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Biomedical subjects

H Tamai

Publications and source records attributed to H Tamai.

At least 145 records · Page 8Linked to original sources

Effects of monoclonal antibody against CD45RB on peripheral blood mononuclear cell proliferation and on HLA-DR and adhesion molecule expression on thyrocytes of patients with autoimmune thyroid disease.

To evaluate the role of CD45 (especially that of the ectodomain region B) on immunocyte-thyrocyte signaling in patients with autoimmune thyroid disease (AITD), we have examined the in vitro and in vivo effects of a monoclonal antibody (mAb) against with CD45RB, termed MT3. MT3 was added to cultured peripheral blood mononuclear cells (PBMC) from patients with AITD and was additionally injected into severe combined immunodeficient (SCID) mice to which Graves' thyroid cells and intrathyroidal lymphocytes were engrafted. MT3 stimulated proliferation of PBMC when cultured for 2 to 3 days in patients with Hashimoto's thyroiditis (HT) and Graves' disease (GD) and in normal controls (NC). However, when cultured for 7 days, the stimulation index [SI: counts per minute (cpm) with mAb/cpm without mAb] was lowered by MT3 in NC and GD patients. However, the mean SI was not lowered in patients with HT. In SCID mice, the concentrations of human immunoglobulin G, antithyroglobulin and antithyroperoxidase antibodies in sera were not significantly changed by injecting MT3. The expression of human leukocyte antigen (HLA)-DR and intercellular adhesion molecule (ICAM)-1 on engrafted human thyrocytes decreased after the tissues were engrafted into the control mice to which vehicle alone was injected. However, in the mice injected with MT3, HLA-DR and ICAM-1 expression remained high or up-regulated by the injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Case report: intraglomerular metastasis with neoplastic cell interposition.

A case is described of an 88-year-old man with lung cancer, nephrotic syndrome, and renal dysfunction who died suddenly of an acute myocardial infarction and whose autopsy revealed many adenocarcinoma cells stacked within glomerular capillary lumina of his kidney, entering into basement membrane zones (ie, neoplastic cell interposition). In addition, glomeruli showed a lobular transformation, doubling of glomerular basement membrane, and electron dense deposits along the glomerular basement membrane. These changes were similar to those of membraneoproliferative glomerulonephritis. The association of intraglomerular metastasis and membranoproliferative glomerulonephritis-like lesions led the authors to speculate that the latter glomerular change might have provided an attractive opportunity for circulating tumor cells to be trapped and grow within the glomerular lumina. This mode of metastasis has not been well-recognized. The authors describe the experience, review the literature, and discuss its possible pathogenesis.

Adenocarcinoma↗

Pharmacokinetics of all-trans retinoic acid in pediatric patients with leukemia.

Since all-trans retinoic acid (ATRA) induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL), and its effectiveness appears to be related to the plasma or serum level, a pharmacokinetic study of ATRA was undertaken in nine patients with various leukemias. After oral administration at a dose of 30 mg/m2, the time required to reach the peak plasma level of ATRA (20-1198 ng/ml) was between 120 and 240 min and the apparent plasma elimination half life was 21-51 min. In addition, 13-cis retinoic acid was detected in the plasma of seven patients, indicating the occurrence of ATRA isomerization in vivo. ATRA therapy did not induce complete remission in all patients, even when high plasma levels were achieved. Among the six APL patients given ATRA therapy, one who failed to respond had a very low plasma ATRA level. These findings suggest that it may be useful to monitor plasma levels during oral ATRA therapy in order to achieve an appropriate treatment regimen.

Adolescent↗

A study of untreated Graves' patients with undetectable TSH binding inhibitor immunoglobulins and the effect of anti-thyroid drugs.

OBJECTIVE: We previously reported the clinical characteristics of Graves' disease with undetectable TSH binding inhibitor immunoglobulins (TBII) at first visit, but a study of the prognosis of untreated TBII negative patients with anti-thyroid drug medication has never been undertaken. The aim of this paper is to study the difference between negative and positive TBII Graves' disease in relation to the effect of anti-thyroid drug treatment. PATIENTS: From January 1986 to April 1991, 1545 patients with untreated Graves' disease were referred to Kuma Hospital, Kobe, Japan. Of these, 94 TRAb negative patients were identified. Another 83 TRAb positive patients were randomly selected from the other Graves' disease patients and served as a comparison group. Fifty-six of the 94 patients in the TBII negative group and 52 of the 83 patients in the TBII positive group completed treatment with methimazole only. MEASUREMENTS: The trial was conducted as a retrospective study with a maximum treatment period of 36 months and a follow-up period of a further 12 months. From the original pool of patients, we classified 56 TBII negative patients into two groups according to the clinical course taken; Group A in whom TBII remained undetectable throughout methimazole treatment (9 men and 34 women, age 37.2 +/- 2.2 years), and Group B who became TBII positive (4 men and 9 women, 31.2 +/- 4.4 years). Fifty-two TBII positive patients served as the comparison Group C (8 men and 44 women, age 38.1 +/- 2.0 years). RESULTS: Serum free T4 and free T3 levels in groups A and B were significantly lower before treatment than those of Group C (P < 0.001). The thyroid volumes of Group A and B patients were significantly smaller than those of Group C (P < 0.01). The level of TBII in Groups A and B was significantly lower than that in Group C (8.3 +/- 0.7 and 8.8 +/- 1.1 vs 57.0 +/- 2.8%, respectively, P < 0.001). The level of thyroid stimulating antibody (TSAb) in Groups A and B was significantly lower than that in Group C (478 +/- 71.0 and 761 +/- 140.3 vs 2143 +/- 280%, respectively, P < 0.01), and there were no significant differences in TSAb activities between Groups A and B. The remission rates in Groups A, B and C were 77.4, 36.4 and 36.5%, respectively. These data indicate that Group A has a good prognosis, but Group B has the same prognosis as Group C. CONCLUSION: We conclude that patients in whom TSH binding inhibitor immunoglobulins remained negative have a much better prognosis than TSH binding inhibitor immunoglobulins positive patients or those who become TSH binding inhibitor immunoglobulins positive, having been initially negative.

Adult↗

The correlation between papillary thyroid carcinoma and lymphocytic infiltration in the thyroid gland.

Ninety-five patients with papillary thyroid carcinoma (PTC) who received primary surgical treatment in 1983 at Kuma Hospital and were followed until 1992 were the subjects of this study. Initial therapy was tumor resection for 5 patients, lobectomy for 23 patients, total thyroidectomy with unilateral modified neck dissection for 60 patients, and total thyroidectomy with bilateral modified neck dissection for 7 patients. Clinical stage at diagnosis was as follows. Class I included 28 patients with intrathyroidal disease, class II included 60 patients with positive cervical lymph nodes, and class II included 7 patients with tumor invasion into tissue outside of the thyroid gland. Recurrence of the tumor was evaluated according to lymphocytic infiltration in the thyroid gland. Group A consisted of 36 patients with PTC associated with lymphocytic infiltration, 26 with infiltration surrounding the tumor, 3 with infiltration inside of the tumor, and 7 with both. Group B consisted of the remaining 59 patients with PTC with no lymphocytic infiltration. There were no differences in age, sex, initial tumor size, or initial treatment between groups A and B. Antithyroglobulin antibody and/or antimicrosomal antibody were positive in 16 patients from group A and 4 patients from group B (P < 0.001). Class I included 14 patients from each group, class II included 22 patients from group A and 38 patients from group B, and class III included 7 patients, all from group B. Recurrence of the tumor was found in only 1 group A patient (2.8%), but in 11 patients of group B (18.6%). The percentage of patients free from recurrence over the 10 yr of follow-up in group A was significantly higher than that in group B (by Cox-Mantel test, P < 0.01). The time between initial treatment and recurrence was 2-10 yr. In comparing the clinical stage at the time of initial treatment, recurrence was found in 1 class II patient from group A (4.5%) and in 1 class I (7.1%), 6 class II (15.8%), and 4 class III (57.1%) patients from group B. No patients died during the 10 yr of follow-up. In conclusion, 1) lymphocytic infiltration surrounding the tumor or inside the tumor in PTC might be of use as a means for predicting a favorable prognosis; and 2) class II or class III patients with no lymphocytic infiltration had a high rate of recurrence.

Adult↗

Clinical characteristics of subacute thyroiditis classified according to human leukocyte antigen typing.

We investigated human leukocyte antigen (HLA) class I and class II antigens in 56 Japanese patients with subacute thyroiditis (SAT) who visited our out-patient clinic between 1988 and 1990. We found SAT to be associated with not only HLA-B35 (40 patients; P < 0.000001; relative risk, 18.02), but also with HLA-B67 antigens (9 patients; P < 0.00001; relative risk, 11.20). No heterozygotes of HLA-B35 or HLA-B67 were found in any of the 56 patients with SAT. Either HLA-B35 or HLA-B67 antigen is found in 87% of patients with SAT. When season of onset and clinical course of SAT were compared in the 49 patients with HLA-B35-positive SAT (B35-SAT) and HLA-B67-positive SAT (B67-SAT), we were able to identify certain characteristics: 1) B67-SAT often followed the course from transient thyrotoxicosis to a hypothyroid phase to a euthyroid phase [6 of 9 B67-SAT (67%) vs. 10 of 40 B35-SAT (25%); P < 0.05]; and 2) B67-SAT occurred mostly during the summer or autumn and at a higher rate than did B35-SAR [8 of 9 B67-SAT (89%) vs. 17 of 40 B35-SAT (43%)], whereas B35-SAT occurred throughout the year. We conclude that there are at least two types of SAT that can be classified by association with either HLA-B35 or HLA-B67 antigens.

Acute Disease↗

Lack of effect of thyroxine administration on elevated thyroid stimulating hormone receptor antibody levels in treated Graves' disease patients.

Increased levels of antibodies to TSH receptors are thought to be a major cause of active Graves' disease or recurrence following therapy. It was recently reported that T4 administration during antithyroid drug treatment for Graves' disease resulted in a significant decrease of TSH receptor antibodies compared to drug therapy alone. It is known that these antibodies may remain elevated long after patients become euthyroid, so a large number of patients whose antibodies remained significantly elevated after 1 year of methimazole therapy were evaluated in the study. A total of 330 Graves' disease patients were treated with methimazole for 1 year. TSH receptor antibody titers remained persistently elevated in 195 patients. Thirty-five randomly selected patients were continued on maintenance doses of methimazole for a second year, and 160 patients were treated with a combination of methimazole and thyroxine for a second year. T4 doses needed ranged from 75-100 micrograms/day to maintain serum-free T4 and free T3 within the normal range. After 6 months of combined therapy, 35 patients were found to have suppressed serum TSH levels. The patients were divided after 18 months into three groups: A, B, and C. Group C, consisting of 35 randomly selected patients (8 males and 27 females) whose ages ranged from 12-62 years and who had been maintained on methimazole alone, served as controls. Group B, whose serum TSH levels were suppressed after 6 months of combined therapy, consisted of 9 males and 26 females whose ages were 15-66 years. Group A, 35 randomly selected patients with normal serum TSH levels after methimazole and thyroxine therapy for 6 months, consisted of 8 males and 27 females whose ages were 10-63 years. TSH receptor antibody titers gradually decreased in all three groups with drug therapy, and there was no significant difference in the titers at corresponding times, i.e. 0, 1.0, 1.5, and 2.0 years. After treatment for 2.0 years, all patients of the three groups were followed for a further 12 months. Rates of recurrence among the above three groups were not significantly different during the observation period. In the present study, T4 administration in combination with antithyroidal drugs had no effect on levels of antibodies to TSH receptors and no effect on rates of recurrence. The reason for the discrepant results in the present study from previous reports is not known.

Adolescent↗

4-oxo retinoic acid for refractory acute promyelocytic leukemia in children with all-trans retinoic acid therapy.

Therapy with all-trans retinoic acid (ATRA) achieves complete remission in a high proportion of patients with acute promyelocytic leukemia (APL), but the efficacy is reported to relate to plasma ATRA level after oral administration. The pharmacokinetics of ATRA and 4-oxo all-trans retinoic acid (4-oxo ATRA), a metabolite of ATRA, were studied in four children with APL at the time of initial oral administration. After administration of ATRA at a dose of 30 mg/m2, the peak plasma ATRA level was 20-741 ng/ml and was reached at 60-120 min. The patient with the lowest peak plasma level did not achieve complete remission and had a very high 4-oxo ATRA level compared to the patients with complete remission. These findings suggest that accelerated metabolism of ATRA plays a role in the failure of this agent in the patients without remission.

Administration, Oral↗

Plasma levels of retinol, retinol-binding protein, all-trans beta-carotene and cryptoxanthin in low birth weight infants.

In neonatal medicine, it is thought that retinol is useful for preventing CLD and for fetal development. However, beta-carotene had other vitamin A precursors have not been studied in neonates with CLD or others disorders. Cord blood of neonates including ELBW and VLBW infants was assayed for plasma levels of retinol, RBP, beta-carotene and cryptoxanthin. Plasma beta-carotene levels in ELBW and VLBW were lower than that in term infants, but plasma cryptoxanthin levels in ELBW and VLBW were about the same as in term infants. Plasma retinol and RBP levels showed almost same levels during 23-41 gestational weeks. Maternal smoking reduced plasma beta-carotene but not cryptoxanthin, retinol, or RBP levels. IUGR was associated with increased cryptoxanthin levels in cord blood. Serious neonatal diseases, including CLD and ROP manifested no significant effects on the cord blood vitamin levels. Thus, the occurrence of these diseases at birth could not be predicted by examination of vitamin levels in cord blood.

Cryptoxanthins↗

[Anesthesia for SUMO wrestlers].

We anesthetized 34 sumo wrestlers. All patients were male. Average age was 21.1. Their height was 181.9 +/- 4.5 (mean +/- SD) cm, and they weighted 135.2 +/- 16.9 kg. Anesthetic methods used were spinal anesthesia alone in 17 patients, general anesthesia alone in 9, general anesthesia + epidural anesthesia/or spinal anesthesia/or axillary block in 8. The preoperative data showed findings common to obese patients; liver dysfunction, abnormal blood sugar, and abnormal ECG such as ST depression or left ventricular hypertrophy. For intubation, fiberscopy was required in one patient, and almost all patients required high FIO2, otherwise SaO2 decreased. For spinal anesthesia or epidural anesthesia, we needed long needles of 8 to 15 cm.

Adult↗

[Substance P].

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Amino Acid Sequence↗

Effect of long-term administration of beta-carotene on lymphocyte subsets in humans.

To examine whether or not beta-carotene alters immune indexes, we performed a single-blind trial in healthy male nonsmokers. Lymphocyte subsets were assessed by double labeling with monoclonal antibodies before and after 44 wk of administration of either beta-carotene (60 mg/d; n = 10) or placebo (n = 10). In addition, we measured the beta-carotene concentrations in plasma, mononuclear cells (MNC), platelets, and red blood cells (RBCs), as well as the plasma alpha-tocopherol concentration. An increase of plasma and MNC beta-carotene concentrations to four and three times the baseline value was noted after 2 and 4 wk, respectively. The CD4-CD8 ratio increased after 9 mo of beta-carotene administration whereas natural killer cells, virgin T cells, memory T cells, and cytotoxic T cells remained unaltered throughout the study. No side effects or toxicities were detected by a questionnaire survey and routine laboratory tests.

Adult↗

Immunological findings and thyroid function of untreated Graves' disease patients with undetectable TSH-binding inhibitor immunoglobulin.

OBJECTIVE: TSH-binding inhibitory immunoglobulin (TBII) is undetectable in about 10% of untreated Graves' disease patients, but the clinical characteristics and immunological significance of this finding are unknown. In this study we evaluated the clinical characteristics of TBII negative Graves' disease. PATIENTS: We examined TBII in 1048 untreated patients at Kuma hospital from 1986 to 1990 and found 69 TBII undetectable patients (12 men and 57 women, mean age +/- SEM 35 +/- 2 years, group A). MEASUREMENTS: We compared the clinical characteristics and immunological findings of group A with 57 untreated TBII detectable Graves' patients who were selected randomly (11 men and 46 women, mean age +/- SEM 40 +/- 2 years, group B). T4, TSH, FT4, FT3, 123I thyroid uptake, TBII, thyroid stimulating antibodies (TSAb) and the volume of the thyroid using ultrasonography were measured at the first visit. RESULTS: Serum T4, FT4 and FT3 levels in group A were significantly lower than those in group B (P < 0.001). The values of TSAb in group A were significantly lower than those in group B (593 +/- 67 (mean +/- SE) vs 2143 +/- 280%, respectively, P < 0.001). The 123I thyroid uptake in group A was significantly lower than that in group B (53.1 +/- 1.1 vs 61.4 +/- 1.4%, respectively, P < 0.01). The thyroid volume in group A was significantly smaller than that in group B (39.1 +/- 3.0 vs 51.3 +/- 3.3 ml, respectively, P < 0.01). TSAb was undetectable in about 10% (6) of the TBII negative untreated Graves' patients at their first visit. CONCLUSION: In the present study, untreated TBII negative patients with Graves' disease were characterized by mild elevation of thyroid hormones, mildly elevated 123I uptake, weak TSAb activities and small goitres. The finding of both TBII and TSAb negative titres in untreated Graves' disease patients was also confirmed.

Adult↗

A case of tetrasomy 9p.

A case of mosaic 9p tetrasomy (46,XX/47,XX, + dic[9] [q21]) is reported. Clinical manifestations of the patient were generalized hypotonia, severe mental retardation and characteristic dysmorphic features of 9p tetrasomy. A brief review of the literature is also included.

Chromosome Aberrations↗

Resistance to autoimmune thyroid disease is associated with HLA-DQ.

Genotypes of DQA1 and DQB1 genes were determined by polymerase chain reaction followed by dot blot hybridization with sequence-specific oligonucleotide probes in 105 patients with goitrous autoimmune thyroiditis (Hashimoto's thyroiditis) and in 67 patients with Graves' disease to investigate whether specific DQ alleles were associated with susceptibility or resistance to autoimmune thyroid diseases. Hashimoto's thyroiditis was found to be negatively associated with DQA1*0102 and DQB1*0602 whereas Graves' disease showed a negative association with DQB1*0501. No strongly positive association with a specific DQ allele was found in either disease. These results suggest that the HLA-DQ gene may be a genetic marker for resistance to autoimmune thyroid diseases.

Autoimmune Diseases↗

Insulin response to intravenous glucose in patients with anorexia nervosa showing low insulin response to oral glucose.

To investigate the cause of a low insulin secretory response to an oral glucose tolerance test (OGTT) in patients with anorexia nervosa (AN), we performed iv glucose tolerance tests (IVGTT) before and after treatment in 36 anorectic patients who showed low insulin secretion in response to the OGTT. These patients were subdivided into 3 groups by glucose tolerance curves during the OGTT: normal type, blood glucose level peaking 60 min or earlier after oral glucose ingestion; delayed type, blood glucose level peaking 90 min or later after oral glucose; and flat type, peak blood glucose level of 5.56 mmol/L or less after oral glucose. The results showed that the normal and flat type groups had normal glucose and insulin responses to iv glucose. In the delayed type group, in which the longest duration of AN before therapy was found, initial insulin secretion was decreased in response to both oral and iv glucose, indicating diminished pancreatic beta-cell function. After weight gain, this parameter improved significantly in both tests. The rate of glucose disappearance for the IVGTT was lower both before and after weight gain in this subgroup compared to that in normal controls, suggesting insulin resistance. In conclusion, the low insulin response to oral glucose seen in the flat type group may be due to the disturbance of gastrointestinal factors, such as motility. In contrast, the observations suggest that the delayed type group has beta-cell failure corrected by weight gain and has insulin resistance requiring a longer recovery time; these abnormalities are related to the duration of AN.

Administration, Oral↗

Severe depression associated with ACTH, PRL, and GH deficiency: a case report.

A 68-year-old man was hospitalized in August, 1990 with general malaise, loss of energy, poor appetite and severe depression. He had experienced depressed moods, markedly diminished interest, feelings of worthlessness, diminished ability to think, general malaise and muscle weakness beginning in November, 1989. He was treated for depression at another hospital until his emergent admission to our hospital because of difficulty in walking. Laboratory studies disclosed hyponatremia, low plasma ACTH level (4.2 pmol/L), and a low cortisol level (27.6 nmol/L). Rapid ACTH test elicited an increase in serum cortisol from 75.6 nmol/L to 361.2 nmol/L at 30 min. Ovine corticotropin releasing hormone (CRH) did not stimulate secretion of either ACTH or cortisol. Human growth hormone releasing hormone (GRH) together with thyrotropin releasing hormone (TRH) elicited a normal response of TSH and low responses of GH and PRL. The patient's serum autoantibodies to anterior pituitary cell membranes using GH3 rat pituitary cells and AtT-20 mouse pituitary cells were positive. On the basis of these data, the diagnosis of selective ACTH, GH and PRL deficiency was made and thought to have been caused by lymphocytic adenohypophysitis. Following cortisol replacement therapy, he quickly regained his appetite and was restored to a normal mental state of being.

Adrenocorticotropic Hormone↗

Homocysteine induces iron-catalyzed lipid peroxidation of low-density lipoprotein that is prevented by alpha-tocopherol.

Homocystinuria is an inborn error of methionine metabolism that is characterized by the premature development of arteriosclerosis. As one of the major factors in the pathogenesis of arteriosclerosis, modification of low-density lipoprotein (LDL) has received widespread attention by many investigators. In this study, to elucidate the relationship between elevated homocysteine levels and premature arteriosclerosis, we investigated the role of homocysteine in the iron-catalyzed oxidative modification of LDL. When LDL isolated from a healthy subject was incubated with homocysteine and ferric ion, a gradual decrease of polyunsaturated fatty acids (PUFA), formation of thiobarbituric acid-reactive substances (TBARS) and fluorescent substances, and the fragmentation of apoprotein B (apoB) were observed. The extent of oxidative modification was dependent on the concentration of homocysteine. Modification of LDL was suppressed until the remaining alpha-tocopherol concentration reached a critical level. When the alpha-tocopherol content of LDL was increased by 2.6-fold, both the formation of TBARS and the fragmentation of apoB were suppressed. These results suggest that homocysteine might promote iron-catalyzed oxidation of LDL and imply its role for the development of premature arteriosclerosis.

Adult↗