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2.
Development ; 146(8)2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30918052

RESUMO

The polysaccharide glycogen is an evolutionarily conserved storage form of glucose. However, the physiological significance of glycogen metabolism on homeostatic control throughout the animal life cycle remains incomplete. Here, we describe Drosophila mutants that have defective glycogen metabolism. Null mutants of glycogen synthase (GlyS) and glycogen phosphorylase (GlyP) displayed growth defects and larval lethality, indicating that glycogen plays a crucial role in larval development. Unexpectedly, however, a certain population of larvae developed into adults with normal morphology. Semi-lethality in glycogen mutants during the larval period can be attributed to the presence of circulating sugar trehalose. Homozygous glycogen mutants produced offspring, indicating that glycogen stored in oocytes is dispensable for embryogenesis. GlyS and GlyP mutants showed distinct metabolic defects in the levels of circulating sugars and triglycerides in a life stage-specific manner. In adults, glycogen as an energy reserve is not crucial for physical fitness and lifespan under nourished conditions, but glycogen becomes important under energy stress conditions. This study provides a fundamental understanding of the stage-specific requirements for glycogen metabolism in the fruit fly.


Assuntos
Proteínas de Drosophila/metabolismo , Glicogênio Fosforilase/metabolismo , Glicogênio Sintase/metabolismo , Animais , Drosophila , Proteínas de Drosophila/genética , Feminino , Glicogênio/metabolismo , Glicogênio Fosforilase/genética , Glicogênio Sintase/genética , Masculino , Trealose/metabolismo
4.
Development ; 145(6)2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29467247

RESUMO

Adapting to changes in food availability is a central challenge for survival. Glucose is an important resource for energy production, and therefore many organisms synthesize and retain sugar storage molecules. In insects, glucose is stored in two different forms: the disaccharide trehalose and the branched polymer glycogen. Glycogen is synthesized and stored in several tissues, including in muscle and the fat body. Despite the major role of the fat body as a center for energy metabolism, the importance of its glycogen content remains unclear. Here, we show that glycogen metabolism is regulated in a tissue-specific manner under starvation conditions in the fruit fly Drosophila The mobilization of fat body glycogen in larvae is independent of Adipokinetic hormone (Akh, the glucagon homolog) but is regulated by sugar availability in a tissue-autonomous manner. Fat body glycogen plays a crucial role in the maintenance of circulating sugars, including trehalose, under fasting conditions. These results demonstrate the importance of fat body glycogen as a metabolic safeguard in Drosophila.


Assuntos
Drosophila/metabolismo , Corpo Adiposo/metabolismo , Glicogênio/metabolismo , Açúcares/metabolismo , Adaptação Fisiológica , Animais , Proteínas de Drosophila/metabolismo , Homeostase/fisiologia , Imuno-Histoquímica , Larva/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Inanição/metabolismo
5.
Prev Med Rep ; 7: 187-192, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28706778

RESUMO

Rates of obesity and type 2 diabetes in Kentucky's Cumberland Valley region are among the highest in the United States and limited access to healthy food contributes to these epidemics. The aim of Healthy2Go (H2G), a country store transformation project launched by Spread the Health Appalachia (STHA), was to improve awareness and availability of healthy options in small, rural stores. Ten country stores participated in H2G and received training and technical assistance to increase availability and awareness of healthy foods. Stores made inventory changes; installed point-of-purchase educational and in-store marketing materials directing shoppers to healthier options; provided nutrition education such as healthy recipes; and altered the display and location of healthy items. To measure changes within stores and the potential impact on resident eating and purchasing habits, STHA used four instruments: a modified version of the Nutrition Environs Measures Survey - Corner Stores at baseline and follow-up, a bimonthly store inventory assessment, a final store owner survey, and a Community Nutrition Survey at baseline (n = 287) and follow-up (n = 281). The stores in the H2G program (n = 10) had a 40% increase in stocking fresh produce, a 20% increase in produce variety, and trends towards increasing healthy inventory. During the same period, surveyed residents reported a statistically significant increase in the frequency of healthy food consumption. Small store transformation programs can improve availability of and access to healthy food in rural settings and influence local purchasing patterns.

6.
Sci Rep ; 6: 30582, 2016 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-27469628

RESUMO

In insects, trehalose serves as the main sugar component of haemolymph. Trehalose is also recognized as a mediator of desiccation survival due to its proposed ability to stabilize membranes and proteins. Although the physiological role of trehalose in insects has been documented for decades, genetic evidence to support the importance of trehalose metabolism remains incomplete. We here show on the basis of genetic and biochemical evidence that the trehalose synthesis enzyme Tps1 is solely responsible for the de novo synthesis of trehalose in Drosophila. Conversely, a lack of the gene for the trehalose hydrolyzing enzyme Treh causes an accumulation of trehalose that is lethal during the pupal period, as is observed with Tps1 mutants. Lack of either Tps1 or Treh results in a significant reduction in circulating glucose, suggesting that the maintenance of glucose levels requires a continuous turnover of trehalose. Furthermore, changes in trehalose levels are positively correlated with the haemolymph water volume. In addition, both Tps1 and Treh mutant larvae exhibit a high lethality after desiccation stress. These results demonstrate that the regulation of trehalose metabolism is essential for normal development, body water homeostasis, and desiccation tolerance in Drosophila.


Assuntos
Proteínas de Drosophila/metabolismo , Glucose/genética , Mutação , Trealose/metabolismo , Equilíbrio Hidroeletrolítico/fisiologia , Animais , Proteínas de Drosophila/genética , Drosophila melanogaster , Glucose/metabolismo , Trealose/genética
9.
Australas J Dermatol ; 53(3): e51-3, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22881473

RESUMO

We report a case of cutaneous angiosarcoma occurring on the leg of a 97-year-old Japanese woman. Considering the patient's age and general condition, she was treated with electron beam irradiation, which led to the almost complete disappearance of the tumour. Because cutaneous angiosarcoma is an aggressive tumour with a high propensity for local recurrence and distant metastases, therapy preferably involves a multimodal approach. However, monotherapy with radiation may be effective in some cases of cutaneous angiosarcoma.


Assuntos
Hemangiossarcoma/radioterapia , Neoplasias Cutâneas/radioterapia , Idoso de 80 Anos ou mais , Queimaduras/complicações , Feminino , Hemangiossarcoma/etiologia , Hemangiossarcoma/patologia , Humanos , Perna (Membro)/patologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia
10.
Case Rep Dermatol ; 4(1): 76-9, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22548041

RESUMO

An 83-year-old Japanese man presented with a 2-month history of symptomatic nodules on the left hand. He was not in an immunocompromised condition and reported no causal events. A biopsy specimen demonstrated granulomatous tissue with mixed cell infiltration consisting of neutrophils, histiocytes, lymphocytes, and multinuclear giant cells. No bacillus was detected by PAS, acid-fast stain, immunofluorescent stain or polymerase chain reaction analysis. The isolate was found to be a rapidly growing mycobacterium after 4 weeks of incubation at 25°C on an Ogawa egg slant. Mycobacterium peregrinum was isolated by DNA-DNA hybridization analysis, 16S rRNA gene sequence, and by its production of 3-day arylsulfatase. The patient received 200 mg oral minocycline for 28 weeks. The lesion disappeared after 10 weeks of this treatment.

12.
Jpn J Clin Oncol ; 38(12): 849-56, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18945721

RESUMO

BACKGROUND: Cationic liposomes containing the human interferon beta (HuIFNbeta) gene (IAB-1) was used for the clinical trial for glioma patients. HuIFNbeta gene therapy showed much higher anti-tumor activity compared with the administration of HuIFNbeta protein for melanoma. These results suggest that HuIFNbeta gene therapy is an attractive strategy for the treatment of melanoma. METHODS: Stage IV or III melanoma patients with cutaneous or subcutaneous metastatic lesions were enrolled in this pilot study. IAB-1 was dissolved by sterile PBS at a concentration of 30 microg DNA/ml and was injected into cutaneous or subcutaneous metastatic nodules three times a week for 2 weeks and the effect on the injected and non-injected metastatic lesions was evaluated. RESULTS: Clinical responses were as follows (five patients): mixed response (MR) and no change in each one patient, and progressive disease in three patients. In the MR patient, the IAB-1 injected lesion disappeared clinically and histopathologically and one-half of IAB-1 non-injected skin metastases were transiently inflamed and mostly regressed. In the responded non-injected lesions of this patient, histopathologically, infiltration of CD4 positive T cells was observed around the melanoma cells in the dermis, which expressed the HLA-Class II antigen. Adverse events due to this gene therapy were not recognized in any of the patients. CONCLUSIONS: The efficacy of this gene therapy was generally insufficient; however, some immunological responses were recognized in one patient. No adverse events were observed. HuIFNbeta gene therapy could be an attractive strategy for treatment of a variety of malignancies, including melanoma, though some modifications should be required.


Assuntos
Antineoplásicos/administração & dosagem , Terapia Genética/métodos , Interferon beta/administração & dosagem , Interferon beta/genética , Melanoma/terapia , Neoplasias Cutâneas/terapia , Transdução Genética , Adulto , Idoso , Cátions , Feminino , Humanos , Lipossomos , Masculino , Melanoma/secundário , Pessoa de Meia-Idade , Projetos Piloto , Plasmídeos , Neoplasias Cutâneas/patologia , Transdução Genética/métodos , Resultado do Tratamento
13.
Arch Dermatol Res ; 300(6): 297-301, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18324409

RESUMO

We investigated the anti-tumor effect of human interferon-beta (HuIFN-beta) against malignant melanoma. In vitro study revealed that HuIFN-beta not only inhibited proliferation of melanoma cells (seven cell lines: MM-AN, MM-BP, MM-LH, MM-RU, PM-WK, RPM-EP, RPM-MC) but also induced apoptosis in a dose dependent fashion, though the sensitivity to HuIFN-beta was different among cell lines. In addition, we administered HuIFN-beta into cutaneous metastatic lesions of melanoma and evaluated clinical and histopathological effects. Although the size of the metastatic cutaneous lesion did not change by the intralesional injection of HuIFN-beta, histopathological examination revealed apoptotic changes of melanoma cells along with dense lymphohistiocytic infiltration. The present study confirmed direct and indirect inhibitory effects of HuIFN-beta on human melanoma cells and suggests that local higher concentration of HuIFN-beta is needed to eradicate melanoma lesions.


Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Imunoterapia , Interferon beta/farmacologia , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Apoptose/imunologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Regulação para Baixo , Humanos , Injeções Intralesionais , Interferon beta/uso terapêutico , Melanoma/patologia , Metástase Neoplásica , Neoplasias Cutâneas/patologia , Vacinação
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