Novel mutations in TNFRSF1A in patients with typical tumor necrosis factor receptor-associated periodic syndrome and with systemic lupus erythematosus in Japanese

Molecular defects of TNFRSF1A was investigated in members of a family presenting with typical phenotypes of tumor necrosis factor receptor-associated periodic syndrome (TRAPS) and in patients with the autoimmune disorders, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Genomic DNA from the members of a family with typical TRAPS, as well as from 100 patients with SLE, 100 patients with RA and 100 healthy individuals, was studied for mutations in exons 2, 3 and 4 of the TNFRSF1A gene. All individuals were Japanese. Three novel missense mutations were identified in the TNFRSF1A. The C70G mutation was identified in family members with typical TRAPS, which was the second case in eastern Asian population. In addition, the T61I and R104Q mutations were each identified in 2 of the 100 SLE patients. The T61I mutation was identified in one of the 100 healthy individuals. No mutations were identified in the 100 RA patients. Functional analysis revealed that PMA-induced shedding of TNFRSF1A from PBMCs was impaired in a patient carrying T61I. A larger scale of study will clarify whether these two mutations, T61I and R104Q, are associated with chronic inflammatory disorders, such as SLE, or not.     

Effects of drug adherence on patient outcomes to early treatment for Japanese cedar pollinosis]

Drug adherence is one of the important aspects in caring for patients with allergic rhinitis. To improve clinical efficacy of early treatment for Japanese cedar pollinosis (JCP), we evaluated the effect of drug adherence on patients' outcomes. Patients were randomly selected from 16 ENT clinical sites in Osaka and Wakayama between February 24 and March 8, 2003 (peak pollen season). Efficacy was assessed using patients' ratings of nasal and ocular symptoms and overall assessment in their condition compared with previous season ones. Costs include direct costs of the drugs used for treatment to JCP from January to February. Five hundred one patients taking early treatment were enrolled. Compared to low adherence patients, those who reported higher level of adherence significantly improved overall health condition, and achieved better symptom relief of rhinorrhea and nasal congestion. In multiple logistic regression analysis, the following factors were independent risk factors for low adherence: student (p=0.002), using OTC medications (p=0.006), and short-duration of medication (p=0.001). Low costs were also risk factor for low adherence. We conclude that taking medications for JCP for 22-28 days is the best way to enhance patients' outcomes.     

Distribution of peptidergic terminals of enteric origin in the rat celiac ganglion

We examined the distribution of enterofugal nerve terminals of bombesin-, cholecystokinin- and vasoactive intestinal polypeptide-like immunoreactivity in the rat celiac-superior mesenteric ganglion complex. The majority of these nerve terminals were concentrated in the mesenteric side of the ganglion. The present findings suggest that some functional specialization occurs in the celiac ganglion of the rat.     

Intestinal microflora and aging: Age-related change of lipid metabolism in germ-free and conventional rats

The influence of intestinal microflora and aging on the lipid metabolism in germfree (GF) and conventional (CV) rats, 8 and 40 weeks old, was investigated. Serum cholesterol at the age of 8 and 40 weeks and serum triglyceride (TG) at the age of 40 weeks was higher in GF than in CV rats. Serum cholesterol decreased and serum TG and corticosterone tended to increase in both GF and CV rats with aging. In the rats 40 weeks of age, lipase activity of the pancreas and the duodenal, jejunal, and colorectal contents in GF rats increased, but that of the ileal and cecal contents in GF and CV rats decreased. Intestinal microflora tended to depress the age-related increase of serum TG and lipase activity of the pancreas and the duodenal and jejunal contents Lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) activities of the epididymal adipose tissue were higher in CV than in GF rats at both 8 and 40 weeks of age. The LPL activity increased and the HSL activity decreased in both GF and CV rats with aging. The concentration of cholesterol increased and that of bile acids decreased in the cecal contents of 40-week-old GF rats.     

Conformation and gas permeability of poly(α-amino acid) membranes

The permeability of some poly(?-amino acid) (PAA) membranes like such of poly(N,δ-carbobenzoxy-L -lysine) (PCBL), poly(N,δ-carbobenzoxy-L -ornithine) (PCBO) as well as of copolymers of L -lysine and carbobenzoxy-L -lysine to oxygen and carbon dioxide were determined at different water content especially with regard to their use for artificial lungs. The conformations of these polymer membranes were studied by means of IR-spectra and X-ray diffraction. The results on the diffusion coefficient obtained for PCBL and PCBO were analysed in terms of Eyring's theory. They suggest that the microvoids in the interstices between the α-helices, assumed on the basis of X-ray analyses, play an important role, especially below the glass transition temperature T_g of the side-chains. This seems also to contribute partly to the diffusion of gas through the membrane even above T_g and results in an abnormally high “apparent activation energy” of diffusion in the wet state below T_g. It was found that the permeability of the membrane of partially decarbobenzoxylated PCBL for oxygen in a certain temperature range is higher than that for carbon dioxide. This has never been observed for any other synthetic polymer, because usually carbon dioxide has a higher solubility in these materials than oxygen. In the case of the partially decarbobenzoxylated PCBL membranes, however, the diffusion coefficient of carbon dioxide, and therefore the permeation of this gas, decreases much more than that of oxygen with increasing decarbobenzoxylation accompanied by the formation of β-structure and concomitantly the formation of intermolecular hydrogen bonds. Obviously, this phenomenon may be responsible for the permselectivity of these membranes for oxygen compared with carbon dioxide.     

Distribution of indigenous bacteria in the digestive tract of conventional and gnotobiotic rats.

The localization and population levels of the indigenous bacterial flora of conventional rats were investigated by cultural and histological techniques. Lactobacilli predominate in the stomach and upper part of the small intestine and associate with keratinized cells of the nonglandular portion of stomach. Mixtures of varying complexity of pure cultures of indigenous bacteria were inoculated into germfree rats. The distribution of these bacteria was examined to investigate the effect of lactobacilli in controlling the composition of other bacterial species in each portion of the digestive tract. In the stomach and the upper part of the small intestine, lactobacilli controlled the population levels of other bacterial species. In the lower part of the small intestine, not only lactobacilli but also the anaerobes which colonized the large bowel influenced the population levels of other bacterial types. Staphylococci isolated from a conventional rat colonized specifically the keratinized cells of the nonsecreting epithelium of the stomach when the rats were free from lactobacilli. This colonization was not observed after inoculation of lactobacilli into the rats.     

International trends in clinical laboratory testing

During the 20th century, at least until the 1980s, clinical laboratory practice had been rapidly expanded, mainly because of a significant advancement in medicine as a whole and also in laboratory technology. However, recent economic changes in health care environment worldwide have been influencing greatly future trends in clinical laboratory practice. In 1983, the DRG/PPS was introduced in the Medicare hospital care in the United States, and it will be introduced also in out-patient care after the January of 2000. This payment system has been expanded to the HMO, and a drastic change has occurred in clinical laboratory practice, particularly since 1988 when the CLIA'88 was implemented. In Japan, the DRG/PPS is now in the process of preparing for the future introduction into the National Health Insurance System. The clinical laboratory must pursue both quality management and adequate utilization of laboratory tests. In near future, the ISO standards in clinical laboratory testing will prompt to the implementation of quality management in the clinical laboratory. Evidence-based laboratory medicine or systematic review in diagnostic testing will be introduced in order to improve the utilization of clinical laboratory tests.     

Maternal Quercetin Consumption during Pregnancy May Help Regulate Total Cholesterol/HDL-Cholesterol Ratio without Effect on Cholesterol Levels in Male Progeny Consuming High-Fat Diet

Quercetin has been shown to have anti-obesity effects, but it is unknown whether these effects can be transmitted from mothers to their progeny. In this study, we investigated whether maternal quercetin consumption during pregnancy has a protective effect on high-fat diet–induced hyper lipid levels and overweight in progeny. Female mice consumed a control diet or a diet containing 1.0% quercetin during breeding. The male progeny were then divided into four groups that were (1) sacrificed at postnatal day 3; (2) born to dams fed the control diet and also fed the control diet (C-C), (3) born to dams fed the control diet and then fed a 30% high-fat diet (C-HF), or (4) born to dams fed the Q-diet and then fed the HF diet (Q-HF). Maternal consumption of quercetin did not affect body weight or blood lipid parameters in either dams or neonates at postnatal day 3. After 13 weeks, the Q-HF group exhibited greater body and liver weights, and higher blood cholesterol levels than the C-HF group. However, the total cholesterol/ high density lipoprotein (HDL)-cholesterol ratios in the Q-HF and C-C groups remained similar. In conclusion, maternal quercetin consumption does not appear to protect the next generation from high-fat diet–induced hyper cholesterol level in the blood and liver, and consequently overweight, but may help regulate the total cholesterol/HDL-cholesterol ratio.     

A Pilon Fracture With Fibular Head Dislocation Treated With the Use of 3D Preoperative Planning: A Case Report and Literature Review

Pilon fractures with intact fibula have been associated with low-energy trauma. However, the compression force onto the ankle joint can damage the tibiofibular linkage as in a Maisonneuve fracture. Herein, we describe a case of a patient who had a pilon fracture (AO type 43 C3.2) without a fibular fracture. Three-dimensional preoperative simulation by reduction with the surface registration technique was performed as the fibular length was intact and there was no reference for the tibial length. The preoperative simulation revealed superior fibular head dislocation and shortening of the distal tibia. After emergency external fixation on the day of arrival, a 2-staged surgery was performed. During the first operation, the fibular head was reduced and the tibial posterolateral fragment was fixed to restore the tibia length. During the second operation, medial and anterolateral fragments were fixed in order to reduce joint surface of the distal tibia. In general, proximal fibular head fractures are easily overlooked. In the case of pilon fractures with severe length shortening of the tibia without a fibular fracture, a proximal tibiofibular injury should be suspected.