Blockade of inhibition in a pathway with dual excitatory and inhibitory action unmasks a capability for LTP that is otherwise not expressed

Long-term potentiation (LTP) can be readily elicited in a number of hippocampal pathways, but has not been seen in the dentate commissural pathway. The dentate commissural pathway is similar to the commissural/Schaffer collateral projection to CA1 except that it produces powerful inhibition that occurs nearly concurrently with the excitation. The present study evaluates whether this inhibition prevents the pathway from expressing LTP. Acute neurophysiological experiments were carried out in urethane anesthetized rats. To locally block inhibition in the dentate gyrus, a recording micropipette filled with 8 mM bicuculline was positioned in the dentate gyrus. A control saline-filled micropipette was positioned nearby. The commissural pathway was activated by stimulating electrodes in the contralateral CA3/CA4 region. Brief high-frequency stimulation of the commissural pathway reliably elicited LTP at the bicuculline electrode but not at the control electrode. This LTP required a threshold level of stimulation for its initiation, suggesting that like most other examples of LTP, the LTP in the commissural system depended upon activation of a voltage-dependent receptor. The high-frequency stimuli used to induce LTP produced an extracellular negativity at the bicuculline electrode that was not present at the control electrode. This negative potential was selectively blocked by ketamine and MK801, suggesting that the negative potential reflects N-methyl-D-aspartate (NMDA) receptor activation. Taken together, these results suggest that LTP is not normally expressed by the dentate commissural pathway because the simultaneous inhibition prevents the depolarization-related relief of Mg2+ blockade of the NMDA receptor.     

An epitope of the transferrin receptor is exposed on the cell surface of high-grade but not low-grade human lymphomas

In attempting to identify antigens that are differentially expressed on tumor cells following transformation from follicular small cleaved cell lymphoma (FSC) to immunoblastic lymphoma (IL), we identified a unique epitope of the transferrin receptor (TfR). The epitope is available for binding in aggressive lymphomas but not in indolent lymphomas or normal cells. An immunoglobulin G2a (IgG2a) antibody that binds this epitope, Trump, was produced by screening on tumor cells from a patient who initially had a low-grade lymphoma which subsequently converted to a high-grade lymphoma. Immunoprecipitation and comodulation studies show that Trump binds to the TfR, but blocking studies and immunostaining reveal that the TfR epitope seen by Trump is distinct from the OKT9 and anti-TfR binding sites. The ability of Trump to discriminate a separate population of more highly malignant cells suggests that the expression of the Trump epitope is determined by the state of activation or degree of malignancy of the cell. In addition, it may be possible to use the Trump antibody diagnostically or therapeutically in the management of lymphomas.     

Plasma calcium and phosphate levels in an adult noninsulin-dependent diabetic population

Summary Duplicate or triplicate measurements of fasting plasma glucose, calcium (Ca), phosphate (Pi), and glycosylated hemoglobins were performed on a group of non-insulin dependent diabetic patients and controls at 3–6 month intervals. In the diabetic group (48 males and 44 females), 18 were on diet only, 21 on diet and oral hypoglycemic treatment, and 51 on diet and insulin. These were a total of 217 measurements for each parameter. Results were compared to 416 measurements obtained from sex and age-matched controls. Plasma Ca levels were higher in the diabetic group (2.48±0.004 vs 2.38±0.006 mmol/liter)P<0.001; plasma Pi levels were similar to those of controls. The difference in plasma Ca was not influenced by age, sex, or mode of treatment. No correlation was found in the three treatment groups between plasma Ca and duration of diabetes nor with patients' weights. The results are consistent with the view that an alteration in calcium homeostasis accompanies the diabetic state.     

A psychosocial taxonomy of patients with diabetes: validation in a primary care setting

Aims The aims of this study were (i) to extend a psychosocial taxonomy of patients with diabetes to a primary care setting, and (ii) to validate the taxonomy using more sophisticated clustering methods across an array of psychological dimensions independent of demographic and medical variables. Methods In a cross‐sectional study, 111 adults with Type 2 diabetes seen in a primary care setting completed the Multidimensional Diabetes Questionnaire and the Brief Symptom Inventory (BSI). They also provided diabetes‐specific self‐report measures along with HbA_1c. Results Four psychosocial patient profiles were identified using model‐based cluster analysis in a US primary care setting. The four profiles represent a replication of two and refinement of a third profile found previously in French‐speaking patients at diabetes education centres. Validation of the profiles using the BSI was replicated for depression and extended to other psychological dimensions. The validity and distinctiveness of the four psychosocial profiles were independent of demographic and diabetes‐specific medical variables. Conclusion Replication and extended validation of the psychosocial taxonomy into primary care may allow healthcare workers to supplement medical treatments with psychosocial interventions that can improve outcomes for patients with diabetes that are practical, individually tailored, and cost‐effective.     

Adenosine plasma concentration in pulmonary hypertension.

OBJECTIVE: In this study, we sought to appreciate the role of adenosine in the regulation of pulmonary vascular tone, especially in the case of clinical pulmonary hypertension, by investigating the relationship between endogenous plasma adenosine levels and pulmonary artery vasoconstriction. METHODS: Adenosine plasma concentrations, were measured simultaneously in the distal right pulmonary artery and in the femoral artery, both at steady state (room air) and during pure oxygen inhalation. Three clinical situations were considered: (1) normal hemodynamics [7 control subjects, mean pulmonary artery pressure (MPAP) = 18.5 +/- 1 mm Hg], (2) moderate pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD), (8 patients, MPAP = 31 +/- 3 mm Hg), (3) severe primary pulmonary hypertension (PPH), (8 patients, MPAP = 70 +/- 5 mm Hg). RESULTS: In every instance, adenosine evaluated by HPLC was higher in the pulmonary than in the systemic circulation. For room air, adenosine plasma concentrations were significantly lower in COPD (0.49 +/- 0.16 mumol l-1) and PPH patients (0.45 +/- 0.14 mumol l-1) than in controls (1.26 +/- 0.12 mumol l-1). During O2 administration, adenosine plasma concentrations all decreased but more so in COPD and PPH patients. The significant correlations between adenosine plasma concentrations and both pulmonary vascular resistance and PvO2, in controls, were not found in COPD or PPH patients. CONCLUSION: The adenosine plasma concentrations in the pulmonary circulation of PPH and COPD patients are low, and may contribute to pulmonary artery hypertension.     

Serotonin and anaesthesia

Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine neurotransmitter(Fig. 1) synthesized in serotonergic neurones in the centralnervous system (CNS), enterochromaffin cells in the gastrointestinaltract, and platelets. 5-HT is involved in a number of physiological systems of relevanceto the anaesthetist, including vascular reactivity, bronchomotortone, platelet aggregation, pain modulation, and nausea andvomiting. The exact sites and modes of action of 5-HT remainill-defined and elusive. Many patients presenting for anaesthesia are taking medicationswith 5-HT agonist or antagonist activity. There is the potentialfor interaction with drugs administered in the perioperativeperiod that modulate 5-HT activity. Toxic effects of excessiveCNS 5-HT concentrations can precipitate intensive care unit(ICU) admission.