John C. Garancis

THE HORMONE‐SYNTHESIZING TROPHOBLASTIC CELL IN VITRO: A MODEL FOR CANCER RESEARCH AND PLACENTAL HORMONE SYNTHESIS

The human trophoblast, the hormonally functional cell of the placenta, differentiates in the first-order cleavage of the fertilized human ovum immediately following conception.1 Hormonal function from the placental trophoblast can be detected in maternal serum by human chorionic gonadotropin (HCG)2 and human placental lactogen (HPL) assays shortly following the 58-cell stage of the human ovum. Thus, trophoblastic cellular differentiation and placental hormone synthesis are among the earliest morphological and biochemical differentiations to occur in the human. This cell type has not been established in vitro. Choriocarcinoma is a unique malignancy of trophoblastic cells which follows normal pregnancy, spontaneous abortion, or hydatiform mole. This tumor closely parallels the normal placenta in hormone function and cellular metabolism, with the exception that the limited invasiveness of the normal placenta during its implantation is far exceeded by that of the malignant tumor, which, proceeding unrestricted, culminates in the death of the patient within a period of less than 1 year.4 A morphological similarity can be observed among the trophoblastic cells of the human blastocyst less than 92 hours after conception (FIGURE l ) , the invading normal placenta of the first trimester (FIGURE 2), and the rapidly proliferating choriocarcinoma (FIGURE 3 ) .

Regulation of pH in rat papillary tubule cells in primary culture.

To investigate the mechanisms responsible for urinary acidification in the terminal nephron, primary cultures of cells isolated from the renal papilla were grown as monolayers in a defined medium. Morphologically, cultured cells were epithelial in type, and similar to collecting duct principal cells. Cell pH measured fluorometrically in monolayers grown on glass slides showed recovery from acid loads in Na+-free media. Recovery was inhibited by cyanide, oligomycin A, and N-ethylmaleimide. Cyanide and oligomycin inhibited recovery less in the presence than in the absence of glucose. When cells were first acid loaded in a Na+-free medium and then exposed to external Na+, pH recovery also took place. This recovery exhibited first-order dependence on Na+ concentration and was inhibited by 5-(N-ethyl-N-isopropyl)amiloride. These studies demonstrate that in culture, collecting duct principal cells possess at least two mechanisms for acid extrusion: a proton ATP-ase and an Na+-H+ exchanger. The former may be responsible for some component of the urinary acidification observed in the papillary collecting duct in vivo; the role of the latter in acid-base transport remains uncertain.

Calcium Oxalate Crystal Interaction with Rat Renal Inner Papillary Collecting Tubule Cells

Rat renal inner papillary collecting tubule cells (RPCT) have been isolated and maintained in primary culture. The cells have been found to be of only one type and they have maintained the characteristics of RPCT cells. The RPCT cells in culture appear as a monolayer with intermittent clumps of rounded cells. When small calcium oxalate monohydrate crystals (COM) or calcium oxalate dihydrate crystals (COD) are added to the monolayer of RPCT cells, the crystals bind on or about these clumps of rounded-up cells. The use of this system as a model for the study of crystal membrane interactions in crystalluria and urolithiasis is discussed.

Chemodectoma involving the cavernous sinus and semilunar ganglion

This paper reports a case of paraganglioma involving the cavernous sinus and semilunar ganglion. The origin of the tumor cells, from paraganglia in this region, is also discussed. Recognition of paraganglia in this area may aid the clinician and pathologist in the differential diagnosis of tumors in this region.

Immune-complex disease in guinea pig lungs: I. Elicitation by aerosol challenge, suppression with cobra venom factor, and passive transfer with serum☆

Abstract Immune-complex disease was elicited in the lungs of ovalbumin-sensitized guinea pigs following an aerosol challenge with specific antigen. An acute inflammatory reaction, characterized by peribronchial polymorphonuclear leukocyte infiltration, edema, and hemorrhage, was observed 2 hr following aerosol challenge. This focal reaction developed into a diffuse reaction within 6 to 12 hr postchallenge. By 24 hr postchallenge, the acute inflammatory process had begun to resolve. The active disease was suppressed with cobra venom factor and was transferred to normal guinea pigs with immune serum.

Progressive multifocal leukoencephalopathy and malignant lymphoma of the brain in a patient with immunosuppressive therapy.

SummaryProgressive multifocal leukoencephalopathy and malignant lymphoma of the brain were noted at postmortem examination in a 68-year-old white woman who was treated with immunosuppressive agents after renal transplantation. The two diseases are not uncommon in patients with immunodeficiency, but their occurrence in the same patient is extremely rare. This association suggests the oncogenicity of papova viruses in man. However, no papovavirus was demonstrated in the tumor by electron microscopy and immunohistochemical staining. The immunohistochemical staining of routine histologiy sections for the common antigen of polyomaviruses by the peroxidase anti-peroxidase technique is shown to be simple and specific for the detection of polyomaviruses in the demyelinated areas of progressive multifocal leukoencephalopathy.

CONTROL MECHANISMS FOR GONADOTROPHIC HORMONE PRODUCTION IN VITRO

SummaryAn internal control mechanism capable of controlling gonadotrophic hormone secretion in the human trophoblast has been identified by incubation of an established cell line with a precursor of progesterone.Biological, biochemical, and electron microscopic findings verify inhibition of gonadotrophic hormone synthesis, depletion of glycogen, activation of phosphorylase, the glycogen-metabolizing enzyme, and ultrastructural appearance of liquid-containing cytoplasmic granules in single cells, indicative of steroid synthesis.

Mast Cells and Calcium in Severe Uremic Itching

Mast cells may be more abundant in the tissues of uremic patients and may contribute to itching via mediator release. Because mast cell (MC) granule release may be inhibited by ultraviolet B (UVB) radiation, we investigated skin MC in the superficial dermis by quantitative histomorphometry before and after whole body UVB for uremic itching. Toluidine blue-stained 3.5 mm punch biopsy specimens were examined with a micrometer grid after separate coding. Upon entry to the study, itching dialysis patients indicated their itching intensity on a visual analog scale (0 to 10). Concurrent study of living, related kidney donors (controls, n = 11) and their recipients (n = 11) showed no differences in MC number per unit area. Compared to controls, skin MC number was not greater in itching dialysis patients (n = 20). MC number decreased after 2 months of UVB from 1.6 +/- 0.6 (standard deviation) to 1.0 +/- 0.7 (n = 11, p = 0.025). Pre-UVB total plasma calcium correlated directly with itching intensity, but not with MC number. Plasma phosphate and intact parathyrin level were not statistically related to itching or MC number. Of the 14 subjects that completed UVB, 8 had objective benefit, and mean itching intensity declined from 7.1/10 to 5.2/10 in the 14 subjects. The conclusion is that although skin MC number may decline with chronic UVB, MC number is not related to uremic itching, and hypercalcemia, but not elevation of parathyrin or plasma phosphate, relates statistically to severe uremic itching.

Reversal of Chronic End-Stage Renal Failure Due to Myeloma Kidney

Excerpt Renal insufficiency occurs commonly in multiple myeloma, and its presence has been considered the single most important factor in determining prognosis (1). Renal insufficiency has been att...

Zollinger-Ellison syndrome: Clinical and histopathologic manifestations☆

Abstract Zollinger-Ellison syndrome is caused by a neuroendocrine tumor of the pancreas that secretes gastrin, causing massive gastric acid secretion. Treatment of the acid hypersecretion may be accomplished with pharmacologic acid inhibition. The goal of surgical treatment should be removal of all gross tumor in those without distant metastases. Cure rates approximate 30% and 20-year survival exceeds 70% even without cure.