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1.
Artigo em Inglês | MEDLINE | ID: mdl-35571608

RESUMO

We investigate the effects of lending relationships between banks and borrowers on loan supply during the economic shock caused by the coronavirus (COVID-19) pandemic. Using bank-firm matched data for Japan to control for several firm- and bank-specific unobserved effects, we show that banks with close relationships with borrowing firms offer more bank loans to these firms during the COVID-19 shock. This effect is larger if the borrowing firms' cash flows decrease substantially during the shock. These results imply that banks acted as liquidity providers for borrowers during sudden and unpredictable shocks if their relationships with firms were close.

2.
Med Mol Morphol ; 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35486188

RESUMO

Female pattern hair loss (FPHL), a type of hair disease common in pre- and postmenopausal women, is characterized by thinning of hair to O-type, mainly at the crown. Although a mouse model of this disease has recently been established, its details are still unknown, and thus, warrants further analysis. In this study, 3 week-old and 7- to 8 week-old C57BL/6 female mice were divided into two groups: one group underwent ovariectomy (OVX), while the other underwent sham surgery. In the 3 week-old mice, the dorsal skin was collected at seven weeks of age, while in the 7- to 8 week-old mice, it was collected at 12 and 24 weeks of age. In the former group, both the pore size of the hair follicles (HFs) and diameter of the hair shaft of telogen HFs decreased upon OVX; while in the latter group, these factors increased significantly. Notably, the thickness of the dermis and subcutis increased significantly in the OVX group. It needs to be further elucidated whether OVX mouse could serve as an ideal mouse model for FPHL, but our results upon evaluation of skin thickness indicate that it could be used to establish a novel treatment for non-hair-related diseases, such as post-menopause-related skin condition.

4.
Dermatol Ther (Heidelb) ; 12(3): 615-629, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35084694

RESUMO

INTRODUCTION: Cutaneous T-cell lymphoma (CTCL) is a chronic condition with low malignancy. The combined use of therapeutic agents and photo(chemo)therapy is widely applied for the treatment of CTCL. The efficacy and safety of bexarotene and photo(chemo)therapy combination therapy were previously confirmed in Japanese patients with CTCL. The efficacy and safety of the bexarotene and photo(chemo)therapy combination therapy was compared with bexarotene monotherapy in Japanese patients with CTCL. METHODS: This was a randomized, open-label, two-parallel-group, active-control specified clinical study in Japanese patients diagnosed with CTCL carried out over 8 weeks with a study extension conducted at two institutions. This study was registered in Japan Registry of Clinical Trials (jRCTs041180094). RESULTS: In the combination therapy group, 22 subjects received oral bexarotene (300 mg/m2 body surface area) once daily, followed by bath-psoralen and ultraviolet (UV) A or narrowband UVB. In the monotherapy group, 24 subjects received oral bexarotene (300 mg/m2) once daily. The efficacy analysis using the modified Severity-Weighted Assessment Tool, which included 39 patients, showed a response rate of 81.0% (17/21) in the combination therapy group and 83.3% (15/18) in the monotherapy group. No statistically significant difference was detected between groups. In the combination therapy group, four subjects showed a complete clinical response or complete response, and subjects with a partial response exhibited a high rate of skin lesion resolution, significantly better than in the monotherapy group. In the safety analysis, which included 46 treated subjects (22 in the combination therapy group and 24 in the monotherapy group), no adverse events or adverse drug reactions were reported in either group. CONCLUSION: Both bexarotene and photo(chemo)therapy combination therapy and bexarotene monotherapy were therapeutically effective in Japanese patients with CTCL and well tolerated. Combination therapy led to a higher skin lesion resolution rate and greater therapeutic effects compared with monotherapy. TRIAL REGISTRATION: jRCTs041180094.


This study evaluated the efficacy and safety of bexarotene monotherapy compared with bexarotene and photo(chemo)therapy combination therapy in Japanese patients with cutaneous T-cell lymphoma (CTCL). The study was a randomized, open-label, two-parallel-group, active-control specified clinical study in patients diagnosed with CTCL performed over an 8-week period with a study extension conducted in two institutions. In the combination therapy group, bexarotene (300 mg/m2 body surface area) was administered orally once daily to 22 subjects, followed by treatment with bath-psoralen and ultraviolet A (bath-PUVA) or narrowband UVB. In the bexarotene monotherapy group, bexarotene (300 mg/m2) was administered orally once daily to 24 subjects. Efficacy was assessed using the modified Severity-Weighted Assessment Tool. Among the 39 subjects analyzed for treatment efficacy, the response rate of the combination therapy group was 81.0% (17/21) and that of the monotherapy group was 83.3% (15/18). Differences between the two treatment groups were not statistically significant. Of the 21 subjects in the combination therapy group, 4 had a complete clinical response or complete response, and those with a partial response showed a higher skin lesion resolution rate than in the monotherapy group. The safety analysis revealed no reports of adverse events or adverse drug reactions among the 46 treated subjects (combination therapy group = 22; monotherapy group = 24). Thus, both bexarotene and photo(chemo)therapy combination therapy and bexarotene monotherapy were therapeutically effective and well tolerated in Japanese patients with CTCL. Patients receiving the combined therapy, however, showed a higher rate of skin lesion resolution.

5.
CEN Case Rep ; 2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35075622

RESUMO

As mRNA COVID-19 vaccines have become widely available, cases of new-onset glomerular disease after receiving COVID-19 vaccination have been reported. Here, we present a case of kidney biopsy-proven new-onset IgA vasculitis after receiving the mRNA-1273 (Moderna) COVID-19 vaccination. A 47-year-old man with a 10-year medical history of hypertension and hyperuricemia visited our hospital 19 days after receiving an initial mRNA-1273 COVID-19 vaccine injection for purpuric eruption on the legs and dorsal regions of the feet. Although the eruptions spontaneously improved within 5 days, they developed again at 15 days after the second injection. A histopathological examination of skin biopsy specimens was reminiscent of leukocytoclastic vasculitis, though direct immunofluorescence did not indicate IgA deposition within small vessel walls. Urinalysis indicated severe proteinuria (3 +) and occult blood (3 +). Thus, a kidney biopsy was performed and light microscopy revealed mild mesangial expansion, hypercellularity, and endocapillary hypercellularity, with cellular and fibrocellular crescents observed in three and one, respectively, of a total of 15 glomeruli. Immunofluorescence also showed diffuse granular mesangial staining (3 +) for IgA. Histopathological features were consistent with IgA vasculitis. Intravenous methylprednisolone at 1000 mg for 3 days was initiated, followed by oral prednisolone (0.6 mg/kg/day). Over the following 2-week period, serum creatinine level improved from 1.24 to 1.06 mg/dL and proteinuria decreased from 2.98 to 0.36 g/g Cr, though occult blood persisted. Findings in the present case indicate that new-onset IgA vasculitis after receiving mRNA-1273 COVID-19 vaccine can be treated with corticosteroid therapy.

10.
Endocr J ; 69(1): 101-105, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-34433736

RESUMO

Bexarotene-induced central hypothyroidism (CH), for which levothyroxine (LT4) replacement is recommended, has been shown to be caused by pituitary but not hypothalamic disorder experimentally, though the underlying mechanism in humans remains unclear. Here, the pathophysiology of bexarotene-induced CH was examined using a TRH stimulation test in cutaneous T-cell lymphoma (CTCL) patients. In this retrospective longitudinal observational study, serum TSH and free T4 (F-T4) levels were measured in 10 euthyroid patients with CTCL during 24 weeks of bexarotene treatment. TRH stimulation testing was performed following CH diagnosis, with LT4 replacement dosage adjusted to maintain F-T4 at the pre-treatment level. After one week of bexarotene administration, all 10 patients developed CH, based on combined findings of low or low-normal F-T4 with low or normal TSH levels. TSH peak response after a stimulation test at one week was reached at 30 minutes. However, that was <4 µIU/mL in all patients, indicating a blunted though not exaggerated and delayed TSH response. In eight who continued bexarotene for 24 weeks, median LT4 replacement dosage was 125 (range, 75-150) µg/day. TSH level at 30 as well as 15, 60, 90, and 120 minutes after TRH stimulation was significantly correlated with LT4 replacement dosage (ρ = -0.913, p = 0.002), whereas TSH and F-T4 basal levels at one week were not. These results suggest that pituitary hypothyroidism is responsible for bexarotene-induced CH, while TSH levels after TRH stimulation precisely reflect residual pituitary-thyroid function in patients receiving bexarotene.


Assuntos
Hipotireoidismo , Linfoma Cutâneo de Células T , Neoplasias Cutâneas , Bexaroteno , Humanos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/diagnóstico , Linfoma Cutâneo de Células T/complicações , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Cutâneas/complicações , Tireotropina , Hormônio Liberador de Tireotropina , Tiroxina , Tri-Iodotironina
12.
J Invest Dermatol ; 2021 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-34911646

RESUMO

Recently, accumulating evidence showed that collagen XVII, a transmembrane protein in hemidesmosomes, exhibits essential roles not only in cellular attachment but also in motility and development. Kosumi et al. determined that collagen XVII is stabilized by activated Wnt/ß-catenin signaling. This novel mechanism of collagen XVII stabilization through the Wnt/ß-catenin pathway may be involved in physiological or pathological events in the skin.

13.
Gan To Kagaku Ryoho ; 48(12): 1511-1513, 2021 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-34911921

RESUMO

We report the case of an 84-year-old man who developed primary diffuse large B-cell lymphoma of the testes during the course of mycosis fungoides treated with topical medication. He was referred to our hospital due to bilateral testicular masses, and bilateral high orchiectomy was performed. A pathological diagnosis of diffuse large B-cell lymphoma was made after an examination of the surgical specimen. Rituximab-combined miniCHOP chemotherapy with prophylactic intrathecal injection resulted in complete remission without recurrence 1 year after diagnosis. People with mycosis fungoides are known to be at a higher risk of secondary malignancies than healthy individuals; hence, a pathological examination is important to confirm the diagnosis.


Assuntos
Linfoma Difuso de Grandes Células B , Micose Fungoide , Neoplasias Cutâneas , Idoso de 80 Anos ou mais , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Micose Fungoide/tratamento farmacológico , Rituximab , Neoplasias Cutâneas/tratamento farmacológico , Testículo
14.
Front Immunol ; 12: 771766, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899722

RESUMO

Background: Recently, we published an article retrospectively summarizing the results in 55 anti-laminin 332 (LM332)-type mucous membrane pemphigoid (MMP) cases examined at Kurume University, which were diagnosed by strict inclusion criteria, including positive reactivity in direct immunofluorescence and absence of antibodies to non-LM332 autoantigens. However, indirect immunofluorescence using 1M-NaCl-split normal human skin (ssIIF) is also valuable for diagnosis of anti-LM332-type MMP. Methods: In this second study, we selected 133 anti-LM332-type MMP cases, which were diagnosed by our different inclusion criteria: (i) immunoglobulin G (IgG) deposition to basement membrane zone (BMZ) by direct immunofluorescence or IgG reactivity with dermal side of split skin by ssIIF, (ii) positivity for at least one of the three subunits of LM332 by immunoblotting of purified human LM332, and (iii) the presence of mucosal lesions. Clinical, histopathological, and immunological findings were summarized and analyzed statistically. Although these cases included the 55 previous cases, the more detailed study for larger scale of patients was conducted for further characterization. Results: Clinically, among the 133 patients, 89% and 43% patients had oral and ocular mucosal lesions, respectively, 71% had cutaneous lesions, and 17% had associated malignancies. Histopathologically, 93% patients showed subepidermal blisters. The sensitivities of ssIIF and direct immunofluorescence are similar but are significantly higher than indirect immunofluorescence using non-split human skin (both p < 0.001). In immunoblotting of purified LM332, patient IgG antibodies most frequently reacted with LMγ2 subunit (58%), followed by LMα3 (49%) and LMß3 (36%). Thirty-four percent patients recognized additional non-LM332 autoantigens. Statistical analysis revealed that autoantibodies against non-LM332 autoantigens might stimulate the production of anti-LMγ2 antibodies. Conclusions: This retrospective study further characterized in more detail the clinical and immunological features of 133 cases of anti-LM332-type MMP, in which the new diagnostic criteria without positive direct immunofluorescence reactivity were useful for the diagnosis. Higher frequency with anti-LMγ2 antibodies suggested more significant pathogenic role of this subunit. Additional autoantibodies to non-LM332 autoantigens detected in one-third of the patients may contribute to complexity in anti-LM332-type MMP, including the induction of anti-LMγ2 antibodies.


Assuntos
Autoanticorpos/sangue , Autoantígenos/imunologia , Moléculas de Adesão Celular/imunologia , Imunoglobulina G/sangue , Penfigoide Mucomembranoso Benigno/diagnóstico , Idoso , Feminino , Humanos , Imunoglobulina A/sangue , Masculino , Pessoa de Meia-Idade , Penfigoide Mucomembranoso Benigno/sangue , Penfigoide Mucomembranoso Benigno/imunologia , Universidades
15.
J Dermatol Sci ; 104(2): 76-82, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34772583

RESUMO

Dysregulated skin immunity is a hallmark of many skin diseases such as atopic dermatitis, autoimmune blistering diseases, and interface dermatitis. Current treatment options for the inflammatory skin diseases are limited and sometimes ineffective, therefore further understanding of pathomechanisms in the inflammatory skin conditions is necessary to develop new therapeutic alternatives. Recent studies suggest that the serine protease, granzyme B, is a key mediator in multiple inflammatory skin diseases, implying that strategies targeting granzyme B may be an attractive treatment option for such diseases. Specifically, granzyme B exhibits not only an intracellular apoptotic function but also extracellular proteolytic roles in inflammatory skin diseases including infectious diseases, pemphigoid diseases, atopic dermatitis, alopecia areata, and interface dermatitis. In this review, we summarize the current understanding with respect to the functions of granzyme B in the pathomechanism of various inflammatory skin diseases and evaluate the possibility of therapeutics targeting granzyme B.


Assuntos
Granzimas/metabolismo , Dermatopatias/metabolismo , Alopecia em Áreas/metabolismo , Animais , Dermatite Atópica/metabolismo , Granzimas/imunologia , Humanos , Dermatopatias Infecciosas/metabolismo , Dermatopatias Vesiculobolhosas/metabolismo
16.
Int J Mol Sci ; 22(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34638746

RESUMO

A 308 nm monochromatic excimer light (MEL) is widely used to treat patients with vitiligo. However, dose optimization still needs to be clarified. This study aimed to obtain objective evidence regarding various doses of MEL irradiation, induced cell level changes in vitro, and skin level alterations in vivo. Cultured human keratinocytes were irradiated with MEL using various doses. After irradiation at low doses, stem cell factor, endothelin-1, and glycoprotein nonmetastatic melanoma protein B, factors that activate and protect melanocytes, were found to be significantly elevated in keratinocytes. After irradiation using medium and high doses, inflammatory cytokines were induced. The amount of ATP released and the level of inflammasome activation, which are known to be related to interleukin-1ß activation, were also increased. The back skin of guinea pigs and mice were irradiated with MEL at varying doses. After irradiation, an increase of epidermal melanin and epidermal melanocytes was confirmed, using the minimal erythemal dose or less. In rhododendrol-induced leukoderma guinea pigs, a much lower dose of MEL irradiation was effective, when compared with the effective dose for control guinea pigs. Our results suggest that a lower irradiation dose of MEL might be sufficient and more suitable for repigmentation in vitiligo treatment.


Assuntos
Queratinócitos/metabolismo , Melanócitos/metabolismo , Pigmentação da Pele/efeitos da radiação , Terapia Ultravioleta , Vitiligo , Animais , Linhagem Celular , Feminino , Cobaias , Humanos , Camundongos , Vitiligo/metabolismo , Vitiligo/radioterapia
17.
Int J Mol Sci ; 22(19)2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34639139

RESUMO

Oxygen in the atmosphere is a crucial component for life-sustaining aerobic respiration in humans. Approximately 95% of oxygen is consumed as energy and ultimately becomes water; however, the remaining 5% produces metabolites called activated oxygen or reactive oxygen species (ROS), which are extremely reactive. Skin, the largest organ in the human body, is exposed to air pollutants, including diesel exhaust fumes, ultraviolet rays, food, xenobiotics, drugs, and cosmetics, which promote the production of ROS. ROS exacerbate skin aging and inflammation, but also function as regulators of homeostasis in the human body, including epidermal keratinocyte proliferation. Although ROS have been implicated in various skin diseases, the underlying mechanisms have not yet been elucidated. Current knowledge on ROS-related and oxidative stress-related skin diseases from basic research to clinical treatment strategies are discussed herein. This information may be applied to the future treatment of skin diseases through the individual targeting of the ROS generated in each case via their inhibition, capture, or regulation.


Assuntos
Radicais Livres/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Dermatopatias/patologia , Animais , Humanos , Dermatopatias/metabolismo
18.
Int J Mol Sci ; 22(19)2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34639184

RESUMO

Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type I transmembrane glycoprotein that plays an important role in cancer metastasis and osteoblast differentiation. In the skin epidermis, GPNMB is mainly expressed in melanocytes and plays a critical role in melanosome formation. In our previous study, GPNMB was also found to be expressed in skin epidermal keratinocytes. In addition, decreased GPNMB expression was observed in the epidermis of lesional skin of patients with vitiligo. However, the exact role of keratinocyte-derived GPNMB and its effect on vitiligo is still unknown. In this study, we demonstrated that GPNMB expression was also decreased in rhododendrol-induced leukoderma, as seen in vitiligo. The extracellular soluble form of GPNMB (sGPNMB) was found to protect melanocytes from cytotoxicity and the impairment of melanogenesis induced by oxidative stress. Furthermore, the effect of rGPNMB was not altered by the knockdown of CD44, which is a well-known receptor of GPNMB, but accompanied by the suppressed phosphorylation of AKT but not ERK, p38, or JNK. In addition, we found that oxidative stress decreased both transcriptional GPNMB expression and sGPNMB protein expression in human keratinocytes. Our results suggest that GPNMB might provide novel insights into the mechanisms related to the pathogenesis of vitiligo and leukoderma.


Assuntos
Queratinócitos/efeitos dos fármacos , Melaninas/metabolismo , Melanócitos/efeitos dos fármacos , Melanoma/tratamento farmacológico , Glicoproteínas de Membrana/metabolismo , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Melanócitos/metabolismo , Melanócitos/patologia , Melanoma/metabolismo , Melanoma/patologia , Glicoproteínas de Membrana/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo
20.
Photodiagnosis Photodyn Ther ; 36: 102484, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34403825

RESUMO

BACKGROUND: Drug-resistant bacterial infections are a global problem. Novel treatment methods that simultaneously control infection and promote wound healing without leading to new resistant bacteria are needed. Photodynamic therapy (PDT) is a useful antibiotic-free treatment approach. Our previous studies have shown that PDT for skin ulcers infected with methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) can achieve infection control and promoting wound healing in vitro and in vivo murine model. Here, we investigated the safety and effectiveness of PDT with 5-aminolevulinic acid (ALA-PDT) for human skin ulcers infected with MRSA and PA. METHODS: ALA-PDT with macrogol ointment containing 0.5% ALA-HCl and 0.005% EDTA-2Na (wavelength 410 nm, 10 J/cm2) was performed on consecutive days in patients aged ≥20 years who had skin ulcers infected with MRSA and PA. RESULTS: Six of our seven patients showed a clear tendency for ulcer area reduction to ≤60% of that measured at baseline. ALA-PDT was judged to be completely safe in all patients; only one patient had an increase in bacterial count. CONCLUSIONS: ALA-PDT is safe and effective for MRSA and PA infected skin ulcers to control and heal wound.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Fotoquimioterapia , Úlcera Cutânea , Animais , Humanos , Camundongos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Pseudomonas aeruginosa , Úlcera Cutânea/tratamento farmacológico
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