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Biomedical subjects

H M Cheng

Publications and source records attributed to H M Cheng.

160 records · Page 9Linked to original sources
PubMed1981

The sorbitol pathway in the human lens: aldose reductase and polyol dehydrogenase.

The sorbitol pathway in human lenses is evaluated on the enzymic level. Adult lenses, normal and nondiabetic as well as diabetic cataracts, are found to contain limited levels of aldose reductase (AR) and high levels of polyol dehydrogenase (PD) relative to the animal lens. AR is confined primarily to the lens epithelium and is two to three times higher in juvenile lenses than in the adult lens. The level of AR in the epithelium of juvenile lenses is sufficient to cause significant osmotic stress. The Km of glucose of AR is roughly 200 mM, whereas the Km for NADPH is 0.06 mM. NADP inhibits human lens AR noncompetitively and has a Ki equivalent to the Km for NADPH. PD occurs in both the lens epithelium and cortex, remains persistently high with age, and decreases with increased cortical involvement. The Km of sorbitol for PD is 1.4 mM and for NAD is 0.06 mM. NADH (Ki 0.002 mM) competitively inhibits PD in the forward direction. PD purified 100-fold from diabetic and nondiabetic cataracts and normal lenses exhibit similar kinetic constants. PD has an extremely high Vmax in the fructose-to-sorbitol direction. The Km of fructose is 40 mM and for NADH is 0.02 mM. At high enough concentration, alrestatin also inhibits PD. The added activities of AR and PD in producing sorbitol and fructose in combination with decreased hexokinase with age may account for diabetic cataract formation in human lenses exposed to a high glucose stress. Nucleotide levels are reported for senile cataractous lenses.

Aging↗
PubMed1980

Thiol oxidation in the crystalline lens. I. The rate-limiting role of hexokinase in aging rat and human lenses.

Reduction of nonprotein disulfides required both glucose or glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide phosphate (NADP). However, hexokinase (HK) was found to be the rate-limiting step: the glucose-supported reduction rate was only 50% of that of G6P-supported activity. This disulfide-reducing activity seemed to decline in the aging lens. Further, the glucose-supported activity dropped substantially if HK was deactivated with diamide; the deactivation was partially reversible. HK activity in aging clear and cataractous human lenses had greatly diminished. This might explain the disproportionate decrease in glucose-supported reduction in the aging lens. The components of the disulfide-reducing mechanism in human lens were reviewed and discussed.

Age Factors↗
PubMed1979

Efficacy of Alrestatin, an aldose reductase inhibitor, in human diabetic and nondiabetic lenses.

Immediately after cataract extraction, lenses from diabetic and nondiabetic patients were collected, classified, and assayed or incubated in high-glucose medium. The distribution of cataract types within the diabetic and nondiabetic groups was almost identical. The aldose reductase (AR) inhibitor AY22,284 (Alrestatin) was as effective in blocking sorbitol formation in diabetic as in nondiabetic lenses. While there was no difference in the level of intralenticular glucose, the diabetic lens produced significantly more sorbitol than did the nondiabetic lens. Also, the activity of polyol dehydrogenase (PD) was much lower in the diabetic population. The diabetic lenses swelled slightly more (P <.2) than nondiabetic lenses in high glucose media, and AY22,284 was effective in reducing the swelling of diabetic lenses in 35.5 mM glucose medium. While these results are preliminary, they suggest that diabetes, in some way, may confer on the human lens an increased susceptibility to osmotic stress via the sorbitol pathway. It is also reassuring to note that an AR inhibitor is no less effective in blocking the more active AR in the diabetic than in the nondiabetic lens. The therapeutic implications of this are discussed.

Aldehyde Reductase↗
PubMed1979

Dermatological and ocular examinations in rabbits chronically photosensitized with methoxsalen.

Four groups of female Dutch-belted rabbits (Oryctulagus cuniculus) were given methoxsalen (12 mg/kg) or placebo by oral intubation and 1 hr later were exposed to UVA for either 2 or 8 hr. This procedure was repeated 5 days each week for 18 mo. A fifth group received no drug and no UVA exposure. The skin of the animals given methoxsalen and UVA showed signs of acute and chronic phototoxicity. Multiple peripheral blood parameters of hepatic, renal and hematologic function were normal and were not different between groups. Complete ophthalmoscopic examinations were performed periodically. No cataracts were seen in any of the animals. This data provides the perspective that in one species the daily dose of methoxsalen and UVA required to induce chronic cutaneous photosensitization is lower than the daily dose required to induce cataracts. It is inadvisable to interpret this data as suggesting that no risk exists for patients being treated with oral methoxsalen photochemotherapy. The experimental evidence supporting photosensitization as a cause of cataracts and implicating a role of lens DNA in this cataractogenesis is reviewed. Because methoxsalen-UVA alterations of lens DNA or protein could lead to delayed onset of cataracts, and because of the serious nature and potential preventability of phototoxic lens opacification, appropriate protective eye wear is recommended for all patients receiving oral psoralen photochemotherapy.

Animals↗
PubMed1977

Stability of mammalian lens phosphofructokinase.

Two interconvertible phosphofructokinase (PFK) forms were found in rat and human lenses; whereas only one predominant form was found in calf lens. PFK isolated from these lenses possessed a common property, i.e., pH-dependent cold (or acid) lability. The inactivation was prevented by including either adenosine triphosphate (ATP) or fructose-6-phosphate (fru-6-P) in the incubating media. The protective effect of ATP or fru-6-P was complete in rat or calf lenses. In human lens, although fru-6-P was fully protective, ATP protected only partially. The inactivation could be reversed by addition of fru-6-P, but not ATP, to the incubating media at 37.5 degrees C. Lens organ culture studies showed that the depletion of lenticular ATP seemed to precipitate the loss of PFK.

Adenosine Triphosphate↗
PubMed1976

Properties of rat lens phosphofructokinase.

Two interconvertible forms of phosphofructokinase (PFK) have been eluted from a DEAE-cellulose column from the supernatant fraction of rat lens homogenates centrifuged at 96,000 x g for 1 hour at 0 to 4 degrees C. The interconversion can be manipulated by a change in the pH of the extracting and eluting buffers. PFK-I is the dominant form at pH between 7.4 to 7.05, while PFK-II dominates at pH 7.4 to 8.2. PFK-II is believed to be the functional form; it is inhibited by high concentrations of ATP and the inhibitory effect is enhanced by more acidic pH. Fructose-6-phosphate counteracts ATP inhibition, but the most potent de-inhibitors are ADP and AMP. Among the inorganic ions tested, sulfate, phosphate, ammonium, and potassium also de-inhibit, whereas calcium further inhibits the enzyme. The behavior of PFK under physiologic conditions and the significance of the presence of two forms of PFK in the lens are discussed.

Adenosine Triphosphate↗
PubMed1976

pH-dependent temperature sensitivity of rat lens phosphofructokinase.

Rat lens phosphofructokinase (PFK) has been found to be cold-labile at acidic pH, even in the presence of sulfate and inorganic phosphate, two known positive effectors. The inactivation appears to be an irreversible process, but can be prevented by including ATP in the incubating media. The enzyme is relatively stable at pH 8.2 incubated at 0 to 4 degrees, 25 degrees, or 37 degrees C. in the absence of the effectors, but is extremely thermolabile if the pH is lowered to 7.30 or lower. The thermolability is counteracted by many effectors, among them sulfate and ATP are the most effective. The physiologic significance of PFK instability and effector protection in the lens are discussed.

Adenosine Triphosphate↗
PubMed1973

Role of glutathione in the morphogenesis of the bacterial spore coat.

There is a marked increase in the half-cystine content of bacterial spores, especially the coat layers at the time of formation of the outer coat. When a cysteine auxotroph of Bacillus cereus T is grown on limiting cysteine, the spores contain the normal content of half-cystine, suggesting an alternate source. Glutathione appears to be such a supply of cysteine since it is hydrolyzed during sporulation and there are increased activities of the hydrolyzing enzymes at the same time. In addition, a cysteine auxotroph with a second alteration, a temperature-sensitive glutathione disulfide reductase, produces lysozyme-sensitive spores at 40 C. These spores appear to be defective in the formation of outer spore coat. During sporulation at 40 C, the double mutant accumulates oxidized glutathione which is a poor substrate for the hydrolytic enzymes. As a result, sporulating cells are deficient in half-cystines which are essential for outer spore coat morphogenesis. This alteration can be overcome by a shift to 30 C or by addition of cystinyl-pencillamine or cysteinyl-glycine to cultures sporulating at 40 C.

Bacillus cereus↗
PubMedDate not supplied

Sugar metabolism in the crystalline lens.

Research on the sugar metabolism of the crystalline lens, past and preent, is reviewed. The chief energy source in the lens is the Embden-Meyerhof pathway; respiration and oxidative phosphorylation become more important as the lens ages. The function of the alpha-glycerophosphate cycle is not fully understood. The mechanisms involved in cataract formation, including those of hypoglycemic cataract and osmotic cataracts, are discussed. Sugar cataracts can be delayed or prevented with such aldose reductase inhibitors as flavonoids. By inhibiting aldose reductase, the formation and accumulation of sugar alcohols is stopped. This approach may be useful as a medical therapy for human diabetic senile cataracts.

Aldehyde Reductase↗
PubMedDate not supplied

A description of human placental syncytiotrophoblast membrane glycosphingolipids.

The glycosphingolipid (GSL) structure of isolated human term placental syncytiotrophoblast microvillous plasma membrane (StMPM) has been investigated by Folch solvent extraction and thin-layer chromatography. StMPM preparations were shown to contain unique hydrophilic GSL species, including two highly glycosylated (greater than 15 saccharide residues/molecule) components. This fraction consistently included four major gangliosides (sialylated GSL), as well as two highly-sialylated (greater than or equal to 4 sialic acid residues/molecule) minor gangliosides.

Cell Membrane↗
PubMedDate not supplied

MR imaging of enucleated human eyes at 1.4 tesla.

Proton magnetic resonance images obtained for nine human eyes with various pathology were correlated with histological findings. One eye with retinal gliosis, three eyes with malignant melanoma, one eye with extraocular squamous cell carcinoma, one pair of eyes with incipient senile cataracts, and one pair of eyes with diabetic cataracts were examined at a field strength of 1.4 T using spin-echo and inversion-recovery signal acquisition protocols. Eyes were examined unfixed and within 24 h of enucleation. Most images were characterized by a homogeneous vitreous and a lens made conspicuous by its low-signal intensity. The anterior chamber, ciliary body, and optic nerve could be seen, but the retina and choroidal layers could not be distinguished. The dynamic range of vitreal signal was quite wide and allowed all lesions in this series to be well-contrasted against the vitreous. In addition, lenticular edema accompanying cataract formation gave a strong signal. Signal differences were apparent between paired cataractous lenses with a 1.6% difference in water content. Magnetic resonance imaging is a modality that promises good contrast for ocular imaging and sensitive detection of incipient cataractous change.

Adult↗
PubMedDate not supplied

Detection of antiphospholipid autoantibody in systemic lupus erythematosus is temperature-dependent.

Non-reactive SLE sera in an ELISA for anticardiolipin antibody (aCL) retested positive in the immunoassay when the sera were first heat-inactivated at 56 degrees C for 30 minutes. This was not a false positive phenomenon since the positive ELISA reactivity of the heated SLE sera was markedly reduced by inhibition with the cardiolipin antigen. Furthermore, the heat-potentiated ELISA reaction was abolished by prior IgG depletion of the SLE sera with Protein A preparation. The unmasked aCL in the heat-treated SLE sera also exhibited selective binding in ELISA to other negatively-charged phospholipids, namely phosphatidylserine and phosphatidic acid but not against either phosphatidylcholine or phosphatidyl-ethanolamine. The data strongly indicate an interaction between antiphospholipid antibodies and heat-sensitive serum component(s), a reduction of the latter resulting in the ELISA detection of the autoantibody.

Autoantibodies↗