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[Detection of porin in inter-mitochondrial contacts].

The binding of monoclonal antibodies (mAb) to the N-terminal part of VDAC with freshly isolated, unfixed rat heart mitochondria has been studied. It was established that mAb do not react with the main portion of the mitochondria. At the same time, successful binding to some of those was observed. Gold particles were organized, as a rule in three types of clusters: (i) thread-like clusters; (ii) small, irregularly shaped clusters, and (iii) big clusters covering the greater part of the mitochondrial surface. In the region of tight junctions between mitochondria, specific binding of mAb to mitochondrial VDAC, such as thread-like and small clusters, was found. In some cases, antibody clusters were localized in the region which separates two mitochondrial compartments differing in configuration of the cristae. When the outer mitochondrial membrane was partially stripped off, this membrane was extensively labelled by antibodies. It is concluded that the N-terminus of porin is localized on the inner surface of the outer mitochondrial membrane, so that some damage of the outer membrane appears to be required to allow the N-terminal porin antibody to contact the antigenic determinant. Such a damage is apparently more probable in the place of contacts of two mitochondria or two mitoplasts covered by the common outer membrane. In any case, the data obtained strongly suggest that porin is present in the junction region.

Animals↗

Molecular cloning of a K(+) channel from the malaria parasite Plasmodium falciparum.

In most living cells, K(+) channels are important for the generation of the membrane potential and for volume regulation. The parasite Plasmodium falciparum, which causes malignant malaria, must be able to deal with large variations in the ambient K(+) concentration: it is exposed to high concentrations of K(+) when inside the erythrocyte and low concentrations when in plasma. In the recently published genome of P. falciparum, we have identified a gene, pfkch1, encoding a potential K(+) channel, which to some extent resembles the big-conductance (BK) K(+) channel. We have cloned the approximately 6000 nucleotide (nt) fragment from cDNA, studied the pattern of expression of pfkch1 throughout the intraerythrocytic part of the parasite's life-cyclus, and characterized the channel on the basis of similarity to other K(+) channels from pro- and eukaryotic organisms. This P. falciparum K(+) channel could be a potential drug target.

Amino Acid Sequence↗

Partial characterization of endothelin-converting enzyme activity in human serum lipoproteins.

Endothelin (ET)-1 is an endothelium-derived vasoconstrictor and mitogen peptide generated from an intermediate form (big ET-1) by endothelin-converting enzyme(s) (ECE). In this study, we partially characterized ECE activity in human serum lipoprotein fraction. By gel filtration chromatography, lipoprotein ECE activities consisted of three major components: the first and the second peak eluted in the positions of very low density lipoprotein (VLDL) and low density lipoprotein (LDL), respectively, while the third peak eluted earlier than that of high density lipoprotein (HDL), whose apparent molecular weight (550 kDa) was similar to that of apolipoprotein B (apo B). Both VLDL/LDL-associated and free ECE fractions were similarly inhibited by metalloproteinase and serine proteinase inhibitors. Free ECE fraction was precipitable with dextran sulphate and manganese ion in the same manner as lipoprotein ECE. Apo B purified by high performance liquid chromatography had the same ECE activity as lipoprotein ECE, whose activity was removed after immunoprecipitation with polyclonal anti-apo B antibody. Our data suggest that ECE activity in human serum lipoproteins may be associated with an apo B-like component, although it needs to be characterized completely.

Apolipoproteins B↗

Calculation of the ground and excited states of a mixed valence compound [Fe2(OH)3(NH3)6]2+: a class II or class III compound?

The effective group potentials (EGP) approach has been successfully used for the computation of the ground and excited states energies of the mixed valence compound [Fe2(OH)3(NH3)6]2+. It is the first time that for a system as big as the complex presented above the ground and excited states are computed with their own orbitals and studied in such a detailed way. First of all, the NH3 EGP was validated by comparing calculations where NH3 was treated explicitly at different levels of calculations. Once the validation was obtained, the complete spectrum of the compound under interest was calculated and compared with results obtained in a previous work by Barone et al. and the spin Hamiltonian of widespread use. Some deviations from these predictive approaches were observed. This allowed us to emphasize the importance of the dynamic correlation which is not included explicitly in the spin Hamiltonian. Then, the influence of vibration has been studied by computing the potential energy curves obtained when moving the (OH)3 plane. This study shows that our calculations lead to a delocalized compound (class III) as expected according to former experimental data.

Journal Article↗

Imaging of calcium in Drosophila larval motor nerve terminals.

Calcium measurements in the presynaptic terminal are essential in the investigation of mechanisms underlying neurotransmitter release. To enhance the genetic analysis of secretory mechanisms, we have developed Ca2+ imaging techniques for Drosophila larval motor nerve terminals. We studied Ca2+ signals in "big" (type Ib) and "small" (type Is) boutons that innervate ventral longitudinal muscles 6 and 7 in each abdominal segment of Canton-S (CS)-strain 3rd instar larvae. The indicator fluo-3 in conjunction with confocal microscopy was used to detect stimulus-dependent changes in [Ca2+]i. The Ca2+ signals were reliable and reproducible, and the resting fluorescence remained constant throughout the experiments. The Ca2+ signals increased with stimulus frequency from 5 to 20 Hz for both bouton types. No significant differences in the Ca2+ signals were seen between the two bouton types at 5 and 20 Hz, but there was a difference at 10 Hz. The decay of the Ca2+ signal was more prolonged after 20-Hz stimulation than after 5 and 10 Hz. At the single-synapse level, the secretory efficacy of Is synapses is greater than that of Ib synapses, but our data show that factors other than differences in Ca2+ entry may govern the strength of synaptic transmission.

Animals↗

Cholecystokinin-B/gastrin receptor binding peptides: preclinical development and evaluation of their diagnostic and therapeutic potential.

The high sensitivity of pentagastrin stimulation in detecting primary or metastatic medullary thyroid cancer (MTC) suggests widespread expression of the corresponding receptor type on human MTC. Indeed, autoradiographic studies demonstrated cholecystokinin (CCK)-B/gastrin receptors not only in >90% of MTCs but in a high percentage of small cell lung cancers and potentially a variety of gastrointestinal adenocarcinomas. In a pilot study, we have demonstrated the feasibility of radiolabeled gastrin-I to target CCK-B receptor-expressing tissues in vivo in animals and patients (T. M. Behr et al., Eur. J. Nucl. Med., 25: 424-430, 1998). The aim of the present study was to systematically optimize, in a preclinical model, suitable radioligands for targeting CCK-B receptors in vivo. For this purpose, a variety of CCK/gastrin-related peptides, all having in common the COOH-terminal CCK-receptor binding tetrapeptide sequence Trp-Met-Asp-PheNH2 or derivatives thereof, were studied. They were radioiodinated by the Iodogen or Bolton-Hunter procedures. The peptides tested were members of the gastrin- or cholecystokinin families or possessed characteristics of both, which differ by the intramolecular position of a tyrosyl moiety (occurring in native or sulfated form). Their stability and affinity were studied in vitro and in vivo; their biodistribution and therapeutic efficacy were tested in nude mice bearing s.c. human MTC xenografts. Diethylene-triamine-pentaacetate derivatives of suitable peptides were synthesized, evaluated, and labeled with (111)In. All members of the CCK or gastrin family were stable in serum (with t(1/2)s of several hours at 37 degrees C); nevertheless, the stability of those peptides was highest that bore the NH2-terminal pGlu residues (e.g., big gastrin, gastrin-I, caerulein, and others) or D-amino acids. In accordance to their comparably low affinity, nonsulfated members of the CCK family showed fairly low uptake in the tumor and other CCK-B receptor-expressing tissues (e.g., the stomach). Sulfated CCK derivatives performed significantly better but additionally displayed a high uptake in normal, CCK-A receptor-expressing tissues (such as the liver/gallbladder, pancreas, and bowel). Best tumor uptake and tumor:nontumor ratios were obtained with members of the gastrin family, probably because of their selectivity and affinity for the CCK-B receptor subtype. Pilot therapy experiments in MTC bearing animals showed significant antitumor efficacy as compared with untreated controls. (111)In-Labeled diethylene-triamine-pentaacetate derivatives of minigastrin showed excellent targeting of CCK-B receptor-expressing tissues in animals and a normal human volunteer. These data suggest that CCK/gastrin analogues may be a useful new class of receptor binding peptides for diagnosis and therapy of CCK-B receptor-expressing tumors, such as MTC or small cell lung cancer. Nonsulfated gastrin derivatives may be preferable because of their CCK-B receptor selectivity, and hence, lower accretion in normal CCK-A receptor-expressing organs. Further preclinical as well as clinical studies are ongoing.

Amino Acid Sequence↗

[Erectile dysfunction: prevalence and effect on the quality of life; Boxmeer study].

OBJECTIVE: To assess the prevalence of erectile dysfunction (ED), and its influence on both the quality of life, and health care seeking behaviour. METHOD: An age-stratified random sample was drawn from men aged 40-79 years in Boxmeer, the Netherlands (n = 1771), together with their partners. A questionnaire was mailed to the study population to collect data on ED, and the quality of life, both general and disorder related. The prevalence of ED was measured with the direct question 'Do you have problems getting an erection?'. The influence of ED on sexual function was measured with the Dutch version of the Sexual Function Inventory questionnaire. RESULTS: Seventy percent of all men (n = 1233) and 73% of their partners (n = 1071) responded to the questionnaire. The prevalence of ED increased with age class. To the question regarding problems to get an erection, 13% (95% confidence interval: 11-15%) of all men answered affirmatively (40-49 years: 6%; 50-59: 9%; 60-69: 22%; 70-79: 38%). All men aged 40-49 years of age with ED and 16% of men aged 70-79 with ED considered their ED as bothersome. Amongst 40 to 49 year old men with ED, 64% considered their ED as a big or rather a big problem. Amongst older men this percentage was much smaller: 50-59 years: 38%; 60-69: 37%, and 70-79: 27%. Thirty-four percent of all men with ED and 16% of their spouses were dissatisfied with their sex life. Twenty-five percent of men with ED consulted a doctor, with a mean delay of 13 months. ED bore a strong correlation with the general quality of life and comorbidity. CONCLUSION: ED was a common disorder within the population. Its prevalence was higher among older age groups, but they regarded ED as less of a problem than the younger age groups. Only a quarter of all men with ED consulted a physician.

Adult↗

[The estimate of well-being and self-assessed health status in urban population in various acoustic areas].

Comparative analysis among 357 inhabitants, who live in two areas: noisy (above 70 dB /A/) and moderate (below 57 dB /A/) showed significant differences between the groups in many variables under consideration. This differences, after eliminating socio-economic influences and behavior factors such as: gender, age, economical conditions, education or smoking confirmed existence of relation between living condition caused by motorization and life quality, well-being and self assessed health of inhabitants. Details showed, that urban intensive traffic noise disturbs realization of many important daily activities, evoke emotional tension, irritation, nervousness. In group of people from noisy areas more often are observed characteristic mental pressure caused by noise, throat and eyes irritation, disturbances in rest, speech, listen to music, sleep, and when going to sleep. Feeling of discomfort and annoyance dominates. More often there is a need to close or seal up the windows, use earplugs or take a sleeping pills. Relative risk of appearance of disturbances mentioned above or mental and emotional reactions in group of people who are exposed to high noise from 3 do 6 times bigger in comparison with people from quiet area. Apart from a decrease in the mental comfort and live quality, intensive traffic noise has a big influence on well-being and self assessed health status. The intensification of complaints and symptoms of neurotic character are observed in noisy areas. Most of these problems are connected with cardiovascular system (palpitation, constriction in chest, hot flush, tiredness after effort) and excessive nervous stimulation. Long lasting influence of noise is probably also a cause for a frequent nervousness, feeling of tiredness after night sleep and overstress, troubles with concentration or distinct reduction of well-being (feel unhappy and miserable, inability to cope with troubles, reduce ability to take of decisions). Additionally, the escalation of troubles probably connected with bigger air pollution (frequent dry cough, sneezing, nasal stuffing) is observed in areas of intensive traffic noise. Relative risk of appearance mentioned above unfavourably health symptoms in group of people from noisy areas is about 1.5 times higher than in areas below 57 dB /A/. Analyzed data did not confirm hypothesis on influence of traffic noise on increasing appearance of diseases confirmed by physician. In both areas noisy and quiet morbidity are similar. Also consumption of medicines was similar.

Fatigue↗

Effects of backward masking on the responses of the inferior collicular neurons in the big brown bat, Eptesicus fuscus.

Temporal features of sound convey information vital for behaviors as diverse as speech recognition by human and echolocation by bats. However, auditory stimuli presented in temporal proximity might interfere with each other. Although much progress has been made in the description of this phenomenon from psychophysical studies, the neural mechanism responsible for its formation at central auditory structures especially at the inferior colliculus (IC), a midbrain auditory nucleus which practically receives massive bilateral projections from all the major auditory structures in the brainstem, remains unclear. This study was designed to investigate it in vivo by using electrophysiological recording from the inferior collicular neurons of the big brown bat, Eptesicus fuscus. In our results, the responses of 12 (38%, n= 31) neurons to the test sound (leading sound) were obviously inhibited by the masker (lagging sound). The inhibitory effects in these neurons were correlated with the inter-stimulus level difference (SLD) and the inter-stimulus onset asynchrony (SOA) interval. The strength of backward masking increased with the masker intensity increasing, the test sound intensity decreasing and the SOA interval shortening. There were no obvious effects of backward masking on the responses of many other neurons (52%, 16/31), and yet in a part of these neurons, the neural inhibition of responses to the test sound was observed at the special SLD and the special SOA intervals. Moreover, few of the 31 sampled IC neurons (10%, 3/31) displayed facilitating responses to the test sound at the special SLD and the special SOA intervals. These data demonstrate that a lot of IC neurons are involved in the generation of the backward masking of acoustical perception. It is conjectured that the temporal dynamic integration between the leading inhibitory inputs evoked by the masker sound and the excitatory inputs evoked by the test sound might play a key role in shaping the acoustical response characteristics of the IC neurons.

Acoustic Stimulation↗

Benchmarks of Fairness for health care reform in Thailand--combining evidence with opinion of the civic group.

The concept of the Benchmarks of Fairness was tried in Thailand before the big reform of universal coverage policy in 2001. The first phase of the Benchmarks in 1999 involved the analysis of the national health reform proposal as well as the analysis of ongoing field trials of health reforms in two provinces. Though the participants were predominately health personnel, the results suggested the power of combining qualitative viewpoints of participants with the quantitative indicators within the province to move health reforms to more equitable, more efficient and more democratic directions. The second phase of the Benchmarks of Fairness, therefore, tested the possibility of involving wider participation of the civic groups related, and not-related to health, in assessing their provincial health system. The health achievements of the provinces a measured by 81 indicators, in the 9 benchmarks, were provided to the civic groups before focus group discussions in 10 selected provinces to facilitate discussions based on evidence. More qualitative data were obtained from the discussions as well as their judgements on the fairness of their provincial health system. Having completed this second phase, it was recommended that the benchmarks tool could be further endorsed as the basis for monitoring the progress of health reform by province and the effect of health care decentralization. To accomplish this monitoring, the civic groups should have continuous access to evidence, in line with the benchmarks, and they should be provided with the opportunity to express their views, which is helpful in monitoring fairness in the long run.

Benchmarking↗

Human NB-2 of the contactin subgroup molecules: chromosomal localization of the gene (CNTN5) and distinct expression pattern from other subgroup members.

NB-2 is one of the neural recognition molecules in the contactin subgroup, which belongs to the immunoglobulin superfamily. In rat, the six molecules in this subgroup that have been reported to date are contactin, TAG-1, BIG-1, BIG-2, NB-2, and NB-3. We have isolated cDNAs encoding the two splicing isoforms of human NB-2. The long isoform of human NB-2 consists of 1100 amino acids residues that are 91% homologous to rat NB-2 at the amino acid sequence level. The short isoform lacks 74 amino acid residues between residues 19 and 93 of the long isoform. Among various regions of the adult human brain, high-level expression of NB-2 was detected in the amygdala and occipital lobe, whereas expression was low in the corpus callosum, caudate nucleus, and spinal cord. Although there were some differences, the expression pattern of NB-2 was the most similar to that of BIG-1 in the brain. Likewise, contactin and BIG-2 exhibited similar expression patterns. The expression of TAG-1 showed the least regional differences. The human NB-2 gene (CNTN5) was mapped to chromosome 11q21-q22.2 by fluorescence in situ hybridization. Our results suggest that the NB-2 gene may contribute to human neurological disorders.

Alternative Splicing↗

Endothelin in normal lung tissue of newborn mammals: immunocytochemical distribution and co-localization with serotonin and calcitonin gene-related peptide.

We demonstrated immunoreactivity for endothelins (ET)-1, -2, and -3 and for the precursor, big-ET-1, in the pulmonary diffuse neuroendocrine system (PDNES) of newborn cat, rat, hamster, and mouse. ET-like positive neuroepithelial bodies (NEB) were numerous in the intrapulmonary airways and the alveolar parenchyma. Single neuroendocrine cells (NEC) were less often labeled and mainly localized in the larger bronchi. ET-3-reactive neuronal elements were rarely observed. The intensity and number of immunostained NEB were highest for ET-3, followed in declining order by big-ET-1, ET-1, and ET-2. ET-like possessing NEB displayed interspecies differences. We conclude that ET-3 represents a neuroendocrine form of the ET peptide family. NEB expressing several ET isoforms can be grouped into NEB containing either big-ET-1 and ET-1 or ET-3 only. ET-like immunoreactivity was present in a subpopulation of serotonin (5HT)- and/or calcitonin gene-related peptide (CGRP)-positive NEB. As ET, 5HT, and CGRP have potent pulmonary vaso- and/or bronchomotor effects, our observations suggest that they play a separate or synergistic role in regulatory function of the mammalian PDNES, exerting their influence by paracrine, endocrine, and neurocrine pathways or a combination of these.

Amino Acid Sequence↗

Chronic osteomyelitis in a Ugandan rural setting.

OBJECTIVE: To determine the incidence pattern and outcome of chronic osteomyelitis in a rural setting. DESIGN: A prospective descriptive study where a proforma was drafted to study all consecutive patients with features of chronic osteomyelitis over a period of six years, Clinical findings on presentation, treatment, duration of symptoms, initial treatment sought, operative treatment, post operative outcome and demographic data were all documented. SETTING: Mityana hospital, a rural 120 hospital bed, located in Mubende District. It serves Mubende district and the neighbouring districts of Mpigi, Sembabule, Kyenjojo, Kibale and Kiboga. The majority of the population in these districts are mainly peasants involved in cattle keeping and agriculture. PATIENTS: One hundred and twenty patients with chronic osteomyelitis were treated between June 1996 - June 2001. RESULTS: One hundred and twenty patients with chronic osteomyelitis seen in a period of six years, involving various bones of the body. Forty five percent were females, the highest incidence occurred in the age range of 10 - 19 years. The commonest a etiological history was by pricks. The bones most frequently affected were phalanges (43.3%) followed by the tibia (21.6%). Forty four percent of these patients first used local herbs before going to hospital. Fifty five percent of the patients were found to have a big spleen of not less than 12cm below the costal margin and the best treatment option was sequestrectomy and curretage with imperical administration of antibiotics. Complications observed on follow up were: cosmetically bad fingers where curretage and sequestrectomy were done. Distortion of the foot arches where the matarsals were disarticulated and persistent discharging sinuses. CONCLUSION: Chronic osteomyelitis is a debilitating dirty disease endemic in the peasantry communities. It persists because of delay in seeking medical treatment because the first line of treatment is mainly herbs where the terminal phalanges were involved. Sequestrectomy and curettage were a better option to disarticulation because the function of the finger is not interfered with. The biggest number of cases seen involved the phalanges (45.3%) followed by the tibia 21.6% because of the nature of occupation of the rural communities.

Adolescent↗

Economic burden of malaria illness on households versus that of all other illness episodes: a study in five malaria holo-endemic Nigerian communities.

We compared the financial and economic costs of malaria attack to that of a combination of other illness episodes on households in five malaria holo-endemic rural communities. The data was collected from household heads or their representatives using pre-tested interviewer-administered questionnaire. Information was collected on the amount of money household spent to treat both malaria and other illnesses respectively, together with the time lost due to both the groups of illnesses within 1 month prior to the interview. The findings showed that the cost of treating malaria illness accounted for 49.87% of curative health care costs incurred by the households. Average malaria expenditure was $1.84 per household per month, while it was $2.60 per month for the combination of other illness episodes. The average person-days lost due to malaria and the combination of other illnesses were almost equal. If the financial costs of treating malaria and other illnesses are combined, this cost will deplete 7.03% of the monthly average household income, with treatment of malaria illness alone depleting 2.91%. Thus, malaria is a big contributor to the economic burden of disease, in malaria holo-endemic communities. Community-effective malaria control programs are needed to reduce this burden on the households.

Cost of Illness↗

Molecular pharmacology of endothelin converting enzymes.

A critical processing step in endothelin biosynthesis is the conversion of the intermediate "big endothelin" to its biologically active product catalysed by endothelin converting enzyme (ECE). In this commentary we discuss critically the cellular location, structure, and activity of the isoforms of ECE. The current evidence supporting a metallopeptidase ECE as the physiological regulator of endothelin production is described. Its sensitivity to inhibition by the fungal metabolite phosphoramidon and subsequent cloning of the enzyme indicate it to be a type II integral membrane protein homologous with neural endopeptidase-24.11 (E-24.11), the major neuropeptide-degrading ectoenzyme in brain and other tissues. Unlike E-24.11, however, ECE exists as a disulphide-linked dimer of subunit M(r) 120-130 kDa and is not inhibited by other E-24.11 inhibitors such as thiorphan. Alternative splicing produces two forms of ECE with distinct N-terminal tails. These isoforms of ECE-1 show similar specificity converting big endothelin-1 (ET-1) to ET-1 but big ET-2 and big ET-3 are converted much less efficiently. This suggests that additional forms of ECE remain to be isolated. Immunocytochemical studies indicate a predominant cell-surface location for ECE-1, like E-24.11. This is consistent with the conversion of exogenous big ET-1 when administered in vivo and the inhibition of this event by phosphoramidon. However, mature ET-1 can be detected in intracellular vesicles in endothelial cells, suggesting that some processing occurs in the constitutive secretory pathway. This may be mediated by ECE-2, a recently cloned member of the E-24.11/ECE family which has an acidic pH optimum. Selective inhibitors of ECE may have therapeutic applications in cardiovascular and renal medicine.

Amino Acid Sequence↗

Immunological similarity of CEA with alpha 1-acid glycoprotein (orosomucoid).

We have demonstrated that 125 I-CEA (carcinoembryonic antigen) from two commercial sources (Roche and CIS RIA kit) can be precipitated by antibody to alpha 1-acid glycoprotein (AG) dose-dependently. The binding of 125 I-CEA to anti-AG can be displaced by unlabelled AG, though, there was no cross-reaction between AG and anti-CEA. The data strongly suggest that CEA has an immunological similarity to AG. The perchloric acid extract from cancerous tissue was fractionated on a Sephadex G-200 column, and the first eluted fraction (containing large amounts of CEA) was subjected to affinity chromatography using anti-AG bound to Sepharose. The bound fraction was eluted, labelled with 125 I, and then applied to a Sephadex G-200 column with carrier protein. The radioactivity was found mainly in the large molecular size eluted fraction (Fr 1). Almost all radioactivity of Fr 1 was precipitated by anti-AG and anti-CEA. This experiment also demonstrated that a large molecular weight component (Mr: 180 000) obtained from tumor was immunologically related to both CEA and AG. Based on differences in binding affinities between CEA with anti-CEA and with anti-AG we postulate that CEA may be a large molecular precursor of AG (big form of AG).

Carcinoembryonic Antigen↗

Functional evidence for the presence of a phosphoramidon-sensitive enzyme in rat brain that converts big endothelin-1 to endothelin-1.

Endothelin-1 (ET-1) is produced from its precursor, big endothelin-1 (BigET-1), by a putative endothelin-converting enzyme (ECE), but it is not known whether the enzyme is present in the brain. This study was conducted to examine the central hemodynamic effects of BigET-1 and to indirectly determine the presence of an ECE in rat brain. Cardiovascular effects of centrally administered BigET-1 and ET-1 were examined in anesthetized, ventilated rats. BigET-1 (100 pmol) or ET-1 (10 pmol) applied to the IV ventricle produced similar prolonged decreases in mean arterial pressure (MAP) and renal blood flow (RBF). Thus, peak decreases with BigET-1 were (mean +/- S.E.): MAP = -35 +/- 4%; RBF = -27 +/- 5%, while those with ET-1 were: MAP = -36 +/- 5%; RBF = -29 +/- 9%. Pretreatment with phosphoramidon, a metalloprotease inhibitor (90 nmol), abolished the hemodynamic responses elicited by BigET-1 (MAP = -9 +/- 2%; RBF = -3 +/- 2%) but not those produced by ET-1. These data indicate that; i) conversion of BigET-1 to ET-1 in the brain is essential for the expression of hemodynamic actions and ii) a metalloprotease capable of converting BigET-1 to ET-1 is present in rat brain.

Analysis of Variance↗

Surface topography of the cochlear nuclei in humans: two- and three-dimensional analysis.

We used three-dimensional reconstruction to study the cochlear nuclear complex (CN) in postmortem adult brains. Resulting data show that the largest part of the CN surface, particularly the dorsal cochlear nucleus (DCN), is fully within the lateral recess of the fourth ventricle. The surface of another subdivision, the ventral cochlear nucleus (VCN), is also almost entirely within the recess, except for a narrow zone adjacent to the caudoventral border of the nucleus. The caudal portion of the exposed zone of the VCN is in the vicinity of the rootlets of the glossopharyngeal (IX) nerve, and the ventral portion is close to the terminal part of the vestibulocochlear (VIII) nerve. The border between the intraventricular part of the CN and the extraventricular portion and also the terminal part of the VIII nerve approximately coincides with the line of attachment of the inferior medullary velum of the fourth ventricle (tenia of the choroid plexus). In the narrow strip of this ventral most part of the tenia we did not observe big blood vessels or neurons. Accordingly this could be a reasonably safe surgical route to the intraventricular surface of the CN.

Adult↗