Molecular genetics of acute leukaemia

The outlook for patients with acute promyelocytic leukaemia has improved vastly with the use of all-trans retinoic acid. The development of this therapeutic agent stemmed from the finding that an abnormality of the retinoic acid receptor is involved in this disease. In the search for other molecular abnormalities in the acute leukaemias that might serve as therapeutic targets, the chromosomal translocations associated with this group of disorders have been helpful in indicating where to look for potential cancer genes. Some common signal-transduction pathways through which different such genes act have been identified, and compounds that interfere with these pathways are already being screened for.     

Brain region-specific regulation of luteinizing hormone-releasing hormone messenger ribonucleic acid in the male ferret: interactions between pubertal maturation and testosterone

This study examined the regulation of LHRH messenger RNA (mRNA) during pubertal maturation and by testosterone in male ferrets. Prepubertal and postpubertal ferrets were either intact or were castrated and treated with daily injections of oil or 5 mg/kg testosterone propionate for 14 days. In situ hybridization for LHRH mRNA was performed using an 35S-labeled 48-base oligonucleotide complementary to the human LHRH-coding region. Computerized image analysis was performed on cells in the preoptic area, retrochiasmatic area, arcuate nucleus (ARC), and median eminence; cells were classified as labeled if the number of pixels representing silver grains over the cell was 5 or more times the number of background silver grain pixels. Both pubertal maturation of intact males and castration of prepubertal males resulted in an increase in the number of labeled cells in the ARC. These effects were not observed in any of the other three brain regions, suggesting that ARC LHRH-producing neurons are of primary importance in the presumed increase in LHRH release that occurs as a consequence of either pubertal maturation or castration of prepubertal males. Castration of adults did not increase the number of labeled cells in any brain area, but resulted in an increase in silver grains per labeled cell only in the preoptic area. Thus, LHRH mRNA is regulated during puberty primarily in the ARC, and the particular cell group in which LHRH mRNA is most strongly regulated by testosterone changes with pubertal maturation.     

Presence of serum anti-p53 antibodies is associated with pleural effusion and poor prognosis in lung cancer patients

This study was designed prospectively to evaluate the development of anti-p53 antibodies (Abs) in lung cancer patients in relation to their clinical outcome. Sera, derived from 125 lung cancer patients, consisting of 14 small cell lung cancers (SCLC) and 111 non-SCLCs (NSCLC), were surveyed. The p53-null human NSCLC cell line, NCI-H1299, transfected with a human mutant p53 gene was prepared as the source of p53 antigen for immunoblotting analyses to detect the presence of serum anti-p53 Abs. The control group included sera from 10 healthy adults and 14 patients with benign pulmonary diseases. Clinical data including staging and survival were recorded for statistical analyses. The anti-p53 Abs were found in 8% (10 of 125) of the lung cancer patients studied (8.1% of NSCLC versus 7.1% of SCLC patients), whereas none of the control sera had detectable anti-p53 Abs. The presence of anti-p53 Abs was closely associated with malignant pleural effusions (P = 0.001). The p53 Ab-positive patients had a worse prognosis than the p53 Ab-negative patients (P < 0.02; median survival, 20 versus 41 weeks). In both univariate and multivariate analyses, the tumor extension and probably the presence of anti-p53 Abs were significant predictors for cancer death. The development of anti-p53 Abs (n = 9) was also a predictor for poor survival in patients with malignant effusions (n = 51). In conclusion, the presence of serum anti-p53 Abs is closely associated with malignant pleural effusions in lung cancer patients. It may serve as a negative prognostic factor for survival independent of malignant pleural effusions and tumor staging.     

Frequency of recurrent lupus nephritis among ninety-seven renal transplant patients during the cyclosporine era

The catecholamine precursor l-dihydroxyphenylalanine (L-DOPA) is the primary therapeutic intervention for Parkinson's disease. Although short-term exposure (30 min) potentiates dopamine (DA) release by elevating quantal size, longer term exposure to L-DOPA (48 hr) promotes neurite outgrowth from midbrain DA neurons in culture. To characterize long term effects of L-DOPA, we used a pheochromocytoma (PC12) line that extends neurites on exposure to nerve growth factor (NGF). L-DOPA potentiated the outgrowth of processes elicited by NGF. This response did not require conversion of L-DOPA to DA, was not caused by agonist effects at DA receptors, and was not blocked by the tyrosine kinase inhibitor genistein. However, similar results were found after exposure to l-n-acetylcysteine or apomorphine, a DA receptor agonist that produces a quinone metabolite, and seemed to correlate with glutathione synthesis. Long-term process elaboration was blocked by L-buthionine sulfoximine, consistent with mediation by an antioxidant mechanism. L-DOPA potentiation of NGF response was important functionally as seen by increased quantal neurotransmitter release from the L-DOPA/NGF-treated neurite varicosities, which displayed both 2-fold greater quantal size and frequency of quantal release. These results demonstrate potentiation by L-DOPA of morphological and physiological responses to neurotrophic factors as well as synergistic induction of antioxidant pathways. Together with effects on transmitter synthesis, these properties seem to provide a basis for the compound's long term presynaptic potentiation of DA release and therapeutic actions.     

Anesthesia case of the month. Analgesia for fractures until surgery can take place

OBJECTIVE: To emphasize a potentially lethal condition that is virtually impossible to diagnose preoperatively. DESIGN: Case report with review of the literature. SETTING: University Hospital. PARTICIPANT: The patient requiring urgent surgery for heart failure related to severe aortic stenosis and mild mitral stenosis with poor ventricular function. The patient was elderly and suffered from atrial fibrillation. INTERVENTIONS: Preoperative transesophageal echocardiography followed by mitral valve repair and aortic valve replacement. MEASUREMENTS: Clinical outcome and pathological results. RESULTS: Although preoperative TEE demonstrated no left atrial appendage abnormality. After cardiac manipulation prior to the institution of cardiopulmonary bypass a large left atrial mural thrombus was mobilized from the atrial wall and was free floating in the left atrium. CONCLUSIONS: For high risk patients TEE should be applied intraoperatively to avoid undiagnosed left atrial clot dislodgement.     

A Price-Directed Approach to Real-Time Scheduling of Production Operations

Most past approaches to job shop scheduling are either highly myopic, or they are unable to adapt effectively to the stream of unforeseen disruptions that characterizes almost all manufacturing systems. We propose a two-module scheduling system that is both robust and non-myopic. Periodically a Planning Module develops a global view of what is likely to happen in die facility over the next one to four weeks. It then passes information down to the Dispatching Module. The Dispatching Module is based on microprocessors that are located on the factory floor. Whenever a machine is about to become idle, a fast optimization algorithm is run on the closest microprocessor to decide which job should be done next. The data provided by the Planning Module allows this decision to be made in a non-myopic manner.     

Responding for rewarding brain stimulation: cocaine and isradipine plus naltrexone

We recently identified a gene which shows high similarity to the beta-spectrin gene but with a different chromosomal location from either of the two known beta-spectrin genes [T. Nagase, K.-I. Ishikawa, D. Nakajima, M. Ohira, N. Seki, N. Miyajima, A. Tanaka, H. Kotani, N. Nomura, O. Ohara, Prediction of the coding sequences of unidentified human genes: VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro, DNA Res. 4 (1997) 141-150]. In order to further characterize this new spectrin gene and its product, we isolated the rat counterpart of this gene and analyzed it in terms of its protein coding sequence, the tissue distribution of its mRNA and the product, and the regional distribution of the mRNA and the product in the brain. The results indicated that this gene was most abundantly transcribed in the brain and neurons were the predominant cell-type to express this gene. In particular, Purkinje cells were the richest in this gene product, and this new form of beta-spectrin was found more prominently in the dendrites than in the cell bodies. Since the expression pattern and the subcellular localization of this gene product were quiet distinct from those of the two beta-spectrin isoforms already characterized, this beta-spectrin gene would play an important role in neuronal membrane skeleton although it has been overlooked to date.     

Visual half-field Stroop effects with spatial separation of words and color targets

Past inconsistencies in the occurrence of differential visual half-field Stroop effects were addressed in two experiments using a visual half-field presentation technique incorporating brief displays (100 ms) and a fixation task designed to ensure proper eye fixation at display onset. Experiment 1 used displays in which distractor words and color targets were presented in contralateral visual fields. Experiment 2 compared contralateral with ipsilateral displays where words and color targets appeared one above the other in the same visual field. Stroop effects were larger whenever a word occupied the right as opposed to the left visual field, regardless of whether the color target was left or right. Results are consistent with the idea that words are processed more efficiently or automatically in right visual field/left hemisphere presentations.     

Considerations for the orthopedic nurse in diagnosis and treatment of adolescent sports injuries

Injured adolescent athletes are challenging clients for the primary practitioner. Their unique physiological and psychological attributes dictate changes in traditional orthopedic practice and call for a holistic patient focus to address their varied needs. Understanding of common athletic injuries will effectively guide the practitioner's clinical evaluation and assist in recognizing those patients requiring more complex orthopedic diagnosis and care.