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Biomedical subjects

T Inui

Publications and source records attributed to T Inui.

At least 145 records · Page 8Linked to original sources

[Spastic paraparesis and sensory disturbance improved by prednisolone therapy].

We reported a 65-year-old man whose sister was suffering from HTLV-I-associated myelopathy (HAM) and who presented slowly progressive spastic paraparesis, sensory disturbance in the feet, tremors and cerebellar ataxia. He was also positive for serum anti-HTLV-I antibody. He first showed a head tremor at the age of 3 years. He developed a spastic and ataxic gait when aged 15 years, and it became difficult for him to walk at the age of 50 years. Examination at 65 years showed a spastic and ataxic gait and scanning speech. Hyper-reflexia and Bahinski's signs were observed. Sensation in the feet was decreased. The anti-HTLV-I antibody titer in the serum was 1:512 by the PA method, and Western blot analysis revealed bands of P19, P24, P28 and P32. Examination of the cerebrospinal fluid (CSF), including oligoclonal bands, gave normal results. The CSF was negative for anti-HTLV-I antibody. CT and MRI of the head showed cerebellar atrophy. His sister was 60 years old. She had developed a spastic gait at the age of 15 years. Sensory defects and bladder dysfunction developed when aged 35 years. Hyper-reflexia, Babinski's sign and foot clonus were observed. Sensation in the feet was decreased. The urinary residual volume was increased. Ataxia was not observed. The anti-HTLV-I antibody titer in the serum was 1:8,192 by the PA method, and Western blot analysis revealed bands of p24, p28 and p32. Examination of the CSF, including oligoclonal bands, gave only normal results.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Linkage between capsaicin-stimulated calcitonin gene-related peptide and somatostatin release in rat stomach.

Calcitonin gene-related peptide (CGRP) is present in the stomach, and exogenous CGRP stimulates gastric somatostatin release. A study was undertaken to elucidate the functional linkage between CGRP and somatostatin in the stomach. Newborn Wistar rats were made CGRP deficient by intraperitoneal injection of capsaicin 2 days after birth, and then 2.5 mo later, release of CGRP and somatostatin was examined by vascular perfusion of the isolated stomach. In CGRP-deficient rats, neither the content nor basal secretion of gastric somatostatin differed from that in normal rats, and although none of several secretagogues induced CGRP secretion, the somatostatin response to glucagon was well preserved, indicating the presence of normally functioning D cells. On the other hand, arterial infusion of capsaicin significantly increased the release of not only CGRP but also somatostatin from the stomach of normal rats. In CGRP-deficient rats, however, capsaicin produced no corresponding effect. Finally, human CGRP-(8-37), a CGRP-receptor antagonist, completely inhibited the increase of gastric somatostatin induced by both rat alpha-CGRP and capsaicin infusion in normal rats. Thus the capsaicin-induced increase of somatostatin release appears to be mediated by CGRP in the stomach.

Animals↗

Auditory brainstem response (ABR) in spontaneously epileptic rats (SER) and their parent mutants.

Postnatal development of auditory brainstem response (ABR) in spontaneously epileptic rats (SER; zi/zi, tm/tm), a double mutant, their parent mutants, tremor rats (tm/tm) and zitter rats (zi/zi), and Kyo:Wistar rats (control), was studied by repeated ABR recordings from 2 to 13 weeks of age. In tremor rats and Kyo:Wistar rats at 2 weeks of age, ABR pattern was almost the same and 2 or 3 waves were identified. However, no further development in ABR was observed in tremor rats and prolongation of latency and lowering of amplitude were marked. Only wave I with prolonged latency and lowered amplitude was recognized in zitter rats, SER and SER-N (zitter phenotype without epilepsy; zi/zi, tm/+ or zi/zi, +/+). ABR pattern was almost the same from 2 to 13 weeks of age in them. Electrocochleography revealed delay of N1 latency of compound action potential in SER. Vacuolation was observed in the cochlear nuclei and the brainstem of tremor rats and SER from 3 weeks of age in histopathological examination. The organ of Corti and cochlear nerve of tremor rats and SER exhibited no remarkable histopathological findings. The deafness in SER and its parent mutants was considered to occur as a result of impairment of inner ear, cochlear nerve and brainstem as well.

Aging↗

Different binding of stimulatory-type and blocking-type TSH receptor antibody with guinea-pig testis membrane.

A receptor assay using [125I]bTSH-binding to guinea-pig testis membrane was developed. Unlabelled hCG and FSH inhibited [125I]bTSH binding. In patients with Graves' disease and in untreated hyperthyroid patients, almost all long-acting thyroid stimulators and thyroid-stimulating antibodies, respectively did not inhibit [125I]bTSH binding, which on the other hand was inhibited by thyroid stimulation blocking antibodies in patients with primary hypothyroidism. When the inhibitory effect on the binding of [125I]hCG and 125I-synthetic alpha-subunit peptide (alpha 26-46) of hCG to testis membrane was examined, bTSH resulted in a significant inhibition. However, all three kinds of TSH receptor antibodies had no inhibitory effect. This study demonstrated 1. interaction of alpha-subunit of TSH and hCG with the testicular receptor; 2. binding of thyroid stimulation-blocking antibody and lack of binding of thyroid-stimulating antibody to the testicular TSH receptor in spite of binding of these TSH receptor antibodies to the thyroidal TSH receptor, and 3. lack of binding of thyroid-stimulating antibody and thyroid stimulation-blocking antibody to the testicular gonadotropin receptor.

Amino Acid Sequence↗

[Immunohistochemical analysis of adenomatoid tumor of the uterine corpus--comparison with mesothelioma].

Immunohistochemical study was carried out in a case of adenomatoid tumor of the uterine corpus. The patient was a 35-year-old female. The tumor showed classical histochemical and immunohistochemical findings of mesothelioma, i.e., presence of hyaluronic acid on the cellular surface and cytokeratin in the cytoplasm. In addition, the tumor showed positive reaction to anti-vimentin. Furthermore, absence of Ber-Ep4 supports mesothelial origin of this tumor. EMA reaction was reported only in one case in the literature. The result was negative as in our case. Therefore, it was suggested that at least some of the adenomatoid tumor were negative for EMA as in malignant mesothelioma, although this tumor was benign. Therefore, it was suggested that loss of EMA in mesothelial tumor was not always related to anaplastic change.

Adenoma↗

HTLV-I-associated myelopathy (HAM/TSP) with Hashimoto's thyroiditis.

Two cases of HTLV-I-associated myelopathy (HAM/TSP) with Hashimoto's thyroiditis are reported. One patient is a 47-year-old female with goiter and the other a 60-year-old female. Both have slowly progressive spastic paraparesis and have anti-HTLV-I antibodies in their serum and cerebrospinal fluid. Anti-thyroid antibodies are also present in their serum, and biopsy specimens of their thyroids showed the pathological features of Hashimoto's thyroiditis. The association of the two disorders in these patients provides further evidence for the autoimmune hypothesis of the pathogenesis of HAM/TSP, and also suggests a relationship of Hashimoto's thyroiditis with HTLV-I infection.

Autoimmunity↗

[HTLV-I associated myelopathy with Hashimoto's thyroiditis--a report of two cases].

We reported two cases of HTLV-I associated myelopathy with Hashimoto's thyroiditis. Case 1 is a 47-year-old female, who has had Hashimoto's thyroiditis since the age of 29. At the age of 38, she first noticed difficulty in walking which progressed gradually. At the time of examination, she showed a spastic gait, increased deep tendon reflexes in four extremities, hypesthesia of the feet, mild bowel and bladder disturbances. Anti-HTLV-I antibody was increased to the titer of 16,834 in the serum and of 32 in the cerebrospinal fluid by PA method. Hypothyroidism was present and the titers of microsome test and thyroid test were elevated to 102,400. Anti-T4, and anti-T3, and anti-thyroglobulin antibodies were found. Ultrasonography of the thyroid revealed its enlargement and decreased echo signals. Thyroid scintigram showed inhomogeneous 123I uptake and some defective areas of the uptake. Histological examination of the biopsy specimen of the thyroid demonstrated marked lymphocytic infiltration, germinal centers, hypertrophy of follicular epithelium, and interstitial fibrosis, which were consistent with Hashimoto's thyroiditis. Case 2 is a 60-year-old female who has had slowly progressive gait disturbance since her childhood. She became unable to walk at the age of 35. At the time of examination, she had a spastic gait, increased deep tendon reflexes bilaterally, and positive Babinski signs. Anti-HTLV-I antibodies were increased to a titer of 8,192 in the serum and of 32 in the cerebrospinal fluid. Thyroid function was normal. However, anti-thyroid antibodies were positive and histology of the thyroid showed lymphocytic thyroiditis, which were consistent with mild grade of Hashimoto's thyroiditis.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoimmunity↗

The spontaneously epileptic rat (SER), a zitter*tremor double mutant rat: histopathological findings in the central nervous system.

The spontaneously epileptic rat (SER), a mutant homozygous for both zitter and tremor genes, exhibits absence-like seizures and tonic convulsions without external stimulation from 7 to 8 weeks of age. Histopathological studies of the central nervous system revealed the following abnormalities. The 35-day-old SERs which exhibit body tremor, and which have never shown seizures, had marked vacuolation and hypomyelination in the brainstem and cerebellum. The vacuoles were produced by splitting of the myelin sheaths and swelling of the dendrites and were related to primary swelling of the astrocytes. The 2- to 3-month-old SERs with staggering gait and seizures showed focal axonal swelling ('torpedo') and advanced vacuolation in the granular cell layer of the cerebellum in addition to the abnormalities observed at 35 days of age. Degenerative neurons and spheroidal bodies were observed in the substantia nigra and ventral tegmental nucleus. These brain areas are known to be related to tonic convulsions in the several experimental models. The SER is believed to be a useful tool for the investigation of the relationship between the structure and function of the central nervous system in epilepsy. It is probable that the more severe changes in the cerebellum are responsible for the staggering gait.

Animals↗

Coexistence of autoantibody to human thyrotropin (TSH) and autoanti-idiotypic antibody to antihuman TSH antibody in a case with simple goiter.

A 70-yr-old woman with simple goiter showed normal serum levels of T4, T3, free T4, TSH receptor antibody (TRAb) and increased TBG. Discrepancy in serum hTSH level was observed by different assay methods. Coexistence of both autoantibodies for hTSH and for anti-hTSH antibody were demonstrated by the reaction of the patient's antibody with both 125I-hTSH and 125I-anti-hTSH (monoclonal antibody; mAb). These two autoantibodies belong to the polyclonal immunoglobulin G (IgG). The autoantibody for hTSH recognized only beta-subunit of hTSH. Neither stimulating type of TRAb in Graves' disease nor blocking type of TRAb in primary hypothyroidism interfered with the binding of the patient's antibody to 125I-hTSH or 125I-anti-hTSH. Anti-idiotypic antibody (anti-ID antibody) for anti-hTSH antibody was purified by anti-hTSH antibody affinity chromatography. The binding reaction of 125I-anti-hTSH (mAb) with this anti-ID antibody could be inhibited by the unlabeled hTSH. This anti-ID antibody might represent the internal image of the nonbiological active site of TSH molecule, because of absence of thyroid stimulating activity. Goiter in this patient may have occurred by the unbound TSH with IgG (free TSH) and the bound TSH with IgG, because TSH levels in both the whole serum and the IgG free serum (the unbound TSH with IgG) were decreased significantly by T4 treatment. Coexistence of these antibodies may participate in the autoimmune mechanism of an idiotype-anti-idiotype network.

Aged↗

The inhibition by calmodulin of thyroid-stimulating hormone binding to epididymal fat, testis and thyroid membranes in the guinea-pig.

Calmodulin inhibited 125I-labelled TSH binding to the membranes of various target tissues for TSH (thyroid, epididymal fat and testis) of the guinea-pig. This inhibition was abolished by adding EGTA (1 mmol/l). Calmodulin did not inhibit the binding of 125I-labelled epidermal growth factor (EGF) to these membranes. It is suggested that the inhibitory effect of calmodulin on the binding of TSH to the receptor is specific and that this mechanism is due to the direct binding of calmodulin to receptor membranes. The ability of calmodulin to bind to the membranes was calcium-sensitive while that of TSH was not. The binding of 125I-labelled calmodulin to these membranes increased significantly when the endogenous calmodulin in the membranes was removed by EGTA. It was not inhibited by a pure preparation of TSH, but it was inhibited by contaminated calmodulin in a crude TSH preparation. On the other hand, 125I-labelled TSH binding to these membranes did not change after the removal of endogenous calmodulin. In conclusion, exogenous calmodulin has an inhibitory effect on the binding of TSH but not of EGF to the membranes of guinea-pig thyroid, epididymal fat and testis.

Animals↗

Calcitonin gene-related peptide and induction of hyperglycemia in conscious rats in vivo.

The effect of calcitonin gene-related peptide (CGRP) on glucose metabolism was investigated in conscious and unrestrained rats in vivo. Intravenous injection of rat CGRP (5.67 and 0.567 nmol/kg) caused a significant, dose-dependent increase in plasma glucose concentration and a simultaneous dose-dependent increase in plasma insulin level. In contrast, plasma glucagon level was not changed. On the other hand, intravenous infusion of CGRP (46.6 pmol.kg-1.min-1) decreased tolerance to intragastric administration of glucose (IGGTT). Plasma insulin response to IGGTT, however, was not affected by CGRP infusion. Moreover, although intravenous injection of CGRP (5.67 nmol/kg) elicited a significant increase in plasma epinephrine and norepinephrine concentrations, concomitant administration of epinephrine and norepinephrine, inducing a more prominent rise in plasma catecholamines than those induced by CGRP, affected neither plasma glucose nor insulin levels. Finally, plasma insulin levels obtained by simulating CGRP-induced changes in plasma glucose or glucose plus catecholamine levels by infusion of glucose or glucose plus catecholamines were not different from those induced by CGRP injection. These results suggest that CGRP has a hyperglycemic action that is not mediated by sympathetic outflow in conscious rats, and inhibition of insulin secretion, if any, does not play a major role in this hyperglycemic action of CGRP. We have demonstrated specific CGRP receptors linked to adenylate cyclase activation in rat liver plasma membranes; this hyperglycemic effect of CGRP in vivo may be partly due to its direct action on the liver.

Animals↗

Binding of bovine and porcine pituitary glycoprotein hormone alpha-subunit to TSH antibody in serum of patients with Graves' disease.

The characteristics of autoantibodies reactive with bovine (b) TSH were examined in the sera of six patients with Graves' disease selected on the basis of highly negative values in the TSH receptor assay. Test sera were incubated with other 125I-labeled pituitary glycoprotein hormones and their isolated subunits (alpha and beta) [human (h) TSH, bTSH, porcine (p) TSH, pFSH, bFSH, bLH and equine (e) chorionic gonadotropin (CG)] (purity was confirmed by gel-filtration on Sephadex G-100 and SDS-PAGE), and the antibody bound fraction was precipitated by the addition of anti-human gamma-globulin (goat). Almost all sera showed detectable binding to bTSH, pTSH, pFSH, pTSH-alpha, bFSH-alpha, bLH-alpha, but not to hTSH, hTSH-alpha, hTSH-beta, hFSH, hLH, hCG, pTSH-beta, bLH-beta, eCG-alpha. Exceptions were very low binding to bLH-beta by one serum and to pTSH-beta, by two sera. The level of binding (B/T%) of the patients' sera to pTSH-alpha, bFSH-alpha and bLH-alpha was 3.0-27.7%, 2.6-45.3% and 2.2-39.0%, respectively; that of sera from normal healthy adults was 1.9 +/- 0.3%, 0.8 +/- 0.2% and 0.9 +/- 0.2% (mean +/- SD), respectively. These results indicate that the TSH antibodies recognize mainly an epitope in the alpha subunit of bovine and porcine pituitary glycoprotein hormones (TSH, FSH, LH).

Animals↗

[Determination and clinical significance of anti-idiotypic antibody--in model experiments of thyroglobulin and TSH].

Anti-idiotypic (anti-ID) antibody in test serum was determined by the direct binding assay using 125I-anti-human thyroglobulin (hTg). Several positive cases were found in Graves' disease and thyroiditis chronica. Positive anti-ID antibodies could be classified into two types. Type 1 showed the positive anti-hTg antibody and high Tg levels by RIA using double antibody method. Type 2 showed the positive anti-hTg antibody but low Tg levels by RIA. The binding of 125I-hTg to anti-hTg antibody was displaced by anti-ID antibody in type 1, but was not anti-ID antibody in type 2. A case of coexistence of autoantibody to hTSH and auto-anti-ID antibody to anti-hTSH antibody was found. She showed normal thyroid function (T4, T3), but TSH level showed discrepancy by different assay methods. Both autoantibodies for hTSH and for anti-hTSH antibody were demonstrated by the reaction of patient's antibody with both 125I-hTSH and 125I-anti-hTSH (MoAb). These two autoantibodies belong to the polyclonal IgG. The autoantibody for hTSH recognized only the beta-subunit of hTSH. Neither stimulating type of TSH receptor antibody (TRAb) nor blocking type of TRAb interfered with the binding of patient's anti-ID to 125I-anti-hTSH. This binding reaction could be inhibited by the unlabeled hTSH. This anti-ID might represent the internal image of the non-biological active site of TSH molecule, because of absence of thyroid stimulating activity. These anti-ID antibodies may provide evidence supporting a network theory of the immune system.

Adolescent↗

[An autopsy case of multiple myeloma accompanied by extensive nodular infiltration into the extraskeletal tissue].

Discussed is the case of a 41-year-old Japanese man dead at 4 months after start of his clinical course of multiple myeloma of the Bence-Jones protein lambda type of the skull. Autopsy findings revealed that atypical plasmacytes had infiltrated extensively into the testes, the retroperitoneum, including the pancreas and the renal pelvis, the bilateral pleura, the right subclavian soft tissue, and the meningism, but not to the liver, spleen, and lymph nodes. In both testes, which weighted 120 g and 100 g, respectively, myeloma cells were found disseminated throughout the testicular tissue. Such a testicular involvement in cases of a multiple myeloma is extremely rare. The pertinent literature also is reviewed.

Adult↗

Incidence of precancerous foci of mammary glands and growth rate of transplantable mammary cancers in sialoadenectomized mice.

Sialoadenectomies performed on 8-week-old female SHN and GR mice markedly reduced the numbers of precancerous and cancerous lesions in their mammary glands that had been mildly hypoplastic; the mice were necropsied when they were 30 weeks old. The success rate of the mammary cancer transplantation to isogenic male SHN or C3H mice was lower in the sialoadenectomized animals, and growth of the grafted tumors was delayed after gland removal. Some tumor development resumed in the hosts that received mouse epidermal growth factor after surgery. Therefore, we believe this growth factor may play a role in the multistage process of mouse mammary carcinogenesis.

Animals↗

Structure-activity relationship of endothelin: importance of charged groups.

Endothelin (ET)-related peptides including ET-1 (1-39) were synthesized, and their constricting activity in rat pulmonary artery rings and pressor activity in unanesthetized rat were measured to elucidate their structure-activity relationship. The vasoconstrictor activities of ET-2, ET-3 and sarafotoxin S6b were one-half, one-60th and one-third that of ET-1, respectively. Such differences in biological activities should mainly arise from sequence heterogeneity at the N-terminal portion, especially at positions 4 to 7. All of the blocked ETs at the amino or carboxyl termini showed greatly decreased activities. A monocyclic analog, in which Cys3 and Cys11 were replaced by Ala, showed one-third the activity of ET-1; however, its deamino dicarba analog was almost completely inactive. Significant activities were retained even with replacement of amino acids at positions Ser4, Ser5, Leu6, Met7, Lys9, Tyr13, and Trp21 by Ala, Ala, Gly, Met(0), Leu, Phe, and Tyr or Phe, respectively. On the other hand, replacement of Asp8, Glu10 and Phe14 by Asn, Gln and Ala, respectively, resulted in complete loss of the biological activity. These results indicated that two disulfide bonds in ET molecule were not essential for the expression of vasoconstricting activity. Both terminal amino and carboxyl groups, carboxyl groups of Asp8 and Glu10, and the aromatic group of Phe14 seemed to be contributing, more or less, to the expression of the biological activities.

Animals↗