Sonic motor nucleus and its connections with octaval and lateral line nuclei of the medulla in a rockfish, Sebastiscus marmoratus

The sonic motor nucleus and its fiber connections were examined in a rockfish, Sebastiscus marmoratus by means of tracer methods using horseradish peroxidase (HRP), biocytin, and carbocyanine dye (DiI). Sebastiscus has a swimbladder and a pair of extrinsic sonic/drumming muscles. The sonic muscle is ipsilaterally innervated by the occipital nerve which is composed of two ventral roots arising from the sonic motor nucleus. The sonic motor neurons are distributed in the most ventral part of the ventral column from the caudal medulla to the rostral spinal cord, and form a ventrally located columnar nucleus. Each neuron in this nucleus possesses a long thick dendrite and several short dendrites. The long dendrite extends dorsolaterally and branches in the lateral funiculus, whereas the short dendrites branch around their cell bodies. After biocytin injections into the sonic motor nucleus, two groups of premotor neurons were retrogradely labeled bilaterally, one in the dorsomedial portion of the descending octaval nucleus (DO) and the other in the medial zone of the reticular formation (RF) in the medulla. The DO premotor neurons were multipolar with several dendrites branching near the cell bodies, and the RF premotor neurons were bipolar. One of the two dendrites of the RF premotor neurons extends laterally into the ventral portion of the DO, and the other dendrite extends into the ventromedial area in the medulla. In the ventromedial dendritic field of the RF premotor neurons, descending fibers arising from the optic tectum (TO) and torus semicircularis (TS) traverse in the tractus tectobulbaris and terminate bilaterally. After DiI insertion into the ventromedial dendritic field, retrogradely labeled neurons were found bilaterally in the TS and TO. The majority of tectal neurons were located in the stratum griseum centrale. These neurons had two short basal dendrites branching in the cell layer and a long apical dendrite extending to the stratum fibrosum et griseum superficiale and stratum opticum. The toral neurons were bipolar and were distributed throughout the TS. Furthermore, biocytin injections into the medial nucleus of the lateral line system revealed that the nucleus projects bilaterally to the RF premotor neurons. These results show that premotor neurons for the sonic motor nucleus are located in the dorsomedial portion of the DO and the medial zone of the RF in the medulla. It is suggested that the sonic motor nucleus receives auditory input via the DO premotor neurons and input from RF premotor neurons which receive lateral line input via the medial nucleus, vestibular input through the lateral dendrite extending into the ventral portion of the DO, and information from the TO and TS via the tractus tectobulbaris.     

Protective effects of the TNF-ceramide pathway against glutamate neurotoxicity on cultured mesencephalic neurons

Pretreatments with TNF-alpha and lower concentrations of C2-ceramide protected cultured mesencephalic neurons from excitotoxicity in a dose-dependent manner. These protective effects are reduced by cotreatment with N,N-dimethylsphingosine (DMS), an inhibitor of sphingosine kinase. Since the pretreatment with sphingosine-1-phosphate (SPP) showed a neuroprotective effect, our data suggest that protective effects of TNF and C2-ceramide could be attributable to their further metabolism to SPP.     

Shock and acute organ dysfunction

Multiple trauma, hemorrhage, and sepsis may produce various kinds of shock, and such a host as shock could not be controlled and may easily fall into multiple organ dysfunction. Although those mechanisms on the pathogenesis of these sequential inflammatory responses have been clarified recently, the clinical outcome of such patients suffering from severe sepsis and multiple organ dysfunction is still very low. This inflammatory response against the insult shows a sequential manner; cardiovascular system failure, renal system failure, respiratory system failure, central nervous system failure, and finally, hepatic failure. However, the host response to the insult is a kind of defense against the invasion, and the clinical goal might be to stabilize hemodynamic system, metabolic system, and immunologic system. To achieve hemodynamic homeostasis, we use catecholamines and blood transfusion to improve the oxygen supply to important organs and enhance tissue repair. For metabolic homeostasis, early administration of hyperalimentation may be needed, either parenterally or enterally. Enteral feeding may also provided a route for bacterial translocation. To achieve immunologic homeostasis, prophylactic antibiotic administration and metabolic support may be required and should also protect against infection as a secondary invasion. This review explains these mechanisms in terms of the relationship between shock and organ dysfunction and the general features of clinical management.     

Structure and sequence of the mouse V1a and V1b vasopressin receptor genes

The structural organization and 5'-flanking region of the mouse V1a and V1b vasopressin receptor genes were determined. The mouse V1a receptor gene was located within an 8-kb XbaI fragment, and the mouse V1b receptor gene was located within a 14-kb EcoRV fragment. Both genes were comprised of two coding exons that were separated by a 2.3-kb and a 8.0-kb intron, respectively, located before the respective seventh transmembrane domain of the receptor sequence. The availability of these genes would allow us to study the functional role of V1a and V1b receptors by disrupting the gene in mice.     

Control of the dispersing process and pharmacokinetics in rats for lipid A analogue, E5531.

E5531 is a synthetic disaccharide analogue of lipid A which has a low toxicity but retains the ability to reduce production of tumour necrosis factor. This analogue has potential for use in the treatment of septic shock. An injectable formulation of E5531 would be useful, but dispersion in aqueous solution is a problem. In the present study the dispersing process for E5531 was evaluated using the pH-jump method (pH 11.0-->7.3). The size of the aggregates was decreased (reaching 20 nm) with increasing dispersing time in 0.003 M NaOH (pH 11.0). The membrane fluidity of the aggregates increased with increasing dispersing time. When prepared by the normal dilution method (pH 7.3-->7.3), the size of the aggregates remained constant at 140 nm and the membrane fluidity was smaller than that of samples prepared by the pH-jump method. This indicates that during dispersing at basic pH, the hydration proceeded in a normal manner, but then stopped, just after adjustment of the pH to 7.3. This suggests that the degree of hydration of the membrane is dependent on the dispersing time at pH 11.0. Using samples with different degrees of hydration and different membrane fluidity prepared by the pH-jump method, the pharmacokinetics and stability of the aggregates were evaluated after intravenous injection into rats. The data thus obtained confirmed that the membrane fluidity was correlated with the pharmacokinetics and stability in rat plasma. It was concluded that the pharmacokinetics of E5531 in rats can be controlled by changing the degree of hydration and membrane fluidity by means of using different dispersing times in alkaline solution (pH 11.0).     

A mild transient decrease of peripheral red blood cell counts induced by a suprapharmacological dose of pegylated human megakaryocyte growth and development factor in rats.

Previous studies have shown that pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) at suprapharmacological dose induces a mild transient decrease of red blood cell counts according to thrombopoiesis in normal mice. To unravel the mechanism underlying this mild transient decrease of red blood cells, we have studied the effect of PEG-rHuMGDF on the circulating plasma and blood volume, and the serum biochemical parameters of anaemia and splenectomy. Also, we have performed histological studies of the bone marrow and the spleen of PEG-rHuMGDF-treated rats. PEG-rHuMGDF (300 microg kg(-1)]) or vehicle was subcutaneously administered to rats once a day for up to five days. From day 6 after the start of PEG-rHuMGDF administration, the platelet counts and plateletcrit levels were significantly increased, reaching peak values on day 10, and recovering to normal by day 20. The red blood cell counts and the haematocrit levels were significantly decreased on day 6 to 13. The decreases in red blood cell levels and haematocrit produced by PEG-rHuMGDF treatment were mild and had recovered by day 15. The plasma and blood volumes were significantly increased on day 10 in PEG-rHuMGDF-treated rats. No alteration of the serum biochemical parameters for anaemia, iron or total bilirubin, were observed on day 10. The histological examination on day 10 revealed a marked increase in megakaryocytes and a slight decrease in erythropoiesis in the bone marrow of rats that received PEG-rHuMGDF (300 microg kg(-1)). There was also a slight increase in splenic megakaryocytes and erythropoiesis. The decrease of red blood cells by PEG-rHuMGDF was not affected by splenectomy. These results suggest that the mild transient decrease of red blood cells induced by PEG-rHuMGDF treatment for up to five days is based mainly on the increases in the plasma and blood volume. These events are secondary changes due to the regulation of the excess production of megakaryocytes in the marrow and the peripheral platelets.     

Colony stimulating factor-inducing activity of hesperidin.

To evaluate immunomodulating activities of bioflavones, colony-stimulating factor (CSF)-inducing activity of two dihydroflavones, three flavones and three flavonols were tested. These samples were suspended in saline and injected intraperitoneally (i.p.) into mice at a dose of 1 mg 6 h before bleeding. All compounds carrying the glucosyl-rhamnose moiety showed potent activity. Among them, hesperidin exhibited the strongest activity. Serum CSF production in mice injected with 1 mg hesperidin reached a peak at 9 h later. The activity of hesperidin was dose-dependent at a range of 0.3 to 20 mg/mouse.     

An acute fatal occupational cadmium poisoning by inhalation

Summary A 43-year-old male smelter was admitted to a hospital on account of severe dyspnea about 2 days after exposure to brownish-yellow smoke produced by melting of copper scrap. On admission pronounced hypoxemia was revealed, and an oxygen-enriched gas was administered after intubation. Although inspired oxygen concentration was gradually increased, hypoxemia progressed and he died on day 11 in hospital.The principal autopsy finding was chiefly confined to the lungs. Both lungs were heavy (the left weighing 1,470 g; the right 1,710 g) and firm to the touch. Histologically, no normal alveoli were found throughout the entire lung. Some alveolar spaces were occupied by pneumocytes, others by organized exudate with fibrosis. Interstitial fibrosis was present. Patchy areas of inflammatory cell infiltrations as well as intra-alveolar hemorrhages were observed. On the basis of the above findings a diagnosis of diffuse alveolar damage was made.Based on the available evidence (presence of cadmium in the copper scrap, feature of the smoke, clinical signs with latent time, and high cadmium concentration of the lung), the diffuse alveolar damage was considered to have been caused by inhaled cadmium. The pulmonary change of the present case was more advanced in pathologic stage in comparison with those reported in the literature.     

Malignant fibrous histiocytoma. Proliferative compartment and heterogeneity of "histiocytic" cells.

To elucidate the precise origin and characteristics of the proliferating cells in malignant fibrous histiocytoma (MFH), the authors analyzed 33 MFH tumors, using immunohistochemical techniques with a panel of 12 antibodies. All three types of MFH cells (spindle cells, polygonal cells, and bizarre giant cells) stained positively for mesenchymal antigens (FU3 and vimentin) but did not stain for macrophage/histiocyte markers (HAM 56 and CD68). Therefore, the MFH cells may not represent true histiocytes, although they may be mesenchymal-derived cells behaving as "facultative histiocytes" with superficial resemblance to actual histiocytes. Normal histiocytes in the stroma tested positive for macrophage/histiocyte antigens; the most common cells were HAM 56-positive cells constituting 30-80% of nonneoplastic stromal cells, followed by those positive for CD68 (10-50%), Mac 387 (less than 2%), and S-100 protein (less than 1%). Our results indicate the presence of heterogeneity of "histiocytic" cells in MFH. Proliferating-cell nuclear antigen (PCNA) was expressed not only in the spindle and polygonal MFH cells but also in the bizarre giant cells. These findings suggest that all three types of MFH cells participate in the proliferative compartment of MFH. Uneven PCNA staining of the irregular nuclear segments of the bizarre giant cells may result in abnormal DNA synthesis, possibly contributing to the marked diversity of nuclear morphology in MFH. Touton-type and osteoclast-like giant cells did not stain for PCNA but stained positively for histiocytic markers. Therefore, these giant cells may lack proliferative activity and probably result from normal histiocytes fusing together.