Excess body mass is associated with T cell differentiation indicative of immune ageing in children.

Obesity has been associated with accelerated biological ageing and immunosenescence. As the prevalence of childhood obesity is increasing, we wanted to determine if associations between obesity and immunosenescence would manifest in children. We studied 123 Mexican American adolescents aged 10-14 (mean 12·3 ± 0·7) years, with body weights ranging from 30·1 to 115·2 kg (mean 52·5 ± 14·5 kg). Blood samples were obtained to determine proportions of naive, central memory (CM), effector memory (EM), senescent and early, intermediate and highly differentiated subsets of CD4(+) and CD8(+) T cells. Overweight and obese children had significantly lowered proportions of early CD8(+) T cells (B = -11·55 and -5·51%, respectively) compared to healthy weight. Overweight children also had more EM (B = +7·53%), late (B = +8·90%) and senescent (B = +4·86%) CD8(+) T cells than healthy weight children, while obese children had more intermediate CD8(+) (B = +4·59%), EM CD8(+) (B = +5·49%), late CD4(+) (B = +2·01%) and senescent CD4(+) (B = +0·98%) T cells compared to healthy weight children. These findings withstood adjustment for potentially confounding variables, including age, gender and latent cytomegalovirus and Epstein-Barr virus infections. We conclude that excess body mass, even in adolescence, may accelerate immunosenescence and predispose children to increased risks of incurring immune-related health problems in adulthood.

Clinical characterisation and long-term survival of paediatric and juvenile lymphoma in cats: 33 cases (2008-2022).

OBJECTIVES: The aims of this study were to describe the clinical presentation, tumour characteristics, responses to chemotherapy protocols and toxicity in a cohort of cats with lymphoma up to 18 months of age. In addition, the probability of long-term (>2 years) survival was explored. MATERIALS AND METHODS: The medical records of client-owned cats aged up to 18 months diagnosed with lymphoma between 2008 and 2022 at five UK-based veterinary referral hospitals were reviewed. RESULTS: Thirty-three cats were included. The most common anatomical forms were mediastinal (42%), disseminated disease (30%) and renal (15%), with all cats having intermediate to large cell lymphoma. Three out of 29 cats tested were positive for FeLV but none for FIV. Twenty-six cats were treated with multi-agent chemotherapy protocols with complete and partial responses seen in 46% and 50% of cats, respectively. For this group, median progression-free survival was 133 days (95% confidence interval [Cl] 67 to 199) and median survival time was 268 days (95% Cl 106 to 430). Complete response to chemotherapy was associated with a longer progression-free survival. Seven cats were considered long-term survivors (>2 years). Chemotherapy was generally well tolerated with none of the long-term survivors suffering from chronic sequelae from cytotoxic treatment. CLINICAL SIGNIFICANCE: Paediatric and juvenile cats with lymphoma showed a high response rate to multi-agent chemotherapy protocols with rare significant toxicities. The presence of long-term survivors may suggest a more favourable outcome in a subset of patients.

Histiocytic sarcoma in miniature schnauzers: 30 cases.

OBJECTIVES: To summarise the clinical presentation and outcomes in a series of miniature schnauzers diagnosed with histiocytic sarcoma. MATERIALS AND METHODS: Retrospective review of medical records of miniature schnauzers diagnosed with histiocytic sarcoma between 2008 and 2019 at two referral centres in the UK. Signalment, clinical signs at initial presentation, imaging results and clinico- and histopathological findings, treatment type and outcome were recorded. Progression-free survival and overall survival time were calculated. RESULTS: Thirty dogs were included. Twenty-four of 29 dogs undergoing imaging of the thorax had lung and/or mediastinal involvement. The median overall survival time for dogs that were not euthanased within 3 days of diagnosis was 117 days (range 10 to 790). Three dogs underwent surgery; 13 received treatment with lomustine as a sole therapy - with partial responses documented on imaging in five of six dogs and 11 of 13 showing clinical improvement. CLINICAL SIGNIFICANCE: Histiocytic sarcoma should be considered as a differential diagnosis for miniature schnauzers with pulmonary masses. Although responses to treatment were common, they were usually short-lived because of the aggressive nature of the disease.

Impact of parental weight status on a school-based weight management programme designed for Mexican-American children.

BACKGROUND: While overweight and obese children are more likely to have overweight or obese parents, less is known about the effect of parental weight status on children's success in weight management programmes. OBJECTIVES: This study was a secondary data analysis of a randomized controlled trial and investigated the impact of having zero, one or two obese parents on children's success in a school-based weight management programme. METHODS: Sixty-one Mexican-American children participated in a 24-week school-based weight management intervention which took place in 2005-2006. Children's heights and weights were measured at baseline, 3, 6 and 12 months. Parental weight status was assessed at baseline. Repeated measures anova and ancova were conducted to compare changes in children's weight within and between groups, respectively. RESULTS: Within-group comparisons revealed that the intervention led to significant decreases in standardized body mass index (zBMI) for children with zero (F = 23.16, P < .001) or one obese (F = 4.99, P < .05) parent. Between-group comparisons indicated that children with zero and one obese parents demonstrated greater decreases in zBMI compared to children with two obese parents at every time point. CONCLUSIONS: The school-based weight management programme appears to be most efficacious for children with one or no obese parents compared to children with two obese parents. These results demonstrate the need to consider parental weight status when engaging in childhood weight management efforts.

Obesity status transitions across the elementary years: use of Markov chain modelling.

OBJECTIVE: The objective of this study was to assess overweight and obesity status transition probabilities using first-order Markov transition models applied to elementary school children. METHOD: Complete longitudinal data across 11 assessments were available from 1494 elementary school children (from 7599 students in 41 out of 45 schools in a Southeast Texas school district) from kindergarten to the beginning of the fifth grade. Heights and weights were measured by trained school nurses using standard procedures at the beginning and end of each school year for the 11 consecutive assessments. To estimate the transition probabilities, first-order three-state (healthy weight, overweight and obese) Markov transition models were fit to the longitudinal weight status data of all assessment periods. RESULTS: While there was a gradual shift to more children in the overweight or obese category over 5 years, children were most likely to stay in the same weight category as the previous assessment. A consistent seasonal difference in the probability of changing weight status category was seen, with a greater probability of becoming overweight and obese during the summer compared with the school year. The transition probabilities to obesity were higher among boys, Hispanic and non-Hispanic Black, and lower socioeconomic status children. CONCLUSIONS: This study provides the first application of a Markov transition model to child weight status data. The transitions into the overweight and obese categories were small, but persistent, with smaller percentages transitioning out of overweight or obese. Early monitoring and summer intervention strategies are needed to prevent the slow, but relentless, transition into the overweight and obese categories.

Processing of the luteinizing hormone-releasing hormone precursor in the preoptic area and hypothalamus of the rat.

The LHRH precursor is known to contain the decapeptide and a 56 amino acid peptide termed gonadotropin-releasing hormone-associated peptide (GAP). The purpose of our study was to characterize the proLHRH and its processed products from the cell body and fiber region and from the nerve terminal region of LHRH neurons. The median eminence (ME) and a tissue block containing the preoptic area and hypothalamus (POH) were dissected separately. Tissues were homogenized and peptides were separated according to mol wt. Three different LHRH antisera bound to one immunoreactive (IR) substance which eluted at approximately 1200 mol wt. Subsequently, this material coeluted with synthetic LHRH on a reversed-phase column as a single peak. There was approximately 1.6-fold more LHRH-like IR in the ME than in the POH. The four different GAP antisera recognized multiple mol wt forms of GAP-like IR at approximately 16,000 to 14,000, 8,200, 6,500, 3,500, and 2,800 mol wt. There were more of the high mol wt materials and less of the 6500 and lower mol wt materials in the POH than in the ME. The most abundant species in both regions was the 6500 mol wt form. This IR substance coeluted with synthetic rat GAP1-56 on a reversed-phase column as a single peak. These experiments demonstrate 1) that multiple IR forms of the LHRH prohormone exist in the POH of the rat and 2) that nerve terminals of the LHRH neurons contain LHRH, GAP1-56, and some lower mol wt GAP-like substances. These results provide the first information concerning the processing scheme for the LHRH prohormone in the rat brain.

Rapid, divergent changes in spinal and forearm bone density following short-term intravenous treatment of Paget's disease with pamidronate disodium.

Intravenous disodium 3-amino-1-hydroxypropylidene-1,1-bisphosphonate pentahydrate (pamidronate disodium) was used to treat 39 patients (22 males and 17 females, age range 48-85 years) with symptomatic Paget's disease. Patients were stratified into three groups based on the biochemical severity of the disease as assessed by fasting urinary hydroxyproline excretion (HypE, mumol/liter GF, glomerular filtrate): group I (n = 23), HypE < 5.0, treated with 120 mg total dose over 2 or 4 days; group II (n = 6), 5.0 < or = HypE < or = 10.0, 180 mg over 3 or 6 days; and group III (n = 10), HypE > 10.0, 240 mg over 4 or 8 days. Bone mineral density (BMD) was measured before and 3 and 6 months following treatment in the spine (L1-4) using dual-energy x-ray absorptiometry and in the forearm at an ultradistal and a shaft site using single-photon absorptiometry. When groups I-III were combined, nonpagetic and pagetic lumbar spinal BMD had both risen significantly at 3 months compared with the pretreatment values (p < 0.001). In each group, lumbar spinal BMD in pagetic vertebrae rose markedly by 3 months, with no further significant change at 6 months. The percentage rises in the three groups were not different from each other at 3 or 6 months. Nonpagetic lumbar spinal BMD followed a similar and significant trend but with a significantly smaller rise than for pagetic bone. (For the combined groups, nonpagetic BMD rose 5.1 +/- 1.1% SEM, above pretreatment at 6 months; pagetic BMD rose 17.8 +/- 1.6%: significance of comparison = p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Maturation of the prolactin and proopiomelanocortin-derived peptide responses to ether stress and morphine: neurochemical analysis.

The hormonal and neurochemical responses to acute ether stress, morphine, and/or naloxone were analyzed in infantile (13-day-old) and prepubertal (36-day-old) male CD rats in an attempt to identify a possible neurochemical correlate(s) for the previously demonstrated requisite maturation of the PRL response to ether stress. Neuronal serotonin (5-HT), norepinephrine (NE), and dopamine (DA) activities were examined in the medial preoptic hypothalamic area (MPOH), medial basal hypothalamic area (MBH), and median eminence (ME). Ether stress increased plasma PRL, ACTH, and beta-endorphin-like immunoreactivity (beta end) as well as NE metabolism in the MPOH and MBH and neuronal 5-HT activity in the MBH, and decreased neuronal DA activity in the ME of prepubertal animals. Ether stress elicited similar changes in infantile animals, with the important exceptions that plasma PRL, neuronal 5-HT activity in the MBH, and neuronal DA synthesis in the ME were not affected at this earlier age. Morphine increased plasma PRL, ACTH, and beta end levels, elevated neuronal NE and 5-HT activities in the MPOH and MBH, and decreased DA synthesis in the ME in both infantile and prepubertal animals. Naloxone administration did not alter basal hormone concentrations or neuronal monoamine activity in any brain area, but did prevent all of the morphine-induced changes as well as the ether stress-induced changes in PRL, MBH neuronal 5-HT activity, and DA synthesis in the ME of prepubertal animals. In addition, naloxone augmented the ether stress-induced increases in ACTH and beta end in prepubertal rats. Indirect stimulation of 5-HT neurons by administration of the amino acid precursor of 5-HT, 5-hydroxytryptophan, resulted in decreased DA synthesis in the ME of infantile animals and increased plasma PRL levels in that age group, indicating that this portion of the neurochemical connection is already present in infantile animals. Furthermore, the 5-hydroxytryptophan-induced increase in PRL was blocked by pretreatment with naloxone. The results demonstrate that both the ether stress- and morphine-induced increases in plasma PRL, but not in ACTH or beta end, are associated with increased neuronal 5-HT activity in the MBH and a decreased neuronal DA activity in the ME, that these are opiate receptor-mediated effects, and that infantile rats apparently lack a functional opiate-5-HT connection, which matures some time between days 13 and 36 postnatally.

Role of oxytocin on prolactin secretion during proestrus and in different physiological or pharmacological paradigms.

The present study was designed to evaluate the possible physiological role of oxytocin (OXY) on PRL release by examining the effect of administration of potent pharmacological antagonists of OXY on the stimulation of PRL secretion observed in vitro from anterior pituitary (AP) cells in response to OXY administration or in a number of in vivo paradigms. OXY caused a dose-related increase in PRL release from dispersed AP cells and short term AP cell cultures which was blocked by administration of the OXY antagonists [1-deaminopenicillamine, 2-O-methyltyrosine, 8-ornithine]vasotocin (dPOMeOVT) or [1-(beta-mercapto-beta,beta-cyclopentamethylene propanoic acid)2-O-methyltyrosine, 8-ornithine]vasotocin (MPOMeOVT), respectively. The antagonists were given in vivo in a dose that completely blocked suckling-induced milk let-down for up to 90 min. Injection of the antagonists did not alter the 5-hydroxytryptophan-induced increase in plasma PRL or the increase associated with acute ether stress or acute suckling stimuli, suggesting that OXY is not a major component involved in the neuroendocrine mechanisms responsible for those particular increases. On the other hand, iv administration of dPOMeOVT or MPOMeOVT prevented the increase in plasma PRL normally observed on the afternoon of proestrus in the cycling female rat. The characteristic surge of LH was also blocked by high doses of these antagonists. These data demonstrate that PRL secretion undergoes a differential regulation, in that OXY appears to play a major role in regulating the increase in plasma PRL observed on the afternoon of proestrus, but apparently provides little, if any, contribution toward the neuroendocrine regulation of the increases in PRL associated with 5-hydroxytryptophan administration, acute ether stress stimulus, or acute suckling stimulus. The data also suggest that OXY receptors located in the AP that are involved in the OXY-induced increase in PRL release may be similar to those OXY receptors located in mammary and uterine tissue, since specific biological effects of OXY in those tissues are effectively blocked by the OXY antagonists dPOMeOVT and MPOMeOVT. A possible role of OXY neurons in the neural mechanisms triggering the LH surge during proestrus is also suggested.

Role of central epinephrine on the regulation of corticotropin-releasing factor and adrenocorticotropin secretion.

Epinephrine (EPI) has been described to stimulate the hypothalamic-pituitary-adrenal axis. However, whether central EPI neuronal systems play a major physiological role in the regulation of ACTH secretion and whether that role is primarily stimulatory or inhibitory in nature is still controversial. The present study addressed these questions using different inhibitors of phenylethanolamine-N-methyltransferase (PNMT), which were either active peripherally or were both peripherally and centrally active. Male rats received either vehicle or a PNMT inhibitor at various times before further experimental procedures. A large decrease in hypothalamic EPI levels was observed in rats given central PNMT inhibitors, whereas these treatments did not affect hypothalamic norepinephrine (NE) levels. Plasma EPI, but not NE, was decreased to similar levels after treatment with peripheral or central PNMT inhibitors. Basal plasma ACTH decreased slightly during the 12 h after central PNMT inhibition. Central, but not peripheral, inhibition of PNMT significantly decreased the plasma ACTH response to ether vapor stress at 5 and 15 min. This effect was seen 3 or 12 h after PNMT inhibition. The suppression of the stress response was not due to a change in responsiveness of the pituitary to CRF. The hypothalamic content of CRF was significantly decreased 9 and 12 h after inhibition of central PNMT. Blockade of the stress response actually preceded the changes in CRF levels. The content of arginine vasopressin, another potent ACTH secretagogue, was not affected 3, 6, 9, or 12 h after that treatment. The effect on CRF was not observed in rats treated with the peripheral PNMT inhibitor, nor was it caused by manipulation and stress of the animals 12 h before death. The dat demonstrate that central inhibition of PNMT, which produces a selective decrease in hypothalamic EPI levels, blunts the response of plasma ACTH to ether vapor stress, and at later times also causes a selective decrease in CRF content. Furthermore, the altered ACTH response to ether stress is not due to a change in responsiveness of the pituitary to CRF or to an alteration in arginine vasopressin levels. Thus, an endogenous EPI neuronal system appears to stimulate CRF neurons responsible for the increase in ACTH after ether vapor stress.

High concentrations of epinephrine derived from a central source and of 5-hydroxyindole-3-acetic acid in hypophysial portal plasma.

This study was designed to determine if active secretion of epinephrine (EPI) and/or 5-hydroxytryptamine (5-HT) from the hypothalamus into the hypophysial portal vasculature takes place, in addition to the well-known secretion of dopamine (DA). Hypophysial portal plasma was collected from urethane-anesthetized male rats by stalk cannulation (Porter method) or by periodic aspiration of portal blood (Worthington and Fink method). Portal and peripheral plasma concentrations of EPI, 5-HT, DA and 5-hydroxyindole-3-acetic acid (5-HIAA) were concurrently measured by high performance liquid chromatography with electrochemical detection. Significantly higher concentrations of EPI were found in hypophysial portal than in peripheral plasma. After adrenalectomy (ADX), peripheral plasma levels of EPI were undetectable, whereas portal plasma EPI levels were only slightly attenuated. Although 5-HT levels in portal and peripheral plasma were not different, 5-HIAA levels were 3-fold higher in portal plasma. DA was 10-15 fold higher in portal plasma. All the above differences were found independent of the collection method. The high level of 5-HIAA in portal plasma was not due to conversion of 5-HT to 5-HIAA by monoamine oxidase in plasma. The results indicate that in addition to DA, another amine (EPI) and an amine metabolite (5-HIAA) have a concentration gradient in portal vs peripheral plasma. Moreover, the presence of EPI in portal plasma after ADX is a strong indication that EPI is primarily derived from a central source, suggesting that the amine may have a direct physiological role in the regulation of anterior pituitary function.

Evidence for a negative ultrashort loop feedback mechanism operating on the luteinizing hormone-releasing hormone neuronal system.

The present studies were designed to determine whether an ultrashort loop feedback mechanism is involved in the regulation of LHRH secretion. Daily administration of a highly potent LHRH agonist (LHRH-AGO; [D-Ala6,Des-Gly10] LHRH ethylamide) immediately after orchidectomy (ORDX) significantly attenuated the rise of plasma LH from days 2 through 10 after ORDX. Concomitantly with the diminished LH rise after ORDX, a significant increase in LHRH content in the arcuate nucleus was observed in LHRH-AGO-treated rats. Measurement of LHRH levels in hypophyseal portal blood in rats 10 days after ORDX combined with daily agonist treatment revealed a significant decrease in LHRH values in portal plasma compared with those in orchidectomized controls. Arcuate nuclei-median eminence (ME) fragments obtained from ORDX rats treated in vivo with LHRH-AGO for 5 days showed a decreased basal secretion of LHRH and a diminished response to K+ stimulation compared with the release from fragments obtained from ORDX saline-treated controls. To evaluate whether a tonic LHRH inhibitory activity operates within the ME, additional experiments were performed in which ME fragments were incubated in vitro in the presence of a potent LHRH antagonist [( D-pGlu1,D-Phe2,D-Trp3,6]LHRH). The antagonist significantly enhanced the basal secretion of LHRH in a dose-dependent manner. The latter results suggest that LHRH antagonists may enhance LHRH release, perhaps by interacting with LHRH receptors playing an inhibitory role on the endogenous secretion of the decapeptide. These observations strongly suggest a tonic inhibitory or modulatory role of LHRH neurons in the regulation of their own function.

Prolactin release after 5-hydroxytryptophan treatment requires an intact neurointermediate pituitary lobe.

The present study was designed to evaluate the role of the neurointermediate pituitary lobe (NIL) in the 5-hydroxytryptophan (5-HTP)-induced increase in plasma PRL levels. The neurochemical mechanisms involved in this neuroendocrine regulation were also analyzed by examining the concentrations of serotonin (5-HT), norepinephrine, and dopamine as well as their primary metabolites in the median eminence (ME), NIL, and anterior pituitary (AP) after different treatments. Removal of the NIL (NIL-X) did not significantly affect basal plasma PRL concentrations or amine metabolism in the ME or AP. 5-HTP administration resulted in a 5-fold increase in plasma PRL in sham-operated (SHAM) animals, but NIL-X completely abolished this PRL response. 5-HTP injection elicited large increases in 5-HT and 5-hydroxyindole-3-acetic acid concentrations in ME, NIL, and AP in SHAM animals, and similar changes within the ME and AP in NIL-X animals, but did not significantly affect norepinephrine or dopamine metabolism in the ME, NIL, or AP of NIL-X or SHAM animals. Moreover, tissue concentrations of 5-HTP after 5-HTP injection increased similarly in SHAM and NIL-X animals. Inhibition of peripheral decarboxylase activity with MK486 prevented the 5-HTP-induced increase in PRL in SHAM animals and the increase in 5-HT metabolism in both SHAM and NIL-X groups. These data indicate that an intact NIL is required for the 5-HTP-induced increase in plasma PRL, but does not seem to be essential for the regulation of basal PRL release. They also demonstrate that the 5-HTP-induced activation of 5-HT metabolism in both ME and AP is not sufficient, by itself, to enhance PRL release.

Adrenergic agonists induce heterologous sensitization of adenylate cyclase in NS20Y-D(2L) cells.

Adenylate cyclase activity in NS20Y cells expressing D2L dopamine receptors was examined following chronic treatment with norepinephrine and epinephrine. Initial acute experiments revealed that both norepinephrine and epinephrine inhibited forskolin-stimulated cyclic AMP accumulation via D2 receptors. Furthermore, chronic 18 h activation of D2 dopamine receptors by norepinephrine or epinephrine induced a marked increase (>10-fold) in subsequent forskolin-stimulated cyclic AMP accumulation. This heterologous sensitization of adenylate cyclase activity was blocked by D2 dopamine receptor antagonists and by pertussis toxin pretreatment. In contrast, concurrent activation of Galpha(s) or adenylate cyclase did not appear to alter noradrenergic agonist-induced sensitization.

Detection of antiphospholipid antibodies by flow cytometry: rapid detection of antibody isotype and phospholipid specificity.

Laboratory diagnosis of antiphospholipid antibodies is important in patients with clinical features of the antiphospholipid syndrome, such as thrombosis and fetal loss. We have developed a novel method for the detection of antiphospholipid antibodies using flow cytometry. Anionic phospholipids cardiolipin, phosphatidylserine and phosphatidylinositol are coated onto polystyrene beads of different sizes, allowing detection and semiquantitation of their respective phospholipid antibody isotypes. The results of the flow cytometric method closely correlate those of the standardised anticardiolipin enzyme-linked immunosorbent assay (ELISA), but the method is quicker and is versatile in its ability to detect IgG, IgM and IgA antibody isotypes at the same time. The method promises to be useful in evaluating the significance of phospholipid specificity and antibody isotypes in patients with the antiphospholipid syndrome.

Interaction between norepinephrine, oxytocin, and nitric oxide in the stimulation of gonadotropin-releasing hormone release from proestrous rat basal hypothalamus explants.

In the proestrous female rat, norepinephrine, oxytocin and nitric oxide (NO) all participate in the regulation of the preovulatory gonadotropin-releasing hormone (GnRH) surge. Recent studies from our laboratory have demonstrated that oxytocin induces dose-dependent release of GnRH from proestrous basal hypothalamus explants. The present studies were undertaken to determine whether norepinephrine could also stimulate GnRH release from similar explants, to identify the receptors responsible for this effect and to investigate interactions between norepinephrine, oxytocin and NO. Norepinephrine significantly stimulated GnRH release from proestrous basal hypothalamus explants, and coadministration of the alpha(1)-adrenergic antagonist prazosin blocked this effect. Combined administration of oxytocin and norepinephrine stimulated significantly more GnRH release than either drug alone, and this stimulation was blocked by inhibition of NO synthase, or by an oxytocin receptor antagonist. NO production was measured from the same samples using a modified Griess reaction. Oxytocin, but not norepinephrine, significantly increased NO production, as did norepinephrine and oxytocin in combination. Oxytocin receptor antagonist administration attenuated the stimulation of NO production by norepinephrine/oxytocin. These results demonstrate for the first time that oxytocin and norepinephrine dramatically stimulate GnRH release from basal hypothalamus explants harvested on the afternoon of proestrus, and indicate that this involves oxytocin receptor and NO-dependent mechanisms.

Neurotoxin effects on oxytocin, vasopressin and somatostatin in discrete rat brain areas.

Monosodium-L-Glutamate (MSG) produces lesions to monoaminergic and peptidergic neurons in several brain areas. The present study examined the effect of neonatal MSG treatment on oxytocin (OXY), arginine-vasopressin (AVP) and somatostatin (SRIF) concentrations in several discrete brain areas of adult rats. OXY increased in the suprachiasmatic and arcuate nuclei and median eminence (ME) and decreased in the paraventricular nucleus of MSG-treated rats. MSG treatment caused AVP to increase in the arcuate nucleus and ME and decrease in the supraoptic nucleus. SRIF decreased following neonatal MSG treatment in both the ME and neurointermediate pituitary lobe. The results demonstrate that the effects of neonatal MSG treatment on neuropeptide content are not just limited to the arcuate nucleus. Furthermore, taken together with previous results, the data suggest that these changes may be indicative of functional deficits in the neuronal activity of some of these peptidergic neurons which, in turn, may be responsible for the abnormal secretion of several pituitary hormones observed in MSG-treated animals.

Histoplasmosis of skin and lymph nodes and chronic lymphocytic leukemia.

Nodular skin and cervical lymph node lesions of histoplasmosis, unassociated with systemic symptoms of the infection, developed in a 63-year-old man with untreated chronic lymphocytic leukemia. The histologic patterns in both the skin and lymph node were those of a lymphoproliferative disorder, but Histoplasma organisms were found within a few scattered histiocytes after a careful search. The subtle clinical and pathologic presentation might lead one to overlook the organisms and to believe that the leukemic process had progressed, resulting in potentially dangerous systemic involvement of histoplasmosis and unnecessary chemotherapy for his leukemic process. Complete remission of histoplasmosis was obtained with amphotericin B therapy.

Differential effect of neurointermediate lobectomy on central oxytocin and vasopressin.

Removal of the neurointermediate pituitary (NIL) affects the secretion of anterior pituitary (AP) hormones. It is not known if these effects are due to changes in central neuropeptide neurons. Two neuropeptides implicated in the neuroendocrine regulation of AP hormone secretion, and which are located in the NIL, are oxytocin and vasopressin. The present study evaluated whether removal of the NIL affected oxytocin and vasopressin concentrations in discrete brain areas containing cell bodies (paraventricular nucleus), fibers (arcuate nucleus), and/or terminals (median eminence) of these central neurons. Adult male rats underwent removal (NIL-X) or visualization (SHAM controls) of the NIL using a parapharyngeal approach. Oxytocin levels increased in the paraventricular nucleus and median eminence following NIL-X, whereas vasopressin concentrations were relatively unaffected by NIL-X. The data suggest that at least part of the influence of the NIL on AP hormone secretion may result from the ability of feedback from the NIL to differentially affect central neuropeptide neurons.

Physiologically important role for central oxytocin in the preovulatory release of luteinizing hormone.

Recently, our laboratory has provided evidence for a physiologically relevant stimulatory influence of oxytocin (OXY) on the preovulatory luteinizing hormone (LH) surge in cycling female rats. The present study evaluated whether this stimulatory effect of OXY on LH release is exerted at a central or peripheral site of action by comparing the ability of peripheral (intravenous) or central (intracerebroventricular) administration of OXY antisera to influence the preovulatory LH surge. The peripheral injection of a very large dose of OXY antisera (0.8 ml) caused a slight attenuation of the early stages of the LH surge. In contrast, the central administration of 5 microliters of OXY antisera completely abolished the preovulatory LH surge. The data support the hypothesis that OXY exerts a physiologically important stimulatory influence on the preovulatory LH surge which is mediated primarily at a central site of action.