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PubMed1984

The fetal renin-angiotensin system in pregnancy-induced hypertension.

Maternal and fetal blood samples were obtained from 10 normotensive primigravidae and 10 primigravidae with pregnancies complicated by hypertension and proteinuria. Measurements were performed of plasma renin activity (PRA), plasma renin concentration (PRC) and plasma renin substrate (PRS). PRA and PRC were significantly higher in cord artery and cord vein blood than in maternal venous blood in normotensive women, and PRS was significantly lower. PRS levels were lower in maternal plasma of hypertensive women, and, although PRC and PRA were lower in the cord blood of infants born to hypertensive women, these differences did not achieve statistical significance.

Angiotensinogen↗

PubMed1997

The predictive value of the sperm-cervical mucus interaction test on the outcome of in vitro fertilization and ovulation induction combined with intrauterine insemination.

We investigated the effect of the sperm-cervical mucus penetration tests (SPT) on the fertilization rate (FR) and pregnancy rate (PR) in patients treated with either in vitro fertilization (IVF) or ovulation induction combined with intrauterine insemination (OI + IUI). Infertile couples where the women had normal ovarian function and a normal pelvis at laparoscopy and her partner had normal seminology who had failed at least 2 SPTs were treated with either IVF or OI + IUI. These patients were compared with similar couples in whom SPTs were satisfactory (SPT/ve). Group A (SPT+ve) consisted of 46 patients who underwent 78 treatment cycles of IVF and Group B (SPT-ve) comprised 31 patients who underwent 35 IVF cycles. Group C (SPT/ve) consisted of 39 patients who underwent 84 treatment cycles with OI + IUI, and Group D (SPT-ve) consisted of 15 patients who underwent 37 cycles with the same treatment. In patients treated with IVF, the FR and PR per embryo transfer were 77.0% and 20.0% respectively in Group A, and 64.0% and 22.6% respectively in Group B. The difference in FRs was statistically significant (p > 0.001) but there was no difference in the PRs. In patients treated with OI + IUI, the PR per cycle were 22.0% in Group C and 16.2% in Group D. These results indicate that SPT failure was associated with a lower FR in IVF but this did not affect the PRs. Similarly there was no difference in PRs following OI + IUI.

Female↗

PubMed1986

Ventricular parasystole: a chronobiologic study.

Previous works have reported circadian rhythms for several cardiovascular parameters. A chronobiologic rhythm is characterized by: mesor (a rhythm-determined average), amplitude (half difference between the highest and lowest values), and acrophase (timing of high point in degrees and/or in hours) along with 95% confidence limits. We performed 24-hour ECG Holter monitoring in seven patients (mean age, 50.6 years) with ventricular parasystole (VP) in order to determine whether the chronotropic activity of parasystolic foci has a circadian rhythm similar to that of the sinus node. For each Holter recording parasystolic rates (PRs) and heart rates (HRs) were calculated every hour. Furthermore, a mean hourly PR and a mean hourly HR were calculated from the hourly PRs and HRs of the patients. The statistic chronobiologic analysis was done by single and mean cosinor methods. Correlation between mean hourly PR and HR was evaluated by Pearson's 'r' coefficient. A statistically significant rhythm (P less than 0.05) was found for the single and mean rhythms both of HR and PR. In our patients, HR had acrophase at 1.27 P.M., mesor at 73.28 beats/min, and amplitude at 9.53 beats/min, whereas PR had acrophase at 1.42 P.M., mesor at 38.31 beats/min, and amplitude at 3.64 beats/min. Chronobiological data and the high direct correlation between mean hourly HRs and mean hourly PRs (r = 0.96, P less than 0.001) indicate a similar circadian variability of the chronotropic activity of sinus nodes and parasystolic foci. Although several hypotheses can be made, responsiveness of parasystolic foci to circadian variations of the autonomic nervous system tone (sympathetic and/or vagal) and/or circulating substances (particularly catecholamines) seems the more probable one for explaining our findings.

Adolescent↗

PubMed2006

The GYF domain.

GYF domains are small, versatile adaptor domains that recognize proline-rich sequences (PRS). They are present in most eukaryotic species sequenced so far, but in contrast to other PRS-recognition domains (PRD), GYF domains have not experienced the same amplification in metazoa during evolution. Mutational and structural analysis has shown the conserved signature W-X-Y-X(6-11)-GPF-X(4)-M-X(2)-W-X(3)-GYF to be the site of interaction with proline-rich peptides. In contrast, composition and length of the C-terminal half of GYF domains are not conserved. Similar to other PRD, GYF domains bind to many different PRS that converge on a minimal consensus sequence. All GYF domains analyzed so far selected for the core motif PPG, whereas amino-acid preferences adjacent to this motif vary. As a result of this analysis, two subfamilies have been identified: CD2BP2-type and SMY2-type GYF domains. The latter subfamily comprises most GYF domains and is characterized by a shorter beta(1)-beta(2) loop and an aspartate instead of the tryptophan found at position 8 in CD2BP2-type GYF domains. Recent analysis of binding specificities for GYF domains allowed identification of novel interaction partners. Thereby proteomics has contributed to a functional understanding of GYF domain-containing proteins and sets the stage for a more systematic investigation of their functions in vivo.

Amino Acid Motifs↗

PubMed2006

Discovery of natural atypical nonhemolytic Listeria seeligeri isolates.

We found seven Listeria isolates, initially identified as isolates with the Xyl(+) Rha(-) biotype of Listeria welshimeri by phenotypic tests, which exhibited discrepant genotypic properties in a well-validated Listeria species identification oligonucleotide microarray. The microarray gives results of these seven isolates being atypical hly-negative L. seeligeri isolates, not L. welshimeri isolates. The aberrant L. seeligeri isolates were d-xylose fermentation positive, l-rhamnose fermentation negative (Xyl(+) Rha(-)), and nonhemolytic on blood agar and in the CAMP test with both Staphylococcus aureus (S(-) reaction) and Rhodococcus equi (R(-) reaction). All genes of the prfA cluster of L. seeligeri, located in the prs-ldh region, including the orfA2, orfD, prfA, orfE, plcA, hly, orfK, mpl, actA, dplcB, plcB, orfH, orfX, orfI, orfP, orfB, and orfA genes, were checked by PCR and direct sequencing for evidence of their presence in the atypical isolates. The prs-prfA cluster-ldh region of the L. seeligeri isolates was approximately threefold shorter due to the loss of orfD, prfA, orfE, plcA, hly, orfK, mpl, actA, dplcB, plcB, orfH, orfX, and orfI. The genetic map order of the cluster genes of all the atypical L. seeligeri isolates was prs-orfA2-orfP-orfB-orfA-ldh, which was comparable to the similar region in L. welshimeri, with the exception of the presence of orfA2. DNA sequencing and phylogenetic analysis of 17 housekeeping genes indicated an L. seeligeri genomic background in all seven of the atypical hly-negative L. seeligeri isolates. Thus, the novel biotype of Xyl(+) Rha(-) Hly(-) L. seeligeri strains can only be distinguished from Xyl(+) Rha(-) L. welshimeri strains genotypically, not phenotypically. In contrast, the Rha(+) Xyl(+) biotype of L. welshimeri would not present an identification issue.

Animals↗

PubMed1983

Chromosomal location of the gene encoding phosphoribosylpyrophosphate synthetase in Escherichia coli.

A mutant of Escherichia coli with a partially defective phosphoribosylpyrophosphate synthetase (ribosephosphate pyrophosphokinase) has been characterized genetically. The genetic lesion causing the altered phosphoribosylpyrophosphate synthetase, prs, was mapped at 26 min on the linkage map by conjugation. Transductional analysis of the prs region established the gene order as purB-fadR-dadR-tre-pth-prs-hemA-trp. Two additional mutations were identified in the mutant: one in gsk, the gene encoding guanosine kinase, and one in lon, conferring a mucoid colony morphology. The contribution of each mutation to the phenotype of the mutant has been evaluated.

Chromosome Mapping↗

PubMed1991

prsB is an allele of the Salmonella typhimurium prsA gene: characterization of a mutant phosphoribosylpyrophosphate synthetase.

The Salmonella typhimurium prsB mutation was previously mapped at 45 min on the chromosome, and a prsB strain was reported to produce undetectable levels of phosphoribosylpyrophosphate (PRPP) synthetase activity and very low levels of immunologically cross-reactive protein in vitro (N.K. Pandey and R.L. Switzer, J. Gen. Microbiol, 128:1863-1871, 1982). We have shown by P22-mediated transduction that the prsB gene is actually an allele of prsA, the structural gene for PRPP synthetase, which maps at 35 min. The prsB (renamed prs-100) mutant produces about 20% of the activity and 100% of the cross-reactive material of wild-type strains. prs-100 mutant strains are temperature sensitive, as is the mutant PRPP synthetase in vitro. The prs-100 mutation is a C-to-T transition which results in replacement of Arg-78 in the mature wild-type enzyme by Cys. The mutant PRPP synthetase was purified to greater than 98% purity. It possessed elevated Michaelis constants for both ATP and ribose-5-phosphate, a reduced maximal velocity, and reduced sensitivity to the allosteric inhibitor ADP. The mutant enzyme had altered physical properties and was susceptible to specific cleavage at the Arg-101-to-Ser-102 bond in vivo. It appears that the mutation alters the enzyme's kinetic properties through substantial structural alterations rather than by specific perturbation of substrate binding or catalysis.

Alleles↗

PubMed1996

Phosphoribosyl diphosphate synthetase-independent NAD de novo synthesis in Escherichia coli: a new phenotype of phosphate regulon mutants.

Phosphoribosyl diphosphate-lacking (delta prs) mutant strains of Escherichia coli require NAD, guanosine, uridine, histidine, and tryptophan for growth. NAD is required by phosphoribosyl diphosphate-lacking mutants because of lack of one of the substrates for the quinolinate phosphoribosyltransferase reaction, an enzyme of the NAD de novo pathway. Several NAD-independent mutants of a host from which prs had been deleted were isolated; all of them were shown to have lesions in the pstSCAB-phoU operon, in which mutations lead to derepression of the Pho regulon. In addition NAD-independent growth was dependent on a functional quinolinate phosphoribosyltransferase. The prs suppressor mutations led to the synthesis of a new phosphoryl compound that may act as a precursor for a new NAD biosynthetic pathway. This compound may be synthesized by the product of an unknown phosphate starvation-inducible gene of the Pho regulon because the ability of pst or phoU mutations to suppress the NAD requirement requires PhoB, the transcriptional activator of the Pho regulon.

Escherichia coli↗

PubMed1978

Quantitative evaluation of three commercial blood culture media for growth of anaerobic organisms.

The ability of three different commercial blood culture media--brain heart infusion broth (Pfizer), thiol broth (Difco), and PRS-peptone broth (Becton, Dickinson & Co.)--to support the growth of five different anaerobes is described. Inocula of 100 and 1,000 colony-forming units per ml were used to evaluate potential differences in survival, lag time, growth rate, and doubling times of each anaerobe in each medium. In addition, each medium was evaluated for its ability to neutralize the antibacterial effects of whole blood. The results of this study indicate that the PRS-peptone broth is superior to brain heart infusion and thiol broths. Shorter lag times and accelerated generation times and growth rates were noted for more different anaerobes in the PRS-peptone broth. Neither the size of inoculum nor the addition of normal whole blood appeared to alter the survival or growth characteristics of the anaerobes in any medium. However, the addition of normal whole blood did extend the lag time of each anaerobe by approximately 1 to 2 h in each medium.

Anaerobiosis↗

PubMed2006

Altered gag polyprotein cleavage specificity of feline immunodeficiency virus/human immunodeficiency virus mutant proteases as demonstrated in a cell-based expression system.

We have used feline immunodeficiency virus (FIV) protease (PR) as a mutational system to study the molecular basis of substrate-inhibitor specificity for lentivirus PRs, with a focus on human immunodeficiency virus type 1 (HIV-1) PR. Our previous mutagenesis studies demonstrated that discrete substitutions in the active site of FIV PR with structurally equivalent residues of HIV-1 PR dramatically altered the specificity of the mutant PRs in in vitro analyses. Here, we have expanded these studies to analyze the specificity changes in each mutant FIV PR expressed in the context of the natural Gag-Pol polyprotein ex vivo. Expression mutants were prepared in which 4 to 12 HIV-1-equivalent substitutions were made in FIV PR, and cleavage of each Gag-Pol polyprotein was then assessed in pseudovirions from transduced cells. The findings demonstrated that, as with in vitro analyses, inhibitor specificities of the mutants showed increased HIV-1 PR character when analyzed against the natural substrate. In addition, all of the mutant PRs still processed the FIV polyprotein but the apparent order of processing was altered relative to that observed with wild-type FIV PR. Given the importance of the order in which Gag-Pol is processed, these findings likely explain the failure to produce infectious FIVs bearing these mutations.

Amino Acid Sequence↗

PubMed2003

Structural basis for distinctions between substrate and inhibitor specificities for feline immunodeficiency virus and human immunodeficiency virus proteases.

We used feline immunodeficiency virus (FIV) protease (PR) as a mutational framework to define determinants for the observed substrate and inhibitor specificity distinctions between FIV and human immunodeficiency virus (HIV) PRs. Multiple-substitution mutants were constructed by replacing the residues in and around the active site of FIV PR with the structurally equivalent residues of HIV-1 PR. Mutants included combinations of three critical regions (FIV numbering, with equivalent HIV numbering in superscript): I37(32)V in the active core region; N55(46)M, M56(47)I, and V59(50)I in the flap region; and L97(80)T, I98(81)P, Q99(82)V, P100(83)N, and L101(84)I in the 90s loop region. Significant alterations in specificity were observed, consistent with the involvement of these residues in determining the substrate-inhibitor specificity distinctions between FIV and HIV PRs. Two previously identified residues, I35 and I57 of FIV PR, were intolerant to substitution and yielded inactive PRs. Therefore, we attempted to recover the activity by introducing secondary mutations. The addition of G62(53)F and K63(54)I, located at the top of the flap and outside the active site, compensated for the activity lost in the I57(48)G substitution mutants. An additional two substitutions, D105(88)N and N88(74)T, facilitated recovery of activity in mutants that included the I35(30)D substitution. Determination of K(i) values of potent HIV-1 PR inhibitors against these mutants showed that inhibitor specificity paralleled that of HIV-1 PR. The findings indicate that maintenance of both substrate and inhibitor specificity is a function of interactions between residues both inside and outside the active site. Thus, mutations apparently peripheral to the active site can have a dramatic influence on inhibitor efficacy.

Amino Acid Sequence↗

PubMed2004

Mitogen-activated protein kinase feedback phosphorylation regulates MEK1 complex formation and activation during cellular adhesion.

Cell adhesion and spreading depend on activation of mitogen-activated kinase, which in turn is regulated both by growth factor and integrin signaling. Growth factors, such as epidermal growth factor, are capable of activating Ras and Raf, but integrin signaling is required to couple Raf to MEK and MEK to extracellular signal-regulated protein kinase (ERK). It was previously shown that Rac-p21-activated kinase (PAK) signaling regulated the physical association of MEK1 with ERK2 through phosphorylation sites in the proline-rich sequence (PRS) of MEK1. It was also shown that activation of MEK1 and ERK by integrins depends on PAK phosphorylation of S298 in the PRS. Here we report a novel MEK1-specific regulatory feedback mechanism that provides a means by which activated ERK can terminate continued PAK phosphorylation of MEK1. Activated ERK can phosphorylate T292 in the PRS, and this blocks the ability of PAK to phosphorylate S298 and of Rac-PAK signaling to enhance MEK1-ERK complex formation. Preventing ERK feedback phosphorylation on T292 during cellular adhesion prolonged phosphorylation of S298 by PAK and phosphorylation of S218 and S222, the MEK1 activating sites. We propose that activation of ERK during adhesion creates a feedback system in which ERK phosphorylates MEK1 on T292, and this in turn blocks additional S298 phosphorylation in response to integrin signaling.

Animals↗

PubMed2002

Pushing and pulling in association with low back and shoulder complaints.

AIMS: To examine the association between exposure to pushing/pulling at work and low back and shoulder complaints. METHODS: A cross sectional questionnaire survey was carried out among 434 workers from several companies with mainly pushing/pulling tasks. From the same companies 188 workers without physically demanding tasks served as reference. The questionnaire was used to assess the exposure to pushing/pulling and other physical risk factors for low back and shoulder complaints. Mean scores at company level were used to classify groups into medium and high exposed to pushing/pulling and a reference group. Psychosocial factors at work were also assessed. Several pain related questionnaires were used to assess the 12 month prevalence of low back and shoulder complaints in three dimensions: trouble (ache, pain, discomfort), pain intensity, and disability. Prevalence rate ratios (PRs) were calculated using Cox's proportional hazards regression analysis. RESULTS: The 12 month prevalence of low back complaints was almost equal for all three groups. The prevalence of shoulder complaints increased with an increase in exposure level. Adjusted PRs showed that the high exposed group had an increased risk for low back complaints compared to the reference group. For all dimensions of shoulder complaints a clear tendency towards a dose-response relation was observed. The high exposed group had significant PRs for shoulder complaints, ranging from 2.09 to 6.37. Generally, psychosocial factors had a confounding effect for pain intensity and disability, but not for trouble. CONCLUSIONS: For shoulder complaints a dose-response relation was observed for exposure to pushing/pulling. Low back complaints were less consistently associated with pushing/pulling. Stronger associations were observed for more severe cases of low back and shoulder complaints. It is hypothesised that work related psychosocial factors affect these associations.

Adult↗

PubMed2026

Genetic Basis of Pancreatic Steatosis: A Systematic Review of Comparison between African and Non-African Populations.

This systematic review compared genetic evidence of pancreatic steatosis across African and non-African populations to illuminate ancestry-specific mechanisms and precision-prevention opportunities. Following PRISMA guidelines for reporting, a search was conducted across PubMed, Scopus, Web of Science, and NHGRI-EBI GWAS Catalog for studies spanning 2011 to 31st March 2026. Eligible studies included genome-wide association studies (GWAS), polygenic risk score (PRS), and Mendelian randomization (MR) analyses that reported genetic associations with pancreatic fat phenotypes and had explicit ancestry stratification or comparison. Narrative thematic synthesis was performed due to methodological heterogeneity. Six core genetic studies (N > 120,000 participants) were included. The only multi-ethnic GWAS found a strong protective variant of African ancestry, rs73449607 (near PDX1/PLUTO), which reduced pancreatic fat (β = -0.67, P = 4.50 × 10⁻⁸) and explained 14.3% of the variance in African Americans (versus 5.3% overall). UK Biobank race-stratified PRS analyses confirmed the lowest pancreatic fat fraction in Black participants, with the strongest HbA1c PRS-fat association in this group (ρ = 0.23, P < 0.0001). European-dominant GWAS highlighted risk loci, including FUT2 rs601338 (higher fat and chronic pancreatitis risk, OR 1.26). MR studies demonstrated causal links between genetically predicted intra-pancreatic fat deposition (IPFD) and pancreatic ductal adenocarcinoma (PDAC) (OR 2.46 per SD) but not diabetes. African-ancestry genomes confer substantial protection against pancreatic steatosis, whereas non-African genomes are enriched for risk alleles that amplify the non-alcoholic fatty pancreas disease (NAFPD)-to-PDAC cascade. These ancestry-differentiated mechanisms position NAFPD as a precision medicine target.

Africa↗

PubMed2000

Deficits in progesterone-facilitated sexual behaviors and forebrain estrogen and progestin receptors in obese female Zucker rats.

Obese female Zucker rats (fa/fa) are sterile. Among their reproductive abnormalities is hyporesponsiveness to the stimulatory effects of ovarian steroid hormones on sexual behaviors. This study was designed to test the hypothesis that obese Zucker females are deficient in hypothalamic/preoptic area estrogen receptors (ERs) and/or estradiol-induced progestin receptors (PRs). Ovariectomized (OVX) lean and obese Zucker rats were tested for the display of sexual behaviors following injection of estradiol benzoate (EB, 15 or 100 microg/kg) plus progesterone (P, 2 mg/kg). As expected, obese females showed significantly lower lordosis quotients and lordosis ratings than lean animals after injection of the lower, physiological dose of EB followed by P. In contrast, obese and lean females receiving the higher EB dose, prior to P, showed similar levels of sexual receptivity. Two weeks later, these OVX lean and obese females received injections of vehicle, 15 or 100 microg/kg EB, prior to perfusion and tissue processing for PR immunocytochemistry (ICC). Additional groups of OVX virgin females of both genotypes were perfused and tissue from the preoptic area and hypothalamus was processed for ER alpha ICC. No genotypic differences in the number of cells containing ER alpha-immunoreactivity (-IR) in the medial preoptic area (MPOA), ventromedial hypothalamus (VMH) or arcuate nucleus (ARC) were noted, but obese females had significantly fewer ER alpha-IR cells in the anteroventral periventricular nucleus (AVPV) than lean rats. In both genotypes, the number of PR-IR cells in the AVPV, MPOA and VMH was significantly higher following injection of EB (either dose) as compared to vehicle, demonstrating estradiol induction of PRs. Only in the MPOA was there a significant difference between fat and lean females in estradiol-induced PR-IR. Obese females receiving 15 microg/kg EB had fewer PR-IR cells in the MPOA than comparably-treated lean animals. No such genotypic difference was observed following injection of the vehicle or higher dose (100 microg/kg) of EB. These data are consistent with the hypothesis that deficiencies in ER alpha in the AVPV and/or PRs in the MPOA may contribute to obese Zucker females' poor responsiveness to ovarian steroid hormones.

Animals↗

PubMed2002

Postradiation high-grade myofibroblastic sarcoma of the prostate -- a rare entity of prostatic tumors -- responding to liposomal Doxorubicin.

BACKGROUND: Prostatic postradiation sarcoma (PRS) is a very rare malignant disease with a dismal prognosis. Aggressive surgical resection is the most widely used therapy for PRS. Chemotherapy so far has been unsatisfactory, with doxorubicin being the only drug with established activity. Liposomal doxorubicin has been shown to have comparable activity and a more favorable toxicity profile compared with unpegylated doxorubicin. CASE REPORT: A 78-year-old man presented with high-grade myofibroblastic sarcoma 13 years after curatively intended pion irradiation of the prostate with 30 Gy. He was treated with liposomal doxorubicin 40 mg/m(2) every 4-6 weeks up to now with a total dose of 800 mg. Partial remission has been achieved after 17 months of treatment with liposomal doxorubicin. Toxicity is minimal with palmoplantar erythrodysesthesia WHO grade 1, resolving completely after extending treatment intervals to 6 weeks. RESULT: Liposomal doxorubicin led to a sustained tumor stabilization over 17 months in a patient with prostatic postradiation high-grade sarcoma. Postradiation sarcoma (PRS) usually has a dismal prognosis and only very limited therapeutic possibilities. As in sarcomas of different origin, anthracyclines including liposomal doxorubicin seem to have potential antitumor activity in postradiation sarcoma of the prostate.

Adenocarcinoma↗

PubMed1993

A community survey of neurological disorders in Saudi Arabia: the Thugbah study.

We report the findings of a total population survey of Thugbah community in the Eastern Province of Saudi Arabia (SA) to determine its point prevalence of neurological diseases. During this two-phase door-to-door study, all Saudi nationals living in Thugbah were first screened by trained interviewers using a pretested questionnaire (sensitivity 98%, specificity 89%) administered at a face-to-face interview. Individuals with abnormal responses were then evaluated by a neurologist using specific guidelines and defined diagnostic criteria to document neurological disease. The questionnaire was readministered blind by a neurologist to all those with abnormal responses and a 1-in-20 random sample of those without abnormal responses, respectively. The family members of an individual with an abnormal response were also screened to improve accuracy. A total of 23,227 Saudis (98% of the eligible subjects) were screened and those residing in Thugbah on the reference date (22,630) were used to calculate the point prevalence rates. Forty-two percent of those screened were in the first decade of life and only 1.5% were more than 60 years old. There were marginally more females (50.2%) than males (49.8%). Consanguineous marriages especially between first cousins were present in 54.6%. The demographic characteristics of Thugbah community were similar to those in other parts of SA. The overall crude prevalence ratio (PR) for all forms of neurological disease was 131/1,000 population. All subsequent PRs are per 1,000 population. Headache syndromes were the most prevalent disorder (PR 20.7). The PR for all seizure disorders was 7.60, and the epilepsies (6.54) were more frequent than febrile convulsions (0.84). Mental retardation, cerebral palsy syndrome, and microcephaly were common pediatric problems with PRs of 6.27, 5.30 and 1.99, respectively. Stroke, Parkinson's disease, and Alzheimer's disease were uncommon with respective PRs of 1.8, 0.27 and 0.22. Central nervous system (CNS) malformations (0.49) such as hydrocephalus and meningomyelocele were more prevalent than spinal muscular atrophy (0.13), congenital brachial palsy (0.13) and narcolepsy (0.04). Multiple sclerosis was rare (0.04). Osteoarthritis and low back pain syndromes were the main non-neurological conditions seen. The major medical diseases that may be neurologically relevant were diabetes mellitus, hypertension, and connective tissue disorders.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMed1998

Familial HDL deficiency characterized by hypercatabolism of mature apoA-I but not proapoA-I.

We have previously described patients with familial high density lipoprotein (HDL) deficiency (FHD) having a marked reduction in the plasma concentration of HDL cholesterol and apolipoprotein (apo) A-I but lacking clinical manifestations of Tangier disease or evidence of other known causes of HDL deficiency. To determine whether FHD in these individuals was associated with impaired HDL production or increased HDL catabolism, we investigated the kinetics of plasma apoA-I and apoA-II in two related FHD patients (plasma apoA-I, 17 and 37 mg/dL) and four control subjects (apoA-I, 126+/-18 mg/dL, mean+/-SD) by using a primed constant infusion of deuterated leucine. Kinetic analysis of plasma apolipoprotein enrichment curves demonstrated that mature plasma apoA-I production rates (PRs) were similar in patients and control subjects (7.9 and 9.1 versus 10.5+/-1.7 mg x kg[-1] x d[-1]). Residence times (RTs) of mature apoA-I were, however, significantly less in FHD patients (0.79 and 1.66 days) compared with controls (5.32+/-1.05 days). Essentially normal levels of plasma proapoA-I (the precursor protein of apoA-I) in FHD patients were associated with normal plasma proapoA-I PRs (7.8 and 10.4 versus 10.9+/-2.6 mg x kg[-1] x d[-1]) and proapoA-I RTs (0.18 and 0.15 versus 0.16+/-0.03 day). The RTs of apoA-II were, however, less in patients (3.17 and 2.92 days) than control subjects (7.24+/-0.71 days), whereas the PRs of apoA-II were similar (1.8 and 1.9 versus 1.7+/-0.2 mg x kg[-1] x d[-1]). Increased plasma catabolism of apoA-II in FHD patients was associated with the presence in plasma of abnormal apoA-II-HDL (without apoA-I). These results demonstrate that FHD in our patients is characterized, like Tangier disease, by hypercatabolism of mature apoA-I and apoA-II, but unlike Tangier disease, by essentially normal plasma catabolism and concentration of proapoA-I.

Apolipoprotein A-I↗