Excretion of Methyl Mercury in Human Feces

Fecal excretion of methyl mercury was confirmed in four Japanese male subjects. Perhaps the methyl mercury detected in feces is dependent on (a) the unabsorbed methyl mercury in diet, (b) exfoliation of intestinal cells, (c) hepatic bile, and (d) intestinal methylation of inorganic mercury. The calculated amounts of methyl mercury excreted daily in feces were similar to those found in urine.     

Genetic deregulation of the PIK3CA oncogene in oral cancer

The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is one of the most commonly deregulated pathways in human cancers. PI3K comprises a catalytic (p110α) and regulatory subunit (p85), and p110α is encoded by the PIK3CA gene. Here, we summarize the known genetic alterations, including amplifications and mutations, of the PIK3CA oncogene in oral cancer. We discuss in detail PIK3CA mutations and their mutual exclusivity with pathway genes in addition to the incidence of PIK3CA mutations in relation to ethnicity. We describe the constitutive activation of PI3K signaling, oncogenicity, and the genetic deregulation of the PIK3CA gene and its association with oral cancer disease stage. We emphasize the importance of therapeutically targeting the genetically deregulated PIK3CA oncogene and its signaling. We also discuss the implications of targeting Akt and/or mTOR, which are the downstream effectors of PI3K that may possibly pave the way for molecular therapeutic targets for PIK3CA-driven oral carcinogenesis. Furthermore, this critical review provides a complete picture of the PIK3CA oncogene and its deregulation in oral cancer, which may facilitate early diagnosis and improve prognosis through personalized molecular targeted therapy in oral cancer.     

Early-onset sarcoidosis and CARD15 mutations with constitutive nuclear factor-kappaB activation: common genetic etiology with Blau syndrome

Early-onset sarcoidosis (EOS) and inheritable Blau syndrome (BS) share characteristic clinical features of juvenile-onset systemic granulomatosis syndrome that mainly affects skin, joints, and eyes. However, no direct evidence has been shown for the possible common origin of these 2 diseases. Recent discovery of CARD15 mutations in BS families encouraged us to investigate similar CARD15 mutations in EOS patients. Among 10 EOS cases retrospectively collected in Japan, heterozygous missense mutations were found in 9 cases; 4 showed a 1000C>T (R334W in amino acid change) that has been reported in BS, 4 showed novel 1487A>T (H496L), 1538T>C (M513T), 1813A>C (T605P), and 2010C>A (N670K), and 1 case showed double 1146C>G (D382E)/1834G>A (A612T) mutations on different alleles. All 6 of these variants of CARD15 showed increased basal nuclear factor (NF)-kappaB activity. These findings indicate that the majority of EOS and BS cases share the common genetic etiology of CARD15 mutations that cause constitutive NF-kappaB activation.     

Sevelamer hydrochloride reverses parathyroid gland enlargement via regression of cell hypertrophy but not apoptosis in rats with chronic renal insufficiency.

BACKGROUND: Dietary phosphate restriction suppresses parathyroid hormone (PTH) secretion, synthesis, and parathyroid cell proliferation in experimental animals with chronic renal insufficiency (CRI), independently of serum calcium and 1,25(OH)2D3 levels. This study was conducted to examine whether sevelamer hydrochloride (sevelamer), a metal-free phosphate binder, could regress an advanced parathyroid gland (PTG) hyperplasia and enlargement in rats with CRI. METHODS: Male Sprague-Dawley rats were fed a diet containing adenine for 6 weeks to establish CRI. Normal rats and adenine-treated rats were sacrificed to obtain the PTG (baseline group). The adenine diet was changed to a normal diet or diet containing 1 or 3% sevelamer for another 4 weeks. Time course changes of serum levels of calcium, phosphorus, and PTH were measured. At the end of the study, the PTG was weighed and examined histologically. RESULTS: Adenine-treated rats developed severe CRI with marked elevation of serum phosphorus and PTH. The PTG weight markedly increased with enlarged cell volume (i.e. cell hypertrophy) at baseline. Sevelamer treatment rapidly lowered serum phosphorus and PTH levels within 6 days, and after 4 weeks, reduced the PTG weight by 38% compared to adenine-treated rats at baseline. The reduction in PTG weight was due to regression of cell hypertrophy, but not to decreased cell number by apoptosis. Decreased expression of calcium receptor in the PTG at baseline was partially recovered by the sevelamer treatment. CONCLUSIONS: The sevelamer treatment can reduce the PTG weight with a reduction in serum PTH levels via regression of cell hypertrophy but not apoptosis in rats with CRI. Reduced PTG function might contribute to the regression of cell hypertrophy.     

The cellular localization of 5-HT2A receptors in the spinal cord and spinal ganglia of the adult rat

The localization of serotonin_2A (5-HT_2A) receptors in the adult rat spinal cord and dorsal root ganglia was examined by using a polyclonal antibody that recognizes the C-terminus peptides of the mouse 5-HT_2A receptor. Positive cell bodies of 5-HT_2A receptor were found in several regions of the spinal cord. Generally, large-to-intermediate sized neuronal cell bodies were intensely immunolabeled. Motoneurons in the ventral horn were the most intensely labeled. Dot-like immunoreactive profiles were located beneath the cell membrane of motoneurons. Neuronal somata in the intermediolateral nucleus of the thoracic spinal cord were moderately labeled. The immunoreactivity in the dorsal horn was weak. A considerable number of glial cell bodies in the white matter were immunostained. The majority of both small and large sized neurons were 5-HT_2A immunopositive in the dorsal root ganglion.     

Studies on Wakan-Yakus (traditional herbal drugs) : Especially on the effects of Gaiyoh (Artemisiae folium) on blood coagulation

Wakan-Yakus (traditional herbal drugs) such as Akyoh (Glutinum), Gaiyoh (Artemisiae folium), Sanshishi (Gardeniae fructus), Kizutsu (Aurantii fructus), and Taisoh (Zizyphi fructus) were studied in relation to their effects on blood coagulation-fibrinolysis. (1) All of the water extracts of the Wakan-Yakus prolonged aPTT and PT. The potency of the effectiveness on aPTT was in the order of Gaiyoh (Artemisiae folium)> Kizutsu (Aurantii fructus)> Sanshishi (gardeniae fructus)> Taisoh (Zizyphi fructus )> Akyoh (Glutium). (2) Gaiyoh (Aremisiae folium)> Kizutsu (Aurantii fructus) Akyoh (glutinum) Taisoh (Zizyphi fructus) showed the antifibrinolytic effects in this order. On the other hand, Sanshishi showed the accelerating effect on fibrinolysis. (3) The inhibition modes of both thrombin and plasmin by Gaiyoh (Artemisiae folium) were shown to be competitive on Lineweaver-Burk plot. (4) Gayoh (Artemisiae folium) was gel-filtrated on Sephadex G-25 column (1.5×90cm) equilibrated with distilled water at room temperature. Five fractions were obtained, and in the first to fourth fraction, strong anticoagulant effects on aPTT and PT were observed. We pooled first and second to make fraction I, and make fraction II from peak 3. The recovery rate was 4.2 % by weight, and 36.7 % by inhibition activity, and specific activity on the basis of inhibition to aPTT was 34.8 % U/mg in the case with fraction II. Fraction I was found to be the same characteristically on blood coagulation. Fraction II was further purified by Sephadex LH-20 column (1.5 × 80 cm) at room temperature. Three fractions (Fraction IIa, IIb, IIc) were obtained, and the strong inhibitory effects was observed on both aPTT and PT in each fraction. The first fraction (fraction IIa) showed the strong inhibitory effect on aPTT, and the heightened specific activity with 17.6 % as the recovery rate. Fraction IIb showed strong inhibitory effect on fibrinolysis. Fraction IIb and IIc were found to be similar with fraction IIa characteristically on blood coagulation-fibrinolysis, but could separate the substance for coagulation and fibrinolysis each other on the basis of weight/volume. (5) by ex vivo study using rabbits, aPTTs were prolonged gradually after infusion (60 mg of fraction IIa). White blood cells and platelets were decreased gradually.     

A case of malignant lymphoma, an anemone cell tumor of the leg, arising from osteomyelitis

An 80-year-old man, complaining of multiple fungating growth on his right leg, was hospitalized. A review of his previous history revealed that he had undergone three operations because of repeating osteomyelitis. A clinical examination showed that a tumor was localized on the right leg. Light microscopy revealed that tumor was composed of diffuse large round cell proliferations. Malignant lymphoma was suspected, but was difficult to distinguish in the undifferentiated carcinoma. Electron microscopically, extensive cytoplasmic processes resembling microvilli from the circumferential surface membrane were observed, but desmosomes, tonofilaments, secretory products or basal lamina were not seen. Immunohistochemically, IgG was demonstrated on the tumor cells. These findings led us to diagnoses an anemone cell tumor, originating from a malignant lymphoma and arising from osteomyelitis.     

The efficacy of recombinant interleukin 2 in local treatment of superficial bladder tumors

The present study was undertaken to assess the efficacy of recombinant Interleukin 2 (rIL-2: S-6820) in treatment of superficial bladder tumors. Three intratumor injections at a dose of 5 x 10(5) units/day via urethra, were performed every other day under endoscopic control in 12 patients with superficial bladder cancer. On the 15th day after completion of the series of injections, the tumor had disappeared in one patient and 50% regression over was observed in two other patients. Therefore, the response rate to the rIL-2 treatment in our study was 25.0%. Each tumor which responded to the therapy, was single, small and low grade. In the peripheral blood of the 12 patients, an increase in IL-2 receptor-positive lymphocytes and augmentation of natural killer activity were detected after the rIL-2 intratumor injection. There were no serious side effects except for moderate fever in our study.