Transient and sustained effects of dopamine and serotonin signaling in motivation‐related behavior

Pharmacological studies of antidepressants and atypical antipsychotics have suggested a role of dopamine and serotonin signaling in depression. However, depressive symptoms and treatment effects are difficult to explain based simply on brain‐wide decrease or increase in the concentrations of these molecules. Recent animal studies using advanced neuronal manipulation and observation techniques have revealed detailed dopamine and serotonin dynamics that regulate diverse aspects of motivation‐related behavior. Dopamine and serotonin transiently modulate moment‐to‐moment behavior at timescales ranging from sub‐second to minutes and also produce persistent effects, such as reward‐related learning and stress responses that last longer than several days. Transient and sustained effects often exhibit specific roles depending on the projection sites, where distinct synaptic and cellular mechanisms are required to process the neurotransmitters for each transient and sustained timescale. Therefore, it appears that specific aspects of motivation‐related behavior are regulated by distinct synaptic and cellular mechanisms in specific brain regions that underlie the transient and sustained effects of dopamine and serotonin signaling. Recent clinical studies have implied that subjects with depressive symptoms show impaired transient and sustained signaling functions; moreover, they exhibit heterogeneity in depressive symptoms and neuronal dysfunction. Depressive symptoms may be explained by the dysfunction of each transient and sustained signaling mechanism, and distinct patterns of impairment in the relevant mechanisms may explain the heterogeneity of symptoms. Thus, detailed understanding of dopamine and serotonin signaling may provide new insight into depressive symptoms.     

Monolayer cultures of normal human bone cells contain multiple subpopulations of alkaline phosphatase positive cells

Summary Cytochemical staining of normal human bone cells in monolayer cultures for alkaline phosphatase (ALP) indicated that the cultures contained mixed-cell populations. Time course evaluations of the cytochemical staining revealed, in addition to the ALP-negative cell population, at least two subpopulations of ALP-positive human bone cells with different levels of ALP. A cytochemical method has been developed which separates the ALP-positive cells into high and intermediate ALP subpopulations. In this method, human bone cells were stained for ALP using an azo-dye method and incubating at 4°C for 10 and 30 minutes, respectively. We defined the cell population that stained positively for ALP at 10 minutes as strong ALP-positive cells, and both strong and intermediate cells were stained at 30 minutes. The intermediate cells were determined from the difference between the values at the two time points. The intra- and interassay variations of the assay, with the same investigator in blinded investigations, were both less than 10% and the interobserver variation was approximately 25%. Analysis of the distribution of ALP levels in cells with a laser densitometer confirmed the presence of at least three cell subpopulations. 1,25(OH)₂D₃ treatment increased the proportions of both ALP-positive cell populations, whereas TGF-beta treatment increased only the intermediate ALP-positive cell population. On the contrary, fluoride increased the proportion of the strong ALP cells, and IGF-1 had no effect on the proportions of either ALP-positive subpopulation. When the ALP-specific activity was compared with the percentage of each ALP-positive subpopulations for the cells treated with effectors, the ALP-specific activity correlated with the total ALP-positive and with the strong ALP-positive populations but not with the intermediate ALP-positive subpopulation. In summary, this study represents the first evidence that normal human bone cells in monolayer cultures contained at least two subpopulations of ALP-positive cells, and that bone cell effectors could have differential effects on each cell population.     

A case of intraductal papillary mucinous neoplasm with internal pancreatic fistula causing left ureteral obstruction]

A 75-year-old man had been admitted to another hospital because of left abdominal pain, and was given a diagnosis of left hydronephrosis and acute pancreatitis. After a JJ stent insertion and medication, he was transferred to our hospital for further examinations. US and EUS revealed a chronic pancreatitis-like pattern and multicystic lesion in the pancreas head and body. At that time enhanced CT findings showed an extrapancreatic low density area to be inflammatory change, extending from the pancreas body to the left crus of the diaphragm and posteriorly the spreading from the left crus of the diaphragm via the left urinary duct into the left iliopsoas muscle, in which MRI revealed partial high intensity. ERCP and MRCP showed focal irregular narrowing of the pancreatic duct of unknown cause, and we decided that an internal pancreatic fistula due to pancreatitis had induced left ureteral obstruction, caused by a protein plug or alcohol. Follow-up 6 months later showed that extrapancreatic spreading of the low density area had markedly regressed without any change in the ureteral obstruction.     

Surgical treatment of extensive hemangiomas of the liver

The results of treatment of 7 patients with extensive hepatic hemangiomas are analysed. In 6 patients the diagnosis was established before the operation. The liver was resected in 4 patients. One patients with malignant degeneration of the hemangioma was inoperable, in another the hemangioma was not removed because of his old age, and still in another because the process had spread. The authors conclude that in large hemangiomas of the liver in young and middle-aged patients resection of the organ is indicated, especially if there is a destruction cavity and a rapid growth of hemangioma. The operation is not indicated in capillary, surface hemangiomas of a small size, old age of the patient, extension of the process in to the main vascular structures of the other hepatic lobe.     

Effect of systemic zinc administration on delayed neuronal death in the gerbil hippocampus

The divalent cation zinc has been reported to possess several physiological properties such as blocking apoptotic cell death through an inhibitory effect on Ca²⁺-Mg²⁺ endonuclease activity, or modulating the neurotoxicity via glutamate receptor subtypes. In the present study, we investigated the effect of peripherally injected zinc on delayed neuronal death seen in the hippocampus after transient global ischemia, in order to elucidate a possible beneficial role on zinc in ischemic neuronal cell death. Forty-five adult Mongolian gerbils of both sexes underwent transient bilateral clipping of the common carotid arteries for 3 min. In the pretreated animals, ZnCl₂ (20 mg/kg) was injected subcutaneously once, 1 h before ischemia (superacute group; n=6) or twice at 24 and 48 h before ischemia (subacute group; n=14). Histological survey was carried out 3 days later by in situ DNA fragmentation method and 4 days later by hematoxylin-eosin staining by semiquantatively counting dead neurons in the CA1 sector. Subacute zinc pre-administration significantly reduced the nuclear damage and subsequent neuronal death; however, superacutely pre-administered zinc did not protect hippocampal neurons against ischemia but it did not aggravate the effect of ischemia, either. The present study suggested that transfer of exogenous zinc into the intracellular space is required for neuroprotection, presumably via the anti-endonuclease activity.     

Pharyngeal Patency in Response to Advancement of the Mandible in Obese Anesthetized Persons

Background: During anesthesia in humans, anterior displacement of the mandible is often helpful to relieve airway obstruction. However, it appears to be less useful in obese patients. The authors tested the possibility that obesity limits the effectiveness of the maneuver.

Methods: Total muscle paralysis was induced under general anesthesia in a group of obese persons (n = 9; body mass index, 32 +/- 3 kg sup -2) and in a group of nonobese persons (n = 9; body mas index, 21 +/- 2 kg sup -2). Nocturnal oximetry confirmed that none of them had sleep-disordered breathing. The cross-sectional area of the pharynx was measured endoscopically at different static airway pressures. A static pressure-area plot allowed assessment of the mechanical properties of the pharynx. The influence of mandibular advancement on airway patency was assessed by comparing the static pressure-area relation with and without the maneuver in obese and nonobese persons.

Results: Mandibular advancement increased the retroglossal area at a given pharyngeal pressure, and mandibular advancement increased the retropalatal area in nonobese but not in obese persons at a given pharyngeal pressure.     

Successful Repair of the Right Atrial Isomerism, Double Outlet Right Ventricle, Cornmon Atrioventricular Canal, Pulmonary Stenosis, and Total Anomalous Pulmonary Venous Connection

A 6-year-old boy was successfully operated on for double outlet ventricle, common atrioventricular canal with severe valvular regurgitation, right atrial Isomerism, L-loop ventricles, total anomalous pulmonary venous connection, and pulmonary stenosis with hypoplastic left pulmonary artery. The Interventricular rerouting from the left ventricle to the ascending aorta was performed with a spiral patch, the lnteratrlal switching was performed by a Mustard patch, the common atrioventricular orifice was partitioned and valve repair was performed, and an 18-mm valved conduit was inserted between the right ventricle and the pulmonary artery. Although the patient had a small residual ventricular septal defect and pulmonary stenosls, the patient Is alive and well.     

Localization of basic FGF-like immunoreactivity in the hypothalamo-hypophyseal neuroendocrine axis

We examined the localization of basic fibroblast growth factor (basic FGF) in the adult rat brain by immunohistochemical and Western blotting analysis using a specific antibody against a synthetic basic FGF fragment (N-terminal 12 residues). The antibody did not cross-react with acidic FGF. Basic FGF-like immunoreactivity was located exclusively in the neuronal elements and had very heterogenous distribution. Immunoreactive cell bodies were observed in the paraventricular, supraoptic and circular nuclei of the hypothalamus. Numerous immunoreactive neuronal processes originating from these basic FGF-positive cells extended lateroventrally and then caudally to the internal layer of the median eminence. In addition, the neurohypophysis contained a significant number of basic FGF-like immunoreactive fibers. Western-blotting analysis revealed that the hypothalamus and the hypophysis contained a main band of basic FGF immunoreactive with an apparent molecular weight of 17 kDa. These results show that the hypothalamo-hypophyseal neuroendocrine pathway contains basic FGF.     

Relation between Estrogen Receptor and Malignancy of Thyroid Cancer

The relationship between the histological grade of dedifferentiation of thyroid cancer and estrogen receptors (ER) was examined immunohistochemically. Thyroid cancers were from postmenopausal females of almost the same mean age (69-73 years old) and within the same period of time (1974–1983). ER immunoreactivity located in the nucleus of the epithelium was found in all 6 well differentiated papillary cancers, and 5 of them (83.3%) showed ER-immunoreactive (ER-IR) cells amounting to 20 or more per visual field (x 100) under a light microscope. Of the 6 cases of poorly differentiated papillary cancer, 5 (83.3%) had 1-19 ER-IR cells per visual field. ER-IR cells were negative in 5 out of 6 cases (83.3%) of anaplastic cancers. Thus, the number of ER-IR cells tended to decrease with the degree of atypism of thyroid cancer (P < 0.001).