Reproductive hormone levels after pituitary allograft in cyclosporin-treated monkeys

OBJECTIVE: To determine the course of events during the onset of hyperprolactinemic amenorrhea, a nonhuman primate model was sought that did not require suckling or interference with the in situ hypothalamic-pituitary axis. DESIGN: Because removal of the adenohypophysis from hypothalamic influence results in secretion of large quantities of prolactin (PRL) but little of the other adenohypophyseal hormones, we explored the possibility of establishing pituitary allografts in monkeys. Normally cycling female rhesus monkeys were immunosuppressed with a daily regimen of cyclosporin A (CyA; 10 to 15 mg/kg per day) and then subcutaneously grafted with a pituitary from another animal (allograft). Blood samples were obtained daily via saphenous vein puncture during control, only CyA-treatment, and allografted-plus CyA- menstrual cycles. SETTING: Oregon Regional Primate Research Center, Beaverton, Oregon. PARTICIPANTS: Female Macaca mulatta exhibiting regular menstruation. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Prolactin, luteinizing hormone (LH), estradiol (E2), and progesterone (P) levels were determined in harvested serum. RESULTS: Temporary survival of 5 of 11 (45%) allografts was assumed based on elevations in serum PRL. Of the viable grafts, 4 of 5 (80%) resulted in reproductive dysfunction, as first evidenced by delay or loss of the preovulatory rise in E2. When the peak of follicular E2 was delayed, then the LH surge occurred, but it was also delayed. If follicular E2 levels did not peak, then the LH surge was absent as was luteal P production. CONCLUSION: These data suggest that in the etiology of PRL-induced infertility in women, the first event is a suppression of follicular E2 production. In addition, the hypothalamus probably remains responsive to the positive feedback of E2 during early or moderate hyperprolactinemia.     

Growth hormone resistance in uremia

Growth retardation is a major complication in children with uremia. Protein restriction, calorie deficit, metabolic acidosis, renal osteodystrophy, and endocrinologic disturbances contribute to the growth failure. The effect of these factors on growth retardation can be attenuated in part by therapy with vitamin D metabolites, adequate nutrition, alkalization, and dialysis. Linear growth in children with uremia is markedly retarded despite normal or increased levels of circulating serum growth hormone. An increased growth hormone level in children with uremia is due to normal growth hormone secretion from the pituitary gland and impaired growth hormone clearance in the kidney. However, the elevated growth hormone level does not lead to a commensurate rise in serum insulin-like growth factor I (IGF-I); the serum IGF-I level is decreased or normal in relation to the degree of renal failure. This discrepancy suggests growth hormone resistance in the liver in uremia. Recent molecular techniques open a new era in studying the gene expression for growth hormone or IGF-I. There is no doubt today that growth hormone treatment has the beneficial effect of growth promotion in children with uremia, which also suggests endogenous growth hormone resistance in target organs or target cells in uremia.     

Comparitive sensitivity of polymerase chain reaction diagnosis of psittacine beak and feather disease on feather samples, cloacal swabs and blood from budgerigars (Melopsittacus undulates, Shaw 18005).

A longitudinal study was performed in order to investigate virus excretion and viraemia during a clinical outbreak of the psittacine beak and feather disease in budgerigars (Melopsittacus undulatus). Viral nucleic acid was detected in feathers, cloacal swabs and blood samples. Overall, beak and feather disease virus (BFDV) DNA was detected most commonly in feather samples, followed by cloacal swabs, and least frequently from blood samples. In most cases the viraemia was short lived and correlated with clinical signs, such as feather abnormalities. Sequence analysis of the polymerase chain reaction fragment amplified from the replication-associated gene (ORF V1) indicated a close relationship with other BFDV isolates. Overall the highest level of nucleotide identity was found with the ORF V1 of another budgerigar isolate. Our results suggest that feather samples and cloacal swabs should be taken for polymerase chain reaction diagnosis to determine the presence of BFDV in an aviary, but that detection in these samples may not correlate well with psittacine beak and feather disease.     

Experimental axonopathy induced by immunization with campylobacter jejuni lipopolysaccharide from a patient with guillain‐barré syndrome

Campylobacter jejuni (C. jejunj) infection is the most common antecedent in the axonal variant of Guillain‐Barré syndrome (GBS). Antibodies against nerve gangliosides found in GBS patients recognize cross‐reactive epitopes in the lipopolysaccharide (LPS) of C. jejuni. This led to the molecular mimicry hypothesis of GBS. We immunized eleven rabbits with a LPS extracted from HS:19 C. jejuni strain isolated from a patient with GBS and complete Freund's adjuvant (CFA)(group I). In a second experiment we immunized seven rabbits with LPS, CFA and keyhole limpet hemocyanin (KLH)(group II). All group I rabbits developed high titers of anti‐LPS, anti‐GM1, anti‐GD1b antibodies and lower titers of anti‐GD1a. One rabbit, 50 days after initial inoculation, showed tremor and weakness. All rabbits of group II developed high titres of antiganglioside antibodies and six animals showed weakness 59–113 days after initial inoculation. Two rabbits died. Pathology showed mild to moderate, tendentially grouped, axonal degeneration in sciatic nerves of four out of five animals. Control rabbits of group I (immunized with CFA only) did not develop antibodies, controls of group II (immunized with CFA + KLH) developed low titers of IgG anti‐GM1. None developed neurological signs or showed axonal degeneration. C. jejuni LPS is a potent B‐cell stimulator capable to induce a strong antiganglioside response in rabbits. However, to induce the neuropathy is crucial to employ KLH, a glycoprotein known to stimulate both humoral and cellular responses. This animal model reproduces the pathogenetic process hypothesized in axonal GBS with antiganglioside antibodies post C. jejuni infection.     

Neurotransmitter modulation of calcium channels in rat sympathetic neurons.

Adrenergic, cholinergic, and a variety of peptide neurotransmitters are known to modulate Ca currents in peripheral neurons. Using a protocol that allows for simultaneous assessment of effects on dihydropyridine (DHP)-sensitive and DHP-insensitive current components, we compared the actions of norepinephrine (NE), bethanechol (BeCh), and neuropeptide Y (NPY) on Ca currents in neonatal rat superior cervical ganglion neurons. Here, we show that these transmitters selectively depress the activity of DHP-insensitive Ca channels. Intracellular application of GTP-gamma-S, an activator of GTP-binding proteins, also exclusively affected the DHP-insensitive current, whereas 1,2-oleoylacetylglycerol (OAG), a protein kinase C (PKC) activator, depressed both the DHP-sensitive and DHP-insensitive currents. Pertussis toxin interrupted the coupling between NE and its effector, whereas three different inhibitors of PKC did not. Thus, we confirmed that the selective actions of the transmitters on Ca current appear to be mediated via GTP-binding proteins, but we found no evidence for direct involvement of PKC and conclude that the observed actions of OAG are distinct from those mediated by the neurotransmitters studied.