Polymorphism of the serotonin transporter gene modulates brain and physiological responses to acute stress in Japanese men.

A short (S) variant, compared to a long (L) variant, of the promoter region of the serotonin transporter gene-linked polymorphic region (5HTTLPR) has been related to emotional hyper-reactivity. We tested whether the 5HTTLPR could modulate acute stress responses in the brain and, the cardiovascular and neuroendocrine systems. Ten Japanese male participants carrying double copies of the S alleles and 10 Japanese males carrying S and L alleles conducted a mental arithmetic task, and their regional cerebral blood flow by (15)O positron emission tomography and cardiovascular and neuroendocrine parameters were measured. During the acute stress task, the participants with the SS alleles showed stronger reactivity in blood pressure and secretion of epinephrine, compared to the participants with the SL and LL alleles. Furthermore, the SS carriers showed greater activation in stress-related brain regions such as the hypothalamus, cerebellum, midbrain, and pulvinar compared to the SL and LL carriers during the acute stress task. The present findings indicated that the S allele of the 5HTTLPR is associated with greater brain and physiological reactivity to acute stress in Japanese men.

Associations among central nervous, endocrine, and immune activities when positive emotions are elicited by looking at a favorite person.

Recent studies on psychoneuroimmunology have indicated that positive psychological events are related to immune functions; however, limited information is available regarding associations among the central nervous, endocrine, and immune systems when positive emotions are elicited. In the present study, we demonstrated associations among these systems by simultaneously recording brain, endocrine, and immune activities when positive emotions were evoked in participants as they watched films featuring their favorite persons. Interestingly, the activity of peripheral circulating natural killer cells and the peripheral dopamine level were elevated while participants experienced positive emotions, and these values were positively correlated. The following brain regions were significantly activated in the positive condition relative to the control condition: medial prefrontal cortex, thalamus, hypothalamus, subcallosal gyrus, posterior cingulate cortex, superior temporal gyrus, and cerebellum. Further, covariate analyses indicated that these brain regions were temporally associated with endocrine and immune activities. These results suggest that while an individual experiences positive emotions, the central nervous, endocrine, and immune systems may be interrelated and attraction for favorite persons may be associated with the activation of the innate immune function via the dopaminergic system.

Growth hormone insensitivity syndrome associated with syringomyelia and type I Chiari malformation.

A 49-year-old man with syringomyelia and a Type I Arnold-Chiari malformation (Chiari-I) was diagnosed with growth hormone insensitivity syndrome (GHIS). He was short in stature, had high circulating levels of GH, and low circulating levels of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3). His GH responses to the administration of growth hormone-releasing hormone (GHRH) and L-DOPA were normal, but his levels of IGF-I and IGFBP-3 did not increase after the administration of exogenous GH. Direct genomic DNA sequencing revealed neither a mutation nor deletion in this patient's GH receptor (GHR) gene, though one polymorphism was detected, indicating that his GHR gene was normal. This is the first reported case of an association of GHIS with syringomyelia and Chiari-I malformation.

Acute myeloid leukemia and colon carcinoma during the course of acromegaly.

We describe the case of a 70-year-old male with acromegaly who developed colon carcinoma and myelodysplastic syndrome (MDS) during the course of acromegaly. MDS progressed to acute myeloid leukemia, but was refractory to chemotherapy. Acromegaly is a rare disorder caused by excessive amounts of growth hormone (GH) primarily secreted by pituitary adenomas. Patients with acromegaly are more prone to develop various malignancies, but there are few reports of hematological malignancies in such patients. In the present case, excessive endogenous GH and insulin-like growth factor-I levels may have altered cell proliferation and thereby affected the oncogenesis and chemosensitivity of both malignancies.

Multiple endocrine neoplasia type I and Cushing's syndrome due to an aggressive ACTH producing thymic carcinoid.

Thymic carcinoid in multiple endocrine neoplasia type 1 (MEN 1) is previously reported as a non-ACTH producing tumor. The present case is a 39-year-old man with mortal outcome from thymic carcinoid and Cushing's syndrome with high plasma ACTH. The symptom was first observed at age 29 and was relieved after extended thymectomy, with reduction of ACTH level. The tumor was positive for ACTH, Grimelius silver staining and Chromogranin A. The finding of primary hyperparathyroidism, pituitary adenoma, and a novel germline nonsense mutation (W423X) established the diagnosis of MEN 1. Cushing's syndrome due to ACTH producing thymic carcinoid should be also considered as one phenotype of the MEN 1 spectrum.

Distribution of thyrostimulin in the rat: an immunohistochemical study.

OBJECTIVE: To identify the distribution of thyrostimulin, a heterodimer of glycoprotein hormone subunits (A2 and B5) by immunohistochemistry in the rat tissues using specific antipeptide anti-serum which we recently produced. METHOD: Anti-thyrostimulin antibody was raised in New Zealand white rabbits immunized with a conjugate of synthetic A2 or B5 with bovine serum albumin. Immunohistochemical analysis was performed by avidin-biotin complex method. RESULTS: Thyrostimulin immunoreactivity was visualized in the anterior pituitary, central nervous system, adrenal gland, stomach, duodenum, pancreas and testis. When using antiserum pre-incubated with synthetic peptides or rat pituitary homogenate which contains thyrostimulin peptide, no significant stain of the pituitary was detected. CONCLUSION: These findings suggest that thyrostimulin is widely distributed and that the method used is valuable in studying the distribution of thyrostimulin in rats.

Radioimmunoassay for aquaporin-9.

OBJECTIVE: To develop radioimmunoassay for aquaporin-9 (AQP9) and search for its presence in certain rat tissues. METHODS: Anti-AQP9 antiserum has been raised in New Zealand white rabbits immunized with a conjugate of synthetic AQP9 with bovine serum albumin. Radioiodination of AQP9 was performed by chloramin T method followed by purification of radioiodinated material on Sephadex G-25 column. RESULTS: The obtained antibody did not crossreact with other aquaporins, hypothalamic hormones, pituitary hormones, neuropeptides or gut hormones. The assay was performed with a double antibody system. AQP9 was extracted from the tissues with acid acetone. The dilution curve of acid acetone extracts of rat liver in the radioimmunoassay system was parallel to the standard curve. The recovery of tissue AQP9 was about 90%, and the intra-assay and inter-assay variations were 4.8% and 7.9%, respectively. AQP9 was found in the liver, testis and brain. CONCLUSION: These data suggest that this assay system is suitable for the estimation of AQP9 in the tissues.