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Biomedical subjects

H Sakaguchi

Publications and source records attributed to H Sakaguchi.

At least 289 records · Page 16Linked to original sources

[Pharmacokinetic study of adriamycin in the emulsion mixed with lipiodol-difference resulting from composition and methods of preparation, and behavior after mesenteric arterial injection in rat].

We experimentally investigated the pharmacokinetics of adriamycin (ADM) in a similar of transcatheter arterial chemoembolization therapy (TAE) of hepatocellular carcinoma using emulsion of lipiodol (Lp) mixed with ADM followed by gelatin sponge, and the difference resulting from composition and method of preparation of the emulsion as well as behavior after mesenteric arterial injection in rat. In in vitro study, the emulsion with iopamidol (iopamiron 300 : IP) was more stable than with amidotrizoic acid (60% Urografin : UG). The highest stability was found in the mixing ratio of Lp. IP and distilled water at 1 : 0.42 : 0.08. Frequent pumping also made the emulsion more stable. But in optimally composed emulsion, pumping 20 or 50 times made no difference in the stability during 30 min. which may be longer than the time from preparation to injection time of the emulsion in clinical application. After injection of the emulsion into the mesenteric artery which may simulate injection into the hepatic artery in hepatocellular carcinoma, the arterial blood flow was suspended. In the peripheral arteries the emulsion separated into two phases of Lp and ADM solution, forming striped pattern, and Lp embolization of the peripheral artery persisted for over 45 min. while ADM extravasated. These findings suggest that after Lp-TAE, Lp maintains an embolizing effect while ADM penetrates into the surrounding tumor tissue, and that this is an underlying mechanism for the anti-cancer effect of Lp-TAE.

Animals↗

Long-term follow-up of a paediatric case of lipoprotein glomerulopathy.

A paediatric case of lipoprotein glomerulopathy, a new kidney disease characterized by glomerular lipoprotein thrombi, is reported. The patient had massive proteinuria from the age of 8 years, when the nephrotic syndrome was first detected. This was resistant to conventional treatment for more than 10 years. During the course of the disease, the hyperlipidaemia characteristic of hyper-pre-beta-lipoproteinaemia and elevation of apoprotein E persisted, and renal function gradually deteriorated. The renal histopathological findings from four biopsies were essentially the same, with storage of beta-lipoprotein in dilated, balloon-like glomerular capillary lumina. However, the number of glomeruli showing global sclerosis increased and tubulo-interstitial changes progressed in parallel with the gradual clinical deterioration. As in other cases reported in Japan some familial involvement has been noted.

Apolipoproteins E↗

Identification and fine structure of proliferating hepatocytes in malignant and nonmalignant liver diseases by use of a monoclonal antibody against DNA polymerase alpha.

To analyze the process of liver regeneration and the initiation of hepatocellular carcinoma (HCC), we studied histochemically the morphologic features of proliferating parenchymal cells stained for DNA polymerase alpha (DPA), in 31 patients with various diseases, by use of a monoclonal antibody against DPA. In specimens from patients with acute viral hepatitis with confluent necrosis, most stained hepatocytes were small, with basophilic cytoplasm, and were located next to the necrotic areas. Under electron microscopy, stained granules were seen in the nucleus. Most stained hepatocytes had immature organelles. In specimens from patients with cirrhosis of the liver, the number of stained hepatocytes greatly differed in different pseudolobules. In specimens from patients with adenomatous hyperplasia, stained hepatocytes, mostly small and basophilic, were found diffusely; electron microscopy showed slightly indented nuclei with a few organelles and less condensed chromatin than normal. In specimens from patients with HCC, most stained cancer cells were small and basophilic; electron microscopy showed indented nuclei with a few organelles and less than normal condensed chromatin. Staining showed that during regeneration, immature hepatocytes reentered the cell cycle and repaired a large necrotic area. It was conceivable that in the initiation of HCC, some small hepatocytes with indented nuclei and less condensed chromatin might become HCC cells.

Antibodies, Monoclonal↗

A case of lipoprotein glomerulopathy. Light and electron microscopic observations of the glomerulus.

A 41-year-old Japanese woman with lipoprotein glomerulopathy is reported. The patient presented with nephrotic syndrome, hyperlipoproteinemia and an increased level of plasma Apo E. The damaged glomeruli showed various degrees of capillary dilatation and accumulation of some material-often showing stratification, along with mesangial proliferation and mesangial interposition. The accumulated material was stained positive for beta-lipoprotein by the indirect immunoperoxidase technique. Capillary dilatation resulted from gradual accumulation of the lipoprotein as well as destruction of the mesangium, as if being torn off, due to increased intraluminal pressure. The patient's eldest sister also suffers from the same renal disease, suggesting a hereditary predisposition.

Adult↗

Expandable metallic biliary endoprostheses: preliminary clinical evaluation.

A biliary endoprosthesis constructed of self-expanding metallic "Z" stents was placed in 23 patients with obstructive jaundice. The biliary obstruction was due to a malignant neoplasm in 21 patients and a postoperative biliary stricture in two patients. The lesions affected the intrahepatic biliary ducts in 13 patients. Twelve patients had undergone radiation therapy before stent placement. The endoprostheses consisted of 196 expandable metallic biliary stents placed singly (n = 10) or in tandem (n = 186). As many as 18 stents were used to relieve an obstruction in one patient. A transhepatic approach was employed in all patients except one in whom stents were placed through a T-tube tract. Within 1 week after placement, all stents expanded to at least 90% of their original diameter. Three misplaced, two deformed, and two dislodged stents caused no obvious clinical problems. At follow-up, which ranged from 2 to 59 weeks, five patients experienced recurrent jaundice. Two patients with recurrent jaundice due to obstruction of the bile duct containing the stent were treated with external catheter drainage. The expandable biliary endoprosthesis is suggested as an effective treatment for benign and malignant biliary obstruction.

Adult↗

Testicular steroids in spermatic and peripheral veins after single injection of hCG in patients with varicocele.

To determine the function of Leydig cells in patients with varicocele, hCG-stimulated levels of progesterone (Prog), 17 alpha-Hydroxy-4-pregnene-3,20-dione (17OHP), 4-Androstene-3,17-dione (A-dione), testosterone (T), and estradiol-17 beta (E2) in both spermatic and peripheral veins were measured. Seventy-two patients with idiopathic varicocele were divided into four groups: patients in group 1 were untreated, whereas patients in groups 2, 3, and 4 were given a single i.m. injection of 10,000 IU hCG 24 h, 96 h, and 168 h before surgery, respectively. In the spermatic and peripheral veins, levels of Prog, 17OHP, and E2 showed peaks at 24 h, whereas levels of A-dione and T showed peaks at 96 h. Significant increases in the ratios of spermatic veins 17OHP to A-dione and 17OHP to T, and a significant decrease in the ratio of T to E2, was found 24 h following hCG treatment. These results demonstrate that, following hCG injection, there is a transient inhibition of testicular C17-20-lyase activity, probably mediated by E2, even in subfertile males with varicocele.

Adult↗

[Clinico-pathological features in four patients with Fabry's disease. The possible role of degenerative lesions in the interstitial vessels in renal dysfunction].

Clinical courses and histopathological changes of four patients with Fabry's disease were discussed in this report. All of them were male and revealed to have angiokeratomas of the skin and markedly decreased activity of alpha-galactosidase--A in leukocytes. They were from different families. No consanguinity was noted. Two of them, around 40 years of age, showed rapid impairment of renal function with simultaneously development of hypertension, progressing to uremia within several months. Their light and electron microscopic findings in renal biopsies were similar: severe degenerative changes in muscle cells of small arteries and arterioles with remarkable swelling of intima, and multiple sclerosing and collaptic lesions in glomeruli. The other 2 patients were about 20 years old and their renal functions were almost normal. No significant changes but fine vacuolization of epithelial cells of glomeruli were observed in renal biopsy specimens. It is concluded that marked degenerative changes in the vessels due to Fabry's disease might be the principal etiology of hypertension and rapid deterioration of renal function.

Adolescent↗

Beta-adrenergic regulation of gastrin release from gastrinoma cells.

The effect of epinephrine on the plasma gastrin level was investigated in three patients with Zollinger-Ellison syndrome (ZES) and in 14 normal subjects. Two ZES patients had undergone total gastrectomy, and the third had undergone subtotal gastrectomy before our study. A significant increase in plasma gastrin, from 23 +/- 5 pg/ml to 53 +/- 20 pg/ml, in response to intravenous epinephrine (40 ng/kg.min), was observed in the normal subjects. This response was completely abolished by beta-blockade. In the ZES patients, epinephrine (40 ng/kg.min) also resulted in an increase in the plasma concentration of gastrin. The basal and maximum concentrations of gastrin were 580 and 1680 pg/ml in patient 1, 145000 and 320000 pg/ml in patient 2, and 200 and 1800 pg/ml in patient 3, respectively. beta-Adrenergic blockade suppressed the epinephrine-stimulated gastrin release in these patients as well. Graded intravenous doses of epinephrine given to the ZES patients resulted in elevation of the plasma gastrin in a dose-dependent manner. Insulin hypoglycemia caused an increase in both plasma epinephrine and plasma gastrin in ZES patients and normal subjects. A significant correlation between plasma gastrin and epinephrine during insulin hypoglycemia was observed in both groups. Exercise, with use of a bicycle ergometer, resulted in an increase in plasma epinephrine. An increase in plasma gastrin with exercise was observed in the ZES patients, and this was also suppressed by beta-blockade. The results suggest that gastrinoma cells, like normal G cells, are equipped with beta-adrenergic receptors that regulate gastrin release.

Adult↗

[Behavior of anti-cancer drug of transcatheter hepatic segmental arterial chemoembolization using lipiodol mixed with an anti-cancer drug followed by gelatin sponge assessed by Tc-99m pertechnetate].

The behavior of an anti-cancer drug consisting of transcatheter hepatic segmental arterial chemoembolization using Lipiodol mixed with an anti-cancer drug followed by gelatin sponge (segmental Lp-TAE: Seg-Lp-TAE) was assessed in comparison to that of the non-segmental Lp-TAE to whole liver (Lp-TAE) by means of Tc-99m pertechnetate (RI). Injection of Lipiodol mixed with Adriamycin and 740 mBq of RI followed by gelatin sponge was carried out from segmental or subsegmental hepatic artery in 12 cases of hepatocellular carcinoma and from proper or right hepatic artery in 11 cases (9 with hepatocellular carcinoma and 2 with metastatic liver tumor). The distribution and retention of RI were studied from the time activity curves of ROIs in tumor and non-tumor area, and scintigrams at 4 and 24 hours after injection. The integral value ratio of tumor to non-tumor was significantly higher in Seg-Lp-TAE, indicating that es the distribution of RI after Seg-Lp-TAE is selective in the segments where tumor exists. In Seg-Lp-TAE, the T1/2 was higher and the count ratio of tumor to non-tumor was significantly higher at 4 hours and even higher at 24 hours after injection. These results suggest that an anti-cancer drug reinforces the effect on tumor with little adverse effect on normal liver in Seg-Lp-TAE, which is more advantageous to the treatment of hepatocellular carcinoma.

Antineoplastic Agents↗

[The protective effects of glucagon and insulin in an experimental massive hepatic cell necrosis model].

When heat-killed Propionibacterium acnes was intravenously injected into mice and seven days later, a small amount of gram-negative lipopolysaccharide (LPS) was also intravenously injected, most of them died of massive hepatic cell necrosis. However, then glucagon (0.5 mg/kg body weight) and insulin (0.5 units/kg body weight) or glucagon (0.5 mg/kg body weight) individually were administered during this experimental induction of massive hepatic cell necrosis, the survival rate of mice increased and serum transaminase levels improved. Also, the histological changes of the liver improved remarkably. But, insulin (0.5 units/kg body weight) individually was not effective in an experimental massive cell necrosis model. These results suggested that glucagon and insulin was effective in our experimental massive hepatic cell necrosis model.

Animals↗

Effects of antihypertensive agents on blood pressure and the progress of renal failure in partially nephrectomized spontaneously hypertensive rats.

The purpose of this study was to investigate the effects of antihypertensive agents on blood pressure and the development of glomerular changes in salt-loaded, 5/6 nephrectomized spontaneously hypertensive rats (SHR). Thirty-two spontaneously hypertensive rats with 5/6 nephrectomy were divided into 4 groups: a control group (N = 8), and group treated with 10 mg/kg/day trichlormethiazide. (N = 8), 30 mg/kg/day captopril (N = 8), and 200 mg/kg/day nicardipine (N = 8). Each of these antihypertensive drugs was added to the drinking water for 10 weeks and the rats were given the drugs and a high-salt diet (5% NaCl). During the experiment, body weight and systolic blood pressure were measured every 2 weeks. At the end of the study, blood was collected for determination of serum creatinine, blood urea nitrogen, serum protein, serum sodium and potassium, and plasma renin activity and aldosterone concentration. Also renal tissues were obtained for light and electron microscopic examination at the end of the study. Systolic blood pressure in 5/6 nephrectomized SHR loaded with a high salt was significantly reduced by administration of trichlormethiazide (155 +/- 12 versus 204 +/- 12 mm Hg), but not by administration of either captopril or nicardipine. However, levels of serum creatinine were not significantly elevated in rats treated with captopril and nicardipine (control: 0.93 +/- 0.11 mg/dl, captopril: 0.62 +/- 0.01 mg/dl, nicardipine: 0.55 +/- 0.05 mg/dl). In contrast to changes in blood pressure, marked glomerular sclerosis with hyalinosis, which was found in the control group was not ameliorated by treatment with trichlormethiazide. However, these changes were not observed in rats treated with either captopril or nicardipine in spite of the absence of a prominent fall in blood pressure. These data suggest that captopril and nicardipine ameliorated glomerular injury regardless of the level of systolic blood pressure through the direct and/or indirect actions on the glomerulus.

Animals↗

[Morphological study of renal changes with age: the possibility of kidney donations by the elderly].

Samples from seventy autopsy cases ranging from 27 to 79 years of age who had shown no evidence of renal or malignant diseases were examined histologically to clarify renal changes with age. We evaluated scores for renal histological change and referred the scores to clinical laboratory data; blood pressure, complete blood counts (RBC count, hematocrit, hemoglobin), serum chemistry values (creatinine, urea nitrogen, total cholesterol, total protein, sodium, potassium, chloride) and urinalysis (protein, sediment). We found the score to be related to serum creatinine level, blood urea nitrogen level and the degree of hematuria but not related to the other factors. The progression of arteriosclerosis, tubulo-interstitial change and global sclerosis were found to be severe with ageing. Also renal weight decreased with increasing age. However there were great differences among individuals in the extent of changes. We could not assume histological changes were generally severe in those of more than 55-65 years of age. It was impossible to clarify renal states only with clinical findings. Some kidneys had severe histological changes though less than 2.0 mg/dl of serum creatinine level. It suggests that living relatives and cadavers over 60 years old can be donors for renal transplantation when there are no significant findings of abnormality in preoperative evaluations of their physical state. If insufficient examinations are done, we cannot determine which of them will be good donors. Therefore preoperative biopsy is the best way to evaluate donor suitability. To evaluate only clinical data, it is necessary that serum creatinine level be less than 1.2 mg/dl, blood urea nitrogen level be less than 23 mg/dl and there be no hematuria.

Adult↗

[Transarterial hepatic embolization of metastatic liver cancers with reference to 17 cases of survival for more than 2 years].

The evaluation of TAE was studied for 73 patients with metastatic liver cancers but without metastasis in other organs, who were treated with initial TAE more than 2 years ago. Seventeen patients survived for more than 2 years. The primary lesions consisted of colon cancer in 9 patients, the Langerhans islet cell tumor of the pancreas in 4, gastric cancers in 2, breast cancer in 1 and leiomyosarcoma of the colon in 1. The overall 2-year survival rate calculated by the direct method was 23.3% and mean survival period was 15.8 months. The prognosis was good in H1 and V3. Lp-TAE produced better effects but no statistically significant difference was found between the 2-year survivals by Lp-TAE and by GS-TAE.

Adult↗

The ratio of fucosylation of alpha-fetoprotein in hepatoblastoma.

Hepatoblastoma differs from the adult type of hepatoma in clinical and pathologic features. The ratio of fucosylation of serum alpha-fetoprotein (AFP) was determined in seven patients with hepatoblastoma and in 21 infants and children with otherwise elevated serum AFP, using the improved technique of lentil agglutinin-affinity immunoelectrophoresis. The clinical data for the seven patients with hepatoblastoma were also reviewed. The ratio of fucosylation of AFP was significantly higher in all seven patients with hepatoblastoma, whereas it was minimal in all other cases of benign hepatic conditions such as neonatal hepatitis or biliary atresia, as well as in normal newborns. The ratio of fucosylation in hepatoblastoma, however, definitely decreased with the age of the patient at presentation. This finding suggests a correlation between fucosylation and a rapid rate of tumor growth, because all hepatoblastomas are believed to originate early in fetal life.

Carcinoma, Hepatocellular↗

The acetylcholine and catecholamine contents in song control nuclei of zebra finch during song ontogeny.

The acetylcholine (ACh), dopamine (DA) and noradrenaline (NA) concentrations in the song control nuclei, the magnocellular nucleus of the anterior neostriatum (MAN), the caudal nucleus of the ventral hyperstriatum (HVc) and the robust nucleus of the archistriatum (RA) were measured using high performance liquid chromatography (HPLC) at 5 different ages (30, 40, 50, 60 and 90 days after hatching). ACh concentration of these nuclei increased markedly during the critical period for learning and decreased gradually toward adult age. The change either in the HVc or the MAN preceded that in the RA. The developmental changes of catecholamine concentration of each nucleus were different from those of ACh. DA concentrations in the HVc increased at the same time (between 30 and 40 days after hatching) as ACh increased, whereas concentrations of DA and NA in the other two nuclei did not increase. Combined increment of both ACh and DA occurred only in the HVc and this may contribute to plastic change by dual synaptic modification during the critical period of song learning.

Acetylcholine↗