Suzanna Dana - Academia.edu (original) (raw)

Papers by Suzanna Dana

CRC Press eBooks, Oct 31, 2006

Journal of Forensic Sciences, 1992

This paper examines the proposed association of bilateral asymmetry of the jugular foramen as an ... more This paper examines the proposed association of bilateral asymmetry of the jugular foramen as an indicator of handedness observable from cranial morphology. The jugular foramina of 54 subjects were observed for size asymmetry during routine autopsy procedures. Hand preference data were collected on each subject from family members. Of the 54 subjects, 47 were documented as being right-handed and 7 as being left-handed. These values approximate the average percentage of right-handed versus left-handed individuals from larger populations. Jugular foramen asymmetry was qualitatively identified for 36 subjects (66.7%) and was judged equivocal for the other 18 (33.3%). Of the 36 subjects exhibiting asymmetry, 28 (77.7%) showed positive correlation between the asymmetry direction and handedness. This moderate level of congruence, coupled with the result that 4 of the 7 left-handers exhibited dominant right-side foramina, casts doubt on the reliable use of jugular foramen asymmetry for estimating handedness.

Journal of Forensic Sciences, Nov 1, 1987

Three deaths as a result of inhalation of carbon monoxide from the exhaust fumes of automobiles a... more Three deaths as a result of inhalation of carbon monoxide from the exhaust fumes of automobiles are reported. All deaths occurred outside and not in a structure. The individuals were white males, ages 24 to 26 years. Blood carboxyhemoglobin concentrations ranged from 58 (in a decomposing body) to 81%. The three cases illustrate the fact that even in the outdoors death from carbon monoxide inhalation can occur if an individual is in close proximity to a rich source of carbon monoxide.

CRC Press eBooks, Oct 31, 2006

Journal of Biological Chemistry, Oct 1, 1974

Studies in cultured fibroblasts from patients with the clinical syndrome of homozygous familial h... more Studies in cultured fibroblasts from patients with the clinical syndrome of homozygous familial hypercholesterolemia have disclosed two different mutations affecting the functions of the low density lipo- protein receptor. One of these mutations, described previ- ously, results in a functionless receptor that does not bind low density lipoproteins. In the cells of six patients who appear to be homozygous for this mutant allele, i.e., receptor-negative homozygotes, low density lipoproteins neither suppress hydroxymethylglutaryl-CoA reductase (NADPH) (mevalonate:NADP+ oxidoreductase (CoA-acy- lating) EC 1.1.1.34) activity nor stimulate cellular choles- terol esterification, even when examined in the presence of concentrations of lipoprotein 500 times higher than those required to produce maximal biologic effects in normal cells. The second type of mutation, described herein, results in a receptor that has a reduced but not absent function. Fibroblasts from three subjects who possess this mutation, i.e., receptor-defective homozygotes, show partial suppression of the same enzyme activity and a detectable increase in cholesterol esterification capacity in the presence of high levels of low density lipoproteins. It was calculated that their degree of function could be achieved if they possessed only about 10% of the normal binding of low density lipoprotein. This level of binding was too low to be reliably detected by the '5I-labeled low density lipoprotein binding assay. The finding of a second class of mutant cells in which a defect in low density lipoprotein binding is associated with simultaneous de- fects in both suppression of hydroxymethylglutaryl-CoA reductase activity and stimulation of cholesterol ester formation provides further evidence for the coordinate control of these two processes by the low density lipo- protein receptor.

CRC Press eBooks, Oct 31, 2006

... Los traductores, todos ellos profesores de Medicina Legal y Toxicología de la Universidad de ... more ... Los traductores, todos ellos profesores de Medicina Legal y Toxicología de la Universidad de Santiago de Compostela, han realizado una encomiable tarea en la que han sabido aunar con rigor los aspectos idiomático y técnico-científico. ...

Introduction to Medicolegal Casework Five Categories of Medicolegal Cases Cause, Mechanism, and M... more Introduction to Medicolegal Casework Five Categories of Medicolegal Cases Cause, Mechanism, and Manner of Death The forensic autopsy versus an external examination Three steps of medicolegal death investigation Handling of bodies at the scene Handling of bodies from a hospital Handling of bodies at the morgue Identification of bodies The Autopsy Report Heading of report External Examination Evidence of Injury Internal Examination Microscopic Examination Toxicology Findings Opinion Physical Evidence Types of physical evidence Preservation of physical evidence on the body Recovery of physical evidence Procedures for collection of biological evidence Procedures for collection of nonbiological physical evidence DNA analysis Time of Death- Decomposition Factors used in estimating time of death Decomposition Identification of Remains Intact, nondecomposed human remains Decomposed or charred, nonskeletonized human remains Skeletonized human remains Natural Disease Causes of Sudden Natural Death in Adults Cardiovascular disease Central nervous system disorders Respiratory system disorders Gastrointestinal tract disorders Hepatic disorders Adrenal disorders Splenic disorders Miscellaneous causes of sudden death in adults Causes of Sudden Natural Death in Infants and Young Children Sudden infant death syndrome (SIDS) Other disorders associated with sudden death in infants and children Blunt Force Injury Definition Abrasions Contusions Lacerations Combination injuries Blunt force injury to the chest (thorax) Blunt force injury to the abdomen Blunt force injury to the genitalia (internal and external) Skeletal fractures due to blunt force trauma Extremity injuries due to blunt force trauma Head injuries caused by blunt force trauma Neck injuries caused by blunt force trauma Wounds Produced by Pointed, Sharp-Edged, and Chopping Implements Stab wounds Incised wounds Chop wounds Gunshot Wounds Types of small arms Firearms Caliber Ammunition Ballistic comparison of bullets Theory of wounding Gunshot wounds Centerfire Rifle Wounds Microscopic examination of gunshot wounds The effects of intermediary targets Ricochet bullets Shotguns Wounds of bone Caliber determination by size of entrance wounds Perforation of skin and bone Gunshot residue Miscellaneous Suicide General firearm terminology Asphyxia Suffocation Strangulation Chemical asphyxiants Neck holds Deaths During Arrest and in Police Custody: Excited Delirium Syndrome Deaths occurring during arrest - the Excited Delirium Syndrome (EDS) Mechanisms of death in EDS Hogtying - Positional/restraint asphyxia Choke hold-related deaths Tasers Oleoresin capsicum (pepper spray) Deaths occurring in jails Murder of Infants and Children Statistics Neo-naticide Deaths in the first 2 years of life Battered child syndrome Impulse homicides Gentle homicide Shaken baby syndrome Sexually Related Homicides Rape homicides Homosexually related homicides Evidence of chronic anal intercourse Fire and Thermal Injuries Classification of burns according to depth of injury Burn severity factors Documentation of extent and pattern of burn Burn survivability Clothing and burns Six categories of burns Death due to burn injury (immediate or delayed) Charred bodies Classification of fire deaths Antemortem versus postmortem burns Transportation Deaths Motor vehicle deaths Pedestrian deaths Motorcycle deaths Bicycle (pedal-cycle) injuries Aviation-related injuries and death Environmental Deaths Drowning Hyperthermia Hypothermia Lightning Electrocution Ohm's law Factors determining severity of electrical injury Low-voltage versus high-voltage deaths Resistance and current flow Current flow through body Electrocution and loss of consciousness Electrical burns of the skin Suicidal electrocution Ground-fault circuit interrupters (GFCIs) Investigation of suspected electrocutions Third rail electrocutions Electrical shock and pregnancy Stun guns Judicial electrocutions Deaths in Nursing Homes Deaths in nursing homes Signs of neglect Deaths due to hospital bed side rails Deaths due to medical restraints Deaths due to Starvation Malnutrition, starvation deaths in general Nutrition and body weight Physical manifestations of starvation Dehydration deaths Deaths in Association with Pregnancy Deaths secondary to complications of pregnancy Abortion-related deaths Intraoperative Deaths Deaths due to underlying disease Disruption of a vital organ during a procedure Air embolism occurring during surgery Anesthetic-related deaths Cause of death cannot be ascertained Forensic Toxicology Forensic toxicology Tissues to be collected Collection of materials Routine testing Drug screens in medical examiners' offices Thin-layer chromatography Immunoassay methods of analysis Gas chromatography (GC) High-pressure liquid chromatography (HPLC) Gas chromatography-mass spectrometry (GC-MS) Confirmatory testing Poisons Drugs of abuse Medications commonly associated with overdose Ethanol Methyl alcohol and isopropanol Phencyclidine…

Journal of Biological Chemistry, Jul 1, 1973

Proceedings of the National Academy of Sciences of the United States of America, Aug 1, 1975

Receptor-dependent hydrolysis of cholesteryl esters contained in plasma low density lipoprotein (... more Receptor-dependent hydrolysis of cholesteryl esters contained in plasma low density lipoprotein (human fibroblasts/familial hypercholesterolemia/cholesterolImetabolism/atherosclerosis/lysosomal acid hydrolases)

Proceedings of the National Academy of Sciences of the United States of America, Nov 1, 1974

A new mechanism is described for the cellular esterification of cholesterol derived from extracel... more A new mechanism is described for the cellular esterification of cholesterol derived from extracellular lipoproteins. Incubation of monolayers of cultured fibroblasts from normal human subjects with low density lipoproteins led to a 30-to 40-fold increase in the rate of incorporation of either [l4Clacetate or [14C]oleate into the fatty acid fraction of cholesteryl ["4Clesters. This stimulation of cholesteryl ester formation by low density lipoproteins occurred despite the fact that endogenous synthesis of free cholesterol was completely suppressed by the lipoprotein. Thus, exogenous cholesterol contained in low density lipoproteins, rather than endogenously synthesized sterol, appeared to provide the cholesterol substrate for this cellular esterification process. High density lipoproteins and the lipoprotein-deficient fraction of serum neither stimulated cholesteryl ester formation nor inhibited cholesterol synthesis. Both the low density lipoprotein-dependent increase in cholesterol esterification and decrease in free cholesterol synthesis required the interaction of the lipoprotein with its recently described cell surface receptor. Cells from homozygotes with familial hypercholesterolemia, which lack specific low density lipoprotein receptors, showed neither lipoprotein-dependent cholesterol esterification nor suppression of cholesterol synthesis. The reciprocal changes in free cholesterol synthesis and cholesteryl ester formation produced by low density lipoprotein-receptor interactions may play an important role in the regulation of the cholesterol content of mammalian cells.

Proceedings of the National Academy of Sciences of the United States of America, Mar 1, 1975

Studies in cultured fibroblasts from patients with the clinical syndrome of homozygous familial h... more Studies in cultured fibroblasts from patients with the clinical syndrome of homozygous familial hypercholesterolemia have disclosed two different mutations affecting the functions of the low density lipoprotein receptor. One of these mutations, described previously, results in a functionless receptor that does not bind low density lipoproteins.' In the cells of six patients who appear to be homoxygous for this mutant allele, i.e., receptor-negative homozygotes, low density lipoproteins neither suppress hydroxymethylglutaryl-CoA reductase (NADPH) [mevalonate: NADP+ oxidoreductase (CoA-acylating) EC 1.1.1.34] activity nor stimulate cellular cholesterol esterification, even'when examined in the presence of concentrations of lipoprotein 500 times higher than those required to produce maximal biologic effects in normal cells. The second type of mutation, described herein, results in a receptor that has a reduced but not absent function.' Fibroblasts from three-subjects who possess this mutation, i.e., receptor-defective homozygotes, show partial suppression of the same enzyme activity and a detectable increase in cholesterol esterification capacity in the presence of high levels of low density lipoproteins. It was calculated that their degree of function could be achieved if they possessed only about 10% of the normal binding of low density lipoprotein. This level of binding was too low to be reliably detected by the "2I-labeled low

Journal of Biological Chemistry, Nov 1, 1975

Journal of Cellular Physiology, Apr 1, 1975

Analysis of mutant human fibroblasts deficient in a cell surface receptor for low density lipopro... more Analysis of mutant human fibroblasts deficient in a cell surface receptor for low density lipoproteins (LDL) has led to the delineation of an important, hitherto unrecognized, regulatory process for cholesterol metabolism. On normal cells, binding of LDL to this receptor regulates cholesterol metabolism by two mechanisms: (a) suppression of cholesterol synthesis and (b) facilitation of the rate of proteolytic degradation of the lipoprotein. In cells from homozygotes with the autosomal dominant disorder Familial Hypercholesterolemia, a nearly total reduction in LDL receptors results in two secondary abnormalities: (a) overproduction of cholesterol due to an inability of LDL to suppress the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-controlling enzyme in cholesterol biosynthesis, and (b) impairment in the rate of proteolytic degradation of LDL. Cells from heterozygotes possess about 50 per cent of the normal number of LDL recpetors; this leads to a concentration-dependent defect in regulation, so that attainment of rates of cholesterol synthesis and LDL degradation equal to that in normal cells requires a two to three-fold higher concentration of extracellular LDL in the heterozygote. The identification of this genetic regulatory defect in fibroblasts of heterozygotes with Familial Hypercholesterolemia makes available an in vitro system for studying the molecular mechanism by which a dominant mutation affects gene expression in mammalian cells.

Journal of Forensic Sciences, 1987

CRC Press eBooks, Oct 31, 2006

Journal of Forensic Sciences, 1992

This paper examines the proposed association of bilateral asymmetry of the jugular foramen as an ... more This paper examines the proposed association of bilateral asymmetry of the jugular foramen as an indicator of handedness observable from cranial morphology. The jugular foramina of 54 subjects were observed for size asymmetry during routine autopsy procedures. Hand preference data were collected on each subject from family members. Of the 54 subjects, 47 were documented as being right-handed and 7 as being left-handed. These values approximate the average percentage of right-handed versus left-handed individuals from larger populations. Jugular foramen asymmetry was qualitatively identified for 36 subjects (66.7%) and was judged equivocal for the other 18 (33.3%). Of the 36 subjects exhibiting asymmetry, 28 (77.7%) showed positive correlation between the asymmetry direction and handedness. This moderate level of congruence, coupled with the result that 4 of the 7 left-handers exhibited dominant right-side foramina, casts doubt on the reliable use of jugular foramen asymmetry for estimating handedness.

Journal of Forensic Sciences, Nov 1, 1987

Three deaths as a result of inhalation of carbon monoxide from the exhaust fumes of automobiles a... more Three deaths as a result of inhalation of carbon monoxide from the exhaust fumes of automobiles are reported. All deaths occurred outside and not in a structure. The individuals were white males, ages 24 to 26 years. Blood carboxyhemoglobin concentrations ranged from 58 (in a decomposing body) to 81%. The three cases illustrate the fact that even in the outdoors death from carbon monoxide inhalation can occur if an individual is in close proximity to a rich source of carbon monoxide.

CRC Press eBooks, Oct 31, 2006

Journal of Biological Chemistry, Oct 1, 1974

Studies in cultured fibroblasts from patients with the clinical syndrome of homozygous familial h... more Studies in cultured fibroblasts from patients with the clinical syndrome of homozygous familial hypercholesterolemia have disclosed two different mutations affecting the functions of the low density lipo- protein receptor. One of these mutations, described previ- ously, results in a functionless receptor that does not bind low density lipoproteins. In the cells of six patients who appear to be homozygous for this mutant allele, i.e., receptor-negative homozygotes, low density lipoproteins neither suppress hydroxymethylglutaryl-CoA reductase (NADPH) (mevalonate:NADP+ oxidoreductase (CoA-acy- lating) EC 1.1.1.34) activity nor stimulate cellular choles- terol esterification, even when examined in the presence of concentrations of lipoprotein 500 times higher than those required to produce maximal biologic effects in normal cells. The second type of mutation, described herein, results in a receptor that has a reduced but not absent function. Fibroblasts from three subjects who possess this mutation, i.e., receptor-defective homozygotes, show partial suppression of the same enzyme activity and a detectable increase in cholesterol esterification capacity in the presence of high levels of low density lipoproteins. It was calculated that their degree of function could be achieved if they possessed only about 10% of the normal binding of low density lipoprotein. This level of binding was too low to be reliably detected by the '5I-labeled low density lipoprotein binding assay. The finding of a second class of mutant cells in which a defect in low density lipoprotein binding is associated with simultaneous de- fects in both suppression of hydroxymethylglutaryl-CoA reductase activity and stimulation of cholesterol ester formation provides further evidence for the coordinate control of these two processes by the low density lipo- protein receptor.

CRC Press eBooks, Oct 31, 2006

... Los traductores, todos ellos profesores de Medicina Legal y Toxicología de la Universidad de ... more ... Los traductores, todos ellos profesores de Medicina Legal y Toxicología de la Universidad de Santiago de Compostela, han realizado una encomiable tarea en la que han sabido aunar con rigor los aspectos idiomático y técnico-científico. ...

Introduction to Medicolegal Casework Five Categories of Medicolegal Cases Cause, Mechanism, and M... more Introduction to Medicolegal Casework Five Categories of Medicolegal Cases Cause, Mechanism, and Manner of Death The forensic autopsy versus an external examination Three steps of medicolegal death investigation Handling of bodies at the scene Handling of bodies from a hospital Handling of bodies at the morgue Identification of bodies The Autopsy Report Heading of report External Examination Evidence of Injury Internal Examination Microscopic Examination Toxicology Findings Opinion Physical Evidence Types of physical evidence Preservation of physical evidence on the body Recovery of physical evidence Procedures for collection of biological evidence Procedures for collection of nonbiological physical evidence DNA analysis Time of Death- Decomposition Factors used in estimating time of death Decomposition Identification of Remains Intact, nondecomposed human remains Decomposed or charred, nonskeletonized human remains Skeletonized human remains Natural Disease Causes of Sudden Natural Death in Adults Cardiovascular disease Central nervous system disorders Respiratory system disorders Gastrointestinal tract disorders Hepatic disorders Adrenal disorders Splenic disorders Miscellaneous causes of sudden death in adults Causes of Sudden Natural Death in Infants and Young Children Sudden infant death syndrome (SIDS) Other disorders associated with sudden death in infants and children Blunt Force Injury Definition Abrasions Contusions Lacerations Combination injuries Blunt force injury to the chest (thorax) Blunt force injury to the abdomen Blunt force injury to the genitalia (internal and external) Skeletal fractures due to blunt force trauma Extremity injuries due to blunt force trauma Head injuries caused by blunt force trauma Neck injuries caused by blunt force trauma Wounds Produced by Pointed, Sharp-Edged, and Chopping Implements Stab wounds Incised wounds Chop wounds Gunshot Wounds Types of small arms Firearms Caliber Ammunition Ballistic comparison of bullets Theory of wounding Gunshot wounds Centerfire Rifle Wounds Microscopic examination of gunshot wounds The effects of intermediary targets Ricochet bullets Shotguns Wounds of bone Caliber determination by size of entrance wounds Perforation of skin and bone Gunshot residue Miscellaneous Suicide General firearm terminology Asphyxia Suffocation Strangulation Chemical asphyxiants Neck holds Deaths During Arrest and in Police Custody: Excited Delirium Syndrome Deaths occurring during arrest - the Excited Delirium Syndrome (EDS) Mechanisms of death in EDS Hogtying - Positional/restraint asphyxia Choke hold-related deaths Tasers Oleoresin capsicum (pepper spray) Deaths occurring in jails Murder of Infants and Children Statistics Neo-naticide Deaths in the first 2 years of life Battered child syndrome Impulse homicides Gentle homicide Shaken baby syndrome Sexually Related Homicides Rape homicides Homosexually related homicides Evidence of chronic anal intercourse Fire and Thermal Injuries Classification of burns according to depth of injury Burn severity factors Documentation of extent and pattern of burn Burn survivability Clothing and burns Six categories of burns Death due to burn injury (immediate or delayed) Charred bodies Classification of fire deaths Antemortem versus postmortem burns Transportation Deaths Motor vehicle deaths Pedestrian deaths Motorcycle deaths Bicycle (pedal-cycle) injuries Aviation-related injuries and death Environmental Deaths Drowning Hyperthermia Hypothermia Lightning Electrocution Ohm's law Factors determining severity of electrical injury Low-voltage versus high-voltage deaths Resistance and current flow Current flow through body Electrocution and loss of consciousness Electrical burns of the skin Suicidal electrocution Ground-fault circuit interrupters (GFCIs) Investigation of suspected electrocutions Third rail electrocutions Electrical shock and pregnancy Stun guns Judicial electrocutions Deaths in Nursing Homes Deaths in nursing homes Signs of neglect Deaths due to hospital bed side rails Deaths due to medical restraints Deaths due to Starvation Malnutrition, starvation deaths in general Nutrition and body weight Physical manifestations of starvation Dehydration deaths Deaths in Association with Pregnancy Deaths secondary to complications of pregnancy Abortion-related deaths Intraoperative Deaths Deaths due to underlying disease Disruption of a vital organ during a procedure Air embolism occurring during surgery Anesthetic-related deaths Cause of death cannot be ascertained Forensic Toxicology Forensic toxicology Tissues to be collected Collection of materials Routine testing Drug screens in medical examiners' offices Thin-layer chromatography Immunoassay methods of analysis Gas chromatography (GC) High-pressure liquid chromatography (HPLC) Gas chromatography-mass spectrometry (GC-MS) Confirmatory testing Poisons Drugs of abuse Medications commonly associated with overdose Ethanol Methyl alcohol and isopropanol Phencyclidine…

Journal of Biological Chemistry, Jul 1, 1973

Proceedings of the National Academy of Sciences of the United States of America, Aug 1, 1975

Receptor-dependent hydrolysis of cholesteryl esters contained in plasma low density lipoprotein (... more Receptor-dependent hydrolysis of cholesteryl esters contained in plasma low density lipoprotein (human fibroblasts/familial hypercholesterolemia/cholesterolImetabolism/atherosclerosis/lysosomal acid hydrolases)

Proceedings of the National Academy of Sciences of the United States of America, Nov 1, 1974

A new mechanism is described for the cellular esterification of cholesterol derived from extracel... more A new mechanism is described for the cellular esterification of cholesterol derived from extracellular lipoproteins. Incubation of monolayers of cultured fibroblasts from normal human subjects with low density lipoproteins led to a 30-to 40-fold increase in the rate of incorporation of either [l4Clacetate or [14C]oleate into the fatty acid fraction of cholesteryl ["4Clesters. This stimulation of cholesteryl ester formation by low density lipoproteins occurred despite the fact that endogenous synthesis of free cholesterol was completely suppressed by the lipoprotein. Thus, exogenous cholesterol contained in low density lipoproteins, rather than endogenously synthesized sterol, appeared to provide the cholesterol substrate for this cellular esterification process. High density lipoproteins and the lipoprotein-deficient fraction of serum neither stimulated cholesteryl ester formation nor inhibited cholesterol synthesis. Both the low density lipoprotein-dependent increase in cholesterol esterification and decrease in free cholesterol synthesis required the interaction of the lipoprotein with its recently described cell surface receptor. Cells from homozygotes with familial hypercholesterolemia, which lack specific low density lipoprotein receptors, showed neither lipoprotein-dependent cholesterol esterification nor suppression of cholesterol synthesis. The reciprocal changes in free cholesterol synthesis and cholesteryl ester formation produced by low density lipoprotein-receptor interactions may play an important role in the regulation of the cholesterol content of mammalian cells.

Proceedings of the National Academy of Sciences of the United States of America, Mar 1, 1975

Studies in cultured fibroblasts from patients with the clinical syndrome of homozygous familial h... more Studies in cultured fibroblasts from patients with the clinical syndrome of homozygous familial hypercholesterolemia have disclosed two different mutations affecting the functions of the low density lipoprotein receptor. One of these mutations, described previously, results in a functionless receptor that does not bind low density lipoproteins.' In the cells of six patients who appear to be homoxygous for this mutant allele, i.e., receptor-negative homozygotes, low density lipoproteins neither suppress hydroxymethylglutaryl-CoA reductase (NADPH) [mevalonate: NADP+ oxidoreductase (CoA-acylating) EC 1.1.1.34] activity nor stimulate cellular cholesterol esterification, even'when examined in the presence of concentrations of lipoprotein 500 times higher than those required to produce maximal biologic effects in normal cells. The second type of mutation, described herein, results in a receptor that has a reduced but not absent function.' Fibroblasts from three-subjects who possess this mutation, i.e., receptor-defective homozygotes, show partial suppression of the same enzyme activity and a detectable increase in cholesterol esterification capacity in the presence of high levels of low density lipoproteins. It was calculated that their degree of function could be achieved if they possessed only about 10% of the normal binding of low density lipoprotein. This level of binding was too low to be reliably detected by the "2I-labeled low

Journal of Biological Chemistry, Nov 1, 1975

Journal of Cellular Physiology, Apr 1, 1975

Analysis of mutant human fibroblasts deficient in a cell surface receptor for low density lipopro... more Analysis of mutant human fibroblasts deficient in a cell surface receptor for low density lipoproteins (LDL) has led to the delineation of an important, hitherto unrecognized, regulatory process for cholesterol metabolism. On normal cells, binding of LDL to this receptor regulates cholesterol metabolism by two mechanisms: (a) suppression of cholesterol synthesis and (b) facilitation of the rate of proteolytic degradation of the lipoprotein. In cells from homozygotes with the autosomal dominant disorder Familial Hypercholesterolemia, a nearly total reduction in LDL receptors results in two secondary abnormalities: (a) overproduction of cholesterol due to an inability of LDL to suppress the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-controlling enzyme in cholesterol biosynthesis, and (b) impairment in the rate of proteolytic degradation of LDL. Cells from heterozygotes possess about 50 per cent of the normal number of LDL recpetors; this leads to a concentration-dependent defect in regulation, so that attainment of rates of cholesterol synthesis and LDL degradation equal to that in normal cells requires a two to three-fold higher concentration of extracellular LDL in the heterozygote. The identification of this genetic regulatory defect in fibroblasts of heterozygotes with Familial Hypercholesterolemia makes available an in vitro system for studying the molecular mechanism by which a dominant mutation affects gene expression in mammalian cells.

Journal of Forensic Sciences, 1987