Multichannel laser diode to polymer waveguide array coupling with a double-aspheric lens.

An optical system for multichannel coupling of laser arrays to polymer waveguide array probes with a single biconvex lens is developed. The developed cylindrical module with 13 mm and 20 mm in diameter and length, respectively, enables coupling of eight individual optical channels using an aspheric lens. Specific coupling with crosstalk below -13d B for each channel and quasi-uniform coupling over all channels is achieved for a waveguide array with 100 µm lateral facet pitch at the incoupling site. The polymer waveguide technology allows for tapering of the lateral waveguide pitch to 25 µm toward the tip of the flexible waveguide array. SU-8 and PMMA are used as the waveguide core and cladding, respectively. The optical coupling module is designed as a prototype for preclinical evaluation of optical neural stimulators.

[Detection of papillomavirus DNA in the prostate: a virus with underestimated clinical relevance?]. / Die Detektion von Papillomavirus-DNA in der Prostata : Ein Virus mit unterschätzter klinischer Relevanz?

BACKGROUND: Human papillomaviruses (HPV) are the most frequent pathogens of sexually transmitted diseases. They have been associated with an increased incidence of several anogenital tumors. Whether oncogenic HPV are involved in the pathogenesis of prostate cancer has been a subject of great controversy. This study's purpose was to investigate the association between HPV infection and prostate cancer (PCA). MATERIAL AND METHODS: The study included 213 consecutive patients with an average age of 65.7 (+/-8.4) years. Within the framework of transrectal, ultrasonic-guided multibiopsy of the prostate, one additional core was examined by means of polymerase chain reaction (PCR) in relation to bacterial, fungal, and viral (including HPV) DNA, with subsequent DNA sequencing. The collected data were correlated with the histological results and with diverse clinical variables. The influence of several predictors for the existence of PCA was verified with a logistic regression model. RESULTS: No general bacterial DNA (16S rDNA) was detected. Of the 213 patients, 145 (68.1%) showed HPV DNA. In 64% (n=137), high-risk HPV DNA were depicted; these were 18% of the total in each case of HPV genotypes 16 and 18. From our examinations, no significant positive correlation existed between the HPV evidence and the histologically verified PCA that was found in 23.5% of the patients (n=50; odds ratio 1.45; 95% confidence interval 0.71-2.91). The BK virus was not found in any of the cores confirmed through PCR. CONCLUSION: Although no positive correlation between HPV infection and PCA existed in our study, data from the literature suggest an influence of the papillomavirus on PCA oncogenesis. Future studies should highlight to what extent HPV DNA is inserted in the genome of prostate cells and is able to cause subsequent malignant transformation of particular genes.

Treatment of varicocele with reference to age: a retrospective comparison of three minimally invasive procedures.

BACKGROUND: This study investigated whether the therapeutic efficacy and morbidity of three minimally invasive techniques for varicocele correction--laparoscopic varicocelectomy (LV), antegrade sclerotherapy (AS), and retrograde embolization (RE)--differed between children and adults. METHODS: During a 10-year period, 356 procedures for varicocele correction, including 122 cases of LV, 108 cases of AS, and 126 cases of RE, were performed for 314 patients at our institution. Of these patients, 223 were 19 years of age or younger (group 1), and 133 were older than 19 years (group 2). Diagnosis and postoperative results were established clinically and with the use of Doppler ultrasonography. The failure rates and complications for each procedure were retrospectively evaluated and compared between the two age groups. RESULTS: The median follow-up period was 69 months (range, 6-122 months). For 25 patients (19.8%), RE was not feasible for technical reasons. In both groups, LV had a lower failure rate than AS or RE, but the difference between LV and AS was not significant in group 1 (7.7(% vs 11.9%; p > 0.5). Also in group 1, AS was associated with fewer complications than LV 1 (4.5% vs 15.4%; p < 0.05). In group 2, LV was significantly more effective in correcting varicoceles than the other two techniques (p < 0.01). In this group, the complication rates for all three procedures did not differ significantly (p > 0.05). CONCLUSIONS: In our experience, LV was more effective than AS or RE in correcting varicoceles. For children and adolescents, AS may be more indicated because of the slightly lower complication rate and similar recurrence rates, as compared with LV, for this age group. The higher incidence of postoperative hydrocele formation after LV warrants more refined techniques such as the lymphatic-sparing approach.

[Radical cystectomy in the treatment of bladder cancer always in due time?]. / Stellen wir die Indikation zur radikalen Zystektomie immer zeitgerecht?

INTRODUCTION: The aim of this study was to examine how the survival rates for patients with muscle-invasive bladder carcinoma are influenced by the tumor stage at initial presentation. PATIENTS AND METHODS: This study examined the clinical course of 452 patients who underwent radical cystectomy for bladder carcinoma from 1992 to 2004. The patients were divided into three groups according to the histological results of the initial and final transurethral tumor resection (TURB). In group 1 (n=114) patients who presented with a superficial bladder carcinoma which had a high likelihood of progressing underwent radical cystectomy. Group 2 included (n=92) patients who displayed a superficial tumor stage when they first presented and developed progressive muscle-invasive bladder carcinoma under conservative treatment. Group 3 (n=246) comprised patients who were already at the muscle-invasive tumor stage in the course of primary TURB. The histopathological characteristics of all transurethral tumor resections and radical cystectomy were recorded. Progression-free survival rates and overall survival rates in the three groups were then compared. RESULTS: The average patient age at cystectomy was 64.3 (35-80) years, and the average follow-up period was 49 months. Progression-free survival and overall survival of all 452 patients were 56.1 and 53.6%, respectively, after 5 years. The best outcome was a progression-free 5-year survival rate of 78.4% with organ-confined, lymph node-negative tumors (n=213). This result was statistically significant (p<0.01) compared with the progression-free 5-year survival rate of 42.3% for non-organ-confined, lymph node-negative tumors (n=112). Lymph node-positive patients (n=127) achieved a progression-free 5-year survival rate of 29.0% regardless of the tumor infiltration. Group 1 patients achieved a progression-free survival rate of 71.3% and an overall survival rate of 69.1% after 5 years. Group 2 patients achieved a progression-free survival rate of 52.9% and an overall survival rate of 51.4% after 5 years. Group 3 patients achieved a progression-free survival and overall survival of 50.2% and 47.1%, respectively, after 5 years. There was no significant difference between groups 2 and 3 with regard to their progression-free or overall survival rates (p>0.45). However, both groups displayed significantly poorer progression-free and overall survival rates compared with group 1 (p<0.01). CONCLUSION: Our results show that patients with superficial bladder carcinoma with tumor progression to muscle invasion do not have a better prognosis after radical cystectomy than patients presenting initially with muscle-invasive bladder carcinoma. Survival rates in this group can only be improved by singling out patients on the basis of risk factors at an earlier stage and carrying out cystectomy. Due to these results we must expect that waiting for a muscle invasion in patients with superficial bladder carcinoma with a high risk profile results in a significant impairment of prognosis.

Neurochemistry of the nodose ganglion.

Placode-derived general visceral afferent neurons of the nodose ganglion transmit visceral sensory information from specialized sensory endings of the vagus nerve and its branches to the nucleus of the solitary tract. These neurons are critical in relaying information such as elevations in blood pressure, changes in blood oxygenation, passage of contents through the esophagus and intestines, and distention of the heart, stomach, and lungs to the CNS for reflex maintenance of visceral functions. Multiple neurotransmitters, neuropeptides, calcium binding proteins, and other neuroactive substances are associated with neurons of the nodose ganglion. Many neurons colocalize 2 or more neuroactive substances creating the potential for complex interactions of neurochemical signals in the NTS. Neurons of the nodose ganglion also contain a variety of receptors which respond to transmitters, inflammatory mediators, and neurotrophic factors. The contents of these neurochemicals and receptors are not static as alterations in their expression are noted in response to epigenetic influences. Although not yet well understood, potential factors and mechanisms regulating neurochemical events in the nodose ganglion neurons are discussed.

[Coincidence of testicular germ cell tumor and sarcoidosis: A diagnostic challenge]. / Testikulärer Keimzelltumor und Sarkoidose: Eine diagnostische Herausforderung.

Several case reports and small case series have described a total of 66 patients with sarcoidosis and testicular cancer so far. This report describes three additional cases. We highlight the association of sarcoidosis and testicular cancer and comment on the potential impact of this connection on the interpretation of the radiological and pathological findings in suspected cancer relapse. Sarcoidosis, a condition that can be combined with testicular cancer, should always be considered in the differential diagnosis.

[Gemcitabine and carboplatin chemotherapy in advanced transitional cell carcinoma in regard to patients with impaired renal function]. / Gemcitabine/Carboplatin-Chemotherapie in der Behandlung des metastasierten Urothelkarzinoms unter besonderer Berücksichtigung von Patienten mit eingeschränkter Nierenfunktion.

PURPOSE: The aim of this analysis is the evaluation of the activity and toxicity of gemcitabine and carboplatin in patients with advanced urothelial transitional carcinoma (TCC) with special regard to patients with impaired renal function. PATIENTS AND METHODS: 30 consecutive patients with metastatic TCC [mean age: 68 (range: 47 - 82) years, median ECOG-PS:1] were treated with gemcitabine (1000 mg/m (2) on days 1 and 8 of a 21-day schedule) and carboplatin (AUC 4.5 day 1). In 15 patients (considered as renal unfit) a creatinine clearance of less than 60 mL/min (range: 31 - 59 mL/min) was seen. RESULTS: Concerning the survival rate, no significant difference noticed between the two subgroups of renal impaired patients and patients with normal renal function was detected (median 13 vs. 14 months, p = 0.901). An overall response rate of 50 % was obtained. In 16.7 % and 33.3 % of all cases a complete or a partial response was noted. Median time to progression was 5.34 months. The 1-year-survival rate has been calculated as 51.8 %. There was no restriction of renal function under chemotherapy in any single patient. CONCLUSIONS: The chemotherapy combination of gemcitabine and carboplatin is definitely powerful for a first-line-therapy in patients with advanced TCC. Toxicity is well manageable. Due to the dosage for carboplatin by AUC an adaptation to the glomerular filtration rate is possible. Decreases of effectiveness in cases of impaired renal function were not detected. Patients with metastatic TCC should be entered onto well designed, randomised clinical trials with the gemcitabine/carboplatin combination to afford a tailored chemotherapy.

Is it possible to provide a prognosis after radical prostatectomy for prostate cancer by means of a PSA regression model?

BACKGROUND: For over 15 years, studies have been done to evaluate the elimination kinetics of the prostate-specific antigen (PSA) after radical prostatectomy. Even though evaluation of PSA regression in the two-compartment model has become established, no clear data are currently available as to whether a statement can be made with regard to tumor prognosis from a computation of the PSA half-life (PSA-HL). This study focuses on the determination of the PSA-HL in the two-compartment model and on its correlation with the biochemical recurrence-free survival. In addition, a computer program is being developed to simplify the determination of PSA-HL. MATERIAL AND METHODS: Seventy-seven prospective patients were examined who subsequently had a radical prostatectomy at our facility without neoadjuvant or adjuvant hormone deprivation. In addition to preoperative measurement of the PSA value (dO), PSA determinations were carried out postoperatively on days 5, 10 and 60, and at four-monthly intervals thereafter (mean follow-up: 16 months). By means of the computer program developed for this purpose, CTK.TumW, the PSA half-lives for the first (d0-d5, PSA-HL1) and second (d5-d10, PSA-HL2) compartments were subsequently determined and their effect on biochemical recurrence-free survival was assessed. RESULTS: PSA-HL1 and PSA-HL2 were 1.89 (+/- 0.03) and 3.39 (+/- 0.14) days, respectively. Whilst PSA-HL1 did not permit any prognostic statement, the median PSA-HL in the second compartment between patients with and without disease progression differed significantly (4.44 versus 3.12 days; p < 0.001). Discrimination analysis produced a cutoff of 3.8 days for the second compartment; patients with a PSA-HL2 > or = 3.8 days had a significantly worse biochemical recurrence-free survival after 18 months than the other patients (27% versus 93%; p < 0.001). CONCLUSION: The PSA regression kinetics after radical prostatectomy follows a two-compartment model in which the prognostic value of the PSA-HL1 is limited. When a cutoff of 3.8 days is used, evaluation of the PSA-HL in compartment 2 (d5-10) appears to permit a prognostic statement. Due to the limited postsurgical follow-up, the disease process was only assessed as biochemical recurrence-free survival, and a longer follow-up will be necessary to generate data on progression-free survival.

[Silica-containing urinary stones--clinical issues to keep in mind]. / Silikathaltige Harnsteine im Klinikalltag. Was gibt es zu beachten?

Formation of calculi in efferent urinary passages is always due to supersaturation of urinary calculi substances and associated increased crystallization. Apart from the typical calculi, consisting of calcium oxalate, inorganic phosphates, uric acid or cystine, there are occasional signs of rare substance classes. Although more than 50 silicate stones have already been reported internationally, this stone entity remains relatively unknown. In particular, the occurrence of silicate stones in the absence of magnesium trisilicate abuse is extremely rare. A medium-sized left-sided ureterolith was removed from a 54-year-old male patient using a ureteroscope. X-ray diffraction showed it to be a compound stone consisting of 40% silicate. The patient, who in 1986 was living close to the nuclear reactor accident in Chernobyl, showed no signs of a constant uptake of magnesium trisilicate. However, he had undergone partial (2/3) gastrectomy 4 months before for a drug-refractory gastric ulcer, which had been diagnosed at the end of the 1980s and treated with excessive dosages of a magnesium trisilicate antacid preparation until the time of the operation. The patient had also been suffering from unstable angina pectoris since 1986 and treated with Pentalong (pentaerythrityltetranitrate) for 17 years. We were also able to detect silicium dioxide in components of this drug using X-ray diffraction. Silicate uroliths are extremely rare but they can be clearly identified by X-ray diffraction or infrared spectroscopy and distinguished from artifacts or quartz pebbles. Formation of calculi can be prevented by increasing diuresis as well as switching to a different drug and reducing the dosage.

Exacerbation of coronary occlusion induced ventricular arrhythmias by the vagolytic effect of procainamide.

The influence of the vagolytic effect of procainamide on the early ventricular arrhythmias induced by left anterior descending coronary (LAD) occlusion was studied in chloraloseanaesthetised cats. All control animals developed a ventricular arrhythmia (1119 +/- 166 PVCs per hour), with a consistent onset time, duration, and overall mortality due to ventricular fibrillation (ie 20%). In 18 animals pretreated with procainamide (0.5 mg.kg-1.min-1 for 50 min), there was no effect on the ventricular arrhythmia in terms of ectopic frequency (1020 +/- 180 PVCs per hour), time to onset of arrhythmia, duration of arrhythmia, and mortality incidence (ie 16.7%). However, subdividing the data according to whether or not vagal blockade had been produced by procainamide revealed that animals exhibiting complete vagal blockade demonstrated significantly more ectopic beats (1606 +/- 310 PVCs per hour) and 33% developed ventricular fibrillation. Treated animals without complete vagal blockade exhibited an ectopic frequency rate of 620 +/- 98 PVCs per hour and none of the animals developed ventricular fibrillation. The haemodynamic parameters were similar between both procainamide treated subgroups. These results suggest that an important factor in response of the ischaemic heart to the cardiac rhythm effects of procainamide is the degree of vagal blockade induced by this agent.

Serotonin- and substance P-containing projections to the nucleus tractus solitarii of the rat.

The objective of the present study was to determine the location of the neurons that give rise to serotonin- and substance P-containing terminals in the nucleus tractus solitarii. This was done by injecting rhodamine-filled latex microspheres into the nucleus tractus solitarii of rats to retrogradely label neuronal cell bodies and by processing sections from the brains of these animals to determine whether the labelled neurons contained serotonin or substance P immunoreactivity. Serotonin-immunoreactive neurons that projected to the nucleus tractus solitarii were found in the nucleus raphe magnus, nucleus raphe obscurus, nucleus raphe pallidus, and in the ventral medulla, lateral to the pyramidal tract. Substance P-immunoreactive neurons that projected to the nucleus tractus solitarii were found in similar areas but were proportionately less numerous in the nucleus raphe magnus and proportionately more numerous in the nucleus raphe pallidus. It is concluded that neurons in the medullary raphe nuclei, some of which presumably utilize serotonin or substance P as a neurotransmitter, could regulate autonomic function via direct projections to the nucleus tractus solitarii.

Enkephalin-immunoreactive neuronal projections from the medulla oblongata to the intermediolateral cell column: relationship to substance P-immunoreactive neurons.

The present study investigated the ventral medullary distribution of enkephalin-immunoreactive neurons that project to the intermediolateral cell column and the relationship of these neurons to substance P-immunoreactive neurons. Neurons that projected to the intermediolateral cell column were identified by the presence of rhodamine-labeled microspheres within the neuronal cell body after an injection of the microspheres into the intermediolateral cell column of the third thoracic spinal cord segment. Enkephalin- and substance P-immunoreactivities were identified by dual-color immunohisto-chemistry. Enkephalin-immunoreactive neurons that projected to the intermediolateral cell column were present in the raphe magnus, the nucleus reticularis magnocellularis pars alpha, the paragigantocellular reticular nucleus, and the parapyramidal region. These neurons were present throughout the rostrocaudal extent of each of these nuclei. However, in the raphe magnus the greatest number was present at more rostral levels of the nucleus. The morphology and distribution of enkephalin-immunoreactive neurons that projected to the intermediolateral cell column were similar to those of enkephalin-immunoreactive neurons that were not observed to contain rhodamine-labeled microspheres. Substance P- and enkephalin-immunoreactive neurons that projected to the intermediolateral cell column were present in similar distributions in each of the nuclei studied, except the raphe magnus. The raphe magnus contained more enkephalin- than substance P-immunoreactive neurons at rostral levels and more substance P-immunoreactive neurons than enkephalin-immunoreactive neurons at caudal levels. Coexistence of substance P- and enkephalin-immunoreactivities in ventral medullary neurons that projected to the intermediolateral cell column was rarely seen. These studies support the hypothesis that ventral medullary enkephalinergic neurons project to the intermediolateral cell column where they could act to modulate preganglionic sympathetic activity.

Catecholamine-synthesizing neuronal projections to the nucleus tractus solitarii of the rat.

The objective of the present study was to determine the location of the neurons that give rise to catecholamine-containing terminals in the nucleus tractus solitarii. This was done by injecting rhodamine-filled latex microspheres into the nucleus tractus solitarii of rats to retrogradely label neuronal cell bodies and by processing sections from the brains of these animals to determine if the labelled neurons were immunoreactive for the catecholamine-synthesizing enzymes, dopamine-beta-hydroxylase (DBH) and phenylethanolamine-N-methyl transferase (PNMT). Approximately 60% of the DBH-immunoreactive neurons that projected to the nucleus tractus solitarii belonged to the A1/C1 cell group, while an additional 20% belonged to the A5 cell group. Thus, these two ventrolateral rhombencephalic cell groups accounted for nearly 80% of the total number of rhodamine-bead-labelled DBH-immunoreactive neurons in this series of experiments. Only a small number of DBH-immunoreactive neurons of the A2/C2 cell group contained rhodamine-filled latex microspheres. Rarely, DBH-immunoreactive neurons in the locus coeruleus and the nucleus subcoeruleus were found to project to the nucleus tractus solitarii. The majority of the PNMT-immunoreactive neurons that projected to the nucleus tractus solitarii belonged to the C1 cell group. Only small numbers of PNMT-immunoreactive neurons of the C2 and C3 groups were found to contain rhodamine-filled latex microspheres. It is concluded that neurons in the ventrolateral medulla and pons, some of which presumably utilize norepinephrine and/or epinephrine as a transmitter, could regulate autonomic function via direct projections to the nucleus tractus solitarii.

Immunocytochemical studies of the 5-HT(1A) receptor in ventral medullaryneurons that project to the intermediolateral cell column and contain serotonin or tyrosine hydroxylase immunoreactivity.

Activation of serotonin-1A receptors (5-HT(1A)R) in the medulla oblongata lowers sympathetic nerve discharge and blood pressure. Binding sites for 5-HT(1A)R ligands are present in ventral medullary nuclei [e.g., rostral ventrolateral medulla (RVLM), raphe pallidus (RPa), and parapyramidal region (PPR)] that project to sympathetic preganglionic neurons in the intermediolateral cell column (IML). However, the projections and the neurochemical contents of the ventral medullary neurons that are likely to be involved in the hypotensive actions of 5-HT(1A) agonists are unclear. Using a sheep antibody to a fragment of the third intracellular loop of the 5-HT(1A)R, we localized 5-HT(1A)R immunoreactivity (ir) to IML-projecting neurons that were retrogradely labeled with rhodamine beads injected into the IML of adult male rats. The percentages of IML-projecting neurons containing 5-HT(1A)R-ir were 49% in RPa, 34% in PPR, and 44% in RVLM. Using multiple-immunofluorescence labeling, we also demonstrated 5-HT(1A)R-ir in serotonergic (5-HT) and in catecholaminergic (tyrosine hydroxylase; TH-ir) neurons of the ventral medulla. The percentages of 5-HT-ir neurons containing 5-HT(1A)R-ir were 28% in RPa, 18% in PPR, and 31% in raphe obscurus. In addition, 5-HT(1A)R-ir was present in 14% of TH-ir neurons of the RVLM. Moreover, some IML-projecting neurons in the PPR and RPa were doubly immunolabeled for 5-HT(1A)R-ir and 5-HT, and some IML-projecting neurons in the RVLM were doubly immunolabeled for 5-HT(1A)R-ir and TH-ir. These data provide anatomical evidence for the presence of 5-HT(1A)R on serotonergic and catecholaminergic bulbospinal neurons and for their potential role in directly modifying the activity of these ventral medullary neurons.

Axonal transport of neurotrophins by visceral afferent and efferent neurons of the vagus nerve of the rat.

The receptor-mediated axonal transport of [125I]-labeled neurotrophins by afferent and efferent neurons of the vagus nerve was determined to predict the responsiveness of these neurons to neurotrophins in vivo. [125I]-labeled neurotrophins were administered to the proximal stump of the transected cervical vagus nerve of adult rats. Vagal afferent neurons retrogradely transported [125I]neurotrophin-3 (NT-3), [125I]nerve growth factor (NGF), and [125I]neurotrophin-4 (NT-4) to perikarya in the ipsilateral nodose ganglion, and transganglionically transported [125I]NT-3, [125I]NGF, and [125I]NT-4 to the central terminal field, the nucleus tractus solitarius (NTS). Vagal afferent neurons showed minimal accumulation of [125I]brain-derived neurotrophic factor (BDNF). In contrast, efferent (parasympathetic and motor) neurons located in the dorsal motor nucleus of the vagus and nucleus ambiguus retrogradely transported [125I]BDNF, [125I]NT-3, and [125I]NT-4, but not [125I]NGF. The receptor specificity of neurotrophin transport was examined by applying [125I]-labeled neurotrophins with an excess of unlabeled neurotrophins. The retrograde transport of [125I]NT-3 to the nodose ganglion was reduced by NT-3 and by NGF, and the transport of [125I]NGF was reduced only by NGF, whereas the transport of [125I]NT-4 was significantly reduced by each of the neurotrophins. The competition profiles for the transport of NT-3 and NGF are consistent with the presence of TrkA and TrkC and the absence of TrkB in the nodose ganglion, whereas the profile for NT-4 suggests a p75 receptor-mediated transport mechanism. The transport profiles of neurotrophins by efferent vagal neurons in the dorsal motor nucleus of the vagus and nucleus ambiguus are consistent with the presence of TrkB and TrkC, but not TrkA, in these nuclei. These observations describe the unique receptor-mediated axonal transport of neurotrophins in adult vagal afferent and efferent neurons and thus serve as a template to discern the role of specific neurotrophins in the functions of these visceral sensory and motor neurons in vivo.

Bulbospinal thyrotropin-releasing hormone projections to the intermediolateral cell column: a double fluorescence immunohistochemical-retrograde tracing study in the rat.

Whereas the neurochemistry of the peripheral autonomic nervous system has been well characterized, less is known concerning the neurotransmitters utilized by medullary projections onto sympathetic preganglionic neurons residing in the thoracolumbar spinal intermediolateral cell column. Retrograde transport of rhodamine-labeled fluorescent microspheres following discrete microinjection into the thoracic intermediolateral cell column was combined with immunohistochemistry to determine neuroanatomic location of thyrotropin-releasing hormone-immunoreactive neurons which project to the intermediolateral cell column in the rat. The ventromedial group of raphe nuclei including the nucleus raphe pallidus, obscurus, and magnus possessed the greatest number of medullary thyrotropin-releasing hormone-immunoreactive neurons which also contained rhodamine-labeled microspheres. High numbers of intermediolateral cell column-projecting thyrotropin-releasing hormone-immunoreactive neurons were also observed in nucleus reticularis paragigantocellularis lateralis and magnocellularis, the lateral reticular nucleus, and the superficial ventral (arcuate) medullary surface. Despite the observations that nucleus reticularis gigantocellularis, paramedianus, and ventralis pars beta project to the intermediolateral cell column, double-labeled cells were not observed in these nuclei. Furthermore, whereas the nucleus reticularis magnocellularis and gigantocellularis, and the lateral reticular nucleus displayed strong ipsilateral predominance in projecting to the intermediolateral cell column, other medullary reticular and raphe nuclei displayed bilateral projections. The present findings support the hypothesis that thyrotropin-releasing hormone-containing neurons in the ventral medulla project to the intermediolateral cell column, and may influence sympathetic preganglionic neurons.

Distribution, origin and plasticity of galanin-immunoreactivity in the rat carotid body.

The distribution, origin and plasticity of galanin immunoreactivity in the rat carotid body was examined using an indirect immunofluorescence method. Galanin-immunoreactive nerve fibers were observed around the blood vessels as well as around the clusters of glomus and sustentacular cells. A double-immunofluorescence method revealed the coexistence of galanin- and calcitonin gene-related peptide-immunoreactivities in these nerve fibers. In the jugular, petrosal and nodose ganglia which supply the sensory nerve fibers to the carotid body, subpopulations of neurons showed both galanin- and calcitonin gene-related peptide-immunoreactivities. In the superior cervical ganglion, a few neurons were immunoreactive for galanin but not calcitonin gene-related peptide. While the nerve fibers showing both galanin- and calcitonin gene-related peptide-immunoreactivities disappeared after transection of the carotid sinus nerve, many galanin-immunoreactive nerve fibers without calcitonin gene-related peptide-immunoreactivity appeared throughout the operated carotid body. In addition, galanin-immunoreactive glomus cells which were not observed in the normal carotid body, were apparent at one and three days after transection of the carotid sinus nerve. At seven days after the carotid sinus nerve transection, the galanin-immunoreactive glomus cells disappeared. In the superior cervical ganglion, the number of galanin-immunoreactive neurons increased from one day after transection of the carotid sinus nerve. Within three days after the carotid sinus nerve transection in combination with superior cervical ganglion-ectomy, all galanin-immunoreactive nerve fibers disappeared, while many galanin-immunoreactive glomus cells appeared in the operated carotid body. At seven days after this operation, the number of galanin-immunoreactive glomus cells decreased and a few galanin-immunoreactive nerve fibers with or without calcitonin gene-related peptide-immunoreactivities appeared. Transection of the vagus nerve had no effect on the number or distribution of galanin-immunoreactivity in the carotid body. Disappearance of galanin- and calcitonin gene-related peptide-immunoreactive nerve fibers after transection of the carotid sinus nerve suggests that the majority of those nerve fibers originate from petrosal neurons which colocalize galanin- and calcitonin gene-related peptide-immunoreactivity. In addition, the carotid sinus nerve transection may cause the acquisition of galanin-immunoreactivity in originally immunonegative glomus cells, and in nerve fibers which probably originate from the superior cervical ganglion.

Neurokinin B peptide-2 neurons project from the hypothalamus to the thoracolumbar spinal cord of the rat.

The presence and location of CNS neurokinin B peptide-2-like immunoreactive neurons that project to the spinal cord were studied by a combination of retrograde transport of fluorescent dye (FluoroGold) and fluorescence immunocytochemistry. After injections of FluoroGold into the thoracic or lumbar segments of the rat spinal cord, serial sections of brain were stained with antisera directed against neurokinin B peptide-2. The results of the study showed that neurokinin B peptide-2-like immunoreactive neurons were located in the nucleus arcuate, median eminence, ventral and external bed nuclei of the stria terminalis, dorsal hypothalamic area, and medial habenula. Neurokinin B peptide-2 neurons that give rise to the long descending projections from the hypothalamus to thoracolumbar spinal cord were found only in the dorsal hypothalamic area. Approximately 36% of the neurokinin B peptide-2 neurons in the dorsal hypothalamic area projected to the spinal cord, whereas about 28% of the spinal projecting neurons in the dorsal hypothalamic area contained neurokinin B peptide-2-like immunoreactivity. Most of the spinal projecting neurokinin B peptide-2 neurons in the dorsal hypothalamic area had a cell size of 15 x 25 microns. In the spinal cord, immunoreactive neurokinin B peptide-2 fibers and terminals were distributed mainly in the superficial dorsal horn and the central autonomic area, with the highest density in laminae II and X, with less density in laminae IV and V. A few neurokinin peptide-2 fibers and terminals were also found in the ventral horn of the spinal cord. The results of the present study show that hypothalamic neurokinin B peptide-2 neurons are the main source of the spinal neurokinin B peptide-2.

Immunohistochemical study of neuropeptides in vagal and glossopharyngeal afferent neurons in the rat.

The presence and distribution of multiple neuropeptides in vagal and glossopharyngeal afferent ganglia of the rat were studied using immunohistochemistry. Substance P-, calcitonin-gene related peptide-, cholecystokinin-, neurokinin A-, vasoactive intestinal polypeptide-, and somatostatin-immunoreactive neurons were detected in each visceral afferent ganglion. Neurotensin-immunoreactive cells were not observed. In the nodose ganglion (inferior ganglion of the vagus nerve) occasional immunoreactive cells were scattered throughout the main (caudal) portion of the ganglion with small clusters of cells seen in the rostral portion. The pattern of distribution of the various peptides in the nodose ganglion was similar, with the exception of vasoactive intestinal polypeptide-immunoreactive neurons which exhibited a more caudal distribution. The relative numbers of immunoreactive cells varied, with the greatest numbers being immunoreactive for substance P or vasoactive intestinal polypeptide, and the lowest numbers being immunoreactive for neurokinin A and somatostatin. A build-up of immunoreactivity for each of the peptides, except somatostatin and neurotensin, was detected in vagal nerve fibers of colchicine-injected ganglia. Numerous peptide-immunoreactive cells were also found in the petrosal (inferior ganglion of the glossopharyngeal nerve) and jugular (superior ganglion of the vagus nerve) ganglia. No specific intraganglionic distribution was noted although the relative numbers of cells which were immunoreactive for the different peptides varied considerably. Substance P and calcitonin-gene related peptide were found in large numbers of cells, cholecystokinin was seen in moderate numbers of cells, and neurokinin A, vasoactive intestinal polypeptide and somatostatin were seen in fewer cells. These data provide evidence for the presence and non-uniform distribution of multiple peptide neurotransmitters in vagal and glossopharyngeal afferent neurons. In general, relatively greater numbers of immunoreactive cells were located in the rostral compared with caudal nodose ganglion, and in the petrosal and jugular ganglia compared with the nodose ganglion. Thus, multiple neuropeptides may be involved as afferent neurotransmitters in the reflexes mediated by vagal and glossopharyngeal sensory nerves.

Autoradiographic localization of 5-hydroxytryptamine1A, 5-hydroxytryptamine1B and 5-hydroxytryptamine1C/2 binding sites in the rat spinal cord.

Autoradiographic techniques revealed that 5-hydroxytryptamine1A, 5-hydroxytryptamine1B and 5-hydroxytryptamine1C/2 binding sites are differentially distributed in the spinal cords of adult male rats. In the dorsal horn, 5-hydroxytryptamine1A sites were dense in all laminae; 5-hydroxytryptamine1B sites were more dense in laminae I, III and IV than in lamina II; while 5-hydroxytryptamine1C/2 sites were very sparse. The dorsal commissure gray matter also exhibited very dense 5-hydroxytryptamine1A and 5-hydroxytryptamine1B binding. In the intermediate and central gray matter, all three sites were moderately dense at autonomic levels, with exceptionally dense1C/2 binding restricted to the intermediolateral nucleus at rostral thoracic levels. In the ventral horn, 5-hydroxytryptamine1A and 5-hydroxytryptamine1B sites were very sparse (except for very dense 5-hydroxytryptamine1A sites located in the dorsolateral nucleus of the pudendal nerve), while 5-hydroxytryptamine1C/2 sites were relatively dense in motor nuclei. Surprisingly, 5-hydroxytryptamine1B sites were moderately dense in the dorsal column corticospinal tract. These studies will provide an anatomical perspective for interpretation of the complex role of 5-hydroxytryptamine in regulating spinal cord function.