Molecular biology for the cardiologist.
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Animals↗
Biomedical subjects
A Mares
Publications and source records attributed to A Mares.
Expression of a missense mutation in the messenger RNA for beta-myosin heavy chain in myocardial tissue in hypertrophic cardiomyopathy.
We have determined that a missense mutation in exon 13 of the beta-myosin heavy chain (beta MHC) gene is expressed in the messenger RNA (mRNA) isolated from a right ventricular endomyocardial biopsy obtained from the proband of a family with hypertrophic cardiomyopathy. The mutation is the result of a substitution of an adenine for a guanine residue in one allele of the beta MHC gene and creates a second recognition site for the restriction endonuclease Ddel in exon 13. The mutation is inherited in a Mendelian fashion and co-segregates with hypertrophic cardiomyopathy in this family. Complementary DNAs synthesized from RNA isolated from the endomyocardial biopsy were cloned into a plasmid vector and sequenced to confirm the expression of both the normal and mutant allele in mRNA of myocardial tissue. This is the first report of the transcription of a mutant beta MHC gene allele into mRNA of the myocardium.
Base Sequence↗
Detection of a new mutation in the beta-myosin heavy chain gene in an individual with hypertrophic cardiomyopathy.
Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant disease affecting primarily the myocardium. The gene responsible for FHCM has been localized to chromosome 14 in some families and several mutations have been described in the beta-myosin heavy chain (beta MHC), a candidate gene for the disease. We recently identified a family with HCM in whom we did not detect any of the known mutations in the beta MHC gene (the alpha/beta MHC hybrid gene and the missense mutation in exons 13 and 9). However, we did observe a novel 9.5-kb BamHI restriction fragment length polymorphism detected by a beta MHC probe on Southern blots of DNA from the proband of this family. Similarly, a novel 3.8-kb TaqI polymorphism and a novel 4.3-kb HindIII polymorphism were detected on Southern blots of DNA from the same proband. Polymerase chain reaction (PCR) was used to amplify the segment of the beta MHC that was detected by pSC14 probe. PCR amplification of the distal 3'-end of the beta MHC gene yielded an additional product in the DNA template from the proband which was subsequently cloned and sequenced. The sequence analysis showed a 2.4-kb nucleotide deletion involving one allele of the beta MHC gene. The deletion includes part of the intron 39, exon 40 including the 3'-untranslated region and the polyadenylation signal, and part of the beta-alpha MHC intergenic region. This deletion was inherited in Mendelian fashion in an additional three members of this small family of which only the proband has developed clinically diagnosed HCM at a very late onset (age 59 yr), the other three family members are younger and have not developed the disease at the ages of 10, 32, and 33 yr.
Aged↗
[Traumatic rupture of the diaphragm in an infant].
Traumatic rupture of the diaphragm can be caused by both penetrating and blunt trauma. High kinetic energy applied to the abdomen during blunt abdominal trauma creates pressure differences between the abdominal and chest cavities. These sudden changes in pressure rupture the diaphragm. We present a 13-month-old infant admitted after being injured by a car. In addition to rupture of the diaphragm there were pelvic fractures. Chest x-ray on admission was diagnostic for diaphragmatic rupture. The possibility of congenital diaphragmatic hernia was rejected because of increasing ventilatory embarrassment.
Accidents, Traffic↗
Isolation of a human chromosome 14-only somatic cell hybrid: analysis using Alu and LINE-based PCR.
Interspecific somatic cell hybrids containing single human chromosomes are valuable reagents for localization of cloned genes and DNA fragments to specific chromosomes, for the development of chromosome-specific libraries, and for generation of hybrid cell lines containing subchromosomal regions. A CHO somatic cell hybrid containing a single, intact human chromosome 14 (MHR14) was developed and confirmed by LINE PCR amplification gel pattern, by Alu-517 PCR product dot blot hybridization, and by cytogenetic analysis. MHR14 will serve as the chromosome source for the development of a radiation map of human chromosome 14.
Animals↗
Risk factors for acute non-A, non-B hepatitis in the United States and association with hepatitis C virus infection.
The Centers for Disease Control conducted intensive surveillance for acute non-A, non-B hepatitis in four sentinel counties over a 7-year period. Testing for antibody to hepatitis C virus was performed with the newly developed enzyme immunoassay. The incidence of non-A, non-B hepatitis remained relatively stable (average, 7.1 cases per 100,000, but there were significant changes in disease transmission patterns. The proportion of patients with a history of blood transfusion declined from 17% to 6%, but the proportion with a history of parenteral drug use increased from 21% to 42%. The proportion of patients with histories of sexual exposure (6%), household exposure (3%), occupational exposure to blood (2%), or hemodialysis (0.6%) did not change over time. Antibody to hepatitis C virus was found in 45% of patients within 6 weeks of onset of illness and in 68% of patients followed up for at least 6 months. Patients with no history of transfusions were just as likely to be positive for antibody to hepatitis C virus as patients with transfusion-associated hepatitis, indicating that hepatitis C virus is the major causative agent of all non-A, non-B hepatitis in the United States.
Acute Disease↗
The changing epidemiology of hepatitis B in the United States. Need for alternative vaccination strategies.
To determine trends in the incidence and epidemiology of acute hepatitis B in the United States we conducted intensive surveillance for viral hepatitis in four sentinel counties from October 1, 1981, to September 30, 1988. The overall incidence of hepatitis B remained relatively constant throughout the study period (average, 13.2 cases per 100,000 population), but disease transmission patterns changed significantly. The proportions of hepatitis B cases accounted for by homosexual activity and health care employment decreased 62% and 75%, respectively; the proportions of cases accounted for by parenteral drug use and heterosexual exposure increased 80% and 38%, respectively. The percentage of patients for whom no risk factor was identified (30% to 40%) did not change over time. These patients tended to belong to minority populations, and their socioeconomic level was low. The decline in the number of hepatitis B cases among homosexual men probably results from the modification of high-risk sexual behavior; the decline among health care workers is due mostly to hepatitis B immunization. The current strategy for prevention of hepatitis B, which targets high-risk groups for immunization, has failed to have a significant impact on the incidence of disease.
Acute Disease↗
Persistent müllerian duct remnant in a newborn.
Müllerian duct remnant in a newborn is a rare finding. The presented case illustrates well the ultrasonic and radiologic features of the entity.
Disorders of Sex Development↗
Diversity in supercoupling of beta 2-adrenergic receptors in orthostatic hypotension.
Orthostatic hypotension is a clinical condition that frequently involves abnormal adrenergic control of cardiovascular function. Adrenergic function was studied in six patients with symptomatic orthostatic hypotension and in 11 age-matched healthy subjects. The patients demonstrated higher supine mean arterial pressures (MAP; 103 +/- 8 versus 86 +/- 4 mm Hg) and orthostatic hypotension (delta MAP -70 +/- 5 versus +15 +/- 2 mm Hg, p less than 0.001) compared with normal subjects. The delta MAP in phase II of the Valsalva maneuver was significantly greater (-31 +/- 4 versus -7 +/- 4 mm Hg, p less than 0.002) and phase IV heart rate response was blunted (-5 +/- 3 versus -30 +/- 8 beats/min, p less than 0.02) in these patients. More isoproterenol was required to increase heart rate by 25 beats per minute in patients with hypotension (810 +/- 670 versus 3.1 +/- 1.3 micrograms, p less than 0.05), indicating marked chronotropic hyposensitivity. Leukocyte beta 2-adrenergic receptor densities were similar in patients and controls. beta 2-Adrenergic receptor coupling, however, was elevated in patients with hypotension when compared with control subjects (ratio of the low-affinity and high-affinity dissociation constants [KL/KH] 140 +/- 7.4 versus 66 +/- 4.3, p less than 0.001). There were negative correlations between the KL/KH value and the dose of isoproterenol required to decrease MAP by 20 torr (p less than 0.02) and between the KL/KH value and the product of the hormone receptor and MAP (p less than 0.01). However, the patients could be subdivided into a group who could mount a nearly normal hormone receptor times MAP response on standing (group 1A), and a group who could not (group 1B). The group 1A patients had elevated plasma norepinephrine responses associated with milder beta 2-adrenergic receptor supercoupling, whereas group 1B patients had essentially no orthostatic plasma norepinephrine response and had much higher KL/KH values. Thus, though a state of biochemical supersensitivity existed in both patient subgroups, diminished catecholamine exposure was associated, as expected, with beta 2-adrenergic hypersensitivity in group 1B, whereas there was no diminution of catecholamine exposure in the beta 2-adrenergic hypersensitivity observed in group 1A patients.
Aged↗
Spectrum of dysautonomia in mitral valvular prolapse.
PURPOSE: Symptoms suggesting altered autonomic regulation of cardiovascular function have been noted in some patients with mitral valvular prolapse (MVP) but may also occur in patients with other disorders. We evaluated cardiovascular responses to autonomic stimuli in 118 patients with symptoms of dysautonomia, 78 of whom had MVP, and 40 of whom did not, to determine if unique patterns of these responses distinguished patients in one symptomatic subgroup from another. SUBJECTS AND METHODS: The responses of patients to standing, quantitated Valsalva maneuver, facial immersion in ice water, and administration of isoproterenol, phenylephrine, and tyramine were compared with those in 12 asymptomatic patients with MVP and 23 normal volunteers. RESULTS: Constitutional, cardiovascular, and neuropsychiatric symptoms occurred with similar frequency in the two symptomatic patient groups. The most common pattern of abnormal responses in symptomatic patients with or without MVP was (1) an increased heart rate and elevated plasma norepinephrine levels while supine and then while standing quietly for five minutes, (2) an exaggerated increase in heart rate during phase II of Valsalva, (3) a diminished bradycardic response during phase IV of Valsalva, and (4) an exaggerated heart rate response to administration of isoproterenol. The increased heart rate during Valsalva, but not the exaggerated sensitivity to isoproterenol, was correlated with the magnitude of the chronotropic response to standing only in symptomatic patients with MVP. Exaggerated hypertensive overshoot during phase IV of Valsalva was observed in only a few symptomatic patients. No consistent pattern of these abnormalities, however, was noted in any of the patient subgroups. Hemodynamic responses to autonomic stimuli in asymptomatic MVP patients were generally indistinguishable from those observed in normal subjects. CONCLUSION: These findings suggest that abnormal cardiovascular responses to autonomic stimuli may occur in any patient with symptoms of dysautonomia regardless of the presence or absence of MVP and that the pattern of these abnormal responses may be diverse. It is therefore important to characterize the pattern of altered autonomic regulation of cardiovascular function in each patient when considering mechanistic implications or making therapeutic decisions about these patients.
Adolescent↗
Mitral valve prolapse with symptoms of beta-adrenergic hypersensitivity. Beta 2-adrenergic receptor supercoupling with desensitization on isoproterenol exposure.
Autonomic nervous system dysfunction has recently been identified in a subset of patients with mitral valve prolapse. These autonomic nervous system abnormalities may correspond, in part, to biochemical alterations in beta-adrenergic receptors. Nine women with mitral valve prolapse and symptoms and signs of beta-adrenergic hypersensitivity and seven normal volunteer women were studied. Quiet standing (five minutes) increased both heart rate and plasma norepinephrine (p less than 0.05) in symptomatic patients with mitral valve prolapse compared with normal subjects. The dose of isoproterenol required either to increase heart rate 25 beats/minute (0.5 +/- 0.3 microgram versus 1.0 +/- 0.3 microgram) or to decrease mean arterial pressure 20 mm Hg (11.1 +/- 4.8 versus 78.2 +/- 25.2 micrograms) was significantly less in the patients with mitral valve prolapse than in the volunteers. Symptomatic patients with mitral valve prolapse were desensitized by a four-hour isoproterenol infusion, whereas sensitivity in normal control subjects did not change. In the patients with mitral valve prolapse, baseline beta-adrenergic receptor coupling was elevated compared with that in control subjects (220 +/- 7 versus 81 +/- 2; p less than 0.001). Isoproterenol infusion induced uncoupling in these patients (KL/KH = 35 +/- 3, p less than 0.05) but did not alter coupling in normal volunteers. This study demonstrates physiologic and pharmacologic beta-adrenergic hypersensitivity in vivo directly corresponding to biochemical supercoupling in a subset of patients with mitral valve prolapse.
Adult↗
The effect of underreporting on the apparent incidence and epidemiology of acute viral hepatitis.
To determine if passively reported cases of acute viral hepatitis are representative of the affected population, an active surveillance system was set up that identified all persons in Pierce County, Washington, who had been diagnosed by a physician as having acute viral hepatitis in the period March 1 through August 31, 1984. In this county, this was part of an ongoing epidemiologic study of viral hepatitis that had previously included some stimulation of reporting. The active surveillance system covered all primary sources of medical care, including all private physicians who were most likely to see persons with hepatitis. Secondary sources, those that did not provide direct medical care but might be aware of new cases, were also surveyed. The results of active surveillance showed that passive reporting was about 65% complete in Pierce County. No change occurred in the number of hepatitis A cases reported, but hepatitis B cases increased by 50%, and non-A, non-B hepatitis cases increased by 138%. Most of the increase was a result of enhanced reporting from private physicians. The two risk groups most affected by underreporting were homosexual men with hepatitis B and blood transfusion recipients with non-A, non-B hepatitis. During active surveillance, the proportion of persons with hepatitis B who reported homosexual activity was 52% compared with 20% from passive surveillance. Transfusion recipients represented 24% of the non-A, non-B hepatitis reported from active surveillance compared with 9% reported from passive surveillance. Although Pierce County may not be representative of all counties in the United States, persons responsible for public health prevention programs should recognize that data acquired through passive surveillance may not accurately reflect the magnitude of the risk for specific populations or the amount of disease that can be prevented.
Adult↗
Subglottic laryngeal atresia associated with tracheoesophageal fistula. Long-term survival.
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Abnormalities, Multiple↗
[2 or 4 daily doses of cimetidine in the treatment of gastric ulcer?].
In a randomized multicentre study of 149 patients with gastric ulcer the effect of 1000 mg cimetidine daily applied in four separate doses was compared to that of 400 mg cimetidine twice a day. In both patient groups similar healing rates were observed. 80.3% and 74.0%, respectively, of the ulcers healed within 6 weeks, and 93.8% and 90.3%, respectively, within 10 weeks. Abdominal pain and antacid consumption decreased under both regimens to a similar degree. Drug safety was good. Lower cost and simplicity in the administration make the b. i. d. regimen of cimetidine preferable to the q. i. d. regimen in the acute treatment of gastric ulcer.
Alcohol Drinking↗
Congenital ulcerative colitis.
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Colitis, Ulcerative↗
[Reduction of intussusception by barium enema].
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Barium Sulfate↗
Congenital partial gastric antral obstruction, an elusive cause of abdominal pain and vomiting.
The patient with partial gastric antral obstruction due to a diaphragm may present with obstructive symptoms at any age in life. Including the four patients presented, there are now 50 reported cases. Since the diagnosis has been unduly delayed in many adults, it is particularly important that those physicians and surgeons caring for infants and children be aware of this entity. If properly treated in infancy and childhood, many years of suffering and debility can be obviated.
Air↗