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Biomedical subjects

M Hisaoka

Publications and source records attributed to M Hisaoka.

At least 73 records · Page 4Linked to original sources

An ultrastructural comparison of sinusoids in hepatocellular carcinoma, adenomatous hyperplasia, and fetal liver.

Transmission and scanning electron microscopic examinations were performed to evaluate the fine-structural differences in sinusoids of hepatocellular carcinoma, adenomatous hyperplasia of the liver, and fetal livers. In cancerous sinusoids, thickened endothelial cells with loss of sieve plates were conspicuous features. In the sinusoids of adenomatous hyperplasia, scanning electron microscopy showed apparent sieve plates, and basement membrane formation (capillarization) was less conspicuous than in carcinoma. In fetal livers, occasional large gaps as well as small fenestrations in the endothelium were noted. Basement membrane materials were not seen. It was concluded that the sinusoids of hepatocellular carcinoma lost the fine-structural nature of normal sinusoids and showed much more prominent capillarizations than the sinusoids of adenomatous hyperplasia, and that the fine structures of cancerous sinusoids were also different from those of the sinusoids in fetal livers.

Adenoma↗

Primary actinomycosis in the liver.

We present a case of a 71-year-old female with actinomycosis in the liver, which is a rare region to be primarily affected with actinomycosis. The diagnosis was done histopathologically with a partially resected liver specimen taken during surgery for choledocholithiasis. There were no clinical signs of Actinomyces infection before surgery. The hepatic lesion was a 2 cm sized nodule with histological appearances of abscess-forming suppurative inflammation with fibrosis, in which eosinophilic radiate granules with peripheral clubs were found. The Brown-Brenn stain showed Gram-positive branched filamentous bacilli, which were revealed as acid-fastness by the Ziehl-Neelsen method of Putt's modification. These findings were considered to be consistent with actinomycosis of the liver.

Actinomycosis↗

Lymphoepithelial cyst of the pancreas in a 65-year-old man.

A case of an extremely rare cystic lesion of the pancreas is presented. The multilocular cyst was found adjacent to the upper border of the pancreatic body, and the cyst contained bean curd lees-like substances. Histologically, the cyst wall consisted of mature keratinizing squamous epithelium and surrounding lymphoid tissue stroma, and the cyst was filled with keratinized materials. A histopathologic diagnosis of typical lymphoepithelial cyst of the pancreas, proposed by Truong et al (Am J Surg Pathol 11:899-903, 1987), was made. Its histogenesis is still unknown; however, we hypothesize that it might arise from a benign epithelial inclusion of a peripancreatic lymph node, followed by squamous metaplasia of the epithelial inclusion. We recently found a retropyloric lymph node with a squamous epithelial inclusion, which might support this hypothesis regarding the histogenesis of the cyst.

Aged↗

Melanocytic schwannoma in the spinal canal.

A case of melanocytic schwannoma, a rare form of schwannian neoplasm, in the thoracolumbar spinal canal of a 52-year-old man is presented. Histopathologically, the tumor was composed of irregularly interlacing spindle-shaped cells showing cystic degeneration, with occasional pigmented tumor cells. The tumor cells showed a low degree of nuclear pleomorphism without any mitotic figures. These histological features were considered to be consistent with a benign schwannian tumor showing pigmentation. Most of the pigments were considered to be melanin histochemically and immunohistochemically. According to the pathological features of the present tumor and those described previously in the literature, the neoplastic Schwann cells were assumed to have melanogenetic capacity, and the concept of the common neural crest origin of Schwann cells and melanocytes appeared to be demonstrated in the present tumor.

Humans↗

A scanning electron microscopic study of postnatal development of rat peribiliary plexus.

Hepatic microcirculation in the developing stages is not fully clarified. This study aimed at clarifying the development of hepatic microcirculation, especially peribiliary vascular plexuses, in neonatal rats by corrosion cast procedures and scanning electron microscopy. Peribiliary vascular plexuses of large bile ducts at the hilus of 1-day-old rats showed a simple capillary network that directly poured into the portal vein. The hepatic artery promptly tapered down into many small branches and ended in sinusoids or capillary plexuses around portal vein branches near the hilus. Neither apparent hepatic artery branches nor peribiliary vascular plexuses were found in the peripheral areas of the liver. On the seventh day, very loose peribiliary vascular plexuses and small hepatic artery branches appeared up to the peripheral portal tracts, and the peribiliary vascular plexuses of large bile ducts were still capillary networks. After the seventh day, peribiliary vascular plexuses of large and medium-sized portal tracts often poured into side branches of the portal vein rather than directly into the portal vein as shown in the rats from the first day mentioned above. Peribiliary vascular plexuses of the large bile duct in 2-week-old rats showed a double layer, that is, an outer layer composed of arteries and veins and an inner layer of capillary vessels, that resembled peribiliary vascular plexuses of adult livers. After nearly 4 wk, hepatic microcirculations had almost fully developed into those of adult rats. It was concluded that the gradual postnatal development of the hepatic arterial system and the peribiliary vascular plexuses occurred in parallel with the maturation of the intrahepatic biliary trees.

Aging↗

Morphological changes of hepatic microcirculation in experimental rat cirrhosis: a scanning electron microscopic study.

Morphological changes of hepatic microcirculation, especially peribiliary plexus, in experimental rat cirrhosis that resulted from the repeated intraperitoneal injections of N-diethylnitrosamine, 100 mg/kg body weight/one shot/week, were examined by scanning electron microscope. Control rats were treated with saline. Whole blood vessels of the rats were perfused by saline and stuffed with methylmethacrylated resin. Multiple nodular changes were seen in the livers after the five injections (5 wk) of N-diethylnitrosamine, and diffuse nodular transformations mimicking human cirrhosis after six injections (6 wk) were also seen. Overall changes in experimental rats were numerous vascular channels mainly composed of venous branches around the parenchymal nodules, increased arterioportal anastomoses and flattening of veins, especially hepatic vein branches. Peribiliary plexuses of the experimental rats were much richer in the vessels than those of the controls, and many dilated veins, ramified from portal vein branches, were present in the former. Direct connections between peribiliary plexuses and sinusoids or between peribiliary plexuses and portal veins increased in the experimental rats. Studies concerning microcirculatory changes of peribiliary plexuses in experimental rat cirrhosis are rare. It was concluded that the abnormal peribiliary plexuses in this experimental series might participate in a collateral circulation under a state of portal hypertension.

Animals↗

Unusual proliferation of the pancreatic endocrine cells in adults, suggestive of islet cell metaplasia.

We present two adult autopsy cases with malignancy, in which unusual proliferation of the pancreatic endocrine cells was observed. Histopathological examination revealed extensive proliferation of the pancreatic endocrine cells throughout the pancreata in both cases. The islets of the pancreas were enlarged with irregular contours. An admixture of the islet cells, acinar cells and ductular epithelial cells was also observed. Immunohistochemically, these islets were composed of the endocrine cells of various types, i.e. A-, B-, D- and PP-cells, and they showed a predominance of PP-cells. Clinically, endocrine hyperfunction of the pancreas was not detected in either cases. Although this histological change may be described as endocrine cell hyperplasia or dysplasia, the close connection of the islet cells, acinar cells and ductular epithelial cells might rather suggest metaplastic change of the acinar or ductular cells into the islet cells under unknown stimuli.

Carcinoma, Squamous Cell↗

Three-dimensional observation of the rat endocrine pancreas by a scanning electron microscope.

A three-dimensional observation was performed on chemically digested rat pancreata and vascular corrosion casts of it with a scanning electron microscope. The Langerhans islets were sporadically situated in the exocrine tissue and were surrounded by the fibrous capsule, which was so tough that it could not be chemically digested easily. This capsule was considered to play different roles in the collection of the endocrine cells in a functional unit, in the prevention of secreted hormones spreading into the adjacent exocrine and stromal tissue, in the support of the microvascular structure, and in the protection for the islet cells from the pancreatic enzymes, which are leaking into the stromal spaces physiologically. The microvascular structure of the islet, disclosed by the corrosion vascular casts, showed afferent vessels branching into the capillaries at the periphery of the islet and entering the core of it by a twisted course. These findings were considered to be related to the islet cell distribution, that is, A and D cells are at the periphery of the islet and B cells at the center of it. This might support the existence of a hormonal regulating mechanism among endocrine cells. In addition, the efferent vessels from the islet that communicate to the vascular network of the exocrine tissue might suggest that the endocrine system also regulates the exocrine function in a circulatory dynamic state.

Animals↗

Scanning electron microscopic examinations of microvascular casts of the rat liver and bile duct.

Microvascular features of normal rat livers and bile duct system were examined with the vascular casts using methacrylated resin. Portal vein branches not only showed regular tapered down bifurcations but also had many side branches, some of which were directly connected with sinusoids. Terminations of hepatic arterial branches were divided into three types: 1) Many branches pouring into peribiliary capillary plexus (PBP), 2) branches directly pouring into periportal sinusoids and/or peripheral portal vein branches via arterio-portal anastomoses, and 3) anastomoses with periportal vascular plexus. PBP was composed of rich vascular networks. In large portal tracts, the plexus showed two layers, that is, the inner layer made up of a close network of capillary vessels and the outer layer consisting of a loose network of arteries and veins, while the PBP in the small portal tracts was composed of only a single layer of loose capillary network. Transitional features of these two patterns were found in the medium-sized portal tracts. PBP was supplied by afferent vessels from the interlobular hepatic artery as described above, and were directly connected with interlobular branches of the portal vein (internal root). The extrahepatic bile duct revealed a much richer vasculature than the intrahepatic bile duct. Both arterial and venous branches were ramified at almost right angle from a pair of arteries and veins running parallel with the bile duct. Occasional strictures, which might have been sphincter portions of the media, were noted at the branching sites of the artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Juvenile granulosa cell tumor in a three-year-old infant. An immunohistochemical and ultrastructural study.

A three-year-old female infant with a juvenile granulosa cell tumor of the ovary and precocious pseudopuberty is presented. Laboratory tests revealed elevated levels of serum and urinary estrogen. Histological examinations showed an immature follicular pattern surrounded by theca-like stromal tissue. The immunohistochemical localization of estradiol, estriol, progesterone and testosterone was studied by indirect immunoperoxidase staining of cryostat sections. All of these steroid hormones were localized mainly in stromal cells and in some follicular cells. Electron microscopic examination revealed three types of tumor cell, i.e. polygonal cells, spindle cells and transitional cells. Well developed smooth endoplasmic reticulum, mitochondria with tubulovesicular cristae, and lipid droplets in the cytoplasm, which are typical features of steroid synthesis, were conspicuous mainly in the last type of cell. Such transitional cells almost corresponded to steroid-positive cells. These cells were considered to have a close relationship to theca gland cells of developed ovarian follicles and to have mainly participated in steroid synthesis in the present tumor. In addition, some spindle cells showed features of myofibroblasts, such as intracytoplasmic filaments, dense body-like structures, and pinocytotic vesicles. These features suggest that the cells might all be derived from the same progenitor of ovarian mesenchyme.

Child, Preschool↗

Photoinduced electron transfer reaction from N-formyl-L-kynurenine and L-kynurenine to cytochrome C.

The reduction of cytochrome c was found in the presence of N-formyl-L-kynurenine (NFK) and L-kynurenine (KN) during irradiation, suggesting electron transfer to cytochrome c. The reaction occurred both under aerobic and anaerobic conditions. In the former case, oxygen molecules may act mainly as a quencher of excited NFK and KN, and superoxide anion produced by electron transfer may partially contribute to the reduction. The reaction proceeded via the excited triplet state of NFK and KN. The actual reductive chemical species might be an intermediate from excited state NFK or KN, which is assumed to be ketyl radical type species.

Aerobiosis↗

Kinetics of drug action in disease states XII: Effect of experimental liver diseases on the pharmacodynamics of phenobarbital and ethanol in rats.

This investigation was designed to determine if liver diseases can modify the pharmacodynamics of the central nervous system depressants phenobarbital and ethanol. Two experimental models of liver diseases in rats were used: extrahepatic cholestasis produced by bile duct ligation and hepatic necrosis induced by carbon tetrachloride administration. Phenobarbital (both models) or ethanol (cholestasis model only) was infused slowly intravenously until the rats lost their righting reflex. Drug concentrations in serum, brain, and cerebrospinal fluid at that time were determined in the diseased animals as well as in sham-operated or solvent-treated controls. Phenobarbital concentrations at the onset of action were not significantly different between controls and either 5-d or 12-d cholestatic rats, except for total serum concentrations which were lower in the cholestatic groups due to reduced protein binding. Ethanol concentrations were slightly but statistically significantly lower in 12-d cholestatic rats as compared with controls. Neither 5-d nor 12-d carbon tetrachloride-induced hepatic dysfunction had any significant effect on phenobarbital concentrations at the onset of loss of righting reflex, except for a marginal decrease in the cerebrospinal fluid concentration of rats that had been treated for 5 d with the hepatotoxin. It was concluded that, under the experimental conditions, the hepatic diseases investigated did not have appreciable effects on the central nervous system response to the hypnotic action of phenobarbital and ethanol.

Animals↗

Kinetics of drug action in disease states XI: effect of nicotine on the pharmacodynamics and pharmacokinetics of phenobarbital and ethanol in rats.

The purpose of this investigation was to determine if the reported prolongation of barbiturate- and ethanol-induced sleeping times by nicotine in rodents are pharmacodynamic or pharmacokinetic interactions. Adult female rats were pretreated with nicotine, either 0.5 or 1.5 mg/kg ip acutely or 0.5 mg/kg ip daily for 6 d, whereas control animals received saline solution. Phenobarbital or ethanol was infused intravenously at a slow rate until the rats lost their righting reflex. Acute pretreatment with nicotine reduced significantly the serum, brain, and cerebrospinal fluid (CSF) concentrations of phenobarbital and ethanol, respectively, at the onset of the loss of the righting reflex. Chronic pretreatment with nicotine had no such potentiating effects, indicative of rapid development of tolerance to nicotine. Neither acute nor chronic pretreatment with nicotine had any apparent effect on the elimination kinetics of phenobarbital or ethanol, on biochemical indices of hepatic integrity and renal function, or on the permeability of the blood-CSF barrier to protein. Nicotine, unlike morphine, did not increase the nociceptive threshold (tail squeeze) of rats under the experimental conditions. It is concluded that acute, but not chronic, pretreatment with nicotine increases the sensitivity of rats to the hypnotic effects of phenobarbital and ethanol, respectively. These interactions are entirely pharmacodynamic and have no apparent pharmacokinetic component.

Animals↗

Kinetics of drug action in disease states. VI. Effect of experimental diabetes on phenobarbital concentrations in rats at onset of loss of righting reflex.

To investigate the effect of diabetes on the sensitivity of the central nervous system to the hypnotic action of a barbiturate, studies were conducted on adult female Lewis rats made diabetic by injection of either streptozotocin or alloxan. The animals then received a slow i.v. infusion of phenobarbital (PB) until the onset of a defined pharmacologic effect [loss of righting reflex (LRR)] and the PB concentrations at that time in serum (total and unbound drug), brain and cerebrospinal fluid (CSF) were determined. In the experiments on rats with streptozotocin-induced diabetes, animals not treated with insulin had significantly lower serum concentrations of total PB at onset of LRR than did animals treated with insulin and nondiabetic control rats. Otherwise, there were no significant differences in PB concentrations between untreated diabetic and control animals. Additional experiments on untreated diabetic rats showed that, as in normal rats, the PB concentrations in CSF (but not in serum and brain) at onset of LRR were independent of PB infusion rate over a 10-fold range, indicating that PB equilibrates very rapidly between CSF and receptor sites. Experiments in rats with alloxan-induced diabetes showed no significant differences between untreated diabetic, insulin-treated diabetic, alloxan-nonresponding and nondiabetic control rats with respect to PB concentrations at onset of LRR in serum (total and unbound drug), brain and CSF and in serum protein binding. These results show that the central nervous system response to the hypnotic effect of PB is not significantly affected in two different experimental models of diabetes.

Animals↗

Kinetics of drug action in disease states. VII. Effect of experimental renal dysfunction on the pharmacodynamics of ethanol in rats.

This investigation was designed to determine if renal dysfunction is associated with an increased sensitivity to the CNS depressant effect of ethanol. Adult female Lewis rats were given injections of either 2 or 5 mg/kg of uranyl nitrate (saline for controls) or had both ureters ligated (sham operation for controls) to provide different experimental models of renal dysfunction. Normal and renal dysfunction (ureter-ligated) rats were infused i.v. with ethanol at rates of 8.1, 16.3 or 32.6 mg/min; concentrations of ethanol in cerebrospinal fluid, serum and brain at onset of loss of righting reflex were independent of infusion rate in both groups, indicating rapid equilibration of ethanol between the sampling sites and the biophase. Ethanol concentrations in cerebrospinal fluid at onset and offset (after approximately 110 min of sleep) of loss of righting reflex were not significantly different, reflecting negligible acute tolerance development under the experimental conditions. Ethanol concentrations at onset of loss of righting reflex in cerebrospinal fluid, serum and brain of rats with severe renal dysfunction (5 mg/kg of uranyl nitrate-treated and ureterligated groups) were slightly but statistically significantly lower than in normal controls. This difference was relatively much smaller than the difference in phenobarbital concentrations observed in a similar preceding study, which is consistent with the different mechanisms of action of alcohols and barbiturates.

Animals↗

Kinetics of drug action in disease states. IX. Effect of experimental fever on phenobarbital concentrations at onset of loss of righting reflex in rats.

The purpose of this investigation was to determine the effect of fever on the concentration-pharmacologic activity relationship of phenobarbital (PB). Fever was produced in adult female Lewis rats by either bacterial endotoxin or brewer's yeast. Endotoxin elevated body temperature by 0.9 +/- 0.6 degrees C in one study and by 1.0 +/- 0.4 degrees C in another. Brewer's yeast caused a more pronounced and protracted elevation of temperature averaging 1.8 +/- 0.3 degrees C at the time of the pharmacodynamic measurements. PB was administered by slow i.v. infusion until the rats lost their righting reflex. The concentrations of PB at that time in serum, cerebrospinal fluid and brain were appreciably lower in the hyperpyrexic than in control (saline-treated) animals, irrespective of the method used to produce fever. Thus, fever is associated with an increased sensitivity of the central nervous system to the depressant effect of PB. This observation may be of particular relevance to the use of PB for the treatment and prevention of febrile convulsions.

Animals↗

Effect of pregnancy on ethanol concentrations at onset of loss of righting reflex in rats.

To determine if the pharmacodynamics of ethanol are altered in advanced pregnancy, 20-days pregnant Lewis rats and nonpregnant rats of the same age received an i.v. infusion of ethanol, 96 mg/min/kg, until they lost their righting reflex. The concentrations of ethanol at that time in adult and fetal serum, and in the cerebrospinal fluid (CSF) and brain of the adult animals were determined. Ethanol concentrations in the pregnant rats were only slightly (less than 10%) but statistically significantly lower than in nonpregnant controls. Brain/serum, CSF/serum, and CSF/brain concentration ratios of ethanol were essentially identical in pregnant and nonpregnant rats, indicating no apparent effect of pregnancy on the distribution kinetics of ethanol. The serum concentrations of ethanol in mothers and their fetuses were similar and significantly correlated. The results of this investigation show that the central nervous system depressant effect of ethanol is not appreciably altered by pregnancy.

Animals↗

Kinetics of drug action in disease states. XIII. Effect of dialyzable component(s) of uremic blood on phenobarbital concentrations in rats at onset of loss of righting reflex.

The purpose of this investigation was to determine if the previously demonstrated increased sensitivity of the central nervous system of uremic rats to the hypnotic activity of phenobarbital is caused, wholly or in part, by the accumulation of one or more endogenous substances. Blood was obtained from normal donor rats and from rats made uremic by administration of uranyl nitrate 5 days earlier. The serum was dialyzed against water, using a cellophane membrane with a molecular exclusion limit of 12,000 to 14,000 daltons, and the dialysate was lyophilized. A concentrate of the dialysate was administered by i.v. infusion to normal rats who also received a slow i.v. infusion of phenobarbital until they lost their righting reflex. Samples of cerebrospinal fluid, blood (for serum) and the brain were obtained at that time and were assayed for phenobarbital. Compared to the two control groups, i.e., rats infused with serum dialysate from normal animals or with normal saline solution, rats infused with serum dialysate from uremic rats lost their righting reflex at significantly lower phenobarbital concentrations in serum, brain and cerebrospinal fluid. This shows that the serum of uremic rats contains appreciable concentrations of one or more dialysable components capable of potentiating or contributing to the hypnotic activity of phenobarbital.

Age Factors↗