SLASH: a program for analysing the functional groups in molecules

The authors examined the impact of a number of job stressors, including sexual harassment and gender-based discrimination, on female construction workers' level of job satisfaction and psychological and physical health. Results from a telephone survey with 211 female laborers indicated that having responsibility for others' safety and having support from supervisors and male coworkers was related to greater job satisfaction. Increased reported psychological symptoms were also related to increased responsibility, as well as skill underutilization, experiencing sexual harassment and gender-based discrimination from supervisors and coworkers, and having to overcompensate at work. Perceptions of overcompensation at work and job uncertainty were positively associated with self-reports of insomnia. Finally, sexual harassment and gender discrimination were positively related to reports of increased nausea and headaches.     

Neuropsychological and motor functioning after unilateral anatomically guided posterior ventral pallidotomy. Preoperative performance and three-month follow-up

This study presents baseline and 3-month follow-up motor and neuropsychological data for 22 patients with Parkinson's disease (PD) who underwent anatomically guided unilateral posterior ventral pallidotomy (PVP). Postsurgical improvements were seen in psychomotor speed, fine motor accuracy, and dyskinesia, whereas grip strength decreased on the side contralateral to the surgery. No change was detected in overall level of cognitive functioning, nor were changes demonstrated in memory, language, or working memory when the entire sample of patients was evaluated. When the group was divided on the basis of side of surgery, patients with left-sided pallidotomies showed a decline in verbal fluency. Patients and caregivers reported improvement in psychosocial functioning. These initial findings of improved motor performance and largely unaffected cognitive functions are consistent with results obtained with functional PVP and provide support for the use of anatomically guided posterior ventral pallidotomy in the treatment of motor symptoms of PD.     

Nickel-titanium versus stainless-steel finger spreaders in curved canals

Fibro-osseous lesions of the sinonasal region are relatively frequent, but those strictly confined to the nasal cavity are rare. We report an atypical fibro-osseous lesion in the nasal cavity and describe its radiological features. The differential diagnosis is discussed.     

Calcium currents and calcium signaling in rod bipolar cells of rat retinal slices

Combined electrophysiological and imaging techniques were used to study calcium currents (ICa) and their sites of origin at rod bipolar cells in rat retinal slices. We report here for the first time the successful whole-cell patch-clamp recording from presynaptic boutons that were compared with somatic recordings. TTX-resistant inward currents were elicited in response to depolarization. The kinetic and pharmacological properties of ICa were very similar for recordings obtained from the soma and the presynaptic terminals. ICa activated maximally between -30 and -20 mV was enhanced by Bay K 8644 and was blocked by isradipine and nifedipine. Peak amplitude and time to peak were -31.3 +/- 1.2 pA and 3.2 +/- 0.2 msec with somatic recordings (n = 54), whereas the corresponding values were -31.6 +/- 6.1 pA and 3.2 +/- 0.7 msec in recordings obtained directly from terminals (n = 6). ICa showed little inactivation during sustained depolarizations. No T-type ICa was observed with depolarizations from -90 mV. Concomitant with Ca2+ entry, depolarization induced the appearance of transient outward currents that resembled IPSCs and were blocked by GABA and glycine receptor antagonists, suggesting that they arise from activation of amacrine feedback synapses. Upon depolarization, intracellular Ca2+ ([Ca2+]i) rises were restricted to the presynaptic terminals with no somatic or axonal changes and were linearly dependent on pulse duration when using a low-affinity Ca2+ indicator. In cone bipolar cells, ICa inactivated markedly, and [Ca2+]i rises occurred in the axon, as well as in the presynaptic terminals.     

Conformal proton therapy for prostate carcinoma

The suppression of apoptosis may contribute to the carcinogenicity of the peroxisome proliferators (PPs), a class of non-genotoxic rodent hepatocarcinogens. Our previous work demonstrated that the PP nafenopin suppressed both spontaneous and transforming growth factor beta1 (TGFbeta1)-induced hepatocyte apoptosis both in vivo and in vitro. Here, we extend these observations by demonstrating the ability of nafenopin to suppress apoptosis induced by other major candidates for the signalling of cell death in the liver. Treatment of rat or mouse hepatocyte monolayers with TGFbeta1 or the DNA damaging drugs etoposide or hydroxyurea induced high levels of apoptosis. Western blot analysis did not support a role for either p53 or p21waf1 in etoposide-induced apoptosis in rat hepatocytes. Treatment of mouse hepatocytes with an agonistic anti-Fas antibody also resulted in an induction of high levels of apoptosis. Pre-addition and continued exposure to nafenopin suppressed apoptosis induced by all three stimuli. Overall, our studies demonstrate that the ability of nafenopin to protect hepatocytes from apoptosis is not restricted to species or apoptotic stimulus. It is possible, therefore, that the PPs may suppress apoptosis by acting on diverse signalling pathways. However, it seems more likely that nafenopin suppresses hepatocyte apoptosis elicited by each death stimulus by impinging on a core apoptotic mechanism.     

RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs

RasGRP, a guanyl nucleotide-releasing protein for the small guanosine triphosphatase Ras, was characterized. Besides the catalytic domain, RasGRP has an atypical pair of "EF hands" that bind calcium and a diacylglycerol (DAG)-binding domain. RasGRP activated Ras and caused transformation in fibroblasts. A DAG analog caused sustained activation of Ras-Erk signaling and changes in cell morphology. Signaling was associated with partitioning of RasGRP protein into the membrane fraction. Sustained ligand-induced signaling and membrane partitioning were absent when the DAG-binding domain was deleted. RasGRP is expressed in the nervous system, where it may couple changes in DAG and possibly calcium concentrations to Ras activation.     

In vivo assessment of neovascularization of liver metastases using perfusion CT

Neovascularization of tumours produces a high microvessel density. Although diagnostic imaging is unable to visualize microvessels directly, it is possible to demonstrate associated changes in tissue perfusion. The aim of this study was to use the quantitative functional information and high spatial resolution of perfusion computed tomography to study neovascularization of hepatic metastases. Perfusion CT was performed in 13 patients with hepatic metastases from various primary tumours. Arterial perfusion was measured in the metastasis; both arterial and portal perfusion were measured in a small rim of liver tissue immediately adjacent to the metastasis. Perfusion measurements were correlated against survival of the patient in nine cases. Arterial perfusion was increased above normal values, both in the metastasis (median: 0.62 ml min-1 ml-1; range: 0.26-3.05 ml min-1 ml-1) and in the adjacent liver (median: 0.51 ml min-1 ml-1; range: 0.14-1.60 ml min-1 ml-1). Portal perfusion of adjacent liver was highly variable (median: 0.30 ml min-1 ml-1; range: 0.05-1.85 ml min-1 ml-1). Arterial perfusion was positively correlated with portal perfusion within liver tissue adjacent to metastases (p < 0.05, r = 0.58), a reversal of the normal situation. Survival of the patient correlated with arterial perfusion within the metastasis (p < 0.05, r = 0.69) but more closely with arterial perfusion in the adjacent liver (p < 0.02, r = 0.78). In conclusion, alterations in perfusion within metastases and adjacent liver are in accordance with the histological features of neovascularization. Perfusion CT offers a method for studying neovascularization in the living patient and offers prognostic information.     

Androgen receptor and mating-induced fos immunoreactivity are co-localized in limbic and midbrain neurons that project to the male rat medial preoptic area

The repair of DNA damage protects the genome of the cell from the insults of cancer causing agents. This was originally demonstrated in individuals with the rare genetic disease, xeroderma pigmentosum, the prototype of cancer genes, and subsequently in the relationship of mismatch repair to colon cancer. Recent studies suggest that individuals with less dramatic reductions in the capacity to repair DNA damage are observed at polymorphic frequency and these individuals have an increased susceptibility to several types of cancer. Screening of individuals for DNA sequence variation in the exons of 9 DNA repair genes has resulted in identification of 15 different polymorphic amino acid substitution variants. Although the studies to relate these variants to reduced DNA repair capacity and cancer status have not been completed, the available information is sufficient to suggest that DNA repair genes should be incorporated into molecular epidemiology and cancer susceptibility studies. The availability of molecular epidemiology data presents exciting opportunities for refinement of risk estimation models and identification of individuals at increased risk of disease, with resultant opportunities for effective surveillance and early intervention and treatment. The opportunities to acquire susceptibility data are associated with possible perils for establishment of regulations for permissible exposures to carcinogenic agents and also stigmatization of 'at risk' individuals that may result in decreased access to employment opportunities and health care.     

Attention-deficit hyperactivity symptomatology after traumatic brain injury: a prospective study

OBJECTIVE: To study prospectively the course of attention-deficit hyperactivity (ADH) symptomatology in children and adolescents after traumatic brain injury (TBI). It was hypothesized that ADH symptomatology would be significantly related to severity of injury. METHOD: Subjects were children (n = 50) aged 6 to 14 years at the time they were hospitalized after TBI. The study used a prospective follow-up design. Assessments of preinjury psychiatric, behavioral, socioeconomic, family functioning, and family psychiatric history status were conducted. Severity of injury was assessed by standard clinical scales, and neuroimaging was analyzed. RESULTS: The main finding of this study was that change in ADH symptomatology in the first 2 years after TBI in children and adolescents was significantly related to severity of injury. Overall ADH symptomatology during the study was significantly related to a measure of family dysfunction when family psychiatric history, socioeconomic status, and severity of injury were controlled. CONCLUSION: The presence of a positive "dose-response" relationship between severity of injury and change in ADH symptoms, present from the 3-month assessment, was consistent with an effect directly related to brain damage.     

Antiestrogen stimulated human endometrial cancer growth: laboratory and clinical considerations

The new antiestrogen toremifene (TOR) is currently on the market for the treatment of advanced breast cancer in postmenopausal women. TOR is known to exhibit a similar efficacy profile as tamoxifen (TAM) in the treatment of advanced breast cancer and there are studies to suggest that the beneficial side effects of TAM on bone and blood lipids are also achieved with TOR. However, the data concerning the action of TOR on the endometrium is sorely lacking. In light of the estrogenic effect of TAM on the uterus and the 2-3-fold increased incidence in endometrial carcinoma detected in patients receiving TAM therapy, it is imperative to investigate the effect of TOR on endometrial carcinoma. We compared the actions of TAM and TOR on the EnCa101 human endometrial tumor model and find that both antiestrogens have similar growth stimulatory effects. To investigate a potential mechanism of antiestrogen-stimulated endometrial tumor growth, we have examined known activators of the AP-1 signal transduction pathway, the protein kinase C (PKC) family of isozymes, in the EnCa101 human endometrial tumor model. We find that increased PKC isozyme expression correlates with hormone-independent breast cancer as well as antiestrogen-stimulated endometrial cancer.