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Biomedical subjects

S Okuda

Publications and source records attributed to S Okuda.

At least 181 records · Page 10Linked to original sources

[Topographic correlation between basilar artery occlusion and cerebellar involvement--a clinicopathological study].

Nineteen patients (15 men, 4 women) with occlusion of the vertebrobasilar artery were studied in order to identify possible pathomechanism and to define the site of arterial occlusion and the topography of ischemic lesion of the cerebellum. Their mean age at onset was 66.7 years and the final clinicopathological diagnosis were thrombosis of the basilar artery (BA) in 15 patients and embolism in 4. The occlusion of the BA was contiguous to that of the vertebral artery in ten patients. Of these, the occlusion was localized to the caudal portion of the BA in two, to the middle portion in six, and extended to the rostral portion in two. In eight patients, the arterial occlusion was restricted to the BA. Occlusions of the middle portion were observed in four and that of rostral portion in two; in the other two patients, the whole BA was occluded. In one patient, there was no occlusion in the vertebro-basilar artery at the postmortem examination, but infarctions of the base of pons, bilateral cerebellar hemispheres and occipital lobes were confirmed, suggesting recanalization of the occluded BA. Cerebellar lesions were observed in all nineteen patients. Involvements of the area supplied by the superior cerebellar artery (SCA) were found in seventeen, while that of the posterior inferior cerebellar artery (PICA) only in ten. Eight patients had cerebellar lesions supplied by both SCA and PICA. These facts suggest that cerebellar lesions are rather frequent and the SCA areas are more involved than those of the PICA in fatal patients with occlusion of the BA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Role of TGF-beta 1 in experimental glomerulonephritis.

Glomerulonephritis is an inflammation of the kidney characterized by the accumulation of extracellular matrix within the damaged glomeruli. We have shown that TGF-beta 1 is unique in regulating the production of proteoglycans and matrix glycoproteins by glomerular cells in vitro. In an experimental model of glomerulonephritis in rats we found increased proteoglycan and fibronectin synthesis by cultured nephritic glomeruli, which was greatly reduced by addition of antiserum to TGF-beta 1. Conditioned media from glomerular cultures induced elevated proteoglycan synthesis when added to normal cultured mesangial cells. This stimulation was blocked by addition of TGF-beta antiserum. Glomerular histology showed mesangial matrix expansion with a time course that roughly paralleled that of the elevated proteoglycan synthesis by the nephritic glomeruli was increased. Administration of anti-TGF-beta 1 at the time of induction of glomerulonephritis suppressed the elevated extracellular matrix production and dramatically attenuated histological manifestations of the disease. Our results provide direct evidence for a causal role of TGF-beta 1 in the pathogenesis of the experimental disease and suggest a new approach to the therapy of glomerulonephritis.

Animals↗

[Chemoembolization therapy with lipiodol, cisplatin and etoposide for hepatocellular carcinoma].

Chemoembolization using CDDP, VP-16 and lipiodol was carried out for 7 patients with hepatocellular carcinoma (HCC). CDDP/lipiodol, CDDP/VP-16, CDDP/lipiodol (lipiodol 2-10 ml, CDDP 1-2 mg/kg, VP-16 100 mg/body) and gelatine sponge were administered in that order through the catheter located in the proper, or right or left hepatic artery. Three patients underwent hepatic resection 38-50 days after this treatment. Complete necrosis of the tumor was recognized in the one case, although the portion of necrosis did not exceed 70% in large sized HCC as the diameter of more than 10 cm. In 4 unresectable cases the decreases in tumor size were observed by ultrasonography and computed tomography. The response was: 3 partial responses and 1 no change. One out of 4 cases could undergo hepatic resection 17 months after this treatment. Two patients are alive 20 months after this treatment, although one patient died of HCC after 25 months. Serious side effect was not observed.

Aged↗

Effectiveness of periodic checkup by ultrasonography for the early diagnosis of hepatocellular carcinoma.

Periodic checkup by ultrasonography was conducted on patients with chronic liver diseases for early detection of hepatocellular carcinoma. In 19 months, a total of 2004 examinations were performed on a total of 660 cases (179 cases with liver cirrhosis in the compensatory stage, younger than 70 years; 481 cases with chronic hepatitis, aged 40 to 70 years for men and 50 to 70 years for women). Of the 660 cases, 22 HCC cases (3.3%) were detected and finally diagnosed by angiography and/or histologic examination. Four of those cases (18%) had a single nodule smaller than 1 cm in diameter, and 11 cases (50%) had a single nodule smaller than 2 cm. Surgical resection was performed on 12 cases (55%). In comparison with the control group (83 HCC cases not receiving any periodic checkup), the frequency of small liver cancer and the surgical resection rate in the study group were significantly higher. This examination system by periodic ultrasonography checkup of patients with chronic hepatic diseases was effective for early detection and permitted aggressive therapy of hepatocellular carcinoma.

Adult↗

Immunochemical detection of human blood in feces.

We have developed a new immunochemical test for fecal occult blood utilizing enzyme-linked immunosorbent assay (ELISA) of human hemoglobin (HbAo) and transferrin (Tf) simultaneously. The ELISA had a sensitivity of about 15 ng/ml Hb, and the measurable range was 1.5-750 micrograms Hb per g feces. The stability of Tf in feces was greater than that of Hb. In 17 out of 18 patients with colon cancer, 8 out of 15 patients with colon polyps, and 11 out of 20 patients with upper-gastrointestinal disorders. The Hb and Tf values were more than 10 micrograms/g feces, in terms of Hb concentration. The ELISA for human fecal HbAo and Tf might be useful for the diagnosis of gastrointestinal disorders.

Animals↗

Suppression of experimental glomerulonephritis by antiserum against transforming growth factor beta 1.

Glomerulonephritis is an inflammation of the kidney characterized by the accumulation of extracellular matrix within the damaged glomeruli, impaired filtration and proteinuria. In its progressive form, the disease destroys kidney function leading to uraemia and death, unless dialysis therapy or kidney transplantation is available. The pathogenesis of glomerulonephritis is incompletely understood, but the eliciting factor is thought often to be an immunological injury to mesangial and/or other resident cells in the glomeruli. We have used an animal model of acute mesangial proliferative glomerulonephritis to show that this disease is associated with increased production and activity of transforming growth factor beta 1 (TGF-beta 1), an inducer of extracellular matrix production. Here we report that administration of anti-TGF-beta 1 at the time of induction of the glomerular disease suppresses the increased production of extracellular matrix and dramatically attenuates histological manifestations of the disease. These results provide direct evidence for a causal role of TGF-beta 1 in the pathogenesis of the experimental disease and suggest a new approach to the therapy of glomerulonephritis.

Animals↗

Diagnosis of hepatic cavernous hemangioma by fine needle aspiration biopsy under ultrasonic guidance.

Percutaneous aspiration biopsy of the liver using a heparinized 22-gauge needle was performed under ultrasonic guidance in 11 patients with hepatic cavernous hemangioma. Ten (91%) of 11 biopsy specimens obtained were cytologically diagnostic for hemangioma. No indications of malignancy were found. There was no relation between the cytological diagnosis and the location, size, or ultrasonographic findings. No complications were encountered. These findings indicate that cytological examination of the liver by fine needle aspiration biopsy is useful in diagnosing hepatic cavernous hemangioma of any size and in any location, provided optimal route to the lesions is chosen.

Aged↗

Subacute nephrotoxicity of germanium dioxide in the experimental animal.

Germanium (Ge; atomic number 32, atomic weight 72.6) belongs to IVb group of the Periodic Table and is found as a trace metal in soil, rocks, plants, and animals. It is widely used in industry because of its semiconductive nature. Some biological activities have been shown in Ge derivatives. Recently, patients with persistent renal damage after chronic ingestion of germanium dioxide (GeO2)-containing compounds have been reported in Japan. This study aimed to investigate subacute nephrotoxicity of GeO2 in Lewis male rats. The rats were treated orally with GeO2 for 13 weeks (GeO2 group) and were compared with those treated with GeO2 for only the first 4 weeks (GeO2-4-week group) and with untreated controls. Renal dysfunction was demonstrated by the increased serum creatinine, BUN, and serum phosphate and decreased creatinine clearance. Liver dysfunction was observed as demonstrated by the increased GOT and GPT, and hypoproteinemia by the decreased total protein and albumin in the GeO2 group. However, daily urinary protein excretion or urinalysis did not differ among the groups. Kidney weight and Ge content of tissues were significantly elevated in the GeO2 group. With the light microscope, vacuoles and the depositions of PAS-stained particles, which correspond to electron-microscopic dense granules in the swollen mitochondria, were predominantly observed in distal tubular epithelium in the GeO2 group. Even in the GeO2-4-week group of rats, serum creatinine was increased and the above-mentioned histological abnormalities were observed, but were less intense.

Acute Kidney Injury↗

Protection by oral phenylalanine against gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effect of oral administration of L-phenylalanine on the incidence and histology of gastric adenocarcinomas induced by N-methyl-N'-nitro-N-nitrosoguanidine was investigated in inbred Wistar rats. Oral administration of 6% phenylalanine after 25 weeks of treatment with the carcinogen significantly reduced the incidence and number of adenocarcinomas of the glandular stomach at experimental week 52. Oral administration of high dose phenylalanine significantly increased the basal serum gastrin level and significantly decreased the norepinephrine concentration in the antral portion of the gastric wall, as well as the labelling indices of antral mucosa. These findings indicate that orally administered phenylalanine inhibits the development of gastric cancers.

Adenocarcinoma↗

Transforming growth factor-beta regulates production of proteoglycans by mesangial cells.

Accumulation of glomerular extracellular matrix is a prominent feature of most forms of progressive glomerular disease. Since some growth factors may play a role in extracellular matrix production, we examined the effects of transforming growth factor-beta (TGF-beta), interleukin 1, platelet derived growth factor, and tumor necrosis factor on the production of extracellular matrix components by cultured rat mesangial cells. In control experiments we found that mesangial cells produced two distinct proteoglycans identified as the small chondroitin/dermatan sulfate proteoglycans biglycan (PG I) and decorin (PG II) by showing that their mobility on SDS-PAGE changed upon digestion by chondroitinase ABC, and that they reacted with antibodies raised against synthetic peptides from the core protein sequence of human biglycan and decorin. Exposure to TGF-beta for 48 hours stimulated an 8- to 10-fold increase in the biglycan and decorin bands, and induced a structural change detected as a shift in electrophoretic mobility. TGF-beta did not demonstrably affect the production of other matrix proteins by the mesangial cells. The other growth factors tested had no comparable effect on the production of proteoglycans or other extracellular matrix components by these cells. Our results show that TGF-beta is unique among growth factors in its regulatory effects on mesangial cell proteoglycan production. The release or activation of TGF-beta during glomerular injury could mediate the accumulation of proteoglycans in the extracellular matrix and predispose the kidney to development of glomerulosclerosis.

Animals↗

Gastric emptying in patients with fundal gastritis and gastric cancer.

Gastric emptying was compared in patients with gastric cancers and fundal gastritis to determine its value in identifying patients at high risk of gastric cancer. Gastric emptying was measured by the acetaminophen absorption method, and the extent of fundal gastritis was determined by the endoscopic Congo red test. The results showed that gastric emptying was significantly slower in patients with severe fundal gastritis than in those without. Gastric emptying in patients with differentiated adenocarcinomas was significantly slower than in those with undifferentiated adenocarcinoma, its value being similar to that in patients with severe fundal gastritis. The Congo red test showed that the incidence of severe fundal gastritis was significantly greater in patients with differentiated adenocarcinomas than in those with undifferentiated cancers. These findings suggest that delayed gastric emptying may allow prolonged contact between dietary carcinogens and the stomach.

Adenocarcinoma↗

Reduction of gastric ulcer recurrence after suppression of Helicobacter pylori by cefixime.

The effect on the recurrence of gastric ulcers after suppression of Helicobacter pylori by combined treatment with cimetidine and the antimicrobial drug cefixime was investigated. Twenty one of 43 patients with endoscopically proved gastric ulcer and H pylori infection were randomly assigned to receive cimetidine 800 mg daily for 12 weeks; the remaining 22 patients received cimetidine 800 mg daily for 12 weeks plus cefixime 100 mg daily for the last two weeks. After treatment, 88% of 17 patients on cimetidine only remained H pylori positive, whereas combined administration of cimetidine and cefixime had suppressed H pylori in 78% of 18 patients (p less than 0.05). Seventeen patients in the former group whose ulcers healed but who remained H pylori positive and 18 patients in the latter group whose ulcers healed and who were no longer infected with H pylori continued to be followed after treatment. These patients underwent endoscopy to detect ulcer recurrence if symptomatic, or at 12 and 24 weeks if asymptomatic. At 12 weeks, recurrence was observed in seven of 15 (47%) patients in whom H pylori persisted, but in only one of 14 (7%) patients in whom H pylori had been suppressed (p less than 0.05). At 24 weeks, however, recurrence rates were similar between the two groups. These findings indicate that H pylori infection may be closely related to early ulcer recurrence.

Cefixime↗

Germanium dioxide-induced nephropathy: a new type of renal disease.

Chronic renal failure developed in 5 patients who were taking germanium dioxide (GeO2)-containing compounds. Renal functional deterioration was slow but progressive and dialysis treatment was necessitated temporarily in 2 patients. After the discontinuation of GeO2, the impaired renal function tended to improve but remained abnormal for an observation period of 10-40 months. The lack of proteinuria and hematuria was characterized as the clinical manifestations. Renal biopsy specimens revealed the tubular epithelial cell degeneration containing hematoxylin-positive fine granules on light microscopy, and electron-dense inclusions in the swollen mitochondria on electron microscopy. These findings localized mainly in distal segment of the tubules. In the rats given GeO2 orally for 10 weeks, similar histological lesions were evident, as manifested by marked weight loss, anemia, azotemia, and negative proteinuria. In the rats given carboxyethylgermanium sesquioxide, these changes were not observed and Ge concentration of kidney was significantly lower than in the rats given GeO2. The present study indicates that chronic GeO2 intake causes progressive renal dysfunction characterized by the degeneration of distal tubules.

Adolescent↗

Effect of swimming exercise on the progress of renal dysfunction in rat with focal glomerulosclerosis.

The effect of exercise on the progression of experimental renal disease was studied in adriamycin (ADR)-treated rats, a model of sclerosing glomerulonephritis with nephrotic syndrome. Two hours of daily swimming exercise was carried out for 20 weeks in ADR-treated male Lewis rats fed with either an ad libitum intake of regular chow (group 1) or a restricted amount of food (group 3), which was equal to the amount of food freely ingested by ADR-treated rats not undergoing swimming exercise (group 2). Group 3 resulted in a significantly lower serum creatinine, higher inulin clearance and lower glomerular sclerosis index compared to group 2. The progress of renal dysfunction did not differ significantly between group 1 and group 2. Hyperlipidemia, especially, hypertriglyceridemia was significantly lower in the exercise groups than in the sedentary group. Among all the rats, inulin clearance was inversely correlated with either cholesterol (r = 0.560, p less than 0.01) or triglyceride (r = 0.423, p less than 0.05) and the glomerular sclerosis index correlated positively with cholesterol (r = 0.599, p less than 0.005). Systolic blood pressure was 10 mm Hg lower in group 3 than in group 2 and the difference was significant. It is concluded that swimming exercise with a relative restriction of food intake can improve hyperlipidemia and prevent progressive renal dysfunction in ADR-induced nephritic rats.

Animals↗

Elevated expression of transforming growth factor-beta and proteoglycan production in experimental glomerulonephritis. Possible role in expansion of the mesangial extracellular matrix.

Glomerular accumulation of extracellular matrix is a prominent feature of progressive glomerulonephritis. Previously, we have shown that transforming growth factor-beta (TGF-beta) is unique among growth factors in regulating the production of the proteoglycans biglycan and decorin by glomerular mesangial cells in vitro. We now provide evidence of an elevated expression of TGF-beta, proteoglycans, and fibronectin in glomerulonephritis induced in rats by injection of anti-thymocyte serum (ATS). Glomeruli were cultured from rat kidneys at 1, 4, 7, 14, and 28 d after ATS administration. Increased proteoglycan synthesis was detected beginning on day 4, which peaked at a 4,900% increase compared with control on day 7, and returned toward control levels by day 28. The increased proteoglycan synthesis by cultured nephritic glomeruli, as well as that of fibronectin, were greatly reduced by addition of antiserum raised against a synthetic peptide from TGF-beta. Conditioned media from ATS glomerular cultures, when added to normal cultured mesangial cells, induced elevated proteoglycan synthesis that also peaked on day 7 and that mimicked the response to added exogenous TGF-beta. The stimulatory activity of the conditioned media was blocked by addition of TGF-beta antiserum. Prior addition of the immunizing peptide to the antiserum abolished the blocking effect. The main induced proteoglycans were identified as biglycan and decorin by immunoprecipitation with antiserum made against synthetic peptides from the proteoglycan core proteins. Glomerular histology showed mesangial matrix expansion in a time course that roughly paralleled both the elevated proteoglycan synthesis by the ATS glomeruli and the ability of the conditioned media from these glomeruli to induce proteoglycan synthesis. At the same time there was an increased expression of TGF-beta mRNA and TGF-beta protein in the glomeruli. These results suggest a central role for TGF-beta in the accumulation of pathological extracellular matrix in glomerulonephritis.

Animals↗

Color Doppler flow imaging of liver tumors.

A differential diagnosis of liver tumors was attempted on the basis of the pattern of blood flow within and around tumors on color Doppler flow images. The study comprised 35 patients with liver mass lesions: 20 patients had hepatocellular carcinoma, six had hemangiomas, four had metastatic liver cancers, one had cholangiocellular carcinoma, one had focal fatty liver, and three had liver cysts. A basket pattern (a fine blood-flow network surrounding the tumor nodule) was observed in 15 (75%) of the 20 hepatocellular carcinomas. An image of vessels within the tumor (blood flow that runs into and branches within the tumor) was observed in 13 (65%) of the 20 hepatocellular carcinomas. These two findings were observed only in hepatocellular carcinomas; even when the tumor was smaller than 2 cm in diameter, these findings were observed frequently. In the patients with multiple hepatic metastases, a "detour" pattern (a dilated portal vein meandering around the tumor nodules) was observed. In three of the six hemangiomas, a "spot" pattern (color-stained dots or patches in the central region of the tumor) was seen. Our experience suggests that hepatocellular carcinomas have a characteristic appearance on color Doppler flow images.

Adenoma, Bile Duct↗

[A case of idiopathic hypoparathyroidism with extrapyramidal signs and insulin-dependent diabetes mellitus].

A case of a 29-year-old woman with idiopathic hypoparathyroidism was reported. There were neither endocrine nor neurological disorders among her family, except for her mother's hearing loss. She had been suffering from insulin-dependent diabetes mellitus since 21 years of age, and was noticed to be hard of hearing for several years, but never been examined. At the age of 27, choreic movement on her left upper limb and gait disturbance appeared. A year before admission, gait disturbance gradually developed and she could not walk any more. On admission, her height was 137.2 cm and her weight 36.5 kg. She had a round face, uneven teeth and borderline metacarpal sign on her right hand. On neurological examination, Parkinsonism, bucco-lingo-masticatory dyskinesia and bilateral extensor planter reflex were present, but tetany was not observed anywhere. Serum calcium was 3.9 mEq/l, and serum phosphorus 5.3 mEq/l. A CT scan of brain revealed calcifications in the bilateral basal ganglia and thalami, low density area in the left putamen, and atrophy of both caudate nuclei. Serum PTH was less than 100 pg/ml. Ellsworth-Howard's test showed hyperresponsiveness in the secretion of urinary phosphorus and cyclic-AMP. Other endocrinological studies showed no abnormality except for hyporesponsiveness in the secretion of insulin on glucose tolerance test. On the basis of these results, a diagnosis of idiopathic hypoparathyroidism with insulin-dependent diabetes mellitus was made. Administration of alfacalcidol returned serum calcium and phosphorus to normal with considerable clinical benefit. Parkinsonism was gradually improved and she became to be able to walk with a cane after one year of treatment. But buco-lingo-masticatory dyskinesia were not reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗