Distribution and origin of serotoninergic afferents to guinea pig cochlear nucleus

The distribution of serotoninergic fibers in the guinea pig cochlear nucleus was studied with serotonin immunohistochemistry. In addition, the origin of the serotoninergic fibers was determined by combining the retrograde transport of wheat germ agglutinin-apohorseradish peroxidase (gold conjugated) with serotonin immunohistochemistry. Immunoreactivity was present in varicose and nonvaricose fibers that were unevenly distributed throughout the cochlear nucleus. The fibers were most prominent in the superficial layers of the dorsal cochlear nucleus and the anterior spherical cell area of the anteroventral cochlear nucleus. Although less prominent, serotonin-positive fibers were also present in the remaining part of the anteroventral cochlear nucleus and the posteroventral cochlear nucleus. A few positive fibers were present in the auditory nerve root and the dorsal and intermediate acoustic stiae. Double-labeled cells were found throughout the rostral- caudal extent of the serotoninergic system from the caudal linear nucleus to the nucleus raphe pallidus. However, most were confined to the dorsal (52%) and median (18%) raphe nuclei. Some serotoninergic cell groups contained retrogradely labeled cells that were not serotonin immunoreactive, indicating nonauditory afferents to cochlear nucleus containing other neurotransmitter substances. Serotonin may tonically modulate auditory processing within the cochlear nucleus as well as influence certain ascending auditory pathways. Most of the serotonin in the cochlear nucleus comes from superior raphe nuclei that also project to basal ganglia motor systems and limbic strctures. Therefore, the effect of serotonin on the cochlear nucleus may be related to level of arousal or behavioral state. © 1995 Willy-Liss, Inc.     

Diabetes alters μ and κ opioid binding in rat brain regions: comparison with effects of food restriction

Diabetic rats display changes in opioid pharmacology and brain regional levels of opioid peptides and prodynorphin mRNA. Previous investigations of opioid receptor binding, carried out in whole-brain homogenates, have, however, failed to detect changes. In the present study, quantitative autoradiography was used to measure μ and κ opioid receptor binding in discrete brain regions of streptozotocin-treated diabetic rats. Measurement was limited to regions that previously displayed opioid binding changes in chronically food-restricted rats, since our primary aim is to identify brain mechanisms that mediate adaptive responses to persistent metabolic need and adipose depletion. Diabetics displayed strong trends or statistically significant changes which matched seven of the thirteen binding changes observed in food-restricted rats. In no case did diabetics display changes in the opposite direction. The two statistically significant changes common to food-restricted and diabetic rats are increased κ binding in the medial preoptic area and decreased μ binding in the lateral habenula. The possible functional significance of these changes is discussed.     

Laparoscopic bowel surgery registry

Laparoscopic surgery has evolved rapidly since 1989. The American Society of Colon and Rectal Surgeons, the Society of American Gastrointestinal Endoscopic Surgeons, and the American College of Surgeons Commission on Cancer jointly sponsored a registry to identify as early as possible the patterns of practice and acute complications of laparoscopic colectomy. METHODS: Cases were voluntarily registered by community and academic surgeons. Information was entered in the EPI-5 database. RESULTS: One thousand fifty-six cases were contributed by 118 surgeons; 763 patients were completed laparoscopically. The most common indication for surgery was cancer in 453 patients. The right colon (n=364) and sigmoid (n=294) were most frequently resected. Respondents felt adequate cancer resections were performed. Although several unique complications were noted, intraoperative complications were similar in type and frequency to open cases. CONCLUSION: Laparoscopic colorectal surgery can be performed with acceptable complications. It remains unclear if this approach is adequate for long-term management of colon and rectal cancer.Read at the meeting of The American Society of Colon and Rectal Surgeons, Orlando, Florida, May 8 to 13, 1994.     

Patients' perceptions of their clinical interactions: development of the multidimensional desire for control scales

Interventions oriented toward enhancing patient-provider communicationwill benefit from having a satisfactory measure of patients’desires for control in clinical interactions. Findings fromtwo studies are reported describing the development and validationof the Multidimensional Desire for Control (MDC) Scales. A totalof 160 patients with non-insulin-dependent diabetes (NIDDM)participated in the first study, which was designed to developand validate a measure of patients‘ desires for control.Factor analysis yielded three subscales reflecting patients’desires for: (i) personal, (ii) clinician, and (ii) shared controlin the interaction. Alphas for the three subscales were high( 0.75–0.86). Correlations with other measures of controlwere suggestive of good construct validity. The second investigationinvolves a replication study verifying the factorial compositionand validity of the scales. An independent sample of 109 patientswith NIDDM participated in this study. Findings support thereliability of the subscales (0.75–0.81). Furthermore,patients‘ desires for control were significantly associatedwith patient satisfaction, with desire for personal controlnegatively related to patient satisfaction (r = –0.30,–0.41, affective and behavioural dimensions, respectively)and desire for clinician control positively related to satisfaction(r = 0.44, 0.28, 0.31, affective, behavioral, and cognitivedimensions, respectively).     

Microsomal lipid peroxidation induced by Adriamycin,epirubicin, daunorubicin and mitoxantrone: a comparative study

Summary Rat-liver microsomes and NADPH could reduce Adriamycin, epirubicin and daunorubicin to their free radical forms, which enhanced peroxidation of microsomal lipids less than 2-fold in air but 3- to 5-fold at a pO₂ of 4 mm Hg. Mitoxantrone was not reduced by microsomes and had no effect on microsomal peroxidation. Daunorubicin caused more lipid peroxidation than similar concentrations of either Adriamycin or epirubicin, which were equally efficient. In each case peroxidation was iron-dependent and could be catalysed by ferritin. The antioxidants -carotene and -tocopherol inhibited lipid peroxidation at low or high pO₂. The dose-for-dose difference in the cardiotoxicity of epirubicin compared with Adriamycin is not explained by its effect on microsomal lipid peroxidation. However, the lower incidence of cardiotoxicity with mitoxantrone may be a consequence of its inability to form free radical species and promote lipid peroxidation.     

Immunoglobulin mimicry by Hepatitis C Virus envelope protein E2

Hepatitis C virus (HCV) establishes persistent infection in the majority of infected individuals. The currently accepted hypothesis of immune evasion by antigenic variation in hypervariable region 1 (HVR1) of glycoprotein E2 does not however, explain the lack of subsequent immune recognition. Here, we show that the N-terminal region of E2 is antigenically and structurally similar to human immunoglobulin (Ig) variable domains. E2 is recognized by anti-human IgG antibodies and also possesses common amino acid (aa) sequence features of the conserved v-gene framework regions of human Ig light chains in particular but also heavy chains and T cell receptors. Using a position specific scoring system, the degree of similarity of HVR1 to Ig types correlated with immune escape and persistence in humans and experimentally infected chimpanzees. We propose a unique role for threshold levels of Ig molecular mimicry in HCV biology that not only advances our concept of viral immune escape and persistent infection but also provides insight into host-dependent disease patterns.     

Attachment and spreading of fibroblasts on an RGD peptide-modified injectable hyaluronan hydrogel

Hyaluronan (HA) hydrogels resist attachment and spreading of fibroblasts and most other mammalian cell types. A thiol-modified HA (3,3'-dithiobis(propanoic dihydrazide) [HA-DTPH]) was modified with peptides containing the Arg-Gly-Asp (RGD) sequence and then crosslinked with polyethylene glycol (PEG) diacrylate (PEGDA) to create a biomaterial that supported cell attachment, spreading, and proliferation. The hydrogels were evaluated in vitro and in vivo in three assay systems. First, the behavior of human and murine fibroblasts on the surface of the hydrogels was evaluated. The concentration and structure of the RGD peptides and the length of the PEG spacer influenced cell attachment and spreading. Second, murine fibroblasts were seeded into HA-DTPH solutions and encapsulated via in situ crosslinking with or without bound RGD peptides. Cells remained viable and proliferated within the hydrogel for 15 days in vitro. Although the RGD peptides significantly enhanced cell proliferation on the hydrogel surface, the cell proliferation inside the hydrogel in vitro was increased only modestly. Third, HA-DTPH/PEGDA/peptide hydrogels were evaluated as injectable tissue engineering materials in vivo. A suspension of murine fibroblasts in HA-DTPH was crosslinked using PEGDA plus PEGDA peptide, and the viscous, gelling mixture was injected subcutaneously into the flanks of nude mice; gels formed in vivo following injection. After 4 weeks, growth of new fibrous tissue had been accelerated by the sense RGD peptides. Thus, attachment, spreading, and proliferation of cells is dramatically enhanced on RGD-modified surfaces but only modestly accelerated in vivo tissue formation.     

Mn2+ activates skinned smooth muscle cells in the absence of myosin light chain phosphorylation

Two effects of Mn²⁺ on skinned fibers from chicken gizzard smooth muscle were observed, dependent on the presence of absence of dithiothreitol (DTT) reducing agent. One involves protein oxidation (in the absence of DTT) with production of a latch-like state, and the other involves direct Mn²⁺ activation of contractile proteins. Cells activated by Mn²⁺ in the presence of ATP and the absence of Ca²⁺, Mg²⁺ and DTT did not relax when transferred to normal relaxing solutions. In contrast, when 5 mM DTT was included in the Mn²⁺ contracting solution to prevent protein oxidation by Mn²⁺, the cells still contracted when exposed to Mn²⁺, but relaxed rapidly when the Mn²⁺ was removed. In the presence of DTT both the Mn²⁺ activation and the relaxation following removal of Mn²⁺ were more rapid than normal Ca²⁺-activated contractions and relaxations. The skinned fibers activated by Mn²⁺ in the absence of DTT showed little active shortening unless DTT was added. This rigor-like state is probably due to oxidation of contractile proteins since the cells relaxed when exposed to a relaxing solution containing DTT (50mM) and then contracted again in response to Ca²⁺ and relaxed normally. The Mn²⁺ activation was not associated with myosin light chain phosphorylation, in contrast to Ca²⁺-activated contractions.A preliminary report of this work was given at the Biophysical Society Meeting, February 1987: Hoar PE, Kerrick WGL (1987) Mn²⁺ activates skinned smooth muscle cells directly without myosin light chain phosphorylation and by reversible oxidation. Biophys J 51:332a