Mechanism for homologous downregulation of thromboxane A2 receptors in cultured human chronic myelogenous leukemia (K562) cells.

Desensitization of the biologic response to thromboxane A2 (TXA2) mimetics has been observed ex vivo in human platelets due to TXA2 receptor uncoupling and downregulation. To define more clearly the mechanisms of homologous TXA2 receptor downregulation, the effects of the TXA2 mimetics U44069 ([15S)-hydroxy-9,11- (epoxymethano) prostadienoic acid] and I-BOP ([1S-(1 alpha 2 beta(5Z),3 alpha(1E,3S),4 alpha))-7-[3-(3-hydroxy-4- (p-iodophenoxy)-1-butenyl)-7-oxabicyclo[2.2.1]heptan-2-yl]-5 -heptenoic acid) on receptor-mediated calcium fluxes and on ligand binding to TXA2 receptors were studied in the K562 cultured human leukemic cell line which possesses many platelet characteristics. Incubation with U44069 resulted in a time-dependent decrease in the amplitude of TXA2 receptor-mediated intracellular free calcium transients. Under the same conditions, binding of [125I] BOP demonstrated a concurrent loss of K562 plasma membrane binding sites to approximately one-third the original number. The loss of [125I]BOP binding was prevented by coincubation with the TXA2 antagonist SQ29548 ([1S-1 alpha,2 beta (5Z), 3 beta,4 alpha]-7- (3-[2-[phenylamino)-carbonyl) hydrazino) methyl)-7-oxabicyclo-(2.2.1)- heptan-2-yl)-5-heptenoic acid]) and was reversed upon removal of U44069 from the culture medium. SQ29548 alone had no affect on receptor density or affinity. Loss of surface receptors was demonstrated to be mediated by agonist-occupied receptor internalization which was inhibited by incubation at 4 degrees C and did not occur with antagonist occupation. The results indicate that homologous downregulation of TXA2 receptors in K562 cells occurs by agonist-mediated active internalization of plasma membrane TXA2 receptors.     

A multidisciplinary treatment approach to postpartum psychoses.

Psychosis after childbirth occurs as a result of unique developmental and social demands. The authors have developed a treatment approach for the management of postpartum psychotic mothers admitted with their babies, based on their experience on an acute psychiatric inpatient unit with a special interest in the treatment of postpartum disorders. Five phases of the acute illness and recovery process are outlined. For each phase, a typical clinical situation, the specific tasks of the phase, and special problem areas are presented. The management guidelines are based on a multidisciplinary team and phase-oriented approach.     

Ultrastructure of aberrant serotonin-immunoreactive fibers in the caudate putamen complex of the aged rat

Degeneration of neurons in the central nervous system is associated with morphological changes. Previous observations made at the light microscopical level indicated degeneration of serotonin-immunoreactive (IR) fibers in the aged rat brain. In this study, a comparison at the ultrastructural level was made between serotonin-IR normal thin and aberrant swollen varicose fibers in the caudate-putamen complex of the aged rat. Ultrastructural features such as the size and content of the thin varicose fibers resembled those in the caudate-putamen complex of the young rat as reported by others. The aberrant profiles were swollen, reaching a size of 6 microns. Their vesicles varied in size and were no longer uniformly round. Moreover, distorted mitochondria and membrane-filled vacuolelike structures were a common feature of the aberrant profiles. These changes are indicative of a degenerative process and give further evidence that, whereas many serotonergic fibers are preserved at high age, other serotonergic fibers are degenerating in the caudate-putamen complex of the aged rat.     

CNQX, a new non-NMDA receptor antagonist, reduces spike wave discharges in the WAG/Rij rat model of absence epilepsy.

The effects on seizures, EEG and behavior of the non-NMDA receptor antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), were studied in the WAG/Rij rat with absence epilepsy. Intracerebroventricular injections (10, 50, and 100 nmol/5 microliters CNQX) showed that CNQX decreases the number of spike wave discharges in a dose-dependent way. Coinjection of CNQX (100 nmol/5 microliters) and AMPA (0.1 pmol/5 microliters), kainic acid (0.01 nmol/5 microliters) or NMDA (50 pmol/5 microliters) attenuated the CNQX response, indicating that CNQX acts on both non-NMDA and NMDA receptors. The observed effects appear to be specific manipulations of the epilepsy not mediated by behavioral changes.     

“Panic-like” symptomatology in schizophrenic and schizoaffective patients with postpsychotic depression: Observations and implications

Approximately one quarter of a series of 45 schizophrenic and schizoaffective patients with operationally diagnosed episodes of postpsychotic depression were also found to have anxiety symptoms consistent with the panic-attack syndrome. The incidence of such attacks was distributed across all demographic groups. Heuristic and treatment implications of this observation are considered.     

A trial of prophylactic thiotepa or mitomycin C intravesical therapy in patients with recurrent or multiple superficial bladder cancers

There were 40 consecutive patients with recurrent or multiple superficial stage Ta or T1 transitional cell cancer assigned randomly to receive prophylactic thiotepa or mitomycin C intravesical chemotherapy. Patients received 8 weekly instillations followed by 22 monthly treatments of either 60 mg. thiotepa or 40 mg. mitomycin C. Of 25 patients randomized to receive mitomycin C 4 had recurrence in a total of 337 patient-months (1.19 per 100 patient-months), while disease recurred in 1 of 15 patients randomized to receive thiotepa who were followed for a total of 220 patient-months (0.45 per 100 patient-months). No significant difference in recurrence rate was noted for either drug group (p equals 0.18). Toxicity requiring cessation of therapy was observed in 7 patients (28 per cent) on mitomycin C and none on thiotepa.     

The role of somatic complaints in the diagnosis of depression in children and adolescents

The question of whether somatic complaints are a significant feature of depression independent of anxiety was explored. Structured interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children) and Child Behavior Checklist data from depressed and nondepressed psychiatric controls were analyzed to explore the interaction of somatic complaints, anxiety, and depression. Seventy percent of the children who met criteria for depression also had significant somatic complaints in contrast to 34% of the controls. Findings revealed that frequency of somatic complaints increased with severity of depression regardless of coexisting anxiety.