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Biomedical subjects

K Hamaguchi

Publications and source records attributed to K Hamaguchi.

At least 181 records · Page 10Linked to original sources
PubMed1988

Antitumor activity of cisplatin analogs against malignant ovarian tumor xenografts into nude mice.

The antitumor activity of new platinum analogs was studied at equitoxic doses to that of cisplatin (CDDP) in BALB/C nu-nu nude mice bearing xenografts of human ovarian malignant tumors. The following two tumor lines were used: OH-1 (serous cystadenocarcinoma) and MP-1 (mucinous cystadenoma, LPM). 1) Antitumor activity was determined for all agents from the T/C ratio for OH-1. In particular, 254-S and JM-8 were found to be much more active than the other agents. 2) Antitumor activity was determined with JM-8 from the abdominal diameter ratio for MP-1. Both JM-8 and CDDP yielded active responses which were evaluated by the CEA value. Therefore, JM-8 and CDDP were considered to be the most active agents for MP-1. 3) We evaluated the mean body weight loss of tumor bearing mice in order to study the side effects, and a great weight loss was observed with 254-S. 4) A large variety of effects were observed in the histological evaluation for the two tumor lines, and were thus difficult to discuss. Our findings suggest the necessity of individual chemotherapy for each histological type of ovarian malignant tumor.

Animals↗
PubMed1987

Unfolding and refolding of a type kappa immunoglobulin light chain and its variable and constant fragments.

By limited proteolysis of a type kappa immunoglobulin light chain (Oku) with clostripain, both the VL and CL fragments were obtained with a high yield. The unfolding and refolding by guanidine hydrochloride of light chain Oku and its VL and CL fragments were studied at pH 7.5 and 25 degrees C with circular dichroism and tryptophyl fluorescence. The concentration of guanidine hydrochloride at the midpoint of the unfolding curve was 1.2 M for the VL fragment and 0.9 M for the CL fragment. As in the case of the CL fragment of light chain Nag (type lambda) [Goto, Y., & Hamaguchi, K. (1982) J. Mol. Biol. 156, 891-910], the unfolding and refolding kinetics of the CL fragment could be explained in principle on the basis of the three-species mechanism U1 in equilibrium U2 in equilibrium N, where N is native protein and U1 and U2 are the slow-folding and fast-folding species, respectively, of unfolded protein. The unfolding and refolding kinetics of the VL(Oku) fragment were described by a single exponential term. Double-jump experiments, however, showed that two forms of the unfolding molecule exist. The equilibrium and kinetics of unfolding of light chain Oku were explained by the sum of those of the VL and CL fragments. On the other hand, the refolding kinetics of light chain Oku were greatly different from the sum of those of the VL and CL fragments.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1987

Role of amino-terminal residues in the folding of the constant fragment of the immunoglobulin light chain.

Three constant fragments with different amino terminals, CL(105-214), CL(109-214), and CL(113-214), were obtained by limited proteolysis with trypsin or papain of a type lambda immunoglobulin light chain. The conformations of the three CL fragments were indistinguishable on the basis of circular dichroism and tryptophyl fluorescence spectra. The stability to heat and guanidine hydrochloride of CL(105-214) was almost the same as that of CL(109-214), but the stability of CL(113-214) was slightly lower than that of CL(105-214) or CL(109-214). The midpoint of the thermal unfolding transition at pH 7.5 was at 60.0 degrees C for CL(105-214), 60.4 degrees C for CL(109-214), and 57.5 degrees C for CL(113-214). The midpoint of the unfolding transition by guanidine hydrochloride at pH 7.5 and 25 degrees C was 1.2 M for CL(105-214) and CL(109-214) and at 1.0 M for CL(113-214). The kinetics of unfolding and refolding by guanidine hydrochloride of these CL fragments were analyzed on the basis of the three-species mechanism, U1 in equilibrium with U2 in equilibrium with N, where U1 and U2 are the slow-folding and fast-folding species, respectively, of unfolded protein and N is native protein. It was found that only the microscopic unfolding rate constant for CL(113-214) is 2-3 times greater than that for CL(105-214) or CL(109-214) and that the other microscopic rate constants for the three CL fragments are all the same. These findings indicated that the amino-terminal residues, Gly-109-Lys-112, or a part of them, stabilize the CL(113-214) fragment by decreasing only the unfolding rate, that the transition state of the folding of the CL fragment is independent of the presence or absence of this peptide, and that, at the last step of folding, the peptide is incorporated into the globular domain, thus stabilizing it.

Amino Acid Sequence↗
PubMed1987

Cell-mediated immunity to bovine P2 protein and neuritogenic synthetic peptide in experimental allergic neuritis.

Cellular reactivity to bovine P2 protein (P2) and its two synthetic peptides, SP66-78 and SP70-78, was serially examined by the lymphocyte proliferation test in animals with experimental allergic neuritis (EAN). SP66-78 and SP70-78 correspond to residues 66-78 and 70-78 of bovine P2. Proliferative response to SP66-78 as well as P2 appeared at day 7 before the onset of EAN and was clearly manifested at day 14 in the active stage, thereafter disappearing in the stable stage, whereas no response to SP70-78 was detected during the course of the disease. These results suggest that cell-mediated immune response to P2 and the specific part residues 66-78 of P2 play an important role in the pathogenesis of EAN.

Animals↗
PubMed1987

Conformation of the constant fragment of the immunoglobulin light chain: effect of cleavage of the polypeptide chain and the disulfide bond.

In order to understand the conformations and stabilities of the immunoglobulin domains, a derivative of the type-lambda constant fragment in which the peptide bond Arg190-Ser191 is cleaved and a derivative of the type-kappa constant fragment in which the peptide bond Arg142-Glu143 is cleaved were prepared by limited proteolysis with the proteinase from mouse submaxillary gland, endoproteinase Arg-C [EC 3.4.21.40]. The cleaved peptide bond of each derivative is located in the loop formed by the intrachain disulfide bond and the two peptides formed are linked by the disulfide bond. The two nicked CL fragments did not assume any ordered conformation. On the other hand, a derivative in which the intrachain disulfide bond is reduced had a conformation very similar to that of the intact CL fragment, although the stability was considerably low. Since the entropy of the nicked fragment should be nearly the same as that of the reduced CL fragment in the unfolded state, a destabilizing effect of cleavage of the polypeptide bond in the folded state in addition to the entropic effect in the unfolded state seems necessary to account for the conformations of the nicked CL fragments.

Ammonium Sulfate↗
PubMed1987

Metal binding and metal-induced conformational change of frog bone gamma-carboxyglutamic acid-containing protein.

Ca2+ or Cd2+ binding and the conformational change induced by the metal binding in two frog bone Gla-proteins (BGP, termed BGP-1 and BGP-2) were studied by equilibrium dialysis and CD measurement. By CD measurement in the far-ultraviolet region, the alpha-helix content of both apoBGPs was found to be 8%. Binding of both Ca2+ and Cd2+ was accompanied with a change in the CD spectrum, and the alpha-helix content increased to 15 and 25% for BGP-1 and BGP-2, respectively. CD measurement in the near-ultraviolet region indicated that the environment of aromatic amino acid residues in the protein molecule was changed by metal binding. Equilibrium dialysis experiments indicated that each of these two protein binds specifically 2 mol of Ca2+, and nonspecifically an additional 3-4 mol of Ca2+ in 0.02 M Tris-HCl/0.15 M NaCl (pH 7.4), at 4 degrees C. According to the two separate binding sites model, BGP-1 has 1 high-affinity Ca2+ binding site (Kd1 = 0.17 mM) and 1 low-affinity site (Kd2 = 0.29 mM), and BGP-2 contains 1 high-affinity site (Kd1 = 0.14 mM) and 1 low-affinity site (Kd2 = 0.67 mM). In addition, 2 Cd2+ bound to a high-affinity binding site on BGP-1 with Kd1 of 10.4 microM, and 1 Cd2+ bound to a low-affinity binding site with Kd2 of 41.5 microM. On the other hand, BGP-2 had three classes of binding sites and 1 Cd2+ bound to each binding site with Kd1 = 3.6 microM, Kd2 = 16.3 microM, Kd3 = 51.7 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Carboxyglutamic Acid↗
PubMed1987

Fluorescence of the tryptophyl residues of the constant fragment of the immunoglobulin light chain.

The constant (CL) domain of the type-lambda immunoglobulin light chain contains two tryptophyl residues. The fluorescence lifetimes of the CL fragment and its two modified forms, the reduced CL, and reduced and alkylated CL fragments, were measured at pH 7.5 and 25 degrees C. The fluorescence decay kinetics of these fragments were described in terms of two lifetimes. The static and dynamic quenching reactions by acrylamide of the tryptophyl residues of these fragments were measured and their dynamic properties were compared with the static properties reported previously (Goto, Y. & Hamaguchi, K. (1979) J. Biochem. 86, 1433-1441; Goto, Y. & Hamaguchi, K. (1986) Biochemistry 25, 2821-2828; Ashikari, Y., Arata, Y., & Hamaguchi, K. (1985) J. Biochem. 97, 517-528). It was found that although the static conformation of the reduced CL fragment is very similar to that of the intact CL fragment, the dynamic conformations of these two fragments differ considerably.

Acrylamides↗
PubMed1987

High-dose intravenous corticosteroids in the treatment of multiple sclerosis.

The effectiveness of high-dose intravenous corticosteroid therapy for acute bouts of multiple sclerosis (MS) was evaluated in comparison with the conventional oral prednisolone therapy. Group I comprised 11 cases of MS treated with oral prednisolone, 30-60 mg daily, and group II comprised 16 cases treated with intravenous corticosteroids; 11 cases given 1000 mg of methylprednisolone for the initial 3 days followed by 100 mg of prednisolone, while the remaining 5 were given 100 mg of prednisolone alone. The initial dosage was maintained for 1 or 2 weeks in each group, tailing off with a period of several weeks of oral prednisolone. The clinical status was evaluated using Kurtzke's expanded disability status scale (EDSS) and functional system scale before and 1, 2 and 4 weeks after the initiation of therapy. EDSS score significantly declined from week 0 (before) to weeks 1, 2 and 4 in group II, respectively, whereas no significant decline of EDSS score was observed in group I. The frequency of improvement (0.5 of an increment in EDSS score) in group II was significantly higher than that in group I at weeks 1, 2 and 4. It was thus suggested that high-dose intravenous corticosteroid therapy might be more useful in acute bouts of MS, especially for obtaining an early improvement, than conventional oral prednisolone therapy.

Administration, Oral↗
PubMed1987

Pseudoidiopathic hypoparathyroidism: report of a case and review of the literature in Japan.

A case of pseudoidiopathic hypoparathyroidism is described. The patient, 47-year-old male, developed numbness and muscle spasms in the extremities in July 1980. Physical and laboratory examinations revealed positive Chvostek and Trousseau's signs, hypocalcemea, mild hyperphosphatemia, normal serum magnesium, prolongation of QTc on EKG, normal reaction to Ellsworth-Howard test and high levels of serum PTH. Treatment with calcium lactate and vitamin D was successful. The literature regarding 16 cases reported in Japan was reviewed.

Humans↗
PubMed1987

Pupillary light reflex in patients with hemispheric cerebrovascular disease.

Pupillary dynamics were investigated in 41 patients with hemispheric CVD by means of computerized open-loop videopupillography. The patients were alert and showed either abnormal high- or low-density areas on CT scan. Fourteen cases were examined in the acute stage (within 7 days from onset), 28 cases in the subacute stage (between 8 and 28 days) and 11 cases in the chronic stage (over 29 days). In the acute stage, the parasympathetic nervous functions (maximum velocity and acceleration of pupillary constriction) were hyporeactive and showed no significant differences between the ipsilateral and contralateral side of the lesion. In the subacute stage, these functions were significantly more hyperreactive on the ipsilateral side than on the contralateral side, that is, the parasympathetic functions of the healthy hemisphere became significantly improved in comparison with those in the acute stage. In the chronic stage, no significant differences were observed between the two sides. In contrast, the sympathetic nervous function (maximum velocity of dilatation) showed no differences with respect to either laterality or the time course after onset. The above data suggest that bilateral parasympathetic hypofunctions exist in the acute stage of hemispheric CVD, with an ipsilateral improvement of these functions with the passage of time, and that such autonomic dysfunctions may play some role in the pathophysiology of CVD.

Aged↗
PubMed1987

[Direct anti-tumor effect of recombinant human IFN-gamma evaluated in ovarian pseudomyxoma peritoneally transplanted into nude mice].

Different doses of recombinant human interferon gamma (IFN-gamma) between 1 X 10(6) and 2 X 10(7) U/kg were administered to nude mice for 21 days continuously. As a result, an anti-tumor effect was noted in comparison with a control group, although there was no significant difference between groups at each dose level. Serum CEA value was found to decrease in the groups as follows: 1 X 10(6) U/kg, 71.5 +/- 10 ng/ml; 3 X 10(6) U/kg, 90.6 +/- 4 ng/ml; 8 X 10(6) U/kg, 56.5 +/- 0.7 ng/ml; 2 X 10(7) U/kg, 47.4 +/- 12 ng/ml. Generally, the level was found to decrease in groups with high-dose administration. There was no difference in histological effect between groups at each dose level, and also no strong anti-tumor effect like that produced with other anti-cancer agents was noted with regard to histological change. It was revealed that recombinant human IFN-gamma was effective for suppression of tumor proliferation in human ovarian tumor, although its histological effect was less effective than that of anti-cancer agents such as Adriamycin and Cis-DDP.

Animals↗
PubMed1987

[Second look operations in ovarian cancer--a clinical study on the detection of recurrent tumors and the judgment on termination of treatment in 84 cases].

Various investigations were conducted on 84 patients undergoing a second look operation (S.L.O.) intended to detect any recurrent tumors and determine the timing of the cessation of therapy. The following conclusions were obtained: Tumors were found in 18 patients (21.4%) whose preoperative diagnosis was neither subjectively nor objectively abnormal. Patients who received S.L.O. had a considerably better 5 year survival rate than the control group. S.L.O. can safely be omitted only in patients with Stage I border line ovarian tumors. S.L.O. is essential in cases where basic surgical procedures were not carried out during the initial operation. No occlusion could be reached as to the best time to perform S.L.O. In almost all of the patients who died, the site of recurrence was somewhere outside the abdominal cavity, but no recurrent tumors had been found during S.L.O. S.L.O. is still a more efficient follow-up method than CA125, TPA or IAP tumor markers, although the preoperative results of these tests reflected the laparotomy findings relatively well.

Adult↗