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Biomedical subjects

J R Walsh

Publications and source records attributed to J R Walsh.

At least 19 recordsLinked to original sources
PubMed2001

Algae permeability to Me(2)SO from -3 to 23 degrees C.

Biphasic transport of water and dimethyl sulfoxide (Me(2)SO), a common cryoprotective agent (CPA), in algal cells was induced and measured on a cryoperfusion stage. A two-step experimental protocol provided data for the volumetric response of Chlorococcum (C.) texanum to impermeable and permeable solutes. First, the cells were exposed to a 500-mOsm sucrose solution, causing immediate shrinkage of the cell to a minimum equilibrium volume. Then an isoosmotic 200-mOsm/300-mOsm CPA/sucrose solution was introduced to the cells, resulting in increased cell volume to a new equilibrium state. Experiments were conducted at temperatures between -3 and 23 degrees C. Cell volumes were measured off-line by computer analysis of video images. A network thermodynamic model was fit to the transient volume data to determine permeabilities of C. texanum to water and Me(2)SO over the full temperature range, and results were calculated with two numeric methods. Biphasic transport was found to be slower at colder temperatures, with water entering the cell faster than Me(2)SO. Experimental results were also compared with data from similar experiments using methanol (MeOH) as the CPA. MeOH influx was calculated to be a magnitude larger than that of water. Additionally, MeOH permeability was at least three orders of magnitude greater than Me(2)SO permeability, and the difference in these solute permeabilities increased as temperature decreased.

Biological Transport, Active↗
PubMed1998

Measurement of cell volume loss in the liquid region preceding an advancing phase change interface.

It is well understood that the solidification of a solution results in a redistribution of solute in the liquid zone. For the freezing of suspensions of cells it is anticipated that accumulation of solute in the region leading a growing ice phase will cause an osmotic response in cells before the ice phase reaches the cells. To measure this phenomenon in a specific algal species, the volume changes in Chlorococcum texanum during freezing were studied using directional solidification cryomicroscopy. The relative cell volume was tracked continuously as a function of temperature and position as cells encountered the moving phase front. The loss of cell volume was measured in the liquid region containing concentrated solute ahead of the growing solid phase.

Cell Size↗
PubMed1992

Determination of tetracyclines in bovine and porcine muscle by high-performance liquid chromatography using solid-phase extraction.

A method is presented for the determination of the three tetracyclines oxytetracycline, tetracycline and chlortetracycline in muscle, spiked at 100 ng/g, using high-performance liquid chromatography (HPLC). The concentration and extraction steps are carried out using Waters Environmental Sep-Pak cartridges. The principal steps involve homogenizing the sample in EDTA-McIlvaine buffer followed by centrifugation and precipitation of the supernatant using trichloroacetic acid. After further filtration and concentration on a Sep-Pak cartridge, the sample is eluted and analysed by HPLC with UV detection and confirmation by diode-array. The column used is a Nova-Pak C18 (4 microns) cartridge (10 cm x 8 mm I.D.). A phosphate-citrate-acetonitrile buffer, utilizing ion suppression, is the mobile phase. The analytes are detectable at levels down to 10 ng/g. The analyte identity can be confirmed at 20 ng/g by the use of diode-array detection and spectral library comparison.

Animals↗
PubMed1992

High-performance liquid chromatography of sulphonamides extracted from bovine and porcine muscle by solid-phase dispersion.

A method has been developed for the analysis of sulphonamides in bovine and porcine muscle, based on solid-phase dispersion. Muscle tissue was blended with pre-washed C18 coated silica (55-105 microns), and the resulting homogeneous solid packed into a polypropylene syringe barrel. Fatty material was washed from the sample using hexane, and the sulphonamide analytes eluted with dichloromethane. The collected fraction was dried under nitrogen and reconstituted in 20% methanol in 0.01 M sodium acetate/acetic acid (pH 5) buffer. After sonication and filtration, the sample was analysed by high-performance liquid chromatography on a C18 column using UV diode array detection. Individual sulphonamides could be detected down to 0.01 ppm, whilst analyte identity could be confirmed by diode array spectrum down to 0.02 ppm.

Animals↗
PubMed1989

Studies on the human metabolism of iproplatin.

We have previously shown that a significant portion of the total platinum in the plasma of patients receiving iproplatin is protein-bound. We have also identified cis-dichloro-bis-isopropylamine platinum(II) (CIP) as a major metabolite of iproplatin. To understand the nature of the bound platinum, we carried out in vitro comparative protein-binding studies for iproplatin and CIP. These studies indicate that when CIP is incubated in plasma, protein binding occurs, with a 2.7-h half-life for the disappearance of CIP; the parent complex does not bind and is stable in plasma for at least 48 h. The time dependence of protein binding with CIP suggests the formation of other chemical species from CIP that may be responsible for the observed protein binding. The results indicate that in patients receiving the drug, the reduction of iproplatin to CIP must take place intracellularly and that CIP or its protein-binding derivatives must efflux from the cells into the plasma. Efflux studies carried out to explore this possibility with cells in the whole blood showed that iproplatin was taken up into cells, but the efflux of protein-binding iproplatin metabolites did not occur. To understand further the nature of the metabolites of iproplatin, we carried out 195Pt-NMR (nuclear magnetic resonance) studies with urine from two patients who received a high dose of iproplatin (500 mg/m2). The predominant signals from the 195Pt-NMR corresponded to the divalent platinum complexes and not to quadrivalent complexes, indicating that the iproplatin metabolites in urine are divalent in nature.

Antineoplastic Agents↗
PubMed1989

Uptake and metabolism of iproplatin in murine L1210 cells.

Iproplatin is structurally unique among the platinum (Pt) agents in the clinic because it is a quadrivalent complex. On the basis of the redox parameters for the Pt(IV) and Pt(II) oxidation states in a chloride system, it has been suggested that Pt(IV) complexes will be reduced to Pt(II) complexes in a biological environment. To test this hypothesis, uptake and metabolism studies of [14C]-iproplatin were carried out in L1210 cells. The L1210 cells raised in DBA2/J mice were incubated in vitro with 50 and 100 microM [14C]-iproplatin at 37 degrees C in Hanks' balanced salt solution, and total uptake and radioactivity associated with acid-insoluble fractions were measured for up to 3 h. Under these conditions, the uptake of iproplatin was linear with time and increased with increasing concentrations of iproplatin in the medium. At all times measured, greater than 35% of radioactivity was associated with the acid-insoluble fraction, suggesting binding to macromolecules. The [14C]-labelled compounds in neutralized acid extracts of cells were separated by reverse-phase high-performance liquid chromatography (HPLC). Three labelled compounds were detected; based on chromatographic elution times, they appeared to be iproplatin, cis-dichloro-bis-isopropylamine platinum(II) (CIP), the reduction product of iproplatin, and a third compound more polar than iproplatin and CIP. The finding of free CIP and the macromolecular binding of radioactivity in the cells suggests that iproplatin is reduced intracellularly.

Animals↗
PubMed1989

Drug-induced illness in the elderly.

The elderly are predisposed to adverse drug reactions because of age-related physiologic changes, interaction of one drug with another, and interaction between a drug and a coexisting medical condition. Recognition of such adverse reactions is essential, because many are reversible and many are even preventable. Assessment of clinical disorders in the elderly should include evaluation of drugs as a causal or aggravating factor. Careful choice and dosage of drugs in the elderly will minimize the likelihood of drug-induced illness.

Aged↗
PubMed1985

The isolation and characterization of lysozyme from human foetal membranes: a comparison with the enzyme from other sources.

Lysozyme (muramidase) was isolated from an acidic extract of human foetal membranes by adsorption and elution from octadecyl silica. It was further purified by gel-filtration and ion-exchange. The final product was homogeneous by high performance liquid chromatography (h.p.l.c.) and electrophoresis. It was indistinguishable from human milk lysozyme by all criteria investigated, including amino acid composition, electrophoretic mobility, retention time on h.p.l.c. and sequence of the first nine residues. Human uterine decidual tissue was shown to contain a similar concentration of lysozyme to foetal membranes. The enzyme was also present at lower concentrations in amnion, placenta and amniotic fluid.

Amino Acids↗
PubMed1981

Limited sequence homology between porcine and rat relaxins: implications for physiological studies.

We have isolated rat relaxin as a single chromatographic component and determined its complete amino acid sequence. Comparison with porcine relaxin reveals a clear sequence homology but the extent of this is much more limited than expected, with only 21 of 53 residues (39.6%) in corresponding positions being identical. In contrast 47 of 51 residues (92.2%) are identical between porcine and rat insulins. These findings suggest that relaxin has been less constrained to conserve its structural features during evolution than has insulin, since the original duplication of a common ancestral gene. Relaxins as a group (and rat and porcine relaxins in particular) show poor immunological cross-reactivity despite a common biological activity. The finding of extensive sequence differences as well as conserved residues between porcine and rat relaxins provides a possible structural basis for these observations, and should facilitate identification of a localized receptor-binding surface region of relaxin. A further important implication of this limited sequence homology is that physiological (and clinical) studies with relaxins should whenever possible be carried out with hormone preparations from the same species.

Amino Acid Sequence↗
PubMed1981

Hematologic disorders in the elderly.

Management of hematologic disorders in older patients must often be weighed in a setting of decreased physiological reserves and concurrent illnesses. Anemia in the elderly should never be attributed to old age. Even a mild anemia in collusion with multiple physical and mental problems may tip the balance for those previously able to cope with their disabilities. Iron deficiency anemia and the anemia of chronic disease are the most common types of anemia in the elderly. Nutritional anemias due to folate or vitamin B(12) deficiency are treatable and should not be overlooked. Newer chemotherapy regimens for acute nonlymphocytic leukemia have been effective in many older patients. Decisions to treat are sometimes difficult, often depending on the aggregate of coexistent physical and mental disorders. The most prevalent type of leukemia in the elderly is chronic lymphocytic leukemia. A benign asymptomatic course requires no therapy, but aggressive disease requires treatment. Multiple myeloma should be suspected in an elderly person who has both unexplained anemia and bone pain. After definitive diagnosis, phlebotomy therapy should be considered for both polycythemia vera and secondary erythrocytosis to reduce blood viscosity and increase cerebral blood flow.

Acute Disease↗
PubMed1980

Use of an octadecylsilica purification method minimizes proteolysis during isolation of porcine and rat relaxins.

Previous attempts to purify relaxin from pregnant sow and rat ovaries have led to the identification of multiple components with very similar molecular weights (around 6000 daltons) and similar, but not identical amino acid compositions. It has been unclear whether these multiple forms of relaxin represented different allelic forms (isohormones), intermediates in a prohormone-hormone conversion, different hormones in their own right responsible for effects on different target tissues, or degradation products. We have applied a purification system using adsorption to small octadecylsilica (ODS) columns to reduce drastically the degree of heterogeneity. Both pig and rat relaxins are isolated as single major components with defined amino acid sequences and with minimal contamination by other molecular forms. These findings indicate that the relaxin heterogeneity previously observed is due to proteolysis of a single major stored form during conventional isolation procedures.

Animals↗
PubMed1977

Hepatic porphyrias. Current concepts.

Acute intermittent porphyria, variegate porphyria, and hereditary coproporphyria are hepatic porphyrias due to enzyme defects that are inherited as autosomal dominants. Porphyria cutanea tarda is considered an acquired disorder. Similar drugs or circumstances are precipitants of acute attacks in all three inherited hepatic porphyrias. The respective biochemical abnormalities are identifiable by simple, readily available laboratory tests. Management of patients with any of the inherited hepatic porphyrias is directed primarily toward prevention of attacks through avoidance of precipitants and through a diet high in carbohydrate. Therapy for porphyria cutanea tarda includes interdiction of alcohol use and repeated phlebotomy.

5-Aminolevulinate Synthetase↗