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Biomedical subjects

D A Russell

Publications and source records attributed to D A Russell.

At least 55 records · Page 3Linked to original sources

Octa-alkyl zinc phthalocyanines: potential photosensitizers for use in the photodynamic therapy of cancer.

The synthesis, characterization and electronic spectra of a series of nine 1,4,8,11,15,18,22,25-octa-alkyl zinc phthalocyanines (ZnPc), potential photosensitizers for the photodynamic therapy of cancer, are described. The substituents on the phthalocyanine (Pc) macrocycle "red-shift" the absorbance maximum, in cyclohexane, of all nine members of this series to a value of 703 +/- 2 nm, with a corrected fluorescence emission maximum for the octadecyl derivative of 715 nm. The solubilities and degree of aggregation of six examples in cyclohexane have been measured. The highest homologue, the octadecyl derivative, remains essentially unaggregated to a concentration of 1.5 x 10(-4) mol dm-3. the photostability of this Pc has been examined and the compound shown to be sensitive to photooxidation processes which lead to its decomposition to 3,6-bis-decylphthalimide. Known singlet oxygen quenchers inhibit the photodecomposition. In a comparative study, the octadecyl ZnPc underwent a more rapid photodecomposition than the corresponding metal-free derivative.

Indoles↗

Continuous noninvasive measurement of in vivo pH in conscious mice.

Extracellular pH was measured continuously and noninvasively in hairless mice using a transcutaneous spectrofluorometric technique and a fluorescent pH probe, bis-carboxyethyl carboxyfluorescein (BCECF). The acid form of BCECF was injected intravenously. An optical fiber system excited the fluorescent probe at 450 and 500 nm alternately, using one branch of a bifurcated, fiber optic bundle. The other branch of the bundle collected the emitted fluorescence which was measured by a photomultiplier tube. The ratio of fluorescence intensities from the two excitation wavelengths was pH dependent. Measurements could be obtained for approximately 60 min following a single injection. Mice exposed to elevated partial pressures of CO2 demonstrated changes in the fluorescence ratio indicative of a dramatic decrease in extracellular pH. If the exposure was brief, the fluorescence signal recovered within 20 min. The fluorescence intensity ratio was calibrated against aqueous BCECF samples in vitro. Fluorescence pH values determined using the in vitro calibration were compared with measurements made on blood samples taken from seven mice. Extracellular pH in hairless mice was found to be approximately 7.5, within the expected physiological range. The variability of the pH signal derived from the fluorescence signal was approximately 0.05 units.

Animals↗

Use of the dental dam in endodontic procedures in dogs.

The rationale and step-by-step use of the rubber dental dam for endodontic procedures in dogs is described. Two methods are employed. One requires an initial investment of less than $200; the other requires no investment by the veterinary practitioner.

Animals↗

Targets for sepsis therapies: tumor necrosis factor versus interleukin-1.

Clinical testing of therapies for sepsis that target tumor necrosis factor and interleukin-1 is currently in progress. It is now clear from early clinical results that patients display a heterogeneous response to anti-cytokine therapies that may be related to the stage or severity of disease. Experimental results show that either cytokine may contribute to the metabolic derangements that lead to organ dysfunction in severe sepsis. They also provide a physiological basis for understanding the benefits of anti-cytokine therapy in the most severely ill patients.

Animals↗

Analysis of L-alanine:2-oxoglutarate aminotransferase isozymes in maize.

Isozyme analysis of L-alanine:2-oxoglutarate aminotransferase (ALT) in maize indicates that there are three genes encoding this enzyme activity. Two of the gene products interact with each other to form heterodimers, while the third gene product does not interact with the other two. Another isozyme that appears after gel electrophoresis and ALT staining is shown to be glutamate dehydrogenase-1. Anaerobic treatment does not result in increased ALT levels, indicating that the previously reported increase in alanine levels caused by this treatment may be due to increases in the level of pyruvate, a substrate of ALT.

Alanine Transaminase↗

Protein Synthesis in Maize during Anaerobic and Heat Stress.

Protein accumulation and protein synthesis were investigated during anaerobic stress and heat shock in maize seedlings (Zea mays L.). Antibodies against alcohol dehydrogenase (ADH) and cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPC) were used to investigate the expression of the genes encoding these proteins during stress treatment. ADH1 protein accumulation is shown to increase about 10-fold in the root after 24 hours of anaerobic treatment. The Gpc gene products are separable into two size classes: the slow mobility GAPC1 and GAPC2 (GAPC1/2), and the faster GAPC3 and GAPC4 (GAPC3/4). The GAPC1/2 antigen did not increase at all, whereas the GAPC3/4 antigen increased less than fourfold. The proteins synthesized in the root during aerobic and anaerobic conditions were compared, and GAPC3/4 was identified as an anaerobic polypeptide. In vitro translations were used to estimate the levels of different mRNAs in roots following anaerobiosis, recovery from anaerobiosis, and heat shock. This was compared with the in vivo protein synthesis rates in roots labeled under identical conditions. In vivo labeling indicates that GAPC and ADH are not heat shock proteins. Although both GAPC3/4- and ADH1-translatable mRNA levels increase about 10-fold during anaerobiosis, in vivo labeling of these proteins (relative to total protein synthesis) is further enhanced, leading to a selective translation effect for ADH1 of threefold, and for GAPC3/4 of sixfold. In contrast, anoxia causes no change in GAPC1/2-translatable mRNA levels or in vivo labeling. As an additional comparison, beta-glucosidase mRNA levels are found to be constant during anoxia, but in vivo synthesis decreases.

Journal Article↗

The maize cytosolic glyceraldehyde-3-phosphate dehydrogenase gene family: organ-specific expression and genetic analysis.

The distribution of the cytosolic glyceraldehyde-3-phosphate dehydrogenase gene family (Gpc) in the maize genome was investigated; a genetic variant of glyceraldehyde-3-phosphate dehydrogenase activity is also described. Restriction fragment length polymorphism analysis of an F2 population shows that the variant is not linked to the three known Gpc genes. However, this trait is linked to one of two genomic DNA fragments that hybridize to a fragment of the Gpc3 coding region, implying the existence of a fourth Gpc gene. Antibodies and cDNA clones were used to investigate the organ-specific expression of the Gpc genes. Results were compared with the expression of the Gpc genes. Results were compared with the expression of the alcohol dehydrogenase 1 (Adh1) gene. RNA and protein levels were examined in seedling roots and shoots, as well as the leaves, developing endosperm and embryo, and the aleurone. In general, it was found that Gpc3 expression behaves in parallel with Adh1 in these organs, and protein levels closely parallel that of RNA for each gene examined. Both Gpc3 and Adh1 show a marked increase in expression during endosperm development, reaching a maximum 15 days after pollination, but no expression is detected in the leaf. Gpc1 expression is similar to that of Gpc2, with an overall decrease in the level of RNA during endosperm development. This expression is discussed in terms of the common sequences found upstream of genes expressed in the developing maize seed.

Blotting, Northern↗

The anaerobic response of soybean.

The effect of anoxia on roots of soybean (Glycine max [L.] Merr., variety ;Williams') was studied at various levels and the results compared to those from previously studied species. While alcohol dehydrogenase (ADH) activity is induced in a manner similar to other plant species, other aspects of the anaerobic response are unique to soybean. A variety of molecular clones was used to analyze changes in soybean and maize RNA levels. Increased RNA accumulation was observed in both species with a maize ADH clone, while a maize aldolase and one of the two different maize glyceraldehyde-3-phosphate dehydrogenase cDNA clones showed induction only in maize. A maize sucrose synthase 1 clone showed induction in maize but no hybridization to soybean RNA samples. The reduction in the number of anaerobically inducible soybean genes relative to maize is consistent with in vivo and in vitro protein synthesis results. Only four major proteins are labeled during anoxia in soybean, one corresponding to ADH, while maize has been reported to have about 20. In either species, in vitro translation yields similar products with RNA from anaerobic and pre-stress plants, indicative of translational control during anoxia. These results are discussed in relation to the differential tolerance of maize and soybean to anaerobic stress.

Journal Article↗

Differences in incidence rates of cancers of the respiratory tract by anatomic subsite and histologic type: an etiologic implication.

Data from nine population-based cancer registries participating in the Surveillance, Epidemiology, and End Results Program (1973-1982) were analyzed to determine whether the incidence of different histologic types of respiratory tract cancers varies by anatomic location. The variation in cancer incidence among respiratory tract subsites was remarkable for squamous cell carcinoma, but the variation was less prominent for adenocarcinoma. The rates of squamous cell carcinoma and adenocarcinoma along the airways correspond closely with the deposition pattern of large and small smoke particles, respectively. Also, the rates of adenocarcinoma parallel the distribution of surface glandular cells of the respiratory tract. Our results support the hypothesis that anatomy and physiology, in conjunction with size of particles in inhaled cigarette smoke, play an important role in the genesis of specific histologic types of respiratory tract cancers.

Adenocarcinoma↗

Differential expression and sequence analysis of the maize glyceraldehyde-3-phosphate dehydrogenase gene family.

Two cDNA clones for maize cytosolic glyceraldehyde-3-phosphate dehydrogenase are described. One is about 97% similar in coding capacity to a previously published clone [Brinkmann et al. (1987). J. Mol. Evol. 26, 320-328], while the other shows only 88% similarity. Evidence points toward the three cDNAs being the products of three genes, to be called Gpc1, Gpc2, and Gpc3. When the least similar clone, corresponding to Gpc3, was used to analyze RNA gel blots, anaerobic treatment for 6 hours induced RNA accumulation in the shoots 15.6-fold, while a 1-hour shift from 28 degrees C to 40 degrees C increased accumulation 5.1-fold. Roots had a higher basal level of expression, leading to a 6.0-fold anaerobic induction, and a 2.4-fold heat stress induction. RNA gel blot analysis using the clone corresponding to Gpc2 showed decreased RNA accumulation within 6 hours of anaerobiosis, while analysis with the previously published clone, corresponding to Gpc1, showed a decrease within 24 hours. Neither Gpc1 nor Gpc2 showed heat stress induction, while some other known anaerobic genes did. Through the use of hybrid selection, in vitro translation, and immune precipitation, the relative expression of the three genes is shown. The role of the observed changes in gene expression is discussed in relation to stress physiology.

Amino Acid Sequence↗

Immunological regulation of colonic ion transport.

Challenge of distal colonic epithelium from Trichinella spiralis-infected guinea pigs with parasite-derived antigen elevated short-circuit current (Isc) for approximately 60 min. The maximum elevation (delta Isc) was approximately 250 microA/cm2 at 5 min after the addition of trichinella antigen. The antigen-induced alterations in Isc were of greater magnitude and duration than those evoked in jejunum. Colonic electrical resistance was transiently reduced after exposure to antigen. There was no significant effect of antigen on electrical parameters of colon from nonimmunized (uninfected) guinea pigs. The antihistamine pyrilamine (10(-5) M) and the prostaglandin synthesis inhibitor indomethacin (10(-6) M) reduced the colonic Isc response to antigen by 40% when used in combination but had insignificant effects when used singly. In contrast, the jejunal Isc response to antigen was totally eliminated by the combined use of those inhibitors. Antigenic stimulation of sensitized colon released histamine and prostaglandin E2 (PGE2). However, the histamine released was only about one-tenth that stimulated by antigen in the jejunum, and PGE2 released was only one-tenth of that stimulated by bradykinin in the colon. PGE2 was not released after antigenic stimulation of jejunum. The antigen-induced colonic delta Isc was reduced approximately 50% by either furosemide or tetrodotoxin. Although histamine- and indomethacin-sensitive factors contribute greatly to the mediation of the antigen-induced delta Isc in jejunum, these autacoids contribute to a lesser extent to the antigen-induced delta Isc in guinea pig colon.

Animals↗

BCG vaccination in leprosy: final results of the trial in Karimui, Papua New Guinea, 1963-79.

The efficacy of BCG vaccine in preventing the clinical manifestations of leprosy in a tuberculosis-free area of Papua New Guinea is reported. Between 1963 and 1966 a total of 5356 subjects, randomized to receive BCG or saline inoculations, were examined for leprosy before the vaccination and surveillance was continued until 1979. BCG afforded 48% protection against clinical leprosy, being most effective against borderline tuberculoid leprosy and in children vaccinated when under 15 years old. Protection was evident within 12 months in those vaccinated between the ages of 10 and 15 years but was delayed in other age groups. There was evidence for accelerated manifestations of tuberculoid leprosy in children vaccinated when under 5 years of age. Tuberculin sensitivity was more likely to be sustained following multiple BCG inoculations; vaccinees with sustained tuberculin sensitivity had the lowest incidence of leprosy, but protection was also evident in tuberculin-negative vaccinees. These results may have implications for ongoing trials of leprosy vaccine incorporating BCG.

Adolescent↗

Translational repression in eukaryotes: partial purification and characterization of a repressor of ferritin mRNA translation.

Mouse and rabbit ferritin mRNAs translate very poorly in rabbit reticulocyte lysates relative to most other mRNAs. This translational deficiency is not seen in wheat germ lysates, suggesting the presence of an inhibitor in reticulocyte lysate that is specific for ferritin mRNA. A specific repressor of ferritin mRNA translation has been partially purified from rabbit reticulocytes by differential ultracentrifugation, ammonium sulfate fractionation, and chromatography on phosphocellulose, DEAE-cellulose, and Sephacryl S-300. The elution profile from the latter suggests an aggregate molecular mass of approximately 180 kDa for the repressor. The inhibitory activity of this repressor against native ferritin mRNA can be relieved by adding in vitro transcripts of ferritin light-chain RNAs that contain the first 92 nucleotides of the 5' untranslated region. No other sequences appear to be necessary for this effect.

Animals↗

Anaphylaxis-mediated epithelial Cl- secretion and parasite rejection in rat intestine.

Immunologically mediated expulsion of Trichinella spiralis infective larvae in the rat was used as a model to test the hypothesis that intestinal anaphylaxis induced by parasite antigen causes ion transport alterations in small intestinal epithelium, and that the small intestinal epithelium, by altering its physiologic state in response to mast cell-derived mediators, functions as an effector tissue in the expulsion process. Experimental results demonstrated that the rapid rejection response and antigen-inducible changes in net intestinal ion transport acquired through active immunization were transferable with serum containing a high titer of anti-trichinella homocytotropic antibody, as measured by the PCA test. Neither response was expressed in nonimmune hosts nor in recipients of serum in which the PCA-detectable antibody was reduced by heat treatment. Net ion transport by jejunal epithelium of both actively and passively immunized rats was measured in Ussing chambers by using the electrical correlate, short circuit current (Isc). Involvement of chloride secretion in antigen-induced alterations in Isc was deduced from the use of chemical agents that effectively and specifically blocked the antigen-induced Cl- secretory response. The results implicate anaphylaxis in both rapid worm rejection and altered epithelial ion transport.

Anaphylaxis↗

Inhibition of the sodium pump by cardioactive DPI 201-106.

The effects of DPI 201-106 were examined on contractions of papillary muscles from the right ventricle of feline heart, on [3H]-ouabain binding and Na+, K+-ATPase activity in feline ventricular membrane particles and on ouabain-sensitive 86Rb uptake in human erythrocytes. DPI 201-106 partially inhibited the Na+ pump at concentrations that caused pronounced positive inotropic effects.

Adenosine Triphosphatases↗

Genetic epidemiology of the susceptibility to leprosy.

To test the hypothesis that genetic factors are operative in the predisposition to leprosy (Hansen's disease) in humans, a genetic epidemiologic investigation was performed on 269 leprosy kindreds containing 552 affected individuals from an isolated population in Papua New Guinea. The community, and not the family, was the basic social unit. Leprosy, an infectious disease, was not communal but strongly familial within the Karimui. Segregation analysis, to determine whether a major gene for the susceptibility to leprosy was segregating within a single multi-generational kindred, could not differentiate between a Mendelian genetic and a purely environmental hypothesis. The composite kindred data, however, suggest a genetic hypothesis for the non-immunologically induced susceptibility to leprosy per se. Within familial kindreds leprosy invariably emanated from a common ancestral sibship, and risk was associated with the closeness of kin but not with infectivity or severity.

Adult↗

Mediastinal lymphangioma and chylothorax: the role of radiotherapy.

An 11-year-old boy with a capillary/cystic lymphangioma of the posterior mediastinum is described, in whom a symptomatic chylothorax proved to be refractory to surgical management. The addition of low dose mediastinal radiotherapy (2,000 cGy/10 fractions) resulted in prompt and permanent resolution of the chylothorax. Although operation is the primary modality of treatment for these lesions, the addition of radiotherapy in such refractory patients appears to be well tolerated and efficacious and should result in few long-term complications.

Child↗

Mast cells in the regulation of intestinal electrolyte transport.

Experiments were performed to determine the ionic basis and physiological messengers of transepithelial ion transport alterations (short-circuit current, Isc) measured during the induction of intestinal anaphylaxis in an Ussing chamber. Antigens derived from Trichinella spiralis, an intestinal parasite, were used to challenge jejunal tissue from guinea pigs immunized by infection with the parasite. Histamine (10(-4) M) caused an increased in Isc that was similar to that induced by antigen. Diphenhydramine (10(-5) M) inhibited the epithelial electrical responses to histamine by 100% and to antigen by 60-70%. Indomethacin (10(-5) M), in combination with diphenhydramine, completely inhibited the antigen-induced rise in Isc. Furosemide (10(-4) M) caused 50-60% inhibition of the increase in Isc induced by antigen and histamine. Antigen challenge of isolated enterocytes did not alter intracellular cAMP content. However, antigen challenge of jejunal segments in which epithelial cells were in contact with sensitized mast cells increased mucosal cAMP content. These results suggest that electrogenic Cl- secretion, mediated in part by cAMP, contributes to antigen-induced jejunal ion transport changes and that histamine and prostaglandins are involved in eliciting these epithelial responses.

Animals↗