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Biomedical subjects

S Koch

Publications and source records attributed to S Koch.

At least 145 records · Page 8Linked to original sources

Hexokinase II mRNA and gene structure, regulation by insulin, and evolution.

A DNA segment that is highly conserved in glucokinase (hexokinase IV) and hexokinase I cDNA was used to identify specific cDNAs in a library prepared from rat adipose tissue mRNA. Some of these cDNAs were identified as being hexokinase I cDNA. Others, although similar to both the glucokinase and hexokinase I cDNAs, were unique. Two of these unique cDNAs overlapped and contained an open reading frame that encoded a protein of 103 kDa which, when expressed in Escherichia coli, had kinetic properties characteristic of hexokinase II. The entire hexokinase II mRNA sequence and the exon-intron structure of the hexokinase II gene were determined. A single transcription initiation site and two distinct termination sites account for the two observed hexokinase II RNA species of 5500 and 4400 nucleotides that were detected when either of the cDNAs was used as a hybridization probe against poly(A)+ RNA isolated from rat adipose tissue. Hexokinase II mRNA was decreased in adipose tissue from diabetic rats, but was restored by insulin treatment to levels found in nondiabetic control rats. Insulin also induced hexokinase II mRNA in two adipose cell lines (3T3-F442A and BFC-1B) and two skeletal muscle cell lines (C2C12 and L6). In L6 cells, this increase was accounted for by a corresponding increase of hexokinase II gene transcription. Comparison of the structures of the hexokinase II and glucokinase genes support the hypothesis that the 100-kDa hexokinase arose by gene duplication and tandem ligation of a 50-kDa glucokinase-like ancestral gene.

Adipose Tissue↗

Childhood anemia in Africa: to transfuse or not transfuse?

Blood transfusions are an important route for HIV transmission in Africa. To explore whether transfusions are necessary in the case management of childhood anemia, a randomized trial was performed in Ifakara, Tanzania, a holoendemic malaria region. 116 children were randomized to receive either treatment for malaria and hookworm alone or, in addition, a transfusion of whole blood which had been tested negative for antibodies against the human immunodeficiency virus. Mean packed cell volume (PCV) at admission was 14.0% in the transfusion and 14.4% in the no transfusion group. Children were followed up for 8 weeks with measurements of PCV at 2 days, 4 weeks and 8 weeks after study entry. PCV was similar in both groups after 4 and 8 weeks (22.9% in the transfusion and 23.6% in the no transfusion group). There was a trend towards more hospital admissions and deaths in the no transfusion group; however, 95% confidence intervals included both a beneficial and an adverse effect of blood transfusions. The costs and benefits of transfusion for childhood anemia in countries with a high HIV prevalence need to be considered carefully before a rational treatment policy can be adopted. For that purpose, a larger randomized trial is urgently needed.

Anemia↗

A phase II study of moderate hypothermia in severe brain injury.

Forty-six patients with severe nonpenetrating brain injury [Glasgow Coma Scale (GCS) 4-7] were randomized to standard management at 37 degrees C (n = 22) and to standard management with systemic hypothermia to 32 to 33 degrees C (n = 24). The two groups were balanced in terms of age (Wilcoxon's rank sum test, p > 0.95), randomizing GCS (chi-square test, p = 0.54), and primary diagnosis. Cooling was begun within 6 h of injury by use of cooling blankets. Metocurine and morphine were given hourly during induction and maintenance of hypothermia. Rewarming was at a rate of 1 degree C per 4 h beginning 48 h after intravascular temperature had reached 33 degrees C. Muscle relaxants and sedation were continued until core temperature reached 35 degrees C. There were no cardiac or coagulopathy-related complications. Seizure incidence was lower in the hypothermia group (Fisher's exact text, p = 0.019). Sepsis was seen more commonly in the hypothermia group, but difference was not statistically significant (chi-square test). Mean Glasgow Outcome Scale (GOS) score at 3 months after injury showed an absolute increase of 16% (i.e., 36.4-52.2%) in the number of patients in the Good Recovery/Moderate Disability (GR/MD) category as compared with Severe Disability/Vegetative/Dead (SD/V/D) (chi-square test, p > 0.287). Based on evidence of improved neurologic outcome with minimal toxicity, we believe that phase III testing of moderate systemic hypothermia in patients with severe head injury is warranted.

Adolescent↗

Transient bilateral internuclear ophthalmoplegia after minor head-trauma.

Following minor occipital head-trauma, a six-year-old boy developed bilateral internuclear ophthalmoplegia (INO) as the only neurological sign. After having excluded all other possible aetiological causes by careful examination, including magnetic resonance imaging, the symptoms eventually were attributed to the trauma. The course of the INO was documented by electro-oculography. A saccades-training programme specially adapted to the boy's age was performed, and complete remission of the oculomotor symptoms occurred after one year.

Child↗

Use of a disposable carbon dioxide detector with emergency intubation in a hyperbaric chamber.

Emergency intubation in a hyperbaric chamber can be complicated by the confined space, inadequate lighting and high levels of background noise. Inadvertent esophageal intubation may be difficult to recognize in these conditions. In more controlled settings such as the operating room, the detection of end-tidal carbon dioxide is the standard procedure for verifying proper placement of the endotracheal tube. Within a hyperbaric chamber, a capnograph may not be readily available for this purpose. We present a case report describing the use of a simple disposable colorimetric carbon dioxide detector for rapid verification of endotracheal tube position following emergency intubation in a hyperbaric chamber.

Adult↗

CD4 T cells in murine acquired immunodeficiency syndrome: polyclonal progression to anergy.

We have examined the kinetics of changes that occur in the helper T cell subset during murine acquired immunodeficiency syndrome, which occurs after infection with the mix of viruses known as BM5. We find that there is expansion of the CD4 T cells by 2 wk, 50% of the CD4 T cells become large as the disease progresses, and the CD4 T cell population is increasingly comprised of cells with a memory/activated phenotype. These effects are apparent by 2 wk postinfection, and the change is nearly complete by 6-8 wk. The phenotypic shift is paralleled by the loss of the ability of the CD4 T cells to proliferate or to produce interleukin 2 (IL-2), IL-3, IL-4, and interferon gamma in response to stimulation with mitogens, superantigen, or anti-CD3. There is no obvious expansion or deletion of CD4 T cells expressing particular V beta genes, as might be expected if a conventional superantigen were driving the changes. The results suggest, however, that the total CD4 population has been driven to anergy by some potent polyclonal stimulus directly associated with viral infection.

Animals↗

A quartz crystal biosensor for measurement in liquids.

The detection of anti-human immunodeficiency virus (HIV) antibodies by means of synthetic HIV peptide immobilized on a piezoelectric quartz sensor is demonstrated. The measurement set-up consists of an oscillator circuit, a suitably modified AT-cut thickness-shear-mode quartz crystal with gold electrodes, which is housed in a special reaction vessel, and a computer-controlled frequency counter for the registration of the measured frequency values. The quartz crystal is adapted for a steady operation in liquids at a frequency of 20 MHz. In phosphate-buffered saline solution the oscillator reaches a stability of about 0.5 Hz within a few seconds, of about 2 Hz within 10 min and about 30 Hz within 1 h. The frequency shift due to the adsorption of various proteins to the uncoated sensor surface has been investigated. It can be shown that a stable adsorptive binding of proteins to an oscillating gold surface is feasible and can be used for the immobilization of a receptor layer (e.g. HIV peptide). Specific binding of the anti-HIV monoclonal antibody to the HIV peptide immobilized on the quartz sensor is demonstrated. Control experiments show, however, additional unspecific binding. According to the experiments, the Sauerbrey formula gives a sufficiently accurate value for the decrease of the resonant frequency due to adsorption or binding of macromolecular proteins on the quartz crystal surface.

Biosensing Techniques↗

Serum lipids, lipoproteins and apolipoproteins in children with and without familial history of premature coronary heart disease.

A positive family history of premature cardiovascular disease is recognized as an independent predictor of risk for cardiovascular death in first degree relatives. It is of great interest whether the progeny of families with manifest coronary heart disease can be discriminated from children with a negative family history. Therefore, we examined serum lipids, lipo- and apolipoproteins in 338 offspring whose fathers and/or mothers had been affected with a myocardial infarction before the age of 55, in comparison with 448 age- and sex-matched, healthy controls. Statistical analyses revealed marked differences between the two groups: In both age groups only high-density lipoprotein cholesterol (HDL-C), as a single parameter, and the ratios of total cholesterol (TC)/HDL-C, as well as low-density lipoprotein cholesterol (LDL-C)/HDL-C, showed a significant difference between the risk and nonrisk groups. Whereas the ratio of apolipoprotein A1 (ApoAI) to apolipoprotein B is the strongest discrimination in children less than or equal to 20 years, the ratio of HDL-C/ApoAI takes this position in the older ones. Apolipoproteins seem to be of considerable importance as risk indicators between offspring who might be at higher risk for later cardiovascular diseases, even in childhood and younger adolescence.

Adolescent↗

Major and minor birth malformations and antiepileptic drugs.

In a study of infants of parents with epilepsy, malformations were twice as prevalent in these children as in controls. Children of mothers with epilepsy had more minor anomalies than those of fathers with epilepsy or controls. At 1 year of age, a greater number of minor anomalies was seen in children of mothers with epilepsy who had received treatment with antiepileptic drugs (AEDs) during pregnancy, whereas at 4 years, no difference was observed. Type of epilepsy, seizures during pregnancy, plasma levels of phenytoin or phenobarbital in the medium range, and fetal intrauterine growth did not correlate with the number of minor anomalies. We suggest that the special genetic background that predisposes to epilepsy also renders the fetus more vulnerable to major and minor anomalies. Although linkage between epilepsy and malformation is stronger than between AEDs and malformations, valproate, phenytoin, and phenobarbital show specific teratogenic effects. In addition, all AEDs unspecifically increase the number of minor anomalies. Under therapeutic conditions, valproate may be regarded as considerably teratogenic and all other observed AEDs as weakly teratogenic.

Abnormalities, Drug-Induced↗

Long-term follow-up of 12 patients with the late-onset variant of argininosuccinic acid lyase deficiency: no impairment of intellectual and psychomotor development during therapy.

To date, two variants of argininosuccinic acid lyase deficiency, the second most common enzymatic defect of the urea cycle, have been described. Most of the previous studies reported on outcomes involving neurological and intellectual impairment in affected children. This study is the first to demonstrate that the physical and mental development of such children can be normal and adequate for their age if they are treated with a low-protein diet and/or arginine supplements. Since 1973, 12 Austrian children suffering from argininosuccinic acid lyase deficiency have been detected in the Austrian Neonates Screening Program and could have been followed up. After confirmation of diagnosis, all the children were administered a daily arginine supplement (3 to 4 mmol/kg per day) in conjunction with either a normal diet or a special diet in which protein intake was restricted to 1.2 to 1.5 g/kg per day. Routine checks, including physical examination, determination of biochemical parameters, and IQ tests, were performed so the further development of these 12 patients with respect to treatment could be observed. It can be concluded that early treatment of partial argininosuccinic acid lyase deficiency results in normal intellectual and psychomotor development.

Amino Acid Metabolism, Inborn Errors↗

Training errors in long distance running.

Among the most common factors causing injury in long distance runners are training errors. Even the most elite runner may lose valuable workout time when training terrain, equipment, or the progression of workouts, is not appropriate. Through this article we hope to help athletic trainers identify specific errors in athletes' training and their related injuries. Additional suggestions are made that will aid the professional in workout modification in order to prevent injury or to expedite recovery.

Journal Article↗

Pharmacokinetics of ritanserin in patients undergoing hemodialysis.

The pharmacokinetics of ritanserin were studied in five patients with chronic renal insufficiency and who were undergoing periodic hemodialysis. Immediately after breakfast, a single 10-mg ritanserin tablet was administered to each patient on a day that they did not undergo dialysis. Plasma ritanserin levels were measured by a specific high-performance liquid chromatographic assay sensitive to 2 ng/mL plasma. After the oral 10-mg dose, the average time to reach the peak plasma concentration, Tmax, was 4.4 +/- 2.2 hours in these uremic patients, with a range of 2 to 8 hours. The average peak plasma concentration was 73.6 +/- 26.9 ng/mL (range: 54.6-120.0 ng/mL). Compared with a previous study in healthy volunteers, the uremic patients had a slower absorption profile, with a 39% reduction in peak plasma concentration and mean delay of 2.5 hours in Tmax. The mean area under the plasma concentration-time curve for ritanserin (2031 +/- 636 ng.hr/mL) was 47% lower compared with that in healthy volunteers (3867 +/- 1413 ng.hr/mL). The observed delayed and lower ritanserin absorption in these uremic patients may be caused by the chronic use of antacids such as aluminum hydroxide and calcium carbonate in all patients and/or by concurrent pathologic changes in the gastrointestinal mucosa of these patients. The regular hemodialysis sessions every 2-3 days did not affect the elimination rate of ritanserin, as the terminal half-life in these patients (39 +/- 23 hr) is similar to that in healthy volunteers (41 +/- 14 hr).

Administration, Oral↗