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Biomedical subjects

C Holmberg

Publications and source records attributed to C Holmberg.

At least 127 records · Page 7Linked to original sources

Anti-peptide antibodies reactive with epitopic domains of porcine amelogenins at the C-terminus.

This was an immunological investigation of the processing of porcine amelogenins in situ. Rabbit and rat anti-peptide sera reacted specifically with the hydrophilic segment of the intact amelogenins at the C-terminus. The immunogens used were the synthetic peptides: (a) C13 composed of PATDKTKREEVDC and (b) C25 composed of MQSLLPDLPLEAWPATDKTKREEVD. These peptides correspond to the C-terminal 12- and 25-residue segments of porcine amelogenin, respectively. Cystine was introduced at the C-terminus of C12 for KLH-binding (C13). Western blot analysis disclosed that: (i) both rabbit and rat anti-C13 sera reacted selectively with the 25-kDa porcine amelogenin and three other minor components (27, 22 and 18 kDa); (ii) anti-C25 peptide sera, additionally, reacted with the 23-kDa amelogenins (a degradation derivative of the 25-kDa protein, lacking the 12-residue segment at the C-terminus) and as trace components, 20-, 16- and 14-kDa moieties. Importantly, all the proteins reactive with the anti-C13 serum were concentrated in the outer secretory enamel adjacent to the ameloblasts, decreasing significantly in the underlying inner secretory enamel. Immunohistochemical studies applying the anti-peptide sera to the developing tooth germs of a minipig also confirmed the localization of reactivity in the outer secretory region. Neither anti-peptide serum reacted with porcine non-amelogenins, serum proteins nor dentine matrix proteins at the dilutions tested. however, it was found that both the anti-C13 and C25 sera reacted with human keratin.(ABSTRACT TRUNCATED AT 250 WORDS)

Amelogenin↗

Factors limiting the erythropoietin response in rapidly growing infants with congenital nephrosis on a peritoneal dialysis regimen after nephrectomy.

To prevent anemia in seven small children with congenital nephrotic syndrome of the Finnish type (age range 1 to 4 years), we gave recombinant human erythropoietin in a dose up to 150 IU/kg/per week. We then studied the limiting factors during 14 weeks. On a peritoneal dialysis regimen after nephrectomy, the patients grew considerably (range +0.1 to 2.2 kg/14 wk; mean + 1.3 kg/14 wk). The amount of blood taken for laboratory studies was estimated. Although the estimated erythrocyte volume increased, the improvement was masked in most patients by enhanced growth. In two patients the target hemoglobin value of 10 gm/dl was reached, and in three patients transfusions were avoided. The reticulocyte count rose in dose-dependent fashion. In five patients protein malnutrition was not prevented, although intake of protein was as recommended. The gradual decrease in serum ferritin values indicated that mobilization of iron stores was adequate. Serum iron values decreased, although in general remaining within normal limits. In six patients the serum copper concentration was low and in two the serum aluminum concentration was slightly elevated. Two patients had several episodes of infection. We conclude that in rapidly growing infants and small children receiving peritoneal dialysis after nephrectomy, the maintenance or elevation of the hemoglobin concentration depends on several limiting and coinciding factors. We speculate that, when protein is limited, body growth has priority over erythropoiesis. A higher dose of erythropoietin might have evoked a better response in hemoglobin concentration but might also have resulted in progression of the protein deficit.

Anemia↗

An inverted repeat preceding the Bacillus subtilis glpD gene is a conditional terminator of transcription.

The Bacillus subtilis glpD gene, encoding glycerol-3-phosphate (G3P) dehydrogenase, is preceded by a promoter and an inverted repeat which is located between the promoter and the glpD coding region. The inverted repeat acts as a transcriptional terminator in vitro. Expression of glpD is induced by G3P in the presence of the glpP gene product. Full-length glpD transcripts can be detected only in glycerol-induced cells. The major glpD transcript is initiated from the glpD promoter but minor amounts of larger transcripts, possibly initiated at upstream glp promoters, can also be found. In uninduced cells short transcripts are present, corresponding to initiation at the glpD promoter and termination at the inverted repeat. Upon induction, these short transcripts disappear and are replaced by full-length glpD transcripts. The 3'-ends of full-length glpD transcripts were mapped to an inverted repeat located immediately downstream of glpD. These results show that glpD of B. subtilis is regulated by termination/antitermination of transcription.

Bacillus subtilis↗

Growth, serum lipoproteins and apoproteins in infants with congenital nephrosis.

Retarded growth and extremely high cholesterol levels have been reported in infants with congenital nephrotic syndrome of the Finnish type (CNF). In an attempt to normalize growth and lipid disturbances the high-calorie diet (130 kcal/kg/d) containing protein 4 g/kg/d and supplemented with unsaturated fatty acids (mean P/S-ratio 1.40) was given to ten infants with CNF from birth. Growth, lipoprotein and apoprotein concentrations were measured. All patients exhibited normal growth, which allows renal transplantation, the only life-saving treatment in CNF, already at an early age. In spite of the diet lipid profiles at 3 and 9 months revealed marked elevation of triglyceride in all lipoproteins, especially in VLDL fraction, compared to controls. The abnormalities increased significantly with time (p for VLDL-TG 0.04). The elevation of serum cholesterol was mainly attributable to the increase of cholesterol in triglyceride-rich particles (chylomicrons, VLDL, IDL). Analysis of VLDL, LDL and HDL revealed significant triglyceride enrichment and cholesterol deficiency in all lipoproteins. The concentrations of the low-molecular weight apoproteins A-I and A-II were significantly decreased, but the concentration of high-molecular apo B was high. Urinary analysis revealed progression and decreasing selectivity of proteinuria with time. Thus the mechanisms leading to lipid abnormalities in CNF are multiple including stimulated hepatic lipoprotein synthesis, impaired conversion of VLDL and IDL to LDL, compositional changes, urinary loss of low-molecular apoproteins and presumably reduced LPL activity. The abnormalities indicate an increased risk of arteriosclerosis in CNF patients.

Apoproteins↗

Pharmacokinetically determined cyclosporine dosage in young children.

To account for the individual variability in cyclosporine pharmacokinetics and the non-existence of dosing recommendations in young children, we studied the pharmacokinetics of cyclosporine before renal transplantation in ten children aged 1.1-2.5 years, to determine the appropriate individual dose. Our aim was to reach a steady-state cyclosporine blood level of 200-300 micrograms/l, 8 h after a dose in the first days after renal transplantation. Cyclosporine was given as a single oral dose (10 mg/kg) or as a 4-h i.v. infusion (3 mg/kg), and the blood concentration was determined for 24 h by a specific monoclonal radioimmunoassay. The mean terminal cyclosporine half-life (t1/2) was 9.3 h (range 2.8-20.4), blood clearance 10.8 ml/min per kilogram (range 6.8-22.7) and volume of distribution 2.8 l/kg (range 1.4-4.7). The bioavailability of oral cyclosporine was low; the mean amount absorbed was 21.8% of the administered dose (range 11-35). The mean calculated dose needed to attain the intended predose blood cyclosporine level of 200-300 micrograms/l at steady-state was 5 mg/kg per day for i.v. and 21 mg/kg per day for oral administration. In view of the short t1/2, we used three doses/day. The validity of the predicted doses is shown by the mean cyclosporine doses used during the first 10 days after transplantation, which were 93.5% of the calculated oral and 96.6% of the calculated i.v. doses. The observed mean cyclosporine concentration during the same period was 196 micrograms/l.

Cyclosporins↗

Evidence for pre-hepatic metabolism of oral cyclosporine in children.

1. The pharmacokinetics of cyclosporine were investigated before renal transplantation in 20 children aged 1.1 to 16.8 years. Cyclosporine was given as a single oral dose (10 mg kg-1) or as a 4 h i.v. infusion (3 mg kg-1). 2. The blood drug concentration was measured by both specific and nonspecific monoclonal radioimmunoassays. 3. The mean oral availability of cyclosporine was 20.6% (range 10.8-34.1%). 4. The mean ratio of AUCs measured by nonspecific and specific r.i.a. was 1.96 (range 1.4-2.7) after oral administration and 1.43 (range 1.1-2.0) after i.v. administration. The mean difference between the ratios was 38.5% (P = 0.0001). The ratio of AUCnonspecific to AUCspecific was inversely related to blood drug clearance (r = 0.57; P = 0.009). 5. The findings are suggestive of presystemic, pre-hepatic metabolism of cyclosporine which could contribute to the low, and highly variable bioavailability of this drug.

Administration, Oral↗

Expression of the gene encoding glycerol-3-phosphate dehydrogenase (glpD) in Bacillus subtilis is controlled by antitermination.

The Bacillus subtilis glpD gene encodes glycerol-3-phosphate (G3P) dehydrogenase. A sigma A type promoter and the transcriptional startpoint for glpD were identified. Between the transcriptional startpoint and glpD there is an inverted repeat followed by a run of T residues. The inverted repeat prevents expression of a reporter gene, xylE, when positioned between this gene and a constitutive promoter. Expression of xylE, like expression of glpD, is induced by G3P and repressed by glucose. Induction also requires the product of the glpP gene. Our results suggest that glpD expression is controlled by antitermination of transcription. The inverted repeat appears to be a target for induction by G3P and GlpP. We speculate that glucose repression is mediated via an inhibitory effect on synthesis or activity of GlpP.

Bacillus subtilis↗

Types of fluid disorder in children with bacterial meningitis.

As part of a prospective study of children with bacterial meningitis we analyzed in 36 patients of our hospital the fluid balance on admission and during the first three days of treatment. On admission 10 of them (28%) had inappropriate antidiuretic hormone secretion SIADH, 10 (28%) hypo-osmolal and 10 (28%) iso-osmolal contraction. Six patients (17%) had no clear fluid disorder. The patients with SIADH had significantly lower mean serum NA+ (127 vs. 132 mEq/l, p less than 0.01) and higher mean urine Na+ (111 vs. 26 mEq/l, p less than 0.01) concentration as well as higher mean urinary Na+/K+ ratio (2.23 vs. 0.365, p less than 0.005) than the patients with hypo-osmolal contraction. They also tended to be younger and have a shorter history of fever. The patients with SIADH had a less strict fluid restriction than the patients with hypo-osmolal contraction, and their fluid balance normalized more slowly. Our findings support initial water restriction for all children with bacterial meningitis.

Child↗

Congenital hypoplastic anemia, diabetes, and severe renal tubular dysfunction associated with a mitochondrial DNA deletion.

Mitochondrial DNA (mtDNA) deletion is associated with a variety of clinical entities. In addition to progressive external ophthalmoplegia and Kearns-Sayre syndrome, mtDNA deletions have been demonstrated in Pearson's syndrome. We report an mtDNA deletion in an infant with a variant of Pearson's syndrome. Not only does she have congenital anemia, severe tubulopathy, and exocrine pancreas insufficiency, but she also has diabetes and cerebral atrophy. However, there are no signs of gut or liver involvement. Bone marrow improved while new tissues were involved, thus showing variability in progression of the disease. Decreased respiratory chain enzyme activities were demonstrated in muscle, and an mtDNA deletion was demonstrated in muscle, kidney, leukocytes, and fibroblasts.

Child, Preschool↗