[Laryngeal neurofibroma: a case report].
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Biomedical subjects
Publications and source records attributed to H J Lin.
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Severe and recurrent purpura fulminans developed in a Chinese boy at one day of age. Results of coagulation studies performed on the patient during attacks were compatible with the diagnosis of disseminated intravascular coagulation. Subsequent investigations have revealed that the patient is homozygous and that his parents are heterozygous for protein C deficiency. Cryoprecipitate and fresh frozen plasma induced a remission, and administration of warfarin has been successful in preventing recurrence of attacks for as long as 8 months without infusion of any plasma components. None of the family members who are heterozygous for protein C deficiency have had thrombotic episodes.
For studies on the coenzyme B12-dependent enzyme, leucine-2,3-aminomutase, (3R)- and (3S)-beta-leucines were synthesized. The 10-camphorsulfonamide p-nitrobenzyl esters could be resolved by normal-phase HPLC. A much better separation was obtained by reversed-phase HPLC of the diastereomeric derivatives obtained by treatment of -leucine with Marfey's reagent (N2-(5-fluoro-2,4-dinitrophenyl)-L-alaninamide).
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The recessive hemochromatosis gene is both linked to the HLA region on chromosome 6 and nonrandomly associated with certain HLA alleles. The use of linked HLA markers to trace known hemochromatosis genes within a family is well known, but using the population associations to detect unsuspected disease genes has not been fully appreciated. Thus, while HLA typing has been utilized to detect asymptomatic affected siblings, it has not been applied to other relatives. We propose a method in which Bayes' rule is used to calculate the probability that designated HLA marker haplotypes, brought into the family by spouses, have attendant hemochromatosis genes. The A3, B14 and A3, B7 haplotypes are such high risk markers. When these haplotypes are inherited from the unaffected parent, the offspring of an individual with hemochromatosis is at marked increased risk for the disease. When A3 and B14 are absent from the HLA marker haplotype, however, the risk of having a hemochromatosis gene is less than that for the general population. This approach should be helpful in identifying family members at a higher risk for developing the disease and who may then undergo appropriate periodic screening.
Based on a two-locus, double recessive model, we derive formulas for the risks that relatives of individuals with gluten-sensitive enteropathy (GSE) will also develop the disease. The calculations take advantage of: the linkage between the HLA locus and one of the two proposed GSE loci, and the preferential association of the HLA-DR3 and DR7 alleles with the GSE disease allele that occupies the HLA-linked locus. We use Bayes' rule to quantitate the strength of the association between the GSE disease allele and the HLA marker allele. This method predicts that siblings of the proband have an overall 10% risk for GSE, which is consistent with observed family data. This predicted risk rises to 30% when siblings are HLA-identical to the proband (also consistent with observed data) or when the sibling has the DR3 allele in the HLA haplotypes not shared with the proband. In those populations where DR7 also is associated with GSE, siblings of probands have a 10% predicted risk for GSE when only one HLA haplotype is shared with the proband and DR7 is included in the unshared haplotype. Other DR alleles are associated with much lower disease risks. By separating individuals into high and low risk groups, HLA typing identifies those individuals who would benefit from further diagnostic procedures. This general strategy should be applicable to other multilocus, marker-associated diseases.
Four young Chinese women took daily doses of an unidentified 'Indian' herbal tea as treatment for psoriasis. Three (one of whom died), developed ascites, hepatomegaly and biochemical abnormalities within 19-45 days. The fourth patient discontinued herbal tea after 21 days when she developed a skin rash. Two patients had portal hypertension, while all had liver histology showing features of veno-occlusive disease. Pyrrolizidine alkaloids were identified spectrophotometrically in the brewed tea, and in the chopped leaves of the herbal mixture; the mean dose in the tea prepared for consumption being 12 mg/day of alkaloid base and 18 mg/day of N-oxide. The mean cumulative dose of alkaloids (base + N-oxide) before onset of symptoms (three patients), was estimated to be 18 mg/kg. In the asymptomatic patient with histological liver disease only, the corresponding dose was 15 mg/kg. These cases thus provide some measure of pyrrolizidine alkaloid toxicity in adults.
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A fifth case is reported of symptomatic porphyria cutanea tarda (PCT) associated with lymphoma (of the histiocytic type) in a 45-year-old female. The PCT was documented in detail histologically and biochemically. The lymphoma was complicated by two paraneoplastic phenomena: inappropriate antidiuretic hormone secretion and peripheral neuropathy. It is possible that the PCT might also be a paraneoplastic phenomenon of the lymphoma. Search for an occult lymphoma may be of diagnostic and therapeutic value in patients presenting with PCT.
A micromethod for the specific measurement of hepatitis B viral DNA polymerase in serum is presented, based on the phosphonoformate inhibition assay (J Med Virol 12: 61-70, 1983). In the micromethod, sample volume is reduced to 120 microL and the ultracentrifugation step is eliminated. The method allows good discrimination between serum infected with hepatitis B virus and uninfected serum. The cutoff value for rate of nucleotide incorporation, based on assays of 41 serum specimens negative for hepatitis B serological markers, was about 15 nU/L (90th percentile). Serum containing hepatitis B surface and antigens exhibited rates of phosphonoformate-inhibitive nucleotide incorporation of 150 (SD 150) nU/L, with an upper 90th percentile range of 17 to 667 nU/L (n = 41). The micromethod makes use of commercially available [32P]dCTP (specific activity about 7000 kCi/mol). 125I-labeled dCTP was found to be unsuitable for this assay. Human DNA polymerases in serum are detected by this method but are excluded from the phosphonoformate-inhibitive fraction.
Hypoglycemia is frequently reported in hemodialysis patients on propranolol. We studied the influence of propranolol on carbohydrate metabolism in sixteen hemodialysis patients (eight on propranolol and eight not) with pre-dialysis oral glucose tolerance tests (OGTT) and pre- and post-dialysis glucagon tests. Propranolol was shown to have significant suppressive effect on the insulin response during OGTT. With glucagon challenge pre- and post-dialysis, despite a similar cAMP response, patients on propranolol had significantly lower glucose response than those not receiving propranolol and it is postulated that this is due to post-receptor post-cAMP inhibition of hepatic glycogenolysis. Moreover, while the glucose response in patients not on propranolol significantly increased after dialysis, no significant change was found in patients on propranolol. The significantly higher C-peptide, insulin and cAMP responses to glucagon challenge in the hemodialysis patients as compared to normal controls may be due to delayed clearance of glucagon, and the further increased responses after dialysis may be due to the removal of a dialyzable factor suppressing these responses.
Long repeated sequences containing up to 18,000 base pairs were found in a human DNA fraction isolated with the nuclease S1-dioxane method. Hybridization studies showed that the long repeats contained a greater proportion of sequences complementary to hnRNA than short repeats. They also exhibited homology to the latter, as shown by cross-hybridization experiments.
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A light microscopic and ultrastructural study of ten consecutive cases each of the clear cell type and nonclear cell type of hepatocellular carcinoma (HCC) showed important differences between the two groups which may help to explain their different biological behavior. The clear cells contained substantial quantities of glycogen and lipid which partly substitute the usual cytoplasmic constituents. An analogy was made between these tumor cells with clear cytoplasm and the clear cells which occurred in the intermediary stages of hepatocellular carcinogenesis in animals in an attempt to explain the better outcome of clear cell HCC.
This paper describes an assay for hepatitis B DNA polymerase which is based on the use of phosphonoformic acid (PFA), a known inhibitor of the viral enzyme, with particulate fractions prepared from blood plasma or serum. The assay makes possible the measurement of the viral enzyme activity in the presence of DNA polymerases unrelated to hepatitis B. The activities of the latter were largely but incompletely suppressed in the presence of 0.4 M KCl, and they were altogether excluded from nucleotide incorporation which was inhibited by PFA. Thus, particulate fractions obtained from HBsAg-negative blood had mean DNA polymerase activities of 1 +/- 1 (SD) pmol/liter/hr with a lower 90th percentile range of 0-3 pmol/liter/hr. Particulate fractions prepared from blood that was positive for both HBsAg and HBeAg had polymerase activities of 58 +/- 66 pmol/liter/hr with an upper 90th percentile range of 4-322 pmol/liter/hr. PFA concentration was optimized using a commercial preparation of the inhibitor, in which the degree of purity was determined. The method utilizes 3H-labeled deoxyribonucleoside triphosphates and is performed on 6 ml of plasma or serum. The effects of precursor concentration and specific activities on the rate of nucleotide incorporation were studied, and the optimal combinations were indicated. Other parameters of the proposed assay were also studied.