). Animals treated with both vIL-10 and CsA demonstrated a synergistic prolongation of allograft survival compared with controls and with animals treated with CsA or vIL-10 treatment alone (36.7 days vs. 11.7, P<0.001 or 36.7 vs.19.6, P<0.001, respectively). Histological study showed that allografts from untreated controls exhibited extensive AR with loss of graft architecture by day 7 posttransplant while those from the vIL-10 group showed less AR. The best pathological scores were seen in vIL-10 + CsA-treated animals. CONCLUSIONS: 1) Delivering Ad-vIL-10 into donor hearts by intracoronary perfusion results in overexpression of vIL-10 and significantly prolongs cardiac allograft survival in a highly histoincompatible rat model. 2) Subtherapeutic doses of CsA do not prolong allograft survival, but act synergistically with vIL-10 to significantly prolong graft survival beyond that achieved with either agent alone.
Adenoviridae↗
Comparative evaluation of surgical stress of laparoscopic and open surgeries for colorectal carcinoma.
PURPOSE: To objectively evaluate the benefits of laparoscopic procedures for colorectal carcinoma, a prospective study to measure the stress response to laparoscopic surgery (n = 15) compared with open surgery (n = 12) was undertaken. In addition, to compare the various parameters relevant to surgical stress, the major surgery group (transthoracic esophagectomy for esophageal carcinoma, n = 4; and left upper abdominal evisceration for gastric carcinoma, n = 3) was assigned. METHODS: Peripheral blood samples were obtained to measure serum interleukin-6, C-reactive protein, peripheral leukocytes, and lymphocyte counts. Additionally, the level of lymphocyte apoptosis was quantified using flow cytometry. RESULTS: The interleukin-6 and C-reactive protein levels were significantly greater in the open group than in the laparoscopy group one day (P < 0.05) and two days (P < 0.05) after surgery, respectively. In the laparoscopy group, lymphocyte counts were significantly higher than in the open group two days after surgery. The laparoscopy and open groups did not differ significantly in their lymphocyte apoptotic index. In the major surgery group, the apoptotic index was significantly higher than in either the laparoscopy group or the open group in the early postoperative period. CONCLUSION: Changes in the various parameters pertinent to surgical stress evaluated in this study suggest that laparoscopic surgery for colorectal carcinoma leads to less postoperative stress than conventional open surgery.
Aged↗
Identification of a new point mutation in the human xanthine dehydrogenase gene responsible for a case of classical type I xanthinuria.
A 60-year-old Japanese man was diagnosed as having hypouricemia at an annual health check-up. The routine laboratory data was not remarkable except that the patient's hypouricemia and plasma levels of xanthine and hypoxanthine were much higher than those of normal subjects. Furthermore, the patient's daily urinary excretion of xanthine and hypoxanthine was markedly increased compared with reference values. The xanthine dehyrogenase activity of the duodenal mucosa was below the limits of detection. Nevertheless, allopurinol was metabolized to oxypurinol in vivo. Based on these findings, a subtype of classical xanthinuria (type I) was diagnosed. The xanthine dehyrogenase protein was detected by Western blotting analysis. Sequencing of the cDNA of the xanthine dehyrogenase obtained from the duodenal mucosa revealed that a point mutation of C to T had occurred in nucleotide 445. This changed codon 149 from CGC (Arg) to TGC (Cys), a finding that has not been previously reported in patients with classical xanthinuria type I.
Allopurinol↗
Regression of lymph node metastases by immunotherapy using autologous breast tumor-lysate pulsed dendritic cells: report of a case.
A 50-year-old woman was diagnosed as having stage IV breast cancer with bilateral supraclavicular lymph node metastasis resistant to CAF therapy. She received immunotherapy using autologous tumor lysate-pulsed dendritic cells (DCs). Four cycles of DC injection into the right supraclavicular lymph nodes resulted in regression of bilateral supraclavicular lymphogenous metastasis. Histological studies revealed an accumulation of CD45+ T lymphcytes in the regressive lymph nodes. This case suggests that immunotherapy with DCs may be a safe and promising approach for the treatment of advanced breast cancer.
Adjuvants, Immunologic↗
Pathogenesis of acne.
Acne vulgaris is a skin disorder of the sebaceous follicles that commonly occurs in adolescence and in young adulthood. The major pathogenic factors involved are hyperkeratinization, obstruction of sebaceous follicles resulting from abnormal keratinization of the infundibular epithelium, stimulation of sebaceous gland secretion by androgens, and microbial colonization of pilosebaceous units by Propionibacterium acnes, which promotes perifollicular inflammation. The clinical presentation of acne can range from a mild comedonal form to severe inflammatory cystic acne of the face, chest, and back. At the ultrastructural level, follicular keratinocytes in comedones can be seen to possess increased numbers of desmosomes and tonofilaments, which result in ductal hypercornification. The increased activity of sebaceous glands elicited by androgen causes proliferation of P. acnes, an anaerobe present within the retained sebum in the pilosebaceous ducts. The organism possesses a ribosome-rich cytoplasm and a relatively thick cell wall, and produces several biologically active mediators that may contribute to inflammation, for instance, by promoting leukocyte migration and follicular rupture. In inflamed lesions, numerous neutrophils and macrophages infiltrate around hair follicles and sometimes phagocytose P. acnes. To examine the participation of neurogenic factors in the pathogenesis of acne, we quantitatively assessed the effects of neuropeptides on the morphology of sebaceous glands in vitro using electron microscopy. Substance P, which can be elicited by stress, promoted the development of cytoplasmic organelles in sebaceous cells, stimulated sebaceous germinative cells, and induced significant increases in the area of sebaceous glands. It also increased the size of individual sebaceous cells and the number of sebum vacuoles for each differentiated sebaceous cell, all of which suggests that substance P promotes both the proliferation and the differentiation of sebaceous glands. In this review, we introduce the general concept of pathogenic factors involved in acne, including typical electron microscopic findings and recent evidence of stress-induced exacerbation of acne from a neurological point of view. An improved understanding of the pathogenesis of acne should lead to a rational therapy to successfully treat this skin disease.
Acne Vulgaris↗
Ultrastructural characteristics of trichilemmal cysts: report of two cases.
Two trichilemmal cysts (TC) on the scalps of two Japanese women were examined at the electron microscopic level. The ultrastructural characteristics of the TC included an abrupt transition from nucleate to anucleate cells, a few oval, small, keratohyaline granules mixed with increasing numbers of tonofibrils from the peripheral layer towards the center, spherical particles with lipid droplets, desmosomal structures in keratinized cells, and the interdigitation of keratin in the uppermost keratinizing cells. The keratinization pattern of the TC was unique in that typical soft or hard keratinization processes did not occur. Trichilemmal keratinization is observed in the trichilemmal sacs that surround the lower ends of catagen or telogen hairs, as well as in the outer root sheaths in the follicular isthmus of anagen hairs. Comparison of the ultrastructure of these two known types of trichilemmal keratinization with the keratinization pattern of the TC in our patients indicates that TC may differentiate into, or originate from, the proliferation of the outer root sheath in the follicular isthmus of anagen hairs.
Adult↗
Update of daily intake of PCDDs, PCDFs, and dioxin-like PCBs from food in Japan.
Total diet study (TDS) samples of 14 food groups from 16 locations in Japan, collected in 1999 and 2000, were analyzed for polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (dioxin-like PCBs) to estimate the update of daily intake of these contaminants from food. The mean daily intake of toxic equivalency (TEQ) for an adult weighing 50 kg, calculated at non-detected isomer concentrations equal to zero (ND = 0), was estimated to be 2.25 pg TEQ/kg b.w./day. When non-detected isomer concentrations are assumed to be equal to half of the limits of detection (ND = 1/2 LOD), the mean daily intake was estimated to be 3.22 pg TEQ/kg b.w./day. These values were below the tolerable daily intake (TDI) of 4 pg TEQ/kg b.w. for PCDD/Fs and dioxin-like PCBs set in Japan. In both the estimates, the mean daily intakes were highest from fish and shellfish (76.9% at ND = 0 and 53.9% at ND = 1/2 LOD of the total TEQs), followed by those from meat and eggs (15.5% at ND = 0 and 11.7% at ND = 1/2 LOD of the total TEQs). Congener specific data revealed that these total TEQ levels were dominated by 1,2,3,7,8-PeCDD, 2,3,4,7,8-PeCDF and 3,3',4,4',5-PeCB in each case (71.7% at ND = 0 and 63.1% at ND = 1/2 LOD of the total TEQs). The dioxin-like PCBs (non-ortho and mono-ortho PCBs) accounted for about 50% of these total TEQs. These data will be very useful in the risk assessment of PCDD/Fs and dioxin-like PCBs from food in Japan.
Adult↗
Ultrastructural characterization of microvasculature in photoaging.
The cutaneous microvasculature was examined by electron microscopy in order to compare its characteristics in photodamaged preauricular skin and in sun-protected postauricular sites of 15 Japanese women aged 58-81 years. The characteristic ultrastructural features of the microvasculature in photodamaged skin compared with those in sun-protected skin included dilated vessels embedded in elastin which depressed endothelial cells, vessels surrounded by a thick amorphous material composed of multiple laminations of a basement membrane-like material, and activated endothelial cells which had increased numbers of cytoplasmic organelles and pinocytotic vesicles. A novel finding of this study in photodamaged vessels was an increased formation of new vessels (angiogenesis) via two distinct pathways. In severe elastosis, activated endothelial cells with densely packed intracytoplasmic microfilaments extended large pseudopods into the elastotic material. In contrast, isolated mesenchymal cells, which possessed immature Weibel-Palade bodies, were scattered around pre-existing vessels within the Grenz zone. In some cases, many mesenchymal cells with electron-lucent cytoplasms aggregated and interconnected by cytoplasmic processes, which was followed by the formation of vascular structures. These results suggest that there are significant ultrastructural differences in vessels between photoaged and intrinsically aged facial skin and that the photodamaged microvascular system is characterized by the co-existence of regressive changes and angiogenesis.
Aged↗