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Biomedical subjects

M Smith

Publications and source records attributed to M Smith.

At least 847 records · Page 47Linked to original sources
PubMed1991

Metabolism of 1-13C-propionate in vivo in patients with disorders of propionate metabolism.

Metabolism of propionate in human subjects was studied using bolus administration of 1-13C-propionate i.v. or orally. The study population consisted of five patients with propionic acidemia (PA), eight with methylmalonic acidemia (MMA; four responsive to vitamin B12), one each with multiple carboxylase deficiency and transcobalamin-II deficiency, and five healthy volunteers. Concentrations of 1-13C-propionate were measured in blood in three patients with PA, two with MMA, and two controls. Breath samples were obtained at intervals during 3 h after the dose, isotopic enrichment of 13CO2 was measured, and the cumulative percentage of recovery of 13C was calculated from the individual's predicted resting energy expenditure. Recovery of 13CO2 and half-time of 1-13C-propionate in PA were significantly less than normal. The same parameters in MMA were below normal, but significantly greater than in PA. Recovery of 13CO2 was well correlated with clinical severity in PA, but did not correlate in MMA. Differences between MMA and PA may indicate different distribution of propionate pools, differences in inducibility of residual enzyme activities, or an alternate pathway for decarboxylation of propionate available in MMA but not PA. Only one patient with PA demonstrated increased 13CO2 production during biotin treatment. In a B12-responsive MMA patient, no differences were noted within 2 d of initiating treatment with B12, but there was an increase in 13CO2 production after 4 mo. Recovery of 13CO2 was normal in the patient with transcobalamin-II deficiency before and after treatment with vitamin B12.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Single amino acid substitutions in recombinant bovine prolactin that markedly reduce its mitogenic activity in Nb2 cell cultures.

Three amino acid residues of bovine PRL (bPRL) have been examined for their roles in the mitogenic activity of the hormone in Nb2 lymphoma cell cultures. The residues of interest, R21, R177, and K187, are conserved in eight pituitary PRLs, but not in the related, nonlactogenic bGH. Using site-specific mutagenesis, a number of recombinant methionyl bPRL variants have been prepared, each of which contained a single amino acid substitution of one of the three residues; a variety of amino acids was used for substitution. Twelve exchanges of R177 (to A, L, N, K, D, E, Y, G, S, Q, H, and F) all led to marked decreases in mitogenic activity. Even the conservative change, R177K, led to a decrease in mitogenic activity of about 90%; all the other R177 substitutions led to even more marked decreases; there was essentially complete loss of activity when the positively charged R177 was replaced by the negatively charged aspartate. Exchanges of R21 (to A, L, N, and K) were less dramatic, with the greatest decrease (79%) occurring in the case of R21A. Exchanges of K187 (to A, L, N, and R) had a relatively minor effect on the mitogenic activity of the hormone. Residues R21 and R177 in bPRL are located in putative helices 1 and 4, respectively; in the three-dimensional structure of the hormone these residues are predicted to be quite closely apposed. The results suggest that R177 and, to a lesser degree, R21 have important roles in the mitogenic activity of bPRL.

Amino Acid Sequence↗
PubMed1991

Skeletal muscle deformation in the lateral muscle of the intact rainbow trout Oncorhynchus mykiss during fast start maneuvers.

Although there is an extensive body of information on the kinematics of the fast start response in teleosts, there is little information on the deformation of the skeletal muscle which produces the changes in body position during a fast start. This study presents preliminary information on the determination of skeletal muscle deformation with implanted ultrasonic dimension gauges in the intact fish during startle behavior. Deformation was measured in the lateral epaxial musculature of the rainbow trout Oncorhynchus mykiss during stage one of fast starts. The results show that ultrasound transit time dimension gauges can be implanted in the skeletal muscle of rainbow trout with minimum trauma and used to record local deformation along the length of the fish. Measurements remained stable over 4-8 h of implantation. Preliminary results show that: (1) muscle at different positions along the fish reaches its minimum length (average 9.6% shortening) at approximately the same time and coincident with the end of stage one of the fast start response; (2) the onset of concave curvature of the entire fish precedes the onset of local shortening at more caudal sites; (3) muscle on the convex side of a bend lengthens while muscle on the concave side shortens, and the two deformations follow a similar time course. These results indicate an asynchronous onset of skeletal muscle contraction in fast starts and support the hypothesis that local skeletal muscle deformation is transmitted caudally through skeletal or other structures.

Animals↗
PubMed1991

Comparative time estimation skills of Hispanic children.

76 Hispanic and 47 Caucasian children from an urban school district located in a racially mixed neighborhood were compared on their ability to make functional time estimates. The findings indicate that initial differences in ability to make time estimations dissipate across Grades 1 to 5.

Child↗
PubMed1991

Acute effects of an oral calcium load in pregnancy and lactation: findings on renal calcium conservation and biochemical indices of bone turnover.

An oral calcium (Ca) tolerance test was used to compare the acute calcaemic, calciuric, parathyroid and bone turnover responses in 21 women at 36 weeks of pregnancy, 27 breast-feeding women studied 22 weeks postpartum and 27 control women. In all groups the oral Ca load increased plasma Ca and urinary calcium excretion (CaE), reduced intact PTH concentration (and consequently reduced renal phosphate and cyclic AMP excretion) and reduced hydroxyproline excretion (HypE, a biochemical index of bone resorption). There were no changes in the biochemical indices of bone formation, serum osteocalcin (elevated in the lactating group) and alkaline phosphatase, in any group. The pregnant women had the same fall in HypE and a greater calcaemic response than the controls. These results suggest that there is increased intestinal Ca absorption efficiency and a normal rate of bone resorption in late pregnancy. In contrast, the lactating women had a greater fall in HypE (from a baseline twice that of controls) and a significantly lower (p less than 0.001) rise in CaE, despite a calcaemic response similar to that of controls. Therefore, in lactation there is increased bone turnover and an increased capacity to reabsorb Ca in the renal tubule, compared to controls. An oral calcium supplement may benefit breast-feeding women, by reducing lactation-related elevated rate of bone resorption and consequent loss of trabecular bone.

Absorption↗
PubMed1991

Low-molecular-weight heparinoid compared with warfarin for prophylaxis of deep-vein thrombosis in patients who are operated on for fracture of the hip. A prospective, randomized trial.

In a randomized, prospective trial, a low-molecular-weight heparinoid (Org 10172 [Lomoparan]) was compared with warfarin for efficacy and safety in preventing deep-vein thrombosis in 263 patients who had an operatively treated fracture of the hip. One group of patients received Org 10172 in a dose of 750 units subcutaneously every twelve hours until the ninth postoperative day; on the seventh postoperative day, warfarin was added to the regimen. The other group received only warfarin. Both drugs were begun preoperatively, immediately after the admission evaluation. In the patients who received warfarin, the desired prothrombin time was one and one-half times the control level. Deep-vein thrombosis was detected by 125I-fibrinogen scanning and impedance plethysmography and was confirmed by phlebography and compression ultrasonography. Deep-vein thrombosis was found in nine (7 per cent) of the 132 patients who received Org 10172 and in twenty-eight (21 per cent) of the 131 patients who received warfarin (p less than 0.001). Adverse reactions were not significantly different in the two groups. Major bleeding complications occurred in eight patients in the Org-10172 group, only four of whom were receiving the drug at the time of bleeding, and in five patients who were receiving warfarin (not significant). There was no difference in intraoperative loss of blood or in requirements for transfusion. We concluded that the low-molecular-weight heparinoid Org 10172 is a safe, convenient, effective antithrombotic agent for the prevention of venous thrombosis after an operation for fracture of the hip.

Aged↗
PubMed1991

High phosphate diet-induced primary hyperparathyroidism: an animal model.

Primary hyperparathyroidism (PHPT) is increasing in incidence and detection, primarily because of the aging of our population and the widespread use of automated serum calcium determination. As a result, a substantial number of "early" cases or "biochemical" PHPT are being detected. The indications for parathyroidectomy in such early cases of PHPT are currently under debate, primarily because of economic issues. These factors underscore the importance of research into the basic mechanisms and natural history of PHPT. We investigated an animal model of diet-induced PHPT that retains two crucial aspects of PHPT: elevation of endogenously produced parathyroid hormone (PTH), accompanied by gross and microscopic changes in the native parathyroid glands. Female Long-Evans rats were divided into six groups of 15 each and fed a control diet (Ca/P of 1:2) or a high-phosphate diet (Ca/P of 1:7) for 1-, 2-, or 3-month intervals. Compared with the control animals, serum PTH levels were elevated at all three time intervals in the experimental group, whereas serum calcium levels were decreased at all time intervals. Serum creatine levels were also elevated at all time intervals, whereas serum phosphorus levels did not change. Parathyroid histopathologic studies demonstrated no change at 1 month, whereas nine of 15 experimental animals showed mild hyperplasia at 2 months and 13 of 14 showed mild to moderate hyperplasia with gland enlargement at 3 months compared with control animals. Histopathologic examination of the kidneys showed no change at 1 month but focal parenchymal inflammation with calcium deposition at 2 and 3 months in the experimental groups. In conclusion, the high-phosphate diet successfully induced the earliest changes of PHPT: elevated PTH levels and parathyroid hyperplasia. However, because renal function was mildly compromised early on, some element of early secondary (renal) hyperparathyroidism may have supervened quickly. Because this model is simple, it may be useful to investigate this complex syndrome further, as well as its natural history and the complications it produces in other organs such as the kidneys.

Animals↗
PubMed1990

Electrochemical, kinetic, and circular dichroic consequences of mutations at position 82 of yeast iso-1-cytochrome c.

Replacement of Phe-82 in yeast iso-1-cytochrome c with Tyr, Leu, Ile, Ser, Ala, and Gly produces a gradation of effects on (1) the reduction potential of the protein, (2) the rate of reaction with Fe(EDTA)2-, and (3) the CD spectra of the ferricytochromes in the Soret region under conditions where contributions from the alkaline forms of these proteins are absent. The reduction potential of cytochrome c is lowered by as little as 10 mV (Tyr-82) or by as much as 43 mV (Gly-82; pH 6.0) as the result of these substitutions. The second-order rate constants for reduction of these cytochromes range from a low of 6.20 (2) x 10(4) for the Tyr-82 variant to a high of 14.8 x 10(4) M-1 s-1 for the Ser-82 variant [pH 6.0, 25 degrees C, mu = 0.1 M (sodium phosphate)]. Analysis of these rates by use of relative Marcus theory produces values of k11corr that range from 10.9 M-1 s-1 for the wild-type protein to 190 M-1 s-1 for the Gly-82 mutant [25 degrees C, mu = 0.1 M, pH 6.0 (sodium phosphate)]. Reinvestigation of the effect of substituting Phe-82 by a Tyr residue on the CD spectrum of the protein now reveals little alteration of the intense, negative Cotton effect in the Soret CD spectrum of ferricytochrome c. On the other hand, substitution of nonaromatic residues of various sizes at this position results in loss of this spectroscopic feature, consistent with previous findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1990

The ANB1 locus of Saccharomyces cerevisiae encodes the protein synthesis initiation factor eIF-4D.

The Saccharomyces cerevisiae anaerobic gene (ANB1) is negatively regulated both by oxygen and heme. We have shown recently that an upstream repressor site located in the 5'-flanking region of this gene controls its expression (Mehta, K.D., and Smith, M. (1989) J. Biol. Chem. 265, 8670-8675). In this paper, we present the complete genomic sequence of the ANB1 locus of S. cerevisiae. The ANB1 locus encodes a protein of 157 residues with an Mr of 17, 134. The deduced amino acid sequence of the ANB1 gene product shows strikingly extensive sequence and structural homology (63.5% identical residues and an additional 15% conservative substitutions) to the 154-amino-acid-long human and rabbit eukaryotic translation initiator factor (eIF)-4D. Factor eIF-4D is the only known mammalian protein that undergoes a unique post-translational modification of Lys-50 to the amino acid hypusine, and interestingly the same lysine is also present in the ANB1 gene product. Results presented provide strong evidence that the ANB1 locus that encodes a transcript, tr-2, and a second locus encoding a transcript, tr-1, together encode two forms of yeast eIF-4D. Interestingly, heme regulates both the loci in an opposite manner; as a result it can dictate the isoform available under conditions of high and low oxygen tension. The ROX1 locus of S. cerevisiae is known to regulate CYC1, COXVb, and ANB1 genes at the transcriptional level; the ROX1 locus thus regulates all known anaerobically expressed genes that are involved in different cellular functions such as respiration and protein synthesis.

Amino Acid Sequence↗
PubMed1990

Changes in a mammalian signal sequence required for efficient protein secretion by yeasts.

A plasmid-encoded gene for a hybrid pre-protein containing most of the bovine prolactin signal peptide (SpPRL) fused to the mature sequence of yeast invertase (IVT) was expressed and the product was processed and secreted by yeast. However, the level of IVT activity was reduced about six-fold when compared to that obtained with the wild type (wt) invertase signal peptide (SpIVT). When the 5'-untranslated sequence of the hybrid mRNA was truncated by 29 nucleotides, a 2.5-fold increase in secreted IVT was observed. Replacement of the PRL codons with preferred yeast codons did not result in any improvement in the production of secreted IVT. An increase in IVT activity to the level observed with the wt SpIVT was obtained by replacement of the Gly residue located between the N terminus and the central lipophilic region of the SpPRL by Ala. Since this amino acid replacement results in a higher probability of the SpPRL assuming an alpha-helical conformation, it suggests that the secondary structure of this region is important in recognition by the yeast secretory apparatus.

Amino Acid Sequence↗
PubMed1990

Selective overexpression of the QUTE gene encoding catabolic 3-dehydroquinase in multicopy transformants of Aspergillus nidulans.

The three enzymes necessary to catabolize quinate to protocatechuate are inducible by quinic acid, and transcription of their corresponding genes is controlled by the action of a positively acting activator gene and a negatively acting repressor gene. Transformed strains of Aspergillus nidulans containing multiple copies of the activator gene (QUTA) but single copies of the other QUT genes retain normal regulation of the gene cluster and do not show any overexpression of the three quinic acid catabolic enzymes. Transformed strains containing equal multiple copies of the activator gene (QUTA) and QUTE (encoding catabolic 3-dehydroquinase), but single copies of the other QUT genes, retain normal regulation of the QUT gene cluster, but selectively overexpress the QUTE gene upon quinic acid induction. Data are presented that strongly suggested that the gene QUTG, which is physically located within the QUT gene cluster and for which no function has been identified, is not required for expression of the gene cluster and does not encode a chlorogenic acid esterase.

Aspergillus nidulans↗