Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorder.

BACKGROUND: Altered serotonergic function is thought to play a role in the pathophysiology of major depressive episodes based upon evidence from neuroimaging, pharmacological, postmortem and genetic studies. It remains unclear, however, whether depressed samples that differ with respect to having shown a unipolar versus a bipolar illness course also would show distinct patterns of abnormalities within the serotonergic system. The current study compared serotonin transporter (5-HTT) binding between unipolar-depressives (MDD), bipolar-depressives (BD) and healthy-controls (HC) to assess whether the abnormalities in 5-HTT binding recently found in depressed subjects with BD extend to depressed subjects with MDD. METHODS: The 5-HTT binding-potential (BP) measured using positron emission tomography (PET) and [(11)C]DASB was compared between unmedicated, depressed subjects with MDD (n = 18) or BD (n = 18) and HC (n = 34). RESULTS: Relative to the healthy group both MDD and BD groups showed significantly increased 5-HTT BP in the thalamus (24%, 14%, respectively), insula (15%) and striatum (12%). The unipolar-depressives had elevated 5-HTT BP relative to both BD and HC groups in the vicinity of the periaqueductal gray (PAG, 20%, 22%, respectively). The bipolar-depressives had reduced 5-HTT BP relative to both HC and MDD groups in the vicinity of the pontine raphe nuclei. Depression-severity correlated negatively with 5-HTT BP in the thalamus in MDD-subjects. CONCLUSIONS: The depressed phases of MDD and BD both were associated with elevated 5-HTT binding in the insula, thalamus and striatum, but showed distinct abnormalities in the brainstem. The latter findings conceivably could underlie differences in the patterns of illness symptoms and pharmacological sensitivity observed between MDD and BD.     

Cellular plasticity cascades in the pathophysiology and treatment of bipolar disorder.

Bipolar disorder (BPD) is characterized by recurrent episodes of disturbed affect including mania and depression as well as changes in psychovegetative function, cognitive performance, and general health. A growing body of data suggests that BPD arises from abnormalities in synaptic and neuronal plasticity cascades, leading to aberrant information processing in critical synapses and circuits. Thus, these illnesses can best be conceptualized as genetically influenced disorders of synapses and circuits rather than simply as deficits or excesses in individual neurotransmitters. In addition, commonly used mood-stabilizing drugs that are effective in treating BPD have been shown to target intracellular signaling pathways that control synaptic plasticity and cellular resilience. In this article we draw on clinical, preclinical, neuroimaging, and post-mortem data to discuss the neurobiology of BPD within a conceptual framework while highlighting the role of neuroplasticity in the pathophysiology and treatment of this disorder.     

5-Fluorouracil versus 5-fluorouracil plus {alpha}-interferon as treatment of metastatic colorectal carcinoma. A randomized study

BACKGROUND:: In 1989, S. Wadler reported very promising results (76% responserate) with a combination of 5-fluorouracil (5-FU) plus     

Origin and Recovery of Colony-forming Units in Locally Curetted Bone Marrow of Mice

Histologic study of locally curettedbone marrow showed a sequence ofblood clot formation, displacement ofthe clot by a primitive reticular tissue,and hematopoietic regeneration. Histologic regeneration of sinusoidal vessels, and recovery was incomplete 12wk later with increased fat, residualtrabecular bone, and cystic areas. Recovery of colony-forming units (CFU)paralleled hematopoietic cellular recovery and did not exceed levels of70% of normal by 12 wk postcurettage.Transplantation of cureted and irradiated mice with T₆T₆ marker chromosomes demonstrated that cells withmarker chromosomes migrated readilyinto irradiated marrow but were excluded from the curetted marrow for 2wk after curettage. Three weeks after,curettage marker cells gained readyaccess to curetted marrow. The earlyexclusion but later appearance oftransplanted marker cells was correlated with the early absence and laterregeneration of sinusoidal vessels. Thehistologic and cytogenetic studies support the concept of a dependence ofhematopoiesis upon a sinusoidal system with an appropriate marrow microenvironment. These studies supportthe concept of a local origin of marrowregeneration within curetted cavitiesbut do not indicate whether the hematopoietic tissue originates from smallnumbers of residual CFU surviving curettage or from multipotential reticularcells. There was no evidence of astimulatory effect upon uncurettedmarrow by the action of curettage.

Submitted on May 20, 1971 Revised on August 13, 1971 Accepted on September 16, 1971     

Intracellular killing of Candida albicans by human polymorphonuclear leucocytes: comparison of three methods of assessment

Three different methods, [3H]uridine uptake, viable count and 51Cr-release were used to assess the intracellular survival of a strain of Candida albicans, 19321, which was lethal for mice injected intravenously. Intracellular survival 1 h after ingestion ranged from 50 to 80% depending on the method employed and the detergent used to lyse the phagocytes. Inhibition of uridine uptake by detergents used to lyse the phagocytes led to difficulty in assessment of intracellular killing by this method.