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Biomedical subjects

S Sugai

Publications and source records attributed to S Sugai.

At least 181 records · Page 10Linked to original sources
PubMed1987

Metastatic calcification in the stomach demonstrated by a bone scan in Bence Jones lambda myeloma.

A 53-year-old male with Bence Jones lambda myeloma developed hypercalcemia and acute renal failure (calcium 14.4 mg/dl, BUN 40 mg/dl, creatinine 3.0 mg/dl) after initial response to chemotherapy. A 99mTc-MDP bone scan revealed unusual isotope accumulation in the left hypochondrium. Extensive calcium deposition was confirmed in the gastric mucosa in the postmortem examination. Detection of gastric calcification by a bone scan is very rare. Only two cases of gastric calcification visualized on bone scans can be found in the literature, one with multiple myeloma) and one in Hodgkin's disease).

Bence Jones Protein↗
PubMed1986

Evidence for identity between the equilibrium unfolding intermediate and a transient folding intermediate: a comparative study of the folding reactions of alpha-lactalbumin and lysozyme.

The refolding kinetics of alpha-lactalbumin at different concentrations of guanidine hydrochloride have been investigated by means of kinetic circular dichroism and stopped-flow absorption measurements. The refolding reaction consists of at least two stages, the instantaneous accumulation of the transient intermediate that has peptide secondary structure and the subsequent slow process associated with formation of tertiary structure. The transient intermediate is compared with the well-characterized equilibrium intermediate observed during the denaturant-induced unfolding. Stabilities of the secondary structures against the denaturant, affinities for Ca2+, and tryptophan absorption properties of the transient and equilibrium intermediates were investigated. In all of these respects, the transient intermediate is identical with the equilibrium one, demonstrating the validity of the use of the equilibrium intermediate as a model of the folding intermediate. Essentially the same transient intermediate was also detected in the folding of lysozyme, the protein known to be homologous to alpha-lactalbumin but whose equilibrium unfolding is represented as a two-state reaction. The stability and cooperativity of the secondary structure of the intermediate of lysozyme are compared with those of alpha-lactalbumin. The results show that the protein folding occurring via the intermediate is not limited to the proteins that show equilibrium intermediates. Although the unfolding equilibria of most proteins are well approximated as a two-state reaction, the two-state hypothesis may not be applicable to the folding reaction under the native condition. Two models of protein folding, intermediate-controlled folding model and multiple-pathway folding model, which are different in view of the role of the intermediate in determining the pathway of folding, are also discussed.

Guanidine↗
PubMed1986

Innocuous character of [ethylenebis(oxyethylenenitrilo)]tetraacetic acid and EDTA as metal-ion buffers in studying Ca2+ binding by alpha-lactalbumin.

The binding of EGTA and EDTA to alpha-lactalbumin, first demonstrated by Kronman and Bratcher (Kronman, M. J., and Bratcher, S. C. (1983) J. Biol. Chem. 258, 5707-5709) and afterwards regarded as a significant source of error in estimating the binding constant of Ca2+ to the protein, has been investigated by comparison of the thermal unfolding curves of the protein in the absence and presence of the chelators and also by measuring the NMR spectra of the protein, the chelators, and the protein-chelator mixtures. The unfolding curve in the presence of a large excess of each chelator has been found to be identical to that in the absence of chelator, indicating that there is essentially no interaction between the chelators and alpha-lactalbumin. The NMR results have also supported this conclusion, and the innocuous character of these chelators as metal-ion buffers in studying the Ca2+-binding properties of alpha-lactalbumin is demonstrated. In order to re-examine the binding constant for Ca2+ of alpha-lactalbumin without the aid of chelating metal-ion buffers, the thermal unfolding curve of the protein in the presence of 0.1 mM excess Ca2+ but without chelators has been compared with the unfolding curve in the absence of Ca2+ at a constant concentration of Na+ (0.010 or 0.10 M) at pH 7.0. The binding constant of alpha-lactalbumin can be calculated from the increment of melting temperature caused by the presence of Ca2+ and from the enthalpy and heat capacity changes in the unfolding. Because Ca2+ binding to the unfolded protein can be neglected under the conditions employed, the binding constant evaluated corresponds to the binding constant to protein that has native structure. The constant obtained is 3-5 X 10(9) M-1 after corrections for binding of Na+ to the protein and for ionic strength, and this shows excellent agreement with the corresponding value previously estimated (2.9 +/- 1.0 X 10(9) M-1), although the latter value was obtained in the presence of EDTA. The apparent Ca2+-binding constant that has been discussed in most previous studies, without taking account of the folding-unfolding equilibrium associated with the binding process, also depends on the concentration of monovalent cations such as Na+, and the present results lead to values of 1.5 X 10(8) and 8.7 X 10(6) M-1 at 0.01 and 0.1 M Na+, respectively.

Buffers↗
PubMed1986

A monoclonal surface immunoglobulin (IgM/D-L) with specificity for surface antigen of ox red blood cells in a patient with leukemic lymphosarcoma.

A patient with B-cell leukemic lymphosarcoma, whose lymphocytes had a monoclonal (IgM/D-L) surface immunoglobulin (SmIg) and formed rosettes with ox red blood cells (ORBC), is described. The leukemic cells were documented to have a monoclonal SmIg and cytoplasmic Ig (CIg) and secreted a monoclonal immunoglobulin (MIg) whose antibody activity was directed to the surface antigen of ORBC. Pretreatment of the leukemic cells with anti-mu, anti-delta, or anti-lambda inhibited E(ox) rosette formation specifically. Pretreatment of the leukemic cells with pronase removed the SmIg and abolished E(ox) rosette formation simultaneously, and regeneration of the SmIg was parallel with recovery of the rosette formation. A small amount of serum MIg could be detected by agarose gel electrophoresis and antiidiotypic antibody against the 19 S component of the serum revealed that the monoclonal SmIg, CIg, and serum MIg shared the same idiotope. This case suggests that lymphocytes of some B-cell malignancies may bind to ORBC through SmIg.

Animals↗
PubMed1986

Conformations of hydrophobic polyelectrolytes.

Recent studies on the (hypercoiled) compact conformation and the pH-induced conformational transition to the extended coil of the hydrophobic poly(acids or bases), which have been well used in industrial and medical circles, are summarized, especially on the basis of our studies on poly(alpha-alkyl acrylic acids) and maleic acid copolymers with hydrophobic aromatic monomers. The stability of the compact conformation and values of various thermodynamic parameters of the transition of the hydrophobic polyelectrolytes suggest the importance of hydrophobic interaction among the side chains to form the compact conformation. Characterization of various physicochemical methods, including 1H-NMR measurements, gives a model of the compact conformation with a more expanded structure than in globular proteins, a free-draining property of the solvent, the conformation fluctuation, etc. Also, the apparent two-state character of each segment in the transition region, a life-time in each state and the cooperative parameter for the compact form formation are discussed. A review of our conformational studies on the hydrophobic-hydrophilic polypeptides is also given. For the anion-induced conformation transition in basic homopoly(alpha-amino acids), hydrophobic characters of the anion and the side chain in the polypeptide are shown to be important, especially in terms of solvation. The difference in the induced conformation by the anion between random and alternating basic copolypeptides is explained by introducing a model which shows the importance of the sequence of hydrophobic and hydrophilic residues in the polypeptide to induce the ordered conformation of the anions. Also, we attempt to explain the difference between the induction of ordered conformation in the basic homo- or copolypeptide in reversed micelles with a large sulfonate (AOT) vs. that in aqueous AOT in terms of the hydrophobic character of the side chains in the polypeptides, AOT and the medium.

Electrolytes↗
PubMed1986

Binding strength of calcium ion to bovine alpha-lactalbumin.

A Ca2+-sensitive electrode was used for determination of the binding strength of Ca2+ to bovine alpha-lactalbumin in 60 mM Tris buffer (pH 7.8-8.5) in the presence of various concentrations of NaCl. The dependence of the apparent binding constant on the concentration of NaCl was consistent with competitive binding of Ca2+ and Na+, and the binding constants of Ca2+ and Na+ were found to be 2.2 (+/- 0.5) X 10(7) M-1 and 99 (+/- 33) M-1, respectively, at 37 degrees C and pH 8.0. The temperature dependence of the binding constant of Ca2+ was examined between 30 and 45 degrees C; extrapolation of the dependence led to a binding constant of approximately 1 X 10(8) M-1 at pH 8.4 and 25 degrees C. The electrostatic contribution and conformational effect of the protein were also taken into consideration, and the intrinsic binding constant of Ca2+ to native alpha-lactalbumin was calculated to be (1.2-1.5) X 10(10) M-1 at 37 degrees C and pH 8.0.

Animals↗
PubMed1986

Ca2+-induced alteration in the unfolding behavior of alpha-lactalbumin.

Comparative studies of the unfolding equilibria of two homologous proteins, bovine alpha-lactalbumin and hen lysozyme, induced by treatment with guanidine hydrochloride have been made by analysis of the peptide and the aromatic circular dichroism spectra. The effect of the specific binding of Ca2+ ion by the former protein was taken into account in interpreting the unfolding equilibria of the protein. Proton nuclear magnetic resonance spectra of alpha-lactalbumin were also measured for the purpose of characterizing an intermediate structural state of the protein. In previous studies, alpha-lactalbumin was shown to be an exceptional protein whose equilibrium unfolding does not obey the two-state model of unfolding, although lysozyme is known to follow the two-state unfolding mechanism. The present results show that the apparent unfolding behavior of alpha-lactalbumin depends on Ca2+ concentration. At a low concentration of Ca2+, alpha-lactalbumin unfolds with a stable intermediate that has unfolded tertiary structure, as evidenced by the featureless nuclear magnetic resonance and aromatic circular dichroism spectra, but has folded secondary structure as evidenced by the peptide circular dichroism spectra. However, in the presence of a sufficiently high concentration of Ca2+, the unfolding transition of alpha-lactalbumin resembles that of lysozyme. The transition occurs between the two states, the native and the fully unfolded states, and the cooperativity of the unfolding is essentially the same as that of lysozyme. Such a change in the apparent unfolding behavior evidently results from an increase in the stability of the native state relative to that of the intermediate induced by the specific Ca2+ binding to native alpha-lactalbumin. The results are useful for understanding the relationship between the protein stability and the apparent unfolding behavior.

Animals↗
PubMed1986

Influence of Ca2+ binding on the structure and stability of bovine alpha-lactalbumin studied by circular dichroism and nuclear magnetic resonance spectra.

Both the Ca2+-bound and Ca2+-free forms of alpha-lactalbumin can assume essentially the same folded conformation as evidenced by similarity in their CD and proton n.m.r. spectra. Thermal unfolding followed by the aromatic CD has shown that the stability of the folded state is markedly enhanced by Ca2+ and that the stabilization is almost entirely entropic; addition of 0.1 mM Ca2+ shifts the transition temperature from 40 degrees to 62 degrees in 0.1M Na+ at pH 7.0. The enthalpy change of the unfolding, coincident between the two forms, is, however, significantly smaller than that known for lysozyme. The n.m.r. spectrum under the condition that both the forms of the protein are in the folded state reflects minor environmental changes of certain protons upon Ca2+ binding, and these changes are shown to afford useful probes for assessment of the location of the binding site. From the pH dependence and temperature dependence of the spectrum and also by using spin decoupling in the aromatic region (6.4-8.7 p.p.m.), it is shown that none of histidyl residues are affected and that at least two tryptophanyl ring protons experience environmental changes upon Ca2+ binding to the folded apo-protein. Effect of free excess Ca2+ on the spectrum has also shown that in native alpha-lactalbumin there is only one Ca2+-binding site that is detectable by the present method.

Animals↗
PubMed1986

Serum monoclonal IgM undetectable by cellulose acetate membrane electrophoresis in four patients with B cell malignant lymphoma.

A small amount of monoclonal IgM was demonstrated in the serum of four B cell malignant lymphoma patients in whom electrophoretically homogeneous protein bands were not detected by either cellulose acetate membrane electrophoresis or immunoelectrophoresis. By using anti-idiotypic (Id) antisera prepared against serum IgM, the M proteins were detected and identified as the products of malignant cells. These findings suggest that the use of more sensitive technics than the usual serum electrophoresis shows that the incidence of M proteins in B cell malignant lymphomas is higher than has been previously reported.

Adult↗
PubMed1986

Lymphoproliferative disorders in Japanese patients with Sjögren's syndrome.

Fourteen Sjögren's syndrome (SS) patients with monoclonal gammopathy (MG), 4 SS patients with malignant lymphoma (ML) and one with pseudolymphoma (PL) were described. Among the 14 MG patients, the IgG class was found in 3, IgA in 6, IgM in 3, and 2 M proteins (IgM/IgG and IgA/IgG) were found in 2 patients. The monoclonal rheumatoid factor (RF) was found in 4 patients (3 IgA and one IgM). Idiotypes (Id) of M proteins were studied in 11 out of 14 patients. The histology of ML showed the diffuse, large cell, medium-sized cell and follicular, mixed cell type. The monoclonal surface membrane Ig (SmIg) and/or cytoplasmic Ig (CIg) were identified (3 IgM and one IgG). A review of the Japanese literature on lymphoproliferative disorders (LPD) in SS patients disclosed additional 15 MG patients (3 IgG, 5 IgA, 6 IgM and one Bence Jones protein) and 22 LPD patients (14 non-Hodgkin's ML, 4 PL, 2 plasmacytomas and 2 thymomas). The literature was also reviewed on LPD in non-Japanese SS patients; 26 patients with MG (4 IgG, 2 IgA, 19 IgM and one Bence Jones protein) and 104 patients with LPD (59 non-Hodgkin's ML, 4 Hodgkin's lymphomas, 23 PL, 5 thymomas, 4 immunoblastic lymphadenopathies (IBL), 2 Lennert's lymphomas and 7 others) were found. These results indicate that non-IgM class MG was more dominant in Japanese than in non-Japanese SS patients and that there was a higher incidence of MG in primary than in secondary SS patients, and also that B cell lymphomas (9 in Japanese and 11 in non-Japanese) were more common in SS patients.

Humans↗
PubMed1986

Monoclonal anti-idiotypic antibodies against monoclonal rheumatoid factors derived from patients with Sjögren's syndrome.

Monoclonal anti-idiotypic antibodies (mA-IDs) were produced against IgM-K, IgA-L and IgA-K monoclonal rheumatoid factors (mRFs), respectively, derived from patients with Sjögren's syndrome (SS). Each mA-ID inhibited the RF activity of the autologous M-protein, but did not inhibit the activity of the other mRFs. As for the specificity of mA-IDs, it was confirmed to bind only to the mRF used for immunization. A cross-reactive idiotype (CRI) was detected in 3 out of 106 polyclonal RFs (pRFs) using AW5/3 mA-ID by double immunodiffusion or ELISA inhibition assay on pRF activity. However, no CRI was detected on AMB1/5 or SF18/2 mA-ID. One of the mA-IDs, AW5/3, cross-reacted with nuclei of proliferating lymphocytes, such as PHA-stimulated lymphocytes, interleukin 2 dependent T cell lines, B-lymphoblastoid cell lines or cultured lymphoma cell lines, but barely reacted with nuclei of normal resting lymphocytes.

Antibodies, Anti-Idiotypic↗
PubMed1986

Conformation of B. stearothermophilus 5S ribosomal RNA.

The thermal melting of B. stearothermophilus 5S ribosomal RNA was studied, by means of derivative optical absorption and CD spectra, and high performance liquid chromatography, in Tris buffers with K+ and Mg2+ at pH 7.6. Biphasic changes in optical absorption and CD ellipticity were observed, which mean the melting of two helices. Change in molecular size was also examined in the melting process. The melting temperatures depended on ionic strength and concentration of Mg2+. Enhanced stability of the helix was indicated, as compared with the corresponding one in B. subtilis 5S ribosomal RNA. In the presence of a large amount of Mg2+, the third melting process was observed at low temperatures, which was suggested due to change in the tertiary structure.

Circular Dichroism↗