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Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 937 records · Page 52Linked to original sources
PubMed1990

Increased plasma plant sterol levels in heterozygotes with sitosterolemia and xanthomatosis.

Plasma sterol levels in a family of sitosterolemia and xanthomatosis were determined by a high performance liquid chromatography. Three affected siblings manifested marked xanthomatosis including subcutaneous soft tissues and generalized atherosclerosis. Two other siblings as well as children of the patients did not show such clinical symptoms and signs. Plasma levels of cholesterol, sitosterol, campesterol, and cholestanol in three affected subjects were 190 +/- 18.5, 25.9 +/- 11.6, 16.1 +/- 7.8, 1.84 +/- 0.92 mg/dl (mean +/- SD), respectively. Four daughters of the affected subjects, who should be considered as obligatory heterozygotes, showed moderately increased levels of these sterols (195 +/- 41.7, 1.33 +/- 0.44, 1.56 +/- 0.69, 0.80 +/- 0.28 mg/dl), which were significantly higher than those of normal subjects. Treatment with cholestyramine had little effect on the increased plasma plant sterol levels, but markedly decreased plasma cholestanol concentrations in two affected siblings. This report presents the clinical features of the patients with sitosterolemia and xanthomatosis and also demonstrates that heterozygotes with this disorder have increased plasma levels of plant sterols as well as cholestanol, and suggests that this rare disease might be inherited as an autosomal co-dominant trait in certain cases. The data also indicate that cholestyramine administration was not effective in this family for treatment of sitosterolemia.

Adult↗
PubMed1990

[Effect of topical injections of native alpha-interferon (HLBI) in the treatment of skin lesions of adult T cell leukemia: report of a case].

A case of adult T cell leukemia associated with prominent skin infiltrations was treated with native alpha-interferon (Human lymphoblastoid interferon; HLBI). Although previous therapy with intramuscular injections of HLBI showed no effect on the skin lesions, this time topical injections of HLBI induced regression and disappearance of skin lesions within one month. Cellular immunity in this patient evaluated by PPD reaction and PHA blastoid transformation had been depressed at the time of systemic administrations of HLBI, but at the beginning of the topical injections of HLBI, they were within normal range. CD4/CD8 ratio reversed to 0.86 after topical injections of HLBI, suggesting the effect of HLBI on cytotoxic T lymphocyte activation. Thus, topical subcutaneous injections of HLBI may be an alternative form of therapy for ATL skin infiltrations when systemic HLBI administration is not effective, especially for the patient with normal cellular immunity.

Aged↗
PubMed1990

[The hypertensive effect induced with angiotensin II and the physiological and pharmacokinetic aspects of two-route chemotherapy using CDDP and STS].

Two-route chemotherapy of CDDP and STS was performed in 16 postoperative patients with ovarian cancer under the hypertensive condition of 20 minutes induced with angiotensin II (AT-II). Plasma total CDDP and filtrable CDDP levels serially determined at 15 and 30 minutes after intraperitoneal administration of CDDP (150 mg/body) were significantly higher than under the same condition except for using AT-II. The extreme vasoconstriction in the kidney and other organs during AT-II induced hypertension would protect these organs from CDDP induced toxicities. Furthermore, STS infused immediately after the cessation of AT-II could neutralize the CDDP preventing the occurrence of toxicities. The elevating plasma levels of CDDP might be beneficial to enhance the anticancer effects of CDDP, since the blood flow in cancer tissue was increased during AT-II induced hypertension.

Angiotensin II↗
PubMed1989

Beta 2-microglobulin decrease in cerebrospinal fluid from parkinsonian patients.

A sandwich enzyme immunoassay (EIA) was established by using purified beta 2-microglobulin (beta 2-MG) as a standard protein and a polyclonal antibody raised against human beta 2-MG. The EIA was applied for the measurement of beta 2-MG levels in human cerebrospinal fluid (CSF) from parkinsonian patients and control patients devoid of neurological diseases. beta 2-MG contents in CSF of the control group and the parkinsonian group were 1.81 +/- 0.11 micrograms/ml CSF and 0.63 +/- 0.09 microgram/ml CSF, respectively. Thus, beta 2-MG content in CSF was reduced in parkinsonian patients to less than 35% of the control value (P less than 0.005). We had previously reported that the activity and content of dopamine beta-hydroxylase (DBH) were decreased in CSF from parkinsonian patients. A significant positive correlation (r = 0.87) was observed between the beta 2-MG content and DBH activity for CSF from 45 patients. These results suggest a probable link between an immunological change and the changes in catecholaminergic neurons in Parkinson's disease.

Adult↗
PubMed1989

Serum dipeptidyl peptidase activities as a possible marker of oral cancer.

Serum glycyl-l-prolyl 4-methyl-coumaryl-7-amide (gly-pro-MCA) hydrolase (DPP IV) and L-lysyl-L-alanyl beta-naphthylamide (lys-ala-beta NA) hydrolase (assumed to be DPP II) activities were measured in patients with oral squamous cell carcinoma and healthy subjects. The mean serum DPP IV activity of all cancer patients was significantly (P less than 0.001) decreased, compared with that of healthy subjects. Although there was no significant difference between the stages by International Union Against Cancer (UICC) classification (1978), DPP IV levels tended to change dynamically, reflecting the clinical status during therapies. The serum DPP IV activity of patients with a fair prognosis was significantly elevated toward the normal range, whereas the activity of patients with a poor prognosis was significantly decreased (P less than 0.05). In contrast, the mean serum lys-ala-beta NA hydrolytic activity of cancer patients was significantly (P less than 0.001) increased, compared with that of healthy subjects, and was changed reciprocally to DPP IV activity. The correlation of these two serum enzyme activities with tumor weights also was observed in animal models using nude mice transplanted with human KB carcinoma cells and hamsters transplanted with BHK21 cells. These results indicate that these serum enzyme levels may become an aid for the diagnosis of malignant tumors and for estimating the prognosis of the patients.

Adult↗
PubMed1989

Difference in the in vitro uptake of bromodeoxyuridine between liver cirrhosis with and without hepatocellular carcinoma.

With the aim of examining increasing deoxyribonucleic acid (DNA) synthesis of liver cirrhotic tissue when hepatocellular carcinoma (HCC) is developing, bromodeoxyuridine labeling indices (BrdU LI) of liver biopsy specimens from 19 control cirrhotic (control LC) patients without HCC, 19 cirrhotic patients with HCC, and from six control subjects were examined using an in vitro labeling technique. The mean BrdU LI +/- SD of HCC cancerous portion, HCC non-cancerous cirrhotic portion, control LC, and of control subjects were 7.2 +/- 2.9%, 3.3 +/- 1.5%, 2.1 +/- 1.7%, and 0.25 +/- 0.09%, respectively. Interesting enough, there was a significant difference (P less than 0.05) between the non-cancerous cirrhotic portion and control LC. Although all 17 non-cancerous cirrhotic portion belonged to the high LI group (greater than or equal to 1.5%), 10 of 19 in the control LC belonged to the low LI group (less than 1.5%) (P less than 0.001). The authors conclude that HCC would develop in the cirrhotics with high DNA synthetic potency.

Adult↗
PubMed1989

Magainin 1-induced leakage of entrapped calcein out of negatively-charged lipid vesicles.

Effects of magainin 1, a novel antimicrobial peptide, on the permeability of lipid vesicles were investigated by using calcein as a trapped fluorescent marker. Magainin 1 induces the leakage of calcein specifically out of negatively-charged vesicles. The peptide binds to bovine brain phosphatidylserine sonicated vesicles according to the Langmuir isotherm with a binding constant of 3.8.10(5) M-1 and a binding-site number of 0.10 per lipid molecule. The leakage seems to occur at a critical binding number of approx. 0.03 per lipid molecule. A circular dichroism study revealed that magainin 1 conforms mainly to an unordered structure both in an aqueous solution and in the presence of egg yolk phosphatidylcholine vesicles, whereas to an amphiphilic helix with the phosphatidylserine vesicles. In conclusion, magainin 1 interacts with acidic lipids through electrostatic interactions followed by hydrophobic interactions to form an amphiphilic helix, inducing the leakage.

Animals↗
PubMed1989

An expert system for early detection of cancer of the breast.

In order to study the relevancy of exploring complex expert systems for use by the lay public, an expert system for the early detection of cancer of the breast has been developed. The system consists of a conversion between a microcomputer and a woman who is anxious about breast cancer. The conversation is divided into two parts: one is listening to the woman's symptoms regarding the breast then giving advice, the other is an explanation of breast cancer and how to detect it in its early stages. After listening to the woman's symptoms, the computer presents its conclusion and suggests courses of action the woman should take. The system is written in Prolog. It was tried by women in a small town at a festival for health, by female patients who visit our hospital, and received a positive reaction.

Algorithms↗
PubMed1989

Homozygous hypobetalipoproteinemia with spared chylomicron formation.

Thirteen members of a family carrying a gene for pedigree of hypobetalipoproteinemia were analyzed for lipoprotein compositions, apolipoprotein (apo) B levels, and apo B isoforms. Judging from low density lipoprotein (LDL)-cholesterol (Chol) and apo B levels, a 75-year-old proband, a father who died of unknown fever, thrombopenia, and anemia, and his wife were heterozygous for hypobetalipoproteinemia. The proband had ataxic movement of hands and gait disturbance in later life. Three of four living siblings had extremely low levels of LDL-Chol (6 mg/dL) and LDL-apo B (2 mg/dL), and were postulated to have homozygous hypobetalipoproteinemia. Electrophoresis revealed marked deficiency of apo B-100, although trace amounts were noted in LDL. In contrast, apo B-48 was present in chylomicrons obtained after a fatty meal in the two patients with homozygous hypobetalipoproteinemia, indicating a selective deficiency of apo B-100 but not apo B-48. The defect in these patients seemingly is different from abnormal apo B-37 reported recently for a family with hypobetalipoproteinemia. Clinically, acanthocytotic red blood cells (8% to 12%), fatty liver, and low levels of serum lipid-soluble vitamins A and D were noted in homozygotes. One heterozygous sibling had 26 mg/dL LDL-Chol and 5 mg/dL LDL-apo B levels. All seven subjects in the third generation had low levels of Chol (85 to 140 mg/dL), LDL-Chol (40 to 63 mg/dL) and LDL-apo B (10 to 20 mg/dL). They also showed mild acanthocytosis (0.5% to 2%) and a decrease of fat-soluble vitamins in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Acanthocytes↗
PubMed1989

Immunocytochemical demonstration of S phase cells by anti-bromodeoxyuridine monoclonal antibody in human prostate adenocarcinoma.

Using a monoclonal antibody to bromodeoxyuridine and immunohistochemistry, we measured the incorporation of this thymidine analogue into the deoxyribonucleic acid of human prostate adenocarcinoma cells exposed in situ. Fifteen patients with prostate cancer were given an intravenous infusion of 500 mg. bromodeoxyuridine at needle biopsy to label tumor cells in the deoxyribonucleic acid synthesis phase (S phase). The tumor specimens were fixed with 70 per cent ethanol, embedded in paraffin, sectioned and stained by an indirect immunoperoxidase method using anti-bromodeoxyuridine monoclonal antibody as the first antibody. The results showed that this method demonstrated bromodeoxyuridine-labeled nuclei satisfactorily in tissue section. The bromodeoxyuridine labeling index, S phase fraction, was determined by counting the number of bromodeoxyuridine-labeled cells in the tissue sections. Grade 3 tumors averaged 4.37 +/- 0.48 per cent labeling versus 2.41 +/- 0.49 per cent in grade 2 tumors, and grade 1 tumor in the series had an S phase fraction of 1.36 +/- 0.39 per cent. The average S phase fractions for single gland, cribriform, fused and medullary were 1.16, 2.30, 3.74 and 4.95 per cent, respectively. The results obtained with S phase fraction measured with bromodeoxyuridine labeling proved to be comparable to the results of histological grade and growth pattern. Thus, the higher S phase fraction may indicate biological malignancy. Moreover, the degree of heterogeneity concerning S phase fraction distribution within prostate cancer tissue could be compared to the morphological appearance. Our preliminary results suggest that the measurement of bromodeoxyuridine labeling index in prostate cancer may prove to be a new objective and quantitative assay of biological potential of individual tumor.

Adenocarcinoma↗
PubMed1989

Prostaglandin-mediated suppression of in vitro growth of erythroid progenitor cells.

In vitro hematopoiesis was evaluated in 37 patients with chronic renal failure (CRF) who developed moderate to severe anemia in order to clarify the relationship between the growth of erythroid progenitor cells and CRF-associated anemia. Bone marrow cells from these patients were cultured in the presence of recombinant erythropoietin. Both early and late erythroid progenitor cells (BFU-E and CFU-E) were significantly suppressed in patients with CRF compared to those in normal controls, while myeloid progenitor cells (GM-CFC) remained normal. Suppression of CFU-E was shown to be mediated by prostaglandin(s) secreted from bone marrow adherent cells. Furthermore, the suppression of CFU-E was inversely correlated with concentrations of uremic serum or parathyroid hormone added to the assay system. These observations suggest a possibility that late erythroid progenitor cells may be preferentially suppressed by the network consisting of parathyroid hormone, bone marrow adherent cells and prostaglandin(s).

Anemia↗
PubMed1989

Positive foci of glutathione S-transferase placental form in the liver of rats given furfural by oral administration.

We observed GST-P-positive liver foci in rats during the course of developing liver cirrhosis by oral administration of furfural, an organic solvent. Male Wistar rats were given furfural-containing diet (20-30 mg/kg diet) for 15-150 days, and killed 14 days after terminating furfural feeding. Immunohistochemical investigation of GST-P-positive liver foci which appeared in rats fed furfural for more than 30 days revealed an increase in number and size of the foci in proportion to the duration of furfural administration. Since furfural is known not to be carcinogenic in rats, this finding will be helpful to understand the enhancing effect of furfural-induced cirrhosis on chemical hepatocarcinogenesis.

Administration, Oral↗
PubMed1989

Estimations of the S phase fraction in situ in transitional cell carcinoma of the renal pelvis and ureter with bromodeoxyuridine labelling.

This report concerns the estimation of the S phase fraction (SPF) in situ and its value in predicting the malignant potential of transitional cell carcinoma of the renal pelvis and ureter. Eighteen patients with transitional cell carcinoma of the renal pelvis and ureter were given a 0.5 h intravenous infusion of the thymidine analogue bromodeoxyuridine (BrdU) (500 mg) at the time of surgery to label tumour cells in the DNA synthesis phase. The tumour specimens were stained by an indirect immunoperoxidase method using anti-BrdU monoclonal antibody as the first antibody. The BrdU labelling index, S phase fraction, was determined by counting the number of bromodeoxy-uridine labelled cells in the tissue sections. All grade 1 tumours had an S phase fraction lower than 10%. The average S phase fraction for non-invasive tumour (12 cases) and invasive tumour (6 cases) were 9.7 and 20.9%, respectively. Two patients with rapid spread of ureteric tumour showed an S phase fraction of 18.4 and 22.3%. The results obtained with the S phase fraction were comparable with histological tumour grade and invasive potential. The higher S phase fraction may indicate greater biological malignancy. We believe that determination of the S phase fraction of transitional cell carcinoma of the renal pelvis and ureter offers a new objective and quantitative assay of the biological potential of individual tumours and might have practical value in their management.

Bromodeoxyuridine↗
PubMed1989

Antiulcer activities of glycyrrhetinic acid derivatives in experimental gastric lesion models.

Glycyrrhetinic acid (Ia) and eighteen related derivatives were examined for antiulcer activity using stress-induced gastric lesions (restraint plus water immersion at 25 degrees C) in mice and rats as screening tests. Among the compounds tested, dihemiphthalate derivatives of 18 alpha- or 18 beta-olean-12-ene-3 beta,30-diol (IV, IIId), 18 beta-olean-9(11)12-diene-3 beta,30-diol (VIc), and olean-11,13(18)-diene-3 beta,30-diol (VIIc) showed potent inhibition of gastric lesion formation at a dose of 12 or 25 mg/kg (p.o.); carbenoxolone sodium (Ib) significantly suppressed the lesion formation at a dose of 500 mg/kg (p.o.). Further evaluation of the antiulcer activity was carried out mainly for compound IIId. Compound IIId (p.o.) prevented the formation of indomethacin-induced or 0.6 N HCl-induced gastric lesions; the latter antiulcer effect was noted even in the combined treatment with indomethacin, suggesting that the effect occurs independently of endogenous prostaglandins. In contrast, compound IIId had no preventive effect against Shay rat ulcer when intragastrically (i.g.) administered; further, no antisecretory effect was seen by i.g. application in pylorus-ligated rats. Administration of compound IIId for 2 weeks accelerated the healing rate of acetic acid-induced gastric ulcer in rats. No significant change in urine excretion was observed after its consecutive administration for 3 d. These results suggest that dihemiphthalate derivatives (IIId, IV, VIc, VIIc) may produce a strong antiulcer activity, probably by strengthening some gastric mucosal defensive mechanism.

Animals↗