PubMed Health⌕ Search

Biomedical subjects

H Watkins

Publications and source records attributed to H Watkins.

72 records · Page 4Linked to original sources
PubMed1993

Independent origin of identical beta cardiac myosin heavy-chain mutations in hypertrophic cardiomyopathy.

The origins of the beta cardiac myosin heavy-chain (MHC) gene missense mutations that cause familial hypertrophic cardiomyopathy (FHC) in 14 families have been evaluated. Of eight different mutations, four were present in single families, while four occurred in two or more families. To investigate the origins of the four shared mutations, we defined the beta cardiac MHC haplotypes of each of the mutation-bearing chromosomes by determining the alleles present at three intragenic polymorphic loci. Two of the mutations (Arg453Cys and Val606Met) have arisen independently in each of three families, being found on different chromosomal backgrounds. A third mutation (Gly584Arg) is associated with identical haplotypes in two families with Portuguese ancestors, suggesting a founder effect. Haplotype analysis was uninformative for the fourth mutation (Arg403Gln). Thus, FHC-causing mutations have arisen independently in at least 12 of the 14 families studied, suggesting that the majority have arisen relatively recently as new mutations. This finding predicts the prevalence of disease-causing beta cardiac MHC mutations to be comparable in all population groups.

Base Sequence↗
PubMed1992

Characteristics and prognostic implications of myosin missense mutations in familial hypertrophic cardiomyopathy.

BACKGROUND: Familial hypertrophic cardiomyopathy is characterized by a variable degree of myocardial hypertrophy and a wide range of symptoms. Different mutations in the beta cardiac myosin heavy-chain gene have been identified in three affected families. However, neither the proportion of cases attributable to myosin mutations nor the effects of different mutations on clinical outcome are known. METHODS: Using a ribonuclease protection assay, we screened the beta cardiac myosin heavy-chain genes of probands from 25 unrelated families with familial hypertrophic cardiomyopathy; this assay is a sensitive method for detecting the presence and location of mutations. We further defined the mutations by analyzing their nucleotide sequences. The clinical features of the disease were compared in families with various myosin mutations. RESULTS: Seven mutations in the beta cardiac myosin heavy-chain gene were identified in 12 of the 25 families. All were missense mutations (i.e., causing the substitution of a single amino acid) clustered in the head and head-rod junction regions of the molecule. Six mutations resulted in a change in the charge of the amino acid. Patients with mutations that changed the charge of the altered amino acid (such as that from arginine to glutamine at nucleotide 403 or from arginine to cysteine at nucleotide 453) had a significantly shorter life expectancy (mean age at death, 33 years), whereas patients with the one mutation that did not produce a change in charge (Val606Met) had nearly normal survival. However, patients with different mutations did not differ appreciably in their clinical manifestations of familial hypertrophic cardiomyopathy. CONCLUSIONS: Different missense mutations in the beta cardiac myosin heavy-chain gene can be identified in approximately 50 percent of families with hypertrophic cardiomyopathy. In those families, a definite genetic diagnosis can be made in all members. Since the location of a mutation or its DNA-sequence alteration (or both) appears to influence survival, we suggest that the precise definition of the disease-causing mutation can provide important prognostic information about affected members.

Amino Acid Sequence↗
PubMed1992

Is angiographic ventriculography necessary for the assessment of ischemic patients?

A total of 53 patients with a provisional diagnosis of ischemic heart disease and without any clinical evidence of valvular, congenital, or primary muscle heart disease were studied by echocardiography and biplane left ventricular cineangiography. For angiographic ejection fraction analysis, a program developed in our department for use on an Apple Macintosh computer interfaced to a digitizing tablet was employed. Echocardiographic outlines of systolic and diastolic images were traced with a digitizing system on the screen and ejection fractions were calculated by a program incorporated in the echo machine. Good echo windows allowing ejection fraction calculations were present in 35 patients. There was a good correlation between angiographic and echocardiographic ejection fraction (r = 0.7, SEE = 0.09), and wall motion assessment revealed no significant discrepancies between the two image modalities. The remaining 18 patients had poor echo windows, preventing accurate echocardiographic determination of the ejection fraction. However, limited assessment of left ventricular size and wall motion was possible in all patients and allowed the identification of those who had impaired left ventricular function as judged by angiography (angiographic ejection fraction < 35%). We conclude that even in patients with poor echo windows echocardiographic assessment of left ventricular function provides clinical information similar to angiography which should not be considered mandatory for the investigation of ordinary ischemic patients.

Cardiac Catheterization↗
PubMed1992

Sporadic hypertrophic cardiomyopathy due to de novo myosin mutations.

Hypertrophic cardiomyopathy occurs as an autosomal dominant familial disorder or as a sporadic disease without familial involvement. While missense mutations in the beta cardiac myosin heavy chain (MHC) gene account for approximately half of all cases of familial hypertrophic cardiomyopathy, the molecular causes of sporadic hypertrophic cardiomyopathy are unknown. To determine whether beta cardiac MHC mutations are also associated with sporadic disease, we screened this gene in seven individuals with sporadic hypertrophic cardiomyopathy. Mutations in the beta cardiac MHC genes were identified in two probands with sporadic disease. In that their parents were neither clinically nor genetically affected, we conclude that mutations in each proband arose de novo. Transmission of the mutation and disease to an offspring occurred in one pedigree, predicting that these are germline mutations. The demonstration of hypertrophic cardiomyopathy arising within a pedigree coincident with the appearance of a de novo mutation provides compelling genetic evidence that beta cardiac MHC mutations cause this disease. We suggest that de novo mutations account for some instances of sporadic hypertrophic cardiomyopathy and that these mutations can be transmitted to children. The clinical benefits of defining mutations responsible for familial hypertrophic cardiomyopathy should also be available to some patients with sporadic disease.

Adult↗
PubMed1991

Preclinical diagnosis of familial hypertrophic cardiomyopathy by genetic analysis of blood lymphocytes.

BACKGROUND: The clinical diagnosis of familial hypertrophic cardiomyopathy is usually made on the basis of the physical examination, electrocardiogram, and echocardiogram. Making an accurate diagnosis can be particularly difficult in children, who may not have cardiac hypertrophy until adulthood. Recently, we demonstrated that mutations in the cardiac myosin heavy-chain genes cause familial hypertrophic cardiomyopathy in some families. We report a diagnostic test for familial hypertrophic cardiomyopathy that relies on the detection of mutations in the beta myosin heavy-chain gene in circulating lymphocytes that we used to evaluate three generations of a family, including the children. METHODS AND RESULTS: Using the polymerase chain reaction, we found that normal and mutant beta cardiac myosin heavy-chain genes are transcribed in circulating lymphocytes. This allowed us to examine beta cardiac myosin heavy-chain messenger RNA from blood lymphocytes, even though ordinary expression of the gene is virtually restricted to the heart. Base sequences amplified from this messenger RNA were analyzed with a ribonuclease protection assay to identify small deletions, abnormal splicing, or missense mutations. Using this technique we identified a novel missense mutation in a patient with familial hypertrophic cardiomyopathy. We evaluated 15 of the patient's adult relatives and found perfect agreement with the clinical diagnosis (8 affected and 7 not affected). Clinical analysis of 14 of the children (age, 1 to 20 years) of these affected family members revealed 1 child with echocardiographic findings diagnostic of familial hypertrophic cardiomyopathy. However, genetic analyses showed that six other children had also inherited the missense mutation and might later manifest the disease. CONCLUSIONS: Transcripts of beta cardiac myosin heavy-chain gene can be detected in blood lymphocytes and used to screen for mutations that cause familial hypertrophic cardiomyopathy. This approach makes practical the identification of mutations responsible for this disorder and may be applicable to other diseases in which direct analysis is difficult because the mutated gene is expressed only in certain tissues. Preclinical or prenatal screening in an affected family will make it possible to study the disease longitudinally and to develop preventive interventions.

Adolescent↗
PubMed1986

Polymicrobial early postpartum endometritis with facultative and anaerobic bacteria, genital mycoplasmas, and Chlamydia trachomatis: treatment with piperacillin or cefoxitin.

A protected, triple-lumen transcervical culture method was used to recover organisms from the endometrium. At least one facultative or one anaerobic species of bacteria was recovered from 82% of the patients, and genital mycoplasmas were recovered from 76% of the women with endometritis. Bacteria together with genital mycoplasmas were present in 61% of the women, bacteria alone were present in 20%, genital mycoplasmas alone were present in 16%, and Chlamydia trachomatis was isolated from 2% of the patients. The most common organisms included Gardnerella vaginalis, Peptococcus spp., Bacteroides spp., Staphylococcus epidermidis, group B Streptococcus, and Ureaplasma urealyticum. A randomized, double-blind regimen of either piperacillin or cefoxitin was equally successful in treating the postpartum endometritis.

Bacteriuria↗
PubMed1986

Endometrial cultures obtained by a triple-lumen method from afebrile and febrile postpartum women.

Transfundal endometrial cultures obtained from afebrile women who delivered vaginally were uniformly free of bacteria and contained Ureaplasma urealyticum in only 2 of 14 women. A protected triple-lumen transcervical method to obtain an endometrial culture recovered organisms from 6 (43%) of the 14 women. Compared with cultures from afebrile women, organisms were recovered from 51 (93%) of 55 febrile postpartum women by using the triple-lumen transcervical culture method (P less than .001). Among febrile women there was a correlation between the recovery of group B Streptococcus, enterococcus, Gardnerella vaginalis, Staphylococcus aureus, and anaerobic bacteria from the cervix and their recovery from the endometrium. Protected transcervical methods used to obtain postpartum endometrial cultures reduce cervical contamination, but semiquantitation of the culture is useful to further increase culture specificity.

Cervix Uteri↗
PubMed1977

Seasonal variation of cardiac failure in northern Nigeria.

The number of patients with cardiac failure admitted to hospital in Zaria, Nigeria, month by month during 1972-75 differed highly significantly between the cooler dry months and the hot wet months. The reasons are uncertain, but seasonal changes in blood-pressure and the effects of heat on the circulation and of humidity on the efficiency of sweating may be responsible.

Aortic Valve Insufficiency↗
PubMed1975

The ribonucleic acid of infectious bronchitis virus.

Analysis of the nucleic acid of infectious bronchitis virus by SDS polyacrylamide gel electrophoresis revealed an RNA of molecular weight 9.0 times 10-6 Daltons. The RNA was shown to have a sedimentation coefficient of 50.

Bronchitis↗
PubMedDate not supplied

The underuse of women's health care services in hungary. A preliminary study.

In order to collect baseline data for a 2-year Women's Health Program in Hungary, a survey was conducted of 369 women residing in one community setting. The purpose of this descriptive exploratory study was to gather preliminary data that would help identify perceptions of inhibitors to utilization of women's health services. An additional purpose was to identify perceived health needs in the study setting and to make recommendations for changes in the existing services. The survey results indicated that women were satisfied overall with their health care. Equivocal responses suggested, however, that patient-provider interactions and lack of understanding regarding preventive health care may contribute to the underuse of services. The authors suggest that public feedback that includes women's opinions and perceived needs is essential in health program planning and evaluation. In order to accomplish this, standardized Hungary-specific research instruments must be developed.

Adolescent↗
PubMedDate not supplied

A mutant tropomyosin that causes hypertrophic cardiomyopathy is expressed in vivo and associated with an increased calcium sensitivity.

Mutant contractile protein genes that cause familial hypertrophic cardiomyopathy (FHC) are presumed to encode mutant proteins that interfere with contractile function. However, it has generally not been possible to show mutant protein expression and incorporation into the sarcomere in vivo. This study aimed to assess whether a mutant alpha-fast tropomyosin (TM) responsible for FHC is actually expressed and determines abnormal contractile function. Since alpha-fast TM is expressed in heart and skeletal muscle, samples from vastus lateralis muscles were studied from two FHC patients carrying an Asp175Asn alpha-fast TM mutation and two healthy control subjects. TM isoforms from whole biopsy samples and single fibers were identified by gel electrophoresis and Western blot analysis. An additional faster-migrating TM band was observed in both FHC patients. The aberrant TM was identified as the Asp175Asn alpha-fast TM by comigration with purified recombinant human Asp175Asn alpha-fast TM. Densitometric quantification of mutant and wild-type alpha-fast TMs suggested equal expression of the two proteins. Contractile parameters of single skinned muscle fibers from FHC patients and healthy control subjects were compared. Calcium sensitivity was significantly increased in muscle fibers containing Asp175Asn alpha-fast Tm compared with fibers lacking the mutant TM. No discernible difference was found regarding cooperativity, maximum force, and maximum shortening velocity. This is the first demonstration that the mutant TM that causes FHC is indeed expressed and almost certainly incorporated into muscle in vivo and does result in altered contractile function; this confirms a dominant-negative, rather than null allele, action. Since the mutant TM was associated with increased calcium sensitivity, this mutation might be associated with an enhancement and not a depression of cardiac contractile performance. If so, this contrasts with the hypothesis that FHC mutations induce contractile impairment followed by compensatory hypertrophy.

Adult↗