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Biomedical subjects

David Chow

Publications and source records attributed to David Chow.

5 recordsLinked to original sources
PubMed2006

Identification of a novel in vitro metabonate from liver microsomal incubations.

In vitro drug metabolism studies during the early drug discovery stage are becoming increasingly important. With the increasing demand for high throughput and quick turnaround time for in vitro metabolism studies, however, careful examination of the results and proper design of the experiments are still crucial. In this communication, we report the identification and mechanism of formation of a novel metabonate from incubations of a diamine-containing compound with liver microsomes. The metabonate appeared to be the major product, and its formation was NADPH- and microsomal protein-dependent. Liquid chromatography/mass spectrometry and NMR analysis of the metabonate indicated an extra carbon and unusual formation of an imidazolidine ring. Further studies revealed that this metabonate was not a true biotransformation product from the diamine compound itself in the microsomal incubation, but rather a product resulting from a condensation reaction between the compound and a metabolite of the solvent (alcohol) used in the incubation. When the microsomal incubations contained a small amount of methanol or ethanol as solvent, the alcohols were metabolized to formaldehyde or acetaldehyde, which then condensed with the diamine compound through an imine intermediate to form the metabonate. The compound itself was metabolically stable in vitro when acetonitrile or dimethyl sulfoxide was used as solvent. During the study of in vitro microsomal stability and metabolite identification of amine-containing compounds, the use of alcohol as solvent should be avoided.

Animals↗
PubMed2003

Ferredoxin from sweet pepper (Capsicum annuum L.) intensifying harpin(pss)-mediated hypersensitive response shows an enhanced production of active oxygen species (AOS).

The hypersensitive response (HR) is a form of cell death associated with plant resistance to pathogen infection. Harpin(pss), an elicitor from the bacterium Pseudomonas syringae pv. syringae, induces a HR in non-host plants. Previously, we reported an amphipathic protein from sweet pepper interfering with harpin(pss)-mediated HR. In this report, we isolated and characterized a cDNA clone encoded that amphipathic protein from sweet pepper. This protein is designated as PFLP (plant ferredoxin-like protein) by virtue of its high homology with plant ferredoxin protein containing an N-terminal signal peptide responsible for chloroplast targeting and a putative 2Fe-2S domain responsible for redox activity. Recombinant PFLP obtained from Escherichia coli was able to significantly increase active oxygen species (AOS) generation when mixed with harpin(pss) in tobacco suspension cells. It also showed enhanced HR when co-infiltrated with harpin(pss) in tobacco leaves. We used a transgenic tobacco suspension cells system that constitutively expresses the Pflp gene driven by the CaMV 35S promoter to study the function of PFLP in enhancing harpin(pss)-mediated hypersensitive cell death in vivo. In response to harpin(pss), suspension cells derived from Pflp transgenic tobacco showed a significant increase both in the generation of AOS and in cell death as compared to the wild type. AOS inhibitors diphenylene iodonium chloride (DPI) and lanthanum chlorate (LaCl3) were used to study the involvement of AOS in harpin(pss)-induced cell death. Our results demonstrate enhanced generation of AOS is necessary to cause enhanced hypersensitive cell death in Pflp transgenic tobacco cells and it is plasma membrane-bound NADPH-oxidase-dependent. Sub-cellular localization studies showed that PFLP is present in the cytoplasm and chloroplast of Pflp transgenic tobacco cells, but only in the chloroplast, not in the cytoplasm, of wild-type tobacco cells. It is possible that PFLP can change the redox state of the cell upon harpin(pss) inoculation to increase AOS generation and hypersensitive cell death. Overall, this study will provide a new insight in the functional properties of ferredoxin in hypersensitive cell death.

Amino Acid Sequence↗
PubMed2002

Painless foot drop: an atypical etiology of a common presentation.

Weakness of the dorsiflexor muscles of the foot is a relatively common presentation. In most cases, the etiology involves a peripheral injury to the common peroneal nerve. These patients usually present with lower motor neuron findings on evaluation. In contrast, if upper motor neuron findings were present a central lesion should be suspected and appropriate imaging studies are performed. We describe a patient with painless foot drop and lower motor findings on examination that was diagnosed with multiple sclerosis. This case demonstrates that multiple sclerosis can masquerade as a peripheral process in some patients.

Journal Article↗
PubMedDate not supplied

Provocative cervical discography symptom mapping.

BACKGROUND CONTEXT: In a small prospective study assessing 10 symptomatic and 10 asymptomatic subjects, Schellhas et al. compared cervical discography to magnetic resonance imaging. Within that study he reported on the distribution of pain for the C3-C4 to C6-C7 levels. Four years later, Grubb and Ellis reported retrospective data from his 12-year experience using cervical discography from C2-C3 to C7-T1 in 173 patients. To date, no large prospective study defining pain referral patterns for each cervical disc has been performed. PURPOSE: To conduct a prospective visual and statistical descriptive study of pain provocation of a cohort of subjects undergoing cervical discography. STUDY DESIGN/SETTING: Prospective multicenter descriptive study. METHODS: Pain referral maps were generated for each disc level from patients undergoing cervical discography with at least two levels assessed. If concordant pain was reproduced in a morphologically abnormal disc, the subject immediately completed a pain diagram. An independent observer interviewed the subject and recorded the location of provoked symptoms. Visual data were compiled using a body sector bit map, which consisted of 48 clinically relevant body regions. Visual maps with graduated color codes and frequencies of symptom location at each cervical disc level were generated. RESULTS: A total of 101 symptom provocation maps were recorded during cervical discography on 41 subjects. There were 10 at C2-C3, 19 at C3-C4, 27 at C4-C5, 27 at C5-C6, 16 at C6-C7 and 2 at C7-T1. Predominantly unilateral symptoms were provoked just as often as bilateral symptoms. The C2-C3 disc referred pain to the neck, subocciput and face. The C3-C4 disc referred pain to the neck, subocciput, trapezius, anterior neck, face, shoulder, interscapular and limb. The C4-C5 disc referred pain to the neck, shoulder, interscapular, trapezius, extremity, face, chest and subocciput. The C5-C6 disc referred pain to the neck, trapezius, interscapular, suboccipital, anterior neck, chest and face. The C6-C7 disc referred pain to the neck, interscapular, trapezius, shoulder, extremity and subocciput. At C7-T1 we produced neck and interscapular pain. Visual maps with graduated color codes and frequencies of symptom location at each cervical disc level were generated. CONCLUSIONS: In conclusion, these results confirm the observations of prior investigators that cervical internal disc disruption can elicit axial and peripheral symptoms. The particular patterns of pain generation allow the discographer to preprocedurally anticipate disc levels to assess. With these data, the number of disc punctures that are required can be limited rather than routinely assessing all cervical discs.

Cervical Vertebrae↗