Search

Using whole-cell patch-clamp techniques, we demonstrate, for the first time, that rat submandibular acinar cells contain a tetraethylammonium (TEA)-insensitive, Ca(2+)-activated K+ conductance which is not attributable to large conductance, voltage-sensitive, Ca(2+)-dependent K+ channels (maxi-K+ channels). Taken together with our recent K+ efflux and fluid secretion studies in intact rat submandibular gland, we postulate that the K+ conductance reported here may be involved in the basolateral K+ efflux pathway activated by cytosolic Ca2+ concentration during secretion by this gland.

The diffusion coefficient of an 19F-labelled organic acid (3-trifluoromethylhippurate: TFMH) was measured in intact human red blood cells (RBCs) and sealed right-side-out ghosts at 22.5 +/- 0.05 degrees C. Diffusion coefficients were measured using stimulated echo and spin-echo pulsed field gradient sequences. The apparent diffusion coefficient (Da) of TFMH in the intracellular space was much smaller than in the extracellular medium. This was due to restricted diffusion of intracellular TFMH since i) the intracellular Da decreased when the diffusion time was increased, and ii) the smaller Da component disappeared when the membrane was permeabilized with saponin. From the intracellular Da values obtained over a range of diffusion times, from 5 ms to 1 s, the apparent radius of the diffusion barrier was estimated to be 3 +/- 1.1 micron assuming spherical geometry. Despite the high protein concentration in the intracellular space of the intact RBC, the intracellular values of Da were similar to the values obtained in the ghosts at the same diffusion times. We therefore conclude that the small diffusion coefficient of intracellular TFMH is mainly explained by the restricted diffusion due to the cell boundary.

not Available.

not Available.

The effect of malnutrition on survival in patients with decompensated liver cirrhosis has not been well defined. Nutritional intervention with branched-chain amino acid (BCAA) can increase serum albumin concentration in patients with decompensated cirrhosis but its effects on survival are unclear. The BCAA to tyrosine ratio (BTR) is a surrogate marker (the normal range of BTR is between 4.41 and 10.05, and a Fischer’s ratio of 1.8 corresponds to a BTR of 3.5) in patients with decompensated liver cirrhosis, and BCAA inhibits hepatic carcinogenesis in patients with compensated cirrhosis. This review discusses data regarding the effect of early administration of BCAA granules based on the ratio of BCAA to BTR on prognosis in patients with cirrhosis.

The prognosis of hepatocellular carcinoma (HCC) depends on tumor extension as well as hepatic function. Hepatic functional reserve is recognized as a factor affecting survival in the treatment of HCC; the Child-Pugh classification system is the most extensively used method for assessing hepatic functional reserve in patients with chronic liver disease, using serum albumin level to achieve accurate assessment of the status of protein metabolism. However, insufficient attention has been given to the status of amino acid (AA) metabolism in chronic liver disease and HCC. Fischer’s ratio is the molar ratio of branched-chain AAs (BCAAs: leucine, valine, isoleucine) to aromatic AAs (phenylalanine, tyrosine) and is important for assessing liver metabolism, hepatic functional reserve and the severity of liver dysfunction. Although this ratio is difficult to determine in clinical situations, BCAAs/tyrosine molar concentration ratio (BTR) has been proposed as a simpler substitute. BTR correlates with various liver function examinations, including markers of hepatic fibrosis, hepatic blood flow and hepatocyte function, and can thus be considered as reflecting the degree of hepatic impairment. This manuscript examines the literature to clarify whether BTR can serve as a prognostic factor for treatment of HCC.

The involvement of large-conductance, voltage- and Ca(2+)-activated K+ channels (maxi-K+ channels) in basolateral Ca(2+)-dependent K(+)-efflux pathways and fluid secretion by the rat submandibular gland was investigated. Basolateral K+ efflux was monitored by measuring the change in K+ concentration in the perfusate collected from the vein of the isolated, perfused rat submandibular gland every 30 s. Under conditions in which the Na+/K(+)-ATPase and Na(+)-K(+)-2Cl- cotransporter were inhibited by ouabain (1 mmol/l) and bumetanide (50 mumol/l) respectively, continuous stimulation with acetylcholine (ACh) (1 mumol/l) caused a transient large net K+ efflux, followed by a smaller K+ efflux, which gradually returned to the basal level within 10 min. These two components of the K+ efflux appear to be dependent on an increase in cytosolic Ca2+ concentration. The initial transient K+ efflux was not affected by charybdotoxin (100 nmol/l) or tetraethylammonium (TEA) (5 mmol/l) but the smaller second component was strongly and reversibly inhibited by charybdotoxin (100 nmol/l) and TEA (0.1 and 5 mmol/l). The initial K+ efflux transient induced by ACh was inhibited by quinine (0.1-3 mmol/l), quinidine (1-3 mmol/l) and Ba2+ (5 mmol/l), but not by verapamil (0.1 mmol/l), lidocaine (1 mmol/l), 4-aminopyridine (1 mmol/l) or apamin (1 mumol/l). Ca(2+)-dependent transient large K+ effluxes induced by substance P (0.01 mumol/l) and A23187 (3 mumol/l) were not inhibited by TEA (5 mmol/l or 10 mmol/l). A23187 (3 mumol/l) evoked a biphasic fluid-secretory response, which was not inhibited by TEA (5 mmol/l). Patch-clamp studies confirmed that the whole-cell outward K+ current attributable to maxi-K+ channels obtained from rat submandibular endpiece cells was strongly inhibited by the addition of TEA (1-10 mmol/l) to the bath. It is concluded that maxi-K+ channels are not responsible for the major part of the Ca(2+)-dependent basolateral K+ efflux and fluid secretion by the rat submandibular gland.

not Available.

not Available.

Hepatocellular carcinoma (HCC) is a major cause of cancer death, and chronic hepatitis B is a serious worldwide problem. The epidemiology of HCC is distinctive. Hepatitis B virus (HBV) plays a major role in hepatocarcinogenesis. Prevention of HBV-related HCC is a key issue in current hepatology. This paper describes the prevention and clinical features of HBV-related HCC, along with a short review of the disease.

Steam distillates from seed oils and seeds, except for the crusts (embryos), of Momordica charantia L. (Japanese name: Nagareishi and Futoreishi) under reduced pressure (250-310 mmHg) by using a cold trap connected to a receiver and by the SDE method, were extracted with a mixed solvent (C 5 H 12 -Et 2 0, 2:1). In the case of steam distillates from seed oils, seven acidic compounds, nineteen n -paraffins (C 12 -C 20 ), a compound C 10 H 16 0 (M + 152) with a unique fragrance, p -cymene, l -menthol, nerolidol, pentadecanol, hexadecanol and squalene were identified. In the case of seeds, except for the crusts (embryos), nine aldehydes (mainly pentanal, trans -2-hexenal, t -2-heptenal and 2( E ), 4( E )-nonadienal), six alcohols, four acids (mainly valeric acid), four esters (mainly amyl formate and amylvalerate), four acetals, 2-butylfuran and 2-hexanone were identified.

We report the successful treatment of multiple lung metastases after hepatic resection for hepatocellular carcinoma (HCC) with combined docetaxel, cisplatin (CDDP), and enteric-coated tegafur/uracil (UFT-E). A 68-year-old man was diagnosed with multiple lung metastases of HCC 7 mo after partial hepatectomy for HCC. Oral UFT-E was given daily and docetaxel and CDDP were given intra-arterially (administered just before the bronchial arteries) every 2 wk via a subcutaneous injection port. One month after starting chemotherapy, levels of tumor marker, protein induced by vitamin K absence II (PIVKA-II), decreased rapidly, and after a further month, chest X-ray and computed tomography revealed the complete disappearance of multiple liver metastases. Two years after the combined chemotherapy, HCC recurred in the liver and was treated but no pulmonary recurrence occurred. In the absence of a standardized highly effective therapy, this combined chemotherapy with docetaxel, CDDP and UFT-E may be an attractive option for multiple lung metastases of HCC.

Hepatocellular carcinoma (HCC) is the commonest primary liver malignancy. Its incidence is increasing worldwide. Surgery, including transplantation resection, is currently the most effective treatment for HCC. However, recurrence rates are high and long-term survival is poor. Conventional cytotoxic chemotherapy has not provided clinical benefit or prolonged survival for patients with advanced HCC. Cisplatin (CDDP) is a key drug for the standard regimens of various cancers in the respiratory, digestive and genitourinary organs. Recently, several encouraging results have been shown in using CDDP in the treatment of advanced HCC patients. This review examines current knowledge regarding the chemotherapeutic potential of CDDP.

A new hemiterpenoid glycoside, phenylpropanoid glycoside, and furocoumarin were isolated from the methanolic extract of the root and rhizoma of Glehnia littoralis FR. SCHMIDT ex MIQ. (Umbelliferae, "Hamabofu" in Japanese). Their structures were determined by the spectral investigations.

AIM: To evaluate sample adequacy, safety, and needle passes of a new biopsy needle device compared to the Quick-Core biopsy needle for transjugular liver biopsy in patients affected by liver disease. METHODS: Thirty consecutive liver-disease patients who had major coagulation abnormalities and/or relevant ascites underwent transjugular liver biopsy using either a new needle device (18 patients) or the Quick-Core biopsy needle (12 patients). The length of the specimens was measured before fixation. A pathologist reviewed the histological slides for sample adequacy and pathologic diagnoses. The two methods’ specimen adequacy and complication rates were assessed. RESULTS: Liver biopsies were technically successful in all 30 (100%) patients, with diagnostic histological core specimens obtained in 30 of 30 (100%) patients, for an overall success rate of 100%. With the new device, 18 specimens were obtained, with an average of 1.1 passes per patient. Using the Quick-Core biopsy needle, 12 specimens were obtained, with an average of 1.8 passes per patient. Specimen length was significantly longer with the new needle device than with the QuickCore biopsy needle (P < 0.05). The biopsy tissue was not fragmented in any of the specimens with the new aspiration needle device, but tissue was fragmented in 3 of 12 (25.0%) specimens obtained using the Quick-Core biopsy needle. Complications included cardiac arrhythmia in 3 (10.0%) patients, and transient abdominal pain in 4 (13.3%) patients. There were no cases of subcapsular hematoma, hemoperitoneum, or sepsis, and there was no death secondary to the procedure. In particular, no early or delayed major procedure-related complications were observed in any patient. CONCLUSION: Transjugular liver biopsy is a safe and effective procedure, and there was significant difference in the adequacy of the specimens obtained using the new needle device compared to the QuickCore biopsy needle. Using the new biopsy needle device, the specimens showed no tissue fragmentation and no increment in major procedure-related complications was observed.

Equilibrium examinations were performed in 198 healthy individuals over 65 years of age, The characteristic findings were as follows.1. Romberg sign appeared in 7.1% of the cases when vestibulospinal reflex testing was performed. It is suspected that the main cause of Romberg sign in elderly people is a disorder of the deep sensation.2. In nystagmus tests, 5 cases (2.6%) of lateral gaze nystagmus and 14 cases (7.1%) of downbeat positioning nystagmus were observed. However, neither spontaneous nystagmus nor positional nystagmus was seen. Judging from these results, nystagmus testing is an important examinations for the diagnosis of vestibular disorders, even in the elderly.3. Eye tracking testing indicates that, as people age, the smooth pursuit eye movement tends to gradually become more difficult.4. Horizontal optokinetic nystagmus testing should that the total number of nystagmus beats was nearly the same as in the elderly the normal range seen in young people, although the maximum velocity of the slow phase was obviously low in comparison with young people.

Isolated paralysis of downward gaze is not very common. Only six cases have been reported with pathological anatomic findings since Andre-Thomas described the first case with autopsy.A 47 year-old male with isolated paralysis of downward gaze was studied. In the neuro-otological examination, although doll's eye phenomenon of downward eye movement was preserved, neither optokinetic nystagmus nor smooth pursuit eye movement were present in the downward direction.In the six cases that been described with autopsy, bilateral focal infarcts of the rostral mesencephalon were observed.In this case, however, there were no abnormal findings in the rostral mesencephalon, though there were bilateral focal infarcts of the thalamus on CT scan. However, it is difficult to explain in the relationship between the isolated paralysis of downward gaze and the findings on the CT scan.

We studied 22 patients who complained of positional vertigo within 1 week of a head injury. In all of the patients, a characteristic rotatory nystagmus with vertiginous sensation was seen by positioning nystagmus testing. The origin of the vertigo was thought to be a partial inner ear disorder because of the nystagmus findings and the clinical prognosis. On the other hand, there was no remarkable association between the involved side and the direction of rotatory nys tagmus in the head-hanging position. The clinical prognosis showed good results in all cases. However, 11 patients who had central nervous system disorders on neuro-otological examination had a longer recovery period when compared with the other 11 patients who showed no disorder of the central nervous system.

Regulation of the endothelial Na+ channel by Nedd4 and by ubiquitination. The epithelial Na+ channel (ENaC) is comprised of three subunits, α, β and γ, and plays an essential role in Na+ and fluid absorption in the kidney, colon and lung. We had identified proline-rich sequences at the C termini of αβγENaC, which include the sequence PPxY, the PY motif. This sequence in β or γENaC is deleted or mutated in Liddle's syndrome, a hereditary form of arterial hypertension. Our previous work demonstrated that these PY motifs bind to the WW domains of Nedd4, a ubiquitin protein ligase containing a C2 domain, three or four WW domains and a ubiquitin protein ligase Hect domain. Accordingly, we have recently demonstrated that Nedd4 regulates ENaC function by controlling the number of channels at the cell surface, that this regulation is impaired in ENaC bearing Liddle's syndrome mutations, and that ENaC stability and function are regulated by ubiquitination. The C2 domain is responsible for localizing Nedd4 to the plasma membrane in a Ca2+-dependent manner, and in polarized epithelial MDCK cells this localization is primarily apical. In accordance, electrophysiological characterization of ENaC expressed in MDCK cells revealed inhibition of channel activity by elevated intracellular Ca2+ levels. Thus, in response to Ca2+, Nedd4 may be mobilized to the apical membrane via its C2 domain, where it binds ENaC via Nedd4-WW:ENaC–PY motifs' interactions, leading to ubiquitination of the channel by the Nedd4-Hect domain and subsequent channel endocytosis and lysosomal degradation. This process may be at least partially impaired in Liddle's syndrome due to reduced Nedd4 binding, leading to increased retention of ENaC at the cell surface.

The 1H-NMR spectra of the acetyl derivatives of eleven sterols were measured in the presence of an up-field lanthanoide shift reagent (LSR), Ho(fod)3, and the effects of the LSR on the methyl proton resonances were examined. Particularly remarkable results observed for the Ho(fod)3-induced shift spectra were as follows: 1) the skeletal and side chain methyls were shifted to the opposite direction each other, 2) the C-26 and C-27 isopropyl methyls in 24(28)-methylene and 24(28)-ethylidene sterol acetates were rendered non-equivalent, and 3) 24α-and 24β-methyl sterol acetates could easily be differentiated each other.

In an isothermal capacitance transient spectroscopy (ICTS) measurement, analysis of the results is based on the assumption of an exponential capacitance transient. We propose the use of Fourier analysis for the ICTS signal which arises from nonexponential transient capacitance. The method allows us to determine deep levels which have adjacent emission time constants.

Scanning electron microscopic observation of the transtympanic infusion of 10% xylocain revealed twisting and disorders of outer hairs especially from the 2nd and 3rd rows of the basal to the 2nd turn of the organ of Corti, and adhesion and fusion of the sensory hairs of the crista ampullaris and otolith organ 1 and 4 days after injection. Four percent xylocain however demonstrated very minor alteration of the sensory hairs and no missing sensory hairs were detected from any cases. The authors hypothesized from electron microscopic observation that adhesion and fusion of vestibular sensory hairs or twisting and disorders of the sensory hairs of the organ of Corti might act to intercept harmful circulation of exclusion of abnormal excitement of hair cells and the innovation of electrical discharge of sensory hairs due not only to the pharmacological effects of xylocain but also to osmotic pressure.

The absolute configuration at C-24 of chondrillasterol [(24R) -24-ethyl-5α-cholesta-7, (E) -22-dien-3β-ol] isolated previously from gourd seed oil (Cucurbitaceae) and its 24S-epimer, spinasterol, was confirmed by carbon-13 nuclear magnetic resonance spectroscopy. A significant chemical shift difference was observed in the C (21) and C (29) signals between the two epimers.