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Biomedical subjects

Y Suma

Publications and source records attributed to Y Suma.

15 recordsLinked to original sources

Augmentation of specific tumor killing activity by tumor-infiltrating lymphocytes (TIL) in the presence of TNF-SAM2.

The effect of TNF-SAM2 on cytotoxic activity of tumor-infiltrating lymphocytes (TIL) was investigated. TIL were prepared from 11 human cancer patients. They were propagated by double in vitro stimulation with anti-CD3 monoclonal antibody and interleukin-2, and cultured for 3 weeks. The cytotoxic activity of TIL was tested with standard 4h 51Cr-release assays in the presence or the absence of TNF-SAM2. In the presence of TNF-SAM2 (500U/ml), the mean cytotoxic activity against autologous tumor cells was significantly augmented compared to that in its absence. However, the fact that cytotoxic activity against K562 and Daudi showed no difference whether substance was present or not, indicates that LAK and NK activity were not affected by TNF-SAM2. Direct cytotoxicity by exogenously added TNF-SAM2 to tumor cells was measured in 9 out of 11 cases and this revealed that cytotoxicity solely by TNF-SAM2 was seen in 3 tumors. However, there was no correlation between the augmentation of cytotoxicity by TIL in the presence of TNF-SAM2 and the cytotoxicity shown by TNF-SAM2 alone. These results suggested that TIL therapy combined with administration of exogenous TNF may exert a synergistically stronger therapeutic effect on cancer.

Cytotoxicity, Immunologic

A case report of recurrent cervical cancer which responded to a combination of biological therapies.

Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) has been challenged to human cancer patients during these years. However, as the efficacy of the therapy alone is still limited, another approach, a combination with other therapies may be required to obtain more favorable antitumor effects. Tumor necrosis factor alpha (TNF) is worth considering for combination, because at least its various potential roles in immune response suggest that it might increase the killing activity of T cells against autologous tumor cells. We attempted to treat the cancer patients with TIL combined with TNF therapy. A patient with recurrent cervical cancer was treated with multiple biological therapies including TIL and TNF therapy, and irradiation. Biological therapies consisted of endogenous and exogenous TNF (EET) therapy, TIL, administration of rTNF-SAM2 combined with hyperthermia and several biological response modifiers such as schizophyllan and lentinan. After 50 days of therapy, the recurrent tumor had remarkably decreased in size, and cystic change of the tumor was observed by CT scanning. By further continuation of these therapies, the disease condition was much improved. As these antitumor effects cannot well be explained by irradiation therapy alone, multiple biological therapies are considered to be potentially effective against the highly malignant advanced tumors.

Adult

Induction of S-adenosylmethionine synthetase isozymes in primary cultures of adult rat hepatocytes.

The activities of S-adenosylmethionine synthetase isozymes were studied using adult rat hepatocytes in primary culture. Hepatocytes from adult rats were isolated and cultured for several days. The activities of the synthetase isozymes did not change during primary culture. The activity of the alpha-form increased with increasing ethionine plus adenine or methionine in the medium, and reached about 5 fold after 2 days. However, the increased activity of the beta-form showed less than twice.

Adenine

Isozymes of S-adenosylmethionine synthetase from rat liver: isolation and characterization.

S-Adenosylmethionine synthetase exists in at least two distinct forms, alpha- and beta-forms, in adult liver. The beta-form was purified to homogeneity from the soluble fraction of rat liver with a yield of about 10%. An antiserum directed against the purified beta-form from rat liver was prepared by injecting the purified enzyme into a rabbit. Ouchterlony double diffusion analysis and immunochemical titrations revealed that the isozymes, alpha- and beta-forms, are identical. Thus, the alpha-form was isolated from rat liver as a single protein using immunoaffinity chromatography against the beta-form. The molecular weights of the beta- and alpha-forms were determined to be 48,000 each by sodium dodecyl sulfate disc gel electrophoresis, and about 100,000, and 200,000, respectively, by Sephacryl S-200 gel filtration. These results indicate that the beta-form consisted of two subunits of 48,000 daltons and the alpha-form of four subunits of 48,000 daltons. The sedimentation coefficient was calculated to be 5.5S for the beta-form and 8.0S for the alpha-form.

Animals

Vector U loop in normal and hypertensive subjects.

The U loops of vectorcardiograms (VCG) were recorded in 100 normal subjects and 123 subjects with hypertension, using a direct-writing vectorcardiograph with memory function. These U loops were examined qualitatively and quantitatively. Subjects with hypertension were classified into four groups on the basis of electrocardiographic findings, and the correlation between findings on the U loop and the severity of hypertension was studied. The U loop of normal subjects was directed similarly to the T loop, showing either an arc or semilunar shape in the horizontal plane. In hypertensive subjects the U loop tended to be displaced anteroinferiorly and to the right with an increase in severity of hypertension. In these subjects the U loop was of slightly greater amplitude than in normal subjects, and was long and slender in shape. Anterior and rightward displacement of the U loop was also observed in hypertensive cases who showed no abnormality in the T wave of standard lead ECGs or in the T loop of the VCG. These findings seem useful as clinical parameters of the hemodynamic state in the early stage of hypertension. Based on these results, it was hypothesized that mechanical factors, such as stretch of the ventricular muscles induced by pressure loading of the left ventricle, may contribute greatly to genesis of the U loop.

Adult

Changes in the activities of S-adenosylmethionine synthetase isozymes from rat liver with dietary methionine.

The activities of S-adenosylmethionine synthetase isozymes in liver were measured after rats received a diet containing excess methionine. The activity of the alpha-form increased with increasing methionine content in the diet, and reached 4-5 fold after 6 days on a 3% methionine diet. However, the activity of the beta-form showed only a 1.5 fold increase. The activity of the gamma-form in kidney showed no significance change.

Animals

The alpha-form of S-adenosylmethionine synthetase isozymes from liver is principally functional.

Treatment of rats with an ethionine plus adenine or a methionine diet leads not only to a marked increase of the alpha-form isozyme of S-adenosylmethionine synthetase in liver, but also to the accumulation of comparable amounts of S-adenosylethionine and S-adenosylmethionine in liver. Transplantation of ascites tumor cells into mice leads to a marked increase only of the beta-form isozyme in the host liver, but the levels of S-adenosylmethionine do not significantly change in liver.

Adenine

A sensitive assay method for the measurement of S-adenosylmethionine in tissue.

An assay method has been developed for the measurement of tissue levels of S-adenosylmethionine based upon the ability of this compound to activate tripolyphosphatase associated with S-adenosylmethionine synthetase beta prepared from rat liver. The method has been used to measure S-adenosylmethionine levels in rat liver after feeding rats on various concentrations of methionine in the diet. The results obtained by this method agree well with those measured by the spectrophotometric method. The limit of sensitivity of the assay was about 0.1 nmol of S-adenosylmethionine in an incubation volume of 0.1 ml (10(-6) M).

Acid Anhydride Hydrolases

Synthesis of S-adenosylmethionine synthetase isozymes from rat and mouse livers. Immunochemical studies.

The alpha- and beta-forms of S-adenosylmethionine synthetase in rat liver were completely fractionated by chromatography on a hydrophobic resin, phenyl-Sepharose. The alpha-form was eluted in low-ionic strength buffer, and the beta-form was eluted with 50% dimethylsulfoxide. The alpha-form is less sensitive to dimethylsulfoxide, whereas the beta-form is strikingly stimulated by dimethylsulfoxide, after removal of the dimethylsulfoxide. The levels of the alpha-form activity in rat liver after treatment with ethionine and adenine for 2 consecutive days, and those of the beta-form activity in mouse liver on the 12th day after transplantation of Ehrlich ascites tumor cells, were increased several fold compared to normal liver. Immunochemical titrations with specific antibody against the beta-form as well as kinetic studies indicated that the observed increase in the levels of each activity from the S-adenosylmethionine synthetase isozymes is due to an increase in the cellular content of the enzyme.

Animals

Effects of zeta potential on the permeability of dialysis membranes to inorganic phosphate.

Some patients on hemodialysis have elevated plasma phosphate values. The chemical and physical properties of dialysis membranes may cause reduced inorganic phosphate clearance, leading to hyperphosphatemia. The zeta potential was determined by a streaming potential method using an electrolytic, aqueous solution to elucidate discrepancies in phosphate ion transport through cellulosic and polymethylmethacrylate membranes. The authors also carried out dialysis experiments at 310K to obtain solute permeability for H32PO4(2-), overall mass transfer coefficient for HPO4(2-), and pure water permeability. This study demonstrates that permeability to inorganic phosphate ion does not vary with zeta potential for cellulosic membranes, but polymethylmethacrylate membranes with highly negative zeta potentials may suppress phosphate removal from patients on hemodialysis.

Chronic Kidney Disease-Mineral and Bone Disorder

Ionic strength affects diffusive permeability to an inorganic phosphate ion of negatively charged dialysis membranes.

Electrolytes undergo electrostatic resistances in reaching membrane surfaces and passing through membrane pores when weakly charged dialysis membranes are used in hemodialysis treatments. Diffusive permeability to an electrolyte of weakly charged dialysis membranes depends upon the effective charge density of the membranes, which varies with ionic strength. The authors carried out dialysis experiments at a temperature of 310 K, with 32P-Na2HPO4 in aqueous NaCl and bovine serum, to obtain diffusive permeability to an inorganic phosphate ion of regenerated cellulose, and polymethylmethacrylate membranes of various fixed charge densities at varying ionic strengths ranging from 1.66 to 100 mol/m3. Diffusive permeability to an inorganic phosphate ion increased with ionic strength. Bovine serum, having an ionic strength of approximately 150 mol/m3, gave higher diffusive permeability to an inorganic phosphate ion. The internal structure of dialysis membranes, such as pore size, surface porosity, and tortuosity, also affects diffusive permeability. The electrolyte diffusion theory gives an effective charge density of -5.3 mol/m3 for the cellulosic membrane. In conclusion, ionic strength enhances diffusive permeability to an inorganic phosphate ion in both aqueous NaCl and bovine serum. Inorganic phosphate ion transport through negatively charged dialysis membranes depends upon the degree of dissociation of inorganic phosphate, the molecular size and valence of hydrated inorganic phosphate ion, the effective charge density and internal structure of the membrane, and ionic strength.

Animals

Development of a regenerated cellulose non-complement activating membrane for hemodialysis.

We have developed a new cellulose membrane in which the active hydroxyl and carboxyl groups of the original cellulose fibers are masked with cationic synthetic polymers. The membrane was shown by in vitro and clinical tests to affect the activation of the complement system very little, and it retains the high dialysis efficiency, good tolerance to steam autoclave sterilization, and economical production cost characteristics of the original cellulose membrane. It thus appears that the new cellulose provides the optimum combination of qualities needed in a hemodialysis membrane.

Cellulose