A case of recurrent biliary cystadenocarcinoma successfully treated with 5FU/CDDP systemic chemotherapy]

We report a case of biliary cystadenocarcinoma which recurred 41 months postoperatively. A 60-year-old woman was admitted for further examination of multiple metastatic tumors and a large amount of ascites. Systemic administration of 5FU and CDDP caused her CEA level to decrease gradually and abdominal computed tomography revealed considerable reduction of the metastatic tumors and ascites. Since her general condition had improved, chemotherapy was continued in the outpatient clinic.     

Intrarenal localization of receptors for alpha-rat atrial natriuretic polypeptide: an autoradiographic study with [125I]-labeled ligand injected in vivo into the rat aorta

We examined intrarenal localization of receptors for alpha-rat atrial natriuretic polypeptide (alpha-rANP) by injecting [125I]-labeled ligand in vivo into the rat aorta. We found that the receptors for alpha-rANP are distributed also on the vasa recta of the outer and inner medulla in addition to the previously reported sites, i.e., the renal arteries, renal pelvis, glomeruli, and inner medullary tissues including collecting tubules. In the vascular bundle of the outer medulla, the majority of grains was preferentially localized on the arterial vasa recta. The electron microscopic autoradiography of the glomerulus showed that the binding sites were mainly localized on the foot process of the podocyte. Since alpha-rANP injected into the aorta under physiological conditions was bound to the glomerulus and vasa recta in the kidney, the effect of ANP on these binding sites may be important in the mechanism of natriuresis.     

Use of cultured tubular cells isolated from human urine for investigation of renal transporter

AIM: To facilitate the understanding of the transporter function of human renal tubular cells, we have developed a simple method using primary cultured proximal tubule (PT) cells isolated from voided urine. METHODS: PT cells grown to confluence on glass coverslips could be identified by parallel arrays of spindle cells and hemicyst formation. Brush-border gamma-glutamyl transpeptidase (gammaGTP) activity was histochemically identified. Apical membrane Na+/H+ exchanger (NHE) activity was measured by monitoring changes in intracellular pH (pHi) after an acid load in a single cell level using the pH-sensitive dye 2'7'-bis-(2-carboxyethyl)-5.6'carboxyfluorescein (BCECF). RESULTS: Amiloride and 5-(N-ethyl-N-isopropyl) amiloride (EIPA) inhibited the NHE activity with half-maximal inhibition values (IC50) of 15.3 and 4.0 microM, respectively. NHE-3 mRNA was detected by the RT-PCR technique in clonally proliferated PT cells. CONCLUSION: These results suggest that cultured PT cells isolated from human urine express amiloride-resistant NHE-3 activity on the apical membranes, which can be compared to functional properties of PT in vivo. Our experimental strategy offers a useful experimental approach to investigating human renal tubular transport function in vitro.     

Elevated plasma levels of transforming growth factor beta1 in patients with muscular dystrophy

The progression of muscular weakness of patients suffering from muscular dystrophies directly correlates with the progressive loss of myofibers, accompanied by fibrosis. Since transforming growth factor beta1 (TGF-beta1) promotes tissue fibrosis, we measured the plasma TGF-beta1 level in patients with various muscular dystrophies in order to determine whether the level is elevated in patients with muscular dystrophy and if the level reflects the severity of tissue fibrosis. The plasma TGF-beta1 level was significantly elevated in patients with Duchenne muscular dystrophy and congenital muscular dystrophy (CMD), but not in those with Becker muscular dystrophy. Growth factors related to muscle fiber regeneration and fibrosis might be a key factor in the progression of muscular dystrophy and could be a target for therapeutic studies.     

Legionella pneumonia which occurred in a private whirlpool bath user

A 88 year old female with active rheumatoid arthritis treated by low dose of prednisolone and methotrexate was admitted to our hospital because of severe bilateral pulmonary infiltration and acute respiratory distress syndrome. On admission, she had consciousness disturbance and was intubated because of severe respiratory failure. We heard from her family of her habit she had taking a private whirlpool bath 2 or 3 times everyday. So, we suspected a Legionella pneumophila infection. We started intravenous erythromycin (EM) (1,500mg/day) and methylprednisolone pulse therapy (1,000mg x 3days) and full controlled mechanical ventilation supported with PEEP. Her respiratory failure was gradually improved and she was discharged on the 44 the hospital day. Legionella pneumophila (serogroup 6) was isolated in her sputum by B-CYE alpha culture. Legionella pneumophila (serogroup 6) was isolated in her private whirlpool bath too. Both samples revealed the same by genetic analysis with pulse field gel electrophoresis (PFGE). This is the first adult case of Legionella pneumophila pneumonia infected from a private whirlpool bath confirmed by genetic analysis. We should always suspect Legionella pneumonia as one of the severe community-acquired pneumonia, because Legionella pneumophila were frequently detected among various water sources including the private whirlpool bath.     

Mitochondrial K<Subscript>ATP</Subscript> channel-dependent and -independent phases of ischemic preconditioning against myocardial infarction in the rat

To obtain insight into the role of the mitochondrial ATP-sensitive K(+) (mitoK(ATP)) channel in ischemic preconditioning (PC), we aimed to clarify the mitoK(ATP) channel-dependent phase of PC in two PC protocols with different intervals between PC ischemia and an index ischemia. The possible contribution of mitoK(ATP) channel opening to protein kinase C activation in PC was also examined by Western blotting. Myocardial infarction was induced by 30-min coronary occlusion/2-h reperfusion in rat hearts in situ, and infarct size was expressed as a percentage of the area at risk (% IS/AR). PC was performed with 2 episodes of 5-min ischemia, and each heart was subjected to 30-min ischemia either 5 min or 20 min after PC. At 5 min after PC, both PKC-delta and -epsilon were translocated and the myocardium was protected against infarction (% IS/AR = 28.3 +/- 2.7 % vs. 72.7 +/- 2.2 in controls p < 0.05). Pretreatment with a selective mitoK(ATP) channel blocker, 5-hydroxydecanoate (5-HD, 10 mg/kg), abolished the cardioprotection but not PKC translocation by PC. At 20 min after PC, PKC translocation remained at the same level as that 5 min after PC, but the anti-infarct tolerance was attenuated (%IS/AR = 43.5 +/- 4.7 %). Injection of 5-HD after PC did not affect anti-infarct tolerance at 5 min after PC but abolished the protection at 20 min after PC without any effects on PKC. These results suggest that the mitoK(ATP) channel plays a role in triggering of PC in a PKC-independent manner and that the role of the mitoK(ATP) channel as a mediator of protection is detectable after, but not before, the PC effect starts to decay without a change in the level of PKC translocation in the rat heart.     

Enhanced constitutive invasion activity in human nontumorigenic keratinocytes exposed to a low level of barium for a long time

We have recently demonstrated that exposure to barium for a short time (≤4 days) and at a low level (5 µM = 687 µg/L) promotes invasion of human nontumorigenic HaCaT cells, which have characteristics similar to those of normal keratinocytes, suggesting that exposure to barium for a short time enhances malignant characteristics. Here we examined the effect of exposure to low level of barium for a long time, a condition mimicking the exposure to barium through well water, on malignant characteristics of HaCaT keratinocytes. Constitutive invasion activity, focal adhesion kinase (FAK) protein expression and activity, and matrix metalloproteinase 14 (MMP14) protein expression in primary cultured normal human epidermal keratinocytes, HaCaT keratinocytes, and HSC5 and A431 human squamous cell carcinoma cells were augmented following an increase in malignancy grade of the cells. Constitutive invasion activity, FAK phosphorylation, and MMP14 expression levels of HaCaT keratinocytes after treatment with 5 µM barium for 4 months were significantly higher than those of control untreated HaCaT keratinocytes. Taken together, our results suggest that exposure to a low level of barium for a long time enhances constitutive malignant characteristics of HaCaT keratinocytes via regulatory molecules (FAK and MMP14) for invasion. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 161–167, 2015.     

Calpain 10 gene polymorphisms are related, not to type 2 diabetes, but to increased serum cholesterol in Japanese

A G-to-A (UCSNP-43) polymorphism of the calpain-10 gene was significantly associated with type 2 diabetes (DM) in Mexican-American, and was postulated, together with a T-to-C (UCSNP-44) polymorphism, as a risk factor for DM. We examined the association of these genotypes with DM in Japanese. Eighty-one subjects with DM and 81 non-diabetic subjects (NGT) were recruited. The number of subjects with genotypes UCSNP-43 G/G, G/A and A/A were 76, 5 and 0, respectively, for the DM and NGT groups. The number of subjects with genotypes UCSNP-44 T/T, T/C and C/C were 66, 14 and 1 for the DM group and 64, 17 and 0 for the NGT group. There was no difference between the groups in terms of frequency of any genotype combinations. No association between the genotypes and DM was observed. We next examined the differences between the genotypes or genotype combinations in terms of the traits related to DM, obesity, hypertension and dyslipidemia. No differences were observed between the genotypes UCSNP43 G/G and G/A, between UCSNP-44 T/T and the others, or between the genotype combination UCSNP-43 G/G and UCSNP-44 T/T and the others, except that the individuals with the genotype combination had significantly increased serum cholesterol levels (212.6 +/- 34.3 vs. 198.5 +/- 29.9, P=0.020). The genotype combination might be a risk factor, not for DM, obesity and hypertension, but for increased serum cholesterol.