PubMed Health⌕ Search

Biomedical subjects

M Knowles

Publications and source records attributed to M Knowles.

At least 55 records · Page 3Linked to original sources
PubMed1989

Mild cystic fibrosis linked to chromosome 7q22 markers with an uncommon haplotype.

Cystic fibrosis is the commonest autosomal recessive genetic disorder among northern Europeans and their descendants. Recently, investigators have mapped the gene for cystic fibrosis to chromosome 7. We report the results of DNA linkage analysis in a consanguineous family with mild cystic fibrosis. The probes used in this study were pmet D. pmet H, XV-2c, KM.19, and pJ3.11. Linkage to the identified cystic fibrosis locus of 7q22 was established with a peak logarithm of the odds (lod) score of 3.00 at a recombination fraction theta =0.00 using the tightly linked marker KM.19. In addition, we found the D haplotype, which is not commonly associated with cystic fibrosis, to be segregating in this family. The D haplotype is composed of the 1.4-kb allele detectable by XV-2c and the 6.6-kb allele detectable by KM.19. The three patients with cystic fibrosis who had consanguineous parents were homozygous DD, were among the least severely affected, and had no pancreatic insufficiency. The five patients with unrelated parents were heterozygous for the D haplotype and the commoner B haplotype, except one patient who was homozygous DD. All affected persons with pancreatic insufficiency had the DB genotype. These DNA linkage studies provide additional evidence for the existence of a cystic fibrosis allele that is associated with mild disease.

Adult↗
PubMed1989

The computed tomographic spectrum of thoracic sarcoidosis.

Thoracic manifestations of sarcoidosis are well recognized on conventional radiographs. Less well known are the CT appearances of sarcoidosis. This article reviews the spectrum of CT findings in sarcoidosis; highlighting distributions of lymphadenopathy on CT, patterns of parenchymal involvement, and pulmonary complications of sarcoidosis as demonstrated by CT.

Humans↗
PubMed1989

Diseases of the chest in AIDS: CT diagnosis.

The advantages of computed tomography for the evaluation of various chest lesions commonly encountered in patients with AIDS are discussed. The significance of limited and extensive lymphadenopathy is considered and examples are presented. Also specifically illustrated are cases of opportunistic pneumocystis, cytomegalovirus, and nocardia pneumonitides and of candida esophagitis; septic emboli; empyema; premature bulla formation ranging from apical bullae to diffuse parenchymal destruction; Kaposi's sarcoma, and lymphoma. Examples of the value of CT in resolving obscure clinical chest problems in AIDS patients are also illustrated.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Status of patients seven years after completion of the hypertension detection and follow-up program in Evans County, Georgia.

The Evans County, Georgia, cohort of the Hypertension Detection and Follow-up Program (HDFP) was reexamined seven years after termination of the trial in 1979. Of the 510 survivors, 91 percent of the black and 91 percent of the white hypertensive subjects were evaluated by blood pressure (BP) levels, electrocardiograms (ECG), height-weight measurements, and questionnaire. The HDFP had treated a randomly selected half of the patients in an intensive stepped care (SC) program and the other half was referred to usual care (RC). At the beginning of the five-year trial, diastolic blood pressure (DBP) levels were higher in blacks in both SC and RC. At the completion of the trial in 1979, black women had mean DBP levels comparable to whites in both SC and RC, but black men displayed higher levels. During the five years of the trial there were no cases of left ventricular hypertrophy (LVH) in SC in either race. In RC the incidence of LVH was slightly higher in blacks than in whites. During the seven-year post-trial period, the incidence of LVH in blacks rose to 13 percent, more than double that of whites. Medication compliance was reduced in black men during this time, most likely because of removal of the supporting elements of HDFP (frequent medical contacts, free medication).In both races, hypertensive subjects underwent weight changes during the seven years of the post-trial period. Weight loss of 15 lb was associated with normotension. Weight gain of 9 to 10 lb over seven years was associated with hypertensive BP levels.The supportive or detrimental effect of weight loss or weight gain on BP levels was thus reconfirmed in this biracial cohort.

Adult↗
PubMed1986

Geographic variation in the onset of decline of ischemic heart disease mortality in the United States.

This report examines geographic variation in the onset of the decline of ischemic heart disease (IHD) mortality in white males aged 35-74 during the period 1968-78. Using a quadratic regression model, State Economic Areas (SEAs) were classified as experiencing onset of the decline in 1968 or earlier, 1969-72, or 1973 or later. In the United States as a whole, approximately one-third of SEAs experienced a late onset of the decline (after 1968). Metropolitan SEAs were in advance of non-metropolitan, and the Northeast and Pacific states showed earlier onset than the South and midsections of the country. The acceleration of the national decline after 1972 appears to be due to declines in areas in which rates had been increasing or in plateau until that time. Evidence about geographic variation in the onset of decline may provide clues about social and environmental factors responsible for the decline.

Adult↗
PubMed1985

Hypolipidemic activity of 6-amino-2-mercapto-5-methyl-pyrimidine-4-carboxylic acid and related derivatives in rodents.

6-Amino-2-mercapto-5-methylpyrimidine-4-carboxylic acid proved to be a potent hypolipidemic agent in rodents at the low dose of 20 mg/kg/d. The agent effectively reduced the liver enzyme activities required for the synthesis of triglycerides and cholesterol. Lower lipid levels in tissue were observed in mice but not in rats. Preliminary studies indicate that the agent accelerated the excretion of cholesterol and its metabolites from the body. The agents lowered the low-density lipoprotein (LDL) cholesterol content and raised the high-density lipoprotein (HDL) cholesterol content. These changes in lipoprotein cholesterol content suggest that the agent may be helpful in protecting against coronary disease. The agent is more effective than the commercially available agent, i.e., clofibrate at 150 mg/kg/d.

Animals↗
PubMed1985

Geographic variation in declining ischemic heart disease mortality in the United States, 1968-1978. I. Rates and change, whites aged 35-74 years.

Despite the well known geographic pattern for heart disease mortality, studies of the decline in ischemic heart disease have not provided a comprehensive examination of its spatial component. In this study, the authors computed and mapped mean rates and per cent change in ischemic heart disease mortality for whites aged 35-74 years, for the period of the Eighth Revision (1968-1978) of the International Classification of Diseases. Visual evidence of clustering and markedly different spatial patterns were found for mean rate and per cent change among the state economic areas of the United States.

Adult↗
PubMed1984

Bioelectric properties and ion flow across excised human bronchi.

Bioelectric properties and ion transport of excised human segmental/subsegmental bronchi were measured in specimens from 40 patients. Transepithelial electric potential difference (PD), short-circuit current (Isc), and conductance (G), averaged 5.8 mV (lumen negative), 51 microA X cm-2, and 9 mS X cm-2, respectively. Na+ was absorbed from lumen to interstitium under open- and short-circuit conditions. Cl- flows were symmetrical under short-circuit conditions. Isc was abolished by 10(-4) M ouabain. Amiloride inhibited Isc (the concentration necessary to achieve 50% of the maximal effect = 7 X 10(-7) M) and abolished net Na+ transport. PD and Isc were not reduced to zero by amiloride because a net Cl- secretion was induced that reflected a reduction in Cl- flow in the absorptive direction (Jm----sCl-). Acetylcholine (10(-4) M) induced an electrically silent, matched flow of Na+ (1.7 mueq X cm-1 X h-1) and Cl- (1.9 mueq X cm-12 X h-1) toward the lumen. This response was blocked by atropine. Phenylephrine (10(-5) M) did not affect bioelectric properties or unidirectional ion flows, whereas isoproterenol (10(-5) M) induced a small increase in Isc (10%) without changing net ion flows significantly. We conclude that 1) Na+ absorption is the major active ion transport across excised human bronchi, 2) Na+ absorption is both amiloride and ouabain sensitive, 3) Cl- secretion can be induced by inhibition of the entry of luminal Na+ into the epithelia, and 4) cholinergic more than adrenergic agents modulate basal ion flow, probably by affecting gland output.

Acetylcholine↗
PubMed1984

Serum retinol and risk of subsequent cancer: extension of the Evans County, Georgia, study.

A previous report from the Evans County, Ga., cohort correlated low base-line retinol levels in 1960-62 to an increased risk of cancer developing in the following 12-14 years. So that this inverse association could be retested, retinol determinations were performed on sera in 135 incident cancer cases, identified during a vital status follow-up in 1981, and in 237 controls matched by race, sex, age, and date of venipuncture. The serum was drawn during the second cohort examination between 1967 and 1969 and stored at -20 degrees C until analysis by high-pressure liquid chromatography in January 1982. Eligible for the study were patients whose initial cancer diagnosis was established more than 24 months after venipuncture. Base-line retinol levels of subsequent cancer cases and their matched controls were similar in the 4 race-sex groups. The risk of cancer at all sites associated with the lowest retinol quintile was similar to that associated with the highest quintile. In multivariate analysis, with control for age, cholesterol, body mass, smoking status, and social class, no significant relationship of serum retinol and case status was found. In summary, these data fail to confirm the strong dose-response relationship between baseline retinol levels and subsequent cancer reported in the previous study.

Female↗
PubMed1983

Relative ion permeability of normal and cystic fibrosis nasal epithelium.

The raised transepithelial electric potential difference (PD) across respiratory epithelia in cystic fibrosis (CF) has suggested an abnormality in ion permeation. We characterized this abnormality further by measuring in the nasal epithelia of CF and normal subjects the concentration-PD relationship for amiloride, an inhibitor of cell Na+ permeability, and PD responses to superfusion with solutions of different composition. Amiloride was more efficacious in the CF subjects but the ED50 was not different from that of normals (approximately 2 X 10(-6) M). Na+ replacement by choline induced effects similar to those of amiloride, i.e. a greater depolarization in CF subjects. A 10-fold increase in the K+ concentration of the perfusate induced a small (less than 10 mV) depolarization in both subject populations. When Cl- in the perfusate was replaced by gluconate or SO2-(4) the nasal PD of normal subjects hyperpolarized (lumen became more negative) by approximately 35 mV. A significantly smaller response (less than 17 mV) was induced in CF homozygotes but not in heterozygotes (38 mV). The smaller response of CF subjects appears to reflect an absolute decrease in luminal surface Cl- permeability because pretreatment with amiloride did not increase the response to Cl- free solution (7 mV). Accordingly, three abnormalities (decreased Cl- permeability, raised PD, greater amiloride efficacy) have been identified in CF respiratory epithelia. Whereas "excessive" active Na+ transport can account for these abnormalities and the dessication of airway surface liquid, it is possible that a lower lumenal cell membrane Cl- permeability and inhibition of a potential path of Cl- secretion can also explain the observations.

Adult↗
PubMed1981

Increased bioelectric potential difference across respiratory epithelia in cystic fibrosis.

To investigate respiratory epithelial function in cystic fibrosis, we measured the transepithelial electrical potential difference across the upper and lower respiratory mucosa in patients with cystic fibrosis and control subjects. The nasal potential difference in the 24 patients with cystic fibrosis exceeded by more than 3 standard deviations the mean voltage in healthy controls, subjects with other diseases, and subjects heterozygous for cystic fibrosis. Potential differences in lower airways were measured in four patients and were significantly greater than in controls (P less than 0.05). Superfusion of the luminal surface with amiloride, an inhibitor of active sodium absorption, induced greater reductions in both nasal and airway potential difference in patients than in controls. We conclude that the increased respiratory-epithelial potential differences appear to be a specific abnormality in homozygotes for cystic fibrosis. The greater reduction in potential difference in response to amiloride suggests that absorption of excess salt and perhaps liquid from respiratory epithelial surfaces contributes to the pathogenesis of lung disease in cystic fibrosis.

Adolescent↗