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Biomedical subjects

H Sakuma

Publications and source records attributed to H Sakuma.

At least 163 records · Page 9Linked to original sources

[Treatment of gastric cancer patients with peritoneal metastasis by continuous hyperthermic peritoneal infusion with mitomycin C and cisplatin].

Following the resection of its primary lesion, continuous hyperthermic peritoneal perfusion (CHPP) with anticancer drug (mitomycin C, cisplatin) containing warmed physiological saline was performed on gastric cancer having peritoneal dissemination, and the effect of CHPP was examined by second look operation (SLO). The subjects were 41 cases of gastric cancer with peritoneal dissemination but without hepatic metastasis, which we have experienced in the past 7 years. The prognosis of these CHPP-treated cases was such that 50% survival period, 3 year survival rate and 5 year survival rate were 398 days, 28.5 and 12%, respectively. Comparison of the effects of CHPP by SLO revealed remarkable diminution of the peritoneal dissemination in 7 (44%) of 16 cases and disappearance of the ascites with a single course of CHPP in 7 of ascitic cases. Long-term survival (greater than 3 years) was noted in 4 of the CHPP-treated cases. Side effects were renal insufficiency, leukopenia and small intestinal perforation in 2(5), 2(5) and 1 cases (2%), respectively. The above results suggested the effectiveness of CHPP for the treatment of gastric cancer having peritoneal dissemination.

Antineoplastic Combined Chemotherapy Protocols↗

[Measurement of intrahepatic shunt using Rutland method].

Intrahepatic shunt ratio was calculated from the fraction of the uptake constant and the blood background, analyzing the data of 99mTc-(Sn)-N-pyridoxyl-5-methyltryptophan (99mTc-PMT) hepatobiliary imaging by Rutland method. Shunt flow and total hepatic blood flow (THBF) were also calculated from the values for the effective hepatic blood flow (EHBF) estimated from the blood clearance technique. In 15 cases of normal volunteer, the average of the shunt ratio, shunt flow, and THBF were 18.4 +/- 5.4 (S.D.)%, 137.8 +/- 49 ml/min, and 753 +/- 83.2 ml/min, respectively. In 8 cases of chronic hepatitis, the values were 35.2 +/- 2.6%, 276 +/- 55.4 ml/min, and 794.1 +/- 119.4 ml/min, respectively. In 12 cases of liver cirrhosis, the values were 51.4 +/- 12.6%, 353.9 +/- 141.3 ml/min, and 685.6 +/- 174.8 ml/min, respectively. In cases of chronic hepatitis and liver cirrhosis, in comparison with normal cases, the values for the shunt ratio and shunt flow were significantly increased (p less than 0.001) and those for EHBF were significantly decreased (p less than 0.001), but those for THBF were not significantly altered. There was a significant inverse correlation between the shunt ratio and EHBF (r = -0.842) in all 35 cases. This method is considered to be useful for differential diagnosis, estimation of the grade of the diseases, and evaluation of pathophysiology of various diffuse liver diseases.

Chronic Disease↗

[Blood kinetics of free-platinum in CDDP hepato-arterial injection therapy].

In CDDP hepato-arterial injection therapy, platinum (Pt) concentration in hepatic and peripheral venous blood were determined in two groups with different injection rates, and the blood kinetics of Pt was examined. Seven cases of digestive cancers having liver metastases were given CDDP (100 mg) selectively into the proper hepatic artery at a constant rate (10 or 40 min). After injection, concentration of non-protein-bound Pt in hepatic and peripheral venous blood were determined. Pt concentration and AUC value were higher in hepatic venous blood at injection rate than peripheral venous blood. On the other hand, Pt concentration in hepatic venous blood in the cases 10 min-injection were higher than those received 40 min-injection, but neither Pt concentration in peripheral venous blood nor incidences of the side effects and abnormal clinical findings were influenced by the injected rates.

Adult↗

[Quantitative assessment of mineral content in metacarpal bone with Fuji computed radiography].

A new microdensitometry method for quantitative assessment of bone mineral content using Fuji computed radiography (FCR) was developed and the results were compared with those obtained by the conventional film-screen method. Using both methods, X-ray pictures of the 2nd metacarpal bone were taken with a reference aluminum step wedge in nine normal subjects and nine parameters representing the width and density of bone marrow and cortex were calculated in the middle of the bone shaft. Interobserver reproducibility assessed for three parameters was significantly higher in the FCR method than the conventional one. The value of sigma GS computed by the FCR method, that is equivalent to the net bone density of the transverse section of the shaft, showed higher correlation with the one obtained by computed tomography in comparison with the conventional method. In our FCR method, moreover, interobserver reproducibility and accuracy was improved by employing automatic manipulation as much as possible in the process of calculation. The exposure dose in the FCR method could be reduced to half of the one in the conventional method without deteriorating the accuracy. In conclusion, our new microdensitometry method with FCR provides high accuracy and good reproducibility for the measurement of bone mineral content with small exposure dose and is likely to be useful for the long-term follow-up of the osteoporotic patients from the variety of causes.

Adult↗

Effects of zinc L-carnosine on gastric mucosal and cell damage caused by ethanol in rats. Correlation with endogenous prostaglandin E2.

The effects of zinc L-carnosine on ethanol-induced damage and the correlation of these effects with endogenous prostaglandin E2 were evaluated in rat gastric mucosa in vivo and in vitro. When given either intragastrically or intraperitoneally, zinc L-carnosine (10 or 30 mg/kg) prevented gross visible damage to gastric mucosa caused by ethanol without affecting the mucosal prostaglandin E2 level. This protective effect of zinc L-carnosine was not inhibited by indomethacin. Histological assessment showed that zinc L-carnosine inhibited deep mucosal necrosis, as did 16,16-dimethyl prostaglandin E2. Zinc L-carnosine (10(-6) or 10(-5) M) inhibited the damage caused by ethanol to gastric cells isolated from rat gastric mucosa in vitro; this effect was not inhibited by indomethacin. The results suggested that zinc L-carnosine protects the gastric mucosa and enhances cellular resistance to ethanol without the mediation of endogenous prostaglandins.

16,16-Dimethylprostaglandin E2↗

Ultrastructure of swollen proximal axons of anterior horn neurons in motor neuron disease.

We have investigated ultrastructurally swellings of the proximal axons directly connected with the somata of anterior horn cells in a patient with motor neuron disease. In the distal portion of the initial segment, the swellings consisted predominantly of increased amounts of neurofilaments running nearly parallel to the longitudinal axis together with other cytoplasmic organelles. In the first internode of the myelinated axon, as the swellings became larger, the neurofilaments lost their parallel orientation and became intermingled. Most of the cell bodies connected with the swellings and their dendrites showed no particular changes. The abnormal neurofilamentous accumulations in the proximal axons suggest abnormal axonal transport, which may be pathogenetically associated with motor neuron disease.

Aged↗

A case of pancreatic oncocytic tumor.

An uncommon case of potentially malignant oncocytoma arising in the pancreatic tail of 54-year-old woman is reported. The tumor was encapsulated and measured 11 x 7 x 6 cm. The tumor cells were uniform in appearance, plump and polyhedral, with distinct finely granular eosinophilic cytoplasm, and were arranged in solid acinar groups. Electron microscopy revealed that the tumor cells contained numerous mitochondria in the cytoplasm. In the present case, the tumor cells showed perineural and small venous invasion in the pancreas and potentially malignant characteristics. However, neither recurrence nor metastasis has been detected 3 years after resection. These findings indicate that the present tumor had apparent low-grade malignancy.

Adenoma↗

Cardiovascular depression and stabilization by central vasopressin in rats.

The role of endogenous vasopressin in cardiovascular homeostasis was examined using vasopressin-deficient rats (Brattleboro) (n = 194) and their parent strain, Long-Evans rats (n = 181). Mean arterial pressure (blood pressure) and heart rate were measured every 4 seconds with or without infusion of drug solution for 21 hours, and mean values and their standard deviations (lability) were calculated. Blood pressure in Brattleboro rats (116 +/- 1.1 mm Hg, mean +/- SEM) was significantly higher than that in Long-Evans rats (96 +/- 0.7 mm Hg, p less than 0.001), whereas heart rates (381 +/- 3.3 and 375 +/- 2.9 beats/min, respectively) were similar. The lability of blood pressure and heart rate in Brattleboro rats (9.2 +/- 0.1 mm Hg and 42.3 +/- 0.7 beats/min) was also greater than that in Long-Evans rats (6.7 +/- 0.1 mm Hg, p less than 0.001 and 38.4 +/- 0.8 beats/min, p less than 0.01, respectively). In Brattleboro rats, intravenous vasopressin (0.1 ng/kg/min or 0.6 ng/kg/min) did not affect blood pressure, although it did reduce heart rate and decreased lability of blood pressure and heart rate. Intracerebroventricular (central) infusion of vasopressin (2 pg/kg/min) in Brattleboro rats induced initial hypertension and tachycardia followed by long-lasting hypotension and bradycardia, whereas in Long-Evans rats it induced only hypertension and tachycardia. In both strains, central vasopressin dramatically decreased the lability of blood pressure and heart rate. Neither intravenous (0.2 ng/kg/min) nor central desmopressin (2 pg/kg/min or 0.2 ng/kg/min), a V2 renal receptor agonist, changed any of these parameters in Brattleboro rats, although both diminished urinary volume. Neither intravenous (50 ng/kg/min) nor central (3.3 pg/kg/min) d(CH2)5-Tyr(Me)-arginine vasopressin, a vasopressin V1 receptor antagonist, modulated any of these parameters in Long-Evans rats. These results suggest that endogenous as well as exogenous vasopressin acts centrally as a cardiovascular inhibitor and stabilizer through a receptor mechanism other than V1 or V2 receptor mechanisms.

Animals↗

Influence of age on the nocturnal fall of blood pressure and its modulation by long-acting calcium antagonists.

The clinical significance of the nocturnal fall of blood pressure (BP) was examined. BP was monitored every 5 min for 24 hrs by means of a finger volume oscillometric device. The nocturnal fall was observed in all age groups (young: less than 40, n = 49; adult: 40 less than or equal to less than 60, n = 110; old: 60 less than or equal to, n = 33). The amplitude of nocturnal fall of BP (averaged daytime blood pressure--averaged nighttime blood pressure) in old patients (systolic = 13 +/- 11, diastolic = 10 +/- 8 mmHg, mean +/- SD) was similar to that in the young patients (systolic = 11 +/- 8, diastolic = 10 +/- 8 mmHg). These 192 subjects were also classified according to mean BP level (MBP) averaged for daytime in the ambulatory blood pressure monitoring records [MBP less than 85 (mmHg), n = 31; 85 less than or equal to MBP less than 100, n = 72; 100 less than or equal to MBP less than 115, n = 49; 115 less than or equal to MBP, n = 25]. BP level did not affect the pattern of circadian variation in the normal subjects or in the essential hypertensive patients at WHO stage I or II. The amplitude of the nocturnal fall in systolic BP increased with the increase in BP level, but this was not the case with diastolic BP (mean daytime BP less than 85 mmHg: systolic = 11 +/- 8, diastolic = 8 +/- 6 mmHg; 85 less than or equal to less than 100: systolic = 14 +/- 8, diastolic = 11 +/- 6 mmHg; 100 less than or equal to less than 115: systolic = 17 +/- 9, diastolic = 11 +/- 8; 115 less than or equal to: systolic 17 +/- 8, diastolic = 11 +/- 6 mmHg). Nitrendipine (8.6 +/- 5.6 mg, 22.5 +/- 11.4 days, n = 14) and nisoldipine (9.3 +/- 6.2 mg, 21.5 +/- 11.4 days, n = 15) administered once daily in the morning or nifedipine slow release tablet, 20 mg twice daily (n = 15, 17.7 +/- 5.2 days) induced a significant downward shift in the circadian BP pattern, in other words, the hypotensive effect was also observed during the night when the BP had already been low. Taken together, the information on the nocturnal behavior of BP would be valuable, especially in treating aged patients with essential hypertension with a long-acting antihypertensive drug.

Aging↗

A cross-sectional survey of home blood pressure in a rural community in northern Japan.

A cross-sectional survey was performed on home blood pressure recordings (home BP) in a rural community in northern Japan. In total, 1190 participants (495 men and 695 women which consist 61.5% of the greater than or equal to 15 year-old regional population, n = 1933) were asked to measure home BP every morning for a month, using a semiautomatic BP measuring device. The actual measurements were done 16.8 +/- 10.2 times (mean +/- SD) for men and 19.0 +/- 9.4 times for women. Home systolic (SBP) and diastolic BP (DBP) was elevated gradually with age in both sexes, although DBP tended to fall after reaching 70 years old in men. SBP and DBP thus measured were significantly lower than those of casual BP of ordinary Japanese people reported by the Ministry of Health and Welfare, Japan, by 11.4 +/- 4.3 mmHg SBP (mean +/- SD) and 5.9 +/- 1.6 mmHg DBP in men, and 12.7 +/- 5.1 mmHg SBP and 8.1 +/- 2.5 mmHg DBP in women. When WHO criteria were applied to the home BP, 2.8% of men and 0.6% of women were considered to be definitely hypertensive, and 7.9% of men and 6.4% of women as of borderline cases, indicating the underestimation of hypertensive population by means of home BP. Based on these data, we demonstrated the values equal to 1SD or 2SDs above the mean in each age group to tentatively determine biological normalcy. It is necessary to define the relationship between home BP and target organ disease or hypertensive complications. A long-term prospective study is also necessary to define the relationship between home BP and long-term morbidity or mortality.

Adolescent↗

Does ambulatory blood pressure monitoring improve the diagnosis of secondary hypertension?

Ambulatory blood pressure monitoring can determine the average blood pressure level and the short- and long-term blood pressure variability (circadian rhythm). The circadian blood pressure rhythm appears to be mediated mainly by the circadian rhythm of the sympathetic tone which is linked to changes in physical and mental activity, e.g. the waking-sleeping cycle. A statistically significant circadian blood pressure rhythm was observed in approximately 80% of mild to moderate essential hypertensive patients as well as in normal subjects. However, in patients with Cushing's syndrome, under glucocorticoid treatment, or with hyperthyroidism, central and/or peripheral autonomic dysfunction (Shy-Drager syndrome, spinal cord injury, brainstem lesions, diabetic neuropathy, uremic neuropathy, etc), chronic renal failure, eclampsia, malignant hypertension, sleep apnea syndrome or systemic atherosclerosis, the normal circadian blood pressure rhythm appears to be eliminated or reversed, while in those with primary aldosteronism, renovascular hypertension, pheochromocytoma without paroxysmal hypertension, diabetes insipidus, acromegaly, hyperparathyroidism or hyperprolactinemia, the nocturnal blood pressure fall has been observed as in normal subjects. The alteration in the circadian blood pressure rhythm was observed with different pathophysiological conditions, although no specific pattern was observed for any condition. A disturbance in any part of the hierarchy of factors that regulate the circadian rhythm of sympathetic neural tone seems to disturb the circadian blood pressure rhythm. We conclude that ambulatory blood pressure monitoring is not critically important in the diagnosis of secondary hypertension although it does help in screening for secondary hypertension.

Autonomic Nervous System Diseases↗

Cytoprotection by histamine in rat gastric mucosa.

The effects of histamine on endogenous prostaglandins and on the damage caused by 0.6 N HCl were tested in rat gastric mucosa. The damage was assessed both macroscopically and microscopically. Histamine increased the prostaglandin E2 level in vivo and stimulated the synthesis of prostaglandin E2 and 6-keto-prostaglandin F1 alpha in vitro. These effects of histamine were inhibited by treatment with cimetidine beforehand. Histamine inhibited both the gross visible mucosal damage and deep necrosis caused by the intragastric instillation of 0.6 N HCl. This effect was overcome by cimetidine or indomethacin, but not by diphenhydramine. These results suggest that histamine stimulates prostaglandin synthesis and induces cytoprotection in rat gastric mucosa, perhaps with the involvement of the H2 receptor.

Animals↗

Circadian blood pressure variations under different pathophysiological conditions.

The daily variation in blood pressure (circadian blood pressure rhythm) is characterized by a nocturnal fall and a diurnal rise. The circadian blood pressure rhythm seems to be mediated mainly by the circadian rhythm of sympathetic tone, linked to changes in physical and mental activities, e.g. the waking-sleeping cycle. Statistically significant circadian blood pressure rhythms have been confirmed in approximately 80% of mild to moderate essential hypertensive patients as well as in normal subjects. However, the normal pattern of circadian blood pressure rhythm is reversed in elderly people and in those with Cushing's syndrome, those undergoing glucocorticoid treatment, and those with hyperthyroidism, central and/or peripheral autonomic dysfunction (Shy-Drager syndrome, tetraplegia, diabetic or uremic neuropathy, etc), chronic renal failure, renal or cardiac transplantation, congestive heart failure, eclampsia, sleep apnea syndrome, malignant hypertension, systemic atherosclerosis and accelerated hypertensive organ damage. However, in those with primary aldosteronism, renovascular hypertension, pheochromocytoma without paroxysmal hypertension, or those with cardiac pacing, a nocturnal blood pressure fall is ordinarily observed. It may be that a fall in cardiac output rather than in peripheral resistance may be mainly responsible for the nocturnal fall in blood pressure. It also seems that a nocturnal heart rate fall is not responsible for it, since the nocturnal blood pressure fall remained unchanged in patients undergoing cardiac pacing and was disturbed in patients with Cushing's syndrome or hyperthyroidism in whom the circadian heart rate rhythm remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic Nervous System Diseases↗

[Multivariate analysis of gastric cancer patients with liver metastases].

In 93 cases of stomach cancer with liver metastasis, the influence of surgery and chemotherapy on the patients' prognosis was examined. Chemotherapy comprised systemic administration of mitomycin C (MMC) (39 cases), intra-hepatoarterial administration of MMC (19 cases) and intra-hepatoarterial infusion of cisplatin (CDDP) + MMC (PM intra-arterial chemotherapy) (24 cases) in the first 1-2 postoperative weeks. MMC and CDDP were given by 1-4 courses every 1-3 weeks. Examination of the prognosis factors by generalized Wilcoxon test revealed significant differences in the extent of lymph node metastasis (N0-2 vs N3,4), possible resection of primary lesion, and chemotherapeutic regimen (PM intra-arterial chemotherapy and other chemotherapeutic regimens). The response rate was 4.3% (1/23), 29.4% (5/17) and 73.8% (17/23) for MMC systemic administration, MMC intra-arterial chemotherapy and PM intra-arterial chemotherapy, respectively, with a significantly high response rate for the latter. Also for the 50% survival period, the latter showed 11.8 months compared with 2.7 months for other chemotherapeutic treatments, indicating its good prognosis regardless of possible resection of the primary lesion. Cox proportional hazard model revealed the latter alone to be a significant independent factor. The above results suggest that the PM intra-arterial chemotherapy is an effective approach to stomach cancer with liver metastasis.

Adult↗

[Intravoxel incoherent motion (IVIM) imaging using an experimental MR unit with small bore].

IVIM images were constructed from a pair of spin echo (SE) sequences on a 2T MR unit with small bore. In the current study, two types of SE were used: the standard SE and the other sensitized to microscopic incoherent motion by adding motion probing gradient on either side of 180 degrees pulse. IVIM images of water and acetone phantoms were generated, and the diffusion coefficients obtained from these materials were consistent with the literature values. IVIM images of implanted human tumor in nude mouse showed relatively high apparent diffusion coefficient (2.0 x 10(-3) mm2/sec). However, in the sacrificed mouse, diffusion coefficient in the tumor was markedly decreased (0.5 x 10(-3) mm2/sec), which suggested the considerable contribution of perfusion to ADC. In conclusion, IVIM imaging was thought to be highly valuable because it can provide functional information about tumor perfusion.

Animals↗

[Measurement of effective hepatic blood flow using 99mTc-PMT SPECT and single blood sampling].

Effective hepatic blood flow (EHBF) was measured from an uptake constant using single blood sampling and 99mTc-PMT hepatobiliary SPECT data. After intravenous injection of 3 mCi (111 MBq) of 99mTc-PMT, serial 1 min SPECT data were obtained for 7 minutes. A time activity curve (TAC) over the heart, that was normalized with the 5 minutes venous sample concentration (%/dose/ml), was used as a blood clearance curve (B(t]. And a TAC of the whole liver, that was normalized with the injected dose of 99mTc-PMT (%/dose), was used as a hepatogram (L(t]. An uptake constant representing EHBF, was estimated from the Rutland's method L. (t)/B(t) was plotted against integral of otB(t)dt/B(t), and the slope of the least square fitted straight line was determined as the uptake constant. In 16 cases, significant correlation was obtained between the 99mTc-PMT hepatic uptake at 5 minutes and the EHBF estimated from the blood clearance (r = 0.85, p less than 0.001). While there was a much better correlation between the EHBF from uptake constant and the EHBF from blood clearance (r = 0.95, p less than 0.001). In conclusion, this analysis for uptake constant of 99mTc-PMT SPECT data enables us to estimate EHBF with single venous sampling and in relatively short acquisition time. This method is thought to be very valuable in clinical practice.

Humans↗

ADP-ribosylation of 24-26-kDa GTP-binding proteins localized in neuronal and non-neuronal cells by botulinum neurotoxin D.

Clostridium botulinum D (strain South Africa) produces ADP-ribosyltransferase which modifies eukaryotic 24-26-kDa proteins. ADP-ribosyltransferase activity was associated with a neurotoxin of 150 kDa (Dsa toxin) as confirmed by the elution profile of Dsa toxin from high performance anion-exchange column. The 24-kDa substrate of Dsa toxin-catalyzed ADP-ribosylation was detected in several tissues examined including rat brain, heart, and liver; bovine adrenal medulla; sea urchin eggs; electric organs of electric fish; and cell lines of neural (N18, N1E115, NS20Y, NG108, PC12, and C6) and non-neural (3T3) origins, suggesting its ubiquitous localization in eukaryotic cells. On the other hand, the 26-kDa substrate was detected only in membrane fractions of neural tissues and neuronal cells, suggesting its specific localization in membrane of nerve terminals. ADP-ribosylation of both the 24-kDa substrate in PC12 membrane and the 24-26-kDa substrates in rat brain membrane was potentiated by either divalent cations or guanine nucleotides, whereas adenine nucleotides did not affect the ADP-ribosylation reaction. Trypsin digestion of the 24-kDa substrate in PC12 membrane and the 24-26-kDa substrates in rat brain membrane extract produced different tryptic fragments indicative of the structural difference between the 24- and 26-kDa substrates. Both the 24- and 26-kDa substrates were less sensitive to trypsin digestion before being ADP-ribosylated by Dsa toxin than after, suggesting the conformational alterations of the 24-26-kDa proteins induced by ADP-ribosylation. These results suggest that Dsa toxin modifies two distinct low molecular mass GTP-binding proteins by ADP-ribosylation to alter their putative function(s).

ADP Ribose Transferases↗