RESUMO
The patient, a 69-year-old man, had a chief complaint of hepatomegaly. The liver was palpated four fingerbreadths below the costal margin, and the spleen was three fingerbreadths below the costal margin. There were no other abnormal findings. Laparoscopy showed that the liver resembled an orange-yellow crayon in appearance and was nodular. The pathological findings of the liver biopsy tissue were consistent with liver cirrhosis. Inside the fibrous septum was an apparent aggregation of enlarged macrophages that phagocytosed lipid components, as well as enlarged Kupffer cells that phagocytosed lipid droplets. Electron microscopy showed the lipid droplets to have a moth-eaten appearance. Using monocytes extracted from the peripheral blood, acid lipase activity was measured by fluorescence spectrometry using 4-methylumbelliferone palmitate as a substrate. This patient's human lysosomal acid lipase activity was 0.020 nM/min per 10(6) cells, corresponding to 5.9% of that in healthy subjects (0.332 ± 0.066 nM/min per 10(6) cells). Cholesterol ester storage disease was therefore diagnosed. The acid lipase A base sequence obtained from leukocytes by direct sequencing was compared with a library. This patient had a point mutation of N250H/N250H in exon 7, a novel gene abnormality that has not previously been reported.
RESUMO
Allergy to laboratory animals is a well known occupational hazard and remains a health concern for individuals in contact with lab animals. This study evaluates the prevalence of allergy symptoms among medical researchers exposed to laboratory animals. We analyzed data from a cross-sectional survey, involving subjects (n=169, 21-59â yr), working in Kochi Medical School, Japan. They were asked to fill out a questionnaire to evaluate symptoms related to contact with laboratory animals. The overall response rate was 86.2%. The prevalence of laboratory animal allergy was 17.6%. The symptoms most reported were allergic rhino-conjunctivitis and asthma. A small number of the subjects received education on the allergy issue and 62.5% of subjects with an allergy to laboratory animals claimed to have atopy. Protection from animal allergens should be a high priority for institutions using lab animals; providing continuous education to animal handlers would be meaningful to reduce and control exposure.
Assuntos
Animais de Laboratório , Hipersensibilidade/epidemiologia , Doenças Profissionais/epidemiologia , Exposição Ocupacional , Adulto , Técnicos em Manejo de Animais/estatística & dados numéricos , Animais , Pesquisa Biomédica , Estudos Transversais , Feminino , Humanos , Hipersensibilidade/imunologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/imunologia , Prevalência , Adulto JovemRESUMO
An 81-year-old woman presented with a chief complaint of swelling of both lower legs. She had a history of surgery for cancers of the stomach, rectum and colon. Among her immediate family members, her son had colon and rectal cancers, and her sister had ovarian cancer. After close examination the patient was diagnosed with small intestine cancer and ascending colon cancer. Gene mutation analyses did not reveal any mutations in DNA mismatch repair genes, but MSH-2 protein expression was lost only in the cancer lesions. Here, we report this rare case of eight metachronous gastrointestinal cancers thought to be HNPCC.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Proteína 2 Homóloga a MutS/análise , Segunda Neoplasia Primária/diagnóstico , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-HistoquímicaRESUMO
It is generally believed that a mechanical signal initiates a cascade of biological events leading to coordinated cardiac remodeling. 14-3-3 family members are dimeric phosphoserine-binding proteins that regulate signal transduction, apoptotic, and checkpoint control pathways. To evaluate the molecular mechanism underlying swimming stress-induced cardiac remodeling, we examined the role of 14-3-3 protein and MAPK pathway by pharmacological and genetic means using transgenic mice with cardiac-specific expression of dominant-negative (DN) mutants of 14-3-3 (DN 14-3-3/TG) and p38alpha/beta MAPK (DNp38alpha and DNp38beta) mice. p38 MAPK activation was earlier, more marked, and longer in the myocardium of the TG group compared with that of the nontransgenic (NTG) group after swimming stress, whereas JNK activation was detected on day 5 and decreased afterward. In contrast, ERK1/2 was not activated after swimming stress in either group. Cardiomyocyte apoptosis, cardiac hypertrophy, and fibrosis were greatly increased in the TG group compared with those in the NTG group. Moreover, we found a significant correlation between p38 MAPK activation and apoptosis in the TG group. Furthermore, DN 14-3-3 hearts showed enhanced atrial natriuretic peptide expression. In contrast, DNp38alpha and DNp38beta mice exhibited reduced mortality and increased resistance to cardiac remodeling after 28 days of swimming stress compared with TG and NTG mice. Besides, treatment with a p38 MAPK inhibitor, FR-167653, resulted in regression of cardiac hypertrophy and fibrosis and improvement in the survival rate in the TG group. These results indicate for the first time that 14-3-3 protein along with p38 MAPK plays a crucial role in left ventricular remodeling associated with swimming stress.