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K Johnson

Publications and source records attributed to K Johnson.

At least 289 records · Page 16Linked to original sources
PubMed1993

[Direct genotypic analysis of myotonic dystrophy: detection of an unstable DNA fragment in carriers].

BACKGROUND: Myotonic dystrophy (DM) is an inherited autosomal dominant disorder. The molecular defect responsible for the disease is the expansion of a CTG triplet at the 3' end of the DM gene. We report the analysis of the gene expansion, its correlation with the clinical severity and with the phenomenon of anticipation. METHODS: Using the cDNA25 probe, we have analyzed 140 affected DM patients from a total of 42 families comprising 303 individuals. According to the clinical status, the affected DM patients were classified as follows: group I, congenital form; group II, classical form, and group III, mild form. RESULTS: A larger than normal fragment was detected in all the DM patients but in none of the controls. The expansion size is 2.5-6 kb in group I, 0.3-5 kb in group II and 0.2-1.5 kb in group III. In 49 parent-child couples which show clinical anticipation, 47 have an increase in size of the fragment from one generation to the next. CONCLUSIONS: Our results show a clear correlation between the severity of the disease and the expansion size. We confirm at the molecular level the phenomenon of anticipation. The direct gene analysis of the DM families allows the diagnosis of all the at-risk individuals and facilitates the genetic counselling of these families.

Adult↗
PubMed1993

Immune-mediated subepithelial blistering diseases of mucous membranes. Pure ocular cicatricial pemphigoid is a unique clinical and immunopathological entity distinct from bullous pemphigoid and other subsets identified by antigenic specificity of autoantibodies.

BACKGROUND AND DESIGN: There is much confusion in the clinical classification of immune-mediated subepithelial blistering diseases of mucous membranes. We conducted a 6-year comprehensive study to better classify this heterogeneous disease group. Indirect immunofluorescence was performed on a salt-split-skin substrate to detect circulating antibasement membrane antibodies (n = 47). Serologic reactivity against cultured keratinocyte antigens was examined by immunoblots (n = 38) and immunoprecipitation (n = 15). The results were correlated with the clinical features and direct immunofluorescence data of the entire patient group (n = 87) without preassignment of clinical diagnoses. chi 2 Statistical analyses compared these results with those of the classic bullous pemphigoid group (n = 36). RESULTS: When compared with the bullous pemphigoid patients, a subset of patients with combined oral mucosal and skin lesions demonstrated marked similarity in direct and indirect immunofluorescence findings and in serologic reactivity to bullous pemphigoid antigens. By contrast, a subset of patients with only ocular lesions exhibited significantly lower in vivo deposits of IgG and C3, higher deposits of fibrin, virtual absence of circulating antibodies, and negative serologic reactivity to bullous pemphigoid antigens. CONCLUSIONS: Ocular patients without skin or mouth lesions, in particular those with negative indirect immunofluorescence, should be distinctively classified as ocular cicatricial pemphigoid, a unique clinical and immunopathologic entity. Patients with mucous membrane involvement who also demonstrate skin lesions and antibodies to the root of salt-split-skin substrate should be classified as anti-BP Ag mucosal pemphigoid, even though they may exhibit severe oral and/or ocular diseases. The remaining mucous membrane patients are heterogeneous. Some can be classified on the basis of autoantibodies to other basement membrane determinants, or if serum autoantibody negative, on the basis of clinical features (ie, pure oral mucosal pemphigoid or overlapping mucosal involvement).

Autoantibodies↗
PubMed1993

Pulmonary follow-up 2.5 years after a randomized, controlled, multiple dose bovine surfactant study of preterm newborn infants.

Forty-seven preterm infants, who were previously enrolled in a prospective, randomized, blinded study at birth to assess the effects of multiple doses of exogenous bovine surfactant to prevent respiratory distress syndrome, underwent lung function evaluation and review of their medical histories at 2 1/2 years of age. During their initial hospitalization there were no differences between the 17 control infants and the 30 surfactant-treated infants in the duration of ventilator or oxygen therapy and the incidence of bronchopulmonary dysplasia. At the follow-up both groups were similar in chronological and corrected ages, weights, lengths, and sex ratios and there were no differences in the occurrence of allergy, asthma, bronchiolitis, eczema, pneumonia, and wheezing. In addition, there was no significant difference regarding the incidence of chest illnesses lasting either 3 or 7 days and in the total number of required rehospitalizations. Functional residual capacity (FRC), tidal volume (VT/kg), compliance (Crs/kg), resistance (Rrs), and time constant of the respiratory system were not significantly different between the two groups at 2 1/2 years of age. We conclude that bovine surfactant, when given during the neonatal period, has little long-term effect on lung function. Neonatal bovine surfactant therapy neither improves nor produces any adverse effects on the developing respiratory system.

Animals↗
PubMed1993

Isolation and ordering of bacteriophage genomic clones corresponding to two YACs from 19q13.3.

We describe a method for rapidly isolating overlapping bacteriophage clones corresponding to the genomic region cloned in a yeast artificial chromosome (YAC) that does not require sub-cloning or lambda DNA preparation. Purified YACs from 19q13.3 were used to screen a flow-sorted chromosome 19 library, and the resulting positive clones were characterized using inter-Alu PCR. In addition, aliquots of the lambda stocks were gridded out, and hybridized with probes known to be present in the YACs, thereby avoiding having to perform DNA preparations. The application of this technique in the identification of lambda clones which span the myotonic dystrophy (DM) locus on 19q13.3 is presented, and its general advantages are discussed.

Bacteriophage lambda↗
PubMed1993

The metabolic response of articular cartilage to abnormal mechanical loading induced by medial or lateral meniscectomy.

The effects of medial versus lateral meniscectomy on articular cartilage (AC) of adult sheep was investigated. In vitro incorporation of 35S into proteoglycans (PGs) and their release into media was used to assess cartilage metabolism. Lateral meniscectomy produced higher loss of PGs from AC and lower 35S-PG biosynthesis than for AC from medial meniscectomized joints. These findings were consistent with the proposed role of the lateral meniscus in joint mechanics.

Animals↗
PubMed1993

Women's health: designing and implementing an interdisciplinary specialty.

Contemporary physicians who wish to specialize formally in the care of women have inherited a surgical postgraduate program that focuses primarily on reproductive health. Mounting evidence suggests a broader perspective is needed. This article describes the role obstetrics-gynecology might play in this advancement.

Education, Medical↗
PubMed1993

Origin of the expansion mutation in myotonic dystrophy.

Myotonic dystrophy (DM) is caused by the expansion of a CTG trinucleotide repeat. The mutation is in complete linkage disequilibrium with a nearly two-allele insertion/deletion polymorphism, suggesting a single origin for the mutation or predisposing mutation. To trace this-ancestral event, we have studied the association of CTG repeat alleles in a normal population to alleles of the insertion/deletion polymorphism and of a (CA)n repeat marker 90 kilobases from the DM mutation. The results strongly suggest that the initial predisposing event(s) consisted of a transition from a (CTG)5 allele to an allele with 19 to 30 repeats. The heterogeneous class of (CTG)19-30 alleles which has an overall frequency of about 10%, may constitute a reservoir for recurrent DM mutations.

Alleles↗
PubMed1993

Evaluation of rooms with negative pressure ventilation used for respiratory isolation in seven midwestern hospitals.

OBJECTIVE: To determine the number and efficacy of respiratory isolation facilities in St. Louis hospitals and to assess the mechanisms in place for evaluating function of hospital ventilation systems. DESIGN: A prospective multi-hospital surveillance study using direct observation and a standardized questionnaire. SETTING: Seven hospitals (including university-affiliated large teaching, private community, private teaching, and private nonteaching adult hospitals, and one pediatric teaching hospital) in St. Louis, Missouri. MEASUREMENTS: Actual direction of airflow in rooms designated for respiratory isolation was measured using smokesticks. Hospital demographic information, respiratory isolation policies, and frequency of ventilation tests were provided by infection control personnel. RESULTS: One hundred twenty-one (3.4%) of 3,574 hospital rooms were designed to have negative pressure ventilation suitable for respiratory isolation. The percentage of isolation rooms in each institution ranged from 0.4% (92 of 486) to 93% (39 of 42). Only three (43%) of seven hospitals had intensive care respiratory isolation rooms, and none had isolation rooms in the emergency department. No hospital had tested routinely the efficacy of the negative pressure ventilation, and two (28%) of seven had tested airflow for the first time in the past year. We tested 115 (95%) of 121 isolation rooms. With the doors closed, 52 (45%) of 115 designated negative pressure rooms actually had positive airflow to the corridor. The number of negative pressure rooms and the presence or absence of anterooms did not predict correct direction of airflow. There was a significant difference among hospitals in the percentage of designated isolation rooms that had truly negative pressure (P < 0.0001). Hospital age, size, and type correlated with correct direction of airflow (P < 0.0001). CONCLUSION: In the hospitals studied, only a small number of rooms were designated for respiratory isolation, and the performance of these was not tested routinely. High-risk areas including intensive care units and emergency rooms were not equipped to provide respiratory isolation. The direction of airflow in respiratory isolation rooms was not always correct and should be evaluated frequently.

Cross Infection↗
PubMed1993

Molecular diagnosis of homozygous myotonic dystrophy in two asymptomatic sisters.

The genetic defect underlying myotonic dystrophy (DM) has been identified as the expansion of an unstable trinucleotide repeat sequence, and this discovery has led to new approaches to diagnosis and genetic counselling in families with the disorder. We report the genetic analysis of a consanguineous DM family in which two asymptomatic sisters had been shown to be homozygous for the 'at risk' haplotype. PCR analysis of the region spanning the trinucleotide expansion demonstrated that both sisters possessed two alleles with repeat sizes normally seen in minimally affected patients. Extensive clinical examination failed to demonstrate any of the symptoms of DM in these women. The implications of this finding, both for understanding the disease mechanism, and for genetic counselling in such situations are discussed.

Adolescent↗
PubMed1993

Myotonic dystrophy: absence of CTG enlarged transcript in congenital forms, and low expression of the normal allele.

Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease. The mutation has been identified as an unstable trinucleotide CTG repeat in a sequence encoding a putative cAMP-dependent protein kinase. The CTG repeat varies in length between affected siblings, and generally increases through generations in parallel with increasing severity of the disease. Congenital myotonic dystrophy, which represents the most severe phenotype, is exclusively maternally inherited. In this report, we show, by Northern blot analysis, that no mutated enlarged transcript is detectable in a 20-week-old DM fetus and in two congenitally affected infants. Furthermore, in skeletal and cardiac muscle of the DM fetus, we observed by RNA analysis, including Northern blot and RT-PCR, an unexpectedly low expression of the paternal wild type allele. Varying degrees of expression of the mutant and/or the normal allele might therefore account for the characteristic features of the congenital form and the extreme variability of the disease.

Alleles↗
PubMed1993

Larger expansions of the CTG repeat in muscle compared to lymphocytes from patients with myotonic dystrophy.

The discovery that there is an expansion of a CTG repeat underlying myotonic dystrophy has led to new approaches in diagnosis and genetic counselling for this disorder. The size of the expansion correlates to a reasonable degree with the clinical symptoms within a given family. We report comparisons of the length of the expansion seen in lymphocytes and muscle samples from eight patients. In all cases the length of the expansion seen in DNA isolated from muscle was larger than that seen in lymphocytes from the same patient. There was no progression of the expansion over a period of 10-15 years in muscle samples from two of these patients even though there had been significant progression of the severity of symptoms during that time.

Adult↗
PubMed1993

Early onset Haemophilus influenzae sepsis in the newborn infant.

Neonatal sepsis caused by Haemophilus influenzae is characterized by an early onset syndrome associated with pneumonia, shock and neutropenia. Over a 30-month period 13 infants referred to this hospital had early onset H. influenzae sepsis. Obstetric complications included preterm labor (92%), prolonged rupture of membranes > 12 hours (63%), maternal fever (64%), chorioamnionitis (43%), vaginal discharge (44%) and premature rupture of membranes (15%). All 13 infants were symptomatic at delivery and 7 required immediate intubation. Pneumonia and respiratory distress were the prominent clinical findings. H. influenzae was isolated from infant blood, maternal blood, placenta and genital tract. Isolates were predominantly non-type b, beta-lactamase-negative. A study to determine the prevalence of H. influenzae colonization of the genital tract among women attending clinic at the hospital with the most cases showed a rate of 0.3%. Perinatal risk factors and clinical findings in the infants are similar to disease caused by other organisms associated with early onset sepsis.

Blood↗