Biomedical subjects

T Ohta

Publications and source records attributed to T Ohta.

At least 451 records · Page 25Linked to original sources

PubMed1997

Efficient production of a functional mouse/human chimeric Fab' against human urokinase-type plasminogen activator by Bacillus brevis.

Expression/secretion vectors for the production of Fab' and single-chain (sc) Fab' by Bacillus brevis have been constructed. For the production of Fab', the cDNAs encoding the L chain and Fd' fragment (Fd with the hinge region) of a mouse-human chimeric Fab' against human urokinase-type plasminogen activator were fused directly with the translation-start and signal-peptide-encoding regions of the mwp gene, the gene for one of the major cell-wall proteins of Bacillus brevis. The two fused genes were placed tandemly downstream from the promoter of the cell-wall protein gene operon (cwp) of B. brevis. For the production of scFab', the two cDNAs were linked with a synthetic oligonucleotide encoding a flexible peptide linker of 17 or 24 amino acids, and fused with the translation start and signal-peptide-encoding regions of the mwp gene. Fab' was efficiently produced by B. brevis, being accumulated at a level of 100 mg/l in the culture medium in a simple shake-flask culture, which is the highest level obtained so far for a gram-positive bacterium. On the other hand, the scFab' remained at a level of a few milligrams per liter in the culture medium. The Fab' produced by B. brevis showed comparable antigen-binding activity to that of the parental antibody. The L chain and Fd' fragment, constituting the Fab', had the correct N-terminal amino acid sequences. These results indicate that B. brevis is a very promising host for the production of native Ig fragments.

Amino Acid Sequence↗

PubMed1997

Complementary expression of glutamine synthetase and carbamoylphosphate synthetase I in ornithine carbamoyltransferase-deficient mouse liver (spf-ash mouse).

Glutamine synthetase and carbamoylphosphate synthetase I expression was examined immunohistochemically in livers of spf-ash homozygous and hemizygous mice, in which one of the urea cycle enzymes (ornithine carbamoyltransferase) is deficient and hyperammonemic disorders are obvious. In the mutant adult mouse liver, only hepatocytes lining central veins expressed glutamine synthetase. In contrast, other hepatocytes expressed carbamoylphosphate synthetase I but not glutamine synthetase. This complementary expression pattern is similar to that seen in wild-type mouse liver. In the liver of mutant young mice, which showed severe retarded growth and abnormal hair and skin development, the developmental expression pattern of both enzymes was also similar to that of the corresponding wild-type liver. However, suppression of carbamoylphosphate synthetase I expression in the pericentral hepatocytes occurred later in the mutant than in wild-type liver. These results show that high plasma concentrations of ammonium ions, which are one of the substrates for both the enzymes, do not change their complementary expression. Instead they support the idea that factor(s) associated with central veins rather than humoral factors direct pericentral hepatocytes to express glutamine synthetase and to suppress carbamoylphosphate synthetase I expression.

Ammonia↗

PubMed1997

Calcium channel subtypes in porcine adrenal chromaffin cells.

The effects of nifedipine, omega-conotoxin GVIA (omega-CgTx) and omega-agatoxin IVA (omega-AgTx) on Ca2+ currents, a 60-mM-K+-induced increase in intracellular Ca2+ concentration (-Ca2+-i) and catecholamine secretion were examined to clarify the subtypes of Ca2+ channels in cultured adrenal chromaffin cells from the pig. Nifedipine, omega-CgTx, and omega-AgTx inhibited Ca2+ currents in a dose-dependent manner, suggesting the presence of L-, N- and P-type Ca2+ channels. The maximal doses of nifedipine (10 microM), omega-CgTx (1 microM), and omega-AgTx (0.1 microM) inhibited Ca2+ currents to 85%, 22%, and 94% of control currents, respectively. The inhibitory effects of these three blockers were observed in the same cell, indicating that at least three subtypes of Ca2+ channels are present in porcine chromaffin cells. The increase in -Ca2+-i and catecholamine secretion induced by 60 mM K+ were inhibited equally by nifedipine (10 microM) and omega-CgTx (1 microM), but not by omega-AgTx (0.1 microM). These results suggest that L-, N- and P-type Ca2+ channels are present in porcine adrenal chromaffin cells, and that the major pathways of Ca2+ entry evoked by a high concentration of K+ are L- and N-type Ca2+ channels.

Adrenal Glands↗

PubMed1997

Endocrine cells in intraductal papillary-mucinous neoplasms of the pancreas. A histochemical and immunohistochemical study.

The endocrine cells in intraductal papillary-mucinous neoplasms (IPN) of the pancreas have rarely been investigated. In the normal pancreatic ducts of normal pancreases (n = 5) there were a few endocrine cells: argyrophil in 5 (100%), chromogranin A in (100%), pancreatic polypeptide (PP) in 3 (60%), and insulin in 7 (20%). These endocrine cells were scattered, and located in the basal portions of pancreatic ducts. In IPN of the pancreas (n = 9), there were many endocrine cells: argyrophil in 7 (78%), argentaffin in 8 (89%), chromogranin A in 8 (89%), PP in 7 (78%), serotonin in 7 (78%), insulin in 4 (44%), and gastrin in 5 (56%). In invasive ductal adenocarcinoma of the pancreas (n = 6), many endocrine cells were also detected: argyrophil cells in (67%), chromogranin A in 3 (50%), insulin in 3 (50%), glucagon in 4 (67%), and somatostatin in 3 (50%). In positive cases, endocrine cells were situated under or among the neoplastic cells and the proportion of endocrine cells in IPN was less than 5% of the total neoplastic cell population. These data show that normal pancreatic ducts contain endocrine cells and that IPN frequently contain argyrophil, argentaffin, chromogranin A, and hormone-containing endocrine cells. These data also suggest that endocrine differentiation occurs during neoplastic transformation and progression of IPN of the pancreas.

Adenocarcinoma, Mucinous↗

PubMed1997

Expression of pancreatic digestive enzymes in normal and pathologic epithelial cells of the human gastrointestinal system.

Pancreatic digestive enzymes have rarely been reported in human nonpancreatic organs. We examined their expression in the epithelial cells of the nonpancreatic gastrointestinal organs, looking for pancreatic alpha-amylase, trypsin, chymotrypsin and pancreatic lipase. Western blotting, enzyme assay and pancreatic alpha-amylase mRNA were also used in selected specimens. In normal tissues, immunoreactivity of one or more of these enzymes was frequently noted in cells of the salivary glands, stomach, duodenum, large pancreatic ducts, extrahepatic bile ducts and gall bladder. The epithelium of the normal oesophagus, small intestine and colon were consistently negative for these enzymes. In pathologic tissues, immunoreactivity for one or more enzymes was present in epithelial cells of pleomorphic adenomas of the salivary glands, oesophageal squamous cell carcinoma, gastric adenoma and adenocarcinoma, pancreatic adenocarcinoma, cholecystitis, adenocarcinoma of the gall bladder and extrahepatic bile duct, and colon adenoma and adenocarcinoma. Western blotting showed a specific band of each enzyme in some specimens of normal stomach. In situ hybridization for pancreatic alpha-amylase mRNA showed specific signals in the normal stomach, but not in the normal colon. Reverse transcriptase polymerase chain reaction analysis for pancreatic alpha-amylase mRNA revealed specific signals in the normal stomach. Enzyme assay revealed that the stomach and gall bladder showed these activities. The data suggest that pancreatic digestive enzymes are produced by several epithelial cell types of the nonpancreatic gastrointestinal organs, that the organs positive for pancreatic enzyme have a common cell lineage, and that neoplasms continue to express or neoexpress these enzymes after neoplastic transformation.

Adult↗

PubMed1997

Depressed natural killer cell activity due to decreased natural killer cell population in a vitamin E-deficient patient with Shwachman syndrome: reversible natural killer cell abnormality by alpha-tocopherol supplementation.

UNLABELLED: Natural Killer (NK) cell activity was examined in a 16-month-old Japanese boy with Shwachman syndrome associated with severe vitamin E deficiency. As evaluated by 51Cr-release assay from K562 cells, NK cell activity was constantly decreased. After 8 weeks of oral alpha-tocopherol (alpha-Toc) supplementation (100 mg/day), NK cell activity had normalised. When alpha-Toc supplementation was interrupted for 16 weeks. NK cell activity again decreased. Flow cytometry of peripheral lymphocytes revealed a lowered number of CD16+ CD 56- fraction, which has the most potent NK cell activity. Single cell-in-agarose assay, to investigate the binding and cytolytic activity of NK cell at the single cell level, revealed that the number of NK cells which bind to K562 cell was decreased, but that the cytolytic activity of the individual binding cell was relatively unaffected. A second supplementation of alpha-Toc for 8 weeks successfully restored NK cell activity, the number of cells expressing NK cell markers and the number of K562-binding cells as compared to the age-matched normal range. CONCLUSION: These results indicate that severe vitamin E deficiency caused impaired NK cell activity due to a decrease in the number of CD16+ CD56- NK cells and that this abnormality is reversible with alpha-Toc supplementation.

Adolescent↗

PubMed1997

Immunohistochemical and immuno-electron-microscopic detection of interferon-gamma-inducing factor ("interleukin-18") in mouse intestinal epithelial cells.

The novel cytokine interferon-gamma-inducing factor ("interleukin-18") is produced by macrophage-like cells in mice with endotoxin shock and induces the production of interferon-gamma by T cells in vitro. To determine the physiological role for mouse interferon-gamma-inducing factor, we studied its tissue distribution in several organs (intestine, spleen, thymus, kidney, and liver) in healthy mice of different ages, including fetal stages. Activity of the cytokine in the organ extracts of adult mice was measured by enzyme-linked immunosorbent assay, and the cellular distribution of interferon-gamma-inducing factor in organs from fetal and adult mice was determined by immunohistochemistry. Intestinal extracts of adult mice showed the highest concentrations among the organs studied. Other organ extracts of adult mice showed lower concentrations of the cytokine. Immunohistochemical analysis revealed that interferon-gamma-inducing factor was localized in the cytoplasm of intestinal epithelial cells from fetal and adult mice. These results show for the first time that intestinal epithelial cells may be the main producers of interferon-gamma-inducing factor under normal physiological conditions and suggest that its constitutive expression in intestinal epithelial cells may have an important role in the induction of mucosal immunity.

Animals↗

PubMed1997

Total resection of the head of the pancreas preserving the duodenum, bile duct, and papilla with end-to-end anastomosis of the pancreatic duct.

Many surgeons have recently attempted operative procedures for limited resection of the head of the pancreas. This site-specific approach has emerged as a result of precise diagnostic radiologic studies that have become available. The author performed a new operative procedure in 2 patients with mucin-producing pancreatic cysts that included total resection of the head of the pancreas with careful regard to its vasculature. The procedure provided a way of resecting the head of the pancreas while preserving the duodenum, bile duct, and papilla. The pancreatic duct was cut 5 mm before the point of confluence with the bile duct, and an end-to-end anastomosis was performed on the pancreatic duct. Both patients were discharged within 1 to 1.5 months after surgery, without complication. The operative procedure requires no processing of the jejunum, only a simple anastomosis of the pancreatic duct.

Anastomosis, Surgical↗

PubMed1997

Fractional esterification rate of cholesterol in high density lipoprotein (HDL) can predict the particle size of low density lipoprotein and HDL in patients with coronary heart disease.

Fractional esterification rate of cholesterol in high density lipoprotein (HDL) (FER[HDL]) can predict the size distribution and physicochemical characteristics of HDL in plasma. In the present study, we investigated the correlation of FER(HDL) with the particle size of low density lipoprotein (LDL) (LDL-size) in 111 patients (81 males and 30 females) with coronary heart disease (CHD). The correlations of FER(HDL) and LDL-size with conventional lipid and lipoprotein parameters were also studied. FER(HDL) was closely associated with LDL-size (males: r = -0.618, females: r = -0.629, P < 0.001). Plasma levels of TG, HDL-cholesterol (HDL-C), HDL2-cholesterol (HDL2-C) and apo B were also associated with LDL-size in male CHD patients (r = -0.534, 0.314, 0.358, and -0.482, P < 0.01 or 0.001), while plasma levels of TG and apo B were associated with LDL-size in female patients (r = -0.350 and -0.348, P < 0.05). In a stepwise multiple regression analysis, FER(HDL) alone accounted for 38 and 40% of the variability in LDL-size in male and female CHD patients, respectively. Other parameters accounted for an additional 6-10%. With respect to the relation between FER(HDL) and HDL subfractions, FER(HDL) related only to HDL2-C (males: r = -0.640, females: r = -0.652, P < 0.001). This result suggests that FER(HDL) is better able to predict the presence (or absence) of large HDL, rather than that of small HDL. All these data taken together, suggest that FER(HDL) is a useful tool to predict the particle size of both LDL and HDL, even in CHD patients.

Aged↗

PubMed1997

Effects of L-dopa and bromocriptine on haloperidol-induced motor deficits in mice.

L-3,4-Dihydroxyphenylalanine (L-DOPA), the precursor of dopamine, and bromocriptine, a dopamine D2 receptor agonist, were investigated in haloperidol-induced motor impairments in mice using both catalepsy and pole tests. In catalepsy test, subcutaneous treatment with haloperidol (0.125, 0.25 and 0.5 mg/kg) caused a cataleptic effect in mice in a dose-dependent manner. This cataleptic effect was evident upto 7 hr after haloperidol treatment. In pole test, haloperidol (0.125, 0.25 and 0.5 mg/kg) produced the prolongation of Tturn and TLA as a marker of bradykinesia in mice and the prolongation lasted at least 7 hr after haloperidol treatment. Intraperitoneal co-pretreatment with L-DOPA (400 mg/kg) + carbidopa (10 mg/kg) in mice decreased the catalepsy induced by haloperidol at a dose of 0.125 mg/kg, while co-pretreatment with L-DOPA (200 and 400 mg/kg) + carbidopa (10 mg/kg) dose-dependently decreased the haloperidol (0.125 mg/kg)-induced bradykinesia. The effect of LDOPA + carbidopa in pole test was more pronounced than that in catalepsy test. Intraperitoneal pretreatment with bromocriptine (2 and 4 mg/kg) in mice reduced the catalepsy and bradykinesia produced by haloperidol at a dose of 0.125 mg/kg. The effect of bromocriptine in pole test was relatively similar to that in catalepsy test. Also, co-pretreatment with LDOPA (400 mg/kg) + carbidopa (10 mg/kg) and pretreatment with bromocriptine (2 and 4 mg/kg) significantly decreased the catalepsy induced by haloperidol at a higher dose of 0.5 mg/kg. These results indicate that co-administration with L-DOPA + carbidopa and single treatment with bromocriptine can decrease haloperidol-induced catalepsy and bradykinesia in mice. Furthermore, our study suggests that pole test as well as catalepsy test is of value in the screening of drugs against neuroleptic-induced motor deficits.

Animals↗

PubMed1997

Surgical strategy for carcinoma of the papilla of Vater on the basis of lymphatic spread and mode of recurrence.

BACKGROUND: Nodal status is one of the most important prognostic factors for carcinoma of the papilla of Vater. The pattern of lymphatic spread and mode of recurrence were analyzed by determining the frequency of nodal involvement and antemortem and postmortem examination of patients with recurrent disease. METHODS: From 1974 to 1994, 36 patients with carcinoma of papilla of Vater underwent pancreatectomy at the Kanazawa University Hospital. A precise evaluation of the nodal involvement was determined by means of careful pathologic review of the extended lymphadenectomy specimen. The mode of recurrence was determined by use of autopsy and radiographic examinations. RESULTS: Fifteen (42%) of 36 patients had nodal involvement. The lymph nodes with the highest metastatic rates were the inferior pancreaticoduodenal lymph nodes (number 13b) and the superior mesenteric lymph nodes (number 14) (13b, 31%; 14, 17%). There were no metastases in the perigastric lymph nodes. A significant relationship existed between the gross appearance of the primary tumor and nodal involvement (protruding, 22%; mixed type, 42%; ulcerative, 100%). The 5-year survival rates were 74% in the absence of nodal metastasis versus 31% with nodal metastasis. The 5-year survival rates for patients with protruding, mixed type, and ulcerative tumors were 75%, 49%, and 17%, respectively. Survival and recurrence were significantly correlated to gross appearance and nodal involvement. Retroperitoneal recurrence and liver metastasis were main modes of recurrence. CONCLUSIONS: Lymph node 13b is important in lymphatic metastasis to the superior mesenteric lymph nodes for carcinoma of papilla of Vater. Nodal dissection around the superior mesenteric artery is needed to improve the prognosis of carcinoma of papilla of Vater except in the nonexposed protruding tumor. Pylorus-preserving pancreatoduodenectomy may be indicated in patients with carcinoma of the papilla of Vater.

Adult↗

PubMed1997

Troglitazone lowers blood pressure and enhances insulin sensitivity in Watanabe heritable hyperlipidemic rabbits.

Although an association has been demonstrated between insulin resistance and hypertension, the mechanism of this association is not clear. Clarification of this point is important in hyperinsulinemic Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model of familial hypercholesterolemia, as hypertension markedly stimulates atherosclerosis in WHHL rabbits. The purpose of the present study was to determine whether troglitazone, a new thiazolidinedione drug for insulin resistance, could reduce blood pressure (BP) by improving hyperinsulinemia in WHHL rabbits. The effects of troglitazone, administered as a food admixture (24 mg/day) for 6 months, on hyperinsulinemia and BP were examined in WHHL rabbits. Insulin sensitivity (IS) was measured by the minimal model method using an intravenous glucose tolerance test (IVGTT). Troglitazone significantly reduced fasting insulin levels and the area-under-the-curve of insulin IVGTT profiles, indicating improved hyperinsulinemia. Troglitazone also significantly increased IS and reduced BP and heart rate (HR). Due to a significant correlation between HR and BP, a covariance analysis was performed. When BP was considered as a covariance factor, the change in HR was significant in treated rabbits. However, when HR was considered as a covariance factor, the change in BP was not significant, suggesting that reduced BP may be partly associated with changes in the sympathetic nervous system activity. In conclusion, troglitazone increases insulin sensitivity and lowers blood pressure in WHHL rabbits. Due to its dual effects on insulin resistance and hypertension, troglitazone offers a new pharmacological approach for the treatment of insulin-resistance syndrome.

Animals↗

PubMed1997

Mechanism of action of gemfibrozil on HDL metabolism and atherosclerosis in WHHL rabbits.

We investigated the mechanism of action of gemfibrozil on high-density lipoproteins (HDL) and apolipoprotein (apo) A-I metabolism and atherogenesis in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model of familial hypercholesterolemia and HDL deficiency. Two-month-old WHHL rabbits were fed either a normal control diet or a diet containing 0.5% gemfibrozil for 12 months. In vivo apo A-I kinetics, the fractional rate of cholesterol esterification in HDL (FER[HDL]), which reflects the reactivity of HDL to lecithin:cholesterol acyltransferase, and a morphometrical analysis of atherosclerotic lesions in the descending thoracic aorta, were examined. At 12 months, the mean levels of serum total cholesterol, LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) in both groups had decreased to approximately 53%, 57%, and 87% of the initial levels (at 0 month), respectively, which is characteristic of homozygous WHHL rabbits of the physiologic influence of aging, and no differences in the levels of serum LDL-C, HDL-C, and triglycerides were found between the two groups. Rabbits treated with gemfibrozil exhibited a decreased FER(HDL) (38% of the controls, P = 0.039). Gemfibrozil induced a significant increase in the total mass of apo A-I (1.7-fold, P < 0.05) and in the rate of apo A-I synthesis (1.6-fold, P < 0.05). The atherosclerotic intimal area was positively correlated with serum LDL-C (P = 0.02) in both groups, but gemfibrozil did not affect the atherosclerotic intimal area. These results indicate that 12 months of treatment with gemfibrozil did not protect against atherosclerosis despite a significant increase in apo A-I synthesis and enhanced HDL function through FER(HDL). It is possible that both the qualitative and quantitative improvement in HDL by gemfibrozil cannot overcome the massive and long-term exposure of the vascular wall to LDL in these animals.

Animals↗

PubMed1997

Release of 5-hydroxytryptamine by hypoxia from epithelioid cells of chicken thoracic aorta.

Epithelioid cells in the chicken thoracic aorta are shown to contain 5-hydroxytryptamine (5-HT) in immunocytochemical studies. To determine whether these cells act as chemoreceptors, as do type I cells of the carotid body, we examined the effects of hypoxia and acidosis on the release of 5-HT from the chicken thoracic aorta. Hypoxia caused the output of 5-HT in incubation medium. A reduction of pH to 6.8 failed to evoke 5-HT release. The response to hypoxia was inhibited by the removal of extracellular Ca2+ and by nifedipine and omega-conotoxin GVIA. These results suggest that epithelioid cells in the chicken thoracic aorta are chemoreceptors which sense a decrease in PO2 and then release 5-HT by Ca2+ influx through voltage-dependent L- and N-type Ca2+ channels. The epithelioid cells in the chicken aorta may be a useful model for pharmacological and physiological studies of 5-HT-containing cells.

Animals↗

PubMed1997

Serum pyridinoline crosslinks as markers of tumour-induced bone resorption.

OBJECTIVE: To assess serum pyridinoline (Py) and deoxypyridinoline (dPy), using a new high-performance liquid chromatography (HPLC) method, as a serum marker to determine the incidence of metastatic bone disease in an animal model and in the monitoring of patients with or without metastatic bone disease from prostate cancer and renal cell carcinoma (RCC). PATIENTS, MATERIALS AND METHODS: Female C3H/He mice (8-12 weeks old) received a subcutaneous injection of tumour-cell suspensions of serially transplanted MBT tumours. The tumour cells induced osteolysis associated with osteoclast proliferation and serum samples were evaluated for Py and dPy using HPLC. The growth of the tumour macroscopically and histologically, and the extent of bone loss assessed by radiography, were compared with the serum Py and dPy level. In the clinical study, patients with or without bone metastases from RCC (24 patients) or prostate cancer (37 patients) were monitored using the same techniques and the number and extent of bone metastases compared with serum Py and dPy levels both in these patients and in 84 healthy control subjects. RESULTS: There was a significant correlation between the bone loss evaluated by radiography and the level of serum Py in the animal model. Patients with bone metastases from RCC had higher values of Py and dPy than patients without known metastatic bone disease. The serum Py level increased in two patients as metastatic bone disease progressed. Similarly, in patients with prostate cancer, the mean level of serum Py and dPy was higher in patients with bone metastasis than in the control group, and also higher than that in patients without metastases. The serum Py and dPy levels could also distinguish patients with metastatic bone disease with and without a lytic component. CONCLUSION: Measurements of serum Py appear to provide a good index of increased bone resorption induced by experimental tumours and in patients with bone metastases from RCC and prostate cancer.

Aged↗

PubMed1997

Involvement of Glu-264 and Arg-235 in the essential interaction between the catalytic imidazole and substrate for the D-lactate dehydrogenase catalysis.

For Lactobacillus pentosus D-lactate dehydrogenase, the binding of 2-ketoacids is markedly stabilized through interactions between the protonated imidazole of His-296, an acid/base catalyst of the enzyme, and the carbonyl oxygen of 2-ketoacids. The replacement of Arg-235 with Gln destabilized the inhibitory binding of oxamate much more than that of formate, acetate, or propionate, and the Arg to Lys substitution specifically diminished only oxamate binding. On the other hand, replacement of a conserved Glu, Glu-264, with Gln severely impaired the enzyme activity and markedly reduced affinity to 2-keto acids. The pH dependence of the oxamate inhibition revealed that the substitutions of Arg-235 and Glu-264 induced a great loss of the imidazole-carbonyl interaction. However, replacement of Glu-264 with Asp, another acidic amino acid, affected the enzyme function less than the Glu to Gln substitution. In addition, both the Arg-235 and Glu-264 substitutions induced marked increases in the primary isotope effect on the catalysis, suggesting that these amino acids stimulate the hydrogen transfer step in the catalysis. We concluded, therefore, that the guanidino and carboxyl groups of Arg-235 and Glu-264, respectively, cooperatively promote the essential imidazole-substrate interaction, enhancing the substrate binding and catalysis.

Arginine↗

PubMed1997

Comparison of intrathecally administered urokinase, tissue-type plasminogen activator, and combination of urokinase and lysine-plasminogen for clot lysis after experimental subarachnoid hemorrhage in dogs.

OBJECTIVE: The purpose of this study was to compare the fibrinolytic effect of urokinase (UK) with that of tissue plasminogen activator (tPA) on subarachnoid clots and to investigate the effect of lysine-plasminogen (Lys-plg) on fibrinolytic therapy. METHODS: We measured subarachnoid clot lysis rate chronologically for 24 hours during continuous intrathecal irrigation with tPA or UK alone in a canine subarachnoid hemorrhage model. Also, we measured the clot lysis rate for 24 hours during continuous irrigation with UK and Lys-plg or with UK after preadministration of Lys-plg in the same model. RESULTS: The rate of clot lysis caused by UK and tPA dose-dependently increased up to 3,000 IU/ml and 125,000 IU/ml, respectively. With the same molar concentrations, the lytic effect of tPA was significantly higher than that of UK. The slope of the dose-response curve, however, was almost the same with both agents, and the slope of the dose-response curve of UK and tPA for a 24-hour irrigation was 25 and 23% per log 10 concentration, respectively. On the other hand, clot lysis with the combined use of UK and Lys-plg was higher than that with the single use of UK. Particularly, the preadministration of Lys-plg markedly enhanced clot lysis by UK at the early stage of irrigation. CONCLUSION: Subarachnoid clot lysis can be accelerated by administration of Lys-plg before UK administration and by use of high concentrations of UK or tPA.

Animals↗

PubMed1997

A new ventriculoperitoneal shunt with a telemetric intracranial pressure sensor: clinical experience in 94 patients with hydrocephalus.

OBJECTIVE: We have developed a telemetric intracranial pressure sensor (OSAKA telesensor; Nagano Keiki Seisakusyo Co. Ltd., Tokyo, Japan) and investigated the clinical usefulness of new ventriculoperitoneal shunting with an OSAKA telesensor, an on-off valve, and a programmable valve. METHODS: The OSAKA telesensor was applied in 94 patients at Osaka Medical College between March 1986 and December 1995. Postoperative management, postoperative course, postural change of intracranial pressure (ICP), and zero drift of the OSAKA telesensor were investigated. RESULTS: ICP was measured easily in all patients with no inconvenience. The setting of the programmable valve was adjusted postoperatively 38 times in 25 patients. Postoperative ICP in the upright position was -14.9 +/- 4.5 mm Hg, and the difference in ICP between the supine and the upright position was about 20 mm Hg. The slope of the decrease in ICP with continuous postural changes from the supine to the upright position was steep until about 30 to 45 degrees but became incrementally less or even rose slightly about this angle. The initial slope was steeper when the shunt was open than when the shunt was closed; it was also steeper postoperatively than preoperatively. This initial slope, therefore, may indicate the intracranial compliance. Seven cases of shunt malfunction were diagnosed correctly by ICP measurements. Zero drift of the OSAKA telesensor was easily corrected by comparing the ICP reading from the telesensor with the puncture pressure in the on-off valve. CONCLUSION: The OSAKA telesensor is very useful in the postoperative care and pathophysiological evaluation of patients with hydrocephalus.

Equipment Design↗