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Biomedical subjects

M Schreiber

Publications and source records attributed to M Schreiber.

At least 73 records · Page 4Linked to original sources
PubMed1998

Treatment of malnutrition with 1.1% amino acid peritoneal dialysis solution: results of a multicenter outpatient study.

A peritoneal dialysis (PD) solution containing 1.1% amino acids as the osmotic agent was evaluated in a 3-month randomized, prospective, open-label study in malnourished PD patients. Patients in the treatment group (DAA) received one or two exchanges daily with the amino acid solution, depending on tolerance, in place of glucose solutions. Controls (DD) received their usual therapy with glucose dialysate. Fifty-four DAA and 51 DD patients completed the study. In DAA, but not in DD patients, there was a significant increase at month 3 in serum insulin-like growth factor-1 (IGF-1) levels and significant decreases in serum potassium (all 3 months) and inorganic phosphorus levels (months 1 and 3), indicating a general anabolic response. Prealbumin and transferrin levels were significantly increased in DAA but not in DD patients at month 1, but the groups did not differ at months 2 and 3. In patients with baseline albumin levels less than 3.5 g/dL (bromcresol green [BCG] method), DAA patients showed increases in albumin, transferrin (months 1 and 2), and prealbumin levels (all 3 months) relative to baseline values, whereas these serum protein levels were unchanged in DD patients, although the changes from baseline did not differ between groups. In this subgroup, midarm muscle circumference (MAMC) did not change in DD or DAA patients. In patients with baseline albumin levels of 3.5 g/dL or greater, DD patients had decreases in albumin and total protein levels at all 3 months and in prealbumin levels at months 1 and 2, relative to baseline. In DAA patients, there were fewer changes in serum proteins. MAMC increased significantly from baseline in DAA but not in DD patients, although changes from baseline did not differ between DAA and DD groups. DAA patients showed no changes in peritoneal membrane transport characteristics. The results indicate that treatment with one or two exchanges daily of this amino acid-based PD solution is safe and provides nutritional benefit for malnourished PD patients.

Amino Acids↗
PubMed1998

Gastrectomy osteopenia in the rat: the role of vitamin B12 deficiency and the type of reconstruction of the digestive tract.

1. The mechanisms underlying gastrectomy osteopenia are not yet clear. The gastrectomy-associated cobalamin (vitamin B12) deficiency may favour osteopenia and skeletal fractures. Also, the exclusion of the duodenum from the food passage may contribute to gastrectomy osteopenia. To investigate this, rats were gastrectomized and the passage of nutrients restored either with the duodenum excluded (Roux Y) or included (Longmire). Sham-operated rats served as controls. In half of the rats in each gastrectomy group the serum B12 levels were normalized by parenteral administration of B12.2. Four months post operation, both gastrectomy groups showed a similar degree of osteopenia. There was normal bone mineralization; serum levels of parathyroid hormone were normal, but decreased for 25-hydroxyvitamin D, and elevated for 1,25-dihydroxyvitamin D; in urine there was decreased pH and excessive hyperphosphaturia.3.B12 therapy had no influence on any of the essential bone and mineral metabolic parameters.4. We conclude that osteopenia in the gastrectomized rat (i) is not due to B12 or folic acid deficiency, calcium deficiency or secondary hyperparathyroidism; (ii) is independent of the type of anatomic reconstruction of the digestive tract; (iii) appears to be related to disturbed vitamin D, phosphorus and acid-base metabolism.

Acid-Base Imbalance↗
PubMed1998

Protective effect of flavonoids and tocopherol in high altitude hypoxia in the rat: comparison with ascorbic acid.

The mixture of flavonoids (silymarin) from Carduus Marianus (0.9 mg.g-1 body weight) and/or ascorbic acid (0.4 mg.g-1 body weight) were administered in the food to 21 day-old (b.w. 35-45 g) rats for one week. Then the animals were exposed, in a hypobaric chamber, to simulated altitude 8,000-12,000 m for one hour. Mean lethal altitude was calculated by the Behrens equation: it was 10,150 m in controls, 10,550 m in ascorbic acid treated, 10,500 m in silymarin and tocopherol treated and 10,450 m in animals, receiving both ascorbic acid and silymarin. Thus silymarin protected the animals against lethality of high-altitude hypoxia. The effect of ascorbic acid and silymarin were not additive.

Altitude Sickness↗
PubMed1998

[New approaches to tissue management in minimal invasive pediatric surgery].

Tissue management in minimally invasive surgery plays an important role in the indication for and feasibility of surgical interventions. Hemostasis and sealing of larger areas are possible with minimally invasive tissue gluing in liquid and bandage-bound form. For effective and efficient application of the precoated collagen fleece (TachoComb) a modularly constructed applicator (AMISA) was designed that is suitable for a wide range of indications in MIS and allows selective leak closure (SLC) in parenchymatous tissues with different lesions (Pneumothorax, Chylothorax, rupture of liver/spleen, biopsies, fistulae).

Aprotinin↗
PubMed1997

Structure and chromosomal assignment of the mouse fra-1 gene, and its exclusion as a candidate gene for oc (osteosclerosis).

We have determined the genomic structure of the mouse fra-1 gene, which consists of four exons and three introns at positions also found in the other members of the fos gene family. Fra-1 is expressed rather highly in the brain and testes of adult mice, and at low levels in most other tissues. Absence of c-Fos leads to significantly reduced serum stimulation of fra-1 expression in gene targeted mouse fibroblasts, demonstrating that mitogen induction of fra-1 is partially mediated by c-Fos/AP-1. A polymorphic (CA)n microsatellite marker was found in intron 2 of fra-1 and used to map the gene to the centromeric region of mouse chromosome 19. Since fra-1 maps to the same genomic region as oc (osteosclerosis), an autosomal recessive disorder leading to the bone remodelling disease osteopetrosis, we tested it as a candidate gene for oc. The segregation of fra-1 in two different crosses of mice carrying oc and an allelism test between oc and a targeted disruption of fra-1 demonstrate that fra-1 and oc are two distinct genes rather than oc being a mutant allele of fra-1.

Amino Acid Sequence↗
PubMed1997

A novel calcium-sensing domain in the BK channel.

The high-conductance Ca2+-activated K+ channel (mSlo) plays a vital role in regulating calcium entry in many cell types. mSlo channels behave like voltage-dependent channels, but their voltage range of activity is set by intracellular free calcium. The mSlo subunit has two parts: a "core" resembling a subunit from a voltage-dependent K+ channel, and an appended "tail" that plays a role in calcium sensing. Here we present evidence for a site on the tail that interacts with calcium. This site, the "calcium bowl," is a novel calcium-binding motif that includes a string of conserved aspartate residues. Mutations of the calcium bowl fall into two categories: 1) those that shift the position of the G-V relation a similar amount at all [Ca2+], and 2) those that shift the position of the G-V relation only at low [Ca2+]. None of these mutants alters the slope of the G-V curve. These mutant phenotypes are apparent in calcium ion, but not in cadmium ion, where mutant and wild type are indistinguishable. This suggests that the calcium bowl is sensitive to calcium ion, but insensitive to cadmium ion. The presence and independence of a second calcium-binding site is inferred because channels still respond to increasing levels of [Ca2+] or [Cd2+], even when the calcium bowl is mutationally deleted. Thus a low level of activation in the absence of divalent cations is identical in mutant and wild-type channels, possibly because of activation of this second Ca2+-binding site.

Amino Acid Sequence↗
PubMed1997

Myxoma T2 protein as a model for poxvirus TNF receptor homologs.

Many poxviruses encode a plethora of immunomodulatory proteins, including homologs of cellular cytokine receptors. These receptor mimics, also referred to as viroceptors, are believed to function by binding and sequestering host cytokines thus preventing their signaling cascade prior to receptor engagement. The M-T2 protein of myxoma virus is a TNF receptor homolog that has two distinct activities: the secreted dimeric M-T2 protein binds and inhibits TNF alpha while the intracellular version permits myxoma virus replication in infected T-lymphocytes by blocking the cellular apoptosis response to the virus infection. Studies with M-T2 mutants reveal that distinct protein domains mediate these two anti-immune properties of this protein.

Animals↗
PubMed1997

Assessment of perioperative glycerol metabolism by stable isotope tracer technique.

The aim of this study was to investigate metabolic changes during and after abdominal hysterectomy with specific regard to glycerol metabolism. Seven otherwise healthy patients with benign uterine myoma were enrolled in this study. Glycerol turnover and hepatic glucose production were measured before and after the operation by using stable-isotope technique ([1,1,2,3,3-2H5]-glycerol, [6,6-2H2]-glucose). Metabolic substrates (glycerol, nonesterified fatty acids, beta-hydroxybutyrate, glucose, lactate) and hormones (insulin, glucagon, cortisol, catecholamines) were determined pre-, intra- and postoperatively. Hysterectomy was associated with an increase of postoperative glycerol turnover from 3.56 +/- 1.28 to 6.46 +/- 2.44 mumol.kg-1.min-1 (P < 0.05). This increment was inversely related to the age of the patients (r = 0.872, P < 0.05). Glycerol concentration tended to increase perioperatively. These changes, however, were not of statistical significance. Hepatic glucose production and glucose plasma levels increased postoperatively from 9.75 +/- 1.61 to 12.79 +/- 1.45 mumol.kg-1.min-1 (P < 0.05) and 4.6 +/- 0.9 to 6.2 +/- 0.9 mmol/L (P < 0.05), respectively. Cortisol and catecholamine levels rose during and after surgery, while insulin and glucagon remained unchanged. The enhanced rate of lipolysis after hysterectomy was not detectable from plasma glycerol levels alone. The results of this study showed that using stable isotope technique allowed a more differentiated look at metabolic pathways than static plasma substrate concentrations, especially under perioperative conditions.

Adult↗
PubMed1997

Escape of HIV-1 is associated with lack of V3 domain-specific antibodies in vivo.

This study was performed to analyse correlates of viral escape in AIDS patients. Peripheral blood mononuclear cells (PBMC) from HIV- donors were inoculated with AIDS patients' serum to detect neutralization-resistant cell-free virus. Infectious virus was detected by polymerase chain reaction (PCR) and analysed by sequencing the V3 region. The escaped virus species was compared with all V3 virus variants found in the patients' PBMC and plasma. In one patient escaped virus was also compared with variants found in CD4+ T cells isolated by FACS from blood, spleen and lymph node. The frequency of the virus variants was determined by cloning and sequence analysis of 20 V3 clones for each PCR amplification. To monitor anti-V3 antibodies by ELISA, each V3 sequence was expressed as fusion with glutathione S-transferase (GST-V3). In our AIDS patients, a V3-directed antibody response against the infectious virus V3 loop was not detectable. In contrast, virus variants unable to infect the donor PBMC in vitro were well recognized by homologous V3-directed antibody. After an interval of 1 year the frequency of these variants clearly decreased, while at the same time the escaped variants grew out and finally represented the predominant viral species both in plasma and PBMC. The infectious variants lacking V3 antibody response were also predominant in CD4+ T cells in spleen and lymph node. Our data indicate that the escape of virus variants is closely related to the lack of V3-directed antibody.

Amino Acid Sequence↗
PubMed1997

Percentage of hypochromic red blood cells as predictor of erythropoietic and iron response after i.v. iron supplementation in maintenance haemodialysis patients.

BACKGROUND: The percentage of hypochromic red blood cells (RBC), defined as those with a cellular haemoglobin < 28 g/dl has been suggested to be a sensitive marker of functional iron deficiency in maintenance haemodialysis (HD) patients. Thus, during rHuEpo therapy an increase in hypochromic RBC to > 10% would indicate that more intensive iron supplementation may be required. METHODS: We investigated 70 HD patients 57.1 +/- 15.3 years old and on maintenance HD for 66.3 +/- 47.9 months without blood loss from gastrointestinal bleeding or from the vascular access, without surgery and without infectious disease or malignancy. During the study period of 12 weeks, each patient received in i.v. dose of 800 mg ferrogluconate. Haemoglobin, haematocrit, and the percentage of hypochromic RBC were measured before and every 4 weeks after the start of the study; serum ferritin, zinc protoporphyrin (ZPP) and C-reactive protein (CRP) were measured at the beginning (baseline) and end of the study. RESULTS: At baseline the percentage of hypochromic RBC was < or = 5.0% in 28 patients, > 5.0 and < or = 10.0% in 25 patients and > 10.0% in 17 patients, suggesting functional iron deficiency in at least 42 patients. Nine patients had serum ferritin values < 100 micrograms/1; nonetheless in these patients the median percentage of hypochromic RBC was 5.9% (range 0.9-14.3%), indicating that an absolute iron deficiency can occur in the presence of normal amounts of hypochromic RBC. There was a significant correlation between serum ferritin levels and hypochromic RBC at the end, but not at the beginning, of the study. However, there was no correlation between ZPP and hypochromic RBC at any time during the study. During i.v. iron supplementation the rHuEpo dose could be reduced by 8.5% in patients with hypochromic RBC < or = 5.0%, by 11.3% in patients with hypochromic RBC > 5.0 and < or = 10.0% and by 23.4% in patients with hypochromic RBC > 10.0%, demonstrating the benefit of i.v. iron in patients with functional iron deficiency. In HD patients in whom serum ferritin levels remained below 290 micrograms/l until the end of the study, a significant reduction of the rHuEpo dosage could be obtained during i.v. iron therapy. This was not the case in patients with serum ferritin > 290 micrograms/l after iron supplementation. We found that the percentage of hypochromic RBC is the most sensitive parameter for predicting hyporesponsiveness in CRP-positive patients. HD patients with hypochromic RBC > 6% and low to moderate increases in serum ferritin levels after i.v. iron supplementation significantly benefit from i.v. iron therapy compared to HD patients with hypochromic RBC < 6%. CONCLUSIONS: Two different aspects should be taken into consideration in HD patients treated with rHuEpo and concomitant i.v. iron therapy: (1) response of the erythropoietic system to rHuEpo, and (2) adequate delivery of the supplemented iron to the erythropoietic system. The patient's percentage of hypochromic RBC and increase in serum ferritin after i.v. iron supplementation should be used to decide whether or not i.v. iron should be given and to monitor this type of therapy in HD patients.

Anemia, Hypochromic↗
PubMed1997

The V3-directed immune response in natural human immunodeficiency virus type 1 infection is predominantly directed against a variable, discontinuous epitope presented by the gp120 V3 domain.

The specific binding of antibodies to the V3 loop in sera from human immunodeficiency type 1 (HIV-1)-infected individuals was investigated. Different V3 structures were analyzed as full-length loops or by pepscan. Our data show that on full-length V3 loops, both variable regions on either side of the tip of the loop (GPGRAF) contribute to a common epitope for type-specific antibodies. Type-specific antibodies bound strongly and at high titers to native V3 loops but negligibly once the loop was denatured. In contrast to the type-specific, discontinuous epitope, the linear, conserved epitopes presented by the full-length V3 loop, the tip, the amino-terminal base, and the carboxy-terminal base were not accessible to serum antibody. When the V3 sequences were analyzed with linear peptides, antibodies bound preferentially to peptides containing the conserved GPGRAF sequence. Thus, two different specificities of V3-directed antibodies were detected in patient sera. Unlike group-specific antibodies directed against GPGRAF peptides, lack of type-specific antibodies directed against the discontinuous epitope was correlated with viral escape from autologous neutralization. Our data suggest that the full-length conformation of the V3 loop is accessible predominantly to highly type-specific antibodies present in sera from HIV-1-infected individuals. These antibodies are directed against discontinuous V3 epitopes, not against conserved linear V3 targets. The implications of these findings for viral escape and blockade of infection with V3-based vaccines are discussed.

Amino Acid Sequence↗
PubMed1997

Distinct domains of M-T2, the myxoma virus tumor necrosis factor (TNF) receptor homolog, mediate extracellular TNF binding and intracellular apoptosis inhibition.

The myxoma virus tumor necrosis factor (TNF) receptor homolog, M-T2, is expressed both as a secreted glycoprotein that inhibits the cytolytic activity of rabbit TNF-alpha and as an endoglycosidase H-sensitive intracellular species that prevents myxoma virus-infected CD4+ T lymphocytes from undergoing apoptosis. To compare the domains of M-T2 mediating extracellular TNF inhibition and intracellular apoptosis inhibition, recombinant myxoma viruses expressing nested C-terminal truncations of M-T2 protein were constructed. One mutant, deltaL113, containing intact copies of only two cysteine-rich domains, was not secreted and was incapable of binding rabbit TNF-alpha yet retained full ability to inhibit virus-induced apoptosis of RL-5 cells. Thus, the minimal domain of intracellular M-T2 protein required to inhibit apoptosis is distinct from that required by the extracellular M-T2 for functional TNF-alpha binding and inhibition. This is the first report of a virus-encoded immunomodular protein with two distinct antiimmune properties.

Animals↗
PubMed1997

Osteopenia following total gastrectomy in the rat--state of mineral metabolism and bone histomorphometry.

Total gastrectomy (GX) in humans is frequently followed by osteopenia, but the details are unclear. The present investigations in the rat were aimed at elucidating its pathogenesis. Seventeen weeks after GX, we evaluated Ca, Mg and P metabolism as well as bone parameters, including fluorochrome-based bone histomorphometry. In GX rats, fecal Mg was increased, but intestinal absorption of P, Ca, and Mg was within normal limits, as was the urinary excretion of Ca, Mg, hydroxyproline and the pyridinium cross-links. In contrast, urinary P as well as cyclic AMP were significantly increased. In serum of GX rats, gastrin and 25-hydroxyvitamin D (25-OHD) were decreased, and Ca, Mg, P, parathyroid hormone (PTH), calcitonin, and the bone marker osteocalcin were normal, whereas 1,25-dihydroxyvitamin D [1,25(OH)2D] was significantly increased. GX rats had significantly reduced bone density and mineral content, severe high-turnover osteopenia, characterized by normal width but significantly decreased maturation time of osteoid, increased bone formation rate, and increased numbers of osteoclasts. We concluded that after GX (1) there is high-turnover osteopenia with normal mineralization and other histomorphometric features resembling those seen in states with hyperphosphaturia and subsequent hypervitaminosis D; (2) normal serum PTH levels and several indirect indicators of parathyroid gland function argue against the presence of (secondary) hyperparathyroidism, whereas increased bone mobilization due to elevated 1,25(OH)2D explains the maintenance of homeostasis of serum minerals, especially Ca, at the expense of bone mineral; (3) a complex interplay of mineral-metabolic effectors exists, among which low 25-OHD-PTH-independent renal phosphate losses, and high 1,25(OH)2D are prominent features. The presented animal model is recommended for future research in this area.

Animals↗
PubMed1997

21-Hydroxylase deficiency: screening and incidence in Israel.

BACKGROUND: Neonatal screening for congenital adrenal hyperplasia was introduced in 1977. However, even today only a few national screening programs exist and their cost effectiveness is still debatable. This study was conducted in order to evaluate the advisability of a national or regional screening program in Israel. METHODS: From June 1987 until December 1992 we screened a countrywide random sample of 113,846 newborns for 21-hydroxylase (21-OH) deficiency measuring 17alpha-OH progesterone (17-OHP) from blood spotted on filter paper. Between January 1993 and August 1995 we continued the screening program concentrating on the population of northern Israel. A total of 56,958 newborns were screened. We compared these findings with the incidence of 21-OH deficiency in the total population born in Israel during the years 1986-1991. RESULTS: In the countrywide screening program, 4 newborns (2 Arabs and 2 Jews) were found to have levels of 17-OHP between 409 and 2,049 nmol/l (2 males and 2 females). This constitutes a low incidence of 1 in 28,462 live births. In the north-Israel screening program 4 newborns (all Arabs) were detected (2 males and 2 females) constituting a much higher incidence of 1 in 14,240 live births. The data obtained from the archives revealed that the incidence of 21-OH deficiency nationwide during the years 1986-1991 was 1:19,000 live births, 1:30,000 for Jews and 1:8,000 for Arabs. The incidence of 21-OH deficiency among Arab newborns in the northern part of the country was as high as 1:5,000 (14:71,130). The female to male (F:M) ratio was 2.6:1 and the ratio of the salt-losing to the simple virilizing variant was 5:1. Two male patients were diagnosed prenatally, 21 patients (17 F and 4 M) during the first month after birth and 6 others subsequently. CONCLUSIONS: The high F:M ratio of 21-OH deficiency in the total population compared to a 1:1 ratio in our random screening programs suggests that 21-OH-deficient male patients in the general population might have been missed or died early due to a salt-losing crisis. The high incidence of this disease in the northern part of the country and especially among the Arabs, suggests that screening in this part of the country, especially among the Arab population, is warranted and might save the lives of some male patients.

Adrenal Hyperplasia, Congenital↗