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J Herbert

Publications and source records attributed to J Herbert.

At least 109 records · Page 6Linked to original sources
PubMed1995

Regional suppression by lesions in the anterior third ventricle of c-fos expression induced by either angiotensin II or hypertonic saline.

Angiotensin II (250 pmol) infused into the cerebral ventricles of male rats induces the expression of c-fos in the subfornical organ, supraoptic and paraventricular nuclei of the hypothalamus, as well as in the lateral parabrachial nucleus, locus coeruleus and the nucleus of the solitary tract in the brainstem. Electrolytic lesions of the anteroventral third ventricle, principally the subcommissural (ventral) median preoptic nucleus, inhibited the dipsogenic response to i.c.v. angiotensin II and also suppressed c-fos expression in supraoptic nucleus, paraventricular nucleus, lateral parabrachial nucleus, locus coeruleus and nucleus of the solitary tract but not in the subfornical organ or dorsal median preoptic nucleus. The stimulating effect of i.c.v. angiotensin II on corticosterone was also reduced. Median preoptic nucleus lesions also suppressed the expression of c-fos following i.v. infusions of 6 micrograms angiotensin II in supraoptic nucleus and paraventricular nucleus but not in subfornical organ, dorsal median preoptic nucleus, lateral parabrachial nucleus, locus coeruleus and nucleus of the solitary tract. Median preoptic nucleus lesions reduced the dipsogenic effects of an intragastric infusion of hypertonic (1.5 M) saline and suppressed c-fos expression in supraoptic nucleus and paraventricular nucleus compared to sham-lesioned rats. However, c-fos expression was unaltered in subfornical organ, dorsal median preoptic nucleus lesions had no effect on the increased corticosterone induced by hypertonic saline. Subfornical organ lesions did not alter dipsogenic responses to i.c.v. angiotensin II, nor was the i.c.v. angiotensin II-induced expression of c-fos suppressed in the basal forebrain. These experiments show that the ventral median preoptic nucleus (but not the subfornical organ), part of the anteroventral third ventricle, is critical for the expression of c-fos in more caudal areas of the brain following i.c.v. angiotensin II. c-fos expression in supraoptic nucleus and paraventricular nucleus following i.v. angiotensin II is also dependent on an intact median preoptic nucleus, suggesting that supraoptic nucleus and paraventricular nucleus activation may be dependent on the median preoptic nucleus, and that suppression following i.c.v. infusions is not due to mechanical obstruction to infused peptide. However, there is a clear separation of the effects of i.c.v. and i.v. angiotensin II on brainstem structures. The median preoptic nucleus (but not the subfornical organ) seems essential for activation following the former but not the latter, suggesting alternative mechanisms for the effect of i.v. angiotension II on the brainstem.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin II↗
PubMed1995

The association of thirst, sodium appetite and vasopressin release with c-fos expression in the forebrain of the rat after intracerebroventricular injection of angiotensin II, angiotensin-(1-7) or carbachol.

The effect intracerebroventricular injections of angiotensin II (0.1 nm), angiotensin-(1-7) (1 or 100 nm) and carbachol (500 ng) on c-fos expression was examined in the forebrain of Lister hooded rats. Intense staining of the c-Fos protein was found in the median preoptic nucleus, organum vasculosum of the lamina terminalis, subfornical organ, paraventricular nucleus and supraoptic nucleus after angiotensin II and carbachol Angiotensin II caused significantly more c-fos expression in the ventral median preoptic nucleus and organum vasculosum of the lamina terminalis than carbachol, whereas in the paraventricular and supraoptic nuclei this was reversed, with carbachol having a greater effect on c-fos expression in these areas. Angiotensin-(1-7), however, only induced c-Fos protein in the organum vasculosum of the lamina terminalis and median preoptic nucleus with the number and the intensity of staining of the nuclei significantly less in both areas than after angiotensin II or carbachol. Separate groups of Lister rats were given i.c.v. injections of the same substances at the same doses, but excluding the lower dose of angiotensin-(1-7), and the intakes of water and 1.8% NaCl over 60 min were measured. Angiotensin II stimulated intakes of both water and NaCl. The effect on water intake was almost immediate (<1 min), whereas NaCl intake did not usually start until at least 5 min after injection. Over 60 min, water (12.4 +/- 1.0 ml) and NaCl (4.2 +/- 0.9 ml) intakes were significantly greater than water (1.1 +/- 0.2 ml) and NaCl (0.6 +/- 0.5 ml) intakes of the controls. Carbachol caused less drinking than angiotensin II, the water intake over 60 min being significantly less (4.8 +/- 0.7 ml) and the latency of response greater (>5 min). Carbachol, unlike angiotensin II, had little effect on NaCl intake (0.7 +/- 0.4 ml). Angiotensin-(1-7) had no effect on water (1.1 +/- 0.3 ml) or NaCl (0.3 +/- 0.3 ml) intakes. The plasma levels of vasopressin were measured after i.c.v. injection of the same three substances in the same doses, again excluding the lower dose of angiotensin-(1-7), in further groups of rats. Angiotensin II and carbachol caused an approximate five-fold increase in plasma vasopressin levels compared to cerebrospinal fluid-injected rats, but angiotensin-(1-7) had no effect on vasopressin release. Therefore, three compounds with widely differing effects on thirst, sodium appetite and vasopressin release induce distinctive patterns of c-fos protein expression in the forebrain. By combining experimental approaches in this way it is possible to determine areas of the brain which are involved in certain behavioural and endocrine responses.

Angiotensin I↗
PubMed1995

CD40 cross-linking inhibits specific antibody production by human B cells.

Ligation of CD40 on B cells is a co-stimulatory signal for proliferation, antibody secretion, heavy chain switching and rescue from apoptosis after somatic mutation in the germinal centre. The importance of these manifold responses to CD40 activation for humoral immunity is exemplified by the inability of boys with X-linked hyper IgM syndrome to make IgG, IgE or IgA due to a mutation in in the gene coding for CD40 ligand (CD40L). In the present study, we have investigated the effect of CD40 ligation on specific antibody production by human B cells to influenza virus. The antibody response was T cell dependent and specific for the strain of influenza virus used as antigen. Addition of either CD40 mAb or recombinant trimeric CD40L profoundly inhibited specific antibody production. Antibody production by unseparated tonsillar mononuclear cells and by T-depleted B cells stimulated with antigen in the presence of T cell replacing factor were equally inhibited with CD40 antibody showing that the effect was due to ligation of CD40 on B cells rather than blocking of T cell help. The specific antibody detected in these experiments was mostly IgG with little or no IgM and was obtained from surface IgM B cells consistent with activation of a secondary (memory) response. Co-stimulation of tonsillar B cells with CD40 antibody and anti-IgG induced proliferation of IgG+ B cells. These results suggest that CD40 ligation can inhibit specific antibody responses and stimulate proliferation in the same IgG+ (memory) B cell subpopulation. Addition of CD40 antibody during the first 24-48 h of the response was required for inhibition, suggesting that the effect was on early B cell activation and/or proliferation required for antibody production. There was no correlation, however, between the ability of CD40 mAb to stimulate proliferation and inhibit antibody production. We suggest that early activation of CD40 in the specific antibody response inhibits the formation of plasma cells and promotes instead the generation of memory cells.

Antibodies, Monoclonal↗
PubMed1995

The effect of long-term castration on the neuronal and physiological responses to acute or repeated restraint stress: interactions with opioids and prostaglandins.

Sixty min supine restraint stress induced a marked, but transient, hypothermic response in intact male rats, which tended to recover towards pre-stress levels or slightly overshoot during the later stages of restraint. Castration reduced the initial hypothermia but increased overshoots. Baseline (pre-stress) core temperature was also higher in castrated than intact rats, but the reduction in stress-induced hypothermia was still present even when this difference had been taken into account. The hypothermic response was not altered during the course of 10 sessions of daily repeated restraint in either intact or castrated rats. Castration did not alter cardiac responses to restraint. Both intact and castrated rats showed marked tachycardia during the initial 12 min of restraint, followed by a gradual fall towards baseline values. Repeated restraint accentuated the second phase of the cardiac response, without modifying the initial tachycardia, in both intact and castrated animals. The response of blood corticosterone levels to the first period of restraint was unaltered by castration but the attenuation observed after 10 sessions of stress was more complete in castrated rats. The neuronal c-fos response 60 min after the last of the series of repeated restraints was less in the hypothalamic paraventricular nucleus, medial amygdala, and locus coeruleus compared with that following the first session, but not in the lateral septum or the bed nucleus of the stria terminalis. Castration did not change the c-fos profile following the same number of restraint sessions. Castration depleted completely the vasopressinergic innervation in the lateral septum, diagonal band of Broca and medial amygdala.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

Regional suppression by water intake of c-fos expression induced by intraventricular infusions of angiotensin II.

Intracerebroventricular (i.c.v.) infusions of angiotensin II (AII) reliably induced c-fos expression in the supraoptic (SON) and paraventricular (PVN) nuclei, as well as other areas of the basal forebrain including the OVLT, subfornical organ (SFO), and bed nucleus (BNST). Double-labelling showed that AII-induced c-fos was observed in both vasopressin (AVP-) and oxytocin (OXY)-containing neurons of the SON and PVN in male rats. Allowing rats to drink water after AII infusions suppressed c-fos expression both AVP- and OXY-stained magnocellular neurons. Intragastric infusions of water were also effective, showing that oro-pharyngeal stimuli were not critical. Maximal suppression occurred in rats in whom water had been infused intragastrically about 5 min before i.c.v. AII infusions, suggesting that changes in osmolarity were responsible. i.c.v. AII also induced c-fos expression in a number of brainstem structures, including the solitary nucleus (NTS), lateral parabrachial nucleus (LPBN), locus coeruleus (LC), and the area postrema (AP). These results indicate that AVP and OXY-containing neurons in the magnocellular parts of the SON and PVN alter their immediate-early gene response to AII after water intake, and that this does not depend upon oro-pharyngeal factors. Furthermore, AII can induce c-fos expression in a number of brainstem nuclei associated with autonomic function, and these do not respond to water intake.

Angiotensin II↗
PubMed1994

CD40 ligand (CD40L) expression and B cell function in agammaglobulinemia with normal or elevated levels of IgM (HIM). Comparison of X-linked, autosomal recessive, and non-X-linked forms of the disease, and obligate carriers.

Hyper-IgM syndrome is a rare immunodeficiency characterized by low or absent IgG, IgA, and IgE with normal or elevated levels of IgM. It can occur as an acquired or familial disorder with either X-linked or autosomal modes of inheritance. The X-linked form (HIGM1) is a result of mutations in the CD40 ligand (CD40L) gene, but the defect in non-X-linked forms of the disease (HIM) has not been determined. We show here that CD40L expression on activated T cells from non-X-linked patients can be detected by CD40Fc, 5c8 Mab, and anti-TRAP, whereas activated T cells from HIGM1 patients either had no detectable CD40L (Type I), or stained with anti-TRAP but not CD40Fc or 5c8 (Type II). Activated T cells from obligate carriers varied from low to normal expression of CD40L. B cells from HIGM1 and non-X-linked HIM patients proliferated in response to CD40L. Costimulation of B cells from HIGM1, from sporadic HIM, or from non-X-linked HIM patients with CD40L plus IL-2 resulted in some IgM production, but no significant IgG or IgA. Costimulation with CD40L plus IL-10 resulted in significant IgG and/or IgA secretion by B cells from some HIGM1 patients, but consistently failed to stimulate IgG or IgA secretion by B cells from non-X-linked patients. In addition, costimulation with CD40L and IL-4 failed to induce IgE secretion by B cells from one non-X-linked HIM patient, and induced a weak response in another. These results suggest that patients with non-X-linked forms of HIM may have an intrinsic B cell defect preventing heavy chain switching, which is not related to expression of CD40L.

Adolescent↗
PubMed1994

Human serum amyloid P component is an invariant constituent of amyloid deposits and has a uniquely homogeneous glycostructure.

Human serum amyloid P component (SAP) is a normal plasma protein and the precursor of amyloid P component (AP), a universal constituent of the abnormal tissue deposits in amyloidosis, including Alzheimer disease. We show here that its single N-linked biantennary oligosaccharide does not display the microheterogeneity usually characteristic of glycoproteins. The protein and the glycan structures of AP were also invariant, their resistance to degradation suggesting a role in persistence of amyloid deposits. Asialo-SAP was rapidly cleared from the circulation in mice by a mechanism dependent on terminal galactose residues and was catabolized in hepatocytes. However blockade of this pathway did not affect the clearance of native SAP. Rapid hepatic uptake and catabolism of human asialo-SAP in man were also directly demonstrated. The protein and glycan homogeneity of SAP and the integrity of AP suggest that the complete glycoprotein structure is important for the normal and the pathophysiological functions of this molecule.

Amyloid↗
PubMed1994

High-dose glucocorticoids in multiple sclerosis patients exert direct effects on the kidney and skeleton.

The effects of acute pharmacologic steroid treatment on skeletal and mineral metabolism were assessed in 56 multiple sclerosis patients who were to receive 1 g intravenous methylprednisolone for 10 days, followed by a 4 day intravenous and 28 day oral glucocorticoid taper. Serum and urine samples were obtained at baseline and then within 3 days, 1, 2, and 3 weeks after beginning steroids. A subset of patients (n = 11) had sampling throughout the 6 weeks of steroid administration and up to 8 weeks afterward. All mean basal biochemistries were normal except 25(OH)D, which was in the "insufficient" range (25-50 nM) at 10 nM. During and after steroid administration, there were no changes in ionized calcium, 25(OH)D, urinary hydroxyproline, or pyridinoline. There was an increase in 1,25(OH)2D and a decrease in serum phosphorus, accompanied by an increase in urinary phosphate clearance, within 3 days of administration (p < 0.006). Serum osteocalcin (BGP) decreased to below assay sensitivity limits within 3 days of steroid administration (p < 0.0002), increasing thereafter but remaining at 50% of baseline by the third week. PTH(1-84) increased to a peak at week 2 (p < 0.02), after both the 1,25(OH)2D peak and the serum phosphorus nadir. Tartrate-resistant acid phosphatase, urinary calcium, and urinary cyclic AMP all increased above baseline (p < 0.05) with a pattern similar to that of PTH. To investigate further the immediate effects of steroid administration, serum samples were obtained at the same four times on both the day before and the day after the first intravenous methylprednisolone dose in a randomly chosen subset of patients (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Effects of naloxone on diurnal rhythms in mood and endocrine function: a dose-response study in man.

This study investigated diurnal variations in the affective and endocrine response to opioid blockade in man and whether there were effects related either to the dose of naloxone or the time of day at which it was given. Normal male subjects were given an intravenous bolus of either 0.2 mg/kg (study 1) or 1 mg/kg naloxone (study 2) or control infusions at two time points (0900 or 1800 hours) in a single-blind crossover design. Before and following each infusion, mood was measured by the Profile of Mood States (POMS) and a visual analogue scale (VAS), and blood samples taken at 15-min intervals. Cortisol, LH ACTH and vasopressin (study 2 only) were measured. Blood pressure and heart rate were also monitored. The lower dose of naloxone had no effect on overall mood (POMS), though tension and confusion were increased in the afternoon. The VAS showed increased depression in the afternoon, and heightened tension, sleepiness and reduced ability to concentrate at both times of day. The higher dose increased overall dysphoria at both time points, though the tension and depression subscales were not altered. VAS depression and tension were increased, and there were changes in sleepiness. Subjective reports showed that 45% of the subjects correctly identified the drug treatment at the lower dose compared with 89% at the higher one. ACTH increased after both doses of naloxone irrespective of time of day. Cortisol was also raised by naloxone; the effect was greater in the afternoon for the lower dose, but not the higher.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1994

Non-photic circadian entrainment in the Syrian hamster is not associated with phosphorylation of the transcriptional regulator CREB within the suprachiasmatic nucleus, but is associated with adrenocortical activation.

The mechanisms which mediate non-photic entrainment of the circadian clock are not known. The free-running circadian rhythm of the wheel-running activity of Syrian hamsters was phase advanced by subcutaneous injection of saline and the associated handling at circadian time (CT) 10 (2 h before activity onset, CT 12). Over several experiments, approximately 80% of the animals were sensitive to this non-photic cue and were, therefore, designated as 'shifters'. Injection at CT 6 had no phase-shifting effect in any animals. A series of six injections presented to shifters at CT 10 over 14 circadian cycles produced a cumulative phase advance to the activity rhythm which free ran from the phase established by the final injection, demonstrating that the non-photic stimulus caused true entrainment of the circadian clock, rather than simply masking its expression. Entrainment by light is associated with the rapid phosphorylation of the transcription regulatory factor, cyclic adenosine monophosphate response element binding protein (CREB), in the suprachiasmatic nuclei (SCN), the principal circadian clock. The induction of immunoreactivity to the phosphorylated form of CREB (P-CREB-ir) was used to determine whether phosphorylation is also activated by a non-photic phase-shifting cue. No significant P-CREB-ir was found in shifters maintained under constant dim red light and sampled at either CT 10.05 or 14.05, i.e., times when animals are sensitive to non-photic stimuli and light pulses, respectively. Exposure of animals to light for 5 min at CT 14 caused a dramatic increase in P-CREB-ir within the SCN at CT 14.05. However, despite being sensitive to the phase-shifting effects of handling and injection at CT 10, none of the shifters sampled 5 min after injection of saline at CT 10 exhibited P-CREB-ir within the SCN. These data demonstrate that non-photic cues do not activate a cellular pathway (phosphorylation of CREB) known to be activated within the SCN by light. To assess the importance of arousal in non-photic entrainment, the effect of injection of saline upon activation of the adrenocortical axis, a peripheral index of arousal, was investigated. As anticipated, there was a marked circadian variation in serum cortisol concentrations. In animals identified as shifters, the levels were low during mid-subjective day (CT 6) and rose in advance of activity onset (CT 10). Injection and handling at CT 6 did not have a did not have a significant effect upon serum cortisol levels. In contrast, injection of shifters at CT 10 was associated with a pronounced rise in serum cortisol levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex↗
PubMed1994

High prevalence of vitamin D deficiency and reduced bone mass in multiple sclerosis.

BACKGROUND: Female patients with multiple sclerosis (MS) are at risk for osteoporosis because of gender, immobility, and corticosteroid use. METHODS: Bone mineral density (BMD) was measured by dual x-ray absorptiometry in 80 female MS patients admitted to a tertiary care hospital. All patients completed a questionnaire that included measurements of dietary intake and sunlight exposure. Biochemical indices of bone metabolism and turnover were measured in a random sample of 52 patients. RESULTS: BMD of the lumbar spine and femoral neck was 1 to 2 SDs lower in MS women compared with a healthy reference population. BMD was lower in patients with more severe MS. The mean 25(OH)D level of the sample population (43 nmol/l) was in the insufficient range, and 12 patients (23%) had frank vitamin D deficiency (< 25 nmol/l). BMD and age-related BMD (z scores) at all skeletal sites measured were lowest when 25(OH)D levels were deficient. Parathyroid hormone (PTH) was frankly elevated in 13% of patients. PTH levels were negatively correlated with 25(OH)D levels and with BMD. Dietary intake of vitamin D was below the recommended level in 80% of patients, and 40% reported no weekly sunlight exposure. After controlling for age, cumulative steroid use was not a determinant of BMD. CONCLUSIONS: BMD was significantly reduced in female MS patients, which might increase fracture risk two- to threefold. Vitamin D deficiency with secondary hyperparathyroidism is prevalent and is probably a significant cause of low BMD in this population. Vitamin D deficiency in the female MS patient might be safely and inexpensively corrected by the routine use of vitamin D supplements.

Adult↗
PubMed1993

Widespread constitutive expression of HSP90 messenger RNA in rat brain.

The distribution of constitutively expressed mRNA encoding 2 isoforms of heat shock protein 90 (HSP90) was investigated in adult rat brain by in situ hybridization with 35S-labeled cRNA probes. HSP90 mRNA density was estimated by semiquantitative autoradiography and by microscopic analysis. The distribution of HSP90 transcripts was similar for the 2 probes. HSP90 mRNA was widespread but not ubiquitous, and labeling intensity varied among different regions. In particular, HSP90 mRNA was abundant in limbic system-related structures, such as the hippocampus, amygdala, mamillary body, piriform cortex, enthorhinal cortex, bed nucleus of the stria terminalis, medial habenular nucleus, and preoptic hypothalamic nuclei. The highest abundance of mRNA was detected in the Purkinje cell layer of the cerebellum. High abundance was also present in pineal body, choroid plexus, cerebellar granule cell layer, and cranial nerve nuclei. HSP90 mRNA was present in moderate abundance throughout the cortical gray mantle, in the caudate-putamen, most other thalamic and hypothalamic nuclei, the pontine and spinal gray matter, and the anterior lobe of the hypophysis. Weak hybridization was observed in white matter fiber tracts, glial cells, and leptomeninges, and none was observed in endothelial cells and the smooth muscle of the cerebral microvasculature. Our findings suggest that HSP90 gene products may serve constitutive neuron-specific functions in the unstressed brain.

Animals↗
PubMed1993

Expression of c-fos in restricted areas of the basal forebrain and brainstem following single or combined intraventricular infusions of vasopressin and corticotropin-releasing factor.

Vasopressin has been shown to be localized in specific central nervous system (CNS) sites. There is considerable evidence that it can act as a central neurotransmitter and it has been ascribed a variety of putative roles in the CNS. To identify those regions of the brain capable of responding to this peptide, 250 pmol vasopressin were infused into the lateral ventricle intracerebroventricular of conscious, handled male rats, and their brains processed for fos-immunohistochemistry 60 min later. Increases in fos-immunoreactivity, compared with cerebrospinal fluid-infused controls, were found in specific regions of the basal forebrain and brainstem: the central nucleus of the amygdala, ventrolateral septum, parvocellular divisions of the paraventricular nucleus of the hypothalamus, dorsal tuberal nucleus and locus coeruleus. Pre-infusion of 2500 pmol of a V1a antagonist prevented or reduced the expression of c-fos by intracerebroventricular vasopressin in all areas except the dorsal parvocellular paraventricular nucleus, implying that in most (but not all) areas the actions of vasopressin are mediated by the V1a receptor. Central administration of vasopressin had no effect on plasma corticosterone levels. Vasopressin and corticotropin-releasing factor act synergistically on the anterior pituitary to cause release of adrenocorticotropic releasing hormone and have corresponding synergistic interactions on behaviour. Infusion of 250 pmol corticotropin releasing factor produced a similar but not identical pattern of fos-like immunoreactivity to that of vasopressin. Activation of the parabrachial nucleus was observed, but there was no significant effect on the lateral septum and apparent increases in the medial parvocellular division of the paraventricular nucleus and locus coeruleus were not significant. Corticotropin releasing factor also caused a marked rise in plasma corticosterone. When the two peptides were infused together (125 pmol each) no evidence for synergy was found, in terms of the number of neurons activated to express c-fos. The induction of differential patterns of fos-like immunoreactivity by vasopressin and corticotropin-releasing factor in specific regions of the limbic forebrain and brainstem has implications for the individual roles they play in the CNS.

Animals↗
PubMed1993

Differential expression of the insulin-like growth factor II and transthyretin genes in the developing rat choroid plexus.

Choroid plexus (CP) development may depend on an inductive interaction between primordial CP epithelium and the overlying mesenchyme. Expression of the two CP epithelial-expressed genes, transthyretin (TTR) and insulin-like growth factor II (IGF-II), were studied by in situ hybridization in the developing rat. Transthyretin mRNA is expressed in abundance in the primordial CP epithelium prior to CP morphogenesis (e10-11) but IGF-II mRNA expression begins later (e13) and increases gradually as morphogenesis proceeds. In the CP stroma (mesenchyme), IGF-II mRNA is abundant prior to CP morphogenesis but decreases as embryogenesis proceeds and is absent in the adult. Our findings suggest that IGF-II may play an early paracrine and later autocrine role in CP development. A model is proposed in which IGF-II synthesized by mesenchyme serves as an inducing principle for CP epithelial differentiation.

Animals↗
PubMed1993

CSF transthyretin in patients with depression.

Some depressed patients may suffer from restricted central hypothyroidism, which could occur if levels of the thyroid hormone transport protein transthyretin were low. CSF transthyretin was measured in eight inpatients with refractory major depression and nine neurological patients. The depressed patients had significantly lower transthyretin levels than the comparison subjects, suggesting that central hypothyroidism, with normal peripheral thyroid concentrations, could occur in some depressed patients.

Adult↗