Takayasu's arteritis and mitral stenosis

A 44-year-old housewife was found to have coarctation of the abdominal aorta secondary to Takayasu's arteritis. Since she also had mitral stenosis, possible etiological relation between Takayasu's arteritis and mitral stenosis is suspected.     

Tc-99m tetrofosmin myocardial perfusion SPECT after dipyridamole combined with low-level exercise in the diagnosis of coronary artery disease

Tc-99m tetrofosmin is a lipophilic, cationic perfusion imaging agent that changes to Tl-201 in detecting coronary artery disease during exercise testing. The purpose of this study is to evaluate the usefulness of Tc-99m tetrofosmin dipyridamole stress imaging combined with low level exercise for the detection of coronary artery disease. We examined 42 patients and 10 normal volunteers who also underwent coronary angiography. A one-day protocol was used: in the stress study, 296 MBq of tetrofosmin was injected and in the rest study 888 MBq was injected. After intravenous administration of dipyridamole (0.142 mg/kg/min for 4 minutes), the patient was exercised on a bicycle ergometer for 3 min (25 Watts). Tetrofosmin was injected 2 minutes after dipyridamole infusion during the exercise. Single photon emission computed tomographic images were obtained 30 minutes after the tracer injection. Images were interpreted as abnormal in 36 of 42 patients with coronary artery disease, and normal in all of 10 normal volunteers. The overall sensitivity of detection of coronary artery disease was 83.3% and the normalcy rate was 100%. The diagnostic values for the detection of significant stenosis in the three major arteries were: LAD sensitivity 83%, specificity 92%; LCX sensitivity 47%, specificity 91%; RCA sensitivity 75%, specificity 83%. Of the 66 arteries with more than 50% stenosis, 48 arteries were correctly identified. Of the 36 with more than 70% stenosis, 31 were identified. Scintigraphic evidence of multivessel disease was found in only 9 patients (50%). A protocol of Tc-99m tetrofosmin SPECT combined with low level exercise after dipyridamole is therefore useful for the detection of the coronary artery disease.     

Accuracy of the Master's exercise test in detecting significant coronary artery disease

To assess the significance and accuracy of noninvasive tests in detecting significant coronary artery disease (CAD; greater than 50% stenosis), the Master's exercise test, treadmill exercise test and dipyridamole-loading myocardial perfusion scintigraphy were performed and their results were compared with coronary angiographic findings in 60 patients with angina but without myocardial infarction. Among these, 27 patients had significant CAD. The Master's test performed in outpatient clinics had an 85% sensitivity and a 76% specificity in detecting significant CAD, when the degree of ST depression was equal to or exceeded 1 mm. The sensitivity further improved to 96% by adding chest pain to the criteria; then all patients with multivessel disease or critical ischemia were identified by the Master's test. Treadmill tests performed after admission had a 78% sensitivity and a 67% specificity. When the severity of ischemia was judged either by exercise capacity or the degree of ST depression or the coronary T wave, the treadmill test was superior to the Master's test. Although patients without significant CAD had longer exercise capacity and the higher maximum heart rate in the treadmill test than did those in the Master's test, these trends were similar but less marked in patients with significant CAD. Dipyridamole-loading myocardial perfusion scintigraphy showed an excellent sensitivity and specificity; 96% and 94%, respectively, in detecting significant CAD. It was particularly useful in distinguishing false positive exercise results due to left ventricular hypertrophy and coronary spasm and that in women, from true positive results. In conclusion, the Master's test is a simple and useful method for screening CAD in community hospitals and in outpatient clinics.     

Immune activation during pregnancy in mice leads to dopaminergic hyperfunction and cognitive impairment in the offspring: a neurodevelopmental animal model of schizophrenia.

BACKGROUND: Maternal viral infection is associated with increased risk for schizophrenia. It is hypothesized that the maternal immune response to viruses may influence fetal brain development and lead to schizophrenia. METHODS: To mimic a viral infection, the synthetic double strand RNA polyriboinosinic-polyribocytidilic acid (poly I:C) was administered into pregnant mice. Behavioral evaluations (thigmotaxis, methamphetamine [MAP]-induced hyperactivity, novel-object recognition test [NORT]), sensorimotor gating (prepulse inhibition [PPI]), and biochemical evaluation of the dopaminergic function of the offspring of phosphate-buffered saline (PBS)-treated dams (PBS-mice) and that of poly I:C-treated dams (poly I:C-mice) were examined. RESULTS: In juveniles, no difference was found between the poly I:C-mice and PBS-mice. However, in adults, the poly I:C-mice exhibited attenuated thigmotaxis, greater response in MAP-induced (2 mg/kg) hyperlocomotion, deficits in PPI, and cognitive impairment in NORT compared with the PBS-mice. Cognitive impairment in the adult poly I:C-mice could be improved by subchronic administration of clozapine (5.0 mg/kg) but not haloperidol (.1 mg/kg). Increased dopamine (DA) turnover and decreased receptor binding of D2-like receptors, but not D1-like receptors, in the striatum were found in adult poly I:C-mice. CONCLUSIONS: Prenatal poly I:C administration causes maturation-dependent increased subcortical DA function and cognitive impairment in the offspring, indicating a neurodevelopmental animal model of schizophrenia.     

Classification of human liver transplant recipients by their preoperative CD8+ T cell subpopulation and its relation to outcome.

The primed status of T cells is markedly different among liver transplant recipients, due to a lifetime of antigen exposure and reduced thymopoiesis by aging, and diseases. This study aims to characterize the preoperative immunological status of CD8+ T cell subpopulations and relate it to the outcome for liver transplant recipients. We classified 112 liver transplant recipients into 5 groups, based on hierarchical clustering of the CD8+CD45 isoform proportion of T cells. In Groups I and II (pediatric), the naive T cell proportion was more than 50%. In adult recipients, Group III was characterized by a naive T cell proportion of 50%, Group IV had the greatest effector/memory T cells (EM), and Group V had the greatest proportion of effector T cells. In Groups IV and V, the effector T cell proportion was considerably higher, and was accompanied by marked downregulation of the CD27+CD28+ subsets and upregulation of interferon gamma (IFN)-gamma, tumor necrosis factor-alpha, and perforin expression. Group V recipients tended to be complicated postoperatively, with a significantly reduced survival rate (1 yr, 66.8%) and markedly reduced Eastern Cooperative Oncology Group performance status.     

Acquisition of interleukin-3 independence in FDC-P2 cells after transfection with the activated c-H-ras gene using a bovine papillomavirus-based plasmid vector.

Since the ras family of proto-oncogenes is supposed to be involved in leukemogenesis by point-mutational activation, we studied the effect of the activated ras gene on the growth of a murine interleukin-3 (IL-3)-dependent cell line, FDC-P2. The human activated c-H-ras gene was transfected into FDC-P2 cells by electroporation using a high-level expression vector, BMGhph, which contains a partial DNA sequence from bovine papillomavirus (BPV) and a hygromycin B (hmB)-resistant gene as a selectable marker. The transformed FDC-P2 cells showed a high incidence of IL-3-independent growth and tumorigenicity in nude mice. These clones did not express or secrete IL-3, suggesting the acquisition of IL-3 independence by a nonautocrine mechanism. The high incidence of autonomous growth may be due to the use of the BMG vector, because (1) the activated ras gene in pBR322 vector (pHs-49) was not so efficient in the induction of IL-3 independence, (2) the c-H-ras genome copies per cell increased in number up to about 50 copies by using the BMG vector, and (3) cotransfection with the activated ras gene and the BPV gene in separate plasmids partly enhanced the incidence of autonomous growth without increasing the copy number of the ras gene compared with transfection with the activated ras gene alone. The present study supports the idea that the activation of ras gene is an important step in malignant transformation of hematopoietic cells and suggests that the BPV gene products may cooperate with ras gene activation probably by affecting the cellular genes that may be involved in multistep leukemogenesis. The BMG vector may be useful to test the transforming ability of oncogenes whose oncogenic potential is relatively low.     

A differentiation-inducing factor produced by the osteoblastic cell line MC3T3-E1 stimulates bone resorption by promoting osteoclast formation

We have reported that the differentiation-inducing factor (DIF) is present in conditioned medium of mouse osteoblast-like cell (MC3T3-E1) cultures. In the present study, the DIF from conditioned medium of MC3T3-E1 cells was partially purified and its biologic activity was examined. The DIF was purified by monitoring the induction of phagocytic activity of mouse myeloblastic leukemia cells (M1). The DIF induced differentiation of not only M1 cells but also mouse myelomonocytic cells (WEHI-3). Furthermore, the DIF increased the in vitro bone-resorbing activity and the osteoclast number in mouse calvaria. The increases were inhibited by the addition of either salmon calcitonin or indomethacin. When mouse bone marrow cells were cultured with the DIF for 8 days, formation of osteoclast-like multinucleated cells was stimulated dose dependently. The DIF from MC3T3-E1 cells appeared to be different from interleukin-1 (IL-1), tumor necrosis factor (TNF), and transforming growth factor beta (TGF-beta). These results suggest that the DIF partially purified from osteoblast-like cell cultures stimulates osteoclastic bone resorption by promoting differentiation and fusion of osteoclast progenitors to form multinucleated osteoclasts.