Mutation of the p53 gene in human astrocytic tumours correlates with increased resistance to DNA-damaging agents but not to anti-microtubule anti-cancer agents

Human brain cancers (gliomas) overexpress large numbers of a receptor for interleukin 13 (IL13), making this receptor an attractive target for anti-glioma therapies. We have recently proposed that the glioma-associated IL13 receptor is different from the one expressed on some hemopoietic and somatic cells. In an attempt to identify an even more glioma-specific target, we have used an antagonist of a related cytokine, IL4, which neutralizes the physiological effects of both IL13 and IL4 on normal cells. Here we demonstrate that the IL4 antagonist also counteracts the action of cytotoxins targeted to the IL13 receptor on normal human cells. Importantly, the IL4 antagonist does not inhibit IL13-based cytotoxins on glioma cells at all. Thus, the IL13 receptor on glioma cells can be categorized as tumor-specific in the presence of an IL4 antagonist. We conclude that IL13 receptor-directed cytotoxins can be delivered to glioma cells without being cytotoxic to normal cells.     

Serum and urinary boron levels in rats after single administration of sodium tetraborate

The pharmacokinetics of boron was studied in rats by administering a 1 ml oral dose of sodium tetraborate solution to several groups of rats (n=20) at eleven different dose levels ranging from 0 to 0.4 mg/100 g body weight as boron. Twenty-four-hour urine samples were collected after boron administration. After 24 h the average urinary recovery rate for this element was 99.6+/-7.9. The relationship between boron dose and excretion was linear (r=0.999) with a regression coefficient of 0.954. This result suggests that the oral bioavailability (F) of boron was complete. Another group of rats (n=10) was given a single oral injection of 2 ml of sodium tetraborate solution containing 0.4 mg of boron/100 g body wt. The serum decay of boron was followed and found to be monophasic. The data were interpreted according to a one-compartment open model. The appropriate pharmacokinetic parameters were estimated as follows: absorption half-life, t1/2a=0.608+/-0.432 h; elimination half-life, t1/2=4.64+/-1.19 h; volume of distribution, Vd = 142.0+/-30.2 ml/100 g body wt.; total clearance, Ctot=0.359+/-0.0285 ml/min per 100 g body wt. The maximum boron concentration in serum after administration (Cmax) was 2.13+/-0.270 mg/l, and the time needed to reach this maximum concentration (Tmax) was 1.76+/-0.887 h. Our results suggest that orally administered boric acid is rapidly and completely absorbed from the gastrointestinal tract into the blood stream. Boric acid in the intravascular space does not have a strong affinity to serum proteins, and rapidly diffuses to the extravascular space in proportion to blood flow without massive accumulation or binding in tissues. The main route of boron excretion from the body is via glomerular filtration. It may be inferred that there is partial tubular resorption at low plasma levels. The animal model is proposed as a useful tool to approach the problem of environmental or industrial exposure to boron or in cases of accidental acute boron intoxication.     

Cytoskeletal role in the transition from compensated to decompensated hypertrophy during adult canine left ventricular pressure overloading

OBJECTIVES: To assess the effects of a vasodilatory beta-adrenoceptor blocker, nipradilol, and a long-acting Ca channel blocker, barnidipine, on insulin sensitivity. DESIGN: Insulin sensitivity was determined using a euglycemic hyperinsulinemic clamp technique before and after a 12-week treatment period in eighteen patients with essential hypertension. RESULTS: Both drugs decreased blood pressure without affecting any serum parameters of glucose and lipid metabolism. Nipradilol significantly augmented glucose infusion rate (GIR) from 3.11+/-0.28 to 4.69+/-0.57mg/kg/min (p=0.027). Barnidipine also increased GIR from 3.91+/-0.43 to 5.29+/-0.43 mg/kg/min (p=0.028). Plasma norepinephrine concentrations significantly increased with barnidipine treatment, while nipradilol had no effect on plasma norepinephrine levels. No adverse events were reported during the study. CONCLUSIONS: These results suggest that vasodilatory beta-blockers such as nipradilol and long-acting Ca channel blockers such as barnidipine may be useful in the treatment of insulin resistant hypertensive patients.     

Fisher syndrome associated with IgG anti-GQ1b antibody following infection by a specific serotype of Campylobacter jejuni

OBJECTIVE: The purpose of the study was to describe clinical and serologic features of Fisher syndrome associated with IgG anti-GQ1b ganglioside antibody following Campylobacter jejuni enteritis. DESIGN: A clinical trial. PARTICIPANTS: Four consecutive patients with Fisher syndrome were studied. INTERVENTION: Samples of sera from four patients were tested for reactivity to GQ1b ganglioside by enzyme-linked immunosorbent assay (ELISA). Campylobacter jejuni strains isolated from samples of stool from three patients were serotyped by the method of Penner and Hennessy and that of Lior. MAIN OUTCOME MEASURES: Serum IgG anti-GQ1b antibody titer and serotypes of C. jejuni. RESULTS: Diplopia occurred 8 to 14 days after the onset of diarrhea. Campylobacter jejuni was isolated from samples of stool from all of the patients. ELISA revealed a high serum IgG anti-GQ1b antibody titer for all four patients. Two patients had high serum titers of other antiganglioside antibodies frequently related to Guillain-Barré syndrome. These two patients developed limb weakness following the onset of ophthalmoplegia. The C. jejuni serotype was Penner's serotype 2 for all three of the patients tested. CONCLUSIONS: These findings suggest that C. jejuni, especially Penner's serotype 2, enteritis could trigger development of Fisher syndrome associated with IgG anti-GQ1b antibody.     

Role of gamma interferon in Helicobacter pylori-induced gastric inflammatory responses in a mouse model

The immune responses to Helicobacter pylori infection play important roles in gastroduodenal diseases. The contribution of gamma interferon (IFN-gamma) to the immune responses, especially to the induction of gastric inflammation and to protection from H. pylori infection, was investigated with IFN-gamma gene knockout (IFN-gamma-/-) mice. We first examined the colonizing abilities of eight H. pylori strains with a short-term infection test in order to select H. pylori strains which could colonize the mouse stomach. Only three strains (ATCC 43504, CPY2052, and HPK127) colonized C57BL/6 wild-type mice, although all of the strains except for ATCC 51110 could colonize IFN-gamma-/- mice. The number of H. pylori organisms colonizing the stomach in wild-type mice was lower than that in IFN-gamma-/- mice. Oral immunization with the CPY2052 sonicate and cholera toxin protected against infection with strain CPY2052 in both types of mouse. These findings suggested that IFN-gamma may play a protective role in H. pylori infection, although the degree of its protective ability was estimated to be low. In contrast, in a long-term infection test done to examine the contribution of IFN-gamma to gastric inflammation, CPY2052-infected wild-type mice developed a severe infiltration of mononuclear cells in the lamina propria and erosions in the gastric epithelium 15 months after infection, whereas CPY2052-infected IFN-gamma-/- mice showed no inflammatory symptoms. This result clearly demonstrated that IFN-gamma plays an important role in the induction of gastric inflammation caused by H. pylori infection.     

Improved Correction of Beam Mismatch of the Precipitation Radar After Orbit Boost of the TRMM Satellite

One effort in developing the Tropical Rainfall Measuring Mission (TRMM) precipitation radar (PR) data processing algorithm is to correct the PR received power for mismatched-beam data after the orbit is boosted. The current standard algorithm employs a beam-mismatch correction algorithm based on the rain-echo radar equation (Takahashi's method). However, there remains a need for improving the estimated power of the mismatched-pulse echo returned from the Earth's surface and weak rain because the echo is represented with the surface-echo radar equation and the noise-power level. The error in Takahashi's method causes a negative bias (around 1 dB) in the PR received power near the main lobe clutter. This paper formulates an improved estimate of the mismatched pulse based on the rain-echo radar equation and the surface-echo radar equation for a flat-Earth surface. The improved estimate is then evaluated numerically and experimentally with the actual data obtained by TRMM/PR for observations over the ocean. The consistency of TRMM/PR data sets between preboost and postboost was improved by eliminating the negative bias (around 1 dB) in the PR received power. The mean rain rate near the surface-echo range increases by 10%, and the angle-bin asymmetry of the mean rainfall rate, which is present in the postboost data corrected by Takahashi's method, is resolved.     

Inside Front Cover: Mobility and Dynamics of Charge Carriers in Rubrene Single Crystals Studied by Flash‐Photolysis Microwave Conductivity and Optical Spectroscopy (Adv. Mater. 5/2008)

Electrodeless photoconductivity measurements of a rubrene single crystal are performed by microwave conductivity and transient optical spectroscopy, demonstrating anisotropy and ambipolarity. From these comprehensive studies, Akinori Saeki, Seiichi Tagawa, and co‐workers discuss on p. 920 the optoelectronic properties of rubrene single crystal in terms of charge recombination of holes and electrons, exciton–exciton annihilation, quantum efficiency of charge carrier generation, triplet contribution, and the extinction coefficients of ionic species accessed by pulse radiolysis.