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Biomedical subjects

J Klein

Publications and source records attributed to J Klein.

At least 325 records · Page 18Linked to original sources
PubMed1996

The pharmacokinetics and pharmacodynamics of the oral iron chelator deferiprone (L1) in relation to hemoglobin levels.

Recently, we demonstrated that administration of the orally active iron chelating agent deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one (L1)) at 6-hour intervals results in significantly greater urinary iron excretion than that induced during administration of the drug at 12-hour intervals. That study was conducted in thalassemia patients, all of whom had received a packed red cell transfusion of 15 cc/kg. 72 hours prior to evaluation of urinary iron excretion, at a time when endogenous erythropoiesis would be expected to be at its lowest. In clinical practice however, thalassemia patients, suppression of endogenous erythropoiesis is not sustained between transfusions. We set out to determine the influence that administration of deferiprone has on urinary iron excretion at lower hemoglobin concentrations, immediately prior to transfusion. We hypothesized that hemoglobin levels will affect the ability of deferiprone to chelate iron. Ten regularly transfused patients with homozygous beta-thalassemia (HBT) aged mean +/- SD, 20.9 +/- 4.7, range 13 - 27 years, receiving long-term therapy with deferiprone, were treated with deferiprone 75 mg/kg/day, administered every 6 hours (or every 12 hours) for 72 hours immediately prior to a blood transfusion in the first month. One month later each patient received the other of the 2 dosing regimens for 72 hours immediately prior to transfusion. The deferiprone-induced 24-hour urinary iron excretion was similar during both dosing regimens; 0.56 +/- 0.45 mg/kg when L1 was given every 6 hours and 0.48 +/- 0.52 mg/kg when L1 was administered every 12 hours (p = 0.79). However, the calculated 24-hour area under the plasma concentration-time curve (AUC0-24) of deferiprone was significantly lower when deferiprone was administered at 6-hour intervals (6,762.8 +/- 1,601.6 mg*min/l), than that observed when deferiprone was administered every 12 hours (8,250.1 +/- 1,235.7 mg*min/l) (p = 0.04). The pharmacokinetics of deferiprone when administered immediately prior to transfusions are different from those following transfusions. More studies assessing total body iron excretion are needed to determine the contribution of the fecal route in iron excretion.

Adolescent↗
PubMed1996

Nicotine and cotinine in maternal and neonatal hair as markers of gestational smoking.

OBJECTIVE: To determine the extent of fetal exposure to cigarette smoke, which cannot be clearly extrapolated from maternal reports, the authors measured concentrations of nicotine and cotinine in maternal and neonatal hair and corroborated these measures with maternal history and measures of pregnancy outcome. DESIGN: Prospective study of 94 mother-infant pairs. SETTING: Newborn nurseries of two hospitals in Toronto. PARTICIPANTS: 93 mothers, including active smokers, passive smokers and nonsmokers, and their newborns (including one set of twins). INTERVENTIONS: Hair collected from mothers and neonates shortly after birth was analysed by radio-immunoassay. MAIN OUTCOME MEASURES: Maternal data on demographic variables, obstetric history, diseases, drugs taken and smoking; infant data on demographic variables and birth indicators (gestational age, method of delivery, weight, head circumference, length, presence of meconium, need for resuscitation, need for special care and congenital malformations); hair concentrations of nicotine and cotinine. RESULTS: Neonates of active smokers had more adverse outcomes than other infants, including lower birth weight, smaller head circumference, shorter length and more perinatal complications. The difference was statistically significant. Amounts of cotinine extracted from mothers' and infants' hair showed significant differences among active smokers, passive smokers and non-smokers. When other people in the household and the mother smoked, neonatal hair concentrations of nicotine and cotinine in the infants were threefold higher than those in the infants of mothers who were the only smokers in their households. CONCLUSIONS: Hair concentrations of nicotine and cotinine are a powerful biological marker of the extent of intrauterine exposure to tobacco smoke.

Adolescent↗
PubMed1996

Axillary artery injury in closed fracture of the humeral neck.

A case of atherosclerotic axillary artery rupture in closed fracture of the proximal part of the humerus is described. It demonstrates a possible serious arterial injury in elderly persons even in case the fracture of the humeral neck is not dislocated. If there are signs of disturbed circulation in these injuries, angiography is indicated irrespective of the type of fracture and mechanism of injury.

Accidental Falls↗
PubMed1995

The limited efficacy of exercise radionuclide ventriculography in assessing prognosis of women with coronary artery disease.

Increasing numbers of women are undergoing stress testing for coronary artery disease evaluation. Limited study is available as to its efficacy in women. Four hundred nineteen patients with coronary artery disease (74 women and 345 men) referred for exercise radionuclide ventriculography between 1979 and 1986 were evaluated in a prospective cohort evaluation with 5-year follow-up. Exercise radionuclide ventriculographic variables were analyzed and compared between women and men. The prognostic efficacy of exercise radionuclide ventriculography was assessed separately for women and men among patients with coronary artery disease by Kaplan-Meier cumulative survival curves, univariate Cox regression analyses, and hierarchical stepwise Cox regression analyses. Overall, women demonstrated higher resting and peak left ventricular ejection fraction response to exercise than men. Ninety-six of 419 patients (23%) had cardiac events at 5-year follow-up. Although left ventricular response to exercise conveyed prognostic information in the combined and male populations (multivariate hierarchical analyses chi-square 11, p = 0.001 for delta left ventricular ejection fraction and chi-square 10, p = 0.002 for worsening exercise wall motion score), these variables were not found to be prognostically useful in women. Women with coronary artery disease demonstrated a worsened functional status, evidenced by greater compromise of exercise capacity, despite having less extensive anatomic disease than their male counterparts. We conclude that sex-related differences in left ventricular response to exercise limit the prognostic utility of exercise ventriculography in women with coronary artery disease.

Aged↗
PubMed1995

Evidence for insertion of a new intron into an Mhc gene of perch-like fish.

The evolution of the major histocompatibility complex (Mhc) has been studied to understand the origin of the immune system, of which it constitutes an essential part. In the present study, the Mhc is used to shed light on questions regarding the origin of introns and the phylogeny of fishes. The organization of the coding (exon) and non-coding (intron) regions of both class I and class II major histocompatibility complex (Mhc) genes is highly conserved in all vertebrate classes; the only variation observed until now is in the number of exons encoding the membrane-anchoring part. Moreover, there is a good correspondence between the exon-intron organization at the DNA level and the division into structurally and functionally defined domains at the protein level. Here we describe the first major exception to this uniformity. The immunoglobulin-like domain of the class II beta-chains in perch-like fishes (Percomorpha) is not encoded in one exon, as it is in all other vertebrates studied thus far, but in two exons. The length of the extra intron varies from gene to gene and from species to species, but is generally less than 200 base pairs (b.p.). Only one of the sequenced introns is about 500 b.p. long. In some of the genes, the intron contains a hexamer repeat. The repeat is present in the transcript at the site at which the intron interrupts exon 3 in the genomic DNA. The intron may therefore have arisen by repeated tandem duplication of this sequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Management of parapneumonic effusions. An analysis of physician practice patterns.

OBJECTIVE: To evaluate physician practices in managing patients with parapneumonic effusions and the impact of practice patterns on clinical outcome. DESIGN: Case series. SETTING: Private, tertiary care medical center. PATIENTS: Thirty-nine hospitalized patients with complicated parapneumonic effusions and a separate group of 191 patients admitted with community-acquired pneumonia. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Evaluation of physician practice patterns in managing complicated parapneumonic effusion and the impact of delaying thoracentesis (> or = 2 days after pleural fluid detection) or pleural drainage (> or = 2 days after pleural fluid criteria for drainage fulfilled) on duration of hospitalization, cost of hospitalization, and need for thoracotomy. RESULTS: Thirty-eight of the 39 patients with complicated parapneumonic effusions underwent thoracentesis that was "delayed" (5.7 +/- 3.1 days) in 16 patients. Delays in thoracentesis were associated with longer hospitalizations (P = .02). Laboratory tests ordered on nonpurulent pleural fluid were incomplete for 16 of 38 patients. Chest tube or surgical pleural drainage was delayed (4.2 +/- 3.5 days) in 10 of 38 patients who underwent thoracentesis. Delays in initiating drainage were associated with prolonged hospitalization (P = .04). Delaying interventions accounted for a mean cost increment per patient of $8462 for delayed thoracentesis and $9332 for delayed drainage. Of the 191 patients with community-acquired pneumonia, 99 (52%) had pleural effusions but only 15 (15%) underwent thoracentesis. CONCLUSIONS: Physicians commonly delay thoracentesis and chest tube drainage to observe parapneumonic effusions for improvement. This practice pattern is associated with longer and more costly hospitalizations.

Adult↗
PubMed1995

Mhc-DRB genes and the origin of New World monkeys.

The major histocompatibility complex (Mhc) is a family of loci characterized by its relatively rapid evolutionary turnover, large genetic distances between genes, and long persistence of allelic lineages effected by balancing selection. These features render the Mhc highly suitable for answering questions concerning speciation and adaptive radiation. The aim of the present study was to use Mhc-DRB genes to make inferences about the founding population of the Platyrrhini. Three segments, each approximately 300 base pairs in length, of the platyrrhine DRB genes were amplified by the polymerase chain reaction and sequenced. The segments were derived from intron 2, exon 3, and exon 6 of DRB genes from different species of New World monkeys. The results of the study have revealed that on a phylogenetic tree, all of the tested platyrrhine genes appear to form a single cluster, while all catarrhine DRB genes form a distinct cluster, although the bootstrap values fail to provide statistically significant support for the separation of these two clades. This observation suggests that the multiple platyrrhine genes originated from a single ancestral gene after the divergence of the Platyrrhini and Catarrhini and thus contradicts the results of an earlier study in which some exon 2 DRB sequences appeared to predate the split of the two primate groups. The inconsistency in the DRB gene phylogeny can be explained by postulating convergent evolution for the peptide-binding region of the DRB exon 2 sequences. The phylogeny of the platyrrhine DRB genes (except for exon 2) is relatively "shallow"; the distances between genes are relatively short (in comparison to the catarrhine DRB genes), and there is a tendency for sequences of individual species to cluster together. The phylogeny of the platyrrhine DRB genes is consistent with the postulate that a small population founded the group and that there is an ongoing adaptive radiation from small, relatively isolated founding populations.

Amino Acid Sequence↗
PubMed1995

Divergence time and population size in the lineage leading to modern humans.

We have developed maximum likelihood (ML) methods for comparisons of nucleotide sequences from unlinked genomic regions. In the case of a single species, the ML method primarily estimates the effective population size (Ne) under both constant size and abrupt expansion conditions. In the case of two or three species, the ML method simultaneously estimates the species divergence time and the effective size of ancestral populations. This allows us to trace the evolutionary history of the human population over the past several million years (my). Available sequences at human autosomal loci indicate Ne = 10,000 in the Late Pleistocene, a figure concordant with the results obtained from mitochondrial DNA sequence and allele-frequency data analysis, and there is no indication of population expansion. The ML analysis of two species shows that humans diverged from chimpanzees 4.6 my ago and that the human and chimpanzee clade diverged from the gorilla 7.2 my ago. Furthermore, the effective population size of humans more than 4.6 my ago is nearly 10 times larger than Ne of modern humans. The effective population size in the human lineage does not seem to have remained constant over the past several million years. The ML model for three species predicts slightly different, but consistent results to those obtained by the two-species analysis.

Animals↗
PubMed1995

Molecular cloning of major histocompatibility complex class II B gene cDNA from the Bengalese finch Lonchura striata.

The only avian major histocompatibility complex (Mhc) genes thus far identified are from species of the relatively small order of Galliformes, while by far the largest order of Passeriformes (songbirds), containing some 60% of extant bird species, has not been studied at all in this regard. The Galliformes emerged more than 55 million years (my) ago, the Passeriformes some 25 my ago. Because of the potential for the use of Mhc genes as markers in the study of songbird populations, an attempt was made to clone class II B genes of a passeriform species, the Bengalese finch Lonchura striata acuticauda. Using a set of primers designed on the basis of known sequences, a probe corresponding to part of exon II was obtained by the polymerase chain reaction. The probe was then used to screen a Bengalese finch cDNA library and to isolate and sequence two nearly full-length clones. The sequences reveal the presence of one presumably functional class II B locus in this bird species.

Amino Acid Sequence↗
PubMed1995

Cloning and characterization of class I Mhc genes of the zebrafish, Brachydanio rerio.

The zebrafish (Brachydanio rerio) offers many advantages for immunological and immunogenetic research and has the potential for becoming one of the most important nonmammalian vertebrate research models. With this in mind, we initiated a systematic study of the zebrafish major histocompatibility complex (Mhc) genes. In this report, we describe the cloning and characteristics of the zebrafish class I A genes coding for the alpha chains of the alpha beta heterodimer and thus complete the identification of all four classes and subclasses of the Mhc in this species. We describe the full class I alpha cDNA sequence as well as the exon-intron organization of the class I A genes, including intron sequences. We identify three families of class I A genes which we designate Brre-UAA, -UBA, and -UCA. The three families originated about the time of the divergence of cyprinid and salmonid fishes. All three families are members of an ancient lineage that diverged from another, older lineage also represented in cyprinid fishes before the radiation of teleost orders. The fish class I A genes therefore evolve differently from mammalian class I A genes, in which the establishment of lineages and families mostly postdates the divergence of orders.

Amino Acid Sequence↗
PubMed1995

Water-soluble poly(acrylamide-allylamine) derivatives of saccharides for protein-saccharide binding studies.

Water-soluble poly(acrylamide-allylamine) copolymers containing covalently bound amino groups, prepared by copolymerization of acrylamide and allylamine, can be used as general carriers for coupling of different types of saccharides or saccharide derivatives. The water-soluble macromolecular carbohydrate derivatives can be easily labelled and used in various solid-phase techniques to study protein-saccharide interaction. Two types of coupling reaction were used to prepare polyacrylamide derivatives of saccharides: reductive amination was applied to couple the reducing disaccharides and a carbodiimide reaction was used to couple heparin via its carboxyl groups to the amino groups of the poly(acrylamide-allylamine) derivative. Peroxidase labelled or biotinylated derivatives were shown to be useful in studies on the binding properties of lectins and proteins from boar seminal plasma.

Acrylic Resins↗
PubMed1995

Validation and application of a subjective knee questionnaire.

Patients' complaints on limitations in activities of daily living (ADL) and sports are possible signs for various injuries of the knee joint. These complaints can be easily assessed by the patient using a questionnaire with visual analogue scale (VAS) responses. A German translation of the English questionnaire concerning knee complaints [4] has been validated and tested for clinical use. It consists of 28 questions. For the statistical analysis, an overall score (VAS score) of the questionnaire was determined. The validation included an expert evaluation on the content of the questionnaire, a test for the reliability, a comparison with subjective knee scoring systems (Cincinnati score, Lysholm score) and a test on VAS score results in patient groups with various knee injuries (discrimination of patients). For the evaluation of operative treatment results, the responsiveness of the questionnaire was tested in patients undergoing arthroscopic meniscus surgery and anterior cruciate ligament reconstruction. The investigation was conducted prior to the operation, 2, 6, 12 and 24 weeks after surgery for both groups and also 36 weeks after surgery for the cruciate ligament patients. Interviews conducted with knee surgeons (so-called knee experts) revealed that 85% judged the questionnaire as being acceptable for clinical use. The reliability of the VAS score for healthy individuals was r = 0.86. The reliability for patients in a postoperative rehabilitation programme was r = 0.92. By means of the VAS score we were able to assess the extent of limitations in knee function in various patient groups with meniscus lesions, insufficiency ot the anterior and posterior cruciate ligaments and chondromalacia.(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1995

Ocular abnormalities in neurofibromatosis 2.

PURPOSE: To evaluate the ocular abnormalities in patients with clinically diagnosed neurofibromatosis 2 and asymptomatic gene carriers. METHODS: Probands were ascertained through a surgical otolaryngology practice. In a cross-sectional study, we examined 49 patients with neurofibromatosis 2, 30 offspring of patients, and, as a comparison group, 18 parents and siblings of patients with sporadic neurofibromatosis 2. The examination included a complete neuro-ophthalmic assessment, physical examination, and, for patients and first-degree relatives at risk, cranial and spinal magnetic resonance imaging with gadolinium enhancement, if not previously performed. RESULTS: The most common ocular abnormalities were posterior subcapsular or capsular, cortical, or mixed lens opacities in 33 (67%) of 49 patients with neurofibromatosis 2 and retinal hamartomas in 11 (22%). We used segregation analysis to determine the mutation carrier status of six at-risk offspring who were 30 years old or younger in two multigeneration families. Three asymptomatic mutation carriers had cataracts, whereas those who were predicted not to carry the mutation did not have cataracts. Asymptomatic mutation carriers may have developmental abnormalities of the eye that are detectable in childhood or adolescence, a finding that may assist in early diagnosis of the disease. CONCLUSIONS: A variety of ocular abnormalities are present in neurofibromatosis 2, including cataracts, retinal hamartomas, and ocular motor deficits. Many of these are developmental or acquired early in life and may assist in presymptomatic diagnosis. For screening at-risk relatives of patients with neurofibromatosis 2, the types of cataract that are most suggestive of neurofibromatosis 2 are plaque-like posterior subcapsular or capsular cataract and cortical cataract with onset under the age of 30 years.

Adolescent↗
PubMed1995

Defensive hostility: relationship to multiple markers of cardiac ischemia in patients with coronary disease.

Three studies assessed whether the combined traits of hostility and defensiveness identify a group of hostile individuals with functionally severe coronary artery disease (CAD). CAD patients completed the Cook-Medley Hostility Inventory (Ho) and the Marlowe-Crowne Social Desirability Scale (MC). Patients were classified into 4 groups: defensive hostile (DH: high Ho, high MC), low hostile (LH: low Ho, low MC), high hostile (HH: high Ho, low MC), and defensive (Def: low Ho, high MC). DH in comparison to HH, LH, and Def CAD patients demonstrate the greatest perfusion defects as measured by exercise thallium scintigraphy; DH patients exhibit the most frequent ischemic episodes during ambulatory electrocardiographic monitoring; and in a laboratory study, DH patients exhibit the most severe mental stress-induced ischemia assessed by echocardiography. Thus, the combination of high hostility and high defensiveness are associated with more functionally severe CAD and may predispose CAD patients to a more adverse prognosis.

Aged↗
PubMed1995

Defects in the structure and expression of the genes for the T cell marker Rt6 in NZW and (NZB x NZW)F1 mice.

Rt6 is a T cell-restricted GPI-anchored membrane protein and a member of the family of mono(ADP-ribosyl)transferases. One of the two murine Rt6 genes is deleted in NZW mice. This finding is reminiscent of the deletion of one of the TCR beta genes in the same mouse strain and it is an intriguing possibility that these gene deletions arose by a common genetic mechanism. The Rt6 locus retained by the NZW mouse (designated Rt6-1) is polymorphic among inbred strains of laboratory mice. The NZW mouse shows several strain-specific restriction fragment length variants in this Rt6 locus and five amino acid substitutions occur in the predicted native Rt6 polypeptide of the NZW mouse relative to the corresponding polypeptides of NZB and BALB/c mice. Whereas transcript levels of the two Rt6 genes appear to be normal in spleen and intestine of NZB mice, the corresponding tissues of NZW mice show reduced levels of transcripts from the Rt6 locus retained in this mouse strain. Moreover, reduced levels of Rt6 mRNA also occur in spleen and intestine of (NZB x NZW)F1 hybrid animals, indicating that F1 animals have inherited a dominant factor from the genetic background of the NZW mouse, resulting in low levels of Rt6 expression. It is conceivable that the alterations in the Rt6 genes of the NZW mouse and/or the factor(s) affecting defective Rt6 expression constitute part of the genetic contribution of the NZW mouse to the autoimmune lupus-like disease in (NZB x NZW)F1 animals.(ABSTRACT TRUNCATED AT 250 WORDS)

ADP Ribose Transferases↗