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Biomedical subjects

O Abe

Publications and source records attributed to O Abe.

18 recordsLinked to original sources

Endogenous urinary 3-hydroxyproline has 96% specificity and 44% sensitivity for cancer screening.

A method for determining the endogenous urinary excretion levels of both 3-hydroxyproline and 4-hydroxyproline that may be useful for cancer screening of the general population and at the workplace is evaluated in this report. The excretion levels of 3-hydroxyproline and 4-hydroxproline were estimated in 97 patients with cancer and in 99 patients with various nonmalignant diseases and were compared with those of 211 healthy persons. Measurable 3-hydroxyproline peaks (by amino acid autoanalyzer) were absent from 93 samples from 211 healthy persons (44%), 50 of 99 patients with nonmalignant disease (50%), and 10 of 96 patients with cancer (10%). The levels of both 3-hydroxyproline and 4-hydroxyproline in cancer patients were significantly higher than those in healthy persons (p < 0.001 and p < 0.01, respectively) and those in patients with nonmalignant diseases (p < 0.05 and p < 0.01, respectively). Cancer patients were classified into three groups according to grade of cancer growth and invasion. The sensitivity of 3-hydroxyproline was 44% and higher than that of 4-hydroxyproline for the detection of stage II cancers (no distant metastasis); the sensitivities of both hydroxyprolines for the detection of stage I (very early cancer) were low. The specificity of these assays for healthy persons and patients with nonmalignant disease was 96% and 92% for 3-hydroxyproline, and 97% and 79% for 4-hydroxyproline, respectively. Urinary 3-hydroxyproline level should be further investigated as a cancer screening method for healthy persons in the community or the workplace, but appears unlikely to detect many cancers in the earliest stages.

Adult

[Phase I study of NK 622 (toremifene citrate)].

A phase I study of NK 622 (toremifene citrate), a novel antiestrogen, was conducted in female patients with cancer. Patients received a single oral dosing or daily once oral dosing for five consecutive days. Any adverse effects were not experienced in the single dosing of 40 or 60 mg of NK 622. In the daily administration of 10, 20, 40, 60, 120, 240 and 480 mg/day, one of three patients who received 20 mg/day experienced grade 1 anorexia, three of four patients received 240 mg/day experienced adverse effects: Grade 1 leukopenia in one patient, Grade 1 general hot flush in one patient, and Grade 1 nausea, hot flush in the face and vertigo, Grade 2 anorexia, fatigue, dull headache and general hot flush in another one patient. These symptoms recovered to normal levels after treatment. Serum hormone levels were examined in postmenopausal patients, and a significant increase of the sex hormone binding globulin level was observed in the patients received 120 and 240 mg/day doses. Serum levels of NK 622 determined as free base (TOR) reached the peak levels in 2 to 4 hours after administration on the 1st and 5th day in daily treatment, while a metabolite N-demethyltoremifene (TOR-1) reached the peak level in 4 to 170 hours. Maximum serum levels and area under the concentration versus time curves of TOR and TOR-1 increased dose-dependently. These values also increased by repetition of the treatment. Half-lives of TOR and TOR-1 in serum ranged in 74.5 to 148.9 hours and 154.1 to 653.1 hours, respectively. From these results, it was concluded that safety and efficacy of NK 622 should be assessed by using 240 mg or less doses in clinical phase II studies where breast cancer patients received long term treatment with NK 622.

Administration, Oral

Isolation and activities of the trypsin-modified Vicia angustifolia proteinase inhibitor lacking carboxyl-terminal hexapeptide.

The Vicia angustifolia proteinase inhibitor was incubated with p-toluenesulfonyl-L-phenylalanine chloromethyl ketone-trypsin (EC 3.4.21.4) and a main product was isolated. The purified product was different to the first trypsin-modified V. angustifolia inhibitor. The C-terminal residues of the new derivative were arginine, which was also the C-terminal of the cleaved antitryptic site; lysine was a newly exposed C-terminal. These results suggest that the new derivative lacks the C-terminal portion of the native inhibitor, which has asparagine at its C-terminus. The liberated C-terminal peptide had the following amino acid sequence: H-Glu-Glu-Val-Ile-Lys-Asn-OH. The derivative lacking the C-terminal hexapeptide still possesses inhibitory activities against trypsin and alpha-chymotrypsin (EC 3.4.21.1), however, its antichymotryptic activity was inactivated by incubation with chymotrypsin at pH 8.0.

Chymotrypsin

Plasma IgA, IgG and IgM and their relationship to breast cancer in British, Japanese and Hawaiian-Japanese women.

The plasma levels of immunoglobulins IgA, IgG and IgM have been measured in 35 British, 44 Hawaiian-Japanese and 37 Japanese healthy adult women. Previous investigations showed that the mean levels of all three immunoglobulins were higher in Japanese than in British normal women. The present study finds that Hawaiian-Japanese women have "Japanese" levels of IgA, "British" levels of IgM and are intermediate for IgG. Thus, plasma IgM concentrations correlate with breast cancer incidence rates in the three racial groups and the reduced amounts of plasma IgM found in Japanese patients with breast cancer support this association.

Asian People

Prostaglandin-induced eosinopenia in splenectomized rats.

PGE1, PGE2, and PGF2alpha over a dose range of 1 to 50 microgram/kg decreased the number of circulating eosinophils in splenectomized rats. Pretreatment with a beta-blocking agent, propranolol, did not alter this effect, but adrenalectomy eliminated it. Anterior hypothalamic destruction also abolished eosinopenia induced by PGE1 and PGF2alpha but not that induced by PGE2.

Adrenalectomy

Trypsin reactivity site of the Vicia angustifolia proteinase inhibitor.

Trypsin [EC 3.4.21.4] modified (reactive site cleaved) Vicia angustifolia proteinase inhibitor was prepared at pH 3 with a catalytic amount of trypsin and purified using columns of Sephadex G-50 and DEAE-Sephadex A-25. The modified inhibitor, which still retained antitryptic activity, lost its activity upon treatment with carboxypeptidase B or citraconic anhydride. End-group analyses revealed that the carboxyl-terminal Arg and the amino-terminal Ser residues were newly exposed end-groups in the modified inhibitor. It takes a much longer incubation time (about 1 h) to exhibit the maximal inhibitory activity against trypsin. Reduction and carboxymethylation of the modified inhibitor produced two fragments on Sephadex G-50 chromatography. The smaller fragment consisted of about 32 amino acid residues and possessed a new carboxyl-terminal Arg residue. The larger fragment consisted of about 80 residues and possessed a Ser residue at its amino-terminus. These results indicate that the small fragment was derived from the amino-terminal portion of the modified inhibitor and the large fragment from the carboxyl-terminal. It is also concluded that an Arg-Ser bond is the reactive site as well as the inhibitory site of the V. angustifolia inhibitor against trypsin. The sequence around the antitryptic site exhibits high degrees of homology with other double-headed inhibitors of legume origin, such as the Bowman-Birk inhibitor, lima beam inhibitor, and the major inhibitor in chick-peas.

Amino Acid Sequence

A comparative study of some pathologic features of mammary carcinoma in Tokyo, Japan and New York, USA.

Epidemiologic and clinical studies conducted in the past 15 years have demonstrated striking differences in the biology of mammary carcinoma among Japanese and American women living in their native countries. These variations have, in part, been related to some differences in the characteristics of the primary tumors between the two groups. As part of a collaborative study we have had an opportunity to compare the stage of disease and to examine and compare histological sections of patients with breast carcinoma treated in 1973-74 at the National Cancer Center Hospital (NCH) in Tokyo and in 1974 at the Memorial Hospital (MH) in New York. The former group consisted of 216 and the latter of 555 carcinomas. Fewer patients in each group had axillary metastases than reported in a prior study of patients treated at MSKCC and in Tokyo 20 to 30 years earlier. Negative axillary nodes were now found in 58% of the MH patients and in 63% of women treated at the NCH. The magnitude of improvement in stage relative to the prior report was similar in both groups. However, it would appear that the change occurred mainly from the mid-1950s to the 1960s in New York and approximately 10 years later in Tokyo. Results of this study confirming prior reports were: (1) higher frequency of colloid and of medullary carcinoma with lymphoid stroma and lesser frequency of lobular carcinoma in the Japanese patients; (2) more intense lymphoid infiltrate in and around primary tumors in Japanese women; (3) higher frequency of rounded or circumscribed tumors in Japanese women; and (4) the more frequent occurrence of intralymphatic tumor emboli within the breast in American women. The difference in the frequency of lobular carcinoma was less striking when comparison was limited to patients with unilateral carcinoma.

Adenocarcinoma, Mucinous