We examined the effects of a newly synthesized gastrin receptor antagonist, AG-041R, on the growth of enterochromaffin-like (ECL) carcinoid tumors in Mastomys natalensis both in vitro and in vivo. AG-041R was as potent as the well known gastrin antagonist L365,260 in inhibiting not only the gastrin-induced release of histamine from but also histidine decarboxylase (HDC) gene expression in the ECL carcinoid tumor cells. AG-041R also inhibited gastrin-induced DNA synthesis and c-fos gene expression in the tumor cells. Furthermore, AG-041R significantly inhibited the growth of the transplanted Mastomys ECL carcinoid tumors in vivo. From these data, it is concluded that endogenous gastrin is involved in the growth of ECL carcinoid tumors in Mastomys natalensis. Moreover, AG-041R is shown to have a potential as an anti-neoplastic agent for ECL carcinoid tumor of the stomach.
Laboratory-based surveillance of Lyme disease in Connecticut during 1984 and 1985 identified 3,098 persons with suspected Lyme disease; 1,149 were defined as cases. Lyme disease incidence in Connecticut towns ranged from none to 1,407 cases per 100,000 population in 1985. A comparison of 1985 data with data from 1977 epidemiologic studies indicated that incidence increased by 129 percent to 453 percent in towns previously known to be endemic for Lyme disease and that Lyme disease had spread northward into towns thought to be free of Lyme disease in 1977. Children aged five to 14 years had the highest incidence. Of persons with Lyme disease, 83 percent had erythema migrans, 24 percent had arthritis, 8 percent had neurologic sequelae, and 2 percent had cardiac sequelae. The distribution of symptoms was age-dependent: case-persons less than 20 years old were almost twice as likely to have arthritis than older case-persons (35 percent versus 18 percent). Of persons with arthritis, 92 percent of those less than 20 years of age, compared to 68 percent of older persons, did not have antecedent erythema migrans. We conclude that Lyme disease is increasing in incidence and geographic distribution in Connecticut. Of those with Lyme disease, children may be more likely than adults to develop arthritis and have it as their first major disease manifestation.
When hepatocytes were freshly isolated from rat liver and incubated for various periods of time at 37 degrees C, the media from the incubation, when completely separated from the cells, actively degraded 125I-insulin. THis soluble protease activity was strongly inhibited by bacitracin but was unaffected by the lysosomatropic agent ammonium chloride (NH4Cl). When hepatocytes were incubated with 125I-insulin at 37 degrees C in the presence or absence of 8 mM NH4Cl the ligand initially bound to the plasma membrane and was subsequently internalized as a function of time. When hepatocytes were incubated at 37 degrees C for 30 minutes with 125I-insulin in the presence of bacitracin and NH4Cl or bacitracin alone and the cells were washed, diluted, and the cell-bound radioactivity allowed to dissociate, the percent intact 125I-insulin in the cell pellet and in the incubation media was greater in the presence of NH4Cl at each time point of incubation. Under these same conditions a higher proportion of the cell-associated radioactivity was internalized and a higher proportion was associated with lysosomes. The data suggest that receptor-mediated internalization is required for insulin degradation by the cell, and that this process, at least in part, involves lysosomal enzymes. Furthermore, the data demonstrate that internalization is not blocked by the presence of bacitracin or NH4Cl in the incubation media, but that degradation is inhibited.
The aim of this study was to evaluate the effect on human lymphocyte chromosomes of the (131)I dosage used in scintigraphy on thyroid patients. Until now, there has been as absence of conclusive reports on the effects produced by such dosage. Samples were obtained from 21 patients, and the blood was collected in two occasions: Twenty-four hours prior (control) and after administration of the radionuclide (test). Cells were placed in 1640 RPMI medium with bovine calf serum and incubated with phytohaemagglutinin for 48 and 72 hr at 37 degrees C. Chromosomes were stained with Giemsa Gurr (2 percent, pH = 6.8), and analyzed by two independent investigators by optical microscopy. Of the 6,300 metaphases analyzed from the 48- and 72-hr cultures, 1,146 and 216 gaps and 682 and 52 breaks were found in the test group, respectively. Of the 6,300 metaphases analyzed from the control group, 291 gaps and 119 breaks were observed in the 48-hr cultures whereas in the 72-hr cultures, 10 gaps, and no breaks were found. Our results show that (131)I is responsible for the observed chromosome alterations (paired t-test, p <.05). We suggest re-evaluating the use of (131)I and replacing it with the (123)I, mainly on those patients at fertile age.
To analyze the risk of cannula sepsis from indwelling umbilical arterial catheters and the indication for prophylactic antibiotics, 137 catheterized neonates with respiratory distress were prospectively placed into either antibiotic-treated (penicillin 50,000U/kg/day and kanamycin 15 mg./kg./day) or non-treated groups. Although bacteria were frequently isolated from blood and catheter tip cultures obtained upon removal of the catheter, especially among non-antibiotic treated infants, these isolates were predominantly non-pathogens and probably skin flora. Corresponding peripheral blood cultures were usually sterile. No cases of cannula-associated sepsis occurred among treated and non-treated newborns. The risk of bacteriologically proven sepsis resulting from an indwelling umbilical artery catheter appears insufficient to justify prophylactic antibiotics.
Depositions for coroners' inquests on 377 deaths, nearly all of them homicides, were reviewed and analyzed for reported causes and circumstances of death. The role of coroner and surgeon and the emergence of the medicolegal autopsy are considered.