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Biomedical subjects

N Sano

Publications and source records attributed to N Sano.

At least 109 records · Page 6Linked to original sources

Cytomegalovirus infection of the liver.

Hepatic involvement of cytomegalovirus (CMV) was studied in 15 autopsy cases with disseminated or solitary CMV infection. Formalin fixed, paraffin embedded tissue sections were examined by immunohistochemistry (IHC) and in situ hybridization (ISH). There were three, five and seven positive cases by routine histology, ISH and IHC, respectively. CMV infection was detected not only in cytomegalic cells but also in many normal looking cells by IHC and ISH. The inflammatory reaction in the liver was not so prominent as expected by reports from western countries. The cause of weak inflammatory response in the liver of our cases was discussed.

Adult↗

[A case of small cell lung cancer associated with pulmonary sarcoidosis].

A 63-year-old man with pulmonary sarcoidosis, diagnosed by mediastinal lymph node biopsy in 1977, was admitted in Feb. 1987 because of shortness of breath and cough. Chest X-ray showed bilateral hilar lymphadenopathy and a tumor shadow in the right lung field. Histological examination of specimens biopsied from the right lung revealed small cell carcinoma (S.C.C.). Bronchoalveolar lavage was performed to evaluate the disease activity of sarcoidosis, and the total number of cells and T-lymphocytes; the ratio of CD4+ cells to CD8+ cells was not increased. He was treated with combination chemotherapy, however, he died of respiratory failure after 7 months. An autopsy was performed, and the lesions were examined histologically. The sarcoid lesion in a lymph node obtained at autopsy was not active, in contrast to that obtained by mediastinal lymph node biopsy. Lung cancer and sarcoidosis are both common diseases, but their coexistence in the same patient is not common, and autopsied cases are rare. In this case, an autopsy was performed, and BAL had been performed prior to his death. The relationship between the BAL findings and the histology of sarcoidosis was examined. Based on the results of autopsy and BAL, the sarcoidosis was inactive prior to death, but had been histologically active 10 years previously. Therefore, this is a very interesting case, since we can examine the relationship between the two diseases, and the progression of each disease. This case also provides an interesting example of differentiation of sarcoidosis from S.C.C. Metastatic invasion of the hilar lymph nodes without bronchial stenosis and changes secondary to stenosis may often occur in patients with small cell lung cancer. Such metastatic invasion closely resembles the bilateral hilar lymphadenopathy of sarcoidosis; therefore, in some cases, it may be extremely difficult to differentiate the two diseases.

Bronchoalveolar Lavage Fluid↗

Biliary excretion of bile acid conjugates in a hyperbilirubinemic mutant Sprague-Dawley rat.

The hepatic transport of bile acid conjugates was studied in the Eisai hyperbilirubinuria rat, a Sprague-Dawley mutant rat with conjugated hyperbilirubinemia. Serum bile acid levels were increased, bile acid-independent bile flow was decreased and biliary glutathione concentrations were markedly decreased in the Eisai hyperbilirubinuria rat. Biliary excretion of sulfobromophthalein was markedly impaired and almost no glutathione conjugate was excreted in the bile of the Eisai hyperbilirubinuria rat. Biliary excretion of lithocholate-3-O-glucuronide and lithocholate-3-sulfate in the Eisai hyperbilirubinuria rat was markedly delayed, whereas that of lithocholate was only slightly delayed. After [14C]chenodeoxycholate infusion (1 mumol/min/100 gm for 60 min), the increases in bile flow and biliary excretion of isotope in the Eisai hyperbilirubinuria rat were not so prominent as those observed in control rats, and the glucuronide of chenodeoxycholate, which constituted about 15% of biliary chenodeoxycholate in control rats, was not observed in the Eisai hyperbilirubinuria rat. Initial uptake of lithocholate and its glucuronide and sulfate by isolated hepatocytes was not impaired in the Eisai hyperbilirubinuria rat; the profiles of cytosolic bile acid binding proteins in Eisai hyperbilirubinuria rat liver were identical to those in control liver. These data indicate that the Eisai hyperbilirubinuria rat has excretory impairment of organic anions, bile acid glucuronide and sulfate and that it has characteristics very similar to those of the hyperbilirubinemic mutant Wistar rats TR- and GY.

Animals↗

[Magnetic resonance imaging of skeletal muscle in patients with Duchenne muscular dystrophy--serial axial and sagittal section studies].

Magnetic resonance imaging of skeletal muscles in thirteen patients with Duchenne muscular dystrophy was performed to estimate pathological changes. Serial axial and sagittal sections of the right lower extremity were recorded. In the early stage, the T1 values of gastrocnemius and soleus muscles were slightly lower than the control values, and in the late stage, the values were much lower in all muscles examined. In sagittal sections, the gastrocnemius muscles in the early stage showed a high density area at the distal region adjacent to soleus muscle, and the soleus muscle showed a high density area adjacent to the gestrocnemius muscle. In serial axial sections, high density areas of the anterior and posterior tibialis muscles appeared first at their proximal and peripheral regions. It was concluded that the sequence of appearance of pathological changes was different not only among individual muscles but also among various regions of each muscle; the high density changes appeared first at myotendon junctions.

Adolescent↗

Glucuronidation of bile acids by their high-dose infusion into rats.

We previously reported that high-dose infusion of ursodeoxycholate into rats caused its extensive glucuronidation. In this study, the glucuronidation of various bile acids after high-dose infusion into rats was examined and the effects of coinfusion of bile acids on the glucuronidation of a trace dose of [14C]deoxycholate were also studied. Sixty minutes after infusion of 14C-bile acids at a rate of 1 mumol/min/100 gm, the glucuronidation of the labeled bile acid in the bile was 31%, 15%, 8% and 3% for deoxycholate, ursodeoxycholate, chenodeoxycholate and cholate, respectively. The infusion of a trace dose of [14C] deoxycholate resulted in only 2% glucuronidation, and coinfusion of taurochenodeoxycholate or tauroursodeoxycholate at a rate of 1 mumol/min/100 gm did not change the percentage of glucuronidation of [14C]deoxycholate. However, coinfusion of chenodeoxycholate, ursodeoxycholate or cholate at the same rate markedly increased the percentage of the [14C]deoxycholate-glycuronide in the bile (35%, 18% and 36%, respectively). Thus glucuronidation of bile acids by high-dose infusion into rats occurs predominantly with deoxycholate and is not specific for ursodeoxycholate, and glucuronidation depends on the unconjugated bile acid load, which might be regulated by the capacity of amidation by the liver.

Animals↗

The ursodeoxycholate dose-dependent formation of ursodeoxycholate-glucuronide in the rat and the choleretic potencies.

The reason for the discrepancy between bile flow and biliary bile acid excretion during ursodeoxycholate infusion in rats is unknown. We found that ursodeoxycholate-glucuronide is formed during ursodeoxycholate infusion at higher doses. Ursodeoxycholate infusion (1 to 3 mumol/min/100 gm body weight) for 90 min caused marked hypercholeresis, and the previously reported discrepancy between bile flow and biliary bile acid excretion was observed when bile acid concentrations were measured by regular enzymatic methods. However, the appearance of ursodeoxycholate-glucuronide was observed on thin-layer chromatography analysis and up to 30% of the ursodeoxycholate in bile was found to be glucuronidated when determined by the enzymatic method after beta-glucuronidase treatment. The choleretic activity of ursodeoxycholate-glucuronide (25.2 microliters/mumol) was about 3 times higher than that of ursodeoxycholate (8.9 microliters/mumol) when infused at 0.25 mumol/min/100 gm body weight and ursodeoxycholate-glucuronide also stimulated higher biliary bicarbonate excretion than ursodeoxycholate. These results indicate that the discrepancy between bile flow and biliary bile acid excretion caused by high-dose infusion of ursodeoxycholate into rats can be explained by glucuronide conjugation of ursodeoxycholate that cannot be detected by the regular enzymatic method. The glucuronidation of ursodeoxycholate might also be important in the ursodeoxycholate-induced increase in biliary bicarbonate excretion.

Animals↗

Effects of 2,2'-azobis (2-amidinopropane) hydrochloride in vivo and protection by vitamin E.

2,2'-Azobis (2-amidinopropane) hydrochloride (AAPH), a compound that decomposes spontaneously to generate free radicals, was administered intraperitoneally to rats. High doses (greater than or equal to 70 mg/kg) were always fatal within a few hours. At nonlethal levels, AAPH was found to be absorbed into the circulation where it remained with a half-life of about 30 min. Lipid peroxidation was observed to occur in the liver and, to a much smaller extent, the kidney and heart of treated rats; levels of thiobarbituric acid-reactive substances were unchanged in the lung and brain, and significantly reduced in the plasma. Serum lipid levels were also lower in the AAPH-treated rats. Orally administered vitamin E, but not its water soluble analog, prevented the accumulation of TBA-reactive substances in the livers of AAPH-treated rats in a dose-dependent manner, but had no effect on mortality or the changes in serum lipid levels. The data suggest that intraperitoneally administered AAPH is absorbed into the circulation and can induce lipid peroxidation in vivo, but that toxicity may also arise through nonradical mechanisms. Furthermore, the free radical toxicity of AAPH in vivo may not be so general as previously suggested.

Amidines↗

Hyperthermia-induced seizures with a servo system: neurophysiological roles of age, temperature elevation rate and regional GABA content in the rat.

A servo system including a microwave generator was applied to raise a rat's body temperature at a pre-set rate. Using this system the effects of age and the temperature elevation rate upon febrile seizures in rats were studied. The relationship between the brain GABA content and hyperthermia was also studied. From the results of the present study, the seizure occurrence rate was found to be highest at the age of 20 days, brain damage was speculated to be severe after hyperthermia-induced seizures with a slow temperature rise, and the regional GABA concentration in subcortical structures was found to increase during hyperthermia. These data indicate that a servo system with a microwave generator is useful for experimental febrile convulsions, and that GABA neurotransmission in subcortical structures might contribute to feed-back regulation against seizures during hyperthermia.

Aging↗

Determination of the primary structure of intermolecular cross-linking sites on the Ca2(+)-ATPase of sarcoplasmic reticulum using 14C-labeled N,N'-(1,4-phenylene)bismaleimide or N-ethylmaleimide.

To determine the intermolecular cross-linking site on the primary structure sarcoplasmic reticulum (SR) Ca-ATPase, the conditions for the specific binding of 14C-labeled 1,4-phenylene bis maleimide (PBM) or 14C-labeled N-ethylmaleimide (NEM) to the ATPase were explored. SR vesicles were preincubated with nonradioactive PBM in the presence of 1 mM vanadate for 1 h, then washed by centrifugation to remove free PBM and vanadate. When the pretreated SR vesicles were allowed to react with 1 mM [14C]PBM in the presence of 1 mM AMPPNP, the amount of [14C]PBM incorporated into the ATPase increased with time in parallel with the formation of dimeric ATPase and reached the maximum labeling density of 1 mol of [14C]PBM per mol of dimeric ATPase at 40 min after the start of the reaction. When the pretreated SR vesicles were allowed to react with 2 mM [14C]NEM in the absence of AMPPNP, a maximum of about 2 mol of NEM was bound per mol of the ATPase monomer. The labeling density of [14C]NEM decreased from 2 to 1 mol per mol of the ATPase when the SR vesicles were allowed to react with [14C]NEM in the presence of AMPPNP. From the analysis of the amino acid composition of the two major [14C]NEM-labeled peptides isolated from the thermolytic digest of the enzyme after the reaction of SR with [14C]NEM in the absence of AMPPNP, we deduced that [14C]NEM was incorporated into Cys377 and Cys614. On the other hand, the labeling of SR in the presence of AMPPNP resulted in inhibition of the [14C]NEM binding to Cys614, leaving Cys377 unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗

Functional relationships between platelet alpha 2-adrenoceptors and sympathetic nerve activity in clinical hypertensive states.

Tritiated yohimbine binding was used to estimate platelet membrane alpha 2-adrenoceptor characteristics in normal subjects (n = 12) and patients with essential hypertension (n = 30), primary hyperaldosteronism (n = 10) and phaeochromocytoma (n = 10). There was a 20-fold increase in mean levels of resting norepinephrine and epinephrine in the phaeochromocytoma group. Total binding sites (Bmax) and dissociation constant (Kd) for 3H-yohimbine did not differ significantly among the four groups. Following curative surgery for phaeochromocytoma, plasma catecholamine levels were normalized but the Bmax remained unchanged. Following surgery for primary hyperaldosteronism, levels of plasma norepinephrine rose but Bmax was not changed. In all but the phaeochromocytoma patients, Bmax values correlated positively (r = 0.437, n = 48, P less than 0.01) with resting plasma norepinephrine. A significant negative correlation was observed between the change in plasma norepinephrine in response to postural change and resting Bmax. Treatment for 2-4 weeks with guanabenz or bethanidine induced a parallel fall in both Bmax and plasma norepinephrine. Treatment with reserpine was followed by a comparable fall in plasma norepinephrine, but Bmax values were unchanged. The findings support the view that platelet alpha 2-adrenoceptor density is functionally regulated in parallel with sympathetic nerve activity rather than circulating catecholamine levels, although it is not known which neuronal substance(s) may participate in this regulation.

Adrenal Gland Neoplasms↗

Shift in the baroreflex-renal noradrenaline spillover curve during the development of congestive heart failure in the rabbit.

1. Changes in renal sympathetic nerve activity (RSNA) were investigated during the development of congestive heart failure (CHF) in rabbits with doxorubicin-induced cardiomyopathy. 2. Controls (saline treated, n = 5) and doxorubicin-treated rabbits (1 mg/kg administered intravenously twice weekly, n = 5) were studied after 4 and 6 weeks treatment. 3. RSNA was estimated by measuring renal noradrenaline spillover rate under resting conditions and in response to changes in arterial pressure induced by phenylephrine and sodium nitroprusside infusions. 4. In the doxorubicin-treated group, resting renal noradrenaline spillover was increased at 4 weeks (24.2 ng/min, s.e.m. = 2.5, n = 5) compared with controls (15.2 ng/min, s.e.m. = 2.4, n = 5; P less than 0.01) and remained elevated. 5. The baroreceptor-renal noradrenaline spillover curve showed a significant upward shift in the doxorubicin-treated group at 4 weeks. After 6 weeks both heart rate and renal noradrenaline spillover responses to hypotension were significantly blunted. 6. It is suggested that increased RSNA occurs early during the development of CHF in doxorubicin-treated rabbits. The observed changes in the baroreflex responses suggest that different mechanisms may contribute to this increased RSNA at different stages of CHF.

Animals↗

Renal norepinephrine spillover and baroreflex responses in evolving heart failure.

Renal sympathetic nerve activity (RSNA), as assessed by norepinephrine (NE) spillover, was examined in conscious rabbits with adriamycin-induced cardiomyopathic heart failure (n = 5) and in control rabbits (n = 5). Each rabbit was studied after 4 and 6 wk of adriamycin (2 mg.kg-1.wk-1) or vehicle under resting conditions and in response to changes in mean arterial pressure (MAP) produced by infusions of sodium nitroprusside and phenylephrine. Basal renal NE spillover rate was significantly increased after 4 wk of adriamycin treatment compared with controls (24.2 +/- 2.5 vs. 15.2 +/- 2.4 ng/min, P less than 0.05). At this stage the two groups had similar systemic hemodynamics and renal blood flows. The baroreflex-renal NE spillover response to hypotension in the adriamycin-treated group showed a significant upward shift. After 6 wk of adriamycin treatment, there were significant falls in resting MAP (74 +/- 3 vs. 86 +/- 2 mmHg, P less than 0.01) and renal blood flow (78 +/- 6 vs. 109 +/- 8 ml/min, P less than 0.05). At this stage of established heart failure, resting renal NE spillover rate remained elevated but there was significant blunting of the baroreflex-renal NE spillover response. These results suggest that, in this model of low-output heart failure, there is an early increase in resting renal sympathetic activity that is sustained. The baroreflex-renal NE spillover curve changes during the course of development of heart failure.

Animals↗

Isolation, culture, and transplantation of intrahepatic biliary epithelial cells and oval cells.

Recent advances made in the isolation, culture, and transplantation of defined populations of intrahepatic biliary epithelial cells and oval cells have permitted direct analysis of the functions, growth properties, and differentiation potential of these respective cell types in their untransformed or transformed states. This review provides a current and comprehensive examination of the various approaches that have been taken to isolate and culture intrahepatic biliary epithelial cells from normal and cholestatic liver and oval cells from preneoplastic liver. Emphasis is placed on comparing the phenotypic features and growth properties of these various biliary cell types in vitro as well as on describing their transplantation into ectopic tissue sites. In addition, the oval cell is evaluated in terms of its potential role as a 'facultative stem cell' during hepatocarcinogenesis.

Animals↗

[Aging effects on upper and lower half visual fields by VECPs and automated static perimetry].

We studied the aging effects on upper and lower half visual fields using pattern VECPs with half fields stimuli and automated static perimetry. The subjects, consisting of 56 normal volunteers ranging in age from 10 to 69 years old, were divided into three groups (10-29, 30-49, 50-69 years old). Their visual acuities were better than 1.0 and refractive errors were within +/- 2.0 diopters. Perimetry was performed with an automated perimeter (Octopus, program 61). An artificial pupil of 3 mm was used after cycloplegia with 1% tropicamide to eliminate senile miosis effects in recording of VECPs. Subjective light sensitivity decreased with age and there was a noticeable hiatus between the third and fourth decades. However the age-related decrease in sensitivity showed no difference between the upper and lower half fields. However VECPs results showed that with aging the P100 peak latency did not increase for lower half field stimuli, but increased for the upper half field stimuli, especially for smaller check sizes. These results suggested that there were different aging processes a in the upper and lower half fields and higher neural factors participated in the effects.

Adolescent↗

[Spatial frequency characteristics of upper and lower hemiretina with pattern reversal VECPs].

We studied the spatial frequency characteristics in the upper and lower hemiretina using pattern reversal VECPs. The subjects were 56 normal volunteers ranging in age from 14 to 69 years old. The latency of the first major positive component (P100) of VECPs was measured using checker board pattern stimuli under varying conditions of spatial frequency (112', 56', 28', 14', 7'). For the upper hemiretinal stimuli, the P100 peak latency vs spatial frequencies curve reached minimum at 56' approximately 28' and increased at both lower and higher frequencies. For the lower hemiretinal stimuli, this curve shifted towards lower frequencies. The results suggested that the spatial frequency characteristics between the upper and lower hemiretina were different.

Adolescent↗

Comparison of biliary excretion and metabolism of lithocholic acid and its sulfate and glucuronide conjugates in rats.

Biliary excretion and biotransformation of tracer doses of [14C]lithocholic acid and its sulfate and glucuronide intravenously injected into bile-drainaged rats were compared. Biliary excretion efficiency was in the order of unconjugate sulfate glucuronide and all conjugates were completely excreted into bile within 60 min after injection. Only tracer doses of radioactivity were found in the liver and urine. About 90% of radiolabeled bile acids in bile were conjugated with taurine immediately after injection of lithocholic acid, whereas lithocholic acid-glucuronide was only partly conjugated with taurine all the time (less than 6%) and excreted into bile mainly as native compound. In the first 10 min, 66% of lithocholic acid-sulfate was conjugated with taurine and it gradually proceeded up to 87%. Hydroxylation at C-6 and C-7 positions of lithocholic acid proceeded time-dependently up to 45%. No hydroxylation was observed with lithocholic acid-sulfate or glucuronide. Differences of biliary excretion rate of these conjugates may be one of the reasons for the delayed decrease of sulfated and glucuronidated bile acids in serum after bile drainage to patients with obstructive jaundice of during the recovery of acute hepatitis than non-esterified bile acids.

Animals↗

Induction of soft tissue tumours in F344 rats by subcutaneous, intramuscular, intra-articular, and retroperitoneal injection of nickel sulphide (Ni3S2).

The carcinogenicity of nickel sulphide (Ni3S2) injected into subcutaneous (s.c.), intramuscular (i.m.), or retroperitoneal intrafat (i.f.) tissue, or the intra-articular space (i.a.) of male F344 rats was studied. Rats were given a single injection of 0.5 mg of Ni3S2 and were observed for 48 weeks. Malignant soft tissue tumours were induced in 18/19 rats (95 per cent) by s.c. injection, 19/20 rats (95 per cent) by i.m. injection, in 16/19 rats (84 per cent) by i.a. injection, and in 9/20 rats (45 per cent) by i.f. injection of Ni3S2. The i.f. injection of Ni3S2 resulted in a lower tumour incidence and the appearance of tumours 10 weeks later than its injection by other routes. The tumours were examined histologically, ultrastructurally, and immunohistochemically with antibodies against desmin, vimentin, and cytokeratin. The 62 tumours induced by injection of Ni3S2 by different routes were identified as rhabdomyosarcomas (RMS, 35), malignant fibrous histiocytomas (MFH, 18), fibrosarcomas (FS, 5), and unclassified sarcomas (4). All 19 tumours induced by i.m. injection of Ni3S2 were rhabdomyosarcomas; those induced by s.c. or i.f. injection were mainly MFHs. However, a number of RMSs were also found in groups that received i.a., s.c., and i.f. injections; five FSs also developed in these groups. Four sarcomas induced by s.c. and i.a. injections were not classified. No synovial sarcoma developed.

Animals↗