Genetic characterization of hantaviruses transmitted by the Korean field mouse (Apodemus peninsulae), Far East Russia

In an epizootiologic survey of 122 rodents captured in Vladivostok, Russia, antibodies positive for hantavirus were found in Apodemus peninsulae (4/70), A. agrarius (1/39), and Clethrionomys rufocanus (1/8). The hantavirus sequences identified in two seropositive A. peninsulae and two patients with hemorrhagic fever with renal syndrome (HFRS) from the Primorye region of Far East Russia were designated as Solovey and Primorye, respectively. The nucleotide sequences of the Solovey, Primorye, and Amur (obtained through GenBank) sequences were closely related (>92% identity). Solovey and Primorye sequences shared 84% nucleotide identity with the prototype Hantaan 76-118. Phylogenetic analysis also indicated a close relationship between Solovey, Primorye, Amur, and other viruses identified in Russia, China, and Korea. Our findings suggest that the Korean field mouse (A. peninsulae) is the reservoir for a hantavirus that causes HFRS over a vast area of east Asia, including Far East Russia.     

Effect of protease-activated receptor-2 deficiency on allergic dermatitis in the mouse ear

To investigate the involvement of protease-activated receptor-2 (PAR-2) in allergic dermatitis, we generated PAR-2-deficient (PAR-2(-/-)) mice. Ear thickness, contact hypersensitivity (CH) induced by topical application of picryl chloride (PC) or oxazolone (Ox) after sensitization, and vascular permeability after ear passive cutaneous anaphylaxis (PCA) were compared between wild-type (WT) and PAR-2(-/-) mice. Ear thickness was almost the same in untreated WT and PAR-2(-/-) mice. Topical application of PC or Ox thickened the ears at 6, 24 and 48 h after challenge with a peak at 24 h in WT mice. In PAR-2(-/-) mice, the ear swelling induced by both PC and Ox was suppressed at every time point, and significant inhibition was found at 24 h in PC-induced CH and at 24 and 48 h in Ox-induced CH. Histopathological observation of the ears at 24 h after challenge revealed that PC- or Ox-induced ear edema and infiltration of inflammatory cells in WT mice were greatly attenuated in PAR-2(-/-) mice. The vascular permeability in the ears after PCA was not different between WT and PAR-2(-/-) mice. These results strongly suggest that PAR-2 plays a crucial role in type IV allergic dermatitis but not in type I allergic dermatitis.     

Inhibition of cholesterol synthesis causes both hypercholesterolemia and hypocholesterolemia in hamsters

Effects of FR194738 ((E)-N-ethyl-N-(6,6-dimethyl-2-hepten-4-ynyl)-3-[2-methyl-2-(3-thienylmethoxy)propyloxy]benzylamine hydrochloride), a squalene epoxidase inhibitor, on lipid metabolism were compared with those of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, in hamsters. Drugs were given for 10 d either as a diet mixture or as a bolus oral gavage, and similar results were obtained with each type of administration. FR194738 (0.01-0.32% as a diet mixture; 10-100 mg/kg as an oral gavage) dose-dependently decreased serum total cholesterol, non high density lipoprotein (HDL) cholesterol, HDL cholesterol and triglyceride levels, and the changes in serum parameters were similar. Pravastatin (0.01-0.32% as a diet mixture; 1-100 mg/kg as an oral gavage) increased serum cholesterol levels, and dose-dependently decreased serum triglyceride levels. Although oral gavage of FR194738 at 32 mg/kg and pravastatin at 3.2 and 10 mg/kg increased hepatic HMG-CoA reductase activity, the degree of the changes was far greater with the latter than the former drug. FR194738 slightly increased hepatic cholesterol content at 32 mg/kg, whereas pravastatin dose-dependently increased hepatic cholesterol content until it leveled off at 32 and 100 mg/kg. It is concluded that inhibition of squalene epoxidase and HMG-CoA reductase triggers both hypercholesterolemic (hepatic cholesterol synthesis) and hypocholesterolemic (hepatic cholesterol uptake) mechanisms. FR194738 appears to induce a greater enhancement of the latter rather than the former, whereas pravastatin has a greater effect on the former.     

Role of peroxisome proliferator-activated receptor-gamma in maintenance of the characteristics of mature 3T3-L1 adipocytes

Peroxisome proliferator-activated receptor (PPAR)-gamma plays an important role in adipogenesis. However, the functions of PPAR-gamma in differentiated adipocytes have remained unclear. The role of PPAR-gamma in mature 3T3-L1 adipocytes was therefore investigated by overexpression of a dominant negative mutant of this protein (PPAR-gamma-DeltaC) that lacks the 16 COOH-terminal amino acids and that has been shown to prevent the thiazolidinedione-induced differentiation of 3T3-L1 cells into adipocytes. Overexpression of PPAR-gamma-DeltaC in mature 3T3-L1 adipocytes by adenovirus gene transfer resulted in a decrease in both cell size and intracellular triglyceride content, an increase in the extent of lipolysis, and a reduction in the rate of free fatty acid uptake. Furthermore, overexpression of this mutant reduced the abundance of mRNAs for several key enzymes that contribute to triglyceride and free fatty acid metabolism as well as the amounts of GLUT4, insulin receptor, insulin receptor substrate (IRS), and C/EBPalpha mRNAs. It also reduced both the concentration of IRS2 and the insulin-stimulated glucose uptake. These results suggest that PPAR-gamma plays an important role in mature 3T3-L1 adipocytes at least in part by maintaining the expression of genes that confer the characteristics of mature adipocytes.     

Medial temporal lobe activation during context-dependent relational processes in episodic retrieval: an fMRI study. Functional magnetic resonance imaging

Previous studies have reported that the medial temporal lobe (MTL) structures contribute to the processing of relations among multiple stimuli in episodic encoding. There have been few studies, however, on the episodic retrieval requiring processing of relations among multiple components that was involved in our events. We used functional magnetic resonance imaging (fMRI) to investigate neural activities during the retrieval of relations within an organized episode and the recognition of an episodic component. Healthy, normal participants memorized 50 four-scene comic strips before fMRI scanning. In the retrieval phase with fMRI scanning, participants were engaged in three tasks: a visual identification (VI) task, a story recall (SR) task, and a picture recognition (PRe) task. In the VI task, participants were asked to judge whether they could identify at least one female character in the two scenes presented vertically. In the SR task, participants were shown the first and last scenes from strips memorized previously and asked to judge whether or not the two scenes were from the same strip. In the PRe task, participants were shown two scenes and asked to judge whether they both belonged to the memorized scenes. The two contrasts of SR with VI and PRe with VI demonstrated some commonly activated areas, such as the bilateral middle frontal gyrus and cerebellum. More importantly, the SR task differentially activated the bilateral parahippocampal gyrus, whereas the PRe task differentially activated right prefrontal areas, including the inferior frontal and precentral gyri. The results suggest that the activity of the MTL structures may be strongly associated with episodic memory retrieval requiring context-dependent relational processing.     

Time-dependent contribution of the hippocampal complex when remembering the past: a PET study

Previous studies of brain-damaged patients and functional neuro-imaging have consistently shown the importance of the hippocampal complex, i.e. the hippocampus and parahippocampal gyrus, in episodic memory retrieval. We wished to determine whether patterns of brain activation during memory retrieval as measured by PET are same or different when the oldness of a to-be-retrieved episode is manipulated. Using cue words, subjects remembered related episodes from three periods of their life, childhood, adolescence and recent period. The results showed an increase of parahippocampal activities during recall of episodes from childhood and recent period, but not from adolescence. These data suggest a possibility of time-dependent hippocampal contribution in episodic recall, which cannot be understood in simple terms of recent remote memory dichotomy.     

A case of preoperative concurrent chemoradiotherapy and curative resection for locally advanced non-small-cell lung cancer

We report the case of a 58-year-old man who underwent complete resection for locally advanced non-small-cell lung cancer (cT4N2M0). The patient received UFT (400 mg/m2 orally on days 1-14 and 22-35) and cisplatin (80 mg/m2 intravenously on days 8, 29) with a total 40 Gy, delivered in 20 fractions on days 1-26. The tumor reduction rate was 76%, and no remarkable toxicities were observed. The patient underwent complete resection and a pathologic complete response was observed. This induction concurrent chemoradiotherapy (followed by surgery) is considered to be effective and safe.     

Muscle MRI findings of HTLV-1-associated myelopathy

We report here the muscle MRI findings in two patients with human T-cell lymphotropic virus type I-associated myelopathy (HAM). It is known that thigh muscles are vulnerable in HAM patients, but detailed information about the affected muscles has not been available. Muscle MRI findings of these patients showed that thigh muscles, especially adductor magnus, and semimembranosus muscles were severely affected, but lower leg muscles were comparatively preserved. In these affected muscles, neurogenic changes were observed by EMG. We concluded that muscle MRI is very useful to estimate the affected muscles in HAM patients.     

Retinopathy in older patients with diabetes mellitus

PURPOSE: We studied the effects of the age and/or disease duration in diabetics on the progression of diabetic retinopathy (DR). METHODS: The population consisted of 3614 type 2 diabetes mellitus (DM) patients. The subjects were divided into three age groups (elderly, > or = 65 years old; middle-aged, 64-40 years old, and younger < 40 years old) for disease duration-adjusted comparison with and without DR and proliferative diabetic retinopathy (PDR). Then, in 503 patients with 8-year follow-up data available, the frequency of development/progression of DR and the rate of progression to PDR were compared among the three groups. Thirdly, in the elderly patients, DR prevalence and the frequency of the development/progression of DR were compared between two groups with different diabetes duration (> or = 6 years and < or = 5 years). RESULTS: The prevalence of DR increased significantly with age (P < 0.001). The prevalence of PDR decreased significantly with age (P < 0.001). The overall frequency of the development and/or progression of DR increased significantly with age (P = 0.002); however, age was not related to the frequency of progression to PDR. In the patients with diabetes duration of 6-15 years, the frequency of the development/progression of DR and of progression to PDR after an 8-year follow up tended to decrease with age. Elderly patients with a diabetes duration of > or = 6 years showed significantly higher rate of prevalence of DR and frequency of development/progression of DR in an 8-year period than those with diabetes of a shorter duration (P < 0.001 and P < 0.001, respectively). CONCLUSION: In elderly DM patients, the prevalence of DR was increased even in the short duration and development/progression rates of DR were increased, while the relative frequency of PDR was decreased. Older-onset DM patients appear to be at a lower risk for progression to PDR.