Microbial uptake and accumulation of (14C carbofuran) 1,3-dihydro-2,2-dimethyl-7 benzofuranylmethyl carbamate in twenty fungal strains isolated by miniecosystem studies.
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Biomedical subjects
Publications and source records attributed to M Lakshmanan.
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A simplified, low iodine diet was developed for outpatient use prior to I-131 scanning and therapy in thyroid cancer. Iodine intake of five subjects on the diet was approximately 50 micrograms a day and this level was maintained for four weeks. The diet required only minimal instruction to be followed reliably. This level of iodine intake may increase radioiodine uptake in thyroid carcinomas.
The mechanism(s) responsible for the different biological potency of L- and D-T3 was investigated in rat L6E9 myoblasts. After incubation with intact cells at 37 C L-T3 cellular and nuclear uptakes were 91% and 70% higher than those of D-T3, respectively, but values for nuclear uptake as a fraction of cellular uptake were similar. The difference between the enantiomers was abolished at 4 C, and metabolic and endocytotic inhibitors reduced nuclear and extranuclear saturable uptake of L-T3 to a similar degree, but had little or no effect on D-T3 uptake. The affinity constants (Ka) for L- and D-T3 binding to isolated nuclei were similar, but the apparent nuclear Ka of L-T3 in intact cells was 5-fold greater than that of D-T3. The findings suggest that stereospecific transport, mainly active at the plasma membrane, occurs in rat skeletal muscle cells. This discriminative pathway of cell entry facilitates L-T3 uptake by an energy-dependent pathway not shared by D-T3 and may explain the greater potency of L-T3 than D-T3.
Since in skeletal muscle circulating L-T3 is the only source for the hormone bound to nuclei, we investigated the intracellular and intranuclear transport of L-T3 in L6E9 rat skeletal muscle cells. The characteristics of this process were assessed by analyzing the nuclear bound L-T3 as a marker of the internalized hormone and by determining the initial rate of L-T3 uptake. [125I]L-T3 cellular uptake at 37 C reached a plateau at 2 h when the nuclear uptake, after an initial lag phase, was still increasing and represented 4.7% of the cellular uptake. Incubation at 4 C caused [125I]L-T3 cellular uptake to decrease by 77% and nuclear uptake to be abolished. A similar effect on [125I]L-T3 nuclear uptake was obtained after myoblasts were incubated at 37 C with a 1000-fold excess of unlabeled L-T3. The addition of various inhibitors of ATP production, cytoskeleton integrity, endocytosis, and Na+, K+-ATPase that did not interfere with [125I]L-T3 binding to the cell surface or to isolated nuclei caused a dose-dependent reduction of both extranuclear and nuclear uptake, ranging from 34-85%. Scatchard analysis revealed the presence on the myoblast surface of L-T3 high affinity (Ka = 1.6 X 10(9) M-1) and low affinity (Ka = 5.4 X 10(6) M-1) binding sites; other iodothyronines exhibited lower affinity for both sites. Kinetic analysis of L-T3 transport after 60-sec incubation at 23 C defined a process with a Km of 17 +/- 5.6 nM and a maximum velocity of 83 +/- 35 pmol/mg DNA. These results indicate the existence in rat myoblasts of a temperature-dependent, energy-requiring, saturable, and stereospecific L-T3 uptake mechanism, probably mediated through an endocytotic pathway, located on the myoblast plasma membrane, that may regulate L-T3 action in skeletal muscle.
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The efficacy of low doses (10 to 20 mg daily) of doxepin in the treatment of depressive disorders in elderly inpatients was assessed by a double-blind study in 24 patients. The patients were treated for a three-week period to test for an early response. The Hamilton Depression Scale and the Geriatric Depression Scale were used to quantify symptoms of depression. The patients treated with doxepin had a significantly greater reduction in depressive symptoms than did those who received a placebo. No side effects were found and there were no major differences in the degree of physical dependency between the doxepin and placebo groups. A depressive disorder is a common occurrence among elderly inpatients and the effectiveness of low dose doxepin therapy without demonstrable side effects argues for the active treatment for this condition.
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Although clinicopathologic conferences (CPCs) have been valued for teaching differential diagnosis, their instructional value may be compromised by hindsight bias. This bias occurs when those who know the actual diagnosis overestimate the likelihood that they would have been able to predict the correct diagnosis had they been asked to do so beforehand. Evidence for the presence of the hindsight bias was sought among 160 physicians and trainees attending four CPCs. Before the correct diagnosis was announced, half of the conference audience estimated the probability that each of five possible diagnoses was correct (foresight subjects). After the correct diagnosis was announced the remaining (hindsight) subjects estimated the probability they would have assigned to each of the five possible diagnoses had they been making the initial differential diagnosis. Only 30% of the foresight subjects ranked the correct diagnosis as first, versus 50% of the hindsight subjects (p less than 0.02). Although less experienced physicians consistently demonstrated the hindsight bias, more experienced physicians succumbed only on easier cases.
Citrinin, a mycotoxin, was studied for its effect on artificial membranes (liposomes). Of the three (net positive, negative and neural) liposomal preparations tested, the membrane carrying a net positive charge was preferentially acted upon by citrinin and in this case even the lowest concentration was found to be sufficient for causing a high degree of damage. This is the first report of evidence that citrinin has a direct effect on membranes. It was shown to exhibit concentration dependency in its lytic activity on artificial membranes leading to leaching of trapped 45Ca2% ions.