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Biomedical subjects

S Goto

Publications and source records attributed to S Goto.

At least 523 records · Page 29Linked to original sources

[Relationship between venous invasion and hematogenous metastasis in the gastric cancer].

We investigated the correlation between venous invasion and hematogenous metastasis in gastric cancer. In 70 patients with gastric cancer, 8 cases had hepatic metastasis at operation (group A), 26 cases were identified with hematogenous recurrence after operation (group B) and 36 cases were disease free over 5 years after operation (group C). Specimens were all step-sectioned and serial sections were stained both with HE and EM. Rates of venous invasion were calculated as following formulae; (number of cancer involving veins/total number of veins investigated) x 100 (%). Results were as follows. 1. Average rates of venous invasion (ARVI) of groups A and B were significantly higher than that of group C (A; 7.6%, B; 2.6%, C; 0.7% p < 0.05). 2. In subserosal or serosal layer, there is no significant difference between ARVI of group A and that of group B. 3. No significant difference was seen between group A and B in rates of venous invasion to larger vein (diameter > 200 microns). These observations suggest that cancer invasion to the veins located in deeper than subserosal layer or ranged in diameter over 200 microns relates to hematogenous metastasis.

Humans↗

[Two case reports of recurrent mediastinitis with chronic mediastinal fistula successfully treated with muscle flap re-transposition].

We experienced two cases of recurrent poststernotomy mediastinitis with chronic mediastinal fistula. Both cases had already received muscle flaps for post operative mediastinitis. However, chronic mediastinal fistula appeared after nine months in the first case, and eleven months in the second case. We removed the infected tissue and the predgets, which were used on the ascending aorta. Then closed the wound by the muscle flap closure. The chronic fistula were closed, and the functional and cosmetic results were excellent.

Female↗

Neuronal induction of 72-kDa heat shock protein following methamphetamine-induced hyperthermia in the mouse hippocampus.

By means of an immunohistochemical technique, we examined the neuronal induction of 72-kDa heat shock protein (HSP72) in response to methamphetamine-induced hyperthermia in the mouse hippocampus. Strong HSP72 immunoreactivity (ir) was found in the neurons of hippocampus proper, particularly in the CA1/2 and medical CA3 subfields, at 10 h after drug injection. By 18 h, those neurons still revealed HSP72-ir, while neurons of the dentate gyrus also appeared positive for HSP72. At this stage, intense HSP72-ir was first detected in non-neuronal cells, i.e. glial and vascular endothelial cells. At 24 h, no apparent HSP72-ir was found in the hippocampal neurons, while only non-neuronal cells still revealed immunoreactivity for HSP72. In addition, no morphological evidence of cell degeneration or loss was noted in the CA1 sector or other hippocampal regions at 5 days after hyperthermic insult. In conclusion, (1) methamphetamine-induced hyperthermia per se is a stressful stimulant causing neuronal induction of HSP72 in the hippocampus neurons, particularly of CA1/2 and medial CA3 sectors, but does not prove fatal to the cells; (2) there is a cell type-specific difference in response to hyperthermic insult by inducing HSP72 and the timing of the induction response in the hippocampal formation; and (3) the animals that underwent drug-induced hyperthermia may be useful as an experimental model for the study of the protective mechanism of heat shock proteins against subsequent harmful stimuli.

Animals↗

Anterior surgery in four consecutive technical phases for cervical spondylotic myelopathy.

Between 1960 and 1990, 175 patients having anterior operations for cervical spondylotic myelopathy were evaluated during the course of four operative phases. Specific attention was paid to spine and spinal cord morphologic changes occurring in 52 patients, who were followed up for more than 12 years. Although overall outcomes were satisfactory, a disturbing incidence of neurologic deterioration caused by spondylolisthesis at levels adjacent to fused segments, kyphosis, and altered cord morphology was noted 10 years after surgery. These changes, observed in patients with multilevel pathology and a narrowed spinal canal, promoted the adoption of more stringent operative criteria, including ultrasonically confirmed 16-mm or greater anterior trough decompressions and the performance of long fusions with vascularized fibular struts.

Cervical Vertebrae↗

gamma-Glutamylcysteine synthetase and active transport of glutathione S-conjugate are responsive to heat shock in K562 erythroid cells.

Effect of heat shock on a glutathione-synthesizing enzyme, gamma-glutamylcysteine synthetase (gamma-GCS), and ATP-dependent outward transport of glutathione S-conjugate was characterized using K562 erythroid cells. When K562 cells grown at 37 degrees C were shifted to 42 degrees C for 2 h, an approximate 1.7-fold increase in the activity of gamma-GCS was observed. Treatment of K562 cells with erythropoietin (EP) for 12 h resulted in a decrease in the activity of gamma-GCS to 64% of the control. However, responsiveness of this enzyme activity in the cells treated with EP to heat shock was similar to that in untreated cells. Changes in the immunological activity of gamma-GCS were also observed in parallel with those in the enzymatic activity. On Northern blot analysis of total RNAs isolated from the cells with human cDNA for gamma-GCS, a substantial induction of mRNA level was found by heat shock and a reduction of EP. These changes were modest but correlated to the mRNA expression of a heat shock protein, HSP 70. Heat shock also had an effect of 1.8-fold stimulation on glutathione S-conjugate transport in K562 cells previously incubated with 1-chloro-2,4-dinitrobenzene. Treatment of the cells with EP resulted in a decrease in this transport by 62%. Similarly, the levels of glutathione S-conjugate-stimulated Mg(2+)-ATPase, which enzyme is thought to be involved in the transport of glutathione S-conjugate, were responsive to heat shock and EP. These results suggest that glutathione synthesis and transport process of glutathione metabolites are responsive to heat shock and play a role in the defense system against stresses. It is also suggested that the regulatory site of the expression of these enzymes by heat shock is independent of that by EP.

Biological Transport, Active↗

Changes of immunoreactivity for synaptophysin ('protein p38') following a transient cerebral ischemia in the rat striatum.

We assessed the chronological change of the expression of synaptophysin, an integral glycoprotein on the presynaptic vesicles, after a transient cerebral ischemic insult in the rat. The ischemic lesion was consistently localized in the dorsolateral part of the striatum, which was clearly visualized by a depletion of calcineurin immunostaining or increases of immunoreactivities for glial fibrillary acidic protein and tyrosine hydroxylase. Immunoreactivity for synaptophysin was transiently increased in the ischemic lesions from 3 to 7 days after cerebral ischemia. Thereafter, synaptophysin immunostaining in the damaged areas gradually decreased and finally almost disappeared one month after surgery. Because synaptophysin is located in the presynaptic vesicle, and thought to be involved in presynaptic functions such as vesicle-membrane fusion and release of neurotransmitters, present findings suggest that loss of the postsynaptic site after ischemic insult induces a transient increase of the presynaptic functions, followed by a decrease of functional presynaptic activity or trans-synaptic retrograde degeneration of axon terminals.

Animals↗

Detection of human papillomaviruses from histologically normal lymph nodes of Japanese cervical cancer patients by nested polymerase chain-reaction assay.

To determine the prognostic significance of human papilloma virus (HPV) DNA in histologically normal lymph nodes, we developed a nested polymerase chain-reaction (PCR) method on HPV16,18 and 33 DNAs for formalin-fixed, paraffin-embedded tissues. We investigated 370 histologically normal lymph nodes from 15 patients treated for stage-IB/IIB (FIGO) invasive cervical cancer. HPV16 DNA was detected in 7 (47%) and HPV18 DNA in 3 (20%) of the cervical cancers. Examination of histologically normal lymph nodes from these 10 patients by nested PCR revealed HPV DNA in 5 (50%) of them; in all cases HPV type in lymph nodes and tumor was the same. Two of these 5 patients had a recurrence (pelvic cavity or lung) and died of cancer, although all 5 had had pelvic radiotherapy after radical hysterectomy and lymphadenectomy. These findings indicate that nested PCR is useful for evaluating early lymph-node involvement retrospectively in HPV-positive cases.

Adult↗

A protein histidine kinase induced in rat liver by peroxisome proliferators. In vitro activation by Ras protein and guanine nucleotides.

A novel protein kinase is induced in rat liver plasma membrane by the administration of peroxisome proliferators. A 36 kDa protein (P36) on the membrane was rapidly phosphorylated in vitro by the kinase and the phosphorylated amino acid was identified as phosphohistidine. Histidine phosphorylation of P36 was activated in vitro by recombinant Ras protein and GTP; both decreased Michaelis constant (Km) for ATP from 1.25 to 0.25 microM. The novel histidine kinase, products of which have been overlooked due to their acid lability, may participate in cellular signaling and peroxisome proliferators may perturb the pathway.

Adenosine Triphosphate↗

Responses to heat shock of alpha B crystallin and HSP28 in U373 MG human glioma cells.

Responses to heat shock of alpha B crystallin and small heat-shock protein HSP28, which are expressed at considerable levels in human astroglioma U373 MG cells (2-4 micrograms of each per mg soluble protein in confluent cultures), were analysed quantitatively by specific immunoassays. Concentrations of alpha B crystallin and HSP28 in soluble extracts of U373 MG cells decreased to about 50% of original values, with an increase in the insoluble fraction, during heat treatment for 15 min at 45 degrees C. The concentrations of alpha B crystallin and HSP28 increased gradually upon return to 37 degrees C, reaching and then exceeding the control levels within 5 h and 10 h, respectively, after heat shock. During centrifugation on sucrose density gradients both alpha B crystallin and HSP28 in extracts from untreated and heat-treated cells sedimented at the same position, which corresponded to a molecular mass of > 540 kDa. This result suggests that the sizes of aggregates of the two proteins in the cytoplasm are not affected by heat shock. Both alpha B crystallin and HSP28 in an extract of U373 MG cells were trapped on and coeluted from an affinity column prepared with antibodies against alpha B crystallin. These results suggest that the two proteins are also associated in U373 MG cells.

Cell Division↗

Cellular colocalization of calcium/calmodulin-dependent protein kinase II and calcineurin in the rat cerebral cortex and hippocampus.

An immunoperoxidase technique was used to locate multifunctional Ca2+/calmodulin-regulated protein phosphatase (calcineurin) and kinase (CaM-kinase II) in the rat cerebral cortex and hippocampus. Immunoreactivities for both enzymes were highly concentrated in the brain regions, where pyramidal-shaped neurons revealed strong immunoreactivities in their perikarya and dendrites. Serial thin section analysis using the polyethylene glycol embedding procedure disclosed that the cellular distribution of calcineurin immunolabelling in the cerebral cortex and hippocampus was similar to that of CaM-kinase II. The present findings suggest that the phosphatase and kinase may interact with each other in such neuronal subsets.

Animals↗

Preparation and evaluation of Eudragit gels. VI: In vivo evaluation of Eudispert rectal hydrogel and xerogel containing salicylamide.

Eudispert hv hydrogel and xerogel preparations containing salicylamide displayed sustained-release plasma profiles when compared with other conventional rectal preparations. The absolute bioavailability of salicylamide was 97.3% for the hydrogel preparation and 98.4% for the xerogel preparation. These results may arise because the gel preparation stays at the application site, the lower part of the rectum, over a fairly long period because of its bioadhesive force. Furthermore, the gastrointestinal and hepatic first-pass elimination of salicylamide can be avoided completely by rectal administration of these preparations. Visual and optical microscopic observation of rectal membranes indicated no irritation or abnormality after administration of Eudispert hv hydrogel and xerogel.

Acrylic Resins↗

Reduction of erythrocyte membrane permeability and protein binding of low-molecular-weight drugs following glycoside derivitization.

The permeability of glycosides (salicin, arbutin, glycyrritin, p-nitrophenyl-beta-D-glucopyranoside, p-nitrophenyl-beta-D-galactopyranoside, p-nitrophenyl-beta-D-lactopyranoside, and p-nitrophenyl-beta-D-maltopyranoside) and their aglycons through human erythrocyte membrane was investigated. The transport rate of the glycosides through human erythrocyte membrane was slower than that of their aglycons. Glycosides with a disaccharide did not permeate the erythrocyte membrane; this observation suggests that the introduction of disaccharide to drugs gives rise to a significant decrease in the leakage of drugs through the erythrocyte membrane. The derivatives of glycosides encapsulated in erythrocytes were not released from these erythrocytes into the outer medium. The transport capacity of the glycosides was not influenced by the kind of suspending medium, but that of the aglycons was influenced by the medium. The glycosides bound to human serum albumin more weakly than their aglycons. Particularly, the glycosides were more difficult to displace from 7-anilinocoumarin-4-acetic acid (site III drug) than their aglycons, except for glycyrritin.

Cell Membrane Permeability↗

Effect of various vehicles on ketoprofen permeation across excised hairless mouse skin.

The effects of glycerides, short-chain alcohols, and their binary vehicles as donor components on the permeation of ketoprofen (KP) across the excised hairless mouse skin were evaluated with the modified LOVEDAY-type diffusion cell. Among single vehicles, Panasate 800 as tricaprylin appeared to be the most favorable lipophilic vehicle, with no toxicity and with a short lag time (0.9 h), and methanol (MeOH) or ethanol (EtOH) as hydrophilic single vehicles showed the highest KP permeation flux (244.1 and 134.1 micrograms/cm2/h, respectively). Furthermore, KP permeation was enhanced remarkably by the combination of EtOH and Panasate 800 compared with each single vehicle as reflected in the decreased lag time and increased flux. The greatest enhancement was observed in the EtOH/Panasate 800 (40/60) binary vehicle (permeation ratio at 24 h, 40.0%; steady-state flux, 314.0 micrograms/cm2/h; lag time, 3.7 h). Further investigations involving stripping studies and KP accumulation within the skin were performed to explain the mechanism of enhancement caused by the above binary vehicle. It was suggested that the mutual enhancement effect of EtOH/Panasate 800 (40/60) binary vehicle is due to decreasing the barrier ability of the stratum corneum by EtOH and the viable skin by Panasate 800.

Alcohols↗

Skin permeation enhancement of tegafur by ethanol/panasate 800 or ethanol/water binary vehicle and combined effect of fatty acids and fatty alcohols.

The effects of vehicle and enhancer on the skin permeation of tegafur across excised hairless mouse skin were investigated. Ethanol, water, panasate 800 (tricaprylin), and their mixtures were used as vehicles, and then a series of fatty acids or fatty alcohols was employed as representative enhancers. The skin permeability of tegafur was dramatically increased by the combination of ethanol and panasate 800, whereas the combination of ethanol and water resulted in only a little increase. The greatest permeation ratio (56.8% of dose at 12 h) was obtained with the ethanol/panasate 800 (40/60) binary vehicle. Furthermore, the skin permeability of tegafur could be enhanced by the addition of fatty acids or fatty alcohols to ethanol/panasate 800 (40/60) and ethanol/water (60/40) binary vehicles. The infinite dose studies suggested that panasate 800 decreased the lag time by increasing the diffusion of tegafur, and ethanol increased the permeation rate by increasing the partition of tegafur into skin. The effects of fatty acids or fatty alcohols added to ethanol as a single vehicle were dramatic, but did not appear in the case of panasate 800 as a single vehicle. In conclusion, panasate 800 was an excellent hydrophobic vehicle in that it minimized time lag and promoted tegafur permeability combined with ethanol. This improvement was further promoted when enhancers were added.

Animals↗

Retransplantation of the liver in the rat.

A successful technique of liver retransplantation in the rat is described. Heterotopic nonauxiliary liver engraftment of a whole liver using cuffed anastomoses is the primary transplant procedure. The graft is implanted in the right hypochondrium and is revascularized by a portal end-to-end anastomosis. Venous drainage is via an end-to-side anastomosis between the donor infrahepatic vena cava and recipient right renal vein. The graft suprahepatic vena cava is ligated. Biliary drainage is achieved by a double stent anastomosis of the biliary ducts. Total parenchymectomy of the recipient's liver is completed leaving intact the intrahepatic and suprahepatic vena cava. Retransplantation in the orthotopic position can thus be attempted, after removal of the first graft, by cuffed anastomoses between the donor and recipient portal veins, infrahepatic vena cava and a double stent anastomosis of the common bile ducts. Anastomosis between the donor and recipient suprahepatic vena cava is completed with a 7/0 Prolene running suture. In the first group of operations (n = 6), a three week survival rate of 50% after retransplantation was obtained. Using the technical lessons of these preliminary cases, 80% of the second group of operations (n = 5), were successful in the long term. Utilization of this new technique may allow further investigations in different fields of research dealing with liver surgery and transplantation.

Animals↗

Protocol for the technique of orthotopic liver transplantation in the rat.

Orthotopic rat liver transplantation (OLT) has been generally accepted as an excellent model for the analysis of pathological, physiological, and immunological aspects related to organ transplantation. However, many researchers require a long training period to achieve a high success rate using this major surgical procedure on small animals. We therefore developed a protocol for learning rat OLT. It is recommended, initially, that the heterotopic heart transplantation (HHT) model be used to master the cuff technique, since this technique is similar to that in OLT and leads to an understanding of another organ transplantation technique. For beginners who advance beyond the HHT step to OLT but cannot finish the anhepatic phase within 30 min, we recommend the use of portosystemic-shunted rats as recipients. These animals have had their spleens transposed subcutaneously more than 3 weeks before use. The use of these modifications and this training program makes it possible to master the techniques and to achieve a high success rate with a short training period.

Animals↗

The effect of a prostaglandin I2 analogue (OP-41483) on energy metabolism in liver preservation and its relation to lipid peroxidative reperfusion injury in rats.

The effect of the stable prostacyclin (PGI2) analogue OP-41483 (OP) on liver preservation was investigated in the rat liver transplant model. In a 1-week survival study, 33 orthotopic liver transplants were performed using Wistar rats. In group A, untreated livers were stored with modified UW (mUW) solution at 4 degrees C. In group B, livers from OP-pretreated donors (2 micrograms/kg, i.v.) were stored with mUW solution containing OP (1 microgram/ml) at 4 degrees C. After 24 h storage, the donor grafts in each group were transplanted to untreated recipients. OP treatment (group B) significantly improved 1-week survival (62.5%, 10/16, P < 0.01 versus group A; 11.8%, 2/17). For the measurement of adenine nucleotides and lipid peroxidation (malondialdehyde, MDA) in liver tissue before preservation, after preservation, and 3 h after transplantation, 20 rat livers in groups A and B were studied. In both groups, the levels of adenosine triphosphate (ATP) declined 6 h after cold preservation, but this degradation of ATP was significantly halted at the level of adenosine monophosphate (AMP) in the OP-treated livers after 24 h of storage. However, OP treatment showed no significant difference in the degree of ATP recovery after transplantation. On the other hand, OP treatment resulted in suppression of the increase in MDA levels and histological amelioration of microcirculatory disturbance 3 h after transplantation. Our data suggested that the combined use of the stable PGI2 analog (OP-41483) and UW solution is beneficial in liver preservation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗

Development of postmolar trophoblastic disease after partial molar pregnancy.

We investigated the clinical characteristics of patients with partial molar pregnancy and patients who developed invasive partial mole. Between 1981 and 1990, 349 patients were followed up by the Aichi prefecture trophoblastic disease registration center after partial molar pregnancy. Ten of the 349 patients with partial molar pregnancy developed invasive partial mole, an incidence (2.87%) significantly lower (P < 0.01) than that for the development of invasive complete mole (174/1410, 12.34%) following complete molar pregnancy during the same period. None of the patients had any histologic evidence of choriocarcinoma after partial molar pregnancy. The medical records of these 10 patients were compared with those of 85 of 174 registered patients with invasive complete mole, whose clinical information could be used. The interval from molar delivery to the diagnosis of invasive mole was under 9 weeks (mean, 4.90 weeks) for the patients with invasive partial mole and was significantly shorter than that for the patients with invasive complete mole, from 2 to 18 weeks (mean, 8.12 weeks) (P < 0.01). All 10 patients with invasive partial mole achieved a negative hCG level (< 0.5 mIU/ml) with eight courses or less of chemotherapy (mean, 5.50 courses). The number of courses was the same as that in the invasive complete mole group (mean, 5.70 courses). None of the patients with invasive partial mole developed recurrence. We conclude that all patients with partial molar pregnancy should be followed up as are those with complete molar pregnancy. Some patients with partial molar pregnancy will develop invasive partial mole with a relatively short interval, but remission can be achieved without the recurrence and choriocarcinoma seldom develops after partial molar pregnancy.

Adult↗