The effect of serotonin and serotonin antagonists on bladder cancer cell proliferation

OBJECTIVE: To investigate the role of serotonin (5-hydroxytryptamine, 5HT) and its antagonists in the proliferation of high-grade bladder cancer cells (HT1376), as high-grade bladder cancer has a rapid rate of progression, invasion and recurrence, and 5HT antagonists inhibit the growth of the prostate cancer cell line (PC3). MATERIALS AND METHODS: HT1376 (human grade III transitional cell carcinoma) cells were incubated with either 5HT or 5HT antagonists (5HT(1A), 5HT(1B), 5HT(1D), 5HT(2), 5HT(3) and 5HT(4)). After 72 h, cell viability was assessed using the crystal violet assay. The presence of 5HT receptor subtypes on HT1376 cells and sections of human bladder cancer tissue was determined by immunohistochemistry and Western blot analysis. RESULTS: 5HT caused a dose-dependent increase in the proliferation of HT1376 cells. The maximum increase in cell proliferation (12%; 12 samples, P < 0.001) was at 10(-8)m as compared to the control at 72 h. At 10(-4)m, 5HT(1A) antagonist (NAN-190 hydrobromide) and 5HT(1B) antagonist (SB224289 hydrochloride) had a 10% (12 samples, P < 0.001) and 93% (12, P < 0.001) inhibitory effect on HT1376 cell growth, respectively, compared to the control at 72 h. There was immunostaining for 5HT(1A) and 5HT(1B) receptors in HT1376 cells and malignant bladder tissue, confirming the presence of these two receptor subtypes. Western blot analysis showed the presence of 5HT(1A) and 5HT(1B) receptor proteins with bands of 46 kDa and 43 kDa, respectively. CONCLUSION: 5HT(1A) and to a greater extent 5HT(1B) antagonists significantly inhibit bladder cancer cell growth. This effect is probably mediated via the 5HT(1A) and 5HT(1B) receptors. These results highlight the potential use of 5HT(1A) and 5HT(1B) antagonists in the treatment of bladder cancer.     

Auditory pattern recognition abilities of aphasic and normal subjects: A preliminary study

A comparison of the ability of aphasic and normal subjects to recognize three element auditory patterns of duration was made under the following conditions: monaural right, monaural left; split left leading and split right leading: dichotic. There were eight possible combinations of elements for each condition. In all conditions the normal group clearly outperformed the aphasic subjects with practically no overlap in their performances. Implications of using nonlinguistic stimuli for testing aphasic individuals, assessing progress, and training in pattern recognition is discussed.     

Metabolic changes in liver of tumor-bearing mice

The hepatic contents of acetyl coenzyme A, free CoA, α-oxoglutarate, and citrate were determined in tumor-bearing mice. Significant decreases in acetyl CoA and free CoA, with a concomitant increase in citrate occurred 24 hr following inoculation of TLX-5 lymphoma cells. Similar changes occurred in mice bearing a C₃H mammary tumor, when the latter was just palpable in situ. There was some indication that in mice bearing Sarcoma 180, the size of the tumor was a factor in inducing these changes. Significant decreases in the α-oxoglutarate content of liver could only be detected in mice bearing the lymphoma or Sarcoma 180. The direction of change in the hepatic contents of acetyl CoA and citrate were opposite to those found in tumor-free animals under gluconeogenic conditions. However, significant increases in citrate would favor gluconeogenesis by inhibition of phosphofructokinase. Starvation of tumor-bearing mice failed to increase the acetyl CoA content of liver or decrease citrate. The data suggest a failure in lipolysis, as well as in the regulation of fatty acid synthesis in liver via changes in citrate.     

Treatment of compulsive rituals with visual screening: A case study with long-term follow-up

The present study reports on the use of visual screening, a mildly aversive response suppression procedure, as a treatment for reducing compulsive behaviors in a four and one-half year-old developmentally disabled boy. Two distinct patterns of compulsive responding were observed: repetitive (stereotyped) shoe-related behaviors and a ritualistic shoe-related act. The effect of visual screening on repetitive shoe-related responses was initially evaluated in a laboratory setting under A-B-A-B-B¹ experimental conditions and systematically extended to the classroom setting in multiple baseline fashion. Visual screening was also contingently applied as treatment for the shoe-related ritual, with the effects analyzed using a similar multiple baseline format across hospital residential unit and natural home settings. Results of the study indicated that visual screening was an effective treatment for suppressing both forms of the subject's compulsive responding and that it was an easily learned and administered procedure from both staff and parent perspectives. Follow-up data across 12 months were obtained and indicated that the effect of treatment was exceptionally durable.     

EEG sleep in primary depression. A longitudinal placebo study.

Characteristic EEG sleep changes in depression are highlighted by a sleep continuity disturbance, delta sleep reduction, and a shortened REM latency. Since these findings have been derived primarily from only a few baseline recordings, questions regarding their persistence and/or variability have not been previously addressed. As part of an extensive set of investigations of EEG sleep in depression, we examined nightly the sleep of 12 hospitalized, non-delusional, primary depressives who were involved in a program of active psychosocial treatment intervention and received only placebo during a 5-week study period. EEG sleep findings revealed a relative lack of change across time, particularly in those parameters reported to be associated with a primary or 'biologic' depressive episode. While some degree of clinical improvement was noted, the group failed to achieve a state of remission or even partial remission as determined by the Hamilton Rating Scale. It appears that the major sleep alterations associated with such disorders persist for up to at least 5 weeks in the absence of pharmacologic or other somatic intervention.     

Cerebrospinal fluid leakage, dural fistulae and meningitis after basal skull fractures

The pathology, clinical presentation and management of dural fistulae after basal skull fracture is discussed. A distinction is made between definite and presumptive evidence of a dural tear. Early recognition is important in order to institute prophylactic treatment. Penicillin and sulphadimidine are recommended from immediately after injury until one week after the cerebrospinal fluid leak has ceased. The indications for operative dural repair are discussed.     

Low-dose heparin in femoral neck fractures

Heparin in low doses was given by subcutaneous injection to 25 patients with femoral neck fractures; a further 26 patients acted as a control group. Deep-vein thrombosis was diagnosed by the ¹²⁵I-fibrinogen test. Thrombosis occurred in 68 per cent of patients in the heparin group and in 50 per cent of the controls. The incidence of deep-vein thrombosis was not increased when operative fixation of the fracture was delayed for more than 24 hours. It appears that the initial thrombosis may occur very soon after the fracture and as a direct response to the trauma, rather than to the operation itself.