Ultrastructural responses by Golgi apparatus of rat submandibular gland to beta-adrenergic, alpha-adrenergic, and cholinergic stimulation

Rat submandibular gland tissue pieces were stimulated in vitro for 30 min with a beta-adrenergic agent or a cyclic AMP analog to stimulate protein secretion, or with alpha-adrenergic or cholinergic agents or a Ca2+ ionophore to stimulate fluid secretion. Acinar cells were examined by transmission electron microscopy. In control tissue, acinar cells showed little evidence of secretory activity. The Golgi apparatus was sparse and was associated with a few small, immature secretory granules with fine fibrillar contents. Following secretory granule discharge stimulated by isoproterenol or dibutyryl cyclic AMP, acinar cells were constricted, and had extensive basolateral membrane folding and tightly packed rough endoplasmic reticulum. Golgi complexes were prominent and had multiple small granules with filamentous contents. After stimulation of fluid secretion by alpha-adrenergic agents (epinephrine, phenylephrine), or cholinergic agents (acetylcholine, carbachol, pilocarpine), or a Ca2+ ionophore (A23187), the Golgi apparatus had compact concave cisternae enclosing aggregates of tubulovesicles. Acinar cells were distended, basolateral membranes were expanded, and rough endoplasmic reticulum was dilated and vesiculated.     

Cytotoxicity of ionophore A23187 for basophils and other human blood cells.

The calcium ionophore A23187(A23) at concentrations exceeding 1 microgram/ml has been shown to be progressively cytotoxic for human blood basophils, neutrophils, lymphocytes, and erythrocytes. Toxicity to basophils was considered to be manifested by the increasing inability of 2-deoxyglucose (2DG) to inhibit histamine release (HR) at increasing concentrations of A23. The toxicity to neutrophils and lymphocytes was demonstrated by decreased lactate production (LP) after incubation with A23 of Ficoll-Hypaque fractions greatly enriched in each respective cell type. Red cells present in dextran-sedimented leukocytes were increasingly susceptible to lysis during washing subsequent to exposure to increasing concentrations of A23. A concentration of 4 microgram A23/ml, which is cytotoxic at 37 degrees C, produced optimal and noncytotoxic HR at 22 degrees C. It was possible to reduce A23 concentrations required for optimal HR by increasing Ca++ from 0.6 to 3 mM.     

Translocation (6;9)(p23;q34) in acute nonlymphocytic leukemia: Three new cases

Several recent reports have described cases of acute nonlymphocytic leukemia with a unique chromosome translocation, t(6;9)(p23;q34). We have studied three additional patients who have acute nonlymphocytic leukemia and t(6;9)(p23;q34). Our findings provide additional support for the suggestion that this translocation is yet another distinct cytogenetic abnormality associated with myeloproliferative disorders.     

Chronic myelogenous leukemia with a complex Ph1 translocation in an XYY male

We encountered a 38-year-old Japanese male patient with chronic myelogenous leukemia (CML), whose bone marrow and peripheral blood cells during the chronic and blastic phases contained a complex Ph¹ translocation and an extra Y chromosome [i.e., 47,XYY,t(9;22;13)(q34;q11;q14)]. A karyotypic analysis of PHA-stimulated lymphocytes showed the constitutional karyotype to be 47,XYY. Thus, it was considered that CML with a complex Ph¹ translocation developed in an XYY male; such a case has not been reported, so far. A B-lymphocyte cell line with the complex Ph¹ translocation was established by the procedure of Epstein-Barr virus transformation. The presence of the complex Ph¹ translocation in the B-lymphocyte cell line suggests that some of the B lymphocytes in this patient originated from the CML clone.     

Effect of prostaglandin D2 and I2 on the airways of rhesus monkeys

Prostaglandin (PG) D2 and PGI2 were evaluated to determine their effect on pulmonary function parameters when aerosolized in anesthetized rhesus monkeys. PGD2 resulted in an increase in frequency (f) and pulmonary resistance (rl) and a decrease in peak expiratory flow rate (PEFR), tidal volume (VT), and dynamic compliance (Cdyn), with the major effect on RL. PGI2 primarily effected an increase in f and a decrease in PEFR and VT. PGI2 had a variable effect, generally a decrease, on RL. The metabolite of PGI2, 6-keto-PGF 1 alpha, had no effect on the rhesus airway. PGF 2 alpha responses were similar to PGD2 except that the PGF 2 alpha produced a less strikingly consistent increase in RL. When PGI2 and PGD2 were aerosolized simultaneously, they simulated previously described antigen responses. Further, PGI2 plus PGD2 produced an airway response at 1/10 the concentration of either agent alone.     

Identification of the major structural proteins of two BALB/c myeloma C-type viruses.

We have analyzed the structural proteins of the C-type viruses produced by cloned lines of the MOPC-21 and FLOPC-1 BALB/c murine myelomas. These viruses, designated MO₂₁-MuMAV and FL₁-MuMAV, respectively, have been shown to be composed of proteins with approximate molecular weights of 90,000, 75,000, 17,000, 12,000, and 10,000 daltons. In addition, these viruses contain a “doublet” with molecular weights of approximately 30,000 daltons. The 90,000- and 75,000-dalton proteins are glycosylated. The p30 “doublet” as well as the NB-ecotropism is retained upon subsequent virus cloning in SC-1 cells, passage through NIH-3T3, or BALB/3T3 cells, or microtiter plate cloning of SC-1 cells replicating cloned virus. The two cloned MuMAVs appeared to possess the p30 proteins of the endogenous BALB/c N- and B-tropic viruses described by Hopkins and co-workers (N. Hopkins, J. Schindler, and R. Hynes, 1977, J. Virol.21, 309–318; J. Schindler, R. Hynes, and N. Hopkins, 1977, J. Virol. 23, 700–707). Subsequent tryptic peptide analysis of the myeloma virus p30 proteins demonstrated that these proteins share extensive homology with, but not identity to, the two prototype BALB/c ecotropic endogenous virus p30 proteins.     

Assessment of biomaterials as components of a reciprocating dialyser during canine dialysis

A recently reported device, the sorbent suspension reciprocating dialyser (SSRD), was investigated for use as a test system for biocompatibility of dialyser components. The device is easy to assemble and operate, and allows minimal blood contact with foreign material outside of dialyser components. Its constant pressure/ variable flow rate operation allows quantification of degree of clotting of dialyser versus time. The effect of heparinization of the blood distribution gaskets (BDG) of the device on performance and dialyser lifetime was investigated. Heparin was bound to the surface of polyethylene gaskets by immersion in a solution of tridodecylmethylammonium chloride (TDMAC)-heparin complex for several hours. Gaskets were then assembled in an SSRD which was then used for experimental dialysis in dogs with AV shunts. Dialysers assembled using non-heparinized gaskets were used as controls. Blood coagulation tendency was quantified by the activated clotting time (ACT) and partial thromboplastin time (PTT), and these values correlated with the rate of clotting of the device. Heparinization of the gaskets resulted in the prevention of clotting in the dialyser until the final minutes of dialysis in all cases, in contrast to the constant decay of blood fill volume and evidence of clotting in the non-heparinized cases. However, dialyser lifetime was not significantly increased by gasket heparinization. At normal initial values of ACT (80–95 s) dialyser clotting occurred in 10–15 mia In tests with non-heparinized gaskets and systemically heparinized dogs, values obtained in the ACT test were observed to decrease during dialysis, indicating the disappearance of heparin from the blood. Both ACT and PTT tests show promise as predictors of dialyser lifetime.     

Leukocyte histamine release in Hymenoptera-allergic patients. Correlation with skin test reactivity and changes following hyposensitization therapy

We have studied 46 Hymenoptera-allergic patients and 11 nonallergic controls by grading the severity of their sting reaction, determining their skin test reactivity, and performing human leukocyte histamine release with a commercial mixed stinging insect extract. A significant correlation was found between increasing severity of sting reaction and increasing skin test reactivity (p < 0.001). In $\text{41}\text{46}$ allergic patients from 15 to 100 per cent release of total cellular histamine occurred, whereas in the 11 nonallergic controls no greater than 10 per cent release of total cellular histamine was observed. Skin test reactivity correlated significantly with cell sensitivity in the allergic patients (p < 0.001). Following hyposensitization therapy, cell sensitivity generally did not change, but significant increases in antigen-neutralizing capacity (A.N.C.) of allergic serum did occur in $\text{11}\text{15}$ Hymenoptera-allergic patients.