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Biomedical subjects

S Baba

Publications and source records attributed to S Baba.

At least 847 records · Page 47Linked to original sources

[Sequential combination therapy with alpha interferon and OK-432 (streptococcal preparation) against advanced renal cell carcinoma].

Renal cell carcinoma (RCC) is one of the most insensitive urologic tumors to either radiotherapy or anticancer chemotherapy. Recently, effectiveness of interferon (IFN) against RCC has been reported. However, because this effect is somewhat limited, a new modality of treatment is needed. We herein report our experience with IFN and OK-432, a streptococcal preparation for patients with advanced RCC. Twenty patients aged from 26 years to 75 years, with an average age of 52.3 years, were entered into this study. Intramuscular injection of human lymphoblastoid interferon (HLBI) at a dose of 3 X 10(6) units was given daily for between 4 and 76 weeks. Treatment with OK-432 then followed HLBI, unless the patient achieved CR or the status of the patient seriously deteriorated during the initial treatment with HLBI. OK-432 was given to 12 patients at a dose of 5KE (Klinische Einheit) 2 days a week for between 10 and 64 weeks. Effectiveness of HLBI therapy was 20% (CR 1 case, MR 3 cases, NC 11 cases, PD 5 cases). With adjuvant OK-432 therapy for patients whose disease proved to be resistant to HLBI, effectiveness was 25% (CR 1 case, MR 2 cases, NC 6 cases, PD 3 cases). The results obtained indicated that OK-432 following IFN is a potentially active antitumor regimen in patients with advanced RCC.

Adult↗

Determination of dexamethasone in human plasma and urine by electron-impact mass spectrometry.

A gas chromatographic-electron-impact mass spectrometric method for the determination of dexamethasone in biological fluids has been developed. Quantitation by isotopedilution mass spectrometry was carried out by selected-ion monitoring on the molecular ions of the tetra(trimethylsilyl) derivative of dexamethasone and of dexamethasone M+9 (m/z 680 and 689, respectively). The sensitivity, specificity, precision and accuracy of the method were demonstrated to be satisfactory for application to pharmacokinetic and bioavailability studies of dexamethasone after administration of a therapeutic dose.

Adult↗

Combined effect of phorbol ester and, A23187 or dibutyryl cyclic AMP on pepsinogen secretion from isolated gastric glands.

In isolated guinea pig gastric glands, pepsinogen secretion was stimulated by the phorbol ester, 12-0-tetradecanoyl-phorbol-13-acetate (TPA) in a dose dependent manner. Calcium-deprivation from the medium resulted in the decrease in TPA-induced pepsinogen secretion. The combination of 0.4 microM Ca2+ionophore A23187 and TPA stimulated pepsinogen secretion slightly higher than the calculated additive value for each agent. This synergistic effect of the agents supports a role of calcium-activated, phospholipid-dependent protein Kinase (protein Kinase C) in gastric pepsinogen secretion. Furthermore, pepsinogen secretion was also stimulated by dibutyryl cyclic AMP (dbc AMP) and dbc AMP slightly enhanced TPA-induced pepsinogen secretion. Results suggest that gastric chief cells possess at least two different secretory pathways for pepsinogen which are probably dependent on protein kinase C and cyclic AMP, respectively.

Animals↗

Increased fructose-lysine of hair protein in diabetic patients.

Fructose-lysine, which is formed by binding glucose to lysine, is changed by acid hydrolysis into furosine. Furosine derived from fructose-lysine of hair was determined by high-performance liquid chromatography according to the method of Schleicher et al. Furosine values were significantly higher in diabetic patients than in healthy subjects, and significantly correlated with the stable components of hemoglobin A1 (HbA1) values. These results suggest that furosine, like HbA1, may become an indicator of past blood glucose control at any time in diabetic patients and be useful in investigating diabetic complications on the level of tissue.

Adult↗

[Evidence for the internalization and degradation of insulin in cultured Bri-7K human lymphocytes].

We have studied the internalization of insulin and the mechanism of insulin degradation in cultured Bri-7K human lymphocytes. The internalization of 125I-insulin was observed by using an acid extraction technique by Heigler's method which removed surface-bound insulin, leaving only intracellular insulin associated with cells. Insulin binding to Bri-7K cells reached a peak at 15 min and showed a gradual fall thereafter at 37 degrees C. Internalization of insulin rose with a peak in 30 min, and its rate was nearly 25% of the total specific cell-associated radioactivity. Insulin degrading activities in Bri-7K cells were examined as to precipitability with trichloroacetic acid (TCA method), Sephadex G-50 column chromatography (gel chromatography method) and the ability to bind to specific receptors on Bri-7K cells (rebinding method). Under conditions demonstrating that the insulin degradation didn't take place in the medium but was cell-mediated, the insulin degradation was not demonstrated by the TCA method. Chromatographic studies showed that the extractable radioactivity consisted almost entirely of intact insulin, whereas the supernatant and the nonextractable radioactivities consisted of large molecular weight material and intact insulin. Thus, the apparent degradation of insulin was not detectable by the TCA and gel chromatography methods, however, using the rebinding method, we could obtain results demonstrating that fair amounts of insulin in the supernatant were degraded. These results suggest that the products of insulin degradation are peptides with a molecular size similar to insulin itself but with little or no receptor binding activity. In conclusion, insulin internalizes into Bri-7K cells at physiological temperature, and the mechanism of insulin degradation in Bri-7K cells seems to be a limiting proteolysis of insulin by specific enzyme(s).

Cell Membrane↗

Covalent linkage of 125I-insulin to a cytosolic insulin-degrading enzyme.

Cytosol extracts high in insulin-degrading activity were cross-linked to 125I-insulin with the bifunctional cross-linker disuccinimidyl suberate. With cytosols from either rat muscle, liver, kidney or brain or human erythrocytes, only a single protein (Mr = 110,000) was specifically labeled. Three different lines of evidence indicated that this labeled protein is insulin-degrading enzyme, a cysteine protease which accounts for most of the insulin-degrading activity in cell extracts. Firstly, the cross-linking of 125I-insulin to this protein is inhibited by unlabeled insulin over the same concentration range of insulin which inhibits degradation. Separated insulin A and B chain were less potent at inhibiting cross-linking, whereas bovine serum albumin and cytochrome c were without effect. Secondly, antibodies to purified insulin-degrading enzyme precipitated the labeled protein in parallel with their ability to precipitate the insulin-degrading activity of the extracts. Thirdly, when the insulin-degrading activity was purified 40,000-fold from erythrocytes, this Mr 110,000 protein co-purified. These results indicate that cross-linking 125I-insulin may be a convenient method for labeling the insulin-degrading enzyme.

Animals↗

Cross-reactivities of neuropeptide Y and peptide YY with pancreatic polypeptide antisera: evidence for the existence of pancreatic polypeptide in the brain.

Highly purified neuropeptide Y (NPY) and peptide YY (PYY) did not cross-react in our human pancreatic polypeptide (hPP) radioimmunoassay, nor did 125I-labelled NPY and PYY, even with anti-hPP serum at low dilution (1:1000). However, both [125I]NPY and [125I]PYY significantly cross-reacted with anti-bovine PP (bPP) serum at low dilution (1:1000, similar to that used in immunohistochemistry). These results suggest that radioassayable hPP-like peptide in the porcine or canine brain is probably pancreatic polypeptide itself, otherwise immunohistochemically detected bPP-like peptide may represent both NPY and PP.

Amino Acid Sequence↗