A mutation correcting the DNA interaction defects of a mutant phage lambda terminase, gpNu1 K35A terminase

Terminase, the DNA packaging enzyme of bacteriophage lambda, is a heteromultimer composed of gpNu1 (181 aa) and gpA (641 aa) subunits, encoded by the lambda Nu1 and A genes, respectively. Similarity between the deduced amino acid sequences of gpNu1 and gpA and the nucleotide binding site consensus sequence suggests that each terminase subunit has an ATP reactive center. Terminase has been shown to have two distinct ATPase activities. The gpNu1 subunit has a low-affinity ATPase stimulated by nonspecific DNA and gpA has a high-affinity ATPase. In previous work, a mutant terminase, gpNu1 K35A holoterminase, had a mild defect in interactions with DNA, such that twofold increased DNA concentrations were required both for full stimulation of the low-affinity ATPase and for saturation of the cos cleavage reaction. In addition, the gpNu1 K35A terminase exhibited a post-cleavage defect in DNA packaging that accounted for the lethality of the Nu1 K35A mutation [Y. Hwang and M. Feiss (1997) Virology 231, 218-230]. In the work reported here, a mutation in the turn of the putative helix-turn-helix DNA binding domain has been isolated as a suppressor of the gpNu1 K35A change. This suppressor mutation causes the change A14V in gpNu1. A14V reverses the DNA-binding defects of gpNu1 K35A terminase, both for stimulation of the low-affinity ATPase and for saturation of the cos cleavage defect. A14V suppresses the post-cleavage DNA packaging defect caused by the gpNu1 K35A change.     

Gabapentin in the acute treatment of refractory bipolar disorder

Background: Gabapentin, a new anti-epileptic agent, has been anecdotally reported to be effective in the treatment of mania. We systematically assessed the response rate in bipolar patients being treated adjunctively with gabapentin for manic symptoms, depressive symptoms, or rapid cycling not responsive to standard treatments.
Method: Twenty-eight bipolar patients experiencing manic (n=18), depressive (n=5), or rapid-cycling (n=5) symptoms inadequately responsive to at least one mood stabilizer were treated in an open fashion with adjunctive gabapentin. Illness response was assessed using the Clinical Global Impression Scale modified for bipolar disorder (CGI-BP). A 'positive response' was operationalized as a CGI response of much or very much improved.
Results: Fourteen of the 18 (78%) treated for hypomania or mania had a positive response to a dosage range of 600–3600 mg/day. Patients with hypomania responded fastest, with a positive response achieved in 12.7±7.2 days. Patients with classic mania had a mean time to positive response of 25±12 days, and in patients with mixed mania it was 31.8±20.9 days. All of the five patients treated for depression had a positive response within 21±13.9 days. Only one of five patients with rapid cycling had a positive response. Gabapentin was well tolerated by all patients, with the most common side-effect being sedation.
Conclusions: Gabapentin appears to have acute anti-manic and anti-depressant properties as an adjunctive agent for refractory bipolar illness. Prospective double-blind studies are needed to further delineate its acute efficacy when used as monotherapy and its prophylactic efficacy as monotherapy or in conjuction with other mood stabilizers.     

Simple scintigraphic parameters with Tc-99m galactosyl human serum albumin for clinical staging of chronic hepatocellular dysfunction

Technetium-99m labeled diethylenetriaminepentaacetic acid (DTPA)-galactosyl human serum albumin (GSA) has been used for hepatocellular functional evaluation. This study proposed new and simple parameters to overcome the limitations of conventional parameters, and they were applied to the clinical staging of chronic liver dysfunction. The study group consisted of 93 patients including 81 with liver dysfunction and 12 control patients. In addition to the two conventional parameters, namely, receptor index (LHL15 = liver count divided by the sum of liver and heart counts at 15 minutes) and clearance index (HH15 = heart count at 15 minutes divided by the heart count at 3 minutes), 6 new parameters for Tc-99m GSA uptake and clearance were generated. The conventional receptor index of LHL15 showed a large variation depending on the size of region of interest (ROI) over the heart. The LHL15 normalized by the ROI size (nLHL15) showed more stable data and a better separation of mild liver dysfunction. A hyperbolic relationship between the LHL15 and HH 15 changed to a linear relationship by using the nLHL15 index. The combination of the liver to heart average count ratio at 15 minutes (LH 15) and T-half (minute) of the heart count also could differentiate each stage well. In conclusion, the use of the ROI-area normalized nLHL is recommended instead of the conventional LHL15. The indices of LH15 and T-half could be alternatively used as practical parameters for clinical staging in liver function.     

Hemiballismus-hemichorea in older diabetic women: a clinical syndrome with MRI correlation

Eight older women from two different continents, all with nonketotic hyperglycemia, presented with hemiballismus-hemichorea (HB-HC) and high signal intensity in the contralateral striatum on T1-weighted MRI scans. Correction of underlying hyperglycemia and supportive care resulted in resolution within days to weeks. This characteristic clinicoradiologic picture suggests a clinical syndrome with benign outcome.     

Social interactions of high school students with mental retardation and their general education peers

The informal social interaction behavior that is typical of a high school lunchroom in which general and special education students are physically included was described. Using systematic observation and social comparison methods, we compared the performance of two groups of students (12 general education students and 12 students with mental retardation). Both similarities and differences were found in the interactions of students with mental retardation and their general education peers with respect to social behaviors, conversational topics, and context within which interactions occurred. However, despite being in proximity, students with mental retardation rarely interacted with any of approximately 500 general education students present in the lunchroom. Implications are discussed for increasing social interaction among high school students.     

The Lancaster red-green test before and after occlusion in the evaluation of incomitant strabismus.

BACKGROUND: Patients with incomitant strabismus can often fuse in a limited area of gaze. Prolongation of neurologically learned fusional vergence tone ("vergence adaptation") in and near this area can result in misleading measurements with standard clinical measures of strabismus. Monocular occlusion for at least 30 minutes eliminates most of the effect of vergence adaptation. The Lancaster red-green test provides an elegant and convenient map of incomitant strabismus. We investigated the efficacy of the Lancaster red-green test before and after monocular occlusion for the investigation of incomitant strabismus. METHODS: We retrospectively studied the results of the Lancaster red-green test in 6 patients with incomitant vertical strabismus in whom we suspected that vergence adaptation might be distorting the pattern of deviation. The test was performed before and after monocular occlusion for 30 to 60 minutes, and the preocclusion and postocclusion results were compared. RESULTS: In the 6 cases studied, the Lancaster red-green test showed at least a 5-PD increase in the hyperdeviation, after monocular occlusion. The increases were mostly in primary gaze and downgaze, which tended to regularize the pattern of deviation. CONCLUSIONS: The combination of monocular occlusion and the Lancaster red-green test is useful for uncovering the effect of vergence adaptation. Such results may often simplify the planning of surgical correction because the incomitance usually decreases after monocular occlusion, making it less likely that surgery will worsen the alignment in the area previously fused. We recommend that monocular occlusion should be considered when planning surgery or even prism correction for incomitant deviations, especially when the initial Lancaster red-green test shows an unexpected incomitant pattern where there is fusion in 1 direction of gaze but not in others.     

The relationship between stereopsis and monocular optokinetic optokinetic nystagmus after infantile cataracts.

PURPOSE: Visual deprivation disrupting binocular development, such as that occurring with congenital cataract, is reported to cause asymmetric monocular optokinetic nystagmus (MOKN), as well as poor sensory and motorfusional outcome. We wanted to determine if symmetric MOKN could develop in cases of congenital cataract with good fusional outcome. METHODS: We tested MOKN (with video and electro-oculographic recordings) and stereoacuity on 5 patients with good visual acuity and satisfactory ocular alignment after surgery for congenital cataract. RESULTS: Stereoacuity was better than 50 seconds of arc in 1 case of monocular cataract and 2 cases of bilateral cataract. These case patients had symmetric MOKN. In a monocular cataract case, symmetric MOKN was observed in spite of questionable stereoacuity (at least 500 arc/s). One patient showed asymmetric MOKN, despite good visual acuity, and stereoacuity of 200 arc/s. CONCLUSIONS: Patients with congenital cataract can have symmetric MOKN and good stereopsis. These cases suggest that MOKN symmetry develops along with good stereopsis, but the quality of stereopsis necessary for development of MOKN symmetry remains unclear.     

(-)-Epiafzelechin: cyclooxygenase-1 inhibitor and anti-inflammatory agent from aerial parts of Celastrus orbiculatus.

An inhibitor of cyclooxygenase (COX)-1 activity of prostaglandin H2 synthase was isolated from aerial parts of Celastrus orbiculatus Thunb. (Celastraceae), an oriental folk medicine for rheumatoid arthritis by activity-guided column chromatographic methods. The COX inhibitor was identified as (-)-epiafzelechin, a member of flavan-3-ols by the structural analysis with HR-EI-mass, 1H-NMR and 13C-NMR spectral data. The compound exhibited a dose-dependent inhibition on the COX activity with an IC50 value of 15 microM. (-)-Epiafzelechin exhibited about 3-fold weaker inhibitory potency on the enzyme activity than indomethacin as a positive control. (-)-Epiafzelechin exhibited significant anti-inflammatory activity on carrageenin-induced mouse paw edema when the compound (100 mg/kg) was orally administrated at 1 h before carrageenin treatment.     

Effect of DW2282 on the induction of methemoglobinemia, hypoglycemia or WBC count and hematological changes

DW2282,(S)-(+)-4-phenyl-1-[1-(4-aminobenzoyl)-indoline-5-sulfonyl] -4,5-dihydro-2-imidazolone hydrochloride, is a new anticancer agent which is thought to exhibit a characteristic mechanism of action in the inhibition of tumor growth. In this study, we estimated the toxicities of DW2282 in mice. When mice were orally dosed for five consecutive days at the dosages of 50, 100 and 150 mg/kg, DW2282 did not induce methemoglobinemia and hypoglycemia at any of these doses. However, increased ALT and AST values were observed in the 150 mg/kg dosing group, and white blood cells (WBC) were significantly decreased at all doses. However, the changes in WBC count, ALT and AST immediately reversed after the cessation of drug administration. In addition, we found that DW2282 did not cause an increase in hemolysis in human blood. Taken together, these data suggested that DW2282 may have a relatively low level of toxicity, and that there may be a quick recovery from any toxicity it does produce.     

Cytokines predict coronary aneurysm formation in Kawasaki disease patients

In this study, we measured serially the serum levels of cytokines including interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R) and tumour necrosis factor (TNF-) in 60 patients with Kawasaki disease (KD) and evaluated the clinical significance of these cytokines in predicting coronary aneurysm formation. Of the 60 patients, 12 were complicated with coronary aneurysm. Blood samples were collected within the 1st week after onset of fever, then once a week for the 1st month, and once a month for another 5 months. The serum levels of IL-6, IL-8, sIL-2R and TNF were measured using an ELISA or RIA method. Our results show that the changes in serum IL-6 and IL-8 were faster than those of sIL-2R and TNF. Within the 1st week, the serum levels of IL-6 and IL-8 were significantly higher in the patients with than in those without coronary aneurysm (P<0.001). In addition, the serum levels of IL-6 and IL-8 obtained in the 1st week were highly correlated (P<0.001) with those of C-reactive protein and erythrocyte sedimentation rate, and the serum levels of sIL-2R and TNF were also increased at the 1st week reaching the highest level in the 2nd week. In the 2nd week, the serum levels of sIL-2R and TNF were significantly higher in the patients with than in those without coronary aneurysm (P<0.05). These findings suggest that the serum levels of IL-6 and IL-8 obtained in the 1st week may serve as useful parameters in predicting coronary aneurysm formation in KD patients.