Terunori Mitsuma

Rapid simultaneous radioimmunoassay for triiodothyronine and thyroxine in unextracted serum.

Abstract A three hour radioimmunoassay for the simultaneous measurement of triiodothyronine and thyroxine in 25λ of unextracted serum has been developed. 8-anilino-1-napthalene sulfonic acid has been used to inhibit binding of the two hormones to thyroxine binding globulin. Comparisons of thyroxine with those obtained by competitive protein binding assay and triiodothyronine with those determined by our previously developed radioimmunoassay afford excellent agreement. The speed, accuracy, sensitivity and specificity of this assay renders it highly attractive for routine clinical determinations and for research applications as well.

Serum triiodothyronine: measurements in human serum by radioimmunoassay with corroboration by gas-liquid chromatography

Serum triiodothyronine (T(3)) has been measured by radioimmunoassay and corroborated by analysis of the identical samples with a previously described gas-liquid chromatographic technique. Special features of the radioimmunoassay procedure which permit determinations in unextracted serum include the use of a T(3)-free serum preparation for the construction of the standard curve and of tetrachlorothyronine to inhibit binding of T(3) to thyroxine-binding globulin.T(3) values by radioimmunoassay were 138 +/-23 ng/100 ml (mean +/-SD) in 82 normal subjects, 62 +/-9 ng/100 ml in 45 hypothyroid patients, and 494 +/-265 ng/100 ml in 60 patients with toxic diffuse goiter. In the hypothyroid group, the range was similar in patients with both primary and secondary hypothyroidism. There was no overlap between the three thyroidal states. Elevated T(3) levels were seen in 40 cases that appeared clinically hyperthyroid but had normal serum thyroxine (T(3)) determinations, a syndrome we have called T(3) toxicosis. Values obtained with radioimmunoassay agreed closely with those we had previously found by gas-liquid chromatography which were 68 +/-2 ng/100 ml in hypothyroidism, 137 +/-23 ng/100 ml in normal subjects, and 510 +/-131 ng/100 ml in untreated toxic diffuse goiter. Since T(3) is very potent and its level varies in different clinical states, accurate T(3) measurements are required to assess a patients thyroid status properly. The radioimmunoassay for T(3) appears to be sufficiently sensitive, precise, and simple to permit its routine clinical application for this purpose.

Nerve growth factor prevents neurotoxic effects of cisplatin, vincristine and taxol, on adult rat sympathetic ganglion explants in vitro.

Anti-cancer drugs, cisplatin, vincristine and taxol clinically induce toxic sensory as well as autonomic neuropathy. Administration of nerve growth factor (NGF) has been found to prevent experimental sensory neuropathies induced by these anti-cancer drugs, but the information about autonomic neuropathy is lacking. We developed an adult rat superior cervical ganglion (SCG) explant culture, which we treated with cisplatin, vincristine and taxol either in the presence or absence of NGF. The maximum length of regenerated neurites was shortened by cisplatin, vincristine and taxol in a dose-dependent manner. However cotreatment with NGF significantly promoted the regeneration of neurites in all drug-treated explants. The effect of NGF was clearly blocked by the anti-NGF antibody. These findings suggest that cotreatment of NGF prevents and reverses the toxic effects of the anti-cancer drugs on the sympathetic neurons.

TRIIODOTHYRONINE AND THYROID-STIMULATING HORMONE RESPONSE TO THYROTROPHIN-RELEASING HORMONE: A NEW TEST OF THYROIDAL AND PITUITARY RESERVE

Abstract Intravenous administration of thyrotrophin-releasing hormone (T.R.H.) induces a prompt rise in immunoassayable thyroid-stimulating hormone (T.S.H.) and triiodothyronine (T3) in normal man. Basal T.S.H. levels are high in primary hypothyroidism and rise dramatically after T.R.H. In patients with hypothyroidism secondary to pituitary disease basal T.S.H. levels are low and show no increase with T.R.H. In contrast, 2 patients with hypothalamic hypothyroidism had nil basal levels of T.S.H., which rose normally after T.R.H. administration. Basal T3 levels were low in all forms of hypothyroidism and did not rise after T.R.H. administration. The failure of T3 to increase normally after T.R.H. in the 2 patients with hypothalamic hypothyroidism in the face of a normal T.S.H. stimulation test suggests a diminished thyroidal reserve in these patients. Intravenous T.R.H. administration may prove of value in the simultaneous assessment of pituitary and thyroidal reserve.

Modulation of pituitary responsiveness to thyrotropin-releasing hormone by triiodothyronine.

The relative roles of triiodothyronine (T(3)) and thyroxine (T(4)) in modulating pituitary responsiveness to thyrotropin-releasing hormone (TRH) have been assessed. (a) 10 hyperthyroid patients with elevated serum T(2) and T(4) levels showed no pituitary response to TRH. After 2 wk of propylthiouracil therapy T(4) levels had fallen to normal in only five patients while T(2) levels were normal in all. Pituitary responsiveness to TRH returned in all patients with normal or high T(4) concentrations. (b) Patients with isolated elevations of serum T(3) (T(3) toxicosis) failed to respond to TRH. TRH responsiveness was restored when T(3) levels fell to normal after propylthiouracil therapy. (c) When pituitary responsiveness to TRH was tested 60 min after a single oral dose of 50 mug of T(3), which increased serum T(3) levels to slightly above the normal range, no rise in thyrotropin (TSH) was seen in six subjects. These findings indicate that T(3) elevations alone can rapidly inhibit pituitary responsiveness to TRH.

HYPERTRIIODOTHYRONINÆMIA AS A PREMONITORY MANIFESTATION OF THYROTOXICOSIS

Abstract Triiodothyronine (T 3 ) levels were raised in four patients from 5 weeks to 9 months before the development of overt hyperthyroidism and before raised serum-thyroxine (T 4 ) levels were found. These observations suggest that hyperthyroid patients may pass through a stage of T 3 toxicosis before developing the usual form of thyrotoxicosis, and that serum-T 3 measurements may be helpful in the early diagnosis of the disease.

T3 TOXICOSIS IN AN IODINE-DEFICIENT AREA

Abstract In contrast to experience in New York where the frequency of triiodothyronine (T3) toxicosis among hyperthyroid patients is 4%, 56 (12·5%) of 449 patients in Chile, an area of iodine deficiency, were hyperthyroid by clinical and laboratory criteria but had normal serum-levels of protein-bound iodine (P.B.I.). 12 patients, investigated more fully, were unequivocally thyrotoxic on clinical grounds. P.B.I. and T4 levels were normal; serum-T3 levels were to raised between 264 and 840 ng. per 100 ml., with a mean of 480 ng. per 100 ml. Urinary iodide excretion was low in the two patients in whom it was assessed. These findings suggest that the frequency of T3 toxicosis is significantly higher in areas of iodine deficiency than in the United States.

Androgen receptor mRNA with increased size of tandem CAG repeat is widely expressed in the neural and nonneural tissues of X-linked recessive bulbospinal neuronopathy.

We detected androgen receptor (AR) mRNA expression in various tissues in the patients with X-BSNP and controls using reverse transcription polymerase chain reaction (RT-PCR) and Northern blot analysis. The AR mRNAs were expressed in a wide variety of tissues including the testis, scrotal skin, liver, skeletal and cardiac muscles, sciatic nerve, sympathetic and dorsal root ganglia and spinal cord, and were all abnormally elongated in the size of the CAG repeat in the patients. The mutant AR gene with increased size of tandem CAG repeat was directly transcribed in various tissues, and would be related to a wide spectrum of phenotypic manifestations in X-BSNP.

Infarction of Superior Cerebellar Artery Presenting as Cerebellar Symptoms

BACKGROUND MRI of the brain has facilitated the diagnosis of cerebellar infarction in the territory of the superior cerebellar artery (SCA). We analyzed the data on patients with SCA infarction who presented with only cerebellar symptoms in an attempt to define its underlying pathophysiology. SUMMARY OF REPORT Ten patients with SCA infarction who presented with cerebellar symptoms were studied by brain MRI, angiography, and underlying pathology. Brain MRI demonstrated an infarct in the SCA territory in the anterior rostral cerebellum of all patients. None had abnormalities in the brain stem. In four patients, a hemorrhagic infarct was present in the same region. Cerebral angiography revealed no obvious SCA occlusion or atherosclerotic vascular disease in any patient. Eight of the 10 patients had heart disease, such as atrial fibrillation or old myocardial infarction. The presumed diagnosis was occlusion of the SCA in its periphery due to cardiogenic embolism. CONCLUSIONS When a patient presents with only cerebellar symptoms and has cerebellar infarction demonstrated by brain MRI, the SCA branch is probably occluded by cardiogenic embolism.

Somatic mosaicism of the expanded CAG trinucleotide repeat in mRNAs for the responsible gene of Machado-Joseph disease (MJD), dentatorubral-pallidoluysian atrophy (DRPLA), and spinal and bulbar muscular atrophy (SBMA).

The CAG trinucleotide repeats in mRNAs for the responsible genes of Machado-Joseph disease (MJD), dentatorubral-pallidoluysian atrophy (DRPLA), and X-linked spinal and bulbal muscular atrophy (SBMA) were examined in various neural and nonneural tissues of affected individuals. The tissue-specific variation of expanded CAG repeat alleles were apparent for mRNAs of all three genes. The expanded CAG repeats of the mRNA were shorter in the cerebellum than in other regions of the central nervous system in DRPLA and MJD, but not in SBMA, and were longer in the liver and colon in MJD. Transcripts of the responsible genes with expanded CAG repeats were detected in all tissues studied, and the tissue-specific variation in the CAG repeat size of the mRNA did not correlate with the tissue-specific severity of pathological involvement in these diseases.