Isolation of a novel Helicobacter species, Helicobacter cholecystus sp. nov., from the gallbladders of Syrian hamsters with cholangiofibrosis and centrilobular pancreatitis

A filamentous, gram-negative, motile bacterium with a single polar sheathed flagellum was isolated from gallbladders of hamsters with cholangiofibrosis and centrilobular pancreatitis. Bacteria grew under microaerophilic conditions at 37 and 42 degrees C, were oxidase, catalase, arginine aminopeptidase, and L-arginine arylamidase positive, reduced nitrate to nitrite, were resistant to cephalothin, and exhibited intermediate susceptibility to nalidixic acid. Sequence analysis of the 16S rRNA gene indicated that the bacterium was a novel member of the Helicobacter genus, most closely related to Helicobacter pametensis. We propose to name this bacterium Helicobacter cholecystus. In epidemiologic studies, isolation of H. cholecystus correlated strongly with the presence of cholangiofibrosis and centrilobular pancreatitis; however, further studies are needed to define the role of this bacterium in pathogenesis.     

Tumor cell cytotoxicity of a novel metal chelator

We have synthesized a novel six-coordinate metal chelator from the triamine cis-1,3,5-triaminocyclohexane by the addition of a 2-pyridylmethyl pendant arm on each nitrogen, which we term tachpyr. The experiments described here were designed to explore whether this compound exhibits potential antitumor activity. When added to MBT2 or T24 cultured bladder cancer cells, tachpyr was profoundly cytotoxic, with an IC50 of approximately 4.6 micromol/L compared with 70 micromol/L for desferioxamine. To explore the mode of action of tachpyr, several metal complexes were prepared, including Fe(II), Ca(II), Mn(II), Mg(II), Cu(II), and Zn(II) tachpyr complexes. Of these, the Zn(II), Cu(II), and Fe(II) complexes were without toxic effect, whereas the Ca(II), Mn(II), and Mg(II) complexes remained cytotoxic. To further probe the role of Zn(II) and Cu(II) chelation in the cytotoxicity of tachpyr, sterically hindered tachpyr derivatives were prepared through N-alkylation of tachpyr. These derivatives were unable to strongly bind Fe(III) or Fe(II) but were able to bind Zn(II) and Cu(II). When added to cells, these sterically hindered tachpyr derivatives were nontoxic, consistent with a role of iron depletion in the cytotoxic mechanism of tachpyr. Further, the addition of tachpyr to proliferating cultures resulted in an early and selective inhibition of ferritin synthesis, an iron storage protein whose translation is critically dependent on intracellular iron pools. Taken together, these experiments suggest that tachpyr is a cytotoxic metal chelator that targets intracellular iron, and that the use of tachpyr in cancer therapy deserves further exploration.     

Meprin A, the major matrix degrading enzyme in renal tubules, produces a novel nidogen fragment in vitro and in vivo

We examined the effect of meprin A, the major matrix degrading metalloproteinase in rat kidney, on the laminin-nidogen complex. N-terminal sequence information from the most abundant 55 kDa fragment revealed that it was a breakdown product of nidogen rather than laminin. In comparison with over 50 nidogen cleavage sites produced by other proteases, the meprin A-induced nidogen cleavage site at amino acid position 899-900, a glutamine-glycine site in the G3 domain, is unique. In addition, these data demonstrate that meprin A degrades the G3 domain of nidogen even in the presence of laminin binding, which usually accords protection from proteolytic degradation. Meprin A also degraded purified nidogen into similar breakdown products. Given that the tubular basement membrane is located on the basilar side of the cell, the location of meprin A on the apical brush border makes it difficult to envision a role for meprin A in injury-induced basement membrane component breakdown. Thus, we examined the possibility that following renal tubular epithelial cell injury, meprin A undergoes a translocation to reach the underlying basement membrane. After renal ischemia-reperfusion there was a marked alteration in meprin A staining with meprin A now distributed throughout the renal tubular cell cytoplasm and directly adherent to the tubular basement membrane. This was in contrast to the usual linear staining of the brush border of tubules in the corticomedullary junction. These data provide unequivocal evidence that following injury, meprin A undergoes redistribution and/or adherence to the tubular basement membrane. Since in our in vitro studies, we identified a distinct meprin-induced 55 kDa nidogen breakdown product, the urine was also examined for the presence of nidogen degradation products after rat renal ischemia-reperfusion injury. Western blots showed a marked increase in the urinary 55 kDa nidogen fragment as early as the first day following ischemia-reperfusion injury and continuing for six days. Taken together, these in vivo data strongly support the notion that the nidogen breakdown products are the result of partial degradation of tubular basement membrane by meprin A following renal tubular ischemia-reperfusion injury.     

On the moment theory of elasticity. Plane deformation. Part I

We propose a model of the moment theory of elasticity in which equations of the classical (momentless) theory of elasticity are supplemented with equilibrium equations (momental equations) and boundary conditions for couple stresses and shear strains are determined by tangential and couple stresses. As a result, the basic relationships between strains and displacements and, hence, the continuity equations for strains preserve the same form as in the momentless theory. The proposed moment theory of elasticity completely includes all basic postulates of the classical theory and supplements it in the case where the law of parity of tangential stresses is not valid. We obtain solutions of some problems which cannot be solved within the framework of the classical theory of elasticity. Moscow State Postal-Tuition Institute of the Food Industry, Moscow, Russia. Translated from Problemy Prochnosti, No. 3, pp. 103–113, May–June, 1998.     

p53 tumour suppressor gene mutations in benign prostatic hyperplasia and prostate cancer

OBJECTIVE: Seminal vesicle cysts combined with ipsilateral renal agenesis represent a rare urological anomaly. We searched the literature to review the clinical presentation, diagnosis and therapeutic treatment options of this anomaly. METHODS: A pooled analysis was performed of 52 cases of seminal vesicle cysts combined with ipsilateral renal agenesis, including our own observation. The evaluation included: patient age at diagnosis, race, laterality (R/L), presence of ureteral remnant in the cyst, presenting symptoms, diagnostic examinations, treatment and outcome. RESULTS: The mean age at diagnosis was 30.2 years. The majority presented in the 2nd, 3rd and 4th decade of their lives. Only 2 patients (4%) were of African origin, all others were Caucasians. The distribution R:L was 2:1. Ureteral remnants were present in 14 patients (27%). The most common symptoms were: dysuria (37%), frequency (33%), perineal pain (29%), epididymitis (27%), pain following ejaculation (21%) and scrotal pain (13%). Infertility was found in 9 patients (17%). The cyst was palpable by digital rectal examination in 79%. All patients underwent intravenous urography, and 88% underwent cystoscopy. Other frequently performed investigations are: ultrasonography (27%), CT scanning (27%), vasovesiculography (46%) and urethrocystography (23%). The final treatment was open surgery in 74%, aspiration in 6%, transurethral deroofing of the cyst in 6% and spontaneous rupture in 4%. In 6% no treatment was given and in 4% the treatment is unknown. All patients were free of symptoms after open exploration. The success rates after transurethral deroofing and aspiration were 75 and 30% respectively. CONCLUSION: Seminal vesicle cysts combined with ipsilateral renal agenesis are a rare urological anomaly, occurring in men in the 2nd to 4th decade of their life. They present with symptoms of bladder irritation and obstruction and with pain in the perineum and scrotum. Epididymitis is frequently found. The diagnostic work-up consists of a digital rectal examination, transrectal and abdominal ultrasonography, CT scan and a cystoscopy. Open surgery and transurethral deroofing of the cyst give excellent results (100 and 75% cure respectively). Aspiration of the cyst should only be used for diagnostic purposes.     

Mosaic organization of DNA nucleotides

Long-range power-law correlations have been reported recently for DNA sequences containing noncoding regions. We address the question of whether such correlations may be a trivial consequence of the known mosaic structure ("patchiness") of DNA. We analyze two classes of controls consisting of patchy nucleotide sequences generated by different algorithms--one without and one with long-range power-law correlations. Although both types of sequences are highly heterogenous, they are quantitatively distinguishable by an alternative fluctuation analysis method that differentiates local patchiness from long-range correlations. Application of this analysis to selected DNA sequences demonstrates that patchiness is not sufficient to account for long-range correlation properties.     

Long-range correlation properties of coding and noncoding DNA sequences: GenBank analysis

An open question in computational molecular biology is whether long-range correlations are present in both coding and noncoding DNA or only in the latter. To answer this question, we consider all 33301 coding and all 29453 noncoding eukaryotic sequences--each of length larger than 512 base pairs (bp)--in the present release of the GenBank to dtermine whether there is any statistically significant distinction in their long-range correlation properties. Standard fast Fourier transform (FFT) analysis indicates that coding sequences have practically no correlations in the range from 10 bp to 100 bp (spectral exponent beta=0.00 +/- 0.04, where the uncertainty is two standard deviations). In contrast, for noncoding sequences, the average value of the spectral exponent beta is positive (0.16 +/- 0.05) which unambiguously shows the presence of long-range correlations. We also separately analyze the 874 coding and the 1157 noncoding sequences that have more than 4096 bp and find a larger region of power-law behavior. We calculate the probability that these two data sets (coding and noncoding) were drawn from the same distribution and we find that it is less than 10(-10). We obtain independent confirmation of these findings using the method of detrended fluctuation analysis (DFA), which is designed to treat sequences with statistical heterogeneity, such as DNA's known mosaic structure ("patchiness") arising from the nonstationarity of nucleotide concentration. The near-perfect agreement between the two independent analysis methods, FFT and DFA, increases the confidence in the reliability of our conclusion.     

Gender-related differences in susceptibility of A/J mouse to benzo[a]pyrene-induced pulmonary and forestomach tumorigenesis

A commercial patient dose verification system utilizing non-invasive metal oxide semiconductor field effect transistor (MOSFET) dosimeters originally designed for radiotherapy applications has been evaluated for use at diagnostic energy levels. The system features multiple dosimeters that may be used to monitor entrance or exit skin dose and intracavity doses in phantoms in real time. We have characterized both the standard MOSFET dosimeter designed for radiotherapy dose verification and a newly developed "high sensitivity" MOSFET dosimeter designed for lower dose measurements. The sensitivity, linearity, angular response, post-exposure response, and physical characteristics were evaluated. The average sensitivity (free in air, including backscatter) of the radiotherapy MOSFET dosimeters ranged from 3.55 x 10(4) mV per C kg(-1) (9.2 mV R(-1)) to 4.87 x 10(4) mV per C kg(-1) (12.6 mV R(-1)) depending on the energy of the x-ray field. The sensitivity of the "high sensitivity" MOSFET dosimeters ranged from 1.15 x 10(5) mV per C kg(-1) (29.7 mV R(-1)) to 1.38 x 10(5) mV per C kg(-1) (35.7 mV R(-1)) depending on the energy of the x-ray field. The high sensitivity dosimeters demonstrated excellent linearity at high energies (90 and 120 kVp) and acceptable linearity at lower energies (60 kVp). The angular response was significant for free-in-air exposures, as illustrated by the sensitivity differences between the two sides of the dosimeter, but was excellent for measurements within a tissue equivalent cylinder. The post-exposure drift response is a complicated but reproducible function of time. Real-time monitoring requires little if any corrections for the post-exposure drift response. The MOSFET dosimeter system brings some unique capabilities to diagnostic radiology dosimetry including small size, real-time capabilities, nondestructive measurement, good linearity, and a predictable angular response.