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Biomedical subjects

R P Schmidt

Publications and source records attributed to R P Schmidt.

At least 19 recordsLinked to original sources
PubMed1999

Clinical pharmacokinetics of 123I-IAZA in healthy volunteers.

123I-labelled iodoazomycin arabinoside (123I-IAZA) is an experimental radiopharmaceutical that has been shown to have clinical utility for imaging regional tissue hypoxia. We report the clinical pharmacokinetics of IAZA, the radiopharmacokinetics of 123I-IAZA and total radioactivity kinetics after injection of 123I-IAZA. Six healthy volunteers each received an intravenous bolus injection of 185 MBq of 123I-IAZA. Thirteen blood samples and a cumulative urine sample were collected over 28 h from each subject. A two-compartment open model best described the disposition characteristics of all three chemical components, with terminal phase half-lives of 179 +/- 24, 232 +/- 41 and 294 +/- 27 min for 123I-IAZA, IAZA and total radioactivity, respectively. 123I-IAZA had a steady-state volume of distribution (Vss) of 0.716 +/- 0.088 l.kg-1 and a systemic clearance (Cls) of 239 +/- 48 ml.min-1. Radioactive decay was responsible for about 37% of clearance; of the remaining radioactivity, about 92% was eliminated renally. Only about 12% of 123I-IAZA was eliminated unchanged in urine, indicating that renal excretion was the major route of elimination for the radioactive metabolites rather than for 123I-IAZA itself. The effective half-lives of 123I-IAZA and total radioactivity reported here are considerably shorter than previously estimated. Our results confirm that 123I-IAZA has appropriate pharmacokinetic and radiopharmacokinetic properties to support clinical hypoxia imaging.

Adult↗
PubMed1993

The MotA protein from bacteriophage T4 contains two domains. Preliminary structural analysis by X-ray diffraction and nuclear magnetic resonance.

Controlled protease cleavage experiments and N-terminal sequence analyses were used to show that the transcriptional activator MotA from bacteriophage T4 has a two-domain structure. The N and C-terminal domains have M(r) values of 10,300 and 11,800, respectively, and were separately cloned and overexpressed in Escherichia coli. One and two-dimensional NMR spectroscopy indicate that both domains have stably folded structures and contain extensive secondary structure. The N-terminal domain is substantially alpha-helical, whereas the C-terminal domain has a high content of beta-strand. The N-terminal domain has been crystallized under three different conditions, all with the space group P3(1(2))21 and similar unit cell dimensions. The best crystals are grown from ammonium sulfate, have cell dimensions a = b = 46.7 A, c = 139.6 A, and diffract to beyond 2.4 A. The high quality of the NMR and diffraction data will allow a complete structural analysis of MotA by a combination of these techniques.

Bacteriophage T4↗
PubMed1992

Purified MotA protein binds the -30 region of a bacteriophage T4 middle-mode promoter and activates transcription in vitro.

The bacteriophage T4-encoded MotA protein is critical for transcription from T4 middle-mode promoters. However, a direct interaction of this protein with a middle-mode promoter has not previously been demonstrated. We have cloned the motA gene and overexpressed the gene product using the T7 expression system. A simple procedure was then developed to purify the MotA protein to homogeneity. Using the purified protein we have demonstrated that MotA protein binds to the -30 region of the middle-mode promoter PuvsY. This promoter has previously been shown to be a necessary component of a T4 replication origin, and thus MotA is also a T4 origin-binding protein. Modified RNA polymerase purified from T4-infected cells was used to establish middle-mode transcription in vitro. Transcription from PuvsY was markedly enhanced by the addition of MotA protein, whether or not the template contained the cytosine modifications characteristic of T4 DNA. However, transcription from PuvsY was apparently independent of the MotA protein when unmodified RNA polymerase from uninfected cells was used.

Base Sequence↗
PubMed1992

Anosognosia during Wada testing.

Anosognosia, the verbally explicit denial of hemiplegia, is more often reported after right- than left-hemisphere lesions. However, this asymmetric incidence of anosognosia may be artifactual and related to the aphasia that often accompanies left-hemisphere lesions. Anosognosia has been attributed to psychological denial and the emotional changes associated with hemispheric dysfunction. Eight consecutive patients undergoing intracarotid barbiturate (methohexital) injections as part of their presurgical evaluations for intractable epilepsy were assessed for anosognosia after their hemiplegia and aphasia had cleared. After their left-hemisphere anesthesia, all subjects recalled both their motor and language deficits. However, after right-hemisphere anesthesia, none of the eight patients recalled their hemiplegia. These results suggest that anosognosia is more often associated with right- rather than left-hemisphere dysfunction and that it cannot be attributed to either psychological denial or the emotional changes associated with hemispheric dysfunction.

Agnosia↗
PubMed1991

Tc-99m HMPAO to demonstrate diffuse cortical necrosis in vivo.

Tc-99m hexamethylpropylene amineoxime (HMPAO) is a novel radiopharmaceutical demonstrated to be a sensitive indicator of abnormalities of cerebral perfusion. Most reports in the literature have evaluated patients with gross perfusion deficits, such as cerebrovascular accidents, and with dementia, where patterns of diffuse perfusion deficit were reported comparable with those seen in PET studies. We report a patient in whom there was the rapid onset of dementia, with the HMPAO images demonstrating diffuse loss of cortical perfusion in a nonfocal, and nonsegmental, fashion. Correlation with postmortem examination demonstrates good concordance between the diffuse nature of HMPAO loss, and diffuse cortical necrosis throughout both cerebral hemispheres. The technique was shown to be more sensitive than transmission CT scanning in demonstrating the extent of the deficit, and it correlated closely with the functional deficits noted in the patient.

Acute Disease↗
PubMed1985

The detection of abscesses with diffusible tracers.

In six patients with suspected infection, scintigraphy with diffusible tracers outlined the margins and central portion of an abscess. An animal model was developed to study this process quantitatively. Small inflammatory lesions yielding volumes of pus of 0.1-0.2 mL were shown to have increased blood volume of 0.7 +/- 0.5 mL, increased blood flow by a factor of three and increased extracellular fluid volume of 10 +/- 6 mL. This supports the patient data and indicates that the pathophysiologic features characterising the clinical studies are hyperemia and oedema associated with an abscess. The slow, central area of tracer diffusion corresponded to the presence of pus. Scintigraphy with 99mTc-DTPA is a convenient way of detecting suspected inflammatory lesions and localising collections of pus.

Abscess↗
PubMed1972

A dean's viewpoint.

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Comprehensive Health Care↗