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Biomedical subjects

S H Hahn

Publications and source records attributed to S H Hahn.

34 records · Page 2Linked to original sources
PubMed1999

Very long chain acyl coenzyme A dehydrogenase deficiency in a 5-month-old Korean boy: identification of a novel mutation.

A 5-month-old Korean boy who presented with lethargy and cardiomyopathy was diagnosed with very long chain acyl coenzyme A dehydrogenase (VLCAD) deficiency by organic acid, fatty acid, acylcarnitine, and molecular genetic analysis. The patient was a compound heterozygote for mutations in the VLCAD gene. One allele contains a 3-bp deletion in exon 6, deleting glutamic acid in codon 130 (E130del ); this allele is of paternal origin. The patient's maternally derived allele is a novel mutation, C1843T in exon 20, which creates a premature termination codon (R615stop ). Although molecular genetic characterization of VLCAD deficiency is limited to a few patients, heterogeneity of mutations is already apparent. However, the E130del is a relatively frequent mutant allele, which has been noted in 2 previously identified patients. The 2 mutant alleles in our patient appear to be responsible for his severe and fatal clinical manifestations.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed1998

Identification of three novel mutations and a high frequency of the Arg778Leu mutation in Korean patients with Wilson disease.

Four mutations--R778L, A874V, L1083F, and 2304delC--in the copper-transporting enzyme, P-type ATPase (ATP7B), were identified in Korean Patients with Wilson disease. Arg778Leu, the most frequently reported mutation of this enzyme, was found in six of eight unrelated patients studied, an allele frequency of 37.5%, which is considerably higher than those in other Asian populations. The novel single nucleotide deletion, 2304delC, was found in one patient. Since a mutation at cDNA nucleotide 2302 (2302insC) had been previously described, this region of the ATP7B gene may be susceptible to gene rearrangements causing Wilson disease.

Adenosine Triphosphatases↗
PubMed1998

Extensive form of aplasia cutis congenita: a new syndrome?

Aplasia cutis congenita is a heterogeneous group of conditions usually involving the scalp as well as any other part of the body and is associated with a number of other congenital anomalies. We report on a newborn male with almost complete absence of skin and subcutaneous tissue in association with choanal atresia, syndactyly, imperforate anus, pulmonary hypoplasia, and other anomalies. To our knowledge, this condition, not only in the extent of the lesion but the associated anomalies, has not been reported previously.

Abnormalities, Multiple↗
PubMed1996

Linear and whorled nevoid hypermelanosis with delayed psychomotor development.

We report a case of a 25-month-old girl presented to us for the evaluation of a severe delayed psychomotor development who also has pigmentary abnormalities. Linear and whorled hyperpigmentations following Blaschko's lines were noticed on her entire body except on her face, palms, soles, eyes and mucous membranes, which closely resembled those found in hypomelanosis of Ito, but inversely pigmented. Histologic examination revealed basal layer hyperpigmentation without incontinence of pigment or dermal melanophages. Chromosomal analysis of cultured peripheral leukocytes and fibroblasts from the hyperpigmented and the hypopigmented skin revealed normal female karyotype with no evidence of mosaicism or chimerism. This entity represents a kind of neurocutaneous syndrome-referred to by some authors as linear and whorled nevoid hypermelanosis.

Child Development↗
PubMed1995

Heterozygosity for an exon 12 splicing mutation and a W234G missense mutation in an American child with chronic tyrosinemia type 1.

Hereditary tyrosinemia type 1, an autosomal recessive disorder caused by deficiency of fumarylace-toacetate hydrolase (FAH), manifests in either an acute or a chronic form. We used reverse transcription and the polymerase chain reaction to amplify the FAH cDNA of a 12-year-old American boy with chronic tyrosinemia type 1. The patient is a compound heterozygote for mutations in the FAH gene. One allele contains a missense mutation in codon 234 changing a tryptophan to a glycine; this allele was of maternal origin. Mutagenesis and transfection into COS cells demonstrated that the W234G mutation abolishes FAH activity. The patient's paternally derived allele is a splicing mutation in the +5 position of intron 12, causing either insertion of a 105 bp fragment due to a cryptic splice site, or skipping of exon 12, or skipping of both exons 12 and 13. The chronic phenotype of tyrosinemia type 1 in this patient may be due to some residual, correct splicing by the allele with the splicing mutation.

Amino Acid Metabolism, Inborn Errors↗
PubMed1995

Normal metallothionein synthesis in fibroblasts obtained from children with Indian childhood cirrhosis or copper-associated childhood cirrhosis.

We previously demonstrated decreased metallothionein (MT) synthesis in cultured fibroblasts obtained from an American boy with findings typical of Indian Childhood Cirrhosis (ICC). We now report normal basal, copper-induced, and zinc-induced MT synthesis in the fibroblasts of two Indian boys and one Irish boy with typical ICC and one Indian boy with copper-associated childhood cirrhosis. This suggests that etiologies other than impaired MT production should be sought as the primary defect in these disorders.

Autoradiography↗
PubMed1995

Monoaminergic effects of folinic acid, L-DOPA, and 5-hydroxytryptophan in dihydropteridine reductase deficiency.

Plasma and CSF concentrations of endogenous L-DOPA, catecholamines, and metabolites of monoamines were assayed in a patient with atypical phenylketonuria due to absent dihydropteridine reductase (DHPR), before and during treatment with folinic acid, Sinemet, and 5-hydroxytryptophan. The patient had low but detectable levels of L-DOPA, 3,4-dihydroxyphenylacetic acid (DOPAC), and 3,4-dihydroxyphenylglycol (DHPG) in plasma and low but detectable levels of these compounds and of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in CSF, with approximately normal plasma and CSF levels of norepinephrine [noradrenaline (NA)]. Folinic acid treatment approximately doubled plasma levels of L-DOPA, NA, DOPAC, and DHPG, compared with values during dietary phenylalanine restriction alone. Detection of L-DOPA, catecholamines, and monoamine metabolites in this patient indicates that monoamine synthesis in humans does not absolutely require DHPR. The results are consistent with the existence of an alternative biochemical pathway, with folinic acid treatment augmenting activity along this pathway. Low plasma levels of L-DOPA, DOPAC, and DHPG may reflect decreased catecholamine synthesis and turnover in sympathetic nerves, with compensatory increases in exocytotic release normalizing plasma NA levels.

5-Hydroxytryptophan↗
PubMed1994

Metallothionein synthesis and degradation in Indian childhood cirrhosis fibroblasts.

Indian childhood cirrhosis (ICC) is a fatal liver disease characterized by the accumulation of copper-sulfur aggregates. We demonstrated that cultured fibroblasts from a patient with ICC contain vesicular aggregates, fibrillar whorls, and crystalloids along with dilated rough endoplasmic reticulum filled with flocculent material. Although the copper content of the fibroblasts was normal, both basal and metal-induced metallothionein (MT) synthesis was reduced in the ICC cells. The lower MT synthesis in ICC cells was seen at copper concentrations of 100, 200, and 400 microM, zinc concentrations of 50 and 100 microM, and a cadmium concentration of 2 microM. The lower MT synthesis in ICC cells was not due to failure of the cells to take up copper because 67Cu uptake kinetics were normal in the mutant cells. MT degradation was also normal in the ICC cells. The size of human MT IIA mRNA was normal in the ICC cells, but its amount was reduced under both basal and metal-induced conditions. The MT IIA gene, which is the predominant MT gene in human beings, showed no sequence alterations in any of its exons, introns, or promoter region in the ICC cells compared with normal cells. These studies demonstrate that this case of ICC represents a genetic disease with some level of expression in cultured fibroblasts; the basic defect may involve insufficient MT mRNA and protein synthesis for the copper load present. However, it remains to be determined whether reduced MT synthesis is a primary or secondary phenomenon.

Base Sequence↗
PubMed1993

Copper effects on metal regulatory factors of cultured human fibroblasts.

The effects of copper on metal regulatory factors were studied in cultured human fibroblasts using mobility shift assays and protein blotting. A mobility shift was apparent on polyacrylamide gels when fibroblast whole cell extracts were reacted with a 32P-labeled 14-base-pair MREa sequence of the hMT IIA gene. Binding was specific, since the shifted band was not competed away by MREa analogs containing two base changes. Known transcription factors SP1, AP1, AP2, and OCT1 did not compete with the fibroblast metal regulatory element binding protein (MREBP) for binding to the MREa probe. When fibroblasts were grown in 200 or 800 microM copper, binding of the MREBP was enhanced. Protein blotting experiments were performed by electrophoresing cell extracts, blotting onto nitrocellulose, and probing with the 32P-labeled MREa 14-mer. A 112-kDa band, apparent in HeLa cell nuclear extract as well as fibroblast whole cell extract, was not influenced by the presence of copper in the growing fibroblasts. A 34-kDa protein, also present in both HeLa cells and fibroblasts, appeared to correspond with the protein causing the mobility shift. Copper added to the fibroblast growth media enhanced binding of the 34-kDa protein to MREa using the blotting procedure. We conclude that the fibroblast 34-kDa MREBP is a positive regulatory factor influenced by copper. Human fibroblasts can be employed to further study metal regulatory factors whose binding to metal regulatory elements is influenced by copper and other heavy metals.

Base Sequence↗
PubMed1991

A clinical study of stress fractures in sports activities.

One hundred thirty-one patients with 169 stress fractures were treated between January 1984 and January 1990. The highest incidence was in teenage girls (25.5%), and the predominant sites were tibia (31.5%) and femur (12.5%). The mean interval between the start of hard training and the onset of symptoms was 2.7 months and the mean amount of increased activities was 93.7%. Volleyball (24.3%) and running (17.3%) had the majority of incidents, and 95 (72.5%) patients were professional athletes. Radionuclide bone scans were needed in 61 (46.6%) patients and 16 (12.2%) showed multiple lesions. Asymptomatic stress fractures were found in 12 (9.2%) patients, and only five showed recurrence at the other sites. Eleven (6.5%) cases were treated operatively, and involved the tarsal navicular (2.9%) and femur (2.4%).

Adolescent↗
PubMed1981

The identification of calmodulin-binding sites on mitochondria in cultured 3T3 cells.

We have uniformly labeled calmodulin with tetramethyl rhodamine isothiocyanate (CaM-RITC) and used the derivative as a molecular probe in order to identify available, unoccupied calmodulin-binding sites. In mildly fixed (3% formalin) cultured 3T3 cells, the biologically active CaM-RITC bound predominantly to mitochondria. Binding was markedly reduced in the presence of 1 mM EGTA. Stelazine, a phenothiozine which binds to calmodulin, prevented the interaction of CaM-RITC with mitochondrial sites. A 10 fold excess of unlabeled CaM competitively inhibited binding. Fluorescently labeled troponin C and parvalbumin did not bind to mitochondria on any other cellular organelle. Rhodamine (TMRITC) alone did not bind to 3T3 mitochondria. Similar results were obtained using 125I-calmodulin binding to isolated rat liver mitochondria. When solubilized mitochondrial proteins were subjected to calmodulin-Sepharose affinity chromatography and eluted with 1 mM EGTA, there were two major polypeptides 120,000 and 67,000 daltons and at least three minor species (100,000, 60,000 and 40,000 daltons). The interaction required an active Ca2+-CaM complex and is specific for CaM. Double fluorescent staining with CaM-RITC and fluorescein-labeled antibodies to tubulin and DNAase I revealed a mitochondrial distribution pattern similar to that of microtubule arrays but unrelated to actin cabling. There was no evidence that CaM-RITC directly interacted with either microtubules or microfilaments.

Animals↗
PubMedDate not supplied

In vivo rehardening of enamel eroded by a cola drink.

There are many concerns about the erosive effects of acidic beverages. In this study, the effects of Pepsi-Cola (pH 2.41) on bovine enamel and the rehardening effect resulting from intraoral exposure of the teeth were determined by microhardness testing (Vicker's Hardness Number). Bovine enamel specimens (VHN 380.00 +/- 12.74) were immersed in 100 ml of Pepsi-Cola for five minutes and subsequently exposed to human intraoral environment through the use of a removable resin plate. Microhardness testing was performed on specimens after one hour, twenty-four hours and forty-eight hours of exposure to an intraoral environment. The microhardness value was significantly (p < 0.05) reduced by the cola beverage (VHN 262.13 +/- 20.34), and significantly (p < 0.05) increased after intraoral exposure for one hour (VHN 299.75 +/- 26.86) and twenty-four hours (VHN 328.00 +/- 18.70). The difference in the microhardness between the twenty-four-hour group and the forty-eight-hour group (VHN 333.50 +/- 15.13) was not significant (p > 0.05). The microhardness value of the forty-eight-hour group was significantly less than the values recorded during the initial pre-study measurements p < 0.05).

Acids↗