Fine-needle aspiration cytology of the adrenal gland. Fifty biopsies in 48 patients.

Fine-needle aspiration biopsy of 50 adrenal masses from 48 patients was performed between 1984 and 1991. The series consisted of 28 males and 20 females, with an age range of 12 months to 79 years (mean age, 55 years). Clinical and/or pathologic follow-up was available in 37 patients. Fine-needle aspiration was diagnostic in all 29 malignant cases having follow-up, with no false-positive diagnoses. There were six primary malignancies (three neuroblastomas, two pheochromocytomas, and one adrenal cortical carcinoma) and 23 metastatic lesions. Of these, the lung was the most frequent primary malignancy (60%), followed by melanoma and renal cell carcinoma (8.6% each). The remaining nonmalignant fine-needle aspiration diagnoses were adrenal cortical neoplasms (most likely adenoma), adrenal cortical hyperplasia, myelolipoma, benign adrenal tissue, and abscess. Based on clinical follow-up, three other adrenal adenomas were not diagnosed by fine-needle aspiration. Six biopsy specimens (12%) were insufficient for diagnosis. Ancillary studies including electron microscopy and/or immunocytochemistry were performed on 13 malignant aspirates and provided additional confirmation of the cytology diagnosis in 12 cases. This study confirms that fine-needle aspiration is a sensitive and highly specific procedure for the evaluation of primary and metastatic malignancies involving the adrenal gland. The technique is less useful in the workup of benign processes but, in some instances, can provide specific diagnostic information.     

The hypothalamic magnocellular neurosecretory system of the guinea pig. II. Immunohistochemical localization of neurophysin and vasopressin in the fetus

The development of the hypothalamic magnocellular neurosecretory system of the fetal guinea pig was examined by immunohistochemistry. Neurophysin was first observed in the supraoptic nucleus (SON), median eminence (ME) and posterior pituitary (PP) on day 40 of gestation. It was not regularly present in the paraventricular nucleus (PVN) until day 47. Vasopressin was first observed in the SON, ME and PP on day 45. In the median eminence immunoreactive deposits indicative of both peptides were observed in both the fibers of the hypothalamo-hypophysial tract (H-HT) in the presumptive zona interna as well as in axons projecting to the developing primary portal plexus.     

The degradation of serum amyloid A protein by activated polymorphonuclear leucocytes: participation of granulocytic elastase

To determine the role of inflammation in amyloidogenesis, we have studied the degradation of human serum amyloid A (SAA) protein by purified preparations of human blood polymorphonuclear leucocytes (PMN) and monocytes. When both PMN and monocytes were incubated in SAA-containing medium, the concentration of SAA as measured by a competitive anti-AA radioimmunoassay decreased over time. The rate of decrease of SAA was similar for both monocytes and PMN and there were no differences between four patients with amyloidosis and three normal controls. Resting PMN from normal volunteers were able to degrade SAA to smaller acid-soluble peptides within 16 hr while zymosan-activated PMN produced significant degradation within 1 hr (31%–50%). The supernatants from zymosan-treated PMN also caused marked SAA degradation within 1 hr.

The following enzyme inhibitors were able to prevent degradation of SAA by PMN supernatants; phenylmethylsulphonyl fluoride, a serine esterase inhibitor; α₁ anti-trypsin and soybean trypsin inhibitor; and acetyl-ala-ala-pro-val-chloromethyl ketone, an elastase inhibitor. The ability of a neutral lysosomal enzyme to degrade SAA was further confirmed by showing that purified PMN elastase significantly degraded ¹²⁵I-SAA.

We conclude that PMN contain one or more lysosomal enzymes capable of degrading SAA, an apoprotein of HDL₃ serum lipoproteins. Alteration in SAA proteolysis by activated PMN may contribute to the deposition of amyloid fibrils in the tissues of patients with chronic inflammatory disease.

     

Detection of altered H-ras proteins in human tumors using western blot analysis

H-ras p21 protein expression was investigated in bladder and colonic tumor tissues using an H-ras specific antibody in Western blot analysis. The specificity of this antibody to H-ras proteins was established using NIH/3T3 transfectants expressing oncogenic counterparts of the different ras gene family members. Use of this antibody to detect altered H-ras proteins was demonstrated using a panel of transfectants bearing different mutated H-ras genes and established cell lines previously characterized in transfection assays. Extension of this technique to direct analysis of human tumor material confirmed previous observations of H-ras activation within a group of bladder tumors and identified three more urothelial tumors expressing altered H-ras proteins. The altered migrational properties of these three were suggestive of point mutational events in 12 (1 case) and 61 (2 cases) codon hot spots. This study extends previous observations on the preferential activation of H-ras in urinary tract tumors and provides a rapid technique for evaluating the status of H-ras proteins in human tumor tissue.     

Role of Drosophila IKK gamma in a toll-independent antibacterial immune response

We have generated, by ethylmethane sulfonate mutagenesis, loss-of-function mutants in the Drosophila homolog of the mammalian I-kappa B kinase (IKK) complex component IKK gamma (also called NEMO). Our data show that Drosophila IKK gamma is required for the Relish-dependent immune induction of the genes encoding antibacterial peptides and for resistance to infections by Escherichia coli. However, it is not required for the Toll-DIF-dependent antifungal host defense. The results indicate distinct control mechanisms of the Rel-like transactivators DIF and Relish in the Drosophila innate immune response and show that Drosophila Toll does not signal through a IKK gamma-dependent signaling complex. Thus, in contrast to the vertebrate inflammatory response, IKK gamma is required for the activation of only one immune signaling pathway in Drosophila.