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There are many new nuclear methods in diagnosing cardiovascular disease. We present about 2 nuclear diagnosing methods. One is about 123I-BMIPP and the other 123I-MIBG. 123I-beta-methyl iodophenyl pentadecanoic acid(123I-BMIPP) is the tracer to evaluate the metabolism of a fatty acid of the heart. A combination of perfusion and fatty acid imagings indicates the recovery of cardiac wall motion can be expected in acute myocardial infarction in zones where 123I-BMIPP decreased uptake is greater than 201T1 perfusion defect. In angina pectoris, especially in unstable angina, 123I-BMIPP may be available to detect myocardial ischemia. 123I-meta-iodobenzylguanidine(123I-MIBG) is the trace that be able to assess the heart with sympathetic innervation. 123I-MIBG scintigraphy is a useful noninvasive method for the assessment of not only myocardial ischemia but also the degree of congestive heart failure. Also, it is a useful in assessment of beta-blocker therapy.
The accuracy of radiological examinations has improved and their diagnostic ability has markedly increased. However, the cost of such examinations has also recently become an issue. In this study, the clinical significance of radiological examinations for sensorineural hearing loss (SNHL) was evaluated and the value of their utilization was reconsidered. A total of 1,276 ears of 724 patients who demonstrated unilateral or bilateral SNHL was studied retrospectively. Findings of radiological examinations such as plain X-ray (X-p), computed tomography (CT) and magnetic resonance imaging (MRI) of the brain or the temporal bone were investigated. Temporal bone X-p was usually performed to rule out acoustic tumors (AT). CT was further performed in 119 patients (16.4%) and MRI in 84 patients (11.6%) in total. The reasons or symptoms for further examination such as CT or MRI were X-p findings or auditory symptoms suspicious for AT or vertigo/dizziness suspicious for intracranial disease. Of five causes with AT, two with a small tumor exhibited normal findings for the internal auditory canal on temporal bone X-p. These small ATs were finally confirmed by MRI. MRI could also detect lacunar infarctions, cerebral atrophy and high jugular bulb which might be related to SNHL. These findings confirmed that MRI is very useful for detecting small ATs and suggested that MRI also reveals cerebral vascular insufficiency in patients with SNHL.
Vpr, one of the accessory gene products of HIV-1, is a 96-residue protein with several functions. It is involved in import of the HIV-1 preintegration complex into the nucleus of nondividing cells, in cellular differentiation, inducing cell cycle arrest at the G(2)/M phase, in immune suppression, and in enhancement of replication of the virus. We found recently that Vpr interferes with the proliferation of mouse NIH3T3 fibroblasts but fails to arrest these cells in the G(2) phase. Thus, it seems possible that Vpr might retard cell proliferation via a novel pathway that is distinct from G(2) arrest. To elucidate the mechanism by which Vpr induces the retardation of cell growth, we developed a panel of expression vectors that encoded Vpr molecules with deletions of specific putative domains, namely, the first alpha-helical domain, the second alpha-helical domain, a leucine zipper-like domain, and an arginine-rich carboxy-terminal domain. These vectors were introduced into HeLa cells since expression of Vpr can induce G(2) arrest in such cells. A carboxy-terminally truncated form of Vpr, C81, which failed to induce G(2) arrest, led to the G(1) arrest and retained the ability to prevent cell proliferation. All the other mutant proteins had completely lost the capacity to induce G(2) arrest and to suppress growth. Substitutions of Ile/Leu for Pro at positions 60, 67, 74, and 81 within the leucine zipper-like domain of Vpr or of C81 revealed that Ile60, Leu67, and Ile74 play an important role in the C81-induced suppression of growth, while Ile74 and Ile81 were found to be indispensable for Vpr-induced G(2) arrest. Collectively, our results strongly suggest that Vpr can retard cell proliferation independently of G(2) arrest of the cell cycle.
A recent physiological report suggested that neurotensin could inhibit the vasopressin releasing from vasopressin-producing neurons in the hypothalamic paraventricular nucleus but not in the supraoptic nucleus. In the present study, the synaptic relationship between the neurotensin-like immunoreactive and vasopressin-like immunoreactive neurons has been examined using a pre-embedding double immunostaining technique in the rat hypothalamic paraventricular nucleus. At the light microscopic level, many neurotensin-like immunoreactive fibers were found near the vasopressin-like immunoreactive neurons. At the electron microscopic level, the neurotensin-like immunoreactive fibers were identified as axon terminals that made many synapses on the vasopressin-like immunoreactive perikarya and dendrites. The synapses were both asymmetrical and symmetrical. These findings of the present study suggest that the inhibitory effect of neurotensin on the vasopressin neurons in the hypothalamic paraventricular nucleus may be due to the direct synapses made by neurotensin-like immunoreactive axon terminals on the vasopressin-like immunoreactive neurons.
Involvement of nitric oxide (NO) has been reported in physiological and pathological conditions in the inner ear. Recently, the presence of nitric oxide synthase (NOS) was demonstrated in the vestibular epithelium. In this study we used nicotinamide adenine dinucleotide phosphate-diapholase staining to monitor NOS activity during degeneration of guinea pig vestibular epithelia affected by streptomycin. Increased NOS activity was observed in affected epithelia in a dose- and time-dependent manner and a NOS inhibitor could protect hair cells from apoptosis. Additionally, cycloheximide significantly reduced NOS activity and the occurrence of apoptosis. These findings suggest that NO is involved in the degenerative process of vestibular epithelia caused by aminoglycosides.
Postnatal development, such as synapse refinement, is necessary for the establishment of a mature and functional central nervous system (CNS). Using differential display analysis, we identified a novel gene, termed Bdm1, that is more abundantly expressed in the adult brain than in the embryonic brain. The full-length Bdm1 cDNA is 2718 base pairs long and contains an open reading frame of 1059 base pairs encoding a 38-kDa protein. Northern blot analysis revealed that expression of Bdm1 mRNA in the brain was weak on embryonic days and increased in the early postnatal period. Bdm1 mRNA was significantly expressed in the brain and heart, but there was no or little expression in other tissues. During the differentiation of mouse carcinoma cells P19 to neuron-like cells by retinoic acid, Bdm1 mRNA was up-regulated almost parallel to neurofilament mRNA. Expression of Bdm1 mRNA was observed appreciably in PC12 cells after neuronal differentiation but not in the nonneural cell lines examined. In situ hybridization demonstrated that Bdm1 was expressed widely in the olfactory bulb, cerebral cortex, hippocampus, cerebellum, thalamus, and medulla oblongata. Taken together, these data suggest that Bdm1 gene plays a role in the early postnatal development and function of neuronal cells.
Intense immunoreactivity for the leptin receptor was detected in the hypothalamic arcuate nucleus (ARC), ventromedial nucleus (VMH), and lateral hypothalamus (LH) by immunohistochemistry. Cytosolic Ca2+ concentration ([Ca2+]i) in single neurons isolated from the ARC, VMH and LH was measured with dual wavelength fura-2 fluorescence imaging. A reduction of the superfusate glucose concentration from 10 to 1 mM increased [Ca2+]i in 21% of ARC neurons and 22% of LH neurons. Leptin at 0.1 nM inhibited the [Ca2+]i increase in 66 and 64% of these glucose-sensitive ARC and LH neurons, respectively. Inversely, 10 mM glucose increased [Ca2+]i in 49% of the VMH neurons, and 0.1 nM leptin at 1 mM glucose also increased [Ca2+]i in 84% of these glucose-responsive neurons. These results reveal that leptin inhibits the ARC and LH neurons and stimulates the VMH neurons via the leptin receptor expressed in these cells.
Transient global ischemia caused by 5 min of cardiac arrest induced delayed neuronal cell death (apoptosis) in the CA1 region of the rat hippocampus. To characterize the molecular mechanisms that regulate apoptosis in vivo, the contributions to cell death of mitogen-activated protein kinase family members were examined in the hippocampal region after brain ischemia-reperfusion. Ischemia-reperfusion led to a strong activation of the JNK/SAPK (c-Jun NH2-terminal protein kinase/stress activated protein kinase), ERK (extracellular signal-regulated kinase), and p38 enzymes. These results with other previous studies suggest that the activation of JNK/SAPK in accordance with p38 contributes to the induction of apoptosis in CA1 neurons.
OBJECTIVE: This study investigated the role of leptin on eating behavior and reproductive function in eating disorders. METHOD: The subjects included 80 eating-disordered women, having different fat mass, eating behavior, and endocrine abnormalities, and 26 control women. Plasma leptin, insulin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), cortisol, insulin growth factor-1 (IGF-1), free T4 levels, percent body fat, eating behavior score, and menstrual status score were evaluated for each subject. RESULTS: In eating-disordered patients, log of leptin levels were significantly correlated with body fat mass, eating behavior score, menstrual status score, and insulin, LH, and FSH levels. Stepwise regression analysis showed that fat mass and eating behavior score were significant determinants of leptin levels. Furthermore, in patients undergoing recovery, leptin levels were determined by fat mass and/or eating behavior. DISCUSSION: These results suggest that leptin may play some role in counteracting the abnormal eating behavior, reproductive function, and fat mass in these disorders.
It has been shown that lipid peroxidation is associated with hepatic fibrosis and stellate cell activation. Sho-saiko-to (TJ-9) is an herbal medicine, which is commonly used to treat chronic hepatitis in Japan, although the mechanism by which TJ-9 protects against hepatic fibrosis is not known. As a result, we assayed the preventive and therapeutic effects of TJ-9 on experimental hepatic fibrosis, induced in rats by dimethylnitrosamine (DMN) or pig serum (PS), and on rat stellate cells and hepatocytes in primary culture, and assessed the antioxidative activities and the active components of TJ-9. Male Wistar rats were given a single intraperitoneal injection of 40 mg/kg DMN or 0.5 mL PS twice weekly for 10 weeks. In each model, rats were fed a basal diet throughout, or the same diet, which also contained 1.5% TJ-9, for 2 weeks before treatment or for the last 2 weeks of treatment. TJ-9 suppressed the induction of hepatic fibrosis, increased hepatic retinoids, and reduced the hepatic levels of collagen and malondialdehyde (MDA), a production of lipid peroxidation. Immunohistochemical examination showed that TJ-9 reduced the deposition of type I collagen and the number of alpha-smooth muscle actin (alpha-SMA) positive-stellate cells in the liver and inhibited, not only lipid peroxidation in cultured rat hepatocytes that were undergoing oxidative stress, but also the production of type I collagen, alpha-SMA expression, cell proliferation, and oxidative burst in cultured rat stellate cells. In addition, TJ-9 inhibited Fe2+/adenosine 5'-diphosphate-induced lipid peroxidation in rat liver mitochondria in a dose-dependent manner and showed radical scavenging activity. Among the active components of TJ-9, baicalin and baicalein were found to be mainly responsible for the antioxidative activity. These findings suggest that Sho-saiko-to (TJ-9) functions as a potent antifibrosuppressant by inhibition of lipid peroxidation in hepatocytes and stellate cells in vivo.
The aim of the present study was to determine the factors controlling leptin secretion and to clarify the role of leptin in eating disorders. The subjects were 152 eating-disordered women with different fat mass, eating behavior, and endocrine abnormalities and 24 age-matched control subjects. The body fat mass, eating behavior score, and plasma leptin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), triiodothyronine (T3), free thyroxine (T4), insulin, and cortisol levels were evaluated for each subject. In patients with eating disorder, logarithmic values for leptin were significantly correlated with the body fat mass (r = .828, P < .001), eating behavior score (r = .777, P < .001), and LH (r = .465, P < .001), FSH (r = .440, P < .001), T3 (r = .572, P < .001), insulin (r = .410, P < .001), and cortisol (r = -.389, P < .001) levels. After adjusting for fat mass, the partial correlations of log leptin with LH, FSH, insulin, and cortisol were not statistically significant, but log leptin remained correlated with T3 (r = .390, P < .01). Stepwise regression analysis showed that the body fat mass and eating behavior score were significant determinants of leptin levels. These results suggest that eating behavior, as well as the body fat mass, is the control factor for leptin secretion in eating disorders.
A simple preembedding avidin-biotin-peroxidase complex technique was used to study the ultrastructural localization of mu-opioid receptor in the rat area postrema. By using low concentrations of the first antiserum for incubation with a short reaction time to 3,3'-diaminobenzidine, the immunostaining was faint at the light microscopic level. However, at the electron microscopic level, strong immunoreaction was observed. Mu-Opioid receptors were found to be localized on the postsynaptic membrane of dendrites, extrasynaptic plasma membrane, and the surface of the small, clear vesicles in axon terminals. Of the total 283 immunopositive profiles observed, 68.2% (193 of 283) were dendrites, 29.3% (83 of 283) were axon terminals, and 2.5% (7 of 283) were myelinated axons. No immunostained neuron bodies were found in the present study; 109 mu-opioid receptor immunoreactive dendrites received synapses (56.5%, 109 of 193) from nonimmunoreactive (84.4%, 92 of 109) or immunoreactive (15.6%, 17 of 109) axon terminals, whereas 84 dendrites (43.5%, 84 of 193) were found without receiving synapses. The present study shows that the mu-opioid receptor in the area postrema plays a role mainly at the synapses.
The distribution and localization of the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor the PAC1 receptor (previously called the type 1 PACAP receptor or PVR1), which binds PACAP, but not vasoactive intestinal peptide, with high affinity] were first investigated in rats with in situ hybridization for its messenger RNA, and with immunohistochemical methods during prenatal and postnatal development. The expression of PACAP receptor messenger RNA was first detected in the rat embryo at the primitive streak stage as early as embryonic day 9, and it was intensely expressed in the neural plate. PACAP receptor messenger RNA was also intensely expressed in the neuroepithelia of the mesencephalon and rhombencephalon at embryonic day 11, and expressed in the basal telencephalon, hippocampal formation neuroepithelium, cortical neuroepithelium and cerebellar neuroepithelium after embryonic day 13. It was also expressed in the olfactory bulb neuroepithelium after embryonic day 16, and in mature regions of the older embryos. In postnatal developing brains, PACAP receptor messenger RNA was intensely expressed in the olfactory bulb, hippocampal formation, cerebellum and other scattered regions. The localization of PACAP receptor-like immunoreactivity coincided well with that of the gene transcripts. We also used reverse transcription-polymerase chain reaction methods to determine the expression of the splice variants of the PACAP receptor gene. At each ontogenetic stage of the rat from embryonic day 9 to postnatal day 60, two major products were detected with reverse transcription-polymerase chain reaction, a thick band (303 base pairs) corresponding to the short splice variant of the receptor that lacks both the "hip" and "hop" cassettes, and a thin band (387 base pairs) corresponding to the splice variant that contains one cassette of "hop" or "hip". There was no evidence for the other larger splice variants. Some of the amplified products were sequenced and found to have the exact sequences of "PACAP receptor" and "PACAP receptor-hopl", which are coupled to different signal transduction pathways. These results indicate that the PACAP receptor is actively expressed in different neuroepithelia from early developmental stages and expressed in various brain regions during prenatal and postnatal development, and that the major splice variants are "PACAP receptor" and "PACAP receptor-hopl". The initial mapping of ontogenetic localization of the PACAP receptor provides the basis for a better understanding of the functions of PACAP and its receptors during the development of the brain.
OBJECTIVE: To clarify the characteristics of fetoplacental blood flow of growth-restricted fetuses with hypercoiled umbilical cord. SUBJECTS: Eight growth-restricted fetuses with hypercoiled cord. METHODS: Flow velocity waveforms of the umbilical cord artery and vein, fetal abdominal aorta and fetal inferior vena cava were analyzed. RESULTS: The resistance index in the umbilical artery in the hypercoiled cases was lower than that in normal fetuses. Early-diastolic reversed flow was observed in the abdominal aorta in some cases. In all cases, umbilical venous pulsation was observed in the entire cord until delivery. In one case, fetal heart failure occurred, resulting in pre-mature delivery. An atrophic type of single umbilical artery was observed in four cases. CONCLUSION: Fetal blood flow disturbance caused by a hypercoiled umbilical cord may be a cause of growth restriction.
OBJECTIVE: To determine the fluid flow velocity waveforms in the fetal peripheral bronchus during fetal breathing movement by means of pulsed Doppler ultrasonography. DESIGN: A preliminary cross-sectional study. SUBJECTS: Twenty-eight normal pregnant women between 32 and 38 weeks of gestation. METHODS: Velocity waveforms from fetal peripheral respiratory fluid flow were acquired from the segmental bronchus (B6 or B8) which runs along the segmental artery (A6 or A8). The maximum velocity of the intrabronchial fluid flow and duration of inspiratory and expiratory phases were quantified. RESULTS: The flow velocity signal from the fluid in the fetal segmental bronchus of 17 of the 28 fetuses was detected. We observed two types of fetal breathing movement. CONCLUSION: During fetal breathing movement, the fluid in the fetal respiratory tract moves in the fetal segmental bronchus. This movement can be detected by pulsed Doppler velocimetry aided by power Doppler ultrasonography.
PURPOSE: To examine the effects of calcitonin gene-related peptide (CGRP) on intraocular pressure (IOP). METHODS: IOP was periodically measured in rabbits treated with intravitreal injection (20 ael) of either: 1) CGRP (10(-4) approximately 10(-7) M) into one eye; 2) CGRP (10(-4) or 10(-6) M) into both eyes 30 min after intravitreal administration of CGRP-(8-37) (10( -3) M), a CGRP1 receptor antagonist, into one eye; 3) CGRP (10(-4 ) or 10(-6) M) into one eye 30 min after intravenous administration (200 mg/kg) of either Nw-nitro-L-arginine methyl ester (L-NAME), a nonselective inhibitor of nitric oxide synthase (NOS), or aminoguanidine (AG), a selective inhibitor of inducible NOS; or 4) CGRP (10(-4) or 10(-6) M) into one eye along with intraperitoneal indomethacin (50 mg/ kg at -1 and 4 h). RESULTS: CGRP (10(-4) and 10(-5) M) produced a biphasic IOP response, which consisted of an early ocular hypertensive phase and a subsequent sustained hypotensive phase. While CGRP (10(-6) M) yielded only a profound IOP reduction. CGRP-(8-37) significantly inhibited the IOP elevation induced by CGRP (10(-4) M) and completely abolished the IOP reduction induced by CGRP (10(-6) M). The IOP increase induced by CGRP (10(-4) M) was completely abolished by L-NAME, but not affected by AG. The IOP reduction induced by CGRP (10(-6) M) was not affected by L-NAME. Indomethacin did not significantly affect the IOP responses to CGRP. CONCLUSIONS: CGRP dose-dependently produces a biphasic IOP response, which is mediated by CGRP1 receptors. It is suggested that constitutive NOS is involved in the early ocular hypertensive response.
OBJECTIVES: The aim of this study was to determine roles of fibronectin and eosinophils in the etiology of nasal polyposis. STUDY DESIGN: We designed a cohort study of cases with nasal polyposis. Sampled nasal polyps were differentiated by their histopathologic characteristics, and compared by size and computed tomography (CT) stage. METHODS: The size of nasal polyps was determined on the basis of the endoscopic findings, and the extent of sinusitis was evaluated by CT staging. Nasal polyp samples were taken from 82 patients during ethmoidectomy and differentiated by morphologic characteristics, infiltration cell types, or fibronectin positivity. Then their sizes and CT stages were compared. In addition, correlation among these histological characteristics was analyzed. RESULTS: Nasal polyps showing edematous morphology, eosinophil infiltration, or fibronectin expression were significantly large in size. Concerning CT stages, only the infiltration cell type showed a significant difference. Significant correlation among edematous morphology, eosinophil infiltration, and fibronectin expression was also recognized. CONCLUSIONS: These findings suggest that interaction between eosinophils and fibronectin may play a role in edema formation, which contributes to the growth of nasal polyps.