Late-onset type cystinosis: report of a case.
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Biomedical subjects
Publications and source records attributed to K H Chen.
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A patient with alcoholism-related illness was found to have a rarely encountered biclonal gammopathy with IgM-kappa and IgM-lambda components. The para-protein bands were readily identified by immunofixation electrophoresis but were not by conventional immunoelectrophoresis. This patient is most appropriately classified as a biclonal gammopathy of undetermined significance, since no cause for this abnormality was found. The literature on biclonal IgM-kappa-lambda gammopathy is reviewed.
A group of Taiwan aborigines, the Toroko, was typed for 21 classical genetic loci. This is part of an ongoing program aimed at a comprehensive study of Taiwan aborigines. In this first paper a short summary of historical, archeological, and anthropological data in the literature is made, and results of the present survey are compared with older results from other aborigine tribes. An analysis of other neighboring populations from southeast Asia has also been carried out in order to give a preliminary answer to the question of origin of Taiwanese aborigines. Fifteen populations were studied for 13 loci by tree analysis, principal components, and isolation by distance. Tree analysis and principal component analysis gave results in fairly good agreement and indicate three major population clusters: a northeast cluster (Ainu, Korea, Japan, and Ryukyu); a southeast cluster (south China, Thailand, Vietnam, Philippines, Taiwan, and Toroko); and a third cluster including Malaya and Borneo. The positions of Polynesia, Micronesia, and Melanesia are somewhat peripheral. Analysis of the tree shows some potential cases of convergence, perhaps owing to admixture, and of divergence. The analysis of isolation by distance shows that geographic propinquity is a reasonably good predictor of general similarity in this area.
The mitochondrial DNAs (mtDNAs) from 116 Oriental and Caucasian blood samples were analyzed for their Hinc II restriction endonuclease cleavage patterns using Southern analysis and 32P human mtDNA probes. Seven distinct patterns were found, all of which could be interrelated by single nucleotide changes. The predominant pattern (mtHinc II-2) was found in 97% of the Caucasians and 73% of the Orientals. This mtDNA morph had one more Hinc II site than did the second most common morph (mtHinc II-1), which was found only in 20% of the Orientals. Three additional patterns were in a single Oriental sample, a fourth in a single Caucasian sample, and a fifth in one member of each population. The polymorphic site that differentiated mtHinc II-1 and mtHinc II-2 was cloned and sequenced. A single nucleotide change was found that created an Hinc II site and changed the amino acid sequence of the URF5 gene. Comparison of these sequences with those of other primates [15] revealed that the Asian mtHinc II-1 and mtHinc II-4 mtDNAs were identical in this region with those of chimpanzees and orangutans. These results suggest that the Asian mtHinc II-1 mtDNA may have been ancestral to other human mtDNAs.
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Cultural phenomena may show considerable stability over time and space. Transmission mechanisms responsible for their maintenance are worthy of theoretical and empirical inquiry; they are complex and each possible pathway has different effects on evolutionary stability of traits, as can be shown theoretically. A survey designed to evaluate the importance of some components of cultural transmission on a variety of traits showed that religion and politics are mostly determined in the family, a mode of transmission which guarantees high evolutionary stability and maintenance of high variation between and within groups.
The mtDNAs of 235 individuals from five ethnic groups were analyzed for restriction site variation by digestion with restriction endonuclease Hpa I, Southern transfer, and hybridization with 32P-labeled human mtDNA. Six different cleavage patterns (morphs) were found, all of which could be related to each other by single nucleotide substitutions. Differences were found in the frequency of these morphs among the populations. The largest difference observed was in the frequency of the morph most common in Caucasians and Orientals compared to the frequency of that found in Africans. This difference apparently originated by the sequence change G-T-C-A-A-C to G-T-T-A-A-C. This alteration permitted recognition by Hpa I but did not alter the amino acid sequence. Two other observed differences were due to separate substitutions occurring in the ribosomal RNA genes. Comparison with primate data shows that the morph with two fragments, found in 12.5% of Oriental and 4% of Bantu samples, might be the ancestral type common to all hominoids. These two conserved sites were localized in tRNA genes in the anticodon loop. Assuming that the two-fragment morph is ancestral, this finding is consistent with previous data suggesting that Asia is genetically central to the radiations that are thought to have given rise to the human ethnic groups.
The fluorescence decay kinetics of pyrene incorporated into artificial and natural membrane vesicles has been studied by pulse fluorimetry. The emission of monomeric pyrene and its excimer embedded in sonicated liposomes prepared from dipalmitoylphosphatidylcholine and a mixture of this phospholipid and dipalmitoylphosphatidylserine follows a multiple exponential decay law at temperatures both below and above their thermal transitions (10--48 degrees C). When pyrene is incorporated into fragmented skeletal sarcoplasmic reticulum vesicles, the emission decay exhibits similar multiple exponential character. The decay of the monomer in the phospholipid vesicles can be adequately described by three exponential terms. The experimental decays observed with both types of vesicles deviate significantly from a previously proposed model in which departure of the decay of pyrene monomer from monoexponentiality is qualitatively related to a time dependence in the diffuslipid vesicles can be adequately described by three exponential terms. The experimental decays observed with both types of vesicles deviate significantly from a previously proposed model in which departure of the decay of pyrene monomer from monoexponentiality is qualitatively related to a time dependence in the diffuslipid vesicles can be adequately described by three exponential terms. The experimental decays observed with both types of vesicles deviate significantly from a previously proposed model in which departure of the decay of pyrene monomer from monoexponentiality is qualitatively related to a time dependence in the diffusion-controlled formation of excimers from ground state and excited monomers. It is suggested that the observed decays are compatible with a reaction scheme involving excited state interaction.
Lysyl oxidase catalyzes the crosslinking of collagen and elastin. Lysyl oxidase activity was measured and localized in rat liver during the evolution of hepatic fibrosis induced by CCl4. Enzyme activity measured with DL-[6-3H]-lysine-labeled collagen substrates in liver and plasma increased sharply after approximately 3 wk of injection, reached a maximum at 6 wk, and then decreased. The increase in activity correlated histologically with early connective tissue septa formation, and the magnitude of increase was significantly greater than that found for the intracellular collagen biosynthetic enzymes protocollagen prolyl hydroxylase and lysyl hydroxylase. Indirect immunofluorescence studies showed that lysyl oxidase was present in association with collagen in the extracellular space. However, it was not possible to correlate the distribution pattern with a particular liver cell type. These observations suggest that serial measurements of lysyl oxidase activity in liver or plasma may be useful for correlating changes in connective tissue formation with histologic connective tissue deposition.
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The action of hydralazine on collagen prolyl hydroxylation was studied in a cell culture system using WI-38 fibroblasts. The prolyl hydroxylation level was determined by a method involving the digestion of collagen by bacterial collagenase and the examination of specific peptides. The presence of low concentrations of hydralazine (0.2 mM) in both "young" and "old" fibroblast cultures strongly inhibited collagen prolyl hydroxylation. The degree of inhibition was greater in serum-deficient cultures. No significant improvement in the degree of hydroxylation was observed by increasing either ascorbate or iron levels in the hydralazine-containing cultures in which hydroxylation was inhibited. Some of the reported side effects of hydralazine seen in patients might be related to its inhibitory effects on mixed function oxidative (MFO) hydroxylation systems. While the ascorbate dependence of the prolyl hydroxylase system of WI-38 decreased with the "age" of the culture, hydralazine inhibition of hydroxylation was dramatic with cultures of all "ages".
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Tamm-Horsfall glycoprotein (THG) purified from normal human pregnancy urine was found to increase polymorphonuclear neutrophil (PMN) phagocytosis (46.57 +/- 3.54% in the medium versus 75.85 +/- 5.37% in the presence of 25 micrograms/ml THG) after 30 min preincubation. The phagocytosis-enhancing activity of THG was dose-dependent (5-50 micrograms/ml) and was possibly mediated by the increased expressions of complement receptor type 1 (CR1) and type 3 (CR3) on the neutrophils. The release of [3H]arachidonic acid and prostaglandin E2 (PGE2), but not thromboxane B2 (TXB2), from neutrophils were also significantly enhanced by THG. Using 3,3'-dihexyloxacarbocyanine iodide as indicator, THG (25 micrograms/ml) depolarized the membrane potential of PMN after 30 min preincubation. In addition, THG exhibited a specific membranotropic effect with PMN. It is conceivable that THG binds to the cell surface and depolarizes the membrane potential of PMN which subsequently enhances the release of arachidonic acid metabolites and the translocation of the complement receptors to the membrane. These biochemical events lead to the increment of PMN phagocytosis and suggests that THG may play an important role in the defense mechanisms of the urinary tract in that a large amount of THG is usually present.
Tamm-Horsfall glycoprotein (THG) purified from pregnancy urine was found to stimulate normal human mononuclear cell (MNC) proliferation at a concentration greater than 10 micrograms/ml. This stimulation was non-specific because the percentage of B and T cell subpopulations including CD20, CD3, CD4, CD8 and CD4/CD8 ratio was not changed by THG. THG not only bound to human mononuclear cells but depolarized the membrane potential, increased 22Na+ uptake and enhanced the expression of IL-2R and HLA-class II antigens on these cells. The concentrations of sIL-2R, sCD4 and sCD8 in the THG-stimulated MNC culture supernatants were significantly increased compared with control supernatants. In addition, overnight incubation of THG (5-50 micrograms/ml) with MNC dose-responsively enhanced the syntheses of IL-1 beta, IL-6 and TNF-alpha by monocytes, with a maximal effect at 25 micrograms/ml. This monokine releasing activity of THG could be neutralized by a specific antibody against THG. When monocytes/macrophages were depleted from mononuclear cells by incubating with lysosomotropic methyl ester of L-leucine, THG retained the capability of stimulating lymphocytes proliferation but to a lesser degree. These results suggest that urinary THG activates monocytes to synthesize large amount of monokines through its membrane effect. The released monokines subsequently stimulate lymphocytes expressing IL-2R and HLA-class II antigens and finally lead to cell proliferation.
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