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Biomedical subjects

A B Shapiro

Publications and source records attributed to A B Shapiro.

32 records · Page 2Linked to original sources
PubMed1991

In vivo evidence of altered chloride but not potassium secretion in cystic fibrosis rectal mucosa.

In cystic fibrosis, cyclic adenosine monophosphate-mediated chloride secretion is abnormal in respiratory, small intestinal, and rectal mucosa. Calcium-mediated chloride secretion is also aberrant in CF small intestinal mucosa in cystic fibrosis, in contrast to the respiratory epithelia, where it appears to be normal. To determine whether this disparity between calcium- and cyclic adenosine monophosphate-mediated chloride secretion exists in cystic fibrosis rectal mucosa in vivo, transrectal potential difference was measured in age-matched adult cystic fibrosis subjects (n = 8) and control subjects (n = 9) in response to 10-minute luminal perfusions of bethanechol (1 mmol/L) or theophylline (5 mmol/L). In response to bethanechol, an initial (1-minute) negative change in potential difference (-1.4 +/- 1.1 mV; mean +/- SEM) was seen in control subjects, in contrast to a positive change in mean potential difference (+2.5 +/- 1.0 mV) in cystic fibrosis subjects (control vs. cystic fibrosis, P less than 0.05). After 1 minute, mean potential differences changes in both control and cystic fibrosis subjects were positive. Theophylline perfusion resulted in a significant (P less than 0.01) difference in potential difference response between groups; at 10 minutes, the potential difference became more negative (-3.6 +/- 1.4 mV) in control subjects and more positive in cystic fibrosis subjects (+3.9 +/- 1.4 mV). To determine whether second messenger-mediated potassium secretion contributed to the observed potential difference changes in response to bethanechol and theophylline, studies were repeated in the presence of barium chloride, a known blocker of potassium conductance. In the control group, barium chloride significantly enhanced the theophylline-induced negative potential difference change (P less than 0.05) and reduced the positive potential difference change seen with bethanechol alone. In subjects with cystic fibrosis, barium chloride completely abolished the previously seen positive potential difference change in response to either bethanechol or theophylline alone. These in vivo studies suggest that there is active potassium secretion in both control and cystic fibrosis rectal mucosa in response to cyclic adenosine monophosphate- and calcium-dependent secretagogues and that the magnitude of the potential difference changes attributable to barium-inhibitable potassium secretion is the same in cystic fibrosis and control subjects. In contrast, it appears that in cystic fibrosis rectal mucosa in vivo, calcium- as well as cyclic adenosine monophosphate-dependent chloride secretion is aberrant.

Adult↗
PubMed1991

Subrenal capsule assay of human tumor chemosensitivity.

Breast and colon tumor response to emoxyl, a nitroxyl derivative of daunomycin, was detected using human tumor heterotransplantation under the renal capsule of immunocompetent mice. The substitution of adriamycin by emoxyl in the combined therapy led to enhanced therapeutic efficacy. The evidence of enhanced response of breast tumors to emoxyl obtained during the histologic examination of xenografts is in good agreement with measurements of tumor fragment weight. It is suggested to use a quantitative kinetic index kappa calculated by the method of equivalent exponents for objective evaluation of tumor response to the drugs.

Aclarubicin↗
PubMed1990

Substrate binding-induced alteration of nucleotide binding site properties of chloroplast coupling factor 1.

Two adenine nucleotide binding sites of chloroplast coupling factor 1 (CF1) were shown previously to switch their properties after exposure of the enzyme to Mg2(+)-ATP or Ca2(+)-ATP (Shapiro, A. B., and McCarty, R. E. (1988) J. Biol. Chem. 263, 14160-14165). The change in binding properties was monitored by fluorescence resonance energy transfer between Lucifer Yellow vinyl sulfone covalently bound to one alpha subunit and trinitrophenyl-ATP (TNP-ATP) tightly bound to nucleotide binding site 1. When the nucleotide binding properties of sites 1 and 3 switch during catalysis, site 3, which is nearer Lucifer Yellow than site 1, switches its nucleotide binding properties with site 1, allowing TNP-ATP to become tightly bound near Lucifer Yellow. The smaller separation allows energy transfer to occur, resulting in decreased Lucifer Yellow fluorescence. In this paper, we show that adenylyl-beta,gamma-imidodiphosphate (AMP-PNP) bound to CF1 and caused nucleotide binding sites 1 and 3 to switch properties, but was not hydrolyzed. Using AMP-PNP, we also found that relaxation of the properties of the sites to the precatalysis state after removal of substrate occurred in the absence of hydrolysis of the last bound nucleotide. When Mg2+ was omitted during exposure of CF1 to ATP, there was very little hydrolysis or nucleotide site switching. When Mg2+ was added to a very low concentration which was more than stoichiometric with CF1, however, site switching occurred at its maximal level with virtually no increase in ATP hydrolysis. These results support a model in which binding of substrate Mg2(+)-ATP, not hydrolysis, causes the putative catalytic sites to switch properties, in agreement with the alternating site catalytic cooperativity hypothesis (Boyer, P. D. (1989) FASEB J. 3, 2164-2178). TNP-ATP, the fluorescence acceptor, did not cause nucleotide site switching when incubated with CF1 in the presence of EDTA to eliminate free Mg2+. Two possible additional nucleotide binding sites were detected, in addition to the three well characterized sites. At least one of these sites was close to the Lucifer Yellow site, judging by the amount of energy transfer caused by partial occupancy with TNP-ATP.

Adenine Nucleotides↗
PubMed1989

Carbon monoxide and myonecrosis: a prospective study.

Myonecrosis has been reported to occur in patients with carbon monoxide (CO) poisoning, and last year we reported a case of non-traumatic rhabdomyolysis in a patient with CO poisoning secondary to smoke inhalation. We prospectively studied the association between CO poisoning and rhabdomyolysis by obtaining serum creatine kinase (CPK) levels on 65 of 81 consecutive patients (range 20-1315 IU/L) who presented to the University of Illinois Hospital Emergency Room during a 3-month period with CO levels greater than 5.0% (range 5.0%-63.9%). Thiocyanate levels were obtained on 45 patients (range 0-3.5 mg/dl). We found no statistically significant correlation by linear regression analysis between CO level and CPK level in these patients. A subjective complaint of weakness was obtained in 4 patients and physical evidence of weakness was found in 1 of these (this was felt to be secondary to a cerebrovascular accident). In none of these 4 patients was an elevated CPK level noted. We did, however, note an association between thiocyanate level and CPK level by linear regression analysis (p less than 0.02). A power curve was a better fit for this data (r2 = 0.7). This data suggests that serum CPK levels should not be routinely obtained on patients with CO poisoning and that cyanide may play a more important role in non-traumatic rhabdomyolysis associated with toxic inhalation than had previously been suspected.

Carbon Monoxide↗
PubMed1988

Alteration of the nucleotide-binding site asymmetry of chloroplast coupling factor 1 by catalysis.

Fluorescence resonance energy transfer was used to show that ATP hydrolysis induces a change in the properties of two nucleotide-binding sites in isolated chloroplast coupling factor 1 (CF1). The fluorescence donor was Lucifer Yellow vinyl sulfone (4-amino-N-[3-(vinylsulfonyl)phenyl]naphthalimide- 3,6-disulfonate), covalently bound to a unique site on the alpha subunit between nucleotide-binding sites 2 and 3. The fluorescence acceptor was the ATP analog 2'(3')-trinitrophenyladenosine 5'-triphosphate (TNP-ATP), incorporated specifically into nucleotide-binding site 1. Energy transfer from Lucifer Yellow to TNP-ATP in site 1 was greater if catalysis occurred before TNP-ATP was incorporated than if no catalysis occurred, indicating that one of the nucleotide-binding sites near the Lucifer Yellow had changed its properties to those of site 1 as a result of catalysis. The amount of energy transfer increased with the degree of substrate excess during catalysis, as expected if catalysis were required for the new site 1 location. ADP, which binds to CF1, but is not a substrate for hydrolysis, caused little energy transfer. Titration of site 3 with TNP-ATP showed greater energy transfer from Lucifer Yellow when catalysis had not occurred, indicating that sites 1 and 3 switched properties as a result of catalysis. The amount of energy transfer declined exponentially with time between removal of substrate and addition of TNP-ATP to site 1, with a half-time of 1.5-2 h at room temperature. This result suggests that the change that results in switching of nucleotide-binding sites 1 and 3 relaxes in the absence of substrate. Our results show that the asymmetry of the nucleotide-binding sites of CF1 is not a permanent feature of the molecule.

Adenosine Triphosphate↗
PubMed1988

Pharmacokinetics of a spin-labeled rubomycin analog.

Pharmacokinetics of a spin-labeled analog of rubomycin (ruboxyl) was studied. Differences were found in ruboxyl pharmacokinetics in normal and tumor-bearing animals. Most of the drug was excreted within 6 h. The differences in pharmacokinetics of ruboxyl and nitroxyl radical were established.

Animals↗
PubMed1988

Myonecrosis in carbon monoxide poisoning.

Myonecrosis is an unusual sequelae to carbon monoxide poisoning with only 16 cases having been reported in the English-language literature. At the University of Illinois Hospital, we encountered a 25-year-old fire academy student who presented to our Emergency Department with a carboxyhemoglobin level of 16% following a training exercise in a smoke-filled room. The patient was not wearing a self-contained breathing apparatus and his duration of exposure was 7-8 min, by which time he had blacked out for about 1 min. Upon arrival, the patient was lethargic, with a moderate inhalation burn. The patient was treated with hyperbaric oxygen at 2 1/2 ATA. Following 90 min of hyperbaric oxygen, slight flexor compartment weakness, along with tenderness of the proximal lower extremities was noted. CPK was elevated to 65,998 (100% mm) with urine dipstick being positive for blood and only occasional rbc's seen in the urine sediment. The patient did well with forced diuresis and alkalinization of the urine. No oliguria was noted and the CPK fell to 893 five days later. This is the only case in the English-language literature who developed myonecrosis from carbon monoxide, despite hyperbaric oxygen treatment. We believe that this case demonstrates that hyperbaric oxygen cannot prevent the development of myonecrosis induced by carbon monoxide.

Adult↗
PubMed1975

Adsorption of small molecules to bovine serum albumin studied by the spin-probe method.

A spin-probe technique is used for quantitative EPR studies of adsorption of small molecules on globular proteins, of the rigidity of their binding to the protein and of the polarity of the environment. In the case of bovine serum albumin it is shown that nitroxyl radical (2, 2, 6, 6-tetramethyl-4-oxy-1-oxyl-piperidine)-stearate (I) has an adsorption behaviour similar to that of the fatty acids, nitroxyl radical (2, 2,4, 4-tetramethyl-1, 2, 3, 4-tetrahydro-5, 6-benzo-gamma-carboline-3-oxyl) (II) to that of the tryptophan molecule. Radical I rotates relative to the protein molecule, while Radical II is rigidly bound to the protein.

Adsorption↗
PubMedDate not supplied

[Spin label study of the structure and conformational properties of fibers from cotton grown from gamma-irradiated seeds].

According to ESR spectra of the radical - probe I it has been shown that there are two regions in cotton cellulose: ordered and disordered ones, pointing to inhibition and free rotation of the radical. 40 spin-labeled samples of cotton filaments and their mutants by the radicals II-IX chemically bound by the cellulose hydroxyl group were obtained. From ESR spectra strong inhibition of iminoxyl radical was established which was the evidenced of high rigidity of disordered regions of cellulose. Conformational changes of cotton cellulose grown from seeds exposed to different doses of gamma-irradiation.

Cellulose↗