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Biomedical subjects

Y Tsuji

Publications and source records attributed to Y Tsuji.

At least 343 records · Page 19Linked to original sources

Rapid detection of a point mutation in thyroid-stimulating hormone beta-subunit gene causing congenital isolated thyroid-stimulating hormone deficiency.

Previous study showed that congenital isolated TSH deficiency in Japan is resulted exclusively from a G-A transition at nucleotide 145 in exon 2 of the TSH beta-subunit gene. All reported cases were from the inbred in Shikoku Island. We describe here a 10-year-old boy with hereditary TSH deficiency in the same area. The patient was born with a weight of 3,225 g to non-consanguineous parents. Evaluation at age 2 months revealed typical manifestations of cretinism without goiter. Serum T4, T3, and TSH values were 2.53 micrograms/dl, 107 ng/dl, and 0.5 microU/ml, respectively. A TRH stimulation test showed no increment of serum TSH value. Other anterior pituitary hormone levels were all within the normal range. Two oligonucleotide primers T1a and T1b were synthesized according to the sequence data. Amplified 169 bp nucleotides in exon 2 of the TSH beta gene with this primer set were digested with MaeI. Both the phenotypically normal brother and normal controls showed only the 169 bp fragment, whereas the proband showed 140 and 29 bp fragments and both parents showed three fragments; 169, 140, and 29 bp. These results were consistent with the point mutation of TSH beta gene in Japanese patients with congenital isolated TSH deficiency. Our PCR method with MaeI digestion contributes to the rapid detection of the homozygous patient and the heterozygous carrier.

Child↗

Effect of platelet-activating factor on cortisol and corticosterone secretion by perfused dog adrenal.

Administration of platelet-activating factor (PAF) to perfused adrenal increased cortisol and corticosterone secretion. With hexadecyl PAF (C16PAF; 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine), the increase was significant at 1 nM and maximal at 10 nM. The responses to 10 nM octadecyl PAF (C18PAF; 1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine) were one fourth of those to 10 nM C16PAF. The addition of C16PAF to dispersed adrenal cells significantly increased cortisol and corticosterone production at 0.1 nM and 10 nM, respectively. C16PAF was about 1000 times more potent than histamine on a molar basis in respect to cortisol response in both perfused adrenal and dispersed adrenal cells. The results suggest that PAF induces cortisol release from dog adrenal.

Adrenal Cortex↗

Successful treatment of a case of hepatocellular carcinoma with tumor necrosis factor and local hyperthermia.

A case of unresectable hepatocellular carcinoma which responded favorably to combined therapy with tumor necrosis factor (TNF) and local hyperthermia is reported. A 58-year-old man was admitted to our hospital in June 1988 for treatment of hepatocellular carcinoma affecting S4 and S8. After three sessions of transcatheter arterial embolization (TAE) therapy, the serum alpha 1-fetoprotein level decreased, and a reduction in the size of the lesions was also noted. Thereafter, the patient received local hyperthermia once a week (60 minutes of irradiation from a Thermotron-RF8 at 1,100W), but the alpha 1-fetoprotein level increased again in February 1989. On examination, enlargement of the S8 lesion and a new nodule in S7 were recognized. Since TAE was contraindicated due to liver dysfunction, human recombinant TNF (1 x 10(6)U) was given by intravenous infusion together with local hyperthermia once a week. Eight sessions of the combined therapy reduced the serum alpha 1-fetoprotein level markedly (7,512.0 to 2,782.0 pg/ml) and after eighteen sessions, 58.1% regression of tumor size (partial response) on computed tomography scans was observed. This anecdotal case supports previous experimental evidence suggesting that TNF plus hyperthermia may be effective for treating unresectable hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

Sperm immobilizing and fertilization-blocking monoclonal antibody 2C6 to human seminal plasma antigen and characterization of the antigen epitope corresponding to the monoclonal antibody.

A monoclonal antibody (Mab 2C6) with strong sperm immobilizing and agglutinating activities was generated by cell fusion between spleen cells from a mouse immunized with human seminal plasma (HSP) and mouse myeloma cells. It also showed a strong inhibitory effect on human sperm-egg interaction. The corresponding antigen was present on the whole surface of ejaculated spermatozoa. In male genital organs, immunostaining with Mab 2C6 was observed in epididymis and seminal vesicle but not in testis. By Western blotting, immunostaining with Mab 2C6 was detected around the 15-25 kDa region under both reducing and non-reducing conditions. The antigen corresponding to Mab 2C6 was susceptible to treatment with periodate or trifluoromethanesulfonic acid. The antigenic activities were slightly increased by treatment with neuraminidase but reduced by further treatment with glycosidases. Enzymatic digestions with pronase and papain also reduced the antigenic activities. The antigen molecules exhibited a strong binding affinity to RCA lectin. These results indicated that Mab 2C6 recognized one of the components which might be secreted from epididymis or seminal vesicle and bind to ejaculated spermatozoa as a sperm coating antigen. The corresponding antigen seems to be a glycoprotein and its carbohydrate moiety has an important role in the conformation of the antigen epitope.

Animals↗

Antitumor activity of a novel chimera tumor necrosis factor (TNF-STH) constructed by connecting rTNF-S with thymosin beta 4 against murine syngeneic tumors.

We have shown the in vivo usefulness of a novel chimera tumor necrosis factor (TNF), called rTNF-STH, which was constituted with human thymosin beta 4 and recombinant human TNF-SAM1. Tumor necrosis was induced by intravenous injection of a smaller amount of rTNF-STH (1 x 10(3) U/mouse, 0.67 microgram/mouse) than rTNF-alpha or rTNF-S (1 x 10(4) U/mouse, 2.5-5 micrograms/mouse). Significant antitumor effects of rTNF-STH to Meth A fibrosarcoma, B16 melanoma, MH134 hepatoma, or Lewis lung carcinoma (3LL) were observed by systemic injection of rTNF-STH at the maximum tolerable dose of 1 x 10(4) U/mouse (6.7 micrograms/mouse); this dose did not cause regression of tumors by conventional rTNF-alpha. rTNF-STH showed a significant prolongation of its half-life in serum. The average calculated half-life of the chimera protein is about 110 min, which is 15 times longer than that of original TNF-SAM1 (7.5 min). On the basis of this prolongation of half-life of rTNF-STH and its efficient hemorrhagic necrotic activity, the antitumor effect of rTNF-STH--as compared with that of the known TNF species--is discussed. Findings indicate that use of the chimera protein to alter the N-terminal region of TNF may be a promising approach to obtain molecules that more favorably attack tumors and other diseases than conventional rTNFs.

Animals↗

Deletion pattern in the 21-hydroxylase gene detected by polymerase chain reaction.

In order to detect deletion mutation and/or gene conversion in the 21-hydroxylase (21-OH) gene, we adopted the polymerase chain reaction (PCR) method followed by electrophoresis. Two pairs of synthesized primers, Ta/1b and 2a/2b, each corresponding to the sequence at the 5' portion of the 21-OH gene, were set for PCR. TaqI digestion of amplified DNA from normal individuals using Ta/1b as primers gave the following three fragments: an active 21-OH gene-derived 559 bp fragment, and pseudogene-derived 364 and 195 bp fragments. Of 16 patients with 21-hydroxylase deficiency (21-OHD) studied, 6 (37%) lacked the 559 bp fragment. These 6 patients also lacked both the 331 and 117 bp MvaI fragments of the PCR product which were obtained with the primers 2a/2b, both being derived from the active 21-OH gene. These results indicate that 6 of the 16 patients have either deletion of the 21-OH gene or conversion of the gene to its tandemly located pseudogene. The method described here provides a rapid diagnosis of 21-OHD.

Adrenal Hyperplasia, Congenital↗

Experimental studies on coronary laser angioplasty.

To establish the method of coronary laser angioplasty using the argon laser, we investigated the optimal condition of laser ablation and the relationship between the size of laser probe and the diameter of the vessel. First, the relationship between laser energy and tissue reaction to the laser was examined using human cadaveric arteries. Subsequently, we recognized that repeated laser ablation is the optimal method with each shot being limited to 5 10 watts (W) in output and 2 seconds of ablation time when using a metal tip probe (MTP) of 1.5 mm in diameter. According to the experimental condition described above, we examined the response of normal coronary arteries to the laser in vivo. If the size of MTP was not suitable for the diameter of the vessel, thermal constriction of the coronary artery was observed; MTP/vessel diameter ratio should be 0.7 or less to avoid vessel constriction by thermal damage from the laser. Neither perforation nor spasm of the coronary artery was found in this experiment. In addition, the ablated area on the coronary artery was healed completely without thrombus formation and coronary stenosis, and it was covered with new endothelium 8 weeks after laser thermal ablation.

Angioplasty, Balloon, Coronary↗

A case of neonatal McCune-Albright syndrome with Cushing syndrome and hyperthyroidism.

We describe a female newborn infant with McCune-Albright syndrome. In addition to the cutaneous pigmentation, she had apparent manifestations of hyperthyroidism and Cushing syndrome since birth. X-ray examinations showed many scattered lucencies in multiple bones. Endocrinological findings were as follows: serum T 4 276 nmol/l; free T 4 125 pmol/l; TSH less than 1 mU/l; serum cortisol greater than 2210 nmol/l; plasma ACTH less than 10 pg/ml; urinary free cortisol 865 nmol/day; estradiol 0.36 nmol/l. Regardless of treatment with antithyroid drugs and an inhibitor of 3 beta-hydroxysteroid dehydrogenase, the patient died of cardiac failure at the age of 4 months. Autopsy findings included a follicle cyst in the right ovary and multinodular hyperplasia in the thyroid and both adrenals. To our knowledge such a severe neonatal form of McCune-Albright syndrome has not been described in the literature.

Adrenal Cortex↗

Minimal deviation adenocarcinoma (adenoma malignum) of the uterine cervix associated with mucinous ovarian carcinoma.

A case of minimal deviation adenocarcinoma (MDA: adenoma malignum) of the uterine cervix associated with ovarian mucinous carcinoma is documented. Diagnosis was possible only retrospectively after surgery by histological examinations including immunohistochemistry. Three courses of chemotherapy, consisting of cisplatin, doxorubicin and ifosfamide, could eradicate the residual diseases of ovarian cancer from the peritoneal cavity, but was insufficiently effective against lymph node metastases of the cervical MDA. Subsequently, the disease flared-up retroperitoneally during the sixth course of treatment course, suggesting chemoresistance developed, and further chemotherapy using different regimens were not effective. Therapeutic intractability of MDA as well as the diagnostic difficulty was again emphasized.

Adenocarcinoma↗

Effects of transcatheter hepatic arterial embolization on coagulation and fibrinolysis in patients with hepatocellular carcinoma.

The changes in coagulation and fibrinolysis were studied in cases of hepatocellular carcinoma with (n = 20) and without (n = 8) transcatheter hepatic arterial embolization (TAE). The plasma levels of thrombin-antithrombin III complex (TAT) and alpha 2 plasmin inhibitor complex (PIC) were significantly elevated after TAE, concurrently with a decrease in antithrombin III and antiplasmin (alpha 2-plasmin inhibitor) levels. The elevation of TAT was most significant (2.4-fold of the pre-TAE level) on day 3, whereas that of PIC was relatively less (1.3-fold on day 3). Tissue plasminogen activator in blood was also significantly increased on day 1, but it was decreased thereafter, although plasminogen activator inhibitor (PAI) remained high for at least 7 days after TAE. In contrast, such hematological changes were not observed in patients without TAE. Thus, both coagulation and fibrinolysis were activated after TAE, but its effect on fibrinolysis was less prominent, due probably to the increased synthesis of PAI.

Adult↗

[The distribution of S-100 protein positive chondrocytes in the human articular cartilages under aging or diseased conditions].

There have been few reports on the localization of S-100 protein positive chondrocytes in the human articular cartilages. We studied 59 articular cartilages of the aged subjects, 65 osteoarthritic (OA) and 39 rheumatoid arthritic (RA) articular cartilages, to detect the histological localization of S-100 protein using immunoperoxidase method (ABC). The results obtained from normal cartilages demonstrated strongly positive cells representing hypertrophic chondrocytes in the perivascular areas of the neonatal articular cartilage and in the deep zone of the infant articular cartilage. The moderately positive cells were found in the intermediate zone of infant and adult articular cartilages. In mild OA, there were many positive chondrocytes in the intermediate zone with erosion of the surface layer, while in moderate or severe OA many strongly positive cells were found in clusters. The hypertrophic cells in the metaplastic cartilage arising from bone marrow in subjects with severe OA, or from pannus after RA were also positive. It is therefore, suggested that S-100 protein may be correlated with the metabolic activity of the cartilage matrix such as collagen and proteoglycan, as reported in the literature. S-100 protein further, appears to be useful for evaluating histologically the activity of cartilage repair in the pathologic human articular cartilages.

Adolescent↗

[Pharmacokinetic and clinical studies on flomoxef in mature and premature infant].

Pharmacokinetic and clinical studies of flomoxef (FMOX) in neonates and premature infants were conducted, and the results obtained are summarized below. 1. Plasma concentrations of FMOX at 15 minutes after one shot intravenous injection of 20 mg/kg to 6 cases were in a rang of 33.0-69.9 micrograms/ml and half-lives (T 1/2's) were between 0.68 and 4.89 hours. The plasma concentration of FMOX at 15 minutes after one shot intravenous injection of 40 mg/kg to 1 case was 79.9 micrograms/ml and the half-life (T 1/2) was 2.45 hours. Drug concentrations in plasma upon 1-hour intravenous drip infusion were 71.1-114.0 micrograms/ml and T 1/2's were 1.64-3.41 hours. T 1/2 tended to be couse shorter as ages of babies increased. 2. Urinary excretion rates in the first 6 hours after one shot intravenous injection of FMOX 20 mg/kg to 1 case and 1-hour intravenous drip infusion of FMOX 40 mg/kg to 2 cases were 60.4%, and 27.2 and 55.3%, respectively. 3. Clinical effects of FMOX against 12 cases of bacterial infections were excellent in 6 cases, good in 5 cases and poor in 1 case, thus the clinical efficacy rate was 91.7%. FMOX was also given to 6 cases for prophylaxis and prophylactic effects were observed in all the cases. 4. No adverse effects were observed in the 21 cases examined, but elevations of S-GOT and S-GPT were found in 1 case. The abnormal laboratory test results were probably due to this drug.

Bacterial Infections↗

[Intraperitoneal cancer chemotherapy using an implantable reservoir in patients with peritonitis carcinomatosa].

Intraperitoneal cancer chemotherapy using an implantable reservoir has been recognized as an effective treatment. In this report, we evaluate treatment results in 20 cases undergoing this chemotherapy and the correlation between reservoir-use period and cumulative survival rates. Twenty patients with an average age of 59.3 years were all observed to have peritoneal dissemination during operations in the period of January 1987 through January 1991. Their primary diseases were 10 cases of gastric cancer, 8 cases of colorectal cancer, 1 case of appendiceal carcinoma, and 1 case of malignant tumor of retroperitoneum. Intraperitoneal reservoirs were implanted in surgically-made pockets in subcutaneous lower abdomen, and their catheters were inserted into Douglas cul de sac. Medications used were CDDP, MMC, and 5-FU. The average number of administration was about 6 or 7, but, the maximum number was 67 in one case. Contrast media or RI infused via reservoirs was recognized to diffuse widely within the peritoneal cavity. Eighteen of 20 cases (90%) obtained good conditions to undergo ambulant treatments. The longest survival records were 827 days in a gastric cancer group, 639 days in a colorectal cancer group, and 326 days in a malignant tumor of retroperitoneum group. Two cases having the former two survival records are still alive at this writing. One case with appendiceal carcinoma is PS 0 and now under out-patient treatment at 2 years and 6 months after operation. The 50% survival period, and 6-month, 1-year, and 2-year cumulative survival rates were 8.8 months, 60%, 40.5%, and 37%, respectively in the gastric cancer group; and 13.5 months, 75%, 63%, and 31.5%, respectively, in the colorectal cancer group. On the contrary, 50% using period, and 6-month, 1-year, and 2-year cumulative using rates were 5.3 months, 40%, 10%, and 10%, respectively, in the gastric cancer group; and 7.9 months, 58%, 0%, and 0%, respectively, in the colorectal cancer group. Evaluation of the correlation between the reservoir use periods and cumulative survival rates has led to the conclusion that cumulative survival rates are extended significantly p = 0.0011 in each cancer group with more than 6 months treatment period compared to within each cancer group with less than 6 months treatment. 1) Intraperitoneal cancer chemotherapy using an implantable reservoir enables patients to receive treatment at outpatient clinics. 2) The continuous treatment for more than 6 months suggests the possibility for longer survival.

Cisplatin↗

[No rearrangement of the breakpoint cluster region in two juvenile chronic myeloid leukemia].

We performed cytogenetic studies and breakpoint cluster region (bcr) rearrangement analysis in two cases of juvenile chronic myeloid leukemia (JCML) which is special type of chronic myeloid leukemia (CML). Case 1 (8-month-old male) and case 2 (3-month-old female) showed clinical and hematologic manifestations similar to CML. Each of case 1 and 2 had normal karyotype and no bcr rearrangement. These findings suggest that JCML is a different heterogeneous disorder from that of adult CML.

Female↗

Mother-to-child transmission of HTLV-1.

Transmission of HTLV-I via mother's milk has been confirmed by epidemiological studies and by animal experiments using carrier mother's milk and a marmoset. The prevalence rates of HTLV-I carriers in children born of carrier mothers in endemic areas and ATL families were higher than in three control groups of young people. Also, the prevalence rates of carrier mothers who were traced from previously identified carrier children in three groups (two endemic areas and ATL family members) were extremely high. When HTLV-I antigen-positive lymphocytes were detected in carrier mother's milk, the child infection rate was higher than in the cases where antigen-positive cells could not be detected in mother's milk. The number of infected cells present in carrier mother's milk was calculated and the volume of milk given to the baby from delivery to weaning was estimated. Then, an equivalent amount of carrier mother's milk was inoculated into a marmoset orally and this marmoset seroconverted 2.5 months after the inoculation. A campaign to stop carrier mothers from giving their breast milk to their babies has been started in Nagasaki. So far, this trial has been shown to be successful in the prevention of mother-to-child infection.

Adolescent↗