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Biomedical subjects

B Wolf

Publications and source records attributed to B Wolf.

At least 271 records · Page 15Linked to original sources
PubMed1985

Clinical findings in four children with biotinidase deficiency detected through a statewide neonatal screening program.

Four children with biotinidase deficiency were identified during the first year of a neonatal screening program for this disease in the Commonwealth of Virginia. Two unrelated probands were identified among the 81,243 newborn infants who were screened. In addition, two siblings of one of these infants were found to be affected. Both probands had mild neurologic symptoms at two and four months, respectively, and the two older children had more severe neurologic abnormalities, cutaneous findings, and developmental delay at two and three years of age. However, none of the affected children had acute metabolic decompensation. Previous studies have shown that the administration of biotin to affected children can be a lifesaving procedure that can reverse acute symptoms and prevent irreversible neurologic damage. Our findings demonstrate that subtle neurologic abnormalities may appear as early as at two months of age and that developmental abnormalities may occur even in the absence of episodes of overt metabolic decompensation. Since screening and treatment are both inexpensive and effective and the incidence of the disease is well within the range of that of other metabolic diseases for which screening is performed, biotinidase deficiency should be added to the group of metabolic diseases for which screening is done in the neonatal period.

Amidohydrolases↗
PubMed1985

Biotinidase deficiency: initial clinical features and rapid diagnosis.

Biotinidase deficiency is the primary defect in most individuals with late-onset multiple carboxylase deficiency. We have reviewed the presenting clinical features of 31 children with the disorder. Seizures, either alone or with other neurological or cutaneous findings, are the most frequent initial symptom observed. Other neurological symptoms, such as hypotonia, ataxia, hearing loss, optic atrophy, and developmental delay, are seen, in addition to skin rash and alopecia. The disorder is also characterized by ketolactic acidosis and organic aciduria. Biotinidase activity may be diagnosed using a simple, rapid, semiquantitative colorimetric procedure. Samples of whole blood spotted on the same filter paper used by most states to screen for phenylketonuria and other inborn errors of metabolism may be sent to an appropriate reference laboratory. None of the common anticonvulsants or sedatives used to treat newborns and children interfere with the test. Because biotinidase deficiency can be treated readily with biotin, this disorder should be considered in children with infantile seizures, especially in the presence of other characteristic neurological or cutaneous features.

Acidosis↗
PubMed1985

Biotinidase deficiency: a novel vitamin recycling defect.

The recent finding that biotinidase deficiency is the primary biochemical defect in late-onset multiple carboxylase deficiency was stimulated new interest in the inherited disorders of biotin-dependent carboxylases. The clinical and biochemical features of biotinidase deficiency are discussed. We also speculate about two exciting areas currently being investigated: the localization of action biotinidase, and the possible role of the enzyme as a binding or carrier protein for biotin.

Adult↗
PubMed1985

Immunocytochemical location of thyrotropin-releasing hormone (TRH) in the B-cells of adult hypothyroid rat pancreas.

Thyrotropin-releasing hormone (TRH) is present in small quantities in the rat adult pancreas. As hypothyroidism increases dramatically the pancreatic content of this peptide, this model was used to localize TRH in the gland by immunocytochemistry. Immunocytochemical staining of semithin (0.5-1.0 micron) and thin (golden) sections was performed as well as antibody and method controls to check the specificity of the immunoperoxidase staining. At the light microscope level, a very faint TRH-like immunoreactivity was apparent in the pancreas of normal untreated animals. In hypothyroid rats, a strong TRH immunostaining was observed in the central portion of the islets of Langerhans. On the contrary, in previously hypothyroid rats made euthyroid, no TRH-like immunoreactivity was found. Serial sections alternately labelled with TRH and insulin antisera revealed the simultaneous occurrence of both immunoreactivities. In addition, the TRH immunoreactive cells were distinct from glucagon- or somatostatin-containing cells. At the electron microscope level, immunoreactive TRH was found over the secretory granules of insulin-containing cells. Hypothyroid animals offer therefore a suitable model for the study of TRH in the pancreas.

Animals↗
PubMed1985

Amino acids in amniotic fluid in the second trimester of gestation.

The concentrations of amino acids in amniotic fluid have been used in the prenatal diagnosis of several inherited metabolic disorders. However, previous studies have usually examined only a small number of control amniotic fluid samples. We have, therefore, measured the amino acids in amniotic fluid samples from 183 normal pregnancies between the 13th and the 23rd wk gestation of women ranging in age from 17 to 43 yr. The concentrations of Ala, Lys, Val, Glu, Pro, Thr, and Gly, in descending order, accounted for about 70% of the amino acids in amniotic fluids. A negative correlation with gestational age (-0.34 to -0.24) was found for Leu, Val, Ile, Phe, Lys, Ala, Asp, Tyr, Glu, and Pro, with Leu showing the greatest rate of change. The concentration of Gln increased slightly (r = 0.18), whereas the other amino acids did not change significantly during this period. Statistically significant positive correlations, at all gestational ages, were observed among Val, Leu, and Ile. These branched-chain amino acids also correlated positively with Phe, Lys, Asp, Thr, Ser, Glu, Pro, Gly, Ala, and Tyr, and the amino acids within this group correlated with each other. Additionally, strong positive correlations were observed between Phe and Tyr and between Gly and Ser. No significant correlations were found between any of the amino acids and maternal age or fetal sex. Significant positive correlations between amino acids may be indicative of common transport or degradative pathways and suggest that maintenance of specific relative concentrations in amniotic fluid may be essential for normal fetal development.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Neurologic symptoms of biotinidase deficiency: possible explanation.

We found that the activity of biotinidase is much lower in human and rat brain or human CSF than in serum or other tissues that have biotin-dependent carboxylase activity. The brain seems to be unable to recycle biotin and depends on biotin transferred across the blood-brain barrier. The biotin-deficient state that results from an inherited lack of biotinidase results in a moderate decrease in brain pyruvate carboxylase activity. This is followed by more severe accumulation of lactate in brain than in other organs, which may explain why affected children have neurologic symptoms before many peripheral features.

Adolescent↗
PubMed1985

Cosuppression of latent and nominal allotypes in individual rabbit lymphocytes.

Endogenous synthesis of latent and nominal allotype was observed in vitro in rabbit peripheral blood lymphocytes (PBL). PBL from rabbits displaying the nominal b4 specificity, as well as the latent b5 and b6 either on the cell surface or in the serum or both, were treated with pronase to remove surface latent and nominal allotypes and cultured in serum-free medium to regenerate the nominal and latent markers. Rosette formation using the mixed anti-globulin assay demonstrated that the nominal b4 and latent b5 and b6 specificities were displayed in the same cell. Cells were seen bearing the b4 + b5, b4 + b6, or b4 + b5 + b6, as double or triple expressors. No latent allotype-bearing cells were detectable in the absence of the nominal allotype. In vitro suppression of nominal surface b4 with anti-b4 antibodies resulted in the cosuppression of the latent b5 and b6. In contrast, in vitro suppression of latent b5 and b6 with anti-b5 and anti-b6 antibodies, respectively, did not cause the cosuppression of the nominal b4 allotype. Cosuppression of latent and nominal markers in the same cell confirms that the biosynthetic machinery for latent and nominal allotypes lies within the same cell.

Animals↗
PubMed1984

Assessment of adverse drug reactions in psychiatric hospitals.

A system for monitoring adverse drug reactions (ADR) in psychiatric inpatients was introduced in psychiatric hospitals in the FRG in May 1979. It consists of intensive drug monitoring (IDM) and a so-called "organized spontaneous reporting system" (OSR). ADR are rated separately according to impact on therapy and probability of causal relationship. With IDM all ADR (Grades I-III) are assessed in a randomly selected sample of inpatients. With OSR only ADR leading to discontinuation of the drugs in question (= ADR Grade III) are assessed. In 406 drug-treated inpatients monitored by IDM in the psychiatric hospitals of Berlin and Munich from May 1979 to Dec. 1981, ADR were observed in 60,4%. In 15% of IDM-patients ADR led to discontinuation of the drugs in question; with OSR the relative frequency of these Grade III ADR was 9,0% in 5096 patients monitored throughout the entire period. Life-threatening events were observed in 1,2% of patients undergoing IDM as well as 1.2% of those undergoing OSR. The most frequently observed ADR by IDM were sedation, extrapyramidal signs, disturbances of the autonomic nervous system and increase in transaminases, and by OSR Parkinsonism, akathisia, sedation, toxic delirium and increased transaminases. The relative frequency of Grade III ADR was similar for neuroleptics and antidepressants (5,4% and 5,3% in OSR); a very low relative frequency of ADR Grade III was found for tranquilizers and hypnotics (0,7% and 0,2%). Methodological aspects of this drug monitoring system are discussed in the light of current literature.

Antidepressive Agents↗
PubMed1984

Clonal diversity and homology of latent and nominal group a immunoglobulin allotypes in the rabbit.

Latent VH immunoglobulin allotypes are expressed unexpectedly and transiently at low concn in the serum of rabbits. Latent group a1 molecules in sera from rabbit colonies in Philadelphia (U.S.A.) and Birmingham (U.K.) were examined for a1 specificity and clonal diversity using reference nominal allotypic reagents and isoelectric focusing (IEF) autoradiography. Latent a1 molecules from rabbits of both colonies had diverse spectrotypic patterns in the pI range 5.5-8.3, as identified with 125I-labelled affinity-purified specificity-tested, anti-nominal a1 antibody. Comparisons of spectrotypes between nominal a1 antigen and latent a1 focused molecules revealed a marked correspondence in banding over the pI range. Reference anti-nominal a1 antibodies could be absorbed out substantially by the IgG fraction of serum from two rabbits containing latent a1 molecules; in a reciprocal fashion absorption with nominal a1 molecules reduced the binding of focused latent a1. The latent a1 molecules from both U.S.- and U.K.-bred rabbits displayed strikingly similar IEF spectra and their antigenic similarities were confirmed by similar absorption capacities of the reference anti-a1 serum. When sequential serum samples from one (U.S.) latent a1 rabbit were compared by IEF, some bands, e.g. those between pH 7.75 and 8.3, appeared to fluctuate in their presence, whereas others, e.g. between pH 5.3 and 7.4, were expressed continuously. We can conclude that latent a1 molecules are clonally complex and some are consistently produced in small amounts. As they also show antigenic similarity, if not identity with nominal a1, we believe that they are probably the product of the same gene (or genes) with an equivalent capacity to be associated with specificity-determining genes even though the level of synthetic activity is lower and possibly governed differently. Anti-a1 antibody was raised in a rabbit in which latent a1 allotype had been previously detected. This antibody was of low avidity and, while inhibitable on RIA by nominal a1 it was not inhibitable by the donor's latent a1 or by a second latent a1 of the same (partially inbred) U.K. colony, but was inhibitable by a latent a1 serum from the Philadelphia, U.S.A. colony. This result suggests that a1 molecules are the products of more than one gene.

Animals↗
PubMed1984

Twenty-four hour variations of thyroid hormones and thyrotrophin concentrations in hypothyroid infants treated with L-thyroxine.

The 24 hour plasma profile of T4, FT4, T3 and TSH was measured in a group of infants treated for congenital hypothyroidism with an oral aqueous preparation of L-T4 (5-7.5 micrograms/kg) given as a single dose at 0800 h. Mean basal plasma T4 was 8.4 +/- 2.0 micrograms/dl (mean +/- SD) and remained constant during the study while mean serum FT4 increased significantly from 1.64 +/- 0.50 ng/dl to a maximum of 2.08 +/- 0.63 ng/dl 4 h after medication. Plasma T3 decreased significantly from 241 +/- 48 ng/dl to 202 +/- 36 ng/dl 6 h after drug administration. Finally, plasma TSH decreased significantly from a mean of 24.2 +/- 18.8 microU/ml to 14.8 +/- 10.5 microU/ml 6 h later. Therefore during treatment of congenital hypothyroidism with L-T4 no specific schedule for T4 sampling is required. However, TSH determination 4 to 8 h after medication could slightly underestimate mean levels. In addition, any attempt to monitor treatment by FT4 determination should take into consideration variations of plasma values in the hours following L-T4 absorption.

Circadian Rhythm↗
PubMed1984

Adverse drug reactions. An epidemiological study at psychiatric hospitals.

A drug monitoring system has been established at psychiatric university hospitals in Berlin, Goettingen, and Munich since 1979 in order to investigate adverse reactions to psychotropic drugs. This report describes the system and presents results obtained over 3 years. 504 randomly selected patients were observed by Intensive Drug Monitoring; 75% of them had an adverse drug reaction (ADR) during hospitalization that was assessed as possible, probable, or definite including all grades (I-III) of severity. 5,096 other patients were monitored by Organized Spontaneous Reporting during treatment with psychotropic drugs: ADRs were responsible for drug withdrawal (severity grade III) in about 10% of them. Parkinsonism, psychomotor disturbance, akathisia, delirium, oversedation and increased transaminases were the most frequent ADRs of this kind. The relative frequency of ADRs was calculated, and ADR-profiles established for drugs most frequently withdrawn. The impact of ADRs on ongoing therapy of patients was assessed. Reliable data obtained by drug monitoring systems can be expected to aid in therapeutic decisions in patients with special risks of side effects to psychotropic drugs.

Adult↗