Ropinirole for restless legs syndrome

Restless legs syndrome (RLS) is a common and underdiagnosed condition that results in a desire to move the extremities often associated with paresthesia/dysesthesia, motor restlessness, worsening of symptoms at rest with at least temporary relief by activity, and worsening of symptoms in the evening or night. We tested the new dopamine agonist ropinirole in 16 patients with RLS in an open-label trial. The mean daily dose was 2.8+/-2.3 mg (range, 0.5-12.0). The 13 patients who completed the study reported a 58.7% improvement (p = 1.08 x 10(-8)) as judged by the abbreviated International Restless Legs Study Group questionnaire. Three patients discontinued the medication secondary to adverse events (rash and nervousness) and other extenuating circumstances. These encouraging preliminary results justify larger and more controlled trials of ropinirole in patients with RLS.     

Development of alarm-call responses in Belding's ground squirrels: the role of dams

Experiences with adult conspecifics can influence the ontogeny of species-typical behaviours in naive young of many species. Two processes of influence, direct and indirect, are proposed to describe the effect of adult behaviours on juvenile development. In Belding's ground squirrels, Spermophilus beldingiexposure to adults experienced with responding to alarm calls may affect how juveniles respond to calls and/or the rate at which juveniles acquire adult-like responses to calls. Because dams and their juvenile offspring interact extensively during early development, the influence of dams on the ontogeny of juvenile alarm-call responses was investigated by conducting playbacks of alarm calls and non-alarm calls to captive ground squirrels. Juveniles were more likely to respond to auditory stimuli if their dam responded, but the responses of unrelated adult females did not influence juveniles. A dam's presence at the time of a playback had no consistent effect, however, on the type of initial response made by her juvenile, its response duration or the vigilance of its postures. The permanent absence of adult models (dams) after weaning appeared to delay the rate at which juveniles developed a discrimination between alarm calls and non-alarm calls, but had no long-term influence on juveniles' expression of responses. Thus, dams indirectly influenced juvenile response development by acting as models of species-typical responses. The outcome of dams' influence was facilitative rather than inductive, because exposure to dams affected the rate of response development but was not necessary for juveniles to acquire alarm-call responses.1997The Association for the Study of Animal Behaviour     

Expression of the HGF/SF receptor, c-met, and its ligand in human colorectal cancers

To characterize the clinical features of childhood tuberculosis, we analyzed the symptoms, signs, and laboratory findings of the 89 children with tuberculosis admitted to the Yokohama City University Hospital from 1975 to 1994. Compared with the numbers of patients admitted from 1975 to 1979, those of patients of the past 5 years (from 1990 to 1994) were reduced by half. Of the 89 subjects, 56.2% were below 3 years of age and 24.7% were under 1 year of age. 51.7% had primary complex and 20.2% had serious tuberculosis (tuberculous meningitis 14.6%, miliary tuberculosis 3.4%, and bone and joint tuberculosis 2.2%). Tuberculous children below 3 years of age consisted of primary complex (60.0%) and serious tuberculosis (32.0%). The majority (86.0%) of tuberculous children below 3 years of age had not received BCG vaccination. In 55 (61.8%) of 89 subjects, the sources of tuberculosis were clarified. Of these subjects, 83.6% were infected in the family. The rate of BCG inocluation tended to decrease with decreasing age, especially that of children below 3 years of age was 14.0%. Of the 89 subjects, only 16.9% proved to be smear-positive. Taken together, in order to eliminate tuberculous children below 3 years of age, the following is necessary; (1) BCG inoculation in early infancy, (2) early diagnosis of index cases with adult tuberculosis, and (3) prompt and appropriate family contact examination.     

Detection of flunixin in greyhound urine by a kinetic enzyme-linked immunosorbent assay

Anxiety levels in a sample of 65 long-term cancer survivors were assessed in a study of the effects of a planned discharge from an oncology clinic. Thirty-one percent of patients scored > or = 8, and 12% > or = 11 on the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS), indicating that anxiety rates in patients in long-standing remission do not greatly differ from patients with active disease. Despite the provision of continued support and guaranteed fast-access return to the clinic if necessary, 28% of patients refused to be discharged. Fear that recurrence would not be detected was the reason most frequently cited. Seventy-five percent of these patients were HADS anxiety cases. A second assessment 4-5 months later of the 41 patients who were discharged showed a slight, but non-significant increase in anxiety rates suggesting that anxiety in cancer survivors may be persistent and not related to clinic attendance.     

Stepwise transplantation of an active site loop between heat-labile enterotoxins LT-II and LT-I and characterization of the obtained hybrid toxins

Members of the cholera toxin family, including Escherichia coli heat- labile enterotoxins LT-I and LT-II, catalyze the covalent modification of intracellular proteins by transfer of ADP-ribose from NAD to a specific arginine of the target protein. The ADP-ribosylating activity of these toxins is located in the A-subunit, for which LT-I and LT-II share a 63% sequence identity. The flexible loop in LT-I, ranging from residue 47 to 56, closes over the active site cleft. Previous studies have shown that point mutations in this loop have dramatic effects on the activity of LT-I. Yet, in LT-II the sequence of the equivalent loop differs at four positions from LT-I. Therefore five mutants of the active site loop were created by a stepwise replacement of the loop sequence in LT-I with virtually all the corresponding residues in LT- II. Since we discovered that LT-II had no activity versus the artificial substrate diethylamino-benzylidine-aminoguanidine (DEABAG) while LT-I does, our active site mutants most likely probe the NAD binding, not the arginine binding region of the active site. The five hybrid toxins obtained (Q49A, F52N, V53T, Q49V/F52N and Q49V/F52N/V53T) show (i) great differences in holotoxin assembly efficiency; (ii) decreased cytotoxicity in Chinese hamster ovary cells; and (iii) increased in vitro enzymatic activity compared with wild type LT-I. Specifically, the three mutants containing the F52N substitution display a greater Vmax for NAD than wild type LT-I. The enzymatic activity of the V53T mutant is significantly higher than that of wild type LT-I. Apparently this subtle variation at position 53 is beneficial, in contrast to several other substitutions at position 53 which previously had been shown to be deleterious for activity. The most striking result of this study is that the active site loop of LT- I, despite great sensitivity for point mutations, can essentially be replaced by the active site loop of LT-II, yielding an active 'hybrid enzyme' as well as 'hybrid toxin'.      

Deletion of cell division cycle 2-like 1 gene locus on 1p36 in non-Hodgkin lymphoma

Our laboratories have documented a significantly high occurrence of chromosome 1p36 rearrangements in non-Hodgkin lymphoma (NHL). The cell division cycle 2-like 1(CDC2L1) (also known as TP58 or PITSLRE) gene, a protein kinase implicated in apoptotic signaling, is located at the very distal region of chromosome 1p36 and is likely to be disrupted by structural rearrangements involving 1p36. To determine the molecular consequences of the recurrent involvement of the 1p36 region, we examined metaphases containing 1p36 abnormalities from 31 specimens derived from 26 patients for the possible deletion of CDC2L1 by fluorescence in situ hybridization (FISH) using the TP58clk-1 DNA probe. Twenty-three cases exhibited the loss of CDC2L1 from the abnormal chromosome 1. In 2 of 26 cases, the gene locus was translocated to the partner chromosome, and in four specimens, all derived from one case, CDC2L1 was not deleted. This pilot investigation suggests that 1p36 rearrangements, and consequently the loss of the CDC2L1 gene locus, is important in NHL. This work also opens avenues for further molecular studies and prognostic correlations.