[Malignant peritoneal mesothelioma].
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
P Weller
Publications and source records attributed to P Weller.
Genes for human U4 small nuclear RNA.
A study of human genes coding for U4 small nuclear RNA is presented. It is known from previous studies that mammalian cells contain three major U4 RNA species, designated U4A, U4B, and U4C (Krol and Branlant, 1981). A clone was isolated from a human DNA library which contained two transcriptionally active genes for U4 RNA. U4 transcription was sensitive to low concentrations of alpha-amanitin, inferring that U4 RNA is a product of RNA polymerase II or RNA polymerase II-like activity. One of the two genes contains a coding region which matches the sequence of U4C RNA perfectly. The coding region of the second gene resembles U4B RNA although there are two differences between the sequence of this gene and the U4B RNA sequence, suggesting that it may encode a minor, hitherto undetected U4 RNA species. The 5'-flanking regions of the two U4 genes contain several almost perfectly conserved sequence motifs. One is located between positions -50 and -60. This motif is present in equivalent positions in the two U4 genes as well as in human U1 and U2 genes. A second motif, which is 19 nucleotides (nt) long and centered around nt position -140, is present in the two U4 genes but absent from U2 RNA genes. A third highly conserved region, located between nt positions -210 and -250, is a putative enhancer element. It includes one copy of the so-called octanucleotide motif, previously identified as adjacent to the early SV40 promoter and immunoglobulin promoters. Another highly conserved sequence motif, CTCTGTGA, is located approximately one helical turn upstream from the octanucleotide motif in both U2 and U4 genes. The human genome appears to contain a family of U4 RNA genes comprising at least 100 copies.
Animals↗
PUVA therapy for drug-resistant graft-versus-host disease.
Ultraviolet irradiation is known to diminish the functional capacity of cells of the immune system. We have used ultraviolet A irradiation in combination with psoralen (PUVA) to treat three patients with drug-resistant graft-versus-host disease (GVHD) of the skin or mouth. Each of the three patients had received an HLA-identical sibling bone marrow transplant for haematological malignancy or severe aplastic anaemia. One patient developed acute GVHD of skin and mouth and two patients developed chronic GVHD of the mouth, which did not respond to conventional immunosuppressive drugs including cyclosporin and methyl prednisolone (all three patients) and anti-thymocyte globulin (two patients). PUVA irradiation to the skin was given at a dose of 0.75-1.25 J (joules) daily for four days per week and that to the mouth at 0.75 J daily four days per week. Before each treatment, 8-methoxypsoralen (0.6 mg/kg) was given orally as a photosensitizer. Each patient improved considerably and in each case the dosage of conventional immunosuppression was reduced. No flare was noted in the two patients with chronic GVHD of the mouth at 1 month after the end of treatment. PUVA irradiation is a useful therapeutic adjunct in GVHD affecting skin and mouth and appears to confer a steroid or cyclosporin sparing effect.
Acute Disease↗
Effects of prostaglandins possessing an alpha,beta-unsaturated carbonyl on tumor growth and differentiation.
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Animals↗
The human myoglobin gene: a third dispersed globin locus in the human genome.
Human myoglobin is specified by a single gene. Unique sequence DNA probes were isolated from the cloned gene and used to test for the presence of the human myoglobin gene in a series of human rodent somatic cell hybrids containing various complements of human chromosomes. The myoglobin gene cosegregated with human chromosome 22. Somatic cell hybrids containing translocation chromosomes carrying part of chromosome 22 were used to locate the myoglobin gene to the region 22q11----22q13. The myoglobin gene is therefore not linked to the alpha-globin gene cluster on chromosome 16 or the beta-globin cluster on chromosome 11, and represents a third dispersed globin locus in the human genome.
Animals↗
Organization of the human myoglobin gene.
Cross-hybridization of the grey seal myoglobin gene to human DNA detected a single human myoglobin gene plus an extensive family of sequences apparently related to the central exon of this gene. The functional human gene is 10.4 kb long and has a haemoglobin-like three exon/two intron structure with long non-coding regions similar to its seal homologue. At least 300 bp of 5'-flanking region are closely homologous between the two genes, with the exception of a divergent purine-rich region 68-114 bp upstream of the cap site. A diverged tandem repetitive sequence based on (GGAT)165 is located 1100-1750 bp upstream from the gene; internal homology units within this sequence suggest sequence homogenization by gene microconversions. A second 33-bp tandem repeat element in the first intron is flanked by a 9-bp direct repeat, shares homology with other tandem repetitive elements in the human genome and may represent a novel form of transposable element.
Animals↗
Photocontact allergy to octyldimethyl PABA.
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4-Aminobenzoic Acid↗
[Antidigoxin Fab-fragments in suicidal digoxin poisoning. Successful treatment of recurrent ventricular fibrillation].
A 49-year-old woman took about 12.5 mg digoxin with suicidal intent. Severe arrhythmias, including recurrent ventricular fibrillation, occurred. Sheep Fab fragments of digoxin-specific antibodies were administered i. v. at a dose of 480 mg. Serum free-digoxin concentration fell within half an hour to 0, with simultaneous rise of total digoxin from 13 micrograms/l to a maximum of 176 micrograms/l after 2 hours. At the same time there was marked improvement in the clinical condition with restoration of a stable sinus rhythm. There were no side effects to the Fab fragment administration.
Antibodies↗
Airway constriction in normal humans produced by inhalation of leukotriene D. Potency, time course, and effect of aspirin therapy.
Five normal human subjects inhaled aerosols generated from solutions of leukotriene D (LTD) to determine the bronchoconstrictor potency and the time course of airway obstruction produced by this constituent of slow-reacting substance of anaphylaxis. The dose-effect and time-effect curves were compared with curves similarly generated for the well-characterized airway constrictor histamine. Leukotriene D was, on average, 5,900 times more potent than histamine on a molar basis in producing an identical decrement in maximal expiratory flow rate at 30% of control vital capacity above residual volume. In addition, although LTD had a rapid onset of effect, similar to that of histamine, the airway obstruction produced by LTD was longer lasting, thereby reflecting more closely the response of asthmatic allergic individuals to antigen inhalation. The response of these subjects to inhalation of LTD was not altered by ingestion of aspirin, suggesting that the airway obstruction was not mediated by cyclooxygenase products of arachidonic acid.
Adult↗
[Immunocoagulopathies as a possible cause of acquired hemorrhagic diathesis].
Spontaneous factor VIII inhibitors may be responsible for severe life-threatening haemorrhages. It is reported on two patients with inhibitors directed against factor VIII: C. In one female patient a rheumatoid arthritis could be made evident as basic disease. Diagnostics, therapy and course are reported and discussed.
Adult↗
Stereoselectivity of the epoxidation of 7,8-dihydrobenzo[a]pyrene by prostaglandin H synthase and cytochrome P-450 determined by the identification of polyguanylic acid adducts.
The stereoselectivity of the oxidation of 7,8-dihydrobenzo[a]pyrene (H2BP) to 9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (H4BP-epoxide) by prostaglandin H (PGH) synthase and cytochrome P-450 has been studied using microsomal preparations from ram seminal vesicles and rat liver. Incubations were performed in the presence of polyguanylic acid and the adducts formed between H4BP-epoxide and guanosine were isolated following the recovery and hydrolysis of the poly(G). When (+/-)-H4BP-epoxide was reacted with poly(G), four diastereomeric adducts were formed by the cis and trans addition of the exocyclic amino group of guanine to the benzylic carbon of the epoxide enantiomers. Each diastereomer was identified by a combination of ultraviolet, nuclear magnetic resonance, circular dichroism, and mass spectroscopy. Under comparable conditions, ram seminal vesicle microsomes in the presence of arachidonic acid triggered the binding of H2BP to poly(G) to a greater extent than rat liver microsomes from untreated and phenobarbital- and methylcholanthrene pretreated animals in the presence of NADPH. Quantitation of the (-)-cis- and (+)-cis-guanosine adducts revealed the degree of stereoselectivity of epoxidation. The ratio of (-)/(+) adducts was 54:46 for PGH synthase and 89:11 (control), 62:38 (phenobarbital), and 69:31 (methylcholanthrene) for cytochrome P-450-catalyzed reactions. PGH synthase catalyzed the epoxidation of H2BP with little or no stereoselectivity in contrast to cytochrome P-450. The utility of the poly(G) binding technique for the elucidation of the stereoselective generation of chiral electrophiles is discussed along with the mechanistic implications of the results.
Animals↗
[Acquired and hereditary defective forms of granulocytic peroxidase].
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Adult↗
[Emergency endoscopy in patients with hereditary hemophilia].
Haemorrhages from the upper gastrointestinal tract are a particularly threatening complication for patients with hereditary haemorrhagic diathesis. Though in the individual case under conservative therapy a temporizing attitude is possible, the source of the haemorrhage should be localized. When the peculiarities of this group of patients are taken into consideration the emergency endoscopy does not evoke a new danger of bleeding, on the contrary it is a decisive prerequisite for the individual therapy according to indication.
Adult↗
[Epidemiology and genetics of hemophilia].
From own examinations a survey of data concerning morbidity and genealogy of haemophilia is presented. Their comparison with data from literature shows that the total number of haemophiliacs referred to the population (1 : 11,000 males) and the relation of haemophilia A : B (4.5 : 1) vastly corresponds in the middle and north European area. The total number of haemophiliacs which is to be expected for a larger space can approximately be estimated, e. g. for the GDR the number amounts to about 1,200 to 1,300 haemophiliacs. Till now this number has not yet been obtained. At a high percentage the manifestation of the disease takes place in the first two years of life. The greatest number of the haemophiliacs is at present 25 to 40 years old. The fertility rate is clearly different between haemophilia A (0.33) and B (0.84). The number of the female conductors of all variants is certainly double the number as that of the haemophiliacs.
Genetic Carrier Screening↗
Hypercholesterolaemia and hypertriglyceridaemia in patients with analgesic nephropathy.
Patients with analgesic nephropathy are reported to have a higher risk of atherosclerosis. One possible reason for this is a high incidence of hyperlipaemia in patients with analgesic nephropathy. In a retrospective study, serum cholesterol and serum triglyceride concentrations of patients with analgesic nephropathy and moderately restricted renal function were significantly higher compared to a control group with other renal diseases of similar age and degree of renal insufficiency. Hyperlipaemia in analgesic nephropathy is not explained by end-stage renal failure on one side or protein loss as in nephrotic syndrome on the other side. Some possible mechanisms for hyperlipaemia in analgesic nephropathy are discussed.
Adult↗
Late results of surgical treatment of transposition of the great arteries.
In summary, many of these patients have achieved a normal working capacity, but as a group there is a statistically significant reduction when compared to healthy children (p < 0.01). There was no significant difference between the group of patients who had their Mustard operation in infancy and later. As yet, there is no suggestion that the older patients, or those with the longest time interval between the operation and the exercise test, have a progressive reduction in working capacity. The decreased working capacity and moderate increase in ventilation suggests restricted cardiac output on exercise. This could be related to the abnormal heart rate response rather than indicating poor ventricular function. Equally, a restricted cardiac output on exercise may be due to inefficiency of atrial transport, tricuspid regurgitation or unmasked pulmonary vascular obstructive disease. Further studies may clarify these points. This study demonstrated that the exercise performance of asymptomatic patients 6-13 years after Mustard's operation was somewhat diminished, compared with a group of normal children. Nevertheless, these patients did lead and enjoy a normal life. Only longitudinal studies may bring the final answer to the important question: How many patients will be alive with normal or near normal exercise tolerance 40-50 years after Mustard's operation? Until such an answer is available, we believe that the Mustard operation should be used in the treatment of TGA, while the alternative techniques are carefully explored.
Arrhythmias, Cardiac↗
[Diagnosis and therapy of idiopathic thrombocytopenic purpura].
To the diagnostics of the idiopathic thrombopenia caused by autoantibodies belong: 1. the clinical findings such as type of haemorrhage and the controls of the capillary function. 2. the proof of antibodies, in which case positive findings are proving, but negative ones do not exclude the immune thrombopenia, 3. smear of the sternal marrow with judgment of the megakaryocytes and formation of thrombocytes, 4. isotopic control of the survival time of the thrombocytes, which is reserved to special insitutions. As therapy essentially three forms have developed: 1. Therapy with glucocorticoids, 2. Immunosuppressive drugs, 3. Splenectomy. In own observations of 48 patients the glucocorticoids bring an actual improvement only for 7 patients, the others fail in therapy or show only a partial remission. The least prospects are in the immunosuppressive drugs, being equal whether preceding or accompanying a glucocorticoid therapy was performed. Most successes (11 out of 16 patients) are to be stated in splenectomy. Following an after-control of all therapeutic methods together a successful therapy results only in one third, in the next two thirds the therapy either fails or at most evokes a partial remission.
Coombs Test↗