Antitumor activity of Propionibacterium acnes (Corynebacterium parvum) and isolated cytoplasmic fractions.

The tumor-inhibitory effect of an intralesional injection of Propionibacterium acnes was of limited duration ("finite"). Our model was the DBA/2 syngeneic mouse injected with P815 mastocytoma cells (5 X 10(5)) into each rear footpad; only the left was treated, leaving the right as a "pseudometastasis." The finite effect occurred at approximately 21 days after the first treatment. Subsequent i.p. treatments with P. acnes did not alter this effect, although they increased mean survival time. With one footpad tumor, we achieved 22% cures with complete regression and no sign of metastatic growth. A RNA fraction from P. acnes produced inhibition of tumor growth, but crude cell walls and cell walls treated with Pronase had no effect. A P. acnes cytoplasmic fraction with tumor-inhibitory activity was pelleted by high-speed centrifugation; this fraction inhibited P815 mastocytoma as fully as whole cells injected in one-fifth the dose on a nitrogen basis and did not cause a local inflammatory reaction. The activity of the pellet also differed from whole cells in that it was equally inhibitory to the pseudometastasis in the contralateral right rear footpad. The cytoplasmic fraction apparently contained at least two active components since activity was obtained at two dilution levels. Such activity was relatively stable at 5 degrees, but it was unstable at -30 degrees.

Effects of planting dates on boll weevils (Coleoptera: Curculionidae) and cotton fruit in the subtropics.

The effects of planting dates 2-3-wk apart on boll weevil, Anthonomus grandis grandis Boheman (Coleoptera: Curculionidae), field-level populations, and feeding and oviposition damage to cotton, Gossypium hirsutum L., squares and bolls, were studied during 2002 and 2003 in the Lower Rio Grande Valley of Texas. Squares were 44-56% more abundant in some later planted treatments than in the earlier planted treatments, but mean cumulative numbers of oviposition- and feeding-damaged squares were 2.7 - 4.8-fold greater in some later planted treatments than in earlier treatments. Increased square production in later planted cotton was offset by boll weevil infestations that occurred when squares are most vulnerable and contribute most toward the pest's reproduction. Early planting avoided boll weevil population buildups in the field when large squares were abundant. Lint yields in 2002 did not differ significantly between the planting date treatments, but in 2003, mean yield in the middle treatment was 23% greater than in the early and late-planted treatments. Insecticide sprays in the earliest planted treatment of each year, based on the 10% damaged squares threshold, were >33% and >43% fewer than in the corresponding middle and latest planting treatments, respectively. Delayed planting, relative to the onset of favorable cotton-growing weather, at the field level, even when not applied uniformly on an areawide scale, is more cost-effective than planting too early or too late.

Genetic polymorphisms at the rat and murine loci coding for dopamine D2-like receptors.

Southern blot hybridization techniques have been used to identify genetic polymorphisms at the D2, D3 and D4 dopamine receptor loci in mice and rats. Genomic DNA from a panel of outbred and inbred strains of rats and inbred strains of mice was digested with a variety of restriction endonucleases. After separation of the restriction digests on the basis of size using agarose gel electrophoresis, 32P-labeled DNA probes coding for the rat D2, D3 and D4 dopamine receptors were used to identify a series of genetic polymorphisms at each of these receptor loci. Genetic polymorphisms were found for the rat and murine D2, D3 and D4 dopamine receptor loci. It is anticipated that these genetic polymorphisms will be useful in pharmacogenetic studies to determine the influence of the D2-like receptors in reward and addictive behaviors.

Non-medicinal ingredients.

Many drug products contain excipients which perform important functions in terms of stability, solubility and identification. Excipients should not be considered as inactive ingredients, as they have been associated with a wide range of adverse reactions in some individuals. Monitoring for excipient toxicity is important. Equally important, is the provision of non-medicinal ingredient information on packaging, patient information leaflets and prescribing information, as most excipient-related toxicity is preventable when the formulation is known.

Typical antipsychotics exhibit inverse agonist activity at rat dopamine D1-like receptors expressed in Sf9 cells.

The baculovirus system has been used to express the rat dopamine D1 receptors in Spodoptera frugiperda (Sf9) cells. A panel of typical antipsychotics including, alpha-flupenthixol, fluphenazine and thioridizine were found to inhibit dopamine-dependent stimulation of adenylyl cyclase. However, these compounds were also found to inhibit adenylyl cyclase activity in the absence of agonist in Sf9 cells expressing dopamine D1-like receptors. Therefore, these nonselective dopamine receptor compounds displayed negative intrinsic or inverse agonist activity. None of the compounds tested were neutral antagonists.

Sudden death in sport before and after introduction of the Basic Fitness Test.

This study examines sudden unexpected deaths in relation to strenuous exercise in the five years following the introduction of the Basic Fitness Test viz: 1978-82 and, by comparison with an identical study of the years 1968-77, shows that the annual exercise associated mortality rate rose from 3.5 per 100,000 before the Basic Fitness Test to 4.75 per 100,000 after its introduction. Sudden unexpected death in relation to strenuous exercise is rare, and its incidence has not importantly changed since the introduction of the Basic Fitness Test.

ALDH-1 expression levels predict response or resistance to preoperative chemoradiation in resectable esophageal cancer patients.

PURPOSE: Operable thoracic esophageal/gastroesophageal junction carcinoma (EC) is often treated with chemoradiation and surgery but tumor responses are unpredictable and heterogeneous. We hypothesized that aldehyde dehydrogenase-1 (ALDH-1) could be associated with response. METHODS: The labeling indices (LIs) of ALDH-1 by immunohistochemistry in untreated tumor specimens were established in EC patients who had chemoradiation and surgery. Univariate logistic regression and 3-fold cross validation were carried out for the training (67% of patients) and validation (33%) sets. Non-clinical experiments in EC cells were performed to generate complimentary data. RESULTS: Of 167 EC patients analyzed, 40 (24%) had a pathologic complete response (pathCR) and 27 (16%) had an extremely resistant (exCRTR) cancer. The median ALDH-1 LI was 0.2 (range, 0.01-0.85). There was a significant association between pathCR and low ALDH-1 LI (p ≤ 0.001; odds-ratio [OR] = 0.432). The 3-fold cross validation led to a concordance index (C-index) of 0.798 for the fitted model. There was a significant association between exCRTR and high ALDH-1 LI (p ≤ 0.001; OR = 3.782). The 3-fold cross validation led to the C-index of 0.960 for the fitted model. In several cell lines, higher ALDH-1 LIs correlated with resistant/aggressive phenotype. Cells with induced chemotherapy resistance upregulated ALDH-1 and resistance conferring genes (SOX9 and YAP1). Sorted ALDH-1+ cells were more resistant and had an aggressive phenotype in tumor spheres than ALDH-1- cells. CONCLUSIONS: Our clinical and non-clinical data demonstrate that ALDH-1 LIs are predictive of response to therapy and further research could lead to individualized therapeutic strategies and novel therapeutic targets for EC patients.

Retinal angiomatous proliferation or retinal anastomosis to the lesion.

Much debate exists within the literature with respect to the variant of neovascular age-related macular degeneration (AMD) known as retinal angiomatous proliferation (RAP). We prefer the term retinal anastomosis to the lesion (RAL), as we believe that the choroidal neovascularization (CNV) lesion precedes the development of an anastomosing retinal vessel to this lesion. Natural history data surrounding RAP lesions are available through analysis of the eyes with subfoveal occult CNV within the placebo arm of the Verteporfin in Photodynamic Therapy (VIP) trial. Although many reports ascribe a poor prognosis to RAP lesions, the data suggest that the true natural history of RAP lesion may be highly variable and similar to that of other CNV lesions. Information from clinical trials suggests that the response of RAP lesions to CNV treatments may also be similar to that of other variants of neovascular AMD.

J/psi and psi(2S) Radiative Transitions to eta_{c}.

Using 2.45x10;{7} psi(2S) decays collected with the CLEO-c detector at the Cornell Electron Storage Ring we present the most precise measurements of magnetic dipole transitions in the charmonium system. We measure B(psi(2S)-->gammaeta_{c})=(4.32+/-0.16+/-0.60)x10;{-3}, B(J/psi-->gammaeta_{c})/B(psi(2S)-->gammaeta_{c})=4.59+/-0.23+/-0.64, and B(J/psi-->gammaeta_{c})=(1.98+/-0.09+/-0.30)%. We observe a distortion in the eta_{c} line shape due to the photon-energy dependence of the magnetic dipole transition rate. We find that measurements of the eta_{c} mass are sensitive to the line shape, suggesting an explanation for the discrepancy between measurements of the eta_{c} mass in radiative transitions and other production mechanisms.

Observation of D+ --> etae + nue.

Using a 281 pb-1 data sample collected at the psi(3770) resonance with the CLEO-c detector at the Cornell Electron Storage Ring, we report the first observation of D+ --> etae + nue. We also set upper limits for D+ --> eta'e + nue and D + --> varphie + nue that are about 2 orders of magnitude more restrictive than those obtained by previous experiments.

First observation of the decay Ds+-->pn.

Using e+e--->Ds*-Ds+ data collected near the peak Ds production energy, Ecm=4170 MeV, with the CLEO-c detector, we present the first observation of the decay Ds+-->pn. We measure a branching fraction B(Ds+-->pn)=(1.30+/-0.36(-0.16)+0.12)x10(-3). This is the first observation of a charmed meson decaying into a baryon-antibaryon final state.

Observation of chicJ radiative decays to light vector mesons.

Using a total of 2.74 x 10(7) decays of the psi(2S) collected with the CLEO-c detector, we present a study of chi(cJ)-->gammaV, where V=rho(0), omega, phi. The transitions chi(c1)-->gammarho(0 and chi(c1)-->gammaomega are observed with B(chi(c1)-->gammarho(0))=(2.43+/-0.19+/-0.22) x 10(-4) and B(chi(c1)-->gammaomega)=(8.3+/-1.5+/-1.2) x 10(-5). In the chi(c1)-->gammarho(0) transition, the final state meson is dominantly longitudinally polarized. Upper limits on the branching fractions of other chi(cJ) states to light vector mesons are presented.

Study of the decays D0-->pi{-}e{+}nu{e}, D{0}-->K{-}e{+}nu{e}, D{+}-->pi{0}e{+}nu{e}, and D{+}-->K0e{+}nu{e}.

By using 1.8x10{6} DDpairs, we have measured B(D{0}-->pi{-}e{+}nu{e})=0.299(11)(9)%, B(D{+}-->pi{0}e{+}nu{e})=0.373(22)(13)%, B(D{0}-->K{-}e{+}nu{e})=3.56(3)(9)%, and B(D{+}-->K{0}e{+}nu{e})=8.53(13)(23)% and have studied the q;{2} dependence of the form factors. By combining our results with recent lattice calculations, we obtain |V{cd}|=0.217(9)(4)(23) and |V{cs}|=1.015(10)(11)(106).

Observation of Upsilon(3S)-->tau+tau- and tests of lepton universality in Upsilon decays.

Using data collected with the CLEO III detector at the CESR e+e- collider, we report on a first observation of the decay Upsilon(3S)-->tau+tau-, and precisely measure the ratio of branching fractions of Upsilon(nS), n=1, 2, 3, to tau+tau- and mu+mu- final states, finding agreement with expectations from lepton universality. We derive absolute branching fractions for these decays, and also set a limit on the influence of a low mass CP-odd Higgs boson in the decay of the Upsilon(1S).

Precision determination of the D0 mass.

A precision measurement of the D0 meson mass has been made using approximately 281 pb(-1) of e+e- annihilation data taken with the CLEO-c detector at the psi(3770) resonance. The exclusive decay D0-->K_{S}phi has been used to obtain M(D0)=1864.847+/-0.150(stat)+/-0.095(syst) MeV. This corresponds to M(D0D*0)=3871.81+/-0.36 MeV, and leads to a well-constrained determination of the binding energy of the proposed D0D*0 molecule X(3872), as Eb=0.6+/-0.6 MeV.

New measurements of Cabibbo-suppressed decays of mesons with the CLEO-c detector.

Using of data collected with the CLEO-c detector, we report on first observations and measurements of Cabibbo-suppressed decays of D mesons in the following six decay modes: pi+ pi- pi0 pi0, pi+ pi+ pi- pi- pi0, pi+ pi0 pi0, pi+ pi+ pi- pi0, eta pi0, and omega pi+ pi-. Improved branching fraction measurements in eight other multipion decay modes are also presented. The measured D --> pi pi rates allow us to extract the ratio of isospin amplitudes A(DeltaI = (3/2) / A(DeltaI = (1/2)) = 0.420 +/- 0.014(stat) +/- 0.016(syst) and the strong phase shift of delta1 = (86.4 +/- 2.8 +/- 3.3) degrees, which is quite large and now more precisely determined.

Measurement of sigma(e+e- -->psi(3770)-->hadrons) at Ec.m.=3773 MeV.

We measure the cross section for e+e- -->psi(3770) -->hadrons at Ec.m.=3773 MeV to be (6.38+/-0.08(+0.41)(-0.30) nb using the CLEO detector at the CESR e+e- collider. The difference between this and the e+e- -->psi(3770) -->DD cross section at the same energy is found to be (-0.01+/-0.08(+0.41)(-0.30) nb. With the observed total cross section, we extract Gamma(ee)(psi(3770))=(0.204+/-0.003(+0.041)(-0.027) keV. Uncertainties shown are statistical and systematic, respectively.

Precision measurements of the timelike electromagnetic form factors of pion, kaon, and proton.

Using 20.7 pb(-1) of e(+)e(-) annihilation data taken at sq.rt(r) = 3.671 GeV with the CLEO-c detector, precision measurements of the electromagnetic form factors of the charged pion, charged kaon, and proton have been made for timelike momentum transfer of |Q(2)| = 13.48 GeV(2) by the reaction e(+)e(-) --> h(+)h(-). The measurements are the first ever with identified pions and kaons of |Q(2)| > 4 GeV(2), with the results F(13.48 GeV(2)) = 0.075 +/- 0.008(stat) +/- 0.005(syst) and F(K)(13.48 GeV(2)) = 0.063 +/- 0.004(stat) +/- 0.001(syst). The result for the proton, assuming G(p)(E) = G(p)(M), is G(p)(M)(13.48 GeV(2)) = 0.014 +/- 0.002(stat) +/- 0.001(syst), which is in agreement with earlier results.

Mycobacterial ribonucleic acid: comparison with mycobacterial cell wall fractions for regression of murine tumor growth.

Mycobacterial ribonucleic acid (RNA) and cell wall skeleton fraction isolated from H37Ra caused P-815 mastocytoma regression in DBA/2 mice provided the animals were presensitized with freshly harvested living H37Ra cells. In the absence of presensitization, only the RNA fraction inhibited. Cell wall skeleton fraction, under these conditions, stimulated tumor growth. Cell wall lipids (from H37Ra) added to H37Ra cell wall skeleton fraction did not increase the inhibitory activity of cell wall skeleton fraction alone. Mycobacterial RNA appeared to be an effective inhibitor of P-815 mastocytoma metastases as shown by (i) the inhibition of a second footpad lesion distant from the one treated and (ii) increase in survival time.

Interferon production by inactivated Newcastle disease virus in cell cultures and in mice.

Youngner, Julius S. (University of Pittsburgh, Pittsburgh, Pa.), Anne W. Scott, Jules V. Hallum, and Warren R. Stinebring. Interferon production by inactivated Newcastle disease virus in cell cultures and in mice. J. Bacteriol. 92:862-868. 1966.-A comparison was made of the effects of ultraviolet (UV) irradiation or heating at 56 C on the interferon-stimulating capacity of Newcastle disease virus in primary chick embryo fibroblast (CE) cultures, in L-cell cultures, and in the intact mouse. The data obtained indicated the critical importance of the host cell system used for interferon production. Virus inactivated by UV irradiation, as well as infective virus, was an effective stimulus of interferon production in L cells and in mice, and this property persisted on continued irradiation. In contrast, in CE cell cultures, infective virus produced no interferon, whereas UV-irradiated virus produced maximal interferon titers when all infectivity was destroyed; continued irradiation resulted in a rapid loss of the interferon-stimulating capacity of the virus. Virus inactivated at 56 C did not produce interferon in CE or L-cell cultures. In the intact mouse, on the other hand, heat-inactivated virus was capable of stimulating the release of significant levels of circulating interferon.