Association of polymorphic markers of the lipid metabolism genes with diabetic polyneuropathy in type 1 diabetes mellitus

A possible association of the polymorphic markers 2/3/4 of the apolipoprotein E gene (APOE) and I /D of the apolipoprotein B gene (APOB) with diabetic polyneuropathy (DPN) was analyzed in patients with type 1 diabetes mellitus (T1DM) with (N=86) or without (N=94) clinical signs of DPN. The two groups did not differ significantly in allele and genotype frequencies of the 2/3/4 polymorphic marker of the APOE gene. Analysis of the allele and genotype frequency distributions of the I/D polymorphic marker of the APOB gene showed that risk of DPN is higher in carriers of allele I or genotype I/I (OR=1.66 and 2.01, respectively) and lower in carriers of allele D (OR=0.60). The results implicate the APOB gene, which codes for one of the major components of the lipid metabolism system, in DPN development in patients with T1DM.__________Translated from Molekulyarnaya Biologiya, Vol. 39, No. 2, 2005, pp. 230–234.Original Russian Text Copyright © 2005 by Voronko, Yakunina, Strokov, Lavrova, Nosikov.     

Decreases in Plasma Aβ1-40 Levels with Aging in Non-Demented Elderly with ApoE-ε4 Allele

This report examines plasma amyloid proteins A40 and A42 and apolipoprotein E (apoE) levels and their relationships with age in non-demented older adults with (N = 32) or without the apoE-4 allele (N = 94). A levels did not differ between the groups whereas the 4 allele was associated with a significant reduction in plasma apoE. In subjects with the 4 allele, increasing age was associated with significant reduction in plasma A40. Subjects without the 4 allele showed a significant positive correlation between A40 and A42 levels. There was also a significant correlation between plasma A40 and apoE levels in all subjects.     

Genetic Association between the Apolipoprotein E (APOE) Gene and Different Forms of Alzheimer's Disease

Allele 4of the apolipoprotein E (APOE) gene is associated with higher risk for family or sporadic Alzheimer's disease (AD) in many, though not all, ethnic groups. The APOEallele and genotype frequency distributions were evaluated in 207 AD patients without vascular disorders, 62 AD patients with vascular disorders (combined AD), and 206 control individuals (ethnic Russians from the Russian population). The frequency of allele 4in patients with early-onset and late-onset AD was three times higher than in controls (P< 0.000001). The increase in the frequency of 4in mixed dementia cases over controls was somewhat less but still significant (P= 0.0019). Relative risk of AD in carriers of allele 4was five times higher than in carriers of alleles 2and 3(P< 0.000001). Allele 2showed evidence of a protective effect in the early-onset AD group (P= 0.015). These results suggest that APOEallele 4is a universal factor of early-onset, late-onset, and combined AD in ethnic Russians from Russia.     

Polymorphism of the Apolipoprotein E Gene and Risk of Myocardial Infarction

The apolipoprotein E (ApoE) gene polymorphism resulting from nucleotide substitutions in exon 4 was analyzed in Russian and Tatar patients with myocardial infarction (MI) from Bashkortostan. Alleles 2, 3, and 4 were identified by PCR. The genotype frequency distribution proved to be age-dependent in healthy Russians, genotype 2/3 increasing in frequency in subjects over 45. Russians who suffered MI under 45 had lower frequencies of genotype E3/3 (50.00% vs. 75.47% in controls of the same age, = 0.013, OR = 0.33) and allele 3 (72.12% vs. 85.85%, = 0.020, OR = 0.43) and a higher frequency of allele 4 (22.12% vs. 10.38%, = 0.030, OR = 2.45). Russians who suffered MI complicated by cardiogenic shock (CS) had a significantly higher frequency of genotype 3/4 and lower frequencies of genotype 3/3 and allele 3 as compared with MI patients without CS. In Tatars, genotype 4/4 occurred at a frequency of 14.29% in patients who suffered MI under 45, and was not detected in healthy subjects of the same age ( = 0.024, OR = 17.85). Thus, the ApoE polymorphism was associated with higher risk of MI in Russians and Tatars under 45.     

Substitutions of the Conserved Thr42 Increased the Roles of the ε-Subunit of Maize CF1 as CF1 Inhibitor and Proton Gate

The conserved residue Thr42 of -subunit of the chloroplast ATP synthase of maize (Zea mays L.) was substituted with Cys, Arg, and Ile, respectively, through site-directed mutagenesis. The over-expressed and refolded -proteins were purified by chromatography on DEAE-cellulose and FPLC on mono-Q column, which were as biologically active (inhibiting Ca²⁺-ATPase activity and blocking proton gate) as the native subunit isolated from chloroplasts. The T42C and T42R showed higher inhibitory activities on the soluble CF₁(–) Ca²⁺-ATPase than the WT. The T42I inhibited the Ca²⁺-ATPase activity of soluble CF₁ and restored photophosphorylation activity of membrane-bound CF₁ deficient in the most efficiently. Far-ultraviolet CD spectra showed that the portions of -helix and -sheet structures of the three mutants were somewhat different from WT. Thus the conserved residue Thr42 may be important for maintaining the structure and function of the -subunit and the basic functions of the -subunit as far as an inhibitor of Ca²⁺-ATPase and the proton gate are related.     

Pyridoxal-5′-phosphate derivatives of substance P: Preparation,spasmogenic activity,and degradation by human plasma

Two fluorescent derivatives of substance P (SP) (Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH₂) were prepared by chemical modification of the native peptide by pyridoxal-5-phosphate (pyridoxal-P). The formation of both pyridoxal-P-derivatives of SP is the result of one modification procedure. The determination of the amino acid composition showed that in one of the derivatives the -amino group of the Lys residue [-(P-pxy)-SP] and in the other the -amino group of the Lys residue and also the N-terminal amino group [,-di-(P-pxy)-SP] of SP had been substituted by pyridoxal-P. -(P-pxy)-SP and ,-di-(P-pxy)-SP have spasmogenic activity with ED₅₀ of 1.8×10^–9 and 4×10^–9 M, respectively, tested on isolated guinea pig ileum. The fluorescence of P-pxy residues permits detection of as little as 1 pmol/ml of -(P-pxy)-SP and 0.5 pmol/ml of ,-di-(P-pxy)-SP. Both analogues of SP obtained are degraded by human plasma more slowly than the native peptide.Abbreviations SP substance P - pyridoxal-P pyridoxal-5-phosphate - P-pxy phospho-pyridoxyl residue - -(P-pxy)-SP substance P modified by pyridoxal-P at the -amino group of the Lys residue - ,-di-(P-pxy)-SP substance P modified by pyridoxal-P at the -amino group of the Lys residue and the N-terminal amino group of SP - (P-pxy)-Lys Lys modified by pyridoxal-P at the -amino group     

Gender- and age-specific contributions of additional DNA sequence variation in the 5′ regulatory region of the <Emphasis Type="Italic">APOE</Emphasis> gene to prediction of measures of lipid metabolism

In the present study of 9,000 individuals representative of the general population, we have considered whether the addition of common single nucleotide polymorphisms (SNPs) in the promoter region of Apolipoprotein E (APOE) improve the statistical explanation of variation in lipid traits and test the hypothesis that the estimated genotype effects are independent of factors indexed by gender and age. To address these questions, we have asked, for each gender and for each 20-year age strata (young: 20–39 years; middle-aged: 40–59 years; old: 60–79 years; very old: 80–100 years), how much trait variation is associated with the traditional 2, 3, and 4 allelic variations defined by the g.2059TC and g.2197CT SNPs in the fourth exon of the APOE gene, and how much additional trait variation is associated with genotypes defined by combining the g.2059TC and g.2197CT SNPs with one, two, or three promoter SNPs. Our study demonstrates that the pleiotropic effects of genotype variation defined by the traditional 2, 3, and 4 alleles on five plasma measures of lipid metabolism manifest differently in women and men and change significantly during the life cycle for high-density lipoprotein cholesterol in women. Multi-site genotypes defined by adding SNPs located in the 5 promoter region to the traditional g.2059TC and g.2197CT SNPs doubled the estimate of genetic variance of high-density lipoprotein and apolipoprotein Al in middle-aged females.     

Interaction of Apolipoprotein E ε 4 With Other Genetic and Non-Genetic Risk Factors in Late Onset Alzheimer Disease: Problems Facing the Investigator

The Apolipoprotein E4 allele (Apo-4) is the major susceptibility gene for late onset Alzheimer Disease (AD) but epidemiological data suggest that the effect of this allele is modified in different individuals by genetic or environmental factors. Age and head injury are major non-genetic factors modifying the Apo-4 risk. There is conflicting data as to whether alleles of other chaperon proteins (such as alpha-1-antichymotrypsin (ACT)) or Apo-4 receptors (such as the VDRL receptor) modify the Apo-4 risk for AD. We analyze problems posed by genetic association studies including those of multiple comparisons and selection of controls, the latter problem exacerbated by the wide variations in Apolipoprotein E allele frequencies observed in different groups and localities.     

Specific antibodies to the N-termini of the interpeptide bridges of peptidoglycan

The synthetic peptides Gly₅--Ahx and l-Ala₃--Ahx, with structural similarity to the interpeptide bridge peptides of staphylococci or micrococci, respectively, were covalently linked to human serum albumin via their carboxylgroups. Antisera to these synthetic peptidyl-protein antigens contained fairly high amounts of antibodies with specificity to the N-terminal parts of the peptide chains attached to the carrier proteins. Antisera to (Gly₅--Ahx)₂₀-albumin gave, without exception, strong precipitin reactions in latex-agglutination with staphylococcal peptidoglycans. The antisera completely failed, however, in any reaction with peptidoglycans of micrococci or other bacteria which did not have these oligo-glycine peptides typical for staphylococci. On the contrary, antisera to (l-Ala₃--Ahx)₂₂-albumin strongly precipitated micrococcal peptidoglycans with oligo-l-alanine interpeptide bridges (e.g. Micrococcus varians, Micrococcus reseus), but showed no significant reaction with peptidoglycans of staphylococci or other bacteria lacking oligo-l-alanine interpeptide bridges.Abbreviations Use Ac acetyl- - -Ahx -amino caproic acid - ATCC American Type Culture Collection, Rockville, Md., U.S.A. - CCM Czechoslovak Collection of Microorganisms, Brno, CSSR - DSM Deutsche Sammlung für Mikroorganismen, München, FRG - IMRU Institute of Microbiology, Rutgers University, N.J., U.S.A. - Kiel Bundesanstalt für Milchforschung, Kiel, FRG - NPS o-nitrophenylsulphenyl- - -OMe methyl ester - -OSu succinimide ester - Z- benzyloxycarbonyl     

Electric field-induced breakdown of lipid bilayers and cell membranes: A thin viscoelastic film model

Summary A simple viscoelastic film model is presented, which predicts a breakdown electric potential having a dependence on the electric pulse length which approximates the available experimental data for the electric breakdown of lipid bilayers and cell membranes (summarized in the reviews of U. Zimmermann and J. Vienken, 1982,J. Membrane Biol. 67:165 and U. Zimmermann, 1982,Biochim. Biophys. Acta 694:227). The basic result is a formula for the time of membrane breakdown (up to the formation of pores): =(/C)/( _m ² ₀ ² U ⁴/24Gh ³+T ²/Gh–1), where is a proportionality coefficient approximately equal to ln(h/2₀),h being the membrane thickness and ₀ the amplitude of the initial membrane surface shape fluctuation ( is usually of the order of unity), represents the membrane shear viscosity,G the membranes shear elasticity modules, _m the membrane relative permittivity, ₀=8.85×10^–12 Fm,U the electric potential across the membrane, the membrane surface tension andT the membrane tension. This formula predicts a critical potentialU _c ;U _c =(24Gh ³/ _m ² ₀ ² )^1/4 (for = andT=0). It is proposed that the time course of the electric field-induced membrane breakdown can be divided into three stages: (i) growth of the membrane surface fluctuations, (ii) molecular rearrangements leading to membrane discontinuities, and (iii) expansion of the pores, resulting in the mechanical breakdown of the membrane.     

Increase in histamine content and enhancement of high affinity IgE receptor FcεRI expression in the human leukemia KU812 cells upon treatment with hydrocortisone

Hydrocortisone was investigated for its ability todifferentiate human leukemia KU812 cells into maturehematopoietic cells including basophils. Hydrocortisonetreatment increased the amount of intracellular histamine byup-regulation of L-histidine decarboxylase (HDC) mRNA andenhanced cell surface expression of the high affinity IgEreceptor FcRI. Histamine is catalyzed from L-histidine byHDC, which in blood cell types is only expressed in basophilsand mast cells. Cells, on which the FcRI expression wasenhanced by hydrocortisone, were shown to release histaminewhen stimulated with anti-IgE antibody after sensitizationwith myeloma IgE, implying that the induced FcRI moleculeswere able to transduce a signal for degranulation. Theseresults suggest that hydrocortisone promotes differentiationof KU812 cells into functionally mature basophilic cells.     

Inhibition of ADP-ribosylation of histone H1 by analogs of diadenosine 5′, 5‴-p1,p4-tetraphosphate

The effects of analogs of diadenosine 5,5-p¹,p⁴-tetraphosphate (Ap4A) were examined on the ADP-ribosylation reaction of histone Hl catalysed by purified bovine thymus poly(ADP-ribose)transferase. Among the compounds tested, Ap4A and ApCH₂PPPA were shown to be the most efficient inhibitors of the enzyme. From kinetic studies of their action, it appears that Ap4A and ApCH₂pppA might be mixed type inhibitors.Abbreviations ADP-ribose adenosine diphosphate ribose - ADPRT poly-(ADP-ribose)transferase - Ap4A diadenosine 5,5-p₁,p₄-tertraphosphate - Ap4A diadenosine 5,5-p¹,p⁴(-1,N⁶-ethenyl-)tetra-phosphate - ApAA diadenosine 5,5-p¹,p⁴(-N⁶(-1,N⁶-)bisethenyl-)tetraphosphate - ApCH₂pppA diadenosine 5,5-p¹,p⁴(-p¹,p²-methylene-)tetraphosphate - AppCH₂ppA diadenosine 5,5-p¹,p⁴(-p²,p³methylene-)tetraphosphate - AppNHppA diadenosine 5,5-p¹,p⁴(-p²,p³-amino-)tetraphosphate - AppCHBrppA diadenosine 5,5-p¹,p⁴(-p²,p³-bromine methyno-)tetraphosphate - CpCH₂ppCH₂PC dicytidine 5,5-p¹,p⁴(-p¹,p²-p³,p⁴-bismethylene-)tetraphosphate - ApCH₂ppCH₂pA diadenosine 5,5-p¹,p⁴(-p¹,p²-p³,p⁴-bismethylene-)tetraphosphate.     

Comparison of the carbohydrate moieties of recombinant soluble Fcε receptor (sFcε RII/sCD23) expressed inSaccharomyces cerevisiae and Chinese hamster ovary cells. Different O-glycosylation sites are used by yeast and mammalian cells

Recombinant human soluble low affinity receptor for the Fc portion of IgE (sFcRII/sCD23) was produced inSaccharomyces cerevisiae or Chinese hamster ovary cells and subjected to carbohydrate analysis. Applied methods included analytical SDS-PAGE, reversed phase HPLC, methylation analysis and sequential degradation with exoglycosidases. The results revealed that sFcRII derived from Chinese hamster ovary cells is glycosylated exclusively at Ser-147, containing mainly the trisaccharide Sia(2–3)Gal(1–3)GalNAc, whereas the yeast derived glycoprotein was glycosylated at Ser-167 and contained only -mannosyl residues. It is shown here for the first time that different amino acids of a given protein can be O-glycosylated when expressed in yeast or Chinese hamster ovary cells.     

Is There a Genetic Basis for the Deposition of β-Amyloid After Fatal Head Injury?

1. Alzheimer's disease is a heterogeneous disorder that may be caused by genetic or environmental factors or by a combination of both. Abnormalities in chromosomes 1, 14, and 21 have all been implicated in the pathogenesis of the early-onset form of the disease, while the 4 allele of the apolipoprotein E gene (on chromosome 19) is now recognized as a risk factor for early- and late-onset sporadic and familial Alzheimer's disease.2. The best-established environmental trigger for the disease is a head injury, based on epidemiological and neuropathological evidence. Approximately 30% of patients who die after a single episode of severe head injury show intracerebral deposition of -amyloid protein (A), a protein that is thought to be central to the pathogenesis of Alzheimer's disease.3. Recent studies have revealed an over-representation of the apoE 4 allele in those head-injured patients displaying A pathology, thus providing the first evidence for a link between a genetic susceptibility (apoE 4) and an environmental trigger (head injury) in the development of Alzheimer-type pathology.     

Embryonic hemoglobins of different animal species

Summary The existence of embryonic hemoglobins is demonstrated in sheep-, calf and pig embryos. The occurrence and disappearance of these hemoglobins is quantitatively determined by cellulose acetate gel electrophoresis; hemoglobins as well as the globin chains, dissociated in 8 molar urea were quantitated. Sedimentation and diffusion experiments in the analytical ultracentrifuge revealed a S₂₀ of 4.3 and a D₂₀ of 6.6 for the examined hemoglobins. Therefore it is concluded that all hemoglobins occurring at different stages of embryonic and fetal development consist of 4 polypeptide chains with a total molecular weight of 66,000. The subsequent formation of the different polypeptide chains during ontogenesis is shown: At first only -chains are formed as demonstrated by the existence of Hb Gower I, consisting of four identical -chains. Subsequently the -chain appears, which leads to Hb Gower 2 (₂₂). The third polypeptide chain formed during the ontogenesis the -chain results finally in the appearance of HbF.In addition the existence of a HbF pig is demonstrated by the fingerprint technique.     

Apolipoprotein E phenotypes and hyperlipidemia

Summary Apolipoprotein E phenotypes were determined in 361 patients with hyperlipidemia and in controls. The E2 isoform was significantly more frequent in the group of hyperlipidemics (P<0.0005). This was not due to a higher frequency of E-2/2 homozygotes with type III hyperlipoproteinemia, but rather to a significantly higher frequency of E2 heterozygotes (P<0.0005). Subgrouping of hyperlipidemics into patients with a) hypertriglyceridemia, b) hypercholesterolemia and c) mixed hyperlipidemia revealed i) that isoform E2 was significantly more frequent in patients with hypertriglyceridemia (0.001>P>0.005), ii) that isoform E4 was significantly more frequent in patients with hypercholesterolemia (0.01>P>0.005) and iii) that isoforms E2 (P>0.005) and E4 (0.05>P>0.025) were both more frequent in patients with mixed hyperlipidemia. Roughly 20% of patients with mixed hyperlipidemia had one of the rare phenotypes E-4/4,-4/2 or-2/2. We conclude that alleles 2 and 4 both contribute to the susceptibility for, and/or phenotypic expression of hyperlipidemia. Whereas the gene 2 seems to exert its influence on plasma lipoproteins by an abnormal gene product (E2) that has reduced binding activity to lipoprotein receptors, the mechanism underlying the association of the 4 gene with hyperlipidemia is presently unclear.     

The structural features of effective antagonists of the luteinizing hormone releasing hormone

Summary The structure-activity data of 6 years on 395 analogs of the luteinizing hormone releasing hormone (LHRH) have been studied to determine effective substituents for the ten positions for maximal antiovulatory activity and minimal histamine release. The numbers of substituents studied in the ten positions are as follows: (41)¹-(12)²-(12)³-(5)⁴-(47)⁵-(52)⁶-(16)⁷-(18)⁸-(4)⁹-(8)¹⁰. In position 1, DNal and DQal were effective with the former being more frequently the better substituent. DpClPhe was uniquely effective in position 2. Positions 3 and 4 are very sensitive to change. D3Pal in position 3 and Ser in position 4 of LHRH were in the best antagonists. PicLys and cPzACAla were the most successful residues in position 5 with cPzACAla being the better substituent. Position 6 was the most flexible and many substituents were effective; particularly DPicLys. Leu⁷ was most often present in the best antagonists. In position 8, Arg was effective for both antiovulatory activity and histamine release; ILys was effective for potency and lesser histamine release. Pro⁹ of LHRH was retained. DAlaNH₂ ¹⁰ was in the best antagonists.Abbreviations AABLys N -(4-acetylaminobenzoyl)lysine - AALys N -anisinoyl-lysine - AAPhe 3-(4-acetylaminophenyl)lysine - Abu 2-aminobutyric acid - ACLys N -(6-aminocaproyl)lysine - ACyh 1-aminocyclohexanecarboxylic acid - ACyp 1-aminocyclopentanecarboxylic acid - Aile alloisoleucine - AnGlu 4-(4-methoxy-phenylcarbamoyl)-2-aminobutyric acid - 2ANic 2-aminonicotinic acid - 6ANic 6-aminonicotinic acid - APic 6-aminopicolinic acid - APh 4-aminobenzoic acid - APhe 4-aminophynylalanine - APz 3-amino-2-pyrazinecarboxylic acid - Aze azetidine-2-carboxylic acid - Bim 5-benzimidazolecarboxylic acid - BzLys N -benzoyllysine - Cit citrulline - Cl₂Phe 3-(3,4-dichlorphenyl)alanine - cPzACAla cis-3-(4-pyrazinylcarbonylaminocyclohexyl)alnine - cPmACAla cis-3-[4-(4-pyrimidylcarbonyl)aminocyclohexyl]alanine - Dbf 3-(2-dibenzofuranyl)alanine - DMGLys N -(N,N-dimethylglycyl)lysine - Dpo N -(4,6-dimethyl-2-pyrimidyl)-ornithine - F₂Ala 3,3-difluoroalanine - hNal 4-(2-naphthyl)-2-aminobutyric acid - HOBLys N -(4-hydroxybenzoyl)lysine - hpClPhe 4-(4-chlorophenyl)-2-amino-butyric acid - Hse homoserine, 2-amino-4-hydroxybutanoic acid - ICapLys N -(6-isopropylaminocaproyl)lysine - ILys N -isopropyllysine - Ind indoline-2-carboxylic acid - INicLys N -isonicotinoyllysine - IOrn N -isopropylornithine - Me₃Arg N^G,N^G,N^G-trimethylarginine - Me₂Lys N ,N -dimethyllysine - MNal 3-[(6-methyl)-2-naphtyl]alanine - MNicLys N -(6-methylpicolinoyl)lysine - MPicLys N -(6-methylpicolinoyl)lysine - MOB 4-methoxybenzoyl - MpClPhe N-methyl-3-(4-chlorphenyl)lysine - MPZGlu glutamic acid,-4-methylpiperazine - Nal 3-(2-naphthyl)alanine - Nap 2-naphthoic acid - NicLys N -nicotinoyllysine - NO₂B 4-nitrobenzoyl - NO₂Phe 3-(4-nitrophenyl)alanine - oClPhe 3-(2-chlorphenyl)alanine - Opt O-phenyl-tyrosine - Pal 3-(3-pyridyl)alanine - 2Pal 3-(2-pyridyl)alanine - 2PALys N -(3-pyridylacetyl)lysine - pCapLys N -(6-picolinoylaminocaproyl)lysine - pClPhe 3-(4-chlorophenyl)alanine - pFPhe 3-(4-fluorophenyl)-alanine - Pic picolinic acid - PicLys N -picolinoyllysine - Pip piperidine-2-car-boxylic acid - PmcLys N -(4-pyrimidylcarbonyl)lysine - Ptf 3-(4-trifluromethyl phenyl)alanine - Pz pyrazinecarboxylic acid - PzAla 3-pyrazinylalanine - PzAPhe 3-(4-pyrazinylcarbonylaminophenyl)alanine - Qal 3-(3-quinolyl)alanine - Qnd-Lys N -quinaldoyllysine - Qui 3-quinolinecarboxylic acid - Qux 2-quinoxalinecarboxylic acid - Tic 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid - TinGly 2-thienylglycine - tNACAla trans-3-(4-nicotinoylaminocyclohexyl)-alanine - tPACAla trans-3-(4-picolinoylaminocyclohexyl)alanine     

Kinetic comparison of caiman ε-crystallin and authentic lactate dehydrogenases of vertebrates

Kinetic comparison of -crystallins isolated from the avian and reptilian species and the authentic lactate dehydrogenases (LDHs) was undertaken in order to clarify the identities of these structural lens proteins in relation to their enzymatic activity. Caiman -crystallin similar to the previously characterized duck -crystallin appeared to possess a genuine and stable LDH activity as detected by nitro blue tetrazolium staining on polyacrylamide gels and conventional kinetic assays. Kinetic parameters for pyruvate,l-lactate, NAD⁺, and three structural analogues of the coenzyme in this -crystallin catalyzed reaction were also determined and compared. Despite the structural similarities between -crystallins and chicken heart LDH, differences in charge and kinetic properties have been revealed by native isozyme electrophoresis and kinetic analysis as examined by initial velocity and substrate inhibition studies. It is found that the kinetic data analyzed for caiman -crystallin were more fitted with a compulsory ordered Bi-Bi sequential mechanism similar to those for the authentic LDHs and duck -crystallin. Caiman -crystallin has for the first time been established as a heart-type LDH based on the kinetic analysis and comparison with the authentic heart- and muscle-type LDHs from pig and chicken.     

Apolipoprotein E polymorphism in Northern Indian patients with coronary heart disease: Phenotype distribution and relation to serum lipids and lipoproteins

Apolipoprotein E (apo E), a genetic determinant of plasma lipid levels and coronary heart disease (CHD) needs to be investigated in Asian Indians since they have a propensity to develop dyslipidemia and accelerated atherosclerosis. We studied apo E phenotypes and plasma lipid levels in 52 Northern Indian male patients (aged 38–71 years) with angiographically proven CHD, and compared them to 50 healthy blood donors taken as the control group. High levels of Lp(a), (p < 0.05), and a definite trend towards lower levels of HDL-C (p < 0.05), was observed in the CHD patients as compared to the control subjects. The frequency of apo E allele 3 was 0.86 and 0.862, and 4 allele was 0.12 and 0.08 in the patients and controls, respectively. However, a lower frequency of the E2 allele was observed in the patient group (2 = 0.02) as compared to the controls (2 = 0.06) (p = ns). In individuals with apo E3/E3 phenotype, significantly lower HDL-C levels was observed in the CHD patients as compared to the control subjects (p < 0.05). A positive correlation was observed between apo E phenotypes and Lp(a) levels in the CHD subjects as compared to the controls (p < 0.05), the level being significantly high in CHD subjects with at least one E4 allele. To conclude, in this sample of Northern Indian subjects with CHD, there is a significant correlation between apo E3/E3 phenotype and low levels of HDL-C as compared to the control subjects. Further, apo E phenotype is positively correlated with high Lp(a) levels in the CHD subjects having at least one E4 allele. However, these relationships need to be explored in a larger sample of subjects.