Direct visualization and correlation of liver stereotactic body radiation therapy treatment delivery accuracy with interfractional motion.

This study used the visualization of hypo-intense regions on liver-specific MRI to directly quantify stereotactic body radiation therapy (SBRT) spatial delivery accuracy. Additionally, the interfractional motion of the liver region was determined and compared with the MRI-based evaluation of liver SBRT spatial treatment delivery accuracy. Primovist® -enhanced MRI scans were acquired from 17 patients, 8-12 weeks following the completion of liver SBRT treatment. Direct visualization of radiation-induced focal liver reaction in the form of hypo-intensity was determined. The auto-delineation approach was used to localize these regions, and center-of-mass (COM) discrepancy was quantified between the MRI hypo-intensity and the CT-based treatment plan. To assess the interfractional motion of the liver region, a planning CT was registered to a Cone Beam CT obtained before each treatment fraction. The interfractional motion assessed from this approach was then compared against the localized hypo-intense MRI regions. The mean ± SD COM discrepancy was 1.4 ± 1.3 mm in the left-right direction, 2.6 ± 1.8 mm in an anteroposterior direction, and 1.9 ± 2.6 mm in the craniocaudal direction. A high correlation was observed between interfractional motion of visualized hypo-intensity and interfractional motion of planning treatment volume (PTV); the quantified Pearson correlation coefficient was 0.96. The lack of correlation was observed between Primovist® MRI-based spatial accuracy and interfractional motion of the liver, where Pearson correlation coefficients ranged from -0.01 to -0.26. The highest random and systematic errors quantified from interfractional motion were in the craniocaudal direction. This work demonstrates a novel framework for the direct evaluation of liver SBRT spatial delivery accuracy.

Surgical margins for borderline and malignant phyllodes tumours.

BACKGROUND: Phyllodes tumours represent less than 1% of all UK breast neoplasms. Histological features allow classification into benign, borderline or malignant, which has a significant impact on prognosis and recurrence. Currently, there is no consensus for the optimal surgical excision margin. This systematic review aims to provide a comparative summary of outcomes (local recurrence, metastasis and survival) for borderline and malignant phyllodes tumours resected with either ≥1cm or <1cm margins. METHODS: MEDLINE and Embase were systematically searched (1990 to July 2019), in line with PRISMA guidelines. Study quality was assessed using the Newcastle-Ottawa scale. RESULTS: Ten retrospective studies were included (Newcastle-Ottawa scale mean score: 5.6, range: 8-4). Nine reported local recurrence rates, four reported distant metastasis and four reported survival. Meta-analysis pooling demonstrated no statistically significant difference between <1cm and ≥1cm margins in terms of local recurrence rates (relative risk [RR] 1.43, 95% confidence interval [95% CI] 0.70 - 2.93; p=0.33, n=456), distant metastasis (RR 1.93, 95% CI 0.35 - 10.63; p=0.45, n=72) or mortality (RR 1.93, 95% CI 0.42 - 8.77; p=0.40, n=58) for borderline and malignant tumours. Additionally, two studies demonstrated no significant difference in local recurrence for borderline tumours excised with <0.1cm margins compared to ≥1cm. CONCLUSION: Current evidence suggests that margins <1cm may provide adequate tumour excision. This could enable breast conservation in patients with smaller breast-to-tumour volume ratios, with improved cosmetic outcomes and patient satisfaction. A prospective, multi-institutional trial would be appropriate to further elucidate the safety of smaller margins.

Direct enzyme-substrate affinity determination by real-time hyperpolarized (13)C-MRS.

A specialized kinetic analysis of real-time hyperpolarized [1,1,2,2-D4, 1-(13)C]choline (13)C-magnetic resonance spectroscopy enabled the determination of initial rates of metabolic enzyme activity (choline oxidase), enzyme-substrate affinity (Km), and inhibition. In a clinical MRI scanner, metabolite levels lower than 16 µM were detected at a temporal resolution of 1 s.

Detection of radiation-induced lung injury using hyperpolarized (13)C magnetic resonance spectroscopy and imaging.

Radiation-induced lung injury limits radiotherapy of thoracic cancers. Detection of radiation pneumonitis associated with early radiation-induced lung injury (2-4 weeks postirradiation) may provide an opportunity to adjust treatment, before the onset of acute pneumonitis and/or irreversible fibrosis. In this study, localized magnetic resonance (MR) spectroscopy and imaging of hyperpolarized (13)C-pyruvate (pyruvate) and (13)C-lactate (lactate) were performed in the thorax and kidney regions of rats 2 weeks following whole-thorax irradiation (14 Gy). Lactate-to-pyruvate signal ratio was observed to increase by 110% (P < 0.01), 57% (P < 0.02), and 107% (P < 0.01), respectively, in the thorax, lung, and heart tissues of the radiated rats compared with healthy age-matched rats. This was consistent with lung inflammation confirmed using cell micrographs of bronchioalveolar lavage specimens and decreases in arterial oxygen partial pressure (paO2), indicative of hypoxia. No statistically significant difference was observed in either lactate-to-pyruvate signal ratios in the kidney region (P = 0.50) between the healthy (0.215 ± 0.100) and radiated cohorts (0.215 ± 0.054) or in blood lactate levels (P = 0.69) in the healthy (1.255 ± 0.247 mmol/L) and the radiated cohorts (1.325 ± 0.214 mmol/L), confirming that the injury is localized to the thorax. This work demonstrates the feasibility of hyperpolarized (13)C metabolic MR spectroscopy and imaging for detection of early radiation-induced lung injury.

Functional, global and cognitive decline correlates to accumulation of Alzheimer's pathology in MCI and AD.

BACKGROUND: Cognitive, global and functional instruments have been extensively investigated for correlations with neuropathological changes such as neurofibrillary tangles (NFTs), plaques, and synapse loss in the brain. OBJECTIVE: Our objective is to correlate the functional, global and cognitive decline assessed clinically with the neuropathological changes observed in a large prospectively characterized cohort of mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS: We examined 150 subjects (16 MCI and 134 AD) that were prospectively assessed and longitudinally followed to autopsy. MCI subjects clinically met Petersen criteria for single or multi-domain amnestic MCI. AD subjects clinically met NINCDS-ADRDA criteria for probable or possible AD. All subjects received the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), and the Mini Mental State Examination (MMSE) ante-mortem. Plaque and tangle counts were gathered for hippocampus, entorhinal cortex, frontal, temporal and parietal cortices. Braak staging was performed as well. RESULTS: The GDS, FAST and MMSE correlated with plaque counts in all regions. The GDS, FAST and MMSE correlated with tangle counts in in all regions. The three instruments also correlated with the Braak score. The MMSE and GDS correlate better than the FAST in most regions. CONCLUSIONS: Accumulation of neuropathology appears to correlate with functional, global, and cognitive decline as people progress from MCI through AD.

The effective atomic number revisited in the light of modern photon-interaction cross-section databases.

The effective atomic number, Z(eff), has been calculated for fatty acids and cysteine. It is shown that Z(eff) is a useful parameter for low-Z materials at any energy above 1 keV. Absorption edges of medium-Z elements may complicate the energy dependence of Z(eff) below 10 keV. The notion of Z(eff) is perhaps most useful at energies where Compton scattering is dominating, and where Z(eff) is equal to the mean atomic number, Z, over a wide energy range around 1 MeV.

Pathological correlates of cognitive decline in Alzheimer's disease.

Although Alzheimer's disease (AD) has been investigated for more than 100 years, it was not until the 60s that quantitative measures of the disease progression and severity in relation to function and neuropathology were made by Blessed and his colleagues. With the increasing understanding of the pathological changes of AD that take place, there is growing interest in identifying which pathological marker most reliably predicts the dementia and the cognitive profile. Markers of pathology that have been investigated include senile plaques, neurofibrillary tangles, synaptic loss, and neurochemical changes. Many clinical measures have been evaluated as well including Clinical Dementia Rating, Mini Mental State Examination, and Functional Assessment Staging as ways of both predicting the presence of pathological changes of AD as well as correlating with the specific measures of pathology. Accumulation of neuropathology appears to correlate with functional, global, and cognitive decline as people progress through AD. This review will summarize evidence of which neuropathological change correlates robustly with cognitive decline and which cognitive index predicts pathological changes in AD. In general, tangles and synaptic loss are better correlates of cognitive decline and correlate better.

Monte Carlo simulations: a useful tool to extend in vivo calibrations and explore alternative approaches.

Designing and testing new equipment can be an expensive and time consuming process or the desired performance characteristics may preclude its construction due to technological shortcomings. Cost may also prevent other types of scenario being tested. An alternative is to use Monte Carlo simulations to make the investigations. This paper exemplifies how Monte Carlo code calculations can be used to fill the gap by describing two investigations: (1) the possible self-attenuation of homogeneously distributed natural uranium in a lung phantom; and (2) the effect of activity deposited in the ribs on the activity estimate from a lung count.

Monitoring methods and dose assessment for internal exposures involving mixed fission and activation products containing actinides.

Internal dose assessment for intakes of radionuclide mixtures is a difficult task. When the radionuclide mixture contains both the easy to detect gamma emitters, e.g., 60Co and 95Zr, and difficult to detect alpha emitters such as 239Pu and 241Am, a single monitoring method, such as in-vivo counting, is inadequate for detection and dose assessment. Recent experience with task related monitoring for such radionuclide mixtures at Ontario Power Generation CANDU nuclear power plants has offered an opportunity to review this topic and suggest a strategy for monitoring that involves a combination of in-vivo and in-vitro methods. Using the radionuclide composition data in a mixture from an actual case as an example, this paper describes a monitoring strategy for mixed fission and activation products, including the advantages and pitfalls of reliance on surrogate radionuclides for signaling the presence of actinides in the mixture. The described monitoring strategy is consistent with the recommendations of ICRP Publication 78, which advocates a "combination of techniques so as to make the best possible evaluation of an unusual situation, for example, a programme of both body activity and excreta measurements." The use of experience and professional judgement for interpreting the combined in-vivo and in-vitro data for interim and ultimate intake and dose assessment is discussed and emphasized.

Expression of estrogen and progesterone receptors in glutamate and GABA neurons of the pubertal female monkey hypothalamus.

We have previously reported direct glutamate (Glu) synapses upon GnRH-containing neurons in the primate hypothalamus, and extensive interactions between Glu and aminobutyric acid (GABA) neurons in areas associated with reproductive function. Both Glu and GABA are known to affect peripubertal GnRH neurohormone release, but their relative roles remain unclear. In a developmental survey, estrogen receptors (ER) and progesterone receptors (PR) were virtually undetectable after immunostaining the hypothalamus of prepubertal monkeys, but were clearly evident in neurons of adults. We hypothesized, therefore, that Glu and GABA neurons which develop ER or PR expression during puberty may participate in reactivation of the hypothalamic-pituitary-gonadal axis. To identify those neurons in midpubertal female cynomolgus monkeys, we performed immunofluorescence staining for ER or for PR in separate sets of hypothalamic sections, and then immunostained for Glu or for glutamate decarboxylase (GAD, to identify GABA neurons) using a contrasting fluorophore. ER and PR were localized in the cytoplasm and nuclei of Glu and GAD neurons in nine hypothalamic and related brain regions. Quantitation revealed intranuclear ER in an average of 80% of the Glu neurons in all regions analyzed, and an average of 84% of the GAD neurons in all regions except the supraoptic nucleus (28%). Intranuclear PR expression was more variable, occurring in an average of 93% of the Glu neurons in seven regions, but in only 41% in the medial preoptic area, and 0% in the arcuate-periventicular zone. In addition, while intranuclear PR was seen in 96% of the GAD neurons in the septum, it appeared in 67% of the GAD neurons in the paraventricular nucleus, 47% in the medial preoptic area, 40% in the periventricular zone, and was absent from neurons in the supraoptic nucleus and mammillary bodies. In summary, certain subpopulations of Glu and GABA neurons in principal hypothalamic regions of the female monkey express ER and PR at midpuberty. Taken together with previous findings, these results suggest that Glu and GABA neurons which become sensitive to steroid hormones may help regulate GnRH neurohormone release and promote the onset of puberty. Since neuronal expression of ER or PR connotes sensitivity to gonadal feedback, and intranuclear translocation signals transcriptional activation, these results provide insights into the specific neuronal events involved in the peripubertal transition in primates.

Estrogen and progesterone receptor expression in neuroendocrine and related neurons of the pubertal female monkey hypothalamus.

Expression of hypothalamic estrogen receptors (ER) and progesterone receptors (PR) is barely evident in prepubertal monkeys but is prominent in adults. To investigate whether adult patterns of ER and PR expression are established in mid-pubertal female cynomolgus monkeys, we labeled neuroendocrine (NEU) neurons by microinjection of retrograde tracer into the median eminence, and then identified ER and PR by specific immunostaining in separate sets of hypothalamic sections. ER and PR appeared in the cytoplasm and nuclei of cells identified exclusively as neurons, and retrograde tracer remained clearly visible in the cytoplasm of NEU neurons after immunostaining. Numbers of NEU and related neurons expressing ER or PR were quantified in principal hypothalamic regions. In the supraoptic nucleus, almost all neurons analyzed (n = 580) contained ER (94%) with many also NEU (73% ER + NEU), while lesser amounts of the neurons examined (n = 214) expressed PR (75%) and were NEU (53% PR + NEU). In the paraventricular nucleus, most of the neurons analyzed (n = 302) contained ER (90% ER; 54% ER + NEU), but few of the neurons studied (n = 269) contained PR (34% PR; 19% PR + NEU). In the periventricular zone, nearly all neurons examined (n = 795) contained ER (95% ER; 48% ER + NEU), but fewer of those studied (n = 298) exhibited PR (79% PR; 47% PR + NEU). In the arcuate-periventricular zone, all neurons examined (n = 542) contained ER (100%) but few were NEU (4% ER + NEU), while nearly all neurons studied (n = 418) contained PR (95%), some of which were NEU (21% PR + NEU). Neurons expressing ER were also prevalent in areas without NEU labeling, including the diagonal band of Broca, medial preoptic area, and mammillary bodies, but were less common in the septum and dorsomedial hypothalamus. Likewise, neuronal PR expression was seen frequently in the mammillary bodies, but occurred less often in the diagonal band of Broca, medial preoptic area, and dorsomedial hypothalamus. Neurons in the suprachiasmatic nucleus and lateral hypothalamic area lacked retrograde labeling. These results identify the principal sites and subsets of NEU and related neurons which express ER and PR in the mid-pubertal female monkey hypothalamus. They appear to correlate well with known populations of steroid-sensitive NEU neurons present in these areas in adults. The data also suggest that functional patterns of ER and PR expression arise upon reactivation of the hypothalamic-pituitary-gonadal axis at puberty. The degrees of receptor expression and of nuclear translocation most likely reflect peripubertal changes in the levels of gonadal steroids. Taken together, these results provide important insights into the mechanisms and development of neuroendocrine control during the pubertal period in primates.

Retention and excretion of 95Zr-95Nb in humans.

This note describes the retention and excretion of 95Zr-95Nb in humans based on a recent CANDU experience and a literature survey of reported cases. Two data bases, QUEST and INIS were used for the survey. Three reported cases were discovered: two for occupational exposures and one for public exposure from nuclear weapons fallout. Human lung retention from these three cases, plus whole body retention and some limited fecal excretion data from a recently occurred exposure at a CANDU station, were reviewed and tested against predictions based on ICRP Publication 30 model. Based on the fits of this model to the reported data it seems that the three occupational exposures exhibit class Y behavior while the public exposure exhibits class W behavior. For only one case is the chemical compound known with certainty: ZrO2. Zirconium oxides are currently classified as class W in ICRP Publications 30 and 54. This work confirms a suggestion that oxides of zirconium be classified as class Y and should be taken into account by the ICRP in its future publications.

Glutamate and GABAergic neurointeractions in the monkey hypothalamus: a quantitative immunomorphological study.

Glutamate (Glu) and gamma-aminobutyric acid (GABA) are the most abundant excitatory and inhibitory neurotransmitters in the mammalian hypothalamus. Glu and GABA-containing neurons have both been shown to synapse with gonadotropin-releasing hormone (GnRH) and other neuroendocrine systems in the hypothalamus of several species. Since their direct interactions could play a pivotal role in governing neuroendocrine function, we performed double-label immunostaining for Glu and for glutamic acid decarboxylase (GAD) as a marker for GABAergic neurons in hypothalamic sections from adult female cynomolgus monkeys. Ultrastructural analysis of 785 Glu-immunoreactive (-ir) and GAD-ir elements in the medial septum (MS), arcuate nucleus-ventral hypothalamic tract (VHT1), supraoptic nucleus (SON), paraventricular nucleus (PVN), and median eminence (ME) revealed that 63% were Glu-ir, 28% were GAD-ir, and 9% were Glu + GAD-ir. In addition, we observed surprisingly consistent labeling of 2-4% somata (SOM), 65-80% dendrites (DEN), and 15-30% axons and terminals (AXO) in all of these areas. Characterization of 177 interactions (36% synapses, 64% contacts) by pre/post-transmitter content indicated that 29% contained Glu/GAD, 15% Glu/Glu, and 15% Glu/Glu + GAD, while 16% were unlabeled/Glu, 9% were unlabeled/GAD, and 16% expressed other transmitter combinations. Regional analysis of these interactions showed that 43% occurred in the MS, 22% in VHT1, 14% in SON, 9% in PVN, and 12% in the ME. AXO/DEN interactions made up 51% of all labeled interactions characterized, and were comprised 29% of Glu/GAD, 22% of Glu/Glu, and 18% of the Glu/Glu, and 18% of the Glu/Glu + GAD type. AXO/DEN synapses were more prevalent than contacts in all areas except the PVN and of course the ME, where anatomical synapses do not occur. AXO/SOM interactions represented approximately 15% of all those identified, and were predominantly unlabeled/Glu (71%) and unlabeled/GAD (18%) synapses. Almost all (95%) AXO/SOM synapses and 75% of the contacts occurred in the MS. DEN/DEN interactions, 28% of the total, were composed 50% of Glu/GAD, 12% of Glu/Glu, and 18% of the Glu/Glu+GAD type. The relatively few DEN/DEN synapses all appeared in the MS, whereas much more abundant DEN/DEN contacts were more widely distributed. DEN/SOM interactions, 6% of the total, appeared only as contacts, with the majority (60%) again located in the MS. In addition, the MS contained 48% of all asymmetrical synapses (vs. 35% in VHT1 and 17% in SON), 62% of all symmetrical synapses (vs. 19% in VHT1 and 14% in SON), and 35% of all contacts (vs. 21% in VHT1 and 12% in SON) identified.(ABSTRACT TRUNCATED AT 400 WORDS)

A critical review of 55Fe dosimetric models.

The available literature on 55Fe dosimetry has been devoted to environmental exposures and medical iron kinetic studies. For occupational dosimetry, ICRP (1979, 1988) published a non-recycling dosimetric model for iron. These ICRP publications do not provide information on iron excretion. Johnson and Dunford (1985) published dose conversion factors and urinary excretion curves based on the ICRP (1980) and MIRD (1983) iron metabolic models. A critical review of these models was undertaken to select a model for occupational dose assignment. The review indicated that the information and recommendations in ICRP (1988) and Johnson and Dunford (1985) are dependent on unrealistic assumptions that do not agree with known iron metabolism. Therefore, an alternative model is proposed for dosimetric application. Calculations of dose conversion factors and urinary excretion curve for class W55Fe inhalation exposure (1 micron AMAD) using the proposed model are compared with predictions based on ICRP (1980) and Johnson and Dunford (1985) models. The difference in the practical outcome (i.e., dose assignment) is examined by applying the proposed and reviewed models to a realistic bioassay case. The Johnson and Dunford (1985) model yields a dose estimate which is roughly a factor of ten higher than values predicted by ICRP (1980) and the proposed model. Some of the disagreement is due to uncertainty in the fraction of radio-iron excretion via urine. Further research on this subject is recommended. In the interim, the proposed model is recommended for occupational dose assignment.

Glutamate-immunoreactive neurons and their gonadotropin-releasing hormone-neuronal interactions in the monkey hypothalamus.

Glutamate (Glu) is the most prevalent excitatory neurotransmitter in the brain and has been implicated in the regulation of GnRH secretion in several mammalian species, including the monkey. To investigate the neuroanatomical basis for Glu-GnRH interactions, we performed an immunocytochemical study at both the light and electron microscopic levels on the brains of four female and five male macaques. Initially, we determined the location of Glu-immunoreactive (-ir) elements using a monoclonal antibody specific for glutaraldehyde-fixed Glu (Glu-2) and 3,3'-diaminobenzidine-4-HCl (DAB). Glu-ir was observed in the cytoplasm and to a variable degree in the nuclei of neurons in the diencephalon. Cytoplasmic staining was particularly intense in numerous neurons in the arcuate nucleus, supraoptic nucleus, and many paraventricular nucleus neurons. Short Glu-ir processes were evident in these and other hypothalamic regions and were extremely dense in the infundibular stalk and median eminence. Prior absorption of the Glu-2 antibody with a Glu-glutaraldehyde-BSA conjugate completely abolished all immunostaining in both neuronal nuclei and cytoplasm. Double label Glu-GnRH immunostaining for light microscopy was performed using Glu-2 and DAB without enhancement, and a polyclonal antibody (LR1 or LR2) with silver-enhanced DAB for Glu and GnRH, respectively. Glu-ir interactions with GnRH-ir cell bodies were not apparent, but a few Glu-ir axons seemed to contact GnRH-ir dendrites in the organum vasculosum of the lamina terminalis, medial septum, and arcuate nucleus regions. Reciprocal interactions occurred more frequently, however, in which GnRH-ir axons and dendritic fibers engaged Glu-ir cell bodies en passant, particularly toward the medial and posterior hypothalamus. For ultrastructural analyses, Glu-ir elements were stained with the Glu-2 antibody and 15 nm immunogold or DAB. Electron microscopy demonstrated that Glu-ir was associated with clear microvesicles within the neuronal cytoplasm. Glu-ir processes made classical asymmetrical synapses with one another and received asymmetrical synapses from unlabeled afferents. In sections double labeled for Glu with immunogold and for GnRH with DAB, axo-somatic interactions were not observed. However, axo-dendritic Glu-GnRH synapses were seen, which usually exhibited Glu-ir labeling of terminal vesicles and inconsistent postsynaptic densities, with GnRH-ir neurosecretory granules sometimes congregated in the apposing dendrite or spine. Surprisingly, reverse GnRH-Glu interactions were observed more frequently.(ABSTRACT TRUNCATED AT 400 WORDS)

Neuropeptide Y system of the female monkey hypothalamus: retrograde tracing and immunostaining.

Neuropeptide Y (NPY) stimulates the release of hypothalamic gonadotropin-releasing hormone (GnRH) as well as pituitary gonadotropins in the presence of ovarian steroids, but inhibits release in their absence. In primates, however, the effects of NPY depend largely upon the site and method of administration. In ovariectomized monkeys, NPY infusion into the stalk-median eminence reportedly causes a dose-response increase in GnRH secretion in the absence of gonadal steroids. To help elucidate these findings, we investigated the NPY system and its neuroendocrine (NEU) component in the primate brain by retrograde tracing and immunostaining. One adult female and 1 juvenile female cynomolgus monkey were given microinjections of retrograde tracer into the median eminence (ME). Two weeks later, they were perfused with fixative, and series of 40-microns frontal vibratome sections were collected at 500-microns intervals through 4 mm of the forebrain. Injection sites were not visible in the juvenile female monkey ME, so this animal served as a neurosurgical and injection control. Sections were immunostained using a polyclonal NPY antiserum and the peroxidase antiperoxidase (PAP) technique. NPY immunostaining in another adult female cynomolgus monkey and in a late fetal female and a neonatally castrated adult male rhesus monkey gave essentially similar results. NPY-immunoreactive (NPY-IR) neurons were widely distributed throughout the caudate nucleus, but appeared concentrated within specific hypothalamic areas. Their number, as well as the number of NEU neurons, was nearly equal in bilaterally paired areas and on both sides of the hypothalamus overall. Ratios of retrogradely labeled NPY-IR neurons to the number of NPY-IR somata were expressed as percentages of NEU NPY-IR neurons for each side and in each area. These averaged 65% in the supraoptic nucleus (SON), 41% in the paraventricular nucleus (PVN), 32% in the medial preoptic area (MPOA), which has only one quarter of their number of NPY-IR cells, and 11% in the medial basal hypothalamus (MBH). NPY-IR fiber densities were highest in the area olfactoria, medial septal and ventromedial nuclei. They were high in the tuberculum olfactorium, lateral septum, nucleus accumbens, MPOA, PVN, dorsomedial nucleus and regions of the MBH including the arcuate nucleus, tuber cinereum and ventral hypothalamic tract (VHT). NPY fiber densities were moderate in the vertical portion of the diagonal band of Broca, the ventral part of the caudate nucleus, the anterior commissural nucleus and the lateral preoptic area, as well as the anterior and lateral hypothalamic areas, the anterior ventral periventricular area, the suprachiasmatic nucleus and the dorsolateral SON.(ABSTRACT TRUNCATED AT 400 WORDS)

Occupational exposure of electrical utility linemen to pentachlorophenol.

Occupational exposure to pentachlorophenol (PCP) for a crew of electrical utility linemen was monitored over a 6-month period by using total PCP in urine per gram of creatinine as a biological monitoring parameter. Urine samples were collected from three groups: A, B, and control, at a 4-week frequency during 1989. Group A was required to use new gloves after each 4-week work period; Group B changed gloves on a need basis as per normal operating procedure. The control group consisted of members of the administrative office staff who were not occupationally exposed. The used gloves returned by Group A were monitored for contamination. On the basis of analysis of the collected data the following conclusions were noted. (1) The linemen experienced a seasonal exposure pattern with exposures peaking in July and August. This seasonal effect was also observed with glove contamination data. (2) The glove contamination levels were significantly associated with urine PCP concentrations when both these variables were expressed as geometric means for the individuals in Group A. Inclusion of work experience as an additional variable enhances this association. Less experienced linemen tended to perform more activities with higher current exposure and had higher urine and glove PCP measurements and higher correlations between these variables than more experienced linemen. (3) Over the study period, the difference in long-term exposures of Group A and Group B linemen was not statistically significant. (4) The long-term individual exposures, calculated as the geometric mean of each individual's sequential sample readings, were all below the biological monitoring guideline value of 1000 micrograms PCP/g creatinine.

Interactions between vasopressin- and gonadotropin-releasing-hormone-containing neuroendocrine neurons in the monkey supraoptic nucleus.

Vasopressin (VP) is a hypophysiotropic hormone which is also implicated in the control of gonadotropin-releasing hormone (GnRH) secretion. We examined whether VP- and GnRH-immunoreactive (-IR) elements interact directly in the supraoptic nucleus (SON) of cynomolgus monkeys. Neuroendocrine (NEU) neurons in 4 juveniles were retrogradely labeled from the median eminence with wheat germ agglutinin apohorseradish peroxidase conjugated to gold before aldehyde perfusion. Frontal vibratome sections were immunostained for GnRH with peroxidase-antiperoxidase (PAP) and for VP with 5- or 15-nm gold. Many of the GnRH-IR and more than half the VP-IR cell bodies in the SON were NEU. VP-IR elements formed axodendritic and axosomatic symmetrical synapses with one another. In addition, VP-IR boutons also synapsed with NEU GnRH-IR neurons. Although GnRH axon terminals and dendrites contacted VP-IR dendrites and NEU cell bodies, we were unable to find convincing examples of GnRH/VP synapses through serial sections, perhaps due to the use of PAP-diaminobenzidine as the GnRH (afferent) immunolabel. In summary, our study demonstrates anatomical synapses between VP-IR and other VP and GnRH-IR neurons in the SON, in which postsynaptic VP or GnRH cell bodies were NEU. On the other hand, reciprocal GnRH/VP contacts but no true synapses were seen. However, the results suggest coordinated roles for VP and GnRH in NEU control of gonadotropin secretion. Whether VP itself and/or coexistent neuroeffectors act directly on NEU GnRH secretion remains to be determined. As such, VP neurons could help coordinate suppression of gonadotropins and augmentation of glucocorticoids during the stress response in primates.

Opioid synapses on vasopressin neurons in the paraventricular and supraoptic nuclei of juvenile monkeys.

Opioid peptide- as well as vasopressin-containing neurons synapse on gonadotropin releasing hormone neurons in juvenile macaques. In this study we performed double-label immunostaining for opioid and vasopressin neurons in the paraventricular and supraoptic nuclei in order to assess their interrelationships. Neuroendocrine neurons in the hypothalamus were prelabeled by microinjection of electron-dense retrograde tracer into the median eminence, and were easily identified in frontal Vibratome sections. Sections through the paraventricular and supraoptic nuclei were immunostained for vasopressin with the peroxidase-antiperoxidase technique, and for opioids using the indirect immunogold method. By light microscopy, opioid-immunoreactive inputs appeared to innervate an average of 39% of the vasopressin neurons in the paraventricular nucleus and 33% in the supraoptic nucleus, and were more prevalent anteriorly. Clusters of opioid afferents formed cup-like calices around major processes of many vasopressin neurons, especially in the paraventricular nucleus. Electron microscopy revealed that these groups of opioid axon terminals made frequent symmetrical and fewer asymmetrical synapses on both neuroendocrine and non-neuroendocrine vasopressinergic cell bodies and dendrites. Our study did not reveal vasopressin-opioid synapses in these hypothalamic nuclei, but this does not preclude the possibility of their existence elsewhere. These results indicate that opioid afferents modulate vasopressin neuronal activity in the monkey paraventricular and supraoptic nuclei. Previous results have suggested that corticotropin releasing hormone acts via vasopressinergic neurons to stimulate opioid neuronal activity and to inhibit gonadotropin releasing hormone release. Taken together, the data suggest that stressful stimuli could initiate a series of neuropeptidergic interactions which ultimately alter pulsatile gonadotropin releasing hormone secretion and thus gonadotropin secretion in primates.