Angiotensinogen gene polymorphism as a risk factor for ischemic stroke.

While gene polymorphism for angiotensinogen (AGT) is reported to contribute to the regulation of blood pressure and salt sensitivity, its effect on the risk of ischemic stroke remains controversial. We hypothesized that polymorphism of the AGT gene could be a risk factor for ischemic stroke. Major clinical risk factors and the AGT gene M235T polymorphism were examined in 147 consecutive stroke patients and 133 healthy age-matched controls. All patients were categorized into four stroke types (single lacuna, multiple lacunae, large-artery atherosclerosis and branch atheromatous disease in brainstem) and two vascular groups (large and perforating arterial lesions). The AGT gene M allele significantly increased the risk of single lacuna, multiple lacunae and small arterial lesions, in male patients (p=0.029, 0.031 and 0.026, respectively). Synergistic effects of the AGT gene polymorphism and clinical risks were not observed. In conclusion, AGT M allele may present a risk of lacunar infarctions in Japanese men, independent of hypertension.     

Hypoxia‐inducible factor 1α may be a marker for vasculitic neuropathy

Neuromuscular biopsy is still an essential method for diagnosing vasculitic neuropathy, although its diagnostic sensitivity is at most 60%. Our objective was to examine the expression of hypoxia‐inducible factor 1α (HIF‐1α) in peripheral nerves and to evaluate its usefulness in diagnosing vasculitic neuropathy, especially for discrimination from other axonal neuropathies. Forty‐one patients with vasculitic neuropathy consisting of 20 definite, 14 probable and seven possible diagnoses, 15 patients with metabolic neuropathy, five with motor neuron disease and six with chronic inflammatory demyelinating polyneuropathy were included. Nerve biopsy specimens were immunohistochemically examined for HIF‐1α and various cell markers. Distinct immunoreactivity (IR) was observed in nuclei of endoneurial cells in 54% (22/41) of vasculitic patients, while specimens from metabolic neuropathies showed less nuclear IR and the difference of mean density of HIF‐1α‐positive nuclei was significant. Two patients with possible vasculitis who showed HIF‐1α‐positive nuclei in endoneurium, were later confirmed to have vasculitis by skin biopsies. Most of the cells expressing HIF were demonstrated to be Schwann cells. There was a trend in the vasculitic patients with early phase nerve damage to display higher endoneurial HIF‐1α‐IR. HIF‐1α may be an immunohistochemical marker for vasculitic neuropathy, especially when the observed section contains no vasculitic lesions.     

N10 potential as an antidromic motor evoked potential in a median nerve short-latency somatosensory evoked potential study.

When stimulating the mixed nerve to record evoked potential, both sensory and motor fibers are activated before entering the spinal cord. The N10 potential has been described as an antidromic motor evoked potential based on results obtained by recording at the anterior midneck. In the present study, we examined the changes in latencies of Erb's potential, N10, and N13 by stimulating the median nerve distally at the wrist and proximally at the elbow. The conduction velocity of N10 calculated by the difference between N10 latencies at the two stimulation points was consistent with motor conduction velocity, although N13 conduction velocity estimated by the same method reflected a sensory conduction velocity. A positive relation was also observed between the indirect latency from the stimulation point to the anterior root as calculated using the equation (F - M - 1) / 2 (ms) and the direct latency to the negative peak of the N10 potential. Our data support the notion that N10 represents antidromic motor potential originating in the spinal entry zone of the anterior root.     

Three-dimensional two-layer collagen matrix gel culture model for evaluating complex biological functions of monocyte-derived dendritic cells

Dendritic cell-like cells (Mo-DCs) generated from peripheral blood monocytes with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been used as tools to treat cancer patients (DC-vaccines). Because Mo-DCs have multiple antigen presentation-related functions, including phagocytosis, migration, cytokine production, and T cell stimulation, establishment of a method for simultaneously evaluating the various functions of Mo-DCs is important. We developed a new in vitro three-dimensional two-layer collagen matrix culture model that consists of a collagen gel containing Mo-DCs as the lower layer and a collagen gel containing necrotic GCTM-1 tumor cells and/or T cells as the upper layer. We used this system to observe simultaneously multiple functions of Mo-DCs by phase-contrast or fluorescence microscopy and to assess IL-12 secretion during more than 2 weeks of culture. We also observed interactions between Mo-DCs and necrotic GCTM-1 or T cells on an individual cell basis by time-lapse videomicroscopy. In addition, we collected Mo-DCs from the collagen gels by collagenase treatment and analyzed the expression of antigen presentation-related molecules such as HLA-DR, CD80, CD83, and CD86 on Mo-DCs. This model may be a useful tool for evaluation of the various functions of Mo-DCs used as DC vaccines and for studies of the complex behaviors of Mo-DCs in vivo.     

Posthepatectomy hepatitis shortens tumor-free intervals in hepatitis C virus-associated hepatocellular carcinoma patients

In hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC), serum alanine aminotransferase (ALT) is frequently sustained on a high level after hepatectomy, with the formation of recurrent HCC tumors during follow-up periods. We investigated whether or not postoperative serum ALT level affects the interval before recurrence in hepatitis C virus-associated HCC. The subjects studied were 50 hepatectomized HCC patients who were HCV-Ab(+), and underwent a curable surgery in our Hospital from June 1990 to December 1999. We assessed the significance of the postoperative serum ALT level affecting tumor-free survival rates, as compared with other clinicopathological parameters, using univariate and multivariate Cox proportional hazard analysis. Thereafter, tumor-free and overall survival rates after hepatectomy were compared between high and low ALT groups, using Kaplan-Meier plotting and a log-rank test. The factor of ALT levels (a high or low ALT group) was most strongly associated with a tumor-free survival rate. Both tumor-free and overall survival rates were significantly poorer in the high ALT group than in the low ALT group among HCV-associated HCC cases (p<0.05). The results in this study suggest that postoperative hepatitis, which is indicated by sustained high ALT levels, may shorten the interval before recurrence in HCV-associated HCC. We should take care to control postoperative hepatitis to improve the prognoses of HCV-associated HCC cases.     

CYTOLOGICAL and ULTRASTRUCTURAL CHARACTERISTICS OF DNA SYNTHESIZING MESOTHELIAL CELLS IN PLEURAL EFFUSION

Cytologic examination of 3H-thymidine-labeled mesothelial cells in the pleural fluid revealed that single and small-sized cells with slight basophilic cytoplasm scarcely stainable by PAS and colloidal iron are in the DNA-synthetic phase and that these are exfoliating cells from the pleural surface. While abnormal labeling in a few arranged and binuclear cells suggesting accelerated or disturbed mesothelial mobilization was frequently found in congestive cardiac failure, liver cirrhosis, and uremia, it never occurred in single and large-sized activated cells possessing rich PAS-positive granules, cells in large clusters or sheet-like arrangements, or multinuclear giant cells. Transmission electron microscopical observation of these labeled cells proved that a smooth cellular surface and scant intracytoplasmic organelles, by which undifferentiated cells are generally characterized, are essential for DNA-synthesizing mesothelial cells. Probably as a result of some pleural irritation, surface lining cells immediately enter the cell cycle and at once revert to an undifferentiated form capable of DNA synthesis, after which they may be released as a single form, and differentiate and transform into mature, activated cells with a bleb-like surface structure or microvilli, and finally may proliferate in the fluid. ACTA PATHOL. JPN. 36: 1279–1296, 1986.     

Prevalence of Japanese cedar pollinosis among schoolchildren in Japan

BACKGROUND: Japanese cedar pollinosis is an important allergic rhinoconjunctivitis in Japan in spring. We investigated the relationship between the amount of pollen in the air and the prevalence of the disease and sensitization to Japanese cedar pollen in this ecological study. METHODS: The IgE antibody to Japanese cedar pollen (JCP-IgE) was determined in human serum and rhinoconjunctival symptoms were surveyed in 407-510 children in May or June every year from 1995 to 2001. Japanese cedar pollinosis was defined as being JCP-IgE >or=1.5 IU/ml and having any rhinoconjunctival symptom lasting 3 weeks or longer in March or April. RESULTS: Prevalence rates of Japanese cedar pollinosis were 13.8-22.9%. Prevalence rates of being JCP-IgE >or=1.5 IU/ml were 39.0-50.1%, and those of being JCP-IgE >or=15.01 IU/ml were 11.4-23.2%. All prevalence rates were significantly related to the amount of pollen in the air. The proportion of subjects with rhinoconjunctival symptoms was relatively constant in each stratum of low JCP-IgE levels (<0.35, 1.50-2.99, 3.0-14.9 IU/ml). CONCLUSION: High exposure to Japanese cedar pollen was associated with higher levels of JCP-IgE antibody and a high prevalence of Japanese cedar pollinosis. The relationship between the level of JCP-IgE and the proportion of subjects with symptoms was relatively constant.