1 alpha,25-Dihydroxyvitamin D3 inhibits proliferative response of T- and B-lymphocytes in a serum-free culture

The contribution of 1 alpha,25-dihydroxyvitamin D3 to the proliferative response of human B- and T-lymphocytes was examined in a serum-free culture, in which B-cells were stimulated with Staphylococcus aureus Cowan I, and T-cells with phytohemagglutinin, respectively. 1 alpha, 25-dihydroxyvitamin D3 inhibited mitogen-induced B-cell proliferation at a dose of 10(-7) M (P less than 0.01). T-cell proliferation was inhibited at the lower dose range between 10(-9) M and 10(-7) M. Thus, although 1 alpha, 25-dihydroxyvitamin D3 acts directly on B-cells, it appears that, under physiological circumstance, 1 alpha, 25-dihydroxyvitamin D3 regulates human B-cell growth indirectly through the effect on T-cells.     

Adverse effects of branched chain amino acid transfusion on type-II citrullinemia--report of an adult case

A 24-year-old man was admitted to our hospital, because two days before the admission he had abruptly lost consciousness following generalized convulsive seizures. He had a past history of transient amnesia and a favor for peanuts. His grandparents had a record of consanguinity. On admission, he was comatose and flaccid with his four extremities. Laboratory examination revealed the followings; mild degree of abnormal liver function, slight elevation of blood ammonia, irregular theta basic rhythm on EEG, marked brain edema on CT and a normal liver ultrasonography. From the second hospital day, in addition to antiepileptic drugs and adrenocorticosteroids, branched chain amino acid was administered to reactivate damaged brain functions. Thereafter, the concentration of blood ammonia increased to more than 3,000 micrograms/dl, and as a result he fell into status epilepticus. On the fourth hospital day, the levels of citrulline in the plasma and urine taken on the first hospital day were found to have increased by 20 and 100 times, respectively. Although the transfusion of branched chain amino acid was stopped, he died while in coma on the 12th hospital day. Enzymatic analyses of necropsied liver specimens revealed that the quantitative activity of argininosuccinate synthetase had decreased to less than 10% in his urea cycle. In this patient, it was noted that, after transfusion of branched chain amino acid, his brain activities turned worse and blood ammonia was markedly elevated. There is a possibility that intravenous administration of branched chain amino acid may interrupt the urea cycle balance in an adult patient of citrullinemia with dysfunction of the brain, kidney and muscle, especially with brain edema.(ABSTRACT TRUNCATED AT 250 WORDS)     

The molecular genetics of rheumatoid arthritis disease gene

Rheumatoid arthritis(RA) is a chronic polyarthritis of unknown etiology affecting approximately 1% of the population worldwide. Previous studies have shown that the ratio of the risk for siblings of patients with the disease versus the prevalence of that disease in the general population (lambda s) is much greater in RA, suggesting that genetic factors may be involved in familial clustering. Using microsatellite marker analysis and sib-pair linkage study, we have identified three chromosome regions D1S214/253, D8S556 and DXS1232/984 as candidate loci for RA disease genes. In this article, we review the molecular genetic findings on the RA disease genes located respectively at each of the above chromosome regions. We show that the death receptor 3(DR3) gene, a Fas family member, containing nucleotide polymorphism is the candidate disease gene located at D1S214/253. We also identify the mutant forms of angiopoietin-1(Ang-1) and Dbl proto-oncogenes respectively as the candidate genes located at D8S556 and DXS1232/984. We surmise that these mutations are responsible for the impairment of apoptosis induction, angiogenesis and leukocyte function in the patients, which may predispose to autoimmunity.     

Evaluation of sorafenib for advanced hepatocellular carcinoma with low α-fetoprotein in arrival time parametric imaging using contrast-enhanced ultrasonography

Purpose

To determine the usefulness of arrival time parametric imaging (AtPI) using contrast-enhanced ultrasonography (CEUS) with Sonazoid in evaluating early response to sorafenib for hepatocellular carcinoma (HCC).

Methods

Twenty-one advanced HCC patients with low α-fetoprotein (AFP) levels (≤35 ng/ml) who received sorafenib for at least 4 weeks were enrolled in this study. CEUS was performed before and 2 weeks after treatment, and the images of the target lesion in the arterial phase were analyzed by AtPI. In the color mapping images obtained by AtPI, the mean arrival time of the contrast agent in the target lesion from the reference point (mean time: MT) was calculated. In each patient, differences between MT before and MT 2 weeks after treatment were compared. MT (+) and MT (?) groups were defined as difference of 0 s or greater and less than 0 s, respectively. Overall survival was evaluated between the two groups.

Results

In the MT (+) (11 patients) and MT (?) (10 patients) groups, the median survival time was 792 and 403 days, respectively, which was statistically significant.

Conclusions

The results suggested that AtPI was useful for evaluating early response to sorafenib for advanced HCC with low AFP level.

     

Mathematical basis of affected sib-pair analysis: an extension to X-linked loci

Most clinical genetic studies are done without knowing their mathematical basis. However, because the results of such studies rely on the correctness of the mathematical calculations involved, we cannot ignore the mathematics of genetic studies. In this study, the mathematical basis of the sib-pair method, which has been widely used in recent genome-wide studies, was extended to studies focusing on the X chromosome, and then applied to study a clinical microsatellite marker on the X chromosome. Our calculation involves classifying marker types on the X chromosome for an affected sib-pair and an unaffected sib, together with their sexual information and the possible parental marker types applicable to a genome-wide genetic study. The method proposed in this study was then applied to 41 Japanese rheumatoid families, and the locus DXS984 was found to be most likely to be linked with rheumatoid arthritis (RA). This locus, which we found nicely, was also highlighted in a previous study that used the Mapmaker/sibs program, so we can conclude that our calculation provides a solid foundation for understanding and confirming the results obtained using the sib-pair method.     

Effect of the free radical scavenger edaravone on peripheral nerve ischemia–reperfusion injury

We investigated the effects of edaravone, a free radical scavenger, on peripheral nerve ischemia–reperfusion injury caused by ligation of vessels supplying the sciatic and tibial nerves in rats. The control group was administered a placebo, the standard‐dose group was given 3 mg/kg of edaravone intraperitoneally every 24 hours, and the low‐dose group was given 1 mg/kg of edaravone. At 7 days after reperfusion, neurological and electrophysiological parameters were improved in the standard‐dose group as compared with the control group. After 14 days, however, these differences were no longer observed. After 21 days, persistent edema and nerve fiber degeneration were noted in the standard‐dose group, but not in the control or low‐dose groups. Edaravone was effective during the early reperfusion period, but chronic inhibition of reactive oxygen species may be detrimental for nerve regeneration after ischemia–reperfusion injury. Further studies are necessary to confirm the long‐term influence of edaravone. Muscle Nerve, 2009     

Transradial approach for transcatheter arterial chemoembolization in patients with unresectable and recurrent hepatocellular carcinoma--a comparison with a conventional transfemoral approach

We evaluated a clinical usefulness and safety of transradial approach for transcatheter arterial chemoembolization (TAE) in patients with unresectable and recurrent hepatocellular carcinoma (HCC) compared with that of conventional transfemoral approach. The two groups (radial group; n=385, 1999.7-2007.3, femoral group; n=150, 1997.4-1999.6) of cases were retrospectively compared with regard to the successful rate of angiography, TAE, interventional time, Lipiodol retention pattern and complications. Hepatic angiography and TAE were completed in 379 (98.4%) of 385 cases in the radial group. There was no inter-group difference of interventional time. Minor complications (dull pain or numbness of puncture site) occurred in 29 (7.6%) patients in the radial group. Transradial approach has some advantages as follows: (1) No time will be required to stop breeding after removal of sheath. (2) The patient may freely walk after the examination. TAE by our new transradial approach for HCC was found to have a therapeutic efficacy with lower complications comparable to that of conventional transfemoral approach.