Long-term potentiation at single fiber inputs to hippocampal CA1 pyramidal cells.

Despite extensive investigation, it remains unclear whether presynaptic and/or postsynaptic modifications are primarily responsible for the expression of long-term potentiation (LTP) in the CA1 region of the hippocampus. Here we address this issue by using techniques that maximize the likelihood of stimulating a single axon and thereby presumably a single synapse before and after the induction of LTP. Several basic properties of synaptic transmission were examined including the probability of neurotransmitter release (Pr), the quantal size (q), and the so-called potency, which is defined as the average size of the synaptic response when release of transmitter does occur. LTP was routinely associated with an increase in potency, whereas increases in Pr alone were not observed. LTP was also reliably induced when baseline Pr was high, indicating that synapses with high Pr can express LTP. These results suggest that the mechanism for the expression of LTP involves an increase in q and is difficult to explain by an increase in Pr alone.     

Fear and the startle reflex: Blink modulation and autonomic response patterns in animal and mutilation fearful subjects

The present study was designed to examine the pattern of startle reflex modulation and autonomic responses for individuals high in animal or blood-injury fear when viewing pictures of their feared objects. Sixteen individuals in each fear group and 16 low-fear control individuals viewed 32 color slides depicting fear-relevant, unpleasant but fear-unrelated, neutral, and pleasant scenes. Free viewing times were assessed in a second phase of the procedure as an index of avoidance behavior. Exposure to pictures of feared objects resulted in a consistent startle reflex potentiation and behavioral avoidance in both fear groups. This activation of the basic aversive system was independent of the autonomic pattern of the fear responses, which differed for the high-fear groups. These results suggest that the probe startle response indexes the organism's basic motivational disposition and add new information to the assessment of fear.     

Mechanisms of tolerance during treatment with nitroglycerin patches for 24 h

Objective: We examined the relationship between tolerance development, counterregulatory responses and arterial vasodilating effects evaluated by digital pulse plethysmography. Methods: Twenty patients with stable angina pectoris were exercise tested before, after 2 and after 24 h of open nitrate patch treatment. Results: The effects observed after 2 h of treatment on exercise duration, ST-segment depression, blood pressure and heart rate were lost in most individuals after 24 h. In contrast, the effects on the arterial pulse curves persisted after 24 h, with a mean change from baseline of 29%, compared to 33% at 2 h. After 24 h, a significant decrease in haematocrit and an increase in body weight were observed. The haematocrit changes correlated with the loss of clinical efficacy (r =0.57 for ST-segment depression, and r =0.54 for exercise duration). Conclusion: Clinical nitrate tolerance may be observed despite maintenance of the arterial vasodilating effects, and tolerance is more related to plasma volume expansion as a counterregulatory mechanism. Received: 28 February 1996/Accepted in revised form: 5 July 1996     

Loss of the nocturnal dip and increased variability of blood pressure in normotensive patients with noninsulin-dependent diabetes mellitus

Summary. Eleven normotensive diabetics with noninsulin-dependent diabetes mellitus (NIDDM) (mean age 52.5 SD 8.2 years) and 11 controls (mean age 47.4 SD 8.9 years) had their ambulatory blood pressure and heart rate recorded non-invasively by the Oxford Medilog System in standard hospital conditions. The results were averaged as hourly means of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), and heart rate (HR) for the 24-h period and similarly for the ‘awake’ period (14.16 h) and the ‘asleep’ period (8–10 h). Hourly means for diabetics and controls showed no differences in blood pressure and heart rate over the 24 h. During sleep, control subjects showed a significant drop in SBP (P < 0.001), DBP (P < 0.001), MAP (P < 0.001) and HR (P < 0.001). However, this nocturnal dip in blood pressure could not be demonstrated in the diabetic group. Blood pressure variability was significantly increased in diabetics compared to controls during waking hours (P < 0.01). These results indicate that in noninsulin-dependent diabetics during sleep there is loss of the nocturnal dip of BP seen in normal subjects, and they have increased BP variability. These may be contributing factors to the development of hypertension and the accelerated target organ damage (TOD) seen in diabetes.,     

Comparative toxicity and tissue retention of selenium in methionine-deficient rats fed sodium selenate or L-selenomethionine

Selenium (Se) toxicity is known to be affected by level of intake of the mineral, but there are conflicting reports on the relative toxicities of the various chemical forms of Se. We monitored Se toxicity in rats fed Torula yeast-based diets containing 0.1, 0.5 or 2.5 micrograms Se/g of diet as either sodium selenate (Na2SeO4) or L-selenomethionine (SeMet). Half the diets were supplemented to contain adequate dietary methionine (Met). Weights were monitored weekly for 6 (Met-adequate) or 7 (Met-deficient) wk, at which time the rats were killed. There were no significant differences in final weight among Met-adequate rats, regardless of level or form of dietary Se. Methionine-deficient rats all gained significantly less weight than their Met-adequate counterparts. Selenosis was most severe in the Met-deficient rats fed 2.5 micrograms Se/g of diet as Na2SeO4, as indicated by significantly impaired weight gains. Nonetheless, Se retention in serum, heart, brain, bone, testes, colon, skin, lungs and pancreas was greater in rats fed SeMet than in those fed Na2SeO4, and Met deficiency further intensified this trend. The kidney was the only organ in which Se levels were markedly higher in the severely poisoned Met-deficient rats fed Na2SeO4. Further research is needed to determine whether elevated kidney Se levels are related to the greater toxicity observed in the Met-deficient rats fed Na2SeO4.     

Apomorphine-induced blinking and yawning in healthy volunteers.

Yawning and spontaneous blink rate (SBR) are two physiological reflexes which have been incompletely examined but one neurobiological step of these two behaviours seems, at least in part, dopamine-dependent. The reference dopaminergic agonist, apomorphine hydrochloride (0.5, 1, and 2 micrograms kg-1 s.c.), was compared with a placebo in a double-blind latin-square design, and was shown to induce yawning and increase SBR in a population of eight healthy volunteers. These two behavioral effects were not dose-related. The individual SBR differences were correlated with the individual number of yawns for all the four treatments at the 10-30 min interval. Thus, parallel yawning and SBR behaviour suggests a similar pharmacological mechanism. Apomorphine-induced yawning and blinking may be therefore of use in the evaluation of central dopaminergic pathways in man.     

Cemented and ingrowth fixation of the Miller-Galante prosthesis. Clinical and roentgenographic comparison after three- to six-year follow-up studies

One hundred thirty-nine cemented and 132 cementless Miller-Galante total knee prostheses were followed between three and six years (average, 43-44 months). The fixation technique was based on patient age, bone quality, and ability to delay full-weight bearing. Clinical follow-up studies were possible on 116 cemented knees. Fifteen knees were lost because of death before the three-year follow-up study, and eight knees required component removal. One hundred twenty-three cementless knees were available for clinical follow-up studies; there were three deaths, and six failures required component removal. No cemented failure was due to fixation, and three cementless failures were due to lack of tibial ingrowth in two and pain of undetermined etiology in one. Preoperative knee scores were slightly significant with cemented knees averaging 48 points and cementless knees averaging 52 points. A similar significant difference was maintained at the final follow-up study. No significant differences were noted for pain, limp, or support scores. Average range of motion was similar in the two groups. Radiolucent lines about the femoral component were rare. Cementless tibial radiolucencies were partial in up to 20% of examined zones, and complete tibial tray radiolucency was seen in only three patients. No correlation between radiolucency and knee scores was seen.     

Production of monoclonal antibodies against human bladder cancer cells and application to immunohistochemical analysis of bladder cancer

Two hybridomas secreting two monoclonal antibodies IgG1 B1.4 and IgG2a B1.6 were obtained by immunizing BALB/c mice with human bladder cancer cell line EJ-1. In immunohistochemical staining of cryopreserved tissues, B1.4 reacted with 0 of 9 grade 1 TCC, 6 of 11 grade 2, all of 6 grade 3 and five metastatic specimens. The antigen recognized by B1.4 was not expressed by normal urothelial cells but were expressed by vascular endothelial cells and muscle of tunica media. The target antigen of B1.6 was expressed by normal urothelial cells and all grade of TCC. In this study, it was demonstrated that poorly differentiated bladder cancer and metastatic specimens of bladder cancer express a vascular carbohydrate antigen. Taking the escape mechanism of immune surveillance, into consideration, it is possible that the antigen recognized by B1.4 is an indicator of metastatic potential of bladder cancer.