High-performance liquid chromatographic determination of m-tyrosine and o-tyrosine in rat urine.
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Animals↗
Biomedical subjects
S Fujimoto
Publications and source records attributed to S Fujimoto.
Carboxyl terminal glycine extended progastrin (gastrin-G) in human gastric mucosa and gastrinomas.
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Duodenal Neoplasms↗
Thermotolerance of xenografted human gastric cancer.
To compare the thermotolerance in vivo of two human gastric cancers with different doubling times, the xenografted tumors were warmed twice at 43.5 +/- 0.1 degree C in a water bath for 20 minutes at a predetermined interval. In the tumors with doubling times of 5.2 and 10.9 days, a 7-day interval heat treatment resulted in a prolongation in tumor tripling times by 156 per cent and 132 per cent, respectively, compared with a single heat treatment for 40 minutes. On the contrary, two heat treatments given at intervals of 3 to 5 days had a short tumor tripling time, compared to that of the 40-minute single treatment. Thus, the thermotolerance of these human gastric cancers gradually increased to a maximum within a 3- to 4-day interval and disappeared completely after a 7-day interval. These results indicate that the times required to reach maximal thermotolerance in these human gastric cancers were longer than those previously demonstrated for human and rodent cancer cell lines in vitro. The development and decay of thermotolerance in these human gastric cancers need to be considered in the design of multiple-fractionated regimens.
Adenocarcinoma↗
The diagnostic accuracy of magnetic resonance imaging in pancreatic carcinoma based on a retrospective analysis of vascular involvement.
A retrospective analysis was made to evaluate the diagnostic accuracy of magnetic resonance (MR) imaging for pancreatic cancer. Twenty-one lesions from 21 patients with pancreatic cancer were examined and all except one, were identified on MR images by a disparity in contrast and/or morphological enlargement. The patients were divided into 3-groups, based on the relationship between the tumor and the portal vein, seen on the MR images. These groups were defined as the separate, touching, and surrounding groups. The MR findings correlated with the findings at laparotomy in 16 patients, 10 of whom underwent tumor excision. In the remaining 4, the MR findings correlated with the angiographic findings. The presence or absence of vascular involvement was correctly diagnosed in 18 of the 21 patients. MR imaging proved useful for detecting pancreatic cancer and cancerous infiltration into the portal vein. MR imaging should therefore aid the surgeon in determining the operability and/or curability of patients with pancreatic cancer.
Adult↗
Methotrexate-resistant mechanisms in human choriocarcinoma cells.
Choriocarcinoma cells grown in the presence of methotrexate (MTX) developed resistance in two ways. HCCM-derived sublines (relatively high MTX resistance) produced enhanced levels of dihydrofolate reductase (DHFR) and had impaired transport of MTX. Altered transport was the primary determinant of response in CC1-derived sublines (low MTX resistance). Since the selection procedures used were identical, it was assumed that altered MTX transport was insufficient to account entirely for the various degrees of resistance. An increased level of DHFR activity was necessary for the development of high MTX resistance. The overproduction of DHFR was the consequence of amplification of the DHFR gene sequence. The incidence of double minutes (DMs) in metaphase paralleled the degree of resistance. However, DMs were also present in cells not showing DHFR gene amplification. Mechanisms other than DHFR gene multiplication were responsible for the de novo synthesis of DMs.
Blotting, Southern↗
Anti-idiotypic antibodies in a patient with a well-functioning renal graft without azathioprine. II. Anti-idiotypic antibodies directed to a clonotype of a certain cytotoxic T lymphocyte.
A recipient who received a renal graft from a living related donor showed good renal function for as long as 15 years after the withdrawal of azathioprine. The patient's creatinine clearance was maintained at 60 ml/min in spite of the administration of only 10 mg of predonisolon per day. Anti-idiotypic antibodies in the patient's serum were found by testing for specific inhibition of the mixed lymphocyte reaction (MLR) and cytotoxic T lymphocyte (CTL) response. The treatment of responder or effector cells with the IgG fraction from the patient's serum resulted in the specific inhibition of the MLR and CTL killing reaction against target cells of the graft donor. These findings indicate that the patient's serum contains anti-idiotypic antibodies against antigen recognition structures of a certain CTL as well as a certain MLR to donor alloantigens.
Adult↗
Augmentation of anti-tumor immunity in low-responder mice by various biological response modifiers: analysis of effector mechanism.
In order to elucidate the role of biological response modifiers (BRMs) in anti-tumor immunotherapy, we examined their effect on the induction of anti-tumor immunity in low-responder mice which hardly exhibit anti-tumor resistance against syngeneic Rous sarcoma virus (RSV)-induced tumors, such as B10 or B10.BR mice. The anti-tumor immunity induction in the low-responder mice was 0% on immunization with mitomycin C-treated syngeneic tumor cells alone. However, if BRMs were used as an adjuvant, BCG cell wall skeleton, OK-432 or lentinan augmented the induction of anti-tumor immunity to 50%, 33% and 33%, respectively. In the low-responder mice treated with BRMs, the anti-tumor immune cells had antigen-specificity at the induction phase of in vitro restimulation but not at the effector phase of target cell lysis by the stimulated cells. When T cells were depleted from immune spleen cells just before in vitro stimulation, cytotoxicity was not induced. Furthermore, cytotoxicity was not induced if accessory cells were removed from immune spleen cells at the induction phase. However, cytotoxicity at the effector phase was not mediated by T-lymphocytes, but by non-T cells. These results suggested that the induced cytotoxicity in low-responder mice was associated with the delayed-typed hypersensitivity-like effector mechanism.
Animals↗
Augmentation of human cytotoxic T lymphocytes against autologous tumor by a factor released from human monocytic leukemia cell line.
A human acute monocytic leukemia cell line, THP-1, releases a factor which activates human cytotoxic (killer) T lymphocytes (CTL) against autologous tumor in vitro. The factor, named cytotoxic (killer) T cell activating factor (KAF), is an acidic protein of 70,000 to 100,000 dalton molecular size. Peripheral blood leukocytes from two patients, bearing epithelioid sarcoma or malignant schwannoma, were cultured for 7 days with individual autologous tumor to induce CTL directed to the corresponding tumor. Monocyte-depleted peripheral leukocytes generated lesser CTL activity than the monocyte-containing leukocyte population. However, the KAF was able to replace the monocyte function. The KAF acted at the CTL generation phase as well as the effector phase. The KAF-activated killer cells possessed CD4-8+ surface phenotype. The CTL killed autologous tumor or other unrelated tumor cell lines only when they shared some of the HLA class I antigens. It was also demonstrated that the KAF does not activate killer cells without proper antigenic stimuli, because the KAF-augmented CTL possess specificity against autologous tumor or other HLA-A or -B matched tumor cell lines. The therapeutic applicability of human KAF for anti-tumor CTL therapy against autologous tumor is discussed.
Adult↗
Hexagonal surface layer of Campylobacter fetus isolated from humans.
Electron microscopic studies of the surface structure of Campylobacter fetus by the freeze-etching method showed two different types of S layer. One was in a hexagonal array, and the other was in a tetragonal array. A high-passage-number strain lost its S layer during cultivation on culture media but regained it after a single animal passage.
Animals↗
Bradykinesia in Parkinson's disease: disorders of onset and execution of fast movement.
Simple reaction time lengthens in parkinsonian patients as the severity of motor disorder progresses. Shortening of reaction time was obtained by giving a warning signal to a greater extent in cases with severer motor disability. The results suggest that inattention, one of several symptoms common to lesions in the frontal lobe and Parkinson's disease, may be a factor in bradykinesia in purposive movements in the disease. The Wisconsin card sorting test and criterion shift task which we devised to deal with a single patients have difficulty in dealing with multiple sets simultaneously, which may be caused also by inattention. In execution of ballistic movement in parkinsonian patients, only a small torque constant in amount and in time can be produced in the beginning, irrespective of the size of force required, and subsequently enough force is built up to reach the target. This was more marked in cases with severe motor disability and in cases with decrease in power. Rigidity, mechanical properties of the limb or disorders in ocular movement were not responsible for the production of the initial small torque. Oculo-manual incoordination in visuomotor tracking tasks is also discussed.
Adult↗
Ultrastructural findings in the wound healing of the colonic mucosa of rabbits.
The wound healing of the rabbit colonic mucosa after experimental excision was observed with the electron microscope. Between 5 and 7 days, considerable numbers of undifferentiated mesenchymal cells (group I), differentiating muscle cells (group II) and histiocyte-like cells (group III) appear in the regions where the muscularis mucosae is re-establishing. Our electron micrographs indicate that group I cells are stem cells which differentiate to group II cells involved in muscle regeneration or to group III cells involved in phagocytosis. The mitotic proliferation of pre-existing smooth-muscle cells at the ulcer margin does not seem to be the major reason for the re-establishment of the muscular layer. Multinucleated cells occurring in this healing mucosa are considered to be formed by successive fusions between the group III cells and to play a role in enclosure of cell debris such as fragments of elastin.
Animals↗
The prediction of thyroid function in infants born to mothers with chronic thyroiditis.
To elucidate the relationship between the mother's TSH-receptor antibody activities and the status of thyroid dysfunction in their offspring, blood was taken from 5 mothers with chronic thyroiditis with potent thyrotropin (TSH)-receptor blocking activity, and the potency of TBII and TSBAb activity was assayed more quantitatively. In those mothers whose infants suffered from neonatal hypothyroidism, the 50% inhibition of binding of labeled TSH to its receptors was obtained at more than 30 to 50-fold dilution, while in those mothers whose infants had transiently increased TSH or were euthyroid, the titers were of less than 30-fold dilution. Similarly, in those mother whose infants suffered from neonatal hypothyroidism, the 50% inhibition of TSH-induced cAMP accumulation was obtained at approximately 400 to 3000-fold dilution, while in those mothers whose infants had transiently increased TSH or were euthyroid, the titers were of less than 50-fold dilution. On the other hand TBII activity was much less potent in serum from patients with Graves' disease. These results suggested that the titration of serum with dilution to obtain 50% inhibition of labelled TSH binding to its receptor may be the simplest way to predict thyroid dysfunction of the newborn infants born to mothers with chronic thyroiditis.
Adolescent↗
Improved immunoassay for the determination of surfactant protein A (SP-A) in human amniotic fluid.
A simple, improved immunoassay for the determination of human surfactant protein A (SP-A) in human amniotic fluid was developed. The immunoreaction with a monoclonal antibody PC6-immobilized plastic bead, peroxidase-labeled monoclonal antibody PE10 and amniotic fluid sample diluting in the buffer containing 0.6% sodium dodecyl sulfate/2% Triton X-100, was carried out simultaneously at 45 degrees C for 30 min in test tubes. After washing the bead with 2% skimmilk in phosphate buffered saline containing 1% Triton X-100, the peroxidase reaction was developed by adding the substrate reagent and the absorbance was measured. The amniotic fluid obtained at full term was used as a standard instead of purified SP-A, because of the stability of the antigenicity. This immunoassay method was used to measure SP-A in 69 samples of amniotic fluid from 22 to 41 weeks of gestation. The result indicated that the SP-A values obtained by the present immunoassay can be used for predicting the fetal lung maturity. This simplified monoclonal immunoassay completed the measurement within 1 hr, and so it could be used routinely in clinical laboratory.
Amniotic Fluid↗
[Extracranial surgery of vertebrobasilar insufficiency. Reconstruction of the vertebral artery in the distal first portion].
Fourteen patients with symptoms of vertebrobasilar insufficiency caused by vertebral artery stenosis in the distal first portion underwent surgical reconstruction. They ranged in age between 42 and 73 years, with a median age of 57 years. Their symptoms included vertigo, dysarthria, syncope, hemiparesis, and homonymous quadrant anopsia. The etiologies of the stenoses involved kinking in 12 cases and mechanical compression due to cervical sympathetic nerve, osteophyte, or fibrous bands in two cases. Digital subtraction angiography revealed that stenosis was maximal at systole and minimal at diastole in six of eight cases. In two of the 14 cases, stenosis was not demonstrated in the neutral position, but stenosis of the left vertebral artery appeared when the head was rotated to the right. Surgical procedures involved 13 decompressions of the vertebral artery and one subclavian artery-vertebral artery bypass using the saphenous vein. Postoperatively, 12 cases of miosis and one of asymptomatic phrenic nerve palsy were observed, but there were no serious complications. All but two patients had complete resolution of their symptoms. Stenosis due to kinking and/or mechanical compression disappeared in all cases after decompression of the vertebral artery. The effects of arterial pulse and neck rotation on vertebral artery stenosis in the distal first portion are discussed.
Adult↗
Inhibitory effect of 6-azauracil on beta-alanine metabolism in rat.
The effect of 6-azauracil on beta-alanine metabolism was investigated in vivo in the rat. Both of the enzymes beta-alanine-oxoglutarate aminotransferase (aminobutyrate aminotransferase) and D-3-aminoisobutyrate-pyruvate aminotransferase [R)-3-amino-2-methylpropionate-pyruvate aminotransferase), which are beta-alanine catabolizing enzymes from rat liver and kidney, were inactivated by 6-azauracil injection, while dihydrouracil dehydrogenase, dihydropyrimidinase, and beta-ureidopropionase, which are pyrimidine metabolizing enzymes, were not affected. The content of beta-alanine was increased, but the level of uridine and uracil in rat liver was not affected, by 6-azauracil. When a crude enzyme preparation was passed through a Sephacryl S-200 column, both enzymes could be separated from each other. beta-Alanine-oxoglutarate aminotransferase and beta-alanine-pyruvate aminotransferase activities in rat liver decreased to 27.4% and 63.9%, respectively, upon 6-azauracil injection, and those in kidney were 11.7% and 38.3%, respectively. From these findings, it is suggested that the accumulation of beta-alanine in 6-azauracil-treated rat liver might be caused by the inhibition of beta-alanine catabolizing enzymes, but not by an increase in the uridine pool nor by the activation of pyrimidine metabolism.
Alanine↗
Idiotypic and anti-idiotypic B-B cell interaction is controlled by major histocompatibility complex-restricted regulation.
We have previously reported that the immunization of BALB/c mice with MOPC-104E myeloma protein (M104E) induced idiotype-specific Ly 1-negative B lymphocytes that had an ability to enhance idiotype-positive anti-dextran antibody production. It was also shown that the cell interaction between idiotypic and anti-idiotypic B lymphocytes was observed in a class II-restricted manner. The effect of monoclonal anti-class II antibody on the B-B cell interaction is investigated in this report. The addition of anti-I-A or anti-I-E monoclonal antibody into the B-B cell interaction system, from both BALB/c (H-2d) and BALB.K (H-2k), inhibited the enhanced antibody production mediated by idiotype-immune B lymphocytes. Interestingly, however, it was revealed that the anti-I-A and anti-I-E antibodies acted differently on each B-lymphocyte population. Pretreatment of an anti-idiotypic (idiotype-immune) enhancing B-lymphocyte population with anti-I-A antibody diminished its enhancing activity, while anti-I-E did not. On the other hand, pretreatment of dextran-immune antibody producing B cells with anti-I-A antibody showed no effect, while anti-I-E inhibited anti-dextran antibody production. When the enhancing B-lymphocyte population of F1 mice was treated with anti-I-A antibody specific for one of their parents' haplotypes, co-operation with the respective haplotype B cells was inhibited, but the other haplotype was not. The inhibitory effect of anti-class II antibodies could only be seen at the early phase of culture period. Taken together, the results of these experiments suggest that the class II antigens are concerned with the self-recognitive cell interaction among B lymphocytes in the frame of idiotype network systems.
Animals↗
[The rationale and practice of CTL therapy against cancer in the mouse and human].
It is essential to investigate and elucidate the immune response especially T cell response to either syngeneic or autologous tumor for establishing a rational immunotherapy of cancer. We reported that major immune effector cells capable of inducing tumor regression are cytotoxic T lymphocytes (CTL). We found that there are at least two distinct CTL subsets directed to syngeneic tumor. One CTL subset which is selectively induced by syngeneic solid tumor is independent from CD4 positive helper T cells but requires a soluble factor (s) released from macrophage-like accessory cells designated killer T cell activating factor (KAF) in its induction and generation directed to the homologous tumor. The other CTL subset which is usually induced by syngeneic tumor of hematocytic origin is dependent on CD4 positive helper T cells in its induction. On the basis of our findings regarding the induction and activation mechanism of CTL to syngeneic tumors in the mouse, we have investigated the mechanisms of human CTL generation to autochthonous tumor in peripheral blood mononuclear cells of cancer patients. It was found that the nature of human CTL and its generation to autochthonous tumor are similar to those of murine CTL to syngeneic solid tumor. We are now establishing a rational cancer specific immunotherapy utilizing intravenous passive cell transfer of in vitro activated CTL to autochthonous tumor into an original cancer patient.
Animals↗
[Pharmacokinetic analysis in intraperitoneal hyperthermic perfusion using mitomycin C in far-advanced gastric cancer].
Postoperative intraperitoneal hyperthermic perfusion (IPHP) using MMC was performed with marked success on 15 gastric cancer patients with peritoneal dissemination or serosal invasion (first surgery group) and on 5 recurrent gastric cancer patients with ascitic retention (recurrent cancer group), and the MMC concentrations was studied in the perfusate and circulating blood. The perfusate contained MMC 10 micrograms/ml at the onset of IPHP, except one recurrent case of 20 micrograms/ml, and IPHP was performed for 120 minutes except in one case given 20 micrograms/ml of MMC. There was little difference in the hepatorenal functions and perfusate temperatures between the first surgery group and the recurrent cancer group. The drug levels were measured by HPLC method with minimal assay levels of 2 ng/ml. Perfusate drug levels in the first surgery group reduced by half at 12 minutes after the start of IPHP, whereas in the recurrent cancer group, they decreased by half about 60 minutes later. Perfusate drug levels in the first surgery group decreased twice as rapidly as in the recurrent cancer group. The area under the curve (AUC) and average drug levels in the first surgery group were 7,900 micrograms.hr/l and 3.3 micrograms/ml, respectively, and those in the recurrent cancer group were 12,620 micrograms.hr/l and 5.3 micrograms/ml, respectively. On the other hand, the drug levels in peripheral blood were almost the same between the two groups. These data suggest that although recurrent gastric cancer is well suited for IPHP because of high AUC, it is worthwhile performing IPHP combined with surgery for gastric cancer with peritoneal seeding, with due consideration for AUC of 7,900 micrograms.hr/l and the average drug level of 3.3 micrograms/ml.
Adult↗