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Biomedical subjects

H Lehmann

Publications and source records attributed to H Lehmann.

At least 91 records · Page 5Linked to original sources
PubMed1987

Haemoglobin Köln in Cape Town. A case report.

A 7-year-old patient presented with an acute haemolytic episode. Investigation showed the presence of an unstable haemoglobin (Hb), identified as Hb Köln. No other members of the family were affected. This disorder has occasionally been seen as a spontaneous mutation. This is the first report of Hb Köln in a South African family, although other unstable Hb variants have been described.

Anemia, Hemolytic, Congenital↗
PubMed1987

Structure and function of a new hemoglobin variant, Hb meilahti (alpha 2 beta 2 36(C2)Pro----Thr), characterized by mass spectrometry.

An abnormal hemoglobin was found by isoelectric focusing in the blood of a Finnish woman with erythrocytosis. Oxygen equilibrium curves of the patient's hemolysate indicated the presence of a variant with a very high oxygen affinity. Structural analysis was carried out by mass spectrometry. In the spectrum of the tryptic digest, an abnormal peptide was found at m/z1278 which corresponded to the mass number of the protonated molecular ion of beta T4 with 36Pro----Thr substitution. The structure was confirmed by the mass spectrum of the chymotryptic digest.

Genetic Variation↗
PubMed1986

Preclinical safety testing of species-specific proteins produced with recombinant DNA-techniques. An attempt to transfer current experience into future testing strategies.

Preclinical toxicity studies in animals with species-specific recombinant DNA products have now been performed for several years. An interim statement on the significance of these animal tests and their ability to predict adverse effects in humans therefore appears indicated, with the aim of deducing future testing strategies. The experience accumulated so far shows that the animal models have failed to predict adverse effects subsequently observed in man. Immunogenicity of these proteins further restricted the usefulness of standard toxicity tests. There is also increasing evidence that animal tests on the toxic potential of impurities contained in the products are markedly inferior in sensitivity to analytical and quality control methods. Thus, modified testing programs are proposed to demonstrate safety rather than target organ toxicity using rodents and small non-rodent species and restricted dosing; furthermore the study duration should be limited by the detection of immunogenic responses.

Animals↗
PubMed1986

Prenatal diagnosis of "dihydrobiopterin synthetase" deficiency, a variant form of phenylketonuria.

Amniocentesis was performed at 19 weeks gestation in a mother who had previously delivered a boy with "dihydrobiopterin synthetase" (DHBS) deficiency. The amniotic fluid contained neopterin in high (136 nmol/l) and biopterin in very low concentrations (1.8 nmol/l). The activity of the phosphate-eliminating enzyme (PEE, also called 6-pyruvoyl tetrahydropterin synthase, substrate: 7,8-dihydroneopterin triphosphate) which is present in liver and erythrocytes and defective in DHBS deficiency, was measured in the erythrocytes of the family members. The fetal sample showed only 2% of the activity of healthy adult controls and was comparable with that of the affected sibling. Obligate heterozygotes had activities around 20% of the controls. Two fetal control samples showed even higher activities than adult erythrocytes, Sepiapterin reductase activities wer normal in all cases. At autopsy, PEE deficiency was confirmed in the liver of the fetus. We concluded that DHBS deficiency (and most probably also GTP cyclohydrolase I deficiency) can be diagnosed by metabolite measurements in amniotic fluid. PEE activity is measurable in erythrocytes, although the assay needs to be improved. Since maternal tetrahydrobiopterin does not cross the placenta, treatment of a tetrahydrobiopterin-deficient fetus with tetrahydrobiopterin in utero is not possible.

Alcohol Oxidoreductases↗
PubMed1986

Hepatic regenerative stimulator substance in the rabbit. Relation to liver regeneration after partial hepatectomy.

The occurrence and activity of hepatic regenerative stimulator substance was investigated in the partially hepatectomized rabbit and related to biochemical and morphological parameters of liver regeneration. Male rabbits were 60% hepatectomized by excising the Spigelian, left lateral and left central lobes of the liver leaving the gallbladder in situ. [3H]Thymidine incorporation into DNA, the fraction of labelled hepatocyte nuclei, the fraction of mitoses and thymidine kinase activity rose from basal levels at 30-40 h after hepatectomy and increased up to 12-fold at 40-60 h. After 7 days, proliferation parameters returned to near prae-hepatectomy values and 82% of the initial liver mass was restored. Hepatic regenerative stimulator substance was biologically active when prepared from rabbit livers between 18-30 h after partial hepatectomy. At 12 and 30 h after intraperitoneal injection of the extract into normal rats, hepatic DNA synthesis was stimulated up to 2-fold in a dose-dependent fashion. The biological activity was protease-sensitive and thus depended on a protein component of the extract. The data demonstrate the existence of hepatic regenerative stimulator substance in regenerating rabbit liver and suggest that it is implicated in the regulation of liver growth after partial hepatectomy.

Animals↗
PubMed1986

Haemoglobin gene frequencies in the Jamaican population: a study in 100,000 newborns.

The gene frequencies of abnormal haemoglobins have been determined in a group of 100,000 Jamaican newborns screened over a period of 8 1/2 years. The population is predominantly of West African origin and the survey represents approximately one quarter of all island deliveries within the period of the study. The common beta globin chain abnormalities beta s and beta c occurred with gene frequencies of 0.055 and 0.019 respectively; beta thalassaemia was relatively rare. In contrast, alpha thalassaemia was quite common, occurring with a gene frequency of 0.183. In addition to these common abnormalities, the frequencies of 256 rare abnormal haemoglobins are described. This survey thus represents a complete and accurate documentation of the alpha and beta globin variants that occur in the Jamaican population.

Gene Frequency↗
PubMed1986

Litter parameters and spontaneous abnormalities in Himalayan rabbits.

A joint study was undertaken in three testing facilities to evaluate cumulative background data of Himalayan rabbits. All litters were derived from control does. The conception rate was high (84.0-95.1%) but the average numbers of corpora lutea (7.9-8.7), implantation sites (6.5-7.5) and viable fetuses (5.8-6.9) were somewhat lower than that of most other strains of rabbit. Altogether 90 malformed fetuses (1.12%) and 425 fetuses with variations (5.27%) occurred among 8,060 virable fetuses.

Animals↗
PubMed1985

The myoglobin of rodents Proechimys guairae (casiragua) and Mus musculus (house mouse).

The amino acid sequences of the myoglobins of two rodents, the casiragua and the house mouse, have been determined. The myoglobin of casiragua differs from that of viscacha (another hystricomorph) at 6 positions. Mouse myoglobin differs from that of mole-rat (another myomorph) at 17 positions, whereas casiragua and mouse differ at 22 positions. Mouse myoglobin possesses several features unique among all known myoglobins (Gly 31, Cys 66, Thr 74 and Glu 113) and one substitution unique among known mammalian myoglobins (Glu 53).

Amino Acid Sequence↗
PubMed1985

A critical comparison of the freehand razor-blade dissection method according to Wilson with an in situ sectioning method for rat fetuses.

Two methods of dissecting rat fetuses are compared: the generally well-known freehand razor-blade dissection method according to Wilson and an in situ sectioning method (ISM). For this purpose the substance EGYT 1978 was used, which induces--inter alia--cardiovascular anomalies. Thirty-nine gravid rats were given either the test drug (EGYT 1978, 400 mg/kg body weight) or the vehicle orally from the 6th to the 15th day of gestation. The fetuses were assigned randomly to either dissection group. Both methods of examination revealed approximately the same number of anomalies per organ system. A comparison of the types of anomaly found showed, however, relevant differences in the nature of the changes revealed by the two methods. The in situ sectioning method was clearly superior to the freehand razor-blade dissection method for the detection of discrete anomalies of the cardiovascular system. We therefore recommend the in situ sectioning method as the method of choice for examining small fetuses from teratological experiments.

Animals↗
PubMed1985

Studies on circulatory stability during bicarbonate hemodialysis with constant dialysate sodium versus acetate hemodialysis with sequential dialysate sodium.

Eight stable patients on maintenance hemodialysis were studied while undergoing (a) acetate hemodialysis with a sequential dialysate sodium concentration from 147 to 137 mEq/L (SNa-HDA) and (b) bicarbonate hemodialysis with a constant dialysate sodium concentration of 140 mEq/L (HDB). Circulatory behavior was observed during both of these methods, and both were found to allow a high volume removal. However, as a consequence of the high sodium load during SNa-HDA, volume was shifted from the extra- to the intravascular space. This stabilizing effect on the circulation disappeared with the sequential decrease of dialysate sodium concentration (despite a constant plasma sodium concentration (despite a constant plasma sodium concentration of approximately 140 mEq/L), which was concomitant with a significant decline of the mean arterial blood pressure and an inadequate compensation of the metabolic acidosis. In contrast, a better circulatory response to comparable volume removal was found during HDB, expressed by a stable mean arterial blood pressure in the presence of well-balanced arterial acid-base values.

Acetates↗
PubMed1985

The first observation of Hb D Punjab beta zero thalassaemia in an English family with 22 cases of unsuspected beta zero thalassaemia minor among its members.

A 36 year old local Englishman from Nuneaton was referred to hospital with suspected glandular fever. Relevant tests were negative and the symptoms subsided in due course. The finding of a hypochromic microcytic blood picture without iron deficiency led to the discovery that he was heterozygous for Hb D and beta thalassaemia. Hb D trait was established in the father of the proband and beta thalassaemia in his mother and a brother. The father's ancestors were miners who came to Nuneaton from Monmouthshire in the 19th century. The mother's ancestors have belonged to the indigenous population of Nuneaton and neighbouring Leicestershire since the 18th century. Twenty local members of her wider family also had thalassaemia. All thalassaemias had a low MCH and raised level of Hb A2. The Hb F level, however, was normal in five, demonstrating the independent segregation of genetic factors influencing the Hb F level in beta thalassaemia trait.

Adolescent↗
PubMed1985

Hemoglobin Hofu associated with beta 0-thalassemia.

A mild anemia (hemoglobin 9 g/dl) was found in a patient from Seville (Spain) with marked morphological abnormalities in the peripheral blood smear. The red cell osmotic fragility showed a mild resistance curve with a mean cell fragility (MCF) of 0.375% NaCl (normal = 0.450). Chemical Chemical and thermal instability test and search for inclusion bodies gave positive results. Hemoglobin electrophoresis at pH 8.9 revealed absence of Hb A, a major component of fast mobility (94%), and increased Hb F and Hb A2 levels (1.5% and 4.6%, respectively). The fast fraction, isolated and purified by means of cellulose acetate electrophoresis, precipitated in acid acetone and treated with urea 8 M and mercaptoethanol, revealed an anomalous beta chain. Trypsin-digested globin peptides were separated by high-voltage electrophoresis at pH 6.4 and ascendant chromatography. With differential staining, an extra peptide was detected in an unusual site, more anodic than alpha Tp4 but in lower position. Peptide map of the fast beta chain, stained with ninhydrin, and also for Tyr, confirmed the position of the new peptide and the absence of the usual beta Tp13. The new peptide, separated by high-voltage electrophoresis at pH 3.5, revealed absence of Val and the presence of an additional Glu residue, which should appear only in position beta 126. The diagnosis of Hb Hofu (alpha 2 beta 2 126 Val----Glu; H4) was reached, thus interpreting its increase and the absence of Hb A, as an association with beta o-thalassemia, producing a mild hemolytic anemia. Evidence was obtained that Hb Hofu is a mild unstable hemoglobin variant.

Adult↗
PubMed1985

A distant gene deletion affects beta-globin gene function in an atypical gamma delta beta-thalassemia.

We describe an English family with an atypical gamma delta beta-thalassemia syndrome. Heterozygosity results in a beta-thalassemia phenotype with normal hemoglobin A2. However, unlike previously described cases, no history of neonatal hemolytic anemia requiring blood transfusion was obtained. Gene mapping showed a deletion that extended from the third exon of the G gamma-globin gene upstream for approximately 100 kilobases (kb). The A gamma-globin, psi beta-, delta-, and beta-globin genes in cis remained intact. The malfunction of the beta-globin gene on a chromosome in which the deletion is located 25 kb away suggests that chromatin structure and conformation are important for globin gene expression.

Adult↗