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Biomedical subjects

C Miller

Publications and source records attributed to C Miller.

At least 541 records · Page 30Linked to original sources

Nutritional absorption in short bowel syndrome. Evaluation of fluid, calorie, and divalent cation requirements.

Eight patients with a short bowel resulting from intestinal resection and clinically stable for at least one year were studied for 10 days. The diet chosen was lactose-free with a low fiber content and contained 22% of total calories as protein, 32% as carbohydrate, and 46% as fat. Total fluid volume was kept constant, and all patients were in positive nitrogen balance. During the 10-day period, blood chemical concentrations, stool, and/or ostomy volume, urine volume, electrolyte excretion, and calorie and divalent cation absorption were measured. In addition it was determined that fluid restriction during meals did not affect these parameters. In these patients the absorptions of fat, carbohydrate, protein, and total calories were 54%, 61%, 81%, and 62%, respectively. Similarly the absorption of the divalent cations, calcium, magnesium, and zinc, were 32%, 34%, and 15%, respectively. We suggest that patients with short bowel syndrome, who have been stable for at least one year and who can tolerate oral diets, do not need to restrict fat or to separate fluids from solids during their meals. Furthermore, they should increase their oral intake to 35-40 kcal/kg ideal body weight in order to counteract their increased losses. The diet should contain 80-100 g protein/day in order to maintain a positive nitrogen balance and a large margin of safety. In addition, these patients may take oral supplementation of calcium, magnesium, and zinc to maintain divalent cation balance.

Aged↗

Purification and characterization of sialic acid containing materials accumulated in cultured skin fibroblasts from a patient with type II sialidosis.

Sialyl conjugates which accumulate in sialidase deficient fibroblasts were made radioactive in the sialic acid moiety by culturing the cells in the presence of [3H]N-acetylmannosamine. The accumulated radioactive compounds were fractionated by anion exchange chromatography and gel filtration. At least nine chromatographically distinct sialyl conjugates were obtained. Neutral and amino sugar analysis of these compounds indicated that all were sialyloligosaccharides of the type which could be derived from glycoproteins containing complex, N-asparagine-linked carbohydrate groups.

Cells, Cultured↗

Treatment of alcohol organic mental disorder with piracetam.

1. The paper presents an investigation of the efficiency of piracetam in alcohol organic mental disorder. 2. A double blind placebo controlled study design was used to compare two dosages of the substance (2 x 3g versus 2 x 12g). 3. The cognitive functions of the patients, especially short term memory and concentration, were assessed on the days 0, 7, 14, 28 and 42 using various psychological instruments. 4. An analysis of 39 patients showed an improvement of cognitive functions in all three groups. 5. Patients receiving drug treatment showed earlier responses than patients receiving placebo; differences between the three investigational groups were not statistically significant. 6. The results achieved make the effect of piracetam appear somewhat questionable.

Adult↗

Trapping single ions inside single ion channels.

Single Ca++-activated K+ channels from rat muscle plasma membranes are inhibited by Ba++. A single Ba++ entering the channel's conduction pore induces a long-lived blocked state. This study employs Ba++ as a probe of the channel's conduction pathway to show that the channel can be forced to close with a single Ba++ ion inside the pore. A Ba++ ion inside the closed channel is trapped and cannot escape until the channel opens. The results demonstrate that in the channel's closed state, the cytoplasmic side of the conduction pore is obstructed to the passage of ions.

Animals↗

Rearrangement of the p53 gene in human osteogenic sarcomas.

p53 is a 53-kDa nuclear protein that is associated with malignant transformation in several tumor model systems. In a survey of 134 human carcinomas, sarcomas, leukemias, and lymphomas obtained at surgery or from peripheral blood, we found rearrangements of the p53 gene only in osteogenic sarcomas (3 of 6 osteogenic sarcomas examined). Normal tissue from one of these patients had an unrearranged gene, indicating that the genetic abnormality in the tumor was acquired. Two of the sarcomas with rearranged genes expressed levels of p53 protein that were elevated relative to other tumors. Rearranged p53 genes were also found in human osteogenic sarcoma cell lines.

Cell Line↗

Single Na+ channels activated by veratridine and batrachotoxin.

Voltage-sensitive Na+ channels from rat skeletal muscle plasma membrane vesicles were inserted into planar lipid bilayers in the presence of either of the alkaloid toxins veratridine (VT) or batrachotoxin (BTX). Both of these toxins are known to cause persistent activation of Na+ channels. With BTX as the channel activator, single channels remain open nearly all the time. Channels activated with VT open and close on a time scale of 1-10 s. Increasing the VT concentration enhances the probability of channel opening, primarily by increasing the rate constant of opening. The kinetics and voltage dependence of channel block by 21-sulfo-11-alpha-hydroxysaxitoxin are identical for VT and BTX, as is the ionic selectivity sequence determined by bi-ionic reversal potential (Na+ approximately Li+ greater than K+ greater than Rb+ greater than Cs+). However, there are striking quantitative differences in open channel conduction for channels in the presence of the two activators. Under symmetrical solution conditions, the single channel conductance for Na+ is about twice as high with BTX as with VT. Furthermore, the symmetrical solution single channel conductances show a different selectivity for BTX (Na+ greater than Li+ greater than K+) than for VT (Na+ greater than K+ greater than Li+). Open channel current-voltage curves in symmetrical Na+ and Li+ are roughly linear, while those in symmetrical K+ are inwardly rectifying. Na+ currents are blocked asymmetrically by K+ with both BTX and VT, but the voltage dependence of K+ block is stronger with BTX than with VT. The results show that the alkaloid neurotoxins not only alter the gating process of the Na+ channel, but also affect the structure of the open channel. We further conclude that the rate-determining step for conduction by Na+ does not occur at the channel's "selectivity filter," where poorly permeating ions like K+ are excluded.

Animals↗

Coupling of voltage-dependent gating and Ba++ block in the high-conductance, Ca++-activated K+ channel.

Voltage-dependent Ca++-activated K+ channels from rat skeletal muscle were reconstituted into planar lipid bilayers, and the kinetics of block of single channels by Ba++ were studied. The Ba++ association rate varies linearly with the probability of the channel being open, while the dissociation rate follows a rectangular hyperbolic relationship with open-state probability. Ba ions can be occluded within the channel by closing the channel with a strongly hyperpolarizing voltage applied during a Ba++-blocked interval. Occluded Ba ions cannot dissociate from the blocking site until after the channel opens. The ability of the closed channel to occlude Ba++ is used as an assay to study the channel's gating equilibrium in the blocked state. The blocked channel opens and closes in a voltage-dependent process similar to that of the unblocked channel. The presence of a Ba ion destabilizes the closed state of the blocked channel, however, by 1.5 kcal/mol. The results confirm that Ba ions block this channel by binding in the K+-conduction pathway. They further show that the blocking site is inaccessible to Ba++ from both the cytoplasmic and external solutions when the channel is closed.

Animals↗

Physicochemical characteristics and biological effects of nickel oxides.

Ten nickel oxides and nickel-copper oxides, which all contained NiO (bunsenite) as the predominant crystalline phase, were assayed as follows: in vitro dissolution tests in water and body fluids; in vitro phagocytosis tests in Chinese hamster ovary and C3H-10T1/2 cells; morphological transformation and cytotoxicity tests in cultured Syrian hamster embryo (SHE) cells; erythropoiesis stimulation assay by intrarenal administration to Fischer-344 rats; and scoring the renal histopathologic responses in rats killed 3 months post-injection. The test compounds differed substantially in their biological effects when tested in the various experimental systems. Based upon highly significant concordance of ranked results in the assays (P less than 0.001), six colligative biological attributes of the compounds were identified: (i) dissolution half-times in rat serum and renal cytosol; (ii) phagocytosis by C3H-10T1/2 cells; (iii) morphological transformation of SHE cells; (iv) erythropoiesis stimulation in rats; (v) induction of tubular hyperplasia in rat kidneys; and (vi) induction of arteriosclerosis in rat kidneys. Strong rank correlation (P less than 0.01) between results of the cell transformation and erythropoiesis stimulation assays is especially notable, since the compounds were tested by blind protocols in independent laboratories. The presence of high surface area and demonstrable Ni(III) were two physicochemical characteristics that were associated with the greatest biological effects of nickel oxides.

Animals↗

Prolongation of pig-to-dog renal xenograft survival by modification of the inflammatory mediator response.

The pathogenesis of hyperacute renal rejection consists of a nonspecific effector cascade that invokes most of the components of a typical acute inflammatory response. Platelet-activating factor (PAF) represents the most recent and perhaps the most significant mediator and promoting agent of this phenomenon. These studies evaluated SRI 63-441, a novel, synthetic, and the most potent PAF receptor antagonist available, alone and in combination with other prostanoids, for their ability to influence this response and to prolong renal xenograft survival and function in a model of pig-to-dog heterotransplantation. Inhibition of PAF by SRI 63-441 alone, at the dosage and schedule used in these experiments, did not significantly prolong xenograft survival or function. However, the combination of SRI 63-441 with either prostacyclin (PGI2) or prostaglandin E1 (PGE1) infusion demonstrated significant synergism, and resulted in a 6-9-fold increase in kidney survival and a 3-20-fold increase in urine output. Neither PGI2 nor PGE1 infusions alone significantly influenced this xenograft model. Electromagnetic flow studies demonstrated significantly delayed diminution in renal artery blood flow in the combination-treated animals. Serial and end-stage histologic examination of kidneys receiving combination therapy demonstrated a delayed onset of the pathologic deterioration and an overall amelioration of the entire process. These studies demonstrate that significant abrogation of a rapid and violent form of hyperacute rejection can be achieved solely by the pharmacologic manipulation of the inflammatory mediator response.

Alprostadil↗

On-line literature searching: comparison of PaperChase and National Library of Medicine data bases.

Two computerized retrieval systems--the National Library of Medicine (NLM) data bases (MEDLINE, TOXLINE, and their respective backfiles) and PaperChase (PC), a subset of the NLM data base, were compared. Comparative parameters of retrieval and costs for literature searching performed on each system were evaluated. Objective measures were used in the evaluation, as well as a subjective assessment of user satisfaction with each system. Data indicate that NLM is a faster and more direct search procedure for a trained individual, making it a more favorable choice in a drug information center. PC is a valuable tool for sites requiring or offering on-line access to many different people searching infrequently. Because P & T Committees must have access to comprehensive and timely literature, knowledge of various retrieval systems is beneficial.

Boston↗

An improved technique for multiple organ harvesting.

A rapid technique for multiple organ harvesting is described which allows removal of all the major organs within 30 to 60 minutes after beginning the donor operation. No preliminary dissection of the liver or kidneys is required or necessary since these organs are cooled by infusion of cold solutions in situ and with subsequent rapid dissection in a bloodless field. The incidence of well functioning kidneys, livers and hearts has been better than with the previous methods. The acceptance of this procedure by other personnel has been almost universal.

Dissection↗

Intercellular junctions between fibroblasts in connective tissues of the eye of macaque monkeys. A thin section and freeze fracture analysis.

Thin-section electron microscopy and freeze fracture were used in the analysis of the intercellular junctions between fibroblasts in connective tissues of the eye of Macaca mulatta, M. fascicularis, and M. arctoides. Fibroblasts located in the subconjunctival loose connective tissue, anterior sclera, scleral spur, iris stroma, ciliary body stroma, and posterior choroid were jointed by three kinds of junctions. Gap junctions were of different sizes and frequently composed of a small number of connexons organized in polygonal aggregates or linear arrays. Tight junctions were represented by isolated strands and never composed a continuous belt around the cells. Intermediate junctions were seen in thin sections but did not have any representation in the interior of the plasma membrane. It remains to be established whether, as is the case in other tissues, pathologic conditions of the eye are accompanied by some changes in the morphology and distribution of intercellular junctions between fibroblasts.

Animals↗