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Biomedical subjects

M Peters

Publications and source records attributed to M Peters.

At least 253 records · Page 14Linked to original sources
PubMed1995

Inter-individual variation in half-life of infused recombinant factor VIII is related to pre-infusion von Willebrand factor antigen levels.

In an attempt to explain the substantial inter-individual variability in half-life of infused factor VIII (FVIII) among haemophilia A patients, we studied the correlation of pre-infusion von Willebrand factor antigen (vWFAg) levels and the half-life of a recombinant-DNA-derived FVIII (r-VIII SQ. Pharmacia, Sweden). Intra-individual variation in half-life was small (range of variation 0-2.1 h) in 12 severely affected haemophiliacs who received two doses of FVIII concentrate. In contrast, inter-individual variation in half-life was large (range of half-lives 6-28.8 h). A strong correlation between half-life and pre-infusion vWFAg levels was present (r = 0.87, P = 0.0003). We conclude that the half-life of infused recombinant FVIII is related to pre-infusion vWFAg levels in severely affected haemophilia A patients.

Adult↗
PubMed1995

Fulminant meningococcal septic shock in a boy with combined inherited properdin and protein C deficiency.

A 7-year-old patient with fulminant septic shock due to Neisseria meningitidis of the uncommon serogroup Y developed extensive gangrene of the limbs. Multiple amputations were necessary and a pulmonary embolism occurred within 2 days post-operatively. Complement and haemostatic system studies, done after recovery, showed a complete absence of properdin antigen and a low protein C antigen and activity level in plasma. Defective haemolytic activity in gel by the alternative pathway of complement activation could be restored with purified properdin, indicating a properdin deficiency type 1. Protein C antigen level as well as activity were in agreement with a protein C deficiency type I. The polymerase chain reaction (PCR) product of exon five of the protein C gene showed a substitution of 72Gly by Arg. Both deficiencies were traced among relatives of the patient. Serum of the father of the patient's mother was also properdin-deficient. Microsatellite haplotyping of the X-chromosome of the patient and his relatives showed that a distinct haplotype cosegregated with the properdin deficiency (Lodscore 2.25; four informative meioses). The protein C type I deficiency was present in the patient's mother and her mother and cosegregated with the mutation found. So far as is known, this is the first patient described with combined inherited properdin deficiency and protein C deficiency.

Adult↗
PubMed1995

Studies of the detection of Listeria monocytogenes by culture and PCR in cerebrospinal fluid samples from ruminants with listeric encephalitis.

A total of 14 cerebrospinal fluid (CSF) samples from ruminants clinically suspected of suffering from listeric encephalitis were examined by polymerase chain reaction (PCR) for the detection of Listeria monocytogenes (L. m.). Of these samples, 11 were examined bacteriologically. Although the clinical diagnosis was confirmed in eight of 11 ruminants by histological and/or bacteriological examination of the brains, L. m. was only detected in one of the CSF samples using PCR, and in none by culture. The PCR-positive CSF sample was obtained from a sheep which had been treated with antibiotics prior to CSF sampling. From these findings, it was concluded that L. m. only occasionally gains access to the meningoventricular system in the course of listeric encephalitis of ruminants and that a reliable aetiological in vivo diagnosis of listeric encephalitis generally cannot be based on the detection of L. m. in the CSF of affected ruminants.

Animals↗
PubMed1995

Isolation of Bacteroides ureolyticus from vaginal discharge of mares.

A total of seven Bacteroides ureolyticus strains were isolated from the cervix and the clitoral fossa of mares with vaginal discharge. No other bacteria capable of causing metritis or vaginitis were isolated from the samples. The isolated strains resembled Taylorella equigenitalis. Both species are catalase, oxidase and alkaline phosphatase positive, but, in addition to these characteristics, B. ureolyticus strains produced urease and they could not tolerate 10% O2. They also failed to be agglutinated in a hyperimmune serum raised against T. equigenitalis; however, B. ureolyticus and T. equigenitalis were agglutinated in the slide agglutination test in a serum produced against one of the B. ureolyticus isolates. Further investigations are needed to clarify the pathologic role of B. ureolyticus in genital infections of mares and other animals.

Animals↗
PubMed1995

Secretory symptoms from metastatic adrenal cortical carcinoma responding to octreotide.

The prognosis of patients with metastatic adrenal cortical carcinoma is poor, and their disabling symptoms are usually unresponsive to conventional therapy. A patient with Cushing's syndrome secondary to a secretory adrenal cortical carcinoma was treated with octreotide, endocrine therapy and chemotherapy having failed. Treatment led to a dramatic relief of her symptoms with a fall in corticosteroid secretion. Somatostatin analogue therapy for this tumour should be encouraged in view of the lack of alternative palliative treatment.

Adrenal Cortex Neoplasms↗
PubMed1995

Identification of a unique form of protein C in the ovine fetus: developmentally linked transition to the adult form.

To investigate fetal development of protein C, a pregnant ovine model was used. Protein C was isolated from ovine plasma, and a polyclonal antibody was raised. Citrated plasma was obtained from undisturbed chronically catheterized fetal lambs. On Western blot, nonreduced adult ovine protein C had a molecular mass of 70 kD. Fetal ovine protein C was determined to have a molecular mass of 4 to 6 kD larger than the adult molecule. Crossed immunoelectrophoresis demonstrated slightly increased anodal migration of the fetal form. Isoelectric focusing demonstrated a decreased pI of the fetal molecule (4.45 versus 4.6). The ovine protein C molecules were deglycosylated with N-glycanase. Deglycosylated fetal protein C migrated more similarly to the adult form, although a portion of the fetal form persisted. These experiments demonstrate the first example of a unique fetal form of a vitamin K-dependent protein and are compatible with increased glycosylation of fetal ovine protein C. It is speculated that altered posttranslational processing may exist as a general process by which certain coagulation proteins are modified during fetal development. mRNA was isolated from maternal and fetal hepatic tissue and analyzed by Northern hybridization. Fetal plasma concentration and hepatic mRNA for protein C were both 40% of normal maternal values from midgestation onward. At term, protein C mRNA increased to adult range (p < 0.025), although plasma protein C concentration decreased slightly (p < 0.001). A transition from fetal to adult protein C form was found beginning 6 d before term birth, with a doubling time of 24 h. These data are compatible with a gestationally determined maturation of ovine protein C.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1995

Dissection of the internal carotid artery after chiropractic manipulation of the neck.

A 29-year-old woman died from a right hemispheric infarction caused by dissection and subsequent thrombosis of the internal carotid artery after chiropractic manipulations of the neck. Pathologic study of several arteries of muscular and elastic type revealed a mediolytic arteriopathy with widespread mucoid degeneration and cystic transformation of the vessel wall caused by segmental degeneration of smooth muscle cells of the tunica media. We hypothesize that mediolytic arteriopathy was a predisposing factor for the dissection of the internal carotid artery after chiropractic manipulations in our patient.

Adult↗
PubMed1995

Estrogens reduce plasma histidine-rich glycoprotein (HRG) levels in a dose-dependent way.

Plasma levels of histidine-rich glycoprotein (HRG) were investigated in three groups of women receiving a different dose of estrogens. First, the effect of low-dose estrogen was studied in a group of 83 postmenopausal women who were treated with 0.625 mg conjugated estrogens (CE). No significant change from baseline levels was found at the end of cycle 3 and cycle 13. Secondly, in 15 mothers and 23 daughters using oral contraceptives (OC) containing 30-50 micrograms ethinyl estradiol (EE) daily the mean HRG level was 14% and 24% lower than in a group of 144 mothers and 134 daughters not taking oral contraceptives, respectively (p < 0.05). Finally, in 11 excessively tall prepuberal girls who received 300 micrograms EE daily to reduce their final height the mean plasma HRG levels were decreased by 68% (p < 0.005). The effect of progestogens administered during low-dose and high-dose estrogen therapy appeared to be minor. The results from these three studies indicate that estrogens reduce plasma HRG levels in a dose-dependent way.

Adolescent↗
PubMed1995

Coagulation activation and tissue necrosis in meningococcal septic shock: severely reduced protein C levels predict a high mortality.

In 35 consecutively admitted children (mean age: 4.3 years) with a clinical diagnosis of meningococcal septic shock (MSS), activation of the coagulation and fibrinolytic pathways was evaluated directly at admittance to the paediatric intensive care unit (ICU). The association of clinical signs and haemostatic abnormalities was assessed. All patients had signs of extensive activation of the coagulation system. The 28-day mortality was 26%. Protein C activity was strongly reduced, especially in non-survivors in whom it was significantly lower than in survivors (5% versus 23%; p < 0.0001). There was a strong negative correlation between protein C activity and the mean size of the skin lesions (r = -0.71, p < 0.001). These results suggest that an acquired protein C deficiency in MSS is related to the pathogenesis of purpura fulminans. Furthermore, no increase in C4b-binding protein (C4BP) and no decrease in the ratio free protein S/total protein S was observed, suggesting that a deficiency of free protein S as a result of increased C4BP does not play a pathogenetic role in meningococcal septic shock.

Adolescent↗
PubMed1995

A rule-based decision support application for laboratory investigations management.

The appropriate management of clinical laboratory requests in specialised clinical units often requires the adherence to pre-defined protocols. We evaluated the impact of a rule-based expert system for clinical laboratory investigations management in a pediatric liver transplantation unit of our hospital. After one year, we observed an overall reduction in laboratory resources consumption for transplanted patients (-27%) and a decrease in the percentage of "STAT" requested tests (-44%). The percentage of tests ordered in agreement with the protocols for those patients increased from 33% before the introduction of the expert system to 45% when the system was used. The system was perceived by the clinicians as increasing the overall benefits in use of clinical resources, improving the laboratory data management, and saving time for the execution of laboratory ancillary tasks.

Clinical Laboratory Information Systems↗
PubMed1995

[Possibilities for geriatric psychosomatic rehabilitation].

Starting out from the insufficiencies in the psychotherapeutic care for elderly patients, the treatment possibilities available in psychosomatic clinics are delineated. Utilization of these possibilities by the elderly is pointed out, some fundamental aspects of gerontopsychosomatic rehabilitation are discussed, and it is shown that specific aspects must be considered in the treatment of this population.

Activities of Daily Living↗
PubMed1995

A point mutation in an invariant splice acceptor site results in a decreased mRNA level in a patient with severe coagulation factor XIII subunit A deficiency.

Amplification and sequencing of exons I-XV of the gene encoding subunit A of coagulation factor XIII (FXIII) in a patient with severe subunit A deficiency revealed a single G-->A base substitution at the last position of intron E, mutating the invariant AG dinucleotide splice acceptor site to AA. Northern blot analysis of FXIII subunit A mRNA levels in peripheral mononuclear leukocytes showed that this mutation leads to an undetectable FXIII subunit A mRNA level, suggesting that the mutant transcript is either highly unstable or only spliced at low efficiency. Despite this low mRNA level we were able to amplify cDNA fragments containing the exonV-exonVI junction. Sequence analysis showed that the AA dinucleotide is not recognized by the splicing machinery. Instead, an AG dinucleotide located seven bases downstream of the mutated splice acceptor site is used as alternative acceptor. The resulting, alternatively spliced, FXIII subunit A transcript contains a deletion of the first seven bases of exon VI, while translation continues out of frame and leads to a premature stop codon 27 bases thereafter.

Base Sequence↗
PubMed1995

The influence of insulin, beta-estradiol, dexamethasone and thyroid hormone on the secretion of coagulant and anticoagulant proteins by HepG2 cells.

As a basis for regulatory studies on the influence of hormones on (anti)coagulant protein production by hepatocytes, we examined the amounts of the plasma proteins antithrombin III (AT III), protein C, protein S, factor II, factor X, fibrinogen, and prealbumin produced by the hepatoma cell line HepG2, into the culture medium, in the absence and presence of insulin, beta-estradiol, dexamethasone and thyroid hormone. Without hormones these cells produced large amounts of fibrinogen (2,452 +/- 501 ng/mg cell protein), AT III (447 +/- 16 ng/mg cell protein) and factor II (464 +/- 31 ng/mg cell protein) and only small amounts of protein C (50 +/- 7 ng/mg cell protein) and factor X (55 +/- 5 ng/mg cell protein). Thyroid hormone had a slight but significant effect on the enrichment in the culture medium of the anticoagulant protein AT III (1.34-fold) but not on protein C (0.96-fold) and protein S (0.91-fold). This hormone also significantly increased the amounts of the coagulant proteins factor II (1.28-fold), factor X (1.45-fold) and fibrinogen (2.17-fold). Insulin had an overall stimulating effect on the amounts of all the proteins that were investigated. Neither dexamethasone nor beta-estradiol administration did substantially change the amounts of these proteins. We conclude that the HepG2 cell is a useful tool to study the hormonal regulation of the production of (anti)coagulant proteins. We studied the overall process of protein production, i.e., the amounts of proteins produced into the culture medium. Detailed studies have to be performed to establish the specific hormonal effects on the underlying processes, e.g., transcription, translation, cellular processing and transport, and secretion.

Antithrombin III↗
PubMed1995

Activation of the intrinsic pathway of coagulation in children with meningococcal septic shock.

Meningococcal septic shock (MSS) is complicated by activation of coagulation, fibrinolytic, and complement systems. We studied the contact system of the intrinsic pathway of coagulation in thirteen children with MSS. Activation was assessed upon admittance to the intensive care unit and 48 h thereafter, based on the measurement of factor XII- (FXII), prekallikrein- and factor XI (FXI) antigen levels, as well as on the detection of FXIa-FXIa inhibitor, FXIIa-C1-inhibitor, and kallikrein-C1-inhibitor complexes, respectively. Levels of FXII, prekallikrein and FXI were reduced to about 50% in all patients on admission, and were significantly higher 48 h later. FXIIa-C1-inhibitor complexes were elevated in 7 patients, and kallikrein-C1-inhibitor complexes in 2 patients. FXIa-alpha 1-antitrypsin complexes were elevated in all patients, FXIa-C1-inhibitor complexes in nine, and FXIa-antithrombin III complexes in one patient. We conclude that patients with MSS have activation of the contact system, which may contribute to activation of coagulation, and thus to morbidity and mortality.

Adolescent↗
PubMed1994

Nonhomologous DNA end joining of synthetic hairpin substrates in Xenopus laevis egg extracts.

Processes of DNA end joining are assumed to play a major role in the elimination of DNA double-strand breaks (DSB) in higher eucaryotic cells. Linear plasmid molecules terminated by nonhomologous restriction ends are the typical substrates used in the analysis of joining mechanisms. However, due to their limited structural variability, DSB ends generated by restriction cleavage cover probably only part of the total spectrum of naturally occurring DSB termini. We therefore devised novel DNA substrates consisting of synthetic hairpin-shaped oligonucleotides which permit the construction of blunt ends and 5'- or 3'-protruding single-strands (PSS) of arbitrary sequence and length. These substrates were tested in extracts of Xenopus laevis eggs known to efficiently join linear plasmids bearing nonhomologous restriction termini (Pfeiffer and Vielmetter, 1988). Sequences of hairpin junctions indicate that the short hairpins are joined by the same mechanisms as the plasmid substrates. However, the bimolecular DNA end joining reaction was only detectable when both hairpin partners had a minimal duplex stem length of 27bp and their PSS-tails did not exceed 10nt.

Animals↗
PubMed1994

Immunoglobulin variable region usage in human intestinal B lymphocytes.

The B cell repertoire was studied in intestinal mononuclear cells from normal individuals and patients with inflammatory bowel disease (IBD) by examining Ig heavy chain variable gene (VH) usage. Using reverse transcription of intestinal mucosal RNA followed by polymerase chain reaction with primers specific for each VH family and a housekeeping gene, a semiquantitative assay of VH family content in RNA samples was developed. While all VH family members were expressed, differences in VH usage in lamina propria intestinal B cells were noted between Crohn's disease, ulcerative colitis, and normal individuals. mRNA transcripts for VH4 were present at seemingly higher levels than their genomic representation and transcripts for VH1 and VH4 appeared to have higher levels in active, compared to inactive, IBD. Thus, within the massive polyclonal intestinal B cell response, there is a skewed VH usage which may be relevant to the antigenic and/or autoimmune response noted in IBD.

B-Lymphocytes↗