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Biomedical subjects

M Dasgupta

Publications and source records attributed to M Dasgupta.

At least 19 recordsLinked to original sources

Severe inhibition of fusion by quasifission in reactions forming 220Th.

Evaporation residue cross sections have been measured following the fusion of 16O with 204Pb, forming the compound nucleus 220Th. These are compared with existing data for the same compound nucleus formed following fusion reactions with 40Ar, 48Ca, 82Se, and 124Sn projectiles. At energies where the reduced cross sections of xn evaporation residues would be expected to be the same for all reactions, those for the heavier projectiles are typically a factor of 10 smaller than those for 16O. This inhibition is attributed to strong competition of quasifission with fusion at the low angular momenta associated with evaporation residue formation.

Journal Article↗

Fusion suppression and sub-barrier breakup of weakly bound nuclei.

The mechanism for the large suppression of complete fusion in the 9Be+208Pb reaction has been investigated through measurement of sub-barrier breakup of 9Be. Excluding breakup through the 8Be ground state, whose lifetime is too long, a prompt breakup component remains, having sufficient probability to explain the observed suppression of complete fusion. This appears to be associated with interactions at the nuclear surface. The fusion suppression is predicted to be almost proportional to the charge of the target nucleus, making it most significant in reactions with heavy nuclei.

Journal Article↗

Unexpected inhibition of fusion in nucleus-nucleus collisions.

Unstable heavy atomic nuclei not found in nature can be created by fusing two stable nuclei, in a process analogous to colliding charged droplets of liquid. Recently, the formation of a handful of super-heavy nuclei with atomic numbers 114 (ref. 1) and 116 (ref. 2) has been achieved by fusion of heavy nuclei. The electrostatic energy of such systems is very large (which is the reason super-heavy nuclei are unstable), so although the two nuclei may initially be captured by the nuclear potential, rather than fusing, they almost always separate after transfer of mass to the lighter nucleus. This process, called quasi-fission, can inhibit fusion by many orders of magnitude. Understanding this inhibition may hold the key to forming more super-heavy elements. Theoretically, inhibition is predicted (ref. 5 and references therein) when the product Z1Z2 of the charges of the projectile and target nuclei is larger than about 1,600. Here we report measurements of three fusion reactions with Z1Z2 around half this value, each forming 216 88Ra. We find convincing model-independent evidence both of inhibition of fusion, and of the presence of quasi-fission. These results defy interpretation within the standard picture of nuclear fusion and fission.

Journal Article↗

Subcutaneous fluid infusion in a long-term care setting.

OBJECTIVE: To study the use of hypodermoclysis in a long-term care setting for chronic fluid supplementation and to compare it to intravenous (IV) fluid in the treatment of acute mild to moderate dehydration. DESIGN: A prospective observational study. PARTICIPANTS: Fifty-five residents of a long-term care facility treated with fluid therapy during a 5-week period. MAIN OUTCOME MEASURES: Efficacy of hydration and adverse effects were obtained from detailed chart review, interviews with healthcare providers, and investigators' observations. RESULTS: The study subjects were frail older people. Hypodermoclysis was used for maintenance fluid needs in 24 residents; none of these residents required any additional fluid therapy for dehydration. In addition, 37 residents received fluids for acute dehydration. In these residents, hypodermoclysis was associated with clinical improvement in 57% and no clinical change in 25%. Recipients of IV fluids improved 81% of the time and the remainder were unchanged. Hypodermoclysis was associated with fewer fluid therapy-related complications relative to IV therapy (P = .04). CONCLUSIONS: Hypodermoclysis is an effective procedure for providing fluids for both chronic maintenance needs and acute situations associated with mild to moderate dehydration in a long-term care setting. Hypodermoclysis appears safer and can avoid transfers to hospital for rehydration.

Aged↗

Antipeptide antibodies as probes of subunit-dependent structural changes in the regulatory domain of the gamma-subunit of phosphorylase kinase.

The gamma-subunit of phosphorylase kinase contains a protein kinase catalytic domain (residues 20-276) and a regulatory domain (residues 276-386). The purpose of the present investigation was to develop monospecific antibodies against four synthetic gamma-subunit regulatory domain peptides (PhK1: 362-386; PhK5: 342-366; PhK9: 322-346; PhK13: 302-326) to use as probes to study the structure of the regulatory domain. Each affinity-purified antibody was characterized with regard to its ability to bind three different structural forms of the gamma-subunit: the isolated gamma-subunit, the gamma-delta complex, and the holoenzyme complex (alpha beta delta gamma)4. Of the four antibodies, binding of affinity-purified anti-PhK13 was most affected by alterations in gamma-subunit interactions. Taken together, the data from this investigation indicate that the regulatory domain of the gamma-subunit can assume different immunochemically distinguishable conformations as the result of interactions among the alpha-, beta-, gamma-, and delta-subunits of phosphorylase kinase.

Amino Acid Sequence↗

Beta 2-microglobulin amyloidosis presenting as esophageal perforation in a hemodialysis patient.

A 45-year-old male with hypertensive end-stage renal disease and on maintenance hemodialysis for 13 years is reported. He presented with life-threatening hematemesis, secondary to esophageal rupture. Immunohistological staining and electron microscopy examination of the esophageal perforation showed depositions of beta 2-microglobulin (beta 2-M) amyoloid. The unique aspect presented here is the localized esophageal involvement with beta 2-M amyloidosis. This is the first reported patient with esophageal perforation, due to the deposition and infiltration of the lower esophagus with beta 2-M which predisposed to its rupture.

Amyloidosis↗

Activation and inhibition of phosphorylase kinase by monospecific antibodies raised against peptides from the regulatory domain of the gamma-subunit.

The C terminus of the catalytic gamma-subunit of phosphorylase kinase comprises a regulatory domain that contains regions important for subunit interactions and autoinhibitory functions. Monospecific antibodies raised against four synthetic peptides from this region, PhK1 (362-386), PhK5 (342-366), PhK9 (322-346), and PhK13 (302-326), were found to have significant effects on the catalytic activities of phosphorylase kinase holoenzyme and the gamma delta complex. Antibodies raised against the very C terminus of the gamma-subunit, anti-PhK1 and anti-PhK5, markedly activated both holoenzyme and the gamma delta complex, in the presence and absence of Ca2+. In the presence of Ca2+ at pH 8.2, anti-PhK1 activated the holoenzyme more than 11-fold and activated the gamma delta complex 2.5-fold. Activation of the holoenzyme and the gamma delta complex by anti-PhK5 was 50-70% of that observed with anti-PhK1. Prior phosphorylation of the holoenzyme by the cAMP-dependent protein kinase blocked activation by both anti-PhK1 and anti-PhK5. Antibodies raised against the peptides from the N terminus of the regulatory domain, anti-PhK9 and anti-PhK13, were inhibitory, with their greatest effects on the gamma delta complex. These data demonstrate that the binding of antibodies to specific regions within the regulatory domain of the gamma-subunit can augment or inhibit structural changes and subunit interactions important in regulating phosphorylase kinase activity.

Amino Acid Sequence↗

The influence of renal function on the pharmacokinetics of unchanged and acyl-glucuroconjugated ketoprofen enantiomers after 50 and 100 mg racemic ketoprofen.

1. To study the effect of renal dysfunction on the pharmacokinetics of ketoprofen (KT), and the possibility of saturation of clearance with elevation of dose, single 50 and 100 mg doses of racemic ketoprofen were administered in a cross-over fashion to seven patients (creatinine clearance, CLCR, 6-72 ml min-1). 2. The stereospecific disposition kinetics of KT enantiomers and their acyl-glucuronide conjugates (KTconj) were determined in plasma and urine for 24 h post-dose. 3. Decreased renal function was associated with a reduced KT oral clearance (CLO) and terminal elimination rate constant (lambda z). Renal clearance of KT conj (CLrconj) was reduced with diminished renal function. 4. Following both 50 and 100 mg doses, there was significant stereoselectivity in the AUC of KT (mean S/R, 0.87 and 0.83, respectively), the AUC of KTconj (mean S/R, 3.4 and 5.2, respectively) and the cumulative urinary excretion of KTconj (mean S/R, 2.1 and 2.2, respectively). The stereoselectivity in renal dysfunction in contrast with the observations previously made in healthy subjects may suggest a disease-related process. 5. CLO remained constant after increasing the dose, indicating linearity in the pharmacokinetics of KT despite reduced CLCR. CLrconj, however, was significantly reduced after the 100 mg dose suggestive of saturation of the urinary clearance and existence of a compensatory pathway. 6. Renal impairment reduces CLrconj and this appears to be the rate-limiting step for clearance of KT due to the observed stronger correlations of CLO with CLrconj than with CLCR. 7. Dose reduction of ketoprofen is indicated only for patients with CLCR < 20 ml min-1.

Anti-Inflammatory Agents, Non-Steroidal↗

Characterization of the regulatory domain of the gamma-subunit of phosphorylase kinase. The two noncontiguous calmodulin-binding subdomains are also autoinhibitory.

Phosphorylase kinase is a multimeric protein kinase (alpha 4 beta 4 gamma 4 delta 4) whose enzymatic activity is conferred by its gamma-subunit. A library of 18 overlapping synthetic peptides spanning residues 277-386 of the gamma-subunit has been prepared to use in identifying important regulatory structures in the protein. In the present study, the library was screened to identify regions that might function as autoinhibitory domains. Peptides from two distinct regions were found to inhibit the Ca2(+)-activated holoenzyme. The same regions were previously found to bind calmodulin (i.e. the delta-subunit; Dasgupta, M. Honeycutt, T., and Blumenthal, D. K. (1989) J. Biol. Chem. 264, 17156-17163). The most potent substrate antagonist peptides were PhK13 (residues 302-326; Ki = 300 nM) and PhK5 (residues 342-366; Ki = 20 microM). Both peptides inhibited the holoenzyme competitively with respect to phosphorylase b and noncompetitively with respect to Mg.ATP. When the pattern of inhibition with both peptides present was analyzed, inhibition was observed to be synergistic and modestly cooperative indicating that the two peptides can simultaneously occupy the protein substrate-binding site(s). These data are consistent with a model in which the regions of the gamma-subunit represented by PhK5 and PhK13 work in concert as regulatory subdomains that transduce Ca2(+)-induced conformational changes in the delta-subunit to the catalytic gamma-subunit through a pseudosubstrate autoinhibitory mechanism.

Amino Acid Sequence↗

Testing antimicrobial susceptibilities of adherent bacteria by a method that incorporates guidelines of the National Committee for Clinical Laboratory Standards.

Membrane filters (0.22-microns pore size) were colonized with 10(4) CFU of logarithmic-phase bacteria per filter under laminar flow conditions in a Modified Robbins Device. Colonized filters were then placed upon agar dilution plates for MIC determinations. Subsequently, filters were transferred to control plates and incubated to obtain MBCs.

Bacterial Adhesion↗