Changes in Na(+) channel expression and nodal persistent Na(+) currents associated with peripheral nerve regeneration in mice

Patients with peripheral neuropathy frequently suffer from positive sensory (pain and paresthesias) and motor (muscle cramping) symptoms even in the recovery phase of the disease. To investigate the pathophysiology of increased axonal excitability in peripheral nerve regeneration, we assessed the temporal and spatial expression of voltage-gated Na(+) channels as well as nodal persistent Na(+) currents in a mouse model of Wallerian degeneration. Crushed sciatic nerves of 8-week-old C57/BL6J male mice underwent complete Wallerian degeneration at 1 week. Two weeks after crush, there was a prominent increase in the number of Na(+) channel clusters per unit area, and binary or broad Na(+) channel clusters were frequently found. Excess Na(+) channel clusters were retained up to 20 weeks post-injury. Excitability testing using latent addition suggested that nodal persistent Na(+) currents markedly increased beginning at week 3, and remained through week 10. These results suggest that axonal regeneration is associated with persistently increased axonal excitability resulting from increases in the number and conductance of Na(+) channels.     

Four-hydroxyphenylpyruvic acid oxidase deficiency with normal fumarylacetoacetase: a new variant form of hereditary hypertyrosinemia

Enzymatic studies on the liver of an infant are described-a case of hypertyrosinemia without hepatic dysfunction. His parents were siblings and the mother had hypertyrosinemia. Excessive amounts of 4-hydroxyphenylpyruvic acid (pHPP), 4-hydroxyphenylacetic acid (pHPL), and 4-hydroxyphenylacetic acid (pHPA) were found to be excreted in the patient's urine as well as in the urine of the mother and the inhibitor of porphobilinogen synthetase was not found. Soluble tyrosine aminotransferase (s-TAT), separated from that of the mitochondrial form (m-TAT) by DE 52 column chromatography, was normal in the patient's liver, both quantitatively and qualitatively. The activities of fumarylacetoacetase in the patient's liver and in the peripheral leucocytes from the parents were normal. The activity of pHPP oxidase in the patient's liver was approximately 5% of the control and the enzyme had a high Km value for pHPP (controls: 0.06 +/- 0.01 mM, patient: 0.23 +/- 0.03 mM). From these results, the patient was thought to be different from previously described types of tyrosinemia and perhaps representative of a new variant form. This is the first report concerning 4-hydroxyphenylpyruvic acid oxidase deficiency alone. Mild metal retardation and mild hypertyrosinemia may be offered as typical clinical features of the disease.     

Mild form of beta-ketothiolase deficiency (mitochondrial acetoacetyl-CoA thiolase deficiency) in two Japanese siblings: identification of detectable residual activity and cross-reactive material in EB-transformed lymphocytes

Mitochondrial acetoacetyl-CoA thiolase (T2) deficiency is an inherited metabolic disorder of isoleucine and ketone body catabolism. We report the cases of two siblings who showed clinically mild forms of this disorder. They did not excrete tiglylglycine in urine. Their EB-transformed lymphocytes contained residual T2 activity, which was confirmed by immunotitration analysis. In immunoblot analysis, the bands corresponding to T2 in the samples of the cell lines from two patients were the most intensely detected among those from 19 T2-deficient cell lines tested     

Further studies on episodic occurrence of congenital dysgenetic hypothyroidism in Osaka, Japan

A total of 1,228,551 newborn babies, who were almost all of babies born in Osaka for 14 years (168 months), were screened for congenital primary hypothyroidism by an identical mass-screening program using the thyrotropin method, and 429 patients with hypothyroidism due to thyroid dysgenesis (dysgenetic hypothyroidism) were found. The occurrence of the patients in every month was not random but episodic and the incidence was higher in the late autumn (from October to December). These observations support a hypothesis that some environmental factors may cause this disorder overtime and the possibility of relation with intrauterine viral infection was discussed.     

Factors Related to Tooth Loss Among Community-Dwelling Middle-aged and Elderly Japanese Men

Background

Using data from a large-scale community-based Japanese population, we attempted to identify factors associated with tooth loss in middle-aged and elderly men.

Methods

A total of 8352 men aged 40 to 79 years who lived in the north of the main island of Japan and underwent health checkups were enrolled between 2002 and 2005. Number of teeth was assessed by the question, “How many teeth do you have (0, 1–9, 10–19, or ≥20)?”. On the basis of the answer to this question, participants were classified into 2 groups (≤19 teeth or ≥20 teeth). Using multivariate logistic regression, factors related to having 19 or fewer teeth were estimated.

Results

The numbers (percentages) of participants who had 0, 1 to 9, 10 to 19, and 20 or more teeth were 1764 (21.1%), 1779 (21.3%), 1836 (22.0%), and 2973 (35.6%), respectively. Among the participants overall and those aged 65 to 79 years, having 19 or fewer teeth was significantly associated with older age, smoking status (current smoking and ex-smoking), and low education level. In addition, men with 19 or fewer teeth were more likely to have a low body mass index and low serum albumin level and less likely to be current alcohol drinkers. Among men aged 40 to 64 years, but not men aged 65 to 79 years, those with 19 or fewer teeth were more likely to have a low serum high-density lipoprotein cholesterol level and high glycosylated hemoglobin (HbA1c) level.

Conclusions

Smoking, low education level, and poor nutritional status were associated with tooth loss among middle-aged and elderly Japanese men.Key words: tooth loss, risk indicator, middle-aged men, elderly men, Japanese, cross-sectional study     

Drug discovery based on microarray

Gene regulatory networks developed from full genome expression libraries from gene perturbation variant cell lines can be used to quickly and efficiently identify the molecular mechanism of action of drugs or lead compound molecules. We developed an extensive yeast gene expression library consisting of full-genome cDNA array data for over 500 yeast strains each with a single gene disruption. Using this data, combined with dose and time course expression experiments with the oral antifungal agent, we used Boolean network discovery techniques to determine the genes whose expression was most profoundly affected by this drug. Our system identified the gene as the most significantly suppressed target molecule due to exposure to the antifungal agent. This process for network based drug discovery can significantly decrease the time and resources necessary to make rational drug targeting decisions.     

Urinary excretion of deoxypyridinoline increases after gastrointestinal surgery

OBJECTIVES: We investigated the effect of gastrointestinal surgery on bone metabolism with special reference to nutrition status and the systemic inflammatory response (SIR). METHODS: We assessed bone resorption by measuring the urinary excretion of deoxypyridinoline (D-Pyr), a specific marker that reflects the amount of degraded collagen. Twenty patients who underwent gastrectomy or colectomy were enrolled in this study. Daily energy intake, nitrogen, calcium, and phosphate balances, and urinary D-Pyr were examined preoperatively and for 14 days after the operation. The nutritional risk index and prealbumin were measured for nutrition assessment, and SIR was evaluated daily based on scorings of body temperature, pulse rate, respiratory rate, and white blood cell number according to our criteria. RESULTS: Urinary D-Pyr excretion had already increased on postoperative day 1 and continued to increase until postoperative day 14. The amounts of postoperative urinary excretion of D-Pyr correlated positively with the SIR scores and the amount of urinary excretion of cortisol, one of the stress-response hormones, and inversely with pre- and postoperative nutritional risk indices. In addition, the patients who experienced complications during the postoperative period excreted larger amounts of D-Pyr. CONCLUSIONS: Because the amount of excreted D-Pyr reflects the loss of the bone matrix, these results may indicate that bone resorption increases after gastrointestinal surgery. The extent of resorption was parallel to the degree of SIR and nutrition status.     

Thermo-chemotherapy using low-dose CPT-11 in a patient with local recurrence of rectal cancer

We report a case of pelvic recurrence of advanced rectal carcinoma, presenting a favorable response with a low dose (25 mg/m2) of CPT-11 (Irinotecan) combined with topical hyperthermia for relapse after treatment with 4 cycles of high-dose (100 mg/m2) CPT-11 chemotherapy alone. This combination therapy was safely carried out on an outpatient basis. The degrees of recovery of the left lower limb pain and edema, and of serum CEA reduction were comparable to those in high-dose chemotherapy alone. No significant adverse effects were encountered in the thermo-chemotherapy attempted. Since hyperthermic treatment enhances the cytotoxic effects of CPT-11 in vitro, topical hyperthermia with low-dose CPT-11 therapy may produce a response comparable to that in high-dose CPT-11 chemotherapy alone. However, an optimal dose and comparative study with other chemotherapeutic agents would be needed. This regimen may be advantageous in the maintenance of quality of life for the palliation of postoperative pelvic recurrence since this treatment can be performed on an outpatient basis.     

Possible chemopreventive effects of bovine lactoferrin on esophagus and lung carcinogenesis in the rat.

A milk component, bovine lactoferrin (bLF), previously shown by us to be a strong chemopreventive of colon carcinoma development, was examined for its influence on other organs using a rat multi-organ carcinogenesis model. Male F344 rats, aged 6 weeks, were treated sequentially with diethylnitrosamine (DEN, i.p.), dihydroxy-di-N-propylnitrosamine (DHPN, in drinking water) and N-nitrosomethylbenzylamine (NMBA, s.c.) during the first 8 weeks (DDN treatment), and then bLF was administered in the basal diet, at a dose of 2, 0.2, 0.02 or 0.002%. Other groups were given DDN treatment or bLF alone as controls. All surviving animals were killed at week 41, and major organs were examined histopathologically for neoplastic lesions. In the esophagus, a tendency for reduction in development of papillomas was evident in the bLF-treated animals, along with a significant suppression of relatively large-sized papillomas (more than 50 mm3 volume) at the 0.2% dose (P<0.05, 11% of the control). The multiplicity of tumors (adenomas and carcinomas) in the lung was also decreased in animals fed 0.02% bLF (1.98+/-0.41 per cm2 lung tissue section, P<0.05) compared to the control group (3.48+/-0.33). No enhancing or inhibitory effects of bLF on tumor development in other organs were noted. The present results indicate that bLF exerts chemopreventive effects in the esophagus and lung in addition to the colon.