Soft signs and neuropsychological performance in schizophrenia

S-2150 is a new 1,5-benzothiazepine derivative that inhibits [3H]diltiazem and [3H]WB4101 bindings to the membrane of rat tissue. The effects of S-2150 on ischemia/ reperfusion injury were studied in anesthetized rats. S-2150 reduced the myocardial infarct size (IS) induced by 20-min coronary artery occlusion followed by reperfusion. To evaluate reperfusion-induced ventricular tachycardia and fibrillation (VT, VF), we occluded the coronary artery for 4 min and then reperfused it. The incidence of arrhythmia was blocked by S-2150, and this effect offered protection against cardiac death. Prazosin did not modify the IS or incidence of reperfusion arrhythmias, but combined treatment with a noneffective dose of diltiazem showed significant cardioprotective effects. We also compared the direct effects of S-2150 and diltiazem on cardiac function and coronary perfusion flow using isolated rat hearts. Both drugs decreased mechanical function and increased coronary flow, with S-2150 being less cardiodepressive and more vasodilatory. S-2150 is cardioprotective at doses comparable to hypotensive doses even though its cardiodepressant effect is much weaker than that of diltiazem. This effectiveness may be partly explained by its dual characteristics: blocking the Ca channel and the alpha 1-adrenoceptor.     

Vitamin K and maintenance of skeletal integrity in adults

One important mechanical property of core composite resins is fracture toughness, KIC, which expresses serviceability in the oral cavity, such as the resistance to marginal fracture. KIC values of eight commercial core composite resins were examined by the single-edge notched-beam (S.E.N.B.) method. Two composites containing about 80 wt% Si3N4 fillers exhibited both the highest KIC value of around 2.0 MN.m-3/2 and the highest hardness value. The other six composites containing 66 to 86 wt% SiO2-based fillers had KIC values of around 1.2 to 2.0 MN.m-3/2, and there was a tendency toward higher KIC values as hardness increased. It was speculated that the clinical acceptability of core composite resins could be broadened, if dental clinicians selected composites with higher KIC values.     

Cloning of two cDNAs encoding calnexin-like and calreticulin-like proteins from maize (Zea mays) leaves: identification of potential calcium-binding domains

The U-turn (uridine turn) is an RNA structural motif that contains a change in backbone direction stabilized by specific interactions across the bend. It was first identified in the anticodon loop and the T-loop of yeast tRNA(Phe) (Quigley & Rich, 1976, Science 194:796-806) and has recently also been found in the crystal structure of the hammerhead ribozyme (Pley HW, Flaherty KM, McKay DB, 1994a, Nature 372:68-74). These U-turn motifs follow a UNR consensus sequence (where N is any nucleotide and R is G or A). Here we report that the frequently occurring GNRA tetraloops also contain a U-turn motif, and we discuss the role of U-turns as abundant tertiary structural motifs in RNA.     

Retrograde iliofemoral endarterectomy facilitated by balloon angioplasty

PURPOSE: The purpose of this study was to explore the feasibility of iliofemoral endarterectomy performed through a single groin incision. METHODS: Thirty-two patients aged 34 to 75 years (mean age 63.4 years) with a male/female ratio of 20:12 underwent 36 lower extremity inflow reconstructions from July 1989 to September 1994. Surgical indications were for limb-threatening ischemia in 24 patients and for claudication in eight patients. The procedures were done for occlusive disease of the external iliac artery and common femoral artery with patients under either spinal (n = 24) or local (n = 12) anesthesia. Intraoperative balloon angioplasty with fluoroscopic guidance preceded open retrograde iliofemoral endarterectomy. Adjunctive procedures included 18 profundaplasties, eight femorofemoral, nine femoropopliteal, and one femorotibial bypasses. RESULTS: Thirty-three of the 36 cases were initially successful. The three failures were in patients with extensive calcification. The mean follow-up has been 36.4 months, and the patency rate was 80.5% at 3 and 4 years. The four failures noted on follow-up were caused by three common iliac artery stenoses and one iliac system occlusion. The former group was successfully treated with balloon angioplasty/stent, and the latter patient required an aortofemoral bypass. No operative deaths or limb loss occurred in this series. CONCLUSIONS: Retrograde iliofemoral endarterectomy facilitated by balloon angioplasty is a safe, easy-to-perform, and viable option for patients with combined external iliac artery and common femoral artery occlusive disease. Midterm results (36.4 months) are favorable, and most hemodynamic failures are easy to correct with standard endovascular techniques.     

Mating behaviour in mixed infections of Schistosoma haematobium and S. mattheei

In mixed infections of Schistosoma haematobium and S. mattheei, homospecific and heterospecific pairs are formed, with a preponderance of homospecific pairs indicating the existence of a mate preference system. S. haematobium apparently exhibits a greater specific mate recognition system than does S. mattheei. In sequential infections when mice are exposed to S. mattheei 4 weeks after infection with S. haematobium, S. haematobium males are better at pairing with S. mattheei females than are S. mattheei males. Hence, genetic exchanges between S. haematobium and S. mattheei giving rise to viable hybrids poses the problem of the genetic identity of these species of schistosomes. The most important reproductive isolating mechanisms are definitive host specificity, S. haematobium being primarily a parasite of man, whereas S. mattheei is a parasite of domestic stock and wild ungulates, and the preference for homospecific pairings in simultaneous infections. In contrast, when S. haematobium is the older infection, S. haematobium males are better than S. mattheei males at pairing with females of either species. Hybridisation is the likely outcome of such interactions. The lack of viability of S. mattheei male X S. haematobium female indicates genetic differences between the two species. Occurrences of natural hybridisation between S. haematobium and S. mattheei may lead to a change in the response of the parasite to chemotherapeutic treatment.     

Workshop on chronic pain, pain control, and patient outcomes in rheumatoid arthritis and osteoarthritis

OBJECTIVE: Coincident with a change in the physician staff in our pediatric intensive care unit (PICU), the frequency and duration of invasive monitoring were decreased. We examined the impact of this change on outcomes, complications, and hospital charges in infants admitted to the PICU with respiratory syncytial virus (RSV) infection. STUDY DESIGN: We reviewed medical records of all children less than 1 year of age who were admitted to the PICU from January 1989 to July 1993 with confirmed RSV infection. Patient characteristics, therapeutic interventions, outcomes, and hospital charges were extracted and compared. RESULTS: Seventy-eight patients were identified, 38 admitted from January 1989 through July 1991 (group 1) and 40 from July 1991 through July 1993 (group 2). The groups were well matched in age, preexisting disease, and cardiorespiratory status on admission. Group 1 had significantly greater use of invasive monitoring, pharmacologic paralysis, inotropes, blood products, antibiotics, and parenteral nutrition. Outcomes were not different, but group 1 patients had significantly longer stays, more complications, and higher hospital charges. CONCLUSIONS: Routine use of invasive monitoring of PICU patients with RSV disease was associated with increased laboratory testing, overtreatment, and significant increases in costs and morbidity without improvement in outcome.     

Cercaria chaetotaxy of 2 Venezuelan strains of Schistosoma mansoni

By means of the silver impregnation of two lots of Schistosoma mansoni cercariae belonging to the strains: JR (32 cercariae) and C5 (45 cercariae), the number and pattern of disposition of the argentophillic papillae were determined with the following results: Average number of total dorsal papillae: 12.1 (JR strain) and 12.0 (C5 strain); the variation coefficients in this surface were less than 4% (JR strain) and bigger in JR than C5 strain. Average number of total ventral papillae: 12.15 (JR), 11.97 (C5); maximum value of the variation coefficient: 6.4% (JR), higher in JR than C5 strain. When the ventral surface was classified in four quadrants, the average number of papillae by quadrant was: quadrant A: 1.15 (JR) and 1.06 (C5): B: 1.06 (JR) and 1 (C5); C: 4.97 (JR) and 4.96 (C5); D: 5.03 (JR) and 4.98 (C5). The variation coefficients were higher in the A and B ventral quadrants, reaching maximum values of 31.9%, and 61.0% for the posterior quadrants C and D. When the ventral surface was divided in three equal parts for determining the position of the most variable papillae of this area, the greatest value of the variation coefficients obtained were for the 2nd thirds of the cercariae: 89.8% and 76.8% for C5 strain and 43.5% and 56.8% for JR strain. In relation to the total lateral papillae, the average numbers were: 17.0 (JR) and 16.6 (C5), with a maximum value of variation coefficient of (8.1% (C5). The average total number of papillae of the tail were: 25.6 (JR) and 26.1 (C5) for the ventral surface and 20.72 (JR) and 21.33 (C5) for the dorsal papillae. The comparison between the percents of the cercariae of two S. mansoni strains with more than 1 papillae on the anterior ventral quadrants A or B (94% JR and 34% C5), resulted with significant differences (P < 0.05).     

Human papillomavirus oncoproteins E6 and E7 independently abrogate the mitotic spindle checkpoint

The E6 and E7 genes of the high-risk human papillomavirus (HPV) types encode oncoproteins, and both act by interfering with the activity of cellular tumor suppressor proteins. E7 proteins act by associating with members of the retinoblastoma family, while E6 increases the turnover of p53. p53 has been implicated as a regulator of both the G1/S cell cycle checkpoint and the mitotic spindle checkpoint. When fibroblasts from p53 knockout mice are treated with the spindle inhibitor nocodazole, a rereplication of DNA occurs without transit through mitosis. We investigated whether E6 or E7 could induce a similar loss of mitotic checkpoint activity in human keratinocytes. Recombinant retroviruses expressing high-risk E6 alone, E7 alone, and E6 in combination with E7 were used to infect normal human foreskin keratinocytes (HFKs). Established cell lines were treated with nocodazole, stained with propidium iodide, and analyzed for DNA content by flow cytometry. Cells infected with high-risk E6 were found to continue to replicate DNA and accumulated an octaploid (8N) population. Surprisingly, expression of E7 alone was also able to bypass this checkpoint. Cells expressing E7 alone exhibited increased levels of p53, while those expressing E6 had significantly reduced levels. The p53 present in the E7 cells was active, as increased levels of p21 were observed. This suggested that E7 bypassed the mitotic checkpoint by a p53-independent mechanism. The levels of MDM2, a cellular oncoprotein also implicated in control of the mitotic checkpoint, were significantly elevated in the E7 cells compared to the normal HFKs. In E6-expressing cells, the levels of MDM2 were undetectable. It is possible that abrogation of Rb function by E7 or increased expression of MDM2 contributes to the loss of mitotic spindle checkpoint control in the E7 cells. These findings suggest mechanisms by which both HPV oncoproteins contribute to genomic instability at the mitotic checkpoint.     

A multidrug resistance transporter from human MCF-7 breast cancer cells

MCF-7/AdrVp is a multidrug-resistant human breast cancer subline that displays an ATP-dependent reduction in the intracellular accumulation of anthracycline anticancer drugs in the absence of overexpression of known multidrug resistance transporters such as P glycoprotein or the multidrug resistance protein. RNA fingerprinting led to the identification of a 2.4-kb mRNA that is overexpressed in MCF-7/AdrVp cells relative to parental MCF-7 cells. The mRNA encodes a 655-aa [corrected] member of the ATP-binding cassette superfamily of transporters that we term breast cancer resistance protein (BCRP). Enforced expression of the full-length BCRP cDNA in MCF-7 breast cancer cells confers resistance to mitoxantrone, doxorubicin, and daunorubicin, reduces daunorubicin accumulation and retention, and causes an ATP-dependent enhancement of the efflux of rhodamine 123 in the cloned transfected cells. BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of MCF-7/AdrVp human breast cancer cells.