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I Kohno

Publications and source records attributed to I Kohno.

At least 73 records · Page 4Linked to original sources
PubMed1995

Calcium ion-dependent monoclonal antibody against human fibrinogen: preparation, characterization, and application to fibrinogen purification.

We have produced a high-affinity monoclonal antibody classified as IgG1 with kappa-type light chains that recognizes the calcium ion(Ca2+)-dependent conformation of the D-domain of human fibrinogen. Binding of fibrinogen in solution to the insolubilized antibody increased in the presence of increasing concentrations of up to 2 mM Ca2+, the half-maximal binding being reached at 130 microM Ca2+. The dissociation constant was estimated to be 1.6 x 10(-8) M at 2 mM Ca2+. The antibody was found also to be dependent on other divalent metal ions including Zn2+, Mn2+, Co2+ and Cu2+, but not Ba2+, Mg2+ or Sr2+. The synthetic Gly-Pro-Arg-Pro-amide peptide, which has recently been shown to bind to close proximity to the calcium binding site in the D-domain, was unable to elicit the conformation for the antigen to be recognized by this antibody. This antibody was found to be a suitable ligand for the immunoaffinity chromatography of normal and abnormal fibrinogens directly from citrated plasma depleted of the vitamin K-dependent proteins or heparinized plasma by eliminating the precipitation procedure widely adopted in conventional techniques of fibrinogen purification. Indeed, fibrinogen Marburg I with the A alpha chains depleted of the carboxy-terminal A alpha(461-610) residue segment has been purified by this technique, although this dysfibrinogen was difficult to purify by conventional precipitation techniques.

Antibodies, Monoclonal↗
PubMed1994

Direct evidence for systemic fibrinogenolysis in patients with acquired alpha 2-plasmin inhibitor deficiency.

To examine whether or not acquired alpha 2-plasmin inhibitor deficiency is associated with systemic fibrinogenolysis, we analyzed the fibrin and fibrinogen degradation products in eight patients with this condition in various disease states. The underlying disease was gastric cancer in three patients, metastatic prostatic cancer in two, acute promyelocytic leukemia in two, and abdominal aortic aneurysm in one patient. In all eight patients, the alpha 2-plasmin inhibitor level was reduced to less than 50% of normal, and plasmin-alpha 2-plasmin inhibitor complex levels were increased. Immunoblotting of serum using an antifibrinogen antibody detected a 250 kDa protein (corresponding to fragments X or DY) in all eight patients. Fragment Y and D monomer were detected in seven of the eight patients, indicating the occurrence of systemic fibrinogenolysis. However, they were not detected in one patient with metastatic prostatic cancer. To determine whether or not fibrinogen degradation was also occurring in the patient without fragment Y, we characterized the 250 kDa protein in all eight patients. The protein was found to be fragment X in the metastatic prostatic cancer patient without fragment Y, while it was fragment DY in the other seven patients. Thus, systemic fibrinogenolysis was present in all eight patients. In the two patients with metastatic prostatic cancer, the level of alpha 2-plasmin inhibitor gradually increased with the reduction of tumor size by treatment. Fragment X, fragment Y, and D monomer were not detected when the alpha 2-plasmin inhibitor level exceeded 60% of normal in both patients. In the other six patients fragment Y and D monomer also disappeared when the alpha 2-plasmin inhibitor level exceeded 60% of normal. These findings suggest that systemic fibrinogenolysis only occurs when the plasma levels of alpha 2-plasmin inhibitor falls below 60% of normal due to activation of the fibrinolytic system by various pathological conditions.

Adult↗
PubMed1994

[Clinical trials for gynecological cancers (especially ovarian cancers) in Japan, current situation and problems--focusing on differences in the system of study used by Japanese Study Group and the Gynecologic Oncology Group in the United States].

One of the major problems in treating ovarian cancers at present is how to cure patients with platinum-resistant tumors. Although clinical trials for ovarian cancers in both Japan and the United States have focused on this issue, most Japanese clinical studies in this field have been of poor quality because group studies have not been functioning efficiently. In spite of a tremendous effort, there are several obstacles to overcome before establishing an efficient study group. Keys to perform productive group studies would be as follows: 1) Since most cancer patients in Japan have been treated by physicians whose subspecialty is not oncology, the organization of cancer centers in major local hospitals or the establishment of qualifications for cancer practice is necessary. 2) Because the term "clinical trial" raises the fears of being a "guinea pig" among Japanese, better education of the public, including patients, families, government bodies and even physicians, is necessary to make them understand that only through clinical trials can effective treatment be achieved in the future. 3) Qualification of research nurses and research secretaries is required to save time and make for competent trials. 4) Sufficient government treating is required to keep any commercial bias out of the trials. Finally, 5) strict quality control by the protocol committee of the study groups is mandatory.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Significant increases in serum CA125 and CA19-9 following torsion from an adenofibroma of the ovary: a case report.

Significant increases in the serum levels of cancer antigen 125 (CA125) and carbohydrate antigen 19-9 (CA19-9) were observed over one month prior to the removal of an ovarian adenofibroma. The serum levels of CA125 and CA19-9 decreased rapidly after surgery. The surface of the tumor at surgery showed marked inflammation, probably induced by the necrosis produced by torsion. Pathologically, most of the tumor was necrotic, and histoimmunochemical staining of the viable cells was weak for CA125 but intense for CA19-9. Clinicopathological observations of the case suggested that CA125 and CA19-9 might be stimulated in the cells by inflammation or that originally existing CA125 and CA19-9 were released from the tumor cells following the cell necrosis.

Adenofibroma↗
PubMed1993

Chronobiologic assessment of antihypertensive therapy.

This paper is an example of the clinical application of chronobiologic methods to the diagnosis of the major killers of modern societies, i.e., hypertension. Passing from the description of the methodology to clinical examples, the article provides convincing evidence of the importance of the chronodiagnostic approach to ambulatory blood pressure monitoring not only for a more accurate diagnosis, but also for a more appropriate therapy.

Adult↗
PubMed1992

Small-angle synchrotron x-ray scattering reveals distinct shape changes of the myosin head during hydrolysis of ATP.

In the energy transduction of muscle contraction, it is important to know the nature and extent of conformational changes of the head portion of the myosin molecules. In the presence of magnesium adenosine triphosphate (MgATP), fairly large conformational changes of the myosin head [subfragment-1 (S1)] in solution were observed by small-angle x-ray scattering with the use of synchrotron radiation as an intense and stable x-ray source. The presence of MgATP reduced the radius of gyration of the molecule by about 3 angstrom units and the maximum chord length by about 10 angstroms, showing that the shape of S1 becomes more compact or round during hydrolysis of MgATP. Comparison with various nucleotide-bound S1 complexes that correspond to the known intermediate states during ATP hydrolysis indicates that the shape of S1 in a key intermediate state, S1-bound adenosine diphosphate (ADP) and phosphate [S1**.ADP.P(i)], differs significantly from the shape in the other intermediate states of the S1 adenosine triphosphatase cycle as well as that of nucleotide-free S1.

Adenosine Triphosphate↗
PubMed1992

Direct evidence for systemic fibrinogenolysis in a patient with metastatic prostatic cancer.

Although the possible occurrence of systemic fibrinogenolysis has been suggested in patients with metastasising prostatic cancer (MPC), direct evidence is lacking. We report on a patient with MPC whose laboratory data were consistent with hyperfibrinolysis: marked decrease of alpha 2-antiplasmin (AP) level (less than 50% of normal), increase of plasmin-alpha 2-antiplasmin complex, D-fragment of fibrin and fibrinogen degradation products [FDP(D)] and cross-linked fibrin degradation products (XDP). The patient neither showed laboratory nor clinical evidence for consumption coagulopathy except for a slight increase in thrombin-antithrombin III complex level. Immunoblotting of the patient's serum using an anti-fibrinogen antibody revealed the presence of a 250 kDa protein in addition to DD fragments. Following reduction of this protein by 2-mercaptoethanol after extraction from SDS-PAGE gel, gamma-chain of fibrinogen (47 kDa) was found by immunoblotting using a monoclonal antibody recognising a 86-302 residue of the gamma-remnant of fibrinogen. Moreover, the 250 kDa protein did not bind to Sepharose 4B to which a monoclonal antibody recognising the N-terminus of fragment D was conjugated. These findings indicated that this protein was not fragment DY, but rather fibrinogen fragment X. With the retraction of the prostatic tumour by an effective therapy, the patient's AP level increased gradually. When the plasma AP level rose to 60% of normal, the fragment X was no longer detectable. These findings suggested that systemic fibrinogenolysis occurred in the patient with MPC only when AP levels were markedly decreased.

Aged↗
PubMed1992

Efficacy of manidipine on circadian blood pressure in essential hypertension.

The 24-h blood pressure (BP) response to once-daily manidipine monotherapy was examined in an open, nonrandomized study of 17 patients with untreated essential hypertension. Manidipine (10-30 mg) was administered once daily for a minimum of 2 weeks. BP and heart rate (HR) were monitored every 30 min for 48 h by an ambulatory BP monitoring device (ABPM-630, Nippon Colin) before and after therapy. Manidipine significantly (p < 0.005) decreased mean systolic and diastolic BP during the entire 24 h, day-active and night-resting periods. The reduction in both systolic and diastolic BP was consistent throughout the whole day. Manidipine also significantly reduced the fractionated pressure-time indices of both systolic and diastolic BP consistently throughout the 24-h period. The circadian amplitude of BP in hypertensive patients, which was higher than that in normal reference subjects, was reduced by manidipine into the reference range. The acrophase of BP in hypertensive patients, which was similar to the reference value, was not altered by manidipine treatment. Manidipine did not change the mean HR during 24-h, day-active or night-resting periods. Therefore, once-daily manidipine monotherapy showed a consistent antihypertensive effect over 24 h and optimized the circadian amplitude of BP without an increase in HR.

Adult↗
PubMed1992

[The pharmacokinetics of intraperitoneal (IP) carboplatin (CBDCA) and dose-up study of intravenous (IV) cyclophosphamide (CPM) in combination with IP CBCDA for advanced ovarian cancer patients].

The pharmacokinetics of IP CBDCA was compared with IV CBDCA and a dose-up study of IV CPM was performed in combination with 400 mg/m2 IP CBDCA for advanced ovarian cancer patients. The maximum concentration of free platinum (F-Pt) in serum following IP CBDCA administration was approximately 1/3 that of F-Pt following IV CBDCA. F-Pt in serum remained more than 90% of total platinum following IP CBDCA until 12 hours after administration. The t1/2 of F-Pt in serum after IP CBDCA administration was two times longer when compared with t1/2 following IV CBDCA, showing the slow peritoneal clearance of CBDCA. The area under curve (AUC) following IP CBDCA was approximately 67% of AUC following IV CBDCA. Cumulative urinary secretion (CUS) of platinum following IP CBDCA was 37% of CUS after IV CBDCA. The maximum tolerable dose of IV CPM in combination with 400 mg/m2 IP CBDCA was 550-600 mg/m2. The dose limiting factor of this combination therapy was leukocytopenia. Thrombocytopenia was mild in this study. Combination of 400 mg/m2 IP CBDCA and 550-600 mg/m2 seemed to be a tolerable and repeatable therapy for most patients with advanced ovarian carcinoma. Since thrombocytopenia was mild and the pharmacokinetics showed the smaller AUC of free platinum in serum following IP CBDCA, a dose-up study for IP CBDCA should be considered.

Adenocarcinoma↗
PubMed1990

[Post-transfusion hepatitis in operated uterine cancer patients].

We examined the incidence of non-A, non-B hepatitis (NANB) in post-transfusion hepatitis in uterine cancer patients treated by surgery at our hospital. The diagnosis of NANB was based on the diagnostic standards for post-transfusion hepatitis of the Japanese Society of Gastroenterology 1985. In 587 patients with blood transfusions from 1978 to 1988, 80 patients (13.6%) were diagnosed as NANB. The proportions of blood components were, preserved whole blood 44.1%, concentrated red blood cells (CRBC)+ fresh frozen plasma 31.2%, and CRBC 12.8%. The proportions of blood components changed over the years, but since 1987 those of blood components in blood transfusion have been greatly decreased. No difference in the incidence of NANB was seen in patients with up to 10 units of blood transfused, but a high incidence was observed to patients who had received over 10 units. The number of patients treated by radical hysterectomy was five hundred and sixty-two (95.7%) out of a total of five hundred and eighty seven. The average blood loss in the operation was 1,392 ml.

Female↗
PubMed1989

[A case of ovarian germ cell tumor].

PVP (CDDP, VBL, PEP) regimens were administered to a case of ovarian embryonal carcinoma (Higuchi-Kato) Group C, which had metastatic lesions of liver, lumbar bones, and paraaortic lymph nodes soon after operation, with good results.

Adolescent↗
PubMed1988

[Dosimetry by a cellulose triacetate film dosimeter in proton-beam irradiation].

The basic characteristics of cellulose triacetate (CTA) film dosimeter have been investigated with 5, 8, and 15 MeV proton beams. The optical density change per unit absorbed dose for 8 and 15 MeV protons is the same as that given for electron beams, but a little smaller for 5 MeV protons. The CTA dosimeter was found to be useful to obtain dose distributions with high spatial resolution in samples exposed to proton beams.

Cellulose↗
PubMed1988

[Pharmacokinetics of carboplatin (CBDCA) and tissue concentration of platinum in gynecologic organs].

A pharmacokinetics and platinum concentration in the gynecologic organs were measured following the intravenous drip infusion of 375 mg/m2 of CBDCA. Total platinum (TP) in plasma decreased biphasically and free platinum (FP) was almost monophasically eliminated. The t 1/2 of FP was about 51 min. and the percentage of FP out of TP at four hours after administration was more than 92%, which was much higher proportion compared with that of cisplatin (CDDP). A cumulative excretion of platinum in the urine within 24 hours was 69%. The platinum concentration in the benign part of portio and endocervix were higher than that of malignant portion, although there were no significant differences in other pelvic organs such as ovary and tubes. However, pelvic lymph-nodes showed less platinum concentration both in metastatic and non-metastatic tissues. Platinum concentration in the tissue did not change significantly with lapse of time. Bone marrow suppression was observed especially in the patients who had received chemotherapy or radiotherapy. No renal toxicity was observed even without any hydration and gastro-intestinal toxicity was much milder than that of CDDP.

Antineoplastic Agents↗
PubMed1987

Therapeutic effect of hyperthermia combined with chemotherapy on vulvar and vaginal carcinoma.

A clinical trial was performed to investigate the efficacy of hyperthermia in combination with chemotherapy for gynecological malignancies. Sixty-nine patients with vaginal or vulvar malignancies (9 primary vulvar, 3 recurrent vulvar, 11 primary vaginal, 4 primary cervical, 40 recurrent cervical, and 2 recurrent ovarian carcinomas) were treated by thermochemotherapy (42 cases) or chemotherapy alone (27 cases). After treatment, 7 patients underwent surgery and 46 patients irradiation. The chemotherapeutic schedule was mainly a combination therapy with bleomycin and mitomycin C (B-M). Microwaves of 2.45 GHz were applied to induce local hyperthermia. The side effects of chemotherapy were not increased by hyperthermia. The rate of partial response plus complete response increased to 84% (16/19) in primary cancers and 45% in recurrent cancers by hyperthermia, compared to the respective values of 40% (2/5) and 17% (3/17) for chemotherapy alone. However, a satisfactory prognosis cannot be expected with thermochemotherapy, unless additional treatments are performed. Subsequent surgery or radiation treatment improved the progression-free interval.

Adult↗