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Biomedical subjects

M T Baer

Publications and source records attributed to M T Baer.

16 recordsLinked to original sources
PubMed2003

Identification of functionally important regions of a haemoglobin receptor from Neisseria meningitidis.

The HmbR outer-membrane receptor enables Neisseria meningitidis to use haemoglobin (Hb) as a source of iron. This protein functions by binding Hb, removing haem from it, and releasing the haem into the periplasm. Functionally important HmbR receptor domains were discerned using a series of HmbR deletions and site-directed mutations. Mutations exhibiting similar defective phenotypes in N. meningitidis fell into two groups. The first group of mutations affected Hb binding and were located in putative extracellular loops (L) L2 (amino acid residues (aa) 192-230) and L3 (aa 254-284). The second group of mutations resulted in a failure to utilize Hb but proficiency in Hb binding was retained. These mutations localized to the putative extracellular loops L6 (aa 420-462) and L7 (aa 486-516). A highly conserved protein motif found in all haem/Hb receptors, within putative extracellular loop L7 of HmbR, is essential for Hb utilization but not required for Hb binding. This finding suggests a mechanistic involvement of this motif in haem removal from Hb. In addition, an amino-terminal deletion in the putative cork-like domain of HmbR affected Hb usage but not Hb binding. This result supports a role of the cork domain in utilization steps that are subsequent to Hb binding.

Amino Acid Sequence↗
PubMed1999

Use of heme-protein complexes by the Yersinia enterocolitica HemR receptor: histidine residues are essential for receptor function.

The abilities of two bacterial active heme transporters, HmbR of Neisseria meningitidis and HemR of Yersinia enterocolitica, to use different heme sources were compared. While HmbR-expressing cells used only hemoglobin (Hb) and heme, HemR-expressing bacteria were able to grow on Hb, heme, myoglobin, hemopexin, catalase, human and bovine serum albumin-heme, and haptoglobin-hemoglobin complexes as sources of iron. Expression of functional HemR allowed Escherichia coli cells to respond to heme-containing peptides, microperoxidases MP-8, MP-9, and MP-11, suggesting the ability of HemR to transport heme covalently linked to other molecules. Comparison of HemR with other heme receptors identified several highly conserved histidine residues as well as two conserved amino acid motifs, the FRAP and NPNL boxes. A site-directed mutagenesis approach was used to investigate the roles of His128, His192, His352, and His461 residues in HemR function. The HemR receptor with histidine changed to lysine at position 128 (HemR(H128K)), HemR(H461L), HemR(H461A), and HemR(H128A,H461A) mutant receptors were unable to use Hb, human serum albumin-heme, and myoglobin as sources of porphyrin and iron. Utilization of free heme was also severely affected, with some residual heme uptake in cells expressing HemR(H128K), HemR(H461A), and HemR(H461L). Conversely, the HemR(H192T), HemR(H352A), HemR(H352K), and HemR(H192T,H352K) mutant receptors were fully functional. All mutant HemR proteins were expressed in the outer membrane at levels similar to that of the wild-type HemR receptor. Nonfunctional HemRs were able to bind heme- and Hb-agarose. A hypothetical model of the HemR function in which two conserved histidine residues, His128 and His461, participate in the transport of heme through the receptor pore is postulated.

Amino Acid Sequence↗
PubMed1997

Pediatric nutrition assessment: identifying children at risk.

Nutrition services are important in the prevention of disabilities as well as in the treatment and/or habilitation of children with chronic illness. Level 1 nutrition care requires some basic knowledge of nutrition to screen for nutritional risk factors, knowledge of and access to referral systems for children identified to be at risk, and ability to use general nutrition education materials. Level 2 involves individualized nutrition assessment and intervention for problems such as anemia, chronic constipation, low- or high-calorie diets, feeding problems, and growth monitoring. Level 3 nutrition services are for children with identified disabilities such as cystic fibrosis, diabetes, and metabolic disorders that require specific complex nutrition interventions. The five major components of assessment of nutritional status in children are: anthropometric, clinical, biochemical, dietary, and feeding skill development.

Adolescent↗
PubMed1997

Vitamin D, calcium, and bone status in children with developmental delay in relation to anticonvulsant use and ambulatory status.

Reports of abnormalities in vitamin D, calcium, and bone status associated with anticonvulsant use are inconsistent and difficult to interpret because of widely varying study designs, particularly for ambulatory status. We examined the relative effects of anticonvulsant use and ambulatory status on vitamin D, calcium, and bone status in a large group (n = 338) of children who had either normal motor function (ambulatory) or were nonambulatory and either receiving anticonvulsants or not; all had developmental delays. Data included diet records, serum analyses (calcium and calcidiol), and hand-wrist radiographs evaluated for bone maturation and quality. Data were analyzed by using a general linear models (GLM) procedure. Dietary and biochemical data were compared with those of a group of 34 normal children. There were no differences in calcium or vitamin D intakes among the four study groups; however, a high percentage of intakes was below the recommended dietary allowances for calcium (56%) and vitamin D (70%). Vitamin D intakes were positively associated with serum calcium (P < 0.005) and calcidiol (P < 0.01) concentrations. Analysis of covariance indicated that ambulatory status but neither anticonvulsant use nor their interaction contributed significantly to the prediction of serum calcium (P < 0.009) and calcidiol (P < 0.0001), the Z scores for number of ossified centers (P < 0.008), bone age (P < 0.0001), and bone area (P < 0.003). A strong interaction between anticonvulsant use and ambulatory status was seen for percentage cortical area (P < 0.0008), which was entirely due to anticonvulsant use in nonambulatory children (effect size = 0.98). Results suggest that ambulatory status is more important than was recognized previously in relation to abnormalities in vitamin D, calcium, and bone statuses; that all nonambulatory children may be at risk for low serum calcidiol and osteopenia; and that routine monitoring of risk and consideration of prophylactic vitamin D supplementation are warranted.

Anticonvulsants↗
PubMed1993

Molecular genetic analysis of a locus required for resistance to antimicrobial peptides in Salmonella typhimurium.

The innate immunity of vertebrates and invertebrates to microbial infection is mediated in part by small cationic peptides with antimicrobial activity. Successful pathogens have evolved mechanisms to withstand the antibiotic activity of these molecules. We have isolated a set of genes from Salmonella typhimurium which are required for virulence and resistance to the antimicrobial peptides melittin and protamine. Sequence analysis of a 5.7 kb segment from the wild-type plasmid conferring resistance to protamine contained five open reading frames: sapA, sapB, sapC, sapD and sapF, organized in an operon structure and transcribed as a 5.3 kb mRNA. SapD and SapF exhibited similarity with the 'ATP binding cassette' family of transporters including the bacterial Opp and SpoOK, involved in the uptake of oligopeptides; the yeast STE6, necessary for the export of a peptide pheromone; and the mammalian mdr, which mediates resistance to chemotherapeutic agents in cancer cells. SapA showed identity with other periplasmic solute binding proteins involved in peptide transport. The SapABCDF system constitutes a novel transporter for enteric bacteria and the first one harboring a periplasmic component with a role in virulence.

ATP-Binding Cassette Transporters↗
PubMed1987

Anticonvulsant medication use and circulating levels of total thyroxine, retinol binding protein, and vitamin A in children with delayed cognitive development.

Circulating thyroxine (T4), retinol binding protein (RBP), and vitamin A were measured in conjunction with nutritional status assessment of 707 cognitively delayed children, ages 3.0-9.0 y. Twenty percent were receiving anticonvulsant (AC) medication. T4 was lower and RBP and vitamin A were higher (p less than 0.0001) among AC than non-AC subjects. Molar ratios of vitamin A:RBP did not differ between the two groups nor did intakes of protein or vitamin A. Lower T4 and higher RBP were found among children who received diphenylhydantoin (DPH), phenobarbital, or AC combinations, but vitamin A was higher only among those who received DPH. RBP and vitamin A were lower (p less than 0.05) among children with infections and vitamin A was lower (p less than 0.05) among those with serum zinc less than 70 micrograms/dL (less than 10.7 mumol/L); differences between AC and non-AC subjects remained when other variables were considered.

Anticonvulsants↗
PubMed1985

Nitrogen utilization, enzyme activity, glucose intolerance and leukocyte chemotaxis in human experimental zinc depletion.

We previously reported significant decreases in plasma, whole blood, urinary, seminal and fecal zinc in six young men consuming a semipurified formula diet providing 0.28 mg zinc and 0.8/kg protein per day for 4-9 weeks. During a one-week baseline period, 15.7 mg of zinc (as ZnSO4) were fed; three of the men were repleted with 6.0, 23.2 or 46.3 mg zinc for 2-5 weeks. Biochemical and functional measures of zinc status other than tissue zinc levels were also monitored. No one parameter appeared to parallel dietary zinc status in all subjects, although significant mean changes were seen in serum and leukocyte alkaline phosphatases. Inconsistent changes were noted in erythrocyte delta-amino levulinic acid dehydratase, plasma alkaline ribonuclease and the serum alkaline phosphatase isoenzymes. Nitrogen balance was unaffected by zinc nutritional status. However, alterations in hair root growth phase and morphology, decreases in lymphocyte counts and in transferrin levels during depletion suggest impairment in protein synthesis. Impaired leukocyte chemotaxis and clinical signs indicative of decreased resistance to infection were also noted.

Adult↗
PubMed1985

Energy and nutrient values from different computerized data bases.

Twenty-four dietary records were analyzed using three computerized nutrient data bases. Differences in mean values were found for 9 of 19 variables evaluated. No one data base consistently yielded highest or lowest values for all nutrients. Mean values appeared to be most consistent among the data bases for energy and the energy-yielding nutrients, calcium, phosphorus, and magnesium. Even when mean values did not differ significantly, values for some individual diets were widely discrepant. Whether comparisons of calculated energy and nutrient values are within or between studies and based on a few or many days of dietary information, values should be recognized as estimates and their limitations and strengths respected.

Child↗
PubMed1984

Tissue zinc levels and zinc excretion during experimental zinc depletion in young men.

Six healthy young men participated in a confined zinc depletion-repletion study which lasted 10 to 11 wk. The depletion period varied from 4 to 9 wk during which the subjects consumed a semipurified formula diet supplying 0.28 mg zinc/day. During a 1-wk initial baseline period, 15.7 mg of zinc as ZnSO4 were fed; 6.0, 23.2, or 46.3 mg of zinc were given during a brief repletion period for three of the men. Plasma, whole blood, urinary, fecal, and seminal zinc decreased significantly by the end of the depletion period. Erythrocyte, saliva, and hair zinc did not change. Plasma and urinary zinc levels were highly correlated when urinary zinc was 150 micrograms/day or more. In five of six subjects a drop in urinary zinc to below 150 micrograms/day was noted before a decrease in plasma zinc to less than 70 micrograms/100 g, indicating that urinary zinc responds more rapidly than plasma zinc to dietary changes and may be useful for evaluating zinc nutriture. The endogenous zinc loss averaged 2.2 mg/day; addition of the loss occasioned by one seminal emission would bring the total to 2.8 mg/day.

Adult↗
PubMed1981

Experimental zinc depletion and altered taste perception for NaCl in young adult males.

Taste perception for saltiness and bitterness was tested in five young men while fed a basal (15 mg Zn/day) and zinc depletion (0.25 mg Zn/day)) diet and in three young men during zinc repletion. The perceived intensity of five NaCl solutions ranging from 0 to 600 mM and five urea solutions also ranging from 0 to 600 mM were rated on a 17-point scale. The intensity ratings for the 75 and 150 mM NaCl solutions were significantly lower (p less than 0.05) during depletion than during the basal period; intensity ratings for 300 and 600 mM NaCl solutions did not change significantly. Bitterness perception was not altered with zinc depletion. The changes in perceived intensity that occurred were not related to parotid salivary zinc concentration, percentage change in plasma zinc with depletion, or the length of time required for depletion. The results suggest that zinc depletion may alter the taste perception of some moderately salty solutions.

Adult↗
PubMed1978

Absorption of mono- and polyglutamyl folates in zinc-depleted man.

The effect of experimental zinc depletion on the intestinal absorption of mono- and polyglutamyl folates was assessed in six healthy male subjects by measuring the increase in serum folate after an oral dose of pteroylmonoglutamate and pteroylheptaglutamate before and after initiation of a zinc-deficient diet. At the beginning of the study, no differences were detected in the absorption of pteroylmono- and heptaglutamate. After zinc depletion, the rise in serum folate after an oral dose of pteroylheptaglutamate was reduced by an average of 53% while pteroylmonoglutamate absorption appeared to be unchanged. These data suggest that zinc depletion results in a decreased intestinal hydrolysis of pteroylpolyglutamate and that intestinal conjugase in man is a zinc-dependent enzyme.

Adult↗