Patterns of spontaneous unit preoptic neurosecretory cell discharges in the rainbow trout, Salmo gairdneri

Extracellular antidromic potentials recorded from the neurosecretory cell body were characterized by the following criteria: constant latency, the ability to follow a high frequency rate of stimulation and the collision test. The latency of the antidromic potentials ranged from 12 to 24 ms (17.46 +/- 3.10 SD) which gave a mean conduction velocity of 0.19 m/s, typical of unmyelinated nerve fibers. Two components could be clearly distinguished in the antidromic potential. A small "A" spike which showed constant latency and a large "B" spike with a variable latency and amplitude. A delay of 6.5 ms between the two spikes could occur and sometimes the "B" spike was blocked leaving only the "A" spike. Four patterns of spontaneous activity seem to emerge: Type I (26% of units, M +/- SD = 0.77 +/- 0.32 sp/s) corresponds to a slow and irregular pattern of activity; Type II (28% of units, M = 1.58 +/- 0.47 sp/s) is hard to classify and may be related to an irregular bursting pattern of activity; Type III (28% of units, M = 2.59 +/- 1.19 sp/s) corresponds to a continuous pattern of activity; Type IV (18% of units) represents a rhythmic pattern of activity with an active phase of about 3 min (M = 2.42 +/- 0.90 min), a silent phase of about 4 min (M = 3.89 +/- 3.02 min) and a maximal frequency of unit discharge in the range 2-18 sp/s. No statistical differences exist for the mean dorsal aortic pressure (DAP) between the four types of neurosecretory cell activity.     

Intraventricular somatostatin-14, arginine vasopressin, and oxytocin: analgesic effect in a patient with intractable cancer pain

The analgesic effect of intraventricular somatostatin-14 (SOM-14), arginine vasopressin (AVP), and oxytocin (OT) were tested in one terminally ill cancer patient with a diffuse mesothelioma suffering intractable continuous and incapacitating thoracic pain. SOM-14 reduced pain by 90% for 48 min; AVP reduced pain by 95% for 75 min, and OT reduced pain by 88% for 77 min. The only notable side effects were seen after the administration of AVP, which induced anesthesia and flaccid paralysis of the lower limbs, from which the patient fully recovered after 20 h.     

Relationship between cAMP and Ca2+ fluxes in human platelet membranes

The effect of cAMP (which involved a 23 kDa protein phosphorylation) has been studied on the Ca2+ uptake and Ca2+ release from a human platelet membrane vesicle fraction. It was tested in the presence of the catalytic subunit of the cAMP-dependent protein kinase (C Sub). The addition of C Sub increased the steady state level of the Ca2+ uptake into the membrane vesicles. The effect was enhanced when tested in the absence of Ca2+ precipitating agent. The response was proportional to the dose of C Sub. Moreover, the effect varied with the Ca2+ concentration. The effect of C Sub has been tested on the inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release. A phosphorylated state of the 23 kDa protein appeared to be necessary. Indeed, a phosphorylation inhibition prevented the IP3 effect and the addition of C Sub increased the percentage of released Ca2+ (without modification of the time course). However, the C Sub dose-dependent response was not linear. The effect of cAMP on the two functions (Ca2+ uptake and Ca2+ release) appears to be different. Therefore, these results led us to suggest a more complex role of cAMP in the regulation of platelet Ca2+ concentration.     

Application of a new method for detecting the phenotype of target binding cells

Summary A new method was developed for detecting the phenotype of target binding cells (TBC) in a single-cell assay system. This methodology was evaluated during a clinical trial of recombinant interferon alfa-2a (rIFN alfa-2a) for the treatment of 10 metastatic renal cell carcinoma patients. Total TBC with K562 targets, HNK-1+ TBC, and HLA-DR+ TBC were quantitated during rIFN alfa-2a therapy. A significantly increased proportion of lymphocytes bound to target cells on day 9 of therapy bore the HNK-1 marker. This proportion subsequently declined to pretreatment levels. Total TBC paralleled the rise and fall in HNK-1+ TBC. HLA-DR+ TBC binding to targets remained constant and low throughout therapy. These findings suggest that rIFN alfa-2a early in therapy (day 9) caused the recruitment of additional HNK-1+ cells into binders. However, with continued therapy, this proportion reverts to pretreatment levels. The results of this clinical trial served to illustrate the ability of the modified single-cell assay system to detect TBC phenotype.Supported in part by Hoffman-La Roche, NIH grant CA 12582, and Jonsson Comprehensive Cancer Center grant CA 15866Dr. Figlin is a recipient of an American Cancer Society Junior Faculty Fellowship-JFCF 762-A     

Study of human chromosome V

Summary The induction of fragile sites on human chromosomes has been demonstrated under various conditions that cause thymidylate stress, including exposure to uridine. In this study, we examined common fragile site expression by initially exposing peripheral lymphocytes to uridine, followed by repair of the fragile sites with media containing various concentrations of thymidine. Lymphocytes were cultured in medium 199 with 2 mM uridine. At 0.5, 1, 2, 3, 8, 10, 12, and 18 h before harvest, the uridine medium was removed and replaced by medium containing thymidine at various concentrations. Our results demonstrate that the effect of uridine on chromosome fragility can be reversed by low concentrations of thymidine (2 M up to 200 M) and the rescuing effect of thymidine can be achieved if the cells were treated prior to 2–3 h before harvest. No repair was found if thymidine was added to culture within 2 h prior to harvesting, suggesting that packing of chromosomes is also an important factor in the expression and repair of fragile sites.