Human growth hormone and prolactin secreting pituitary adenomas analyzed by in situ hybridization

Acidophilic pituitary adenomas commonly produce growth hormone (GH) or prolactin (PRL), according to studies employing immunohistochemical and ultrastructural methods. To examine this question, in situ hybridization with oligonucleotide probes was done on routinely processed tissues received in the pathology laboratory to analyze for the presence of GH and PRL messenger RNA (mRNA) in 4 normal pituitaries, 10 prolactinomas, and 16 GH-secreting adenomas. Most acidophilic cells in normal pituitaries expressed either GH or PRL hormone and the respective mRNAs, but GH mRNA and PRL hormone were also detected in some of the same cells. Patients with a clinical diagnosis of prolactinoma had cells with only PRL mRNA in their tumors, while most (14 of 16) patients with a clinical diagnosis of acromegaly or gigantism had both GH and PRL mRNAs in their tumors. The GH adenomas varied in these studies. In situ hybridization was helpful in characterizing the adenoma from a patient with acromegaly who had immunoreactive PRL, but no immunoreactive GH in the resected tumor; in situ hybridization analysis revealed mRNAs for both GH and PRL in the same tumor cells. Our findings indicate that pituitary adenomas from patients with acromegaly commonly express PRL mRNA. It is concluded that in situ hybridization provides new information about the clinical biology and the histopathologic classification of pituitary adenomas.     

A role for CD1d-restricted NKT cells in injury-associated T cell suppression

Natural killer T (NKT) cells are known to modulate T cell responses during autoimmunity, tolerance, and antitumor immunity; however, their potential role in regulating the immune response to injury has not been reported. Using a murine model of burn injury, we investigated whether CD1d-restricted NKT cells played a role in the T cell suppression that occurs early after injury. A functional role for CD1d stimulation of NKT cells in the injury-related immune suppression was demonstrated by experiments in which the suppression of antigen (Ag)-specific delayed-type hypersensitivity and in vitro T cell-proliferative responses were prevented if mice were given anti-CD1d monoclonal antibody (mAb) systemically just before injury. The CD1d-NKT cell-dependent suppression of the T cell response after injury occurred in the absence of quantitative changes in NKT cells themselves or CD1d(+) Ag-presenting cells. We observed that elevated production of the immunosuppressive cytokine interleukin (IL)-4 correlated with burn-induced immune dysfunction, and we found that NKT cells but not conventional T cells were the source of IL-4 early after injury. Lastly, we observed that the injury-induced production of NKT cell-derived IL-4 could be blocked by systemic treatment of burn-injured mice with anti-CD1d mAb. Together, our results reveal a novel mechanism involving CD1d stimulation of NKT cells in the onset of T cell suppression that occurs subsequent to injury.     

Dexamethasone suppression and multiple hormonal responses (TSH,prolactin and growth hormone) to TRH in some psychiatric disorders

Summary Baseline and TRH-induced changes of thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) were measured in 15 healthy control subjects and 63 psychiatric inpatients with DSM-III diagnoses of major depression (n = 19), schizophrenic disorder (n = 20), alcohol dependence (n = 10), and adjustment disorder (n = 14); baseline and postdexamethasone cortisol (CS) were also determined 3–6 days after the TRH-challenge. All patients and controls were women of similar mean age, weight, height, and they were free from interfering illness or drugs.Baseline TSH and PRL were lower in depression, TRH-induced TSH and PRL responses were lower in the whole patient group, but most markedly in depression and alcohol dependence. Postdexamethasone CS was significantly higher in depression, schizophrenia and alcohol dependence. Basal GH did not differentiate the subgroups; TRH-induced pathological GH responses were sometimes found in the patient groups. The differences were most marked quantitatively in major depression: a multivariate analysis of variance showed that TSH, postdexamethasone CS and PRL were the most important variables in separating patients from controls. A discriminant function derived from these variables classified all controls and 18 of 19 depressed patients correctly; however, 25 of the 44 other patients were also classified with depression.It was confirmed that psychiatric patients show significantly more endocrine disturbances than controls, and this was seen not only in major depression but also in at least three other conditions. Further work is needed to identify other neuroendocrine patterns more specific to depressive disorder.     

Differential indications for the surgical management of fractures of the mandibular condyle

The frequency and importance of collum mandibulae fractures is indicated, especially in connection with the sequels of conservative-functional therapy, and the different classifications and types of fractures are described. The non-surgical approach is evaluated as a treatment. Its inconvenient and sometimes unsatisfactory results necessitate the surgical treatment of certain types of collum mandibulae fractures. Absolute en relative indications for osteosynthetic treatment of condylar fractures are noted, the proposed surgical technique is discussed. The importance of a universal preauricular incision continued in an incision for parotidectomy and resulting in a standard incision or a combined preauricular-submandibular incision, is pointed out. Surgical technique for intra and extra capsular collum fractures is illustrated. Our preference goes to functional stable osteosynthesis using titanium mini-plates and the often obligatory dissection of the facial nerve. The so called "condylar shave" or remodelling condylotomy in analogy with the DAUTREY-operation is a therapeutic contingency in case of bilateral collum mandibulae fractures with unilateral low condylar fracture where classical mini-plate osteosynthesis is done, and intracapsular multi-fractured condylar head on the other side where the condylar shave or rubble clearing is performed The attitude towards children is discussed. The result of this surgical technique is illustrated through the follow-up of 73 surgical treatments of collum fractures in 59 patients. We conclude that surgical osteosynthetic treatment of collum mandibulae fractures with a strict indication in case of dislocated and luxated fractures should be included in the therapeutic range of modern maxillo-facial traumatology.     

Andrology: Relationship between stimulated hyperactivated motility of human spermatozoa and pregnancy rate in donor insemination: a preliminary report

The proportion of spermatozoa exhibiting the vigorous motilitybehaviour termed ’hyperactivation‘ (HA) has beenshown to be increased following removal of seminal plasma andstimulation with chemical agents such as pentoxifylline. Theaim of this study was to examine the relationship between theproportion of HA in cryopreserved semen samples from sperm donorsand the corresponding pregnancy rates achieved by donor insemination.Cryopreserved samples from 20 men were incubated in the presenceor absence of 3 mM pentoxifylline for 1 h and the %HA determinedin each sample. The relationship between pregnancy rate, theproportion of HA spermatozoa in control and pentoxifyllinetreatedgroups and the change in %HA following pentoxifylline treatment(HA) as well as the mean semen characteristics for each donor[sperm count, motility (%), motility index, normal morphology(%), post-thaw motility (%) and post-thaw motility index] wereexamined by logistic regression of the occurrence of clinicalpregnancy with each insemination. Both HA and mean post-thawmotility index were significantly related to pregnancy ratesand together accounted for 64% of the observed variation inpregnancy rates.     

Mitotic counts in rat adenohypophysial thyrotrophs and somatotrophs: Effects of short-term thyroidectomy,thyroxine, and thyrotropin-releasing hormone

The question of whether thyroxine (T₄) and thyrotropin-releasing hormone (TRH) affect mitoses in pituitary thyrotrophs (Tt) and somatotrophs (St) of hypothyroid rats was investigated. Fifteen day thyroidectomized (Tx) rats were used. Groups of Tx animals received T₄ or TRH or both. Except 6 and 24 h TRH groups, the animals were sacrificed 12 h after injections. Unoperated euthyroid rats served as controls. In Tx group adenohypophysial mitoses were significantly increased. T₄ diminished mitoses in Tx rats. Mitotic counts were decreased in 6 and 24 h Tx groups, but increased in 12 h TRH group. TRH plus T₄ in Tx animals had a synergistic effect on adenohypophysial mitoses. In unoperated controls few mitoses were observed in Tt and more mitoses in St. In Tx rats more mitoses were seen in Tt than in St. T₄ alone failed to reduce mitoses in Tt but increased them in St. We concluded that T₄ affects Tt and St replication. In normal rats mitoses occur mainly in St. In Tx rats mitotic activity increased in Tt. TRH plus T₄ have a synergistic motogenic effect on St. T₄ but not TRH affects St replication. It appears that the presence, of T₄ is necessary for St multiplication.     

Lansoprazole in the treatment of heartburn in patients without erosive oesophagitis

BACKGROUND: This randomized, double-blind, multicentre study compared lansoprazole with placebo for symptomatic relief of patients with non-erosive gastro-oesophageal reflux disease (GERD). METHODS: 214 patients with symptomatic, non-erosive GERD (moderate to severe daytime and/or night-time heartburn greater than half the days over the past 6 months and during the 7- to 10-day pre-treatment period) were randomized to either lansoprazole 15 mg or lansoprazole 30 mg, or placebo o.d. for 8 weeks. RESULTS: Daily diary data indicated that on the first treatment day a statistically significantly smaller percentage of lansoprazole patients reported daytime and night-time heartburn and antacid usage, compared with placebo patients. Lansoprazole patients also reported statistically significant less severe daytime and night-time heartburn on the first treatment day. During 0-4, 4-8, and 0-8 weeks of therapy, a statistically significant smaller percentage of days and nights with heartburn, less severe daytime and night-time heartburn, and less antacid usage were observed in the lansoprazole group compared to the placebo group. The percentages of patients with adverse reactions were similar in the lansoprazole and placebo groups. CONCLUSIONS: The results of this study demonstrate that lansoprazole is an appropriate therapy for patients with symptomatic non-erosive GERD.     

The effect of long term and high dose interferon treatment in Chronic hepatitis C

The results of 43 interferon treatments of 35 patients (23 male, 12 female) are reported. The duration of the treatment was 6–18 months, the dose of interferon was 3x3-5 MU weekly. Complete response (HCV RNA became negative) was found in 11, relapse was observed in 3 patients. Partial response (transaminase levels became normal, or less than twice normal value, but patients remained HCV RNA positive) occurred in 23 cases, relapse was obeserved in 16. The therapy had no effect in 9 cases. The higher dose and longer term interferon therapy resulted in a higher rate of response to the treatment and a reduction in the number of relapses. This work was supported by the Hungarian Ministry of Welfare (No. T-10 064/93).     

Effect of intravenous infusion of growth hormone-releasing hormone on the morphology of rat pituitary somatotrophs

The effect of GRH infusion on rat adenohypophysial morphology was studied by light microscopy, immunocytochemistry, in situ hybridization, and electron microscopy. Synthetic rat GRH was intravenously administered by osmotic minipumps at 14.4, 72, 360 and 720 μg/ day/rat for 1 week. In one group treated for 1 week with a daily dose of 720 μg GRH, the rats were killed 7 days after withdrawal of GRH. Control rats in which GRH was replaced by excipient, or those that received no treatment, were included as well. GRH infusion with daily doses of 360 and 720 μg resulted in a significant increase in pituitary weight and weaker GH immunoreactivity compared with other groups. Ultrastructurally, the somatotrophs were increased in size and became sparsely granulated, and the organelles involved in hormone sythesis were very prominent. The intensity of the GH mRNA signal did not differ from control animals, suggesting the desensitization of somatotrophs to GRH. The highest GRH dose induced an increased number of nuclei immunoreactive for proliferation cell nuclear antigen (PCNA). One week after GRH withdrawal, shrinkage of cytoplasm, involution of RER and Golgi complex, and a decrease of cell attachment sites indicated the reversibility of changes induced by GRH. In conclusion, GRH infusion induced, within days, hypertrophy and proliferation of somatotrophs with ultrastructural features of highly stimulated, sparsely granulated cells. Morphological changes were reversible.Endocr Pathol 4:131–139, 1993.     

Altered radioprotective properties of interleukin I alpha (IL-1) in non-hematologic tumor-bearing animals

The radioprotective properties of IL-1 were investigated in the respective murine hosts for the Lewis lung (LLca) and EMT-6 tumors. For these studies, doses of total body irradiation were selected for the C57B1/6 (9.5 Gy) and Balb/c (7.5 Gy) mice that resulted in a 60% mortality over a 30-day interval. When a "priming" dose of 2.5 x 10(5) U IL-1 was administered 24 hr prior to the radiation exposure, animal mortality was markedly reduced (60% vs 5-10%). Under identical experimental conditions, however, the presence of either the LLca or the EMT-6 tumors in their respective host strains was found to compromise the level of radioprotection conferred by this priming dose of IL-1. In Balb/c mice bearing the EMT-6 tumor, a priming dose of IL-1 resulted in only a modest level of radioprotection when compared to non-tumor-bearing control animals (median animal survival increased by 11.5 days). In C57B1/6 mice bearing the LLca tumor, IL-1 failed to demonstrate any evidence of radioprotection. Following a sublethal dose of total body irradiation, the appearance of an accelerated repopulation of the stem cell (8d CFUs and CFU-GEMM) and the myeloid progenitor (CFU-M) compartment in the marrow of the IL-1 primed EMT-6, but not the LLca, tumor-bearing animals was consistent with the hypothesis that the mechanism leading to radioprotection in IL-1 primed rodents involves an accelerated recovery of hematopoietic activity. It was also noted that the presence of the EMT-6 tumor was associated with an increase in the "radiosensitivity" of the Balb/c mouse. Collectively, these data suggest that the use of biological modifiers should be examined under altered physiological conditions prior to attempting to translate them into the clinic.