Biomedical subjects

H Rennert

Publications and source records attributed to H Rennert.

At least 19 recordsLinked to original sources

PubMed2001

Heteroduplex formation in SMN gene dosage analysis.

Most spinal muscular atrophy patients lack both copies of SMN1 exon 7 and most carriers have only one copy of SMN1 exon 7. We investigated the effect of SMN1/SMN2 heteroduplex formation on SMN gene dosage analysis, which is an assay to determine copy number of SMN1 exon 7 that utilizes multiplex quantitative polymerase chain reaction (PCR) with DraI digestion to differentiate SMN1 from SMN2. Heteroduplex formation in PCR is a well-described phenomenon. In addition to demonstrating the presence of heteroduplexes by sequence analysis of purified SMN1 bands, we compared the SMN1 signals in various genotype groups (total n = 260) to those in a group lacking SMN2 (n = 13), and we estimated the relative amounts of SMN1/SMN2 heteroduplexes. The SMN1 signal increased as SMN2 copy number increased despite a constant SMN1 copy number, although not all pairwise comparisons showed a statistically significant difference in the SMN1 signal. In conclusion, SMN1/SMN2 heteroduplexes form in SMN gene dosage analysis, falsely increasing the SMN1 signal. External controls for SMN gene dosage analysis should be chosen carefully with regard to SMN2 copy number. The effect of heteroduplex formation should be considered when performing quantitative multiplex PCR.

Cyclic AMP Response Element-Binding Protein↗

PubMed2001

Detection of clonal T-cell receptor gamma gene rearrangements using fluorescent-based PCR and automated high-resolution capillary electrophoresis.

BACKGROUND: Analysis of T-cell receptor gamma (TCR gamma) gene rearrangements by PCR is a powerful tool for detecting clonal T-cell populations for the diagnosis of lymphoid neoplasms. We report a method for TCR gamma PCR analysis using capillary electrophoresis (CE). METHODS AND RESULTS: To define the threshold for identification of a predominant monoclonal population within a polyclonal background, we developed a novel objective parameter of the peak height ratio (Rn) of the peak of interest and the average of the two immediate flanking peaks. After evaluation of monoclonal, reactive, and normal T-cell populations, an Rn of 3.0 or greater was determined to be consistent with a monoclonal population, whereas an Rn between 1.9 and 3.0 was considered an intermediate range. This CE method was compared with the standard denaturing gradient gel electrophoresis (DGGE) method using previously evaluated clinical specimens. Eleven of 12 clinical specimens (92%) with a definitive diagnosis of T-cell lymphoma were monoclonal by CE, with 100% concordance with the DGGE method. Of nine specimens morphologically suspicious for T-cell lymphoma, five specimens were positive by CE analysis compared with four specimens by DGGE. In addition, 14 specimens for staging from patients with known T-cell lymphoma were studied using both the CE and DGGE methods, with a concordance of 86%. CONCLUSION: CE is a powerful and efficient method for analysis of clonality by TCR gamma PCR.

Biopsy↗

PubMed1999

Duplications and de novo deletions of the SMNt gene demonstrated by fluorescence-based carrier testing for spinal muscular atrophy.

Approximately 95% of individuals with spinal muscular atrophy (SMA) lack both copies of the SMNt gene at 5q13. The presence of a nearly identical centromeric homolog of the SMNt gene, SMNc, necessitates a quantitative polymerase chain reaction approach to direct carrier testing. Adapting a radioactivity-based method described previously, multiplex polymerase chain reaction was performed using fluorescently labeled primers followed by analysis on an ABI 373a DNA sequencer. The SMNt copy number was calculated from ratios of peak areas using both internal and genomic standards. Samples from 60 presumed carriers (50 parents of affected individuals and 10 relatives implicated by linkage analysis) and 40 normal control individuals were tested. Normalized results (to the mean of five or more control samples harboring two copies of the SMNt gene) were consistently within the ranges of 0.4 to 0.6 for carriers (one copy) and 0.8 to 1.2 for normal controls (two copies), without overlap. Combining linkage analyses with direct carrier test results demonstrated de novo deletions associated with crossovers, unaffected individuals carrying two SMNt gene copies on one chromosome and zero SMNt gene copies on the other chromosome, and unaffected individuals with three copies of the SMNt gene. This report demonstrates that fluorescence-based carrier testing for SMA is accurate, reproducible, and useful for genetic risk assessment, and that carrier testing may need to be combined with linkage analysis in certain circumstances.

Centromere↗

PubMed1999

A novel, non-nested reverse-transcriptase polymerase chain reaction (RT-PCR) test for the detection of the t(15;17) translocation: a comparative study of RT-PCR cytogenetics, and fluorescence In situ hybridization.

BACKGROUND: The development of a rapid and simple reverse-transcription polymerase chain reaction (RT-PCR) assay is described that identifies the promyelocytic leukemia- retinoic acid receptor alpha (PML-RARa) hybrid messenger RNA (mRNA), a characteristic feature of acute promyelocytic leukemia (APL). METHODS AND RESULTS: Randomly primed complementary (cDNA) is synthesized from leukocyte RNA and amplified in the presence of Taq Gold in 2 separate reaction tubes containing primer pairs specific for intron 3 (bcr 3, long [L] form mRNA transcript) and intron 6 (bcr 1, short [S] form)/exon 6 (bcr 2, variant [V] form) breakpoints in PML, respectively. The different sized products generated from each RNA transcript (S, L, or V forms) are readily and unambiguously distinguishable after agarose gel electrophoresis without the need for either nested PCR or hybridization. The sensitivity of the assay is 1 in 10,000 to 1 in 100,000. The separate amplification of a b2-microglobulin transcript controls for adequate RNA and cDNA preparation. The newly developed assay was used clinically for the evaluation of 78 patients with APL. It was rapid and more sensitive than cytogenetic karyotyping, both for the diagnosis of APL and the assessment of minimal residual disease (MRD) after therapy. RT-PCR detected PML-RARa mRNA in all cases positive for the t(15;17) translocation by cytogenetics. However, as many as 50% and 80% of the diagnostic specimens and the specimens for MRD assessment, respectively, that were positive by RT-PCR were negative by cytogenetics. The ratio of cases with L-form to S-form PML-RARa fusion transcript was 2:1, whereas 3 cases (10%) had fusion sites in exon 6 of the PML gene (V forms). In addition, approximately 50% of the patients were diagnosed morphologically with microgranular M3V-type leukemia, but no significant correlation with PML breakpoints was found. CONCLUSION: The current assay is rapid, sensitive, and specific without using nested PCR or hybridization.

Biomarkers, Tumor↗

PubMed1999

Acute mastoiditis in children: is surgical treatment necessary?

Acute mastoiditis in children remains an otological problem. Although the widespread use of antibiotics has reduced the need for surgical intervention, surgery is frequently used in the treatment of acute mastoiditis and its complications. The charts of 44 patients hospitalized with signs of acute mastoiditis were reviewed. In 43.2 per cent of all patients, acute mastoiditis was the presenting sign of acute middle-ear infection. Post-auricular erythema and protrusion of the auricle were the most frequent signs at presentation. All four signs (post-auricular erythema, oedema, tenderness, and protrusion of the auricle) were present in 40.9 per cent of patients. No bacterial pathogen was isolated in 45.5 per cent of ear cultures. Complicated acute mastoiditis was diagnosed in 13.7 per cent of the patients. Eighty-seven per cent of patients responded well to intravenous antibiotics and myringotomy, and in 11.4 per cent mastoidectomy or abscess drainage were performed. We conclude that nearly all patients with uncomplicated mastoiditis recover following intravenous antibiotics and myringotomy. Mastoidectomy should be performed in selected cases, such as cases of complicated acute mastoiditis.

Acute Disease↗

PubMed1999

Evidence for early hematopoietic progenitor cell involvement in acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) represents a subtype of acute myeloid leukemia with characteristic morphologic, molecular, and immunophenotypic features. Previous immunophenotypic analyses have shown that leukemic cells in APL typically express the myeloid markers CD33 and CD13 but lack expression of the early hematopoietic progenitor cell antigens CD34 and HLA-DR. We analyzed selected immunophenotypic features of APL by flow cytometry and showed that 7 (41%) of 17 cases contained significant subsets of CD34+ leukemic cells: CD34+ myeloid cells predominated in 2 APL cases. By using a fluorescence-activated cell sorter-fluorescence in situ hybridization approach, we confirmed that the CD34+ cells harbored the t(15;17) translocation characteristic of APL. By using the same experimental approach, CD34+ populations were stratified into primitive CD34+ CD38- and committed CD34+ CD38+ progenitor cell subpopulations; cells in both subsets contained the t(15;17) translocation. The knowledge that APL may be partly or largely CD34+ is important for proper diagnosis. Furthermore, identification of the t(15;17) translocation in CD34+ CD38- blasts indicates that, in at least some cases, the leukemogenic mutation in APL occurs within primitive hematopoietic progenitor cells.

Antigens, CD34↗

PubMed1998

Long-term (10-year) outcome in patients with unstable angina pectoris treated by coronary balloon angioplasty.

OBJECTIVES: We sought to examine completed 10-year survival and event-free survival in patients with stable and unstable angina pectoris treated by coronary balloon angioplasty. BACKGROUND: Patients with unstable angina are at increased risk for recurrent acute coronary events. METHODS: The study included 208 consecutive patients (133 with stable and 75 with unstable angina pectoris) undergoing angioplasty from 1984 to 1986. The balloon crossed the lesion in 185 patients (121 with stable and 64 with unstable angina pectoris). Angioplasty was performed in patients with unstable angina pectoris 12+/-15 days (median 8) after symptom onset. Patients with unstable angina pectoris were classified retrospectively into Braunwald class I (n=3), class II (n=20), class III (n=28), class B (n=52) and class C (n=12). Follow-up data were obtained from hospital charts, telephone interview and official death certificates where applicable. The study had >80% power to detect a clinically significant 20% difference in survival and a 20% difference in event-free survival between the stable and unstable patient groups. RESULTS: Despite similar baseline characteristics, early (40-day) mortality was slightly higher in patients with unstable angina (4.7% [3 of 64 patients] vs. 0.8% [1 of 121 patients], p=NS). Long-term outcome was not different, because survival curves were parallel thereafter (10-year survival was 83% for those with stable and 77% for those with unstable angina, p=NS). Survival free of myocardial infarction or coronary artery bypass graft surgery at 10 years was 53% in patients with stable and 47% in patients with unstable angina (p=NS), and survival free of infarction, bypass surgery or repeat angioplasty was 32% for both groups at 10 years. In patients with Braunwald class III unstable angina, 10-year survival was 80%, as compared with 85% in other patients with unstable angina, due to the early hazard (p=NS). Survival and event-free survival were similar in patients who had had a recent myocardial infarction (Braunwald class C) and in patients with acute electrocardiographic changes. Repeat hospital admissions were not more frequent in patients with unstable angina (3.1+/-3.5 vs. 3.0+/-2.6, p=NS). CONCLUSIONS: Ten-year survival and event-free survival were similar in patients with stable and unstable angina pectoris treated by coronary balloon angioplasty, with no evidence of an increased rate of recurrent cardiovascular events in the unstable group.

Aged↗

PubMed1998

Novel bcl-2 breakpoints in patients with follicular lymphoma.

Using genomic DNA from patients with follicular lymphoma, we performed polymerase chain reaction (PCR) amplifications to detect t(14;18) translocations. Unexpectedly large products of approximately 1 kilobase (kb) were detected by gel electrophoresis in 2 of 50 positive cases. In these 2 cases, sequence analyses showed novel breakpoints in the 3' untranslated region of bcl-2, approximately 800 bp downstream of the major breakpoint region (mbr). The breakpoints in IgH occurred in JH4 in one patient and JH5 in the other. Sequences just upstream of the new bcl-2 breakpoints suggest a mechanism of translocation that may include minisatellite core-mediated recombination. In one of our two patients with novel bcl-2 breakpoints, the approximately 1 kb product obtained using conventional mbr primers was detectable only when a nested PCR was performed. These findings have important implications for diagnosis and minimal residual disease detection in t(14;18)-positive lymphomas.

Adult↗

PubMed1997

Arthrogryposis due to infantile neuronal degeneration associated with deletion of the SMNT gene.

To determine whether SMNT deletion may be associated with arthrogryposis, we tested DNA extracted from paraffin blocks for deletion of SMNT (exons 7 and 8). Analysis of the DNA showed an SMNT deletion in two of four infants with neurogenic arthrogryposis. In addition to loss of anterior horn cells, patients with SMNT deletion had degeneration of central sensory neurons in Clarke's column and the thalamus. Although one of the patients with no deletion also had cortical pathology, clinical and pathologic characteristics of the two patients without deletion were otherwise similar to the two patients with deletion. Arthrogryposis and degeneration of sensory neurons may be associated with deletion of SMNT.

Anterior Horn Cells↗

PubMed1996

Normalized Southern Hybridization to Enhance Testing for Charcot-Marie-Tooth Disease, Type 1A.

Background: Charcot-Marie-Tooth disease, type 1A (CMT,1A) is a common autosomal dominant neuromuscular disorder, which affects both motor and sensory function and is characterized usually by duplication of a region on chromosome 17 through unequal crossover. As a result, affected patients carry three copies of this region. Individuals inheriting the other deleted chromosome involved in the crossover have one copy of the region and manifest herditary neuropathy with susceptibility to pressure palsies (HNPP). One diagnostic approach to CMT,1A exploits Southern blot hybridization and the relative intensity for three polymorphic MspI restriction fragment lenth polymorphism bands within the duplicated area to judge whether patients have two or three copies of this region using a probe such as VAW409R3A. This is usually straightfoward and works well for the majority of samples that display polymorphisms. However, it is difficult to judge dosage for this region in patients who do not demonstrate polymorphic bands. Methods and Results: An assay has been developed in which a simultaneously hybridized probe (pH15), which detects a nonpolymorphic band on chromosome 22 generated by the same restriction enzyme used to digest genomic DNA, is used to normalize the signal from the CMT,1A probe after phosphorimager analysis. Normalized ratios for VAW409R3A-hybridizing Southern bands fell within discrete ranges for patients with three copies (2.72-3.69), two copies (1.60-2.40) and one copy (0.75-1.30) of this region in over 45 patient and control samples studied. Conclusions: This assay appears to provide a reliable and consistent method of analysis.

Journal Article↗

PubMed1996

A prospective study evaluating the usefulness of continuous supplemental oxygen in various endoscopic procedures.

The influence of oxygen supplementation on the prevalence of hypoxemia during endoscopic procedures was studied in 289 patients in a prospective clinical trial. The frequency of oxygen desaturation was found to decrease significantly in patients receiving oxygen via nasal prongs, compared to patients not receiving oxygen supplementation. The effect was demonstrated especially in patients who underwent an additional procedure during their endoscopic examinations. Similar effects were found in patients undergoing gastroscopy, colonoscopy, and endoscopic retrograde cholangiopancreatography. In view of the risks related to hypoxemia and its high prevalence in endoscopic procedures (28-50%) we recommend that a routine oxygen supplementation policy be considered in every patient undergoing endoscopy, especially when additional procedures are to be performed.

Cholangiopancreatography, Endoscopic Retrograde↗

PubMed1994

The structure of the human sterol carrier protein X/sterol carrier protein 2 gene (SCP2).

Sterol carrier protein X (SCPx) is a 58-kDa protein that is localized to peroxisomes. The amino acid sequence of the protein suggests that SCPx may function as a thiolase. The gene encoding SCPx also codes for a 15.3-kDa protein called sterol carrier protein 2 (SCP2). Here we report the structure of this gene (SCP2), which spans approximately 80 kb and consists of 16 exons and 15 introns. Multiple transcription start sites were identified. The 5' flanking region has characteristics of other peroxisomal protein promoters, which include the absence of a TATA box and a G+C-enriched region containing several reverse GC boxes.

Acetyl-CoA C-Acetyltransferase↗

PubMed1993

Sterol carrier protein 2: a role in steroid hormone synthesis?

The intracellular movement of cholesterol is an important regulated step in the process of steroidogenesis. However, the molecular mechanisms by which cholesterol is translocated to key organelles, including the mitochondria, remains poorly understood. Lipid transfer proteins may have an important function in this process. One candidate lipid transfer protein is sterol carrier protein 2 (SCP2). This 13.2 kDa protein enhances the movement of cholesterol between vesicles and isolated mitochondria. It also stimulates mitochondrial pregnenolone synthesis. When introduced into intact cells, anti-SCP2 antibodies reduce steroid secretion. Moreover, expression of SCP2 in COS cells engineered to produce progestins increases steroid formation. SCP2 is abundant in steroidogenic glands and the pattern of SCP2 gene expression is consistent with a role for the protein in hormone synthesis: SCP2 transcripts are more prominent in the most steroidogenic compartments of the ovary and tropic hormones that stimulate steroidogenesis increase SCP2 gene expression. Other evidence that suggests that SCP2 plays important roles in cellular function includes a remarkable conservation of primary structure across species. The mechanisms by which SCP2 promotes intracellular sterol movement have not been elucidated. The protein appears to bind sterols and is synthesized with a 20 amino acid N-terminal "pro-" sequence that may serve to target SCP2 to mitochondria. In addition, the C-terminus of SCP2 contains a peroxisome-targeting sequence. SCP2 is derived from a large gene that encodes transcripts that are translated into larger proteins of 30 and 58 kDa. The 58 kDa protein, which has some structural homologies with thiolases, seems to be specifically targeted to peroxisomes whereas SCP2 has a broader subcellular distribution. The significance of the peroxisome association of SCP2 and steroidogenesis has not been disclosed. However, diseases of peroxisome function, including adrenoleukodystrophy and Zellweger syndrome, have notable deficits in steroid and bile acid metabolism, thus linking peroxisomes and steroidogenesis. SCP2 is deficient in fibroblasts of patients with these diseases.

Animals↗

PubMed1991

Regulated expression of sterol carrier protein 2 in the ovary: a key role for cyclic AMP.

Sterol carrier protein 2 (SCP2) is believed to play an important role in the intracellular movement of cholesterol in steroidogenic cells. We examined the distribution of SCP2 gene expression in the rat ovary and the role of gonadotropins and cyclic AMP in the regulation of SCP2 mRNA levels. In situ hybridization revealed that the most steroidogenically active ovarian compartments (e.g., corpora lutea and theca cells) contain significant amounts of SCP2 mRNA whereas granulosa cells have modest levels. Gonadotropins, which promote follicular growth and luteinization, increased the ovarian content of SCP2 mRNA as assessed by Northern blotting along with increases in cytochrome P450scc mRNA. Using steroidogenic transformed rat granulosa cells (Grs-21), a cyclic AMP analogue (8-Br-cAMP) was found to increase SCP2 mRNA and protein levels within 24 h of treatment. P450scc mRNA was also induced whereas actin mRNA levels were not affected. The 8-Br-cAMP stimulation of SCP2 mRNA accumulation was completely inhibited by actinomycin D and cycloheximide. The cyclic AMP analogue also increased SCP2 mRNA levels in a non-steroid hormone producing transformed rat granulosa cell line Gs-8. We conclude that SCP2 gene expression in the ovary is correlated with the state of differentiation of granulosa cells. Gonadotropic hormones which stimulate luteinization of the cells increase SCP2 gene expression. These actions of gonadotropins appear to be mediated at least in part by cyclic AMP through a mechanism requiring ongoing RNA and protein synthesis. However, SCP2 gene expression is not obligatorily coupled to steroidogenic activity, as cyclic AMP analogues can increase SCP2 mRNA in a line of transformed ovarian granulosa cells incapable of synthesizing hormones.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1991

Cloning and expression of a cDNA encoding human sterol carrier protein 2.

We report the cloning and expression of a cDNA encoding human sterol carrier protein 2 (SCP2). The 1.3-kilobase (kb) cDNA contains an open reading frame which encompasses a 143-amino acid sequence which is 89% identical to the rat SCP2 amino acid sequence. The deduced amino acid sequence of the polypeptide reveals a 20-residue amino-terminal leader sequence in front of the mature polypeptide, which contains a carboxyl-terminal tripeptide (Ala-Lys-Leu) related to the peroxisome targeting sequence. The expressed cDNA in COS-7 cells yields a 15.3-kDa polypeptide and increased amounts of a 13.2-kDa polypeptide, both reacting with a specific rabbit antiserum to rat liver SCP2. The cDNA insert hybridizes with 3.2- and 1.8-kb mRNA species in human liver poly(A)+ RNA. In human fibroblasts and placenta the 1.8-kb mRNA was most abundant. Southern blot analysis suggests either that there are multiple copies of the SCP2 gene in the human genome or that the SCP2 gene is very large. Coexpression of the SCP2 cDNA with expression vectors for cholesterol side-chain cleavage enzyme and adrenodoxin resulted in a 2.5-fold enhancement of progestin synthesis over that obtained with expression of the steroidogenic enzyme system alone. These findings are concordant with the notion that SCP2 plays a role in regulating steroidogenesis, among other possible functions.

Amino Acid Sequence↗

PubMed1990

A cDNA encoding a rat mitochondrial cytochrome P450 catalyzing both the 26-hydroxylation of cholesterol and 25-hydroxylation of vitamin D3: gonadotropic regulation of the cognate mRNA in ovaries.

A cDNA expression library prepared from rat liver RNA was screened with a polyclonal antibody specific for mitochondrial vitamin D3 25-hydroxylase and a cDNA for rabbit liver mitochondrial cytochrome P450c26 (CYP 26), yielding cDNA clones with identical sequences. The deduced amino acid sequence derived from a 1.9-kb full-length cDNA was 73% identical to that of rabbit cytochrome P450c26. A monoclonal antibody was used to demonstrate that the product of the 1.9-kb cDNA clone was targeted to the mitochondrial compartment when expressed in COS cells. Mitochondrial membranes containing the expressed protein showed both vitamin D3 25-hydroxylase and cholesterol 26-hydroxylase activities when reconstituted with ferredoxin reductase and ferredoxin, demonstrating that the same P450, designated as P450c26/25, can catalyze both reactions. Northern blot analysis revealed that the P450c26/25 cDNA hybridizes with a 2.4-kb RNA from rat liver and unstimulated ovaries. Treatment of rats with pregnant mare's serum gonadotropin resulted in a fivefold increase in the 2.4-kb mRNA as well as the appearance of a 2.1-kb mRNA species in the ovaries. Our findings document the presence of a regulated bifunctional mitochondrial cytochrome P450 capable of catalyzing the 25-hydroxylation of vitamin D3 and the 26-hydroxylation of cholesterol.

Amino Acid Sequence↗

PubMed1990

Generation of regulatory oxysterols: 26-hydroxylation of cholesterol by ovarian mitochondria.

De novo synthesis of cholesterol and low-density lipoprotein (LDL) receptor levels are suppressed in the presence of cholesterol. Recent evidence suggests that a cholesterol metabolite (possibly a hydroxysterol), not cholesterol per se, is the effector that inhibits transcription of genes encoding enzymes involved in sterol synthesis and LDL receptors. We found that 26-hydroxycholesterol inhibits human ovarian cell sterol synthesis, and that luteinized human granulosa cells contain 26-hydroxylase messenger RNA (mRNA). We proceeded to characterize the enzyme generating 26-hydroxycholesterol in the rat ovary. Mitochondria derived from ovaries of PMSG-human CG (hCG) primed immature rats (day 3 post-hCG) metabolized [3H] cholesterol into [3H]26-hydroxycholesterol in the presence of nicotinamide adenine dinucleotide phosphate and aminoglutethimide (100 micrograms/ml), added to inhibit metabolism of sterols by the cholesterol side-chain cleavage system. The identity of the product was confirmed by chromatography in several systems; recrystallization to constant specific activity and mass spectrometry. Negligible 26-hydroxylase activity was detected in other ovarian subcellular fractions. 26-Hydroxycholesterol formation progressed at a linear rate for up to 40 min and was linearly related to mitochondrial protein added to the incubation mixture. 26-Hydroxylase was markedly stimulated (5-fold) by calcium (0.2 mM). Maximal rates of 26-hydroxycholesterol formation observed were 1 pmol/min.mg protein. This activity is substantially lower than cholesterol side-chain cleavage measured in the absence of aminoglutethimide. Ketoconazole (1-100 microM) inhibited 26-hydroxylase in a dose-dependent manner. Pregnenolone (1-1000 microM) and progesterone (1-100 microM) inhibited 26-hydroxylase in a dose-dependent manner, with appreciable inhibitory effects in the 1-10 microM range. We suggest that 26-hydroxycholesterol is an intracrine regulator that controls cellular sterol metabolism. Formation of 26-hydroxcholesterol in ovarian cells may be regulated by steroidogenic activity in such a way as to ensure availability of steroid hormone precursors. When steroidogenesis is active, 26-hydroxylase is inhibited by products of the side-chain cleavage system, allowing increased de novo sterol synthesis and LDL uptake. With reduced steroidogenic activity and less demand for cholesterol, 26-hydroxylase is not blocked, permitting formation of 26-hydroxycholesterol with attendant reduction in sterol synthesis and LDL receptor gene expression.

Aminoglutethimide↗

PubMed1990

[Height vertigo, fear of heights, acrophobia].

Height vertigo (acrophobia) is a very frequent phenomenon being of interest for its physiological and psychological background, though usually only of limited significance in neuropsychiatry and otology. The different aspects as to its nature and origin are discussed. If acrophobia has developed into a conditioned reaction of avoidance with pressure of suffering, or acrophobia in persons, who have to work at heights, behavior therapeutic measures with systematic desensibilisation, starting from an imaginative training, are indicated.

Altitude↗