Tumor necrosis and cell detachment

Cell detachment from and around Walker 256 tumors grown in rats is quantitated by a standardized in vitro shaking procedure. The volume of cells detached from cancers of similar size is virtually the same in tumors growing in the liver, the spleen, in intramuscular and in subcutaneous sites. In cystic tumors, greater volumes are detached from the innermost regions of the walls adjacent to necrotic material than from the outermost parts. More liver perenchymal cells are shaken free of liver adjacent to a tumor interface than from regions 0.5 and 1.0 cm distant from it. Detachment of tumor and liver cells is also enhanced by prior incubation of tissue samples with necrotic extracts. It is suggested that the necrotic regions of tumors, and products derived from them, facilitate the detachment of tumor cells and cells composing the normal tissues surrounding them, thereby potentially promoting metastasis and invasion.     

Occupational asthma of bakers.

Two cases of bakers with asthma are discussed. The etiologic mechanisms which play a role in baker's asthma are reviewed. Disodium cromoglycate may be used to minimize symptoms in this disease entity.     

Operant behavior of rats exposed to lead before or after weaning

Rats were exposed to lead (Pb) before or after weaning. For preweaning exposures, nursing dams received 0.2% Pb acetate(1090 ppm Pb) in drinking water. Offspring treated after weaning consumed the same concentration. Tapwater served as the control fluid. Pre-post treatments were distributed among four experimental groups of 10 rats each: tap water-tap water, Pb-tap water, tap water-Pb, Pb-Pb. Operant behavior training began on Postnatal Day 58. Animals performed on a multiple reinforcement schedule of food presentation consisting of fixed-interval, fixedratio, and time out components. Statistical analyses of experimental sessions 4 to 11 (Postnatal Days 72 to 79) revealed that postweaning exposure significantly lengthened the median interval (interresponse time) between consecutive responses on both the interval and ratio schedules. Preweaning exposure alone tended to produce a shortening of the median interresponse time. Other performance indices and subsequent variations of ratio size showed similar but not significantly different relationships among the treatment groups. No significant histopathology was detected. Brain and blood Pb concentrations were consistent with the treatment protocol.     

EVALUATION OF THE RENAL TOXICITY OF HEME PROTEINS AND THEIR DERIVATIVES: A ROLE IN THE GENESIS OF ACUTE TUBULE NECROSIS

This investigation studies the toxicity of heme proteins and/or their break-down products on renal function. Heme proteinemia precedes acute tubule necrosis at a frequency great enough to suggest a causal relationship between the two events. Physiological and metabolic functions of kidney slices are investigated in several models of acute tubule necrosis. Organic acid and organic base transport is depressed earliest. These alterations in tubule function cannot be explained by ischemia or obstruction alone. Heme proteinemia in rats or incubation of renal slices in medium containing heme proteins yields several interesting observations. Neither in vivo or in vitro do hemoglobin and methemoglobin alone produce a depressive effect on the transport systems studied. However, parallel to many clinical situations, when such secondary insults as hypoxia and elevated ammonia concentrations are included in the experimental design, transport functions are depressed. Ferrihemate, a molecule smaller than hemoglobin or methemoglobin, depresses transport function without secondary insults. From these studies it is concluded that heme proteins play a role in tubule dysfunction seen in acute tubule necrosis. A model is presented that collates these data with other factors known to play a part in the pathogenesis of this renal syndrome.     

Studies of Platelet 5-Hydroxytryptamine (Serotonin) in Storage Pool Disease and Albinism

Platelets in patients with storage pool disease are markedly deficient in a nonmetabolic (storage) pool of ADP that is important in platelet aggregation. They are also deficient in ATP, although to a lesser degree. In seven patients with this disorder, including one with albinism, platelet 5-hydroxytryptamine (5-HT) levels were reduced in proportion to the reduction in ATP (r = 0.94). Their platelets show diminished capacity to absorb [(14)C]5-HT, and the type of defect was similar to that produced in normal platelets by reserpine, a drug known to inhibit the uptake of 5-HT by the platelet dense granules. Storage pool-deficient platelets also converted more [(3)H]5-HT to [(3)H]5-hydroxyindoleacetic acid than did normal platelets, and the platelets in one of two patients studied contained increased amounts of 5-HT metabolites. The above findings, together with those reported previously, support the conclusion that the capacity of the dense granules (which may be either diminished or functionally abnormal) for storing 5-HT is decreased in storage pool disease; as a result, the 5-HT that enters the platelet may be more exposed to monoamine oxidases present on mitochondrial membranes. This diminished storage capacity (for 5-HT) may also explain why preincubating platelet-rich plasma with 5-HT for 45 min without stirring inhibits subsequent platelet aggregation by 5-HT to a greater degree in patients with storage pool disease than in normal subjects. The latter finding is also consistent with the theory that the aggregation of platelets by 5-HT is mediated by the same receptors on the plasma membrane that are involved in its uptake. The diminished release of platelet-bound [(14)C]5-HT by collagen that we found in these patients, as well as findings in previous studies, suggests that the release reaction may also be abnormal in storage pool disease.     

A clinical assessment of obturator-wearing cleft palate patients

An attempt was made to understand why some obturator-wearing patients can tolerate systematic pharyngeal section reductions and eventually can discard their obturators without detriment to their speech and vocal quality while others cannot. The age of the patient when treated appears to be the most important and valuable factor in achieving success in an obturator reduction program. This approach for carefully selected young patients seems to be the most advisable step to take in providing them with socially acceptable speech. The probability of many patients eventually not needing to wear obturators appears reasonably good so long as factors such as sex, cooperation, immediate family history of cleft palate, follow-up, and the clinician's persistence are considered.