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M L Johnson

Publications and source records attributed to M L Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1996

Mode of pulsatile follicle-stimulating hormone secretion in gonadal hormone-sufficient and -deficient women--a clinical research center study.

To test the hypothesis that FSH is secreted at least in part within discrete secretory bursts in women and that the characteristics of episodic FSH secretion are altered within differing gonadal hormone environments, we measured FSH by immunoradiometric assay every 10 min for 24 h in premenopausal women during the early follicular (EF), late follicular (LF), and midluteal (ML) phases of the menstrual cycle and in postmenopausal (PM) women (n = 8 in each group). Secretory events were evaluated using multiparameter deconvolution. FSH was secreted in an episodic manner, with the number of secretory bursts (per 24 h; mean +/- SEM) detected in LF (20 +/- 0.79) and PM (20 +/- 0.90) women being greater than that in EF (16 +/- 0.88) and ML (14 +/- 0.93) women. FSH secretory burst mass (milliinternational units per mL) was significantly higher in PM (12 +/- 1.6) than in EF (1.8 +/- 0.21), LF (3.1 +/- 1.3), or ML (0.8 +/- 0.11) women and primarily reflected a relative increase in the maximal secretory rate rather than increased burst half-duration. The estimated half-life (minutes) of endogenous FSH in LF women (155 +/- 18) was shorter than those calculated in EF (251 +/- 24), ML (277 +/- 38), and PM (231 +/- 18) women. Cross-correlation analysis showed strongly positive associations between successively paired serum FSH and LH concentrations in all four groups of women. Deconvolution of simultaneously obtained LH concentration-time series revealed statistically significant concordance (13-25%) between FSH and LH secretory episodes at a lag time of 0 min in EF, LF, and PM women and when LH secretory bursts led FSH secretory bursts by 10 min in ML phase women. However, as 75-87% of FSH and LH secretory pulses were discordant, we infer the operation of distinct control mechanisms in the generation of FSH and LH release episodes. In summary, these results suggest that FSH is secreted within discrete secretory bursts in women, that the mass and frequency of FSH secretory bursts differ in women exhibiting various gonadal hormone environments, and that FSH and LH secretory bursts occur coincidentally at a higher rate than expected on the basis of chance alone, but at such a low overall rate of concordance that distinct mechanisms probably operate to direct episodic FSH and LH secretory activity.

Adult↗
PubMed1996

Sexual dimorphism of renal alpha2-adrenergic receptor regulation in Dahl rats.

Male Dahl salt-sensitive hypertensive (S) rats develop hypertension faster than females. We measured renal alpha2-adrenergic receptor density of inbred Dahl salt-sensitive (SS/JR) and salt-resistant (SR/JR) rats, using [3H]-rauwolscine saturation binding studies. Male and female SS/JR rats were gonadectomized or sham-operated at 6 weeks of age and fed a high salt diet for 4 weeks. Additional intact SS/JR and SR/JR rats of both sexes were fed the high salt diet for a longer period of time (7 weeks instead of 4 weeks). Both blood pressure and renal alpha2-adrenergic receptor density were significantly higher in male than female SS/JR rats on high salt diet for 4 weeks. Gonadectomy did not change blood pressure nor did it change renal alpha2-adrenergic receptor density measured at the 4th week of high salt feeding in either male or female SS/JR rats. When the SS/JR rats were fed high salt diet for a longer period (for 7 weeks), blood pressure of female SS/JR reached the level of males, but the density of renal alpha2-adrenergic receptors was still significantly lower than that of males. Both renal alpha2-adrenergic receptor density and blood pressure were higher in male than female SR/JR. We conclude that higher blood pressure in male Dahl SS/JR and SR/JR rats is associated with higher renal alpha2-adrenergic receptor density compared with their female counterparts.

Adrenergic alpha-Antagonists↗
PubMed1996

Production of heparin-binding endothelial mitogens by bovine uterine fibroblastic and epithelial cells.

This study was conducted to determine whether early-passage cultures of bovine endometrial fibroblastic (Fb, n = 7 uteri) and epithelial (Ep, n = 3 uteri) cells produce endothelial mitogens in vitro and to begin characterization of these mitogens. Confluent cultures of Fb and Ep were incubated for 72 h in serum-free media, and the resulting conditioned media (CM) were evaluated for effects on proliferation of bovine aortic endothelial cells. CM from these Fb cultures (n = 8) and Ep cultures (n = 4) stimulated (147 +/- 10% (mean +/- SEM), p < 0.01, and 124 +/- 8%, p < 0.10, respectively) proliferation of endothelial cells compared with control (unconditioned) media. Most of the mitogenic activity of a sample of Fb CM and a sample of Ep CM from one individual uterus bound to heparin-agarose, and each exhibited two major peaks of activity that eluted at 0.9-1.0 and 1.7-1.8 M NaCl; the Fb CM also exhibited an additional heparin-binding peak eluting at 0-0.1 M NaCl. Pooled Fb CM (n = 8 cultures from 7 animals) also contained mitogenic activity for endothelial cells that bound to heparin-agarose, but exhibited three major peaks, eluting at 0.6, 1.1, and 1.8 M NaCl. Pooled Ep CM (n = 4 cultures from 3 animals) showed only one peak of mitogenic activity, which eluted at 0.9 M NaCl. Further characterization indicated that heat treatment reduced the activity of all heparin-binding Fb CM and Ep CM peaks, except the Fb CM peak eluting at 1.7 M NaCl. Trypsin reduced the activity of all peaks except one. Protein-A-purified antibody against fibroblast growth factor 1 (FGF-1) had no or only a slight effect on the mitogenic activity of the peaks. Mitogenic activity of the Fb CM peak eluting at 0.6 M NaCl was reduced by antibody against FGF-2. Activity of the Fb CM and Ep CM peaks that eluted at 1.7-1.8 M NaCl also was immunoneutralized by antibody to FGF-2. These data demonstrate that early passage cultures of endometrial Fb and Ep cells produce heparin-binding endothelial mitogens that appear to be immunologically related to FGF-2. These heparin-binding endothelial mitogens may influence endometrial vascular growth.

Animals↗
PubMed1995

Molecular compartmentation expressed in cerebellar cultures in the absence of neuronal activity and neuron-glia interactions.

The purpose of the study was to determine if zebrin compartmentation developed in permanently isolated cerebellar cultures, in the presence of agents that block neuronal activity and in the absence of myelination and astrocytic ensheathment of Purkinje cells. Parasagittally oriented organotypic cultures derived from newborn mice and carefully undercut at explantation to exclude extracerebellar afferents were subjected to three conditions: 1) Some were maintained in standard nutrient medium; 2) some were chronically exposed to tetrodotoxin and elevated levels of magnesium to block neuronal activity; and 3) some were exposed to cytosine arabinoside for the first 5 days in vitro (DIV) to destroy granule cells and oligodendrocytes and functionally compromise astrocytes, so that the astrocytic survivors did not ensheath Purkinje cells. Cultures fixed as whole-mount preparations were reacted with antibody to zebrin II. Cultures that were cryostat sectioned were dually reacted with antibody to zebrin II and calbindin. Groups of zebrin+ and zebrin- Purkinje cells were evident after 14 DIV in all of the experimental conditions, indicating that zebrin compartmentation developed 1) in isolated cerebellar explants, 2) in the absence of neuronal activity, and 3) in the absence of neuron-glia interactions such as myelination and glial ensheathment of Purkinje cell somata and dendrites. These results are consistent with the concept that expression of the zebrin+ and zebrin- phenotypes is an intrinsic property of Purkinje cells. The fact that zebrin expression seems to depend on an intrinsic program of differentiation in Purkinje cells suggests some role for zebrin compartmentation in cerebellar function.

Animals↗
PubMed1995

The association between the quality of inpatient care and early readmission.

OBJECTIVE: To determine whether the quality of care during a hospital stay is associated with unplanned readmission within 14 days. DESIGN: Case-control study. SETTING: 12 Veterans Affairs hospitals. PATIENTS: Men discharged after a hospitalization for diabetes (n = 593), chronic obstructive lung disease (n = 1172), or heart failure (n = 748). The ratio of controls (men without an unplanned readmission within 14 days to any Veterans Affairs hospital) to cases (men with such a readmission) was 3:1. MAIN OUTCOME MEASURES: Unplanned readmission to any of the 159 Veterans Affairs hospitals within 14 days of discharge. Quality of care during the index stay was assessed by chart review using disease-specific explicit criteria for the process of inpatient care, which were developed by panels composed of expert physicians. Adherence scores (the percentage of applicable criteria that were met) were calculated for the admission workup, evaluation and treatment, and readiness for discharge. RESULTS: After adjustment was made for demographic characteristics, severity of illness, and need for care, adherence scores correlated with early unplanned readmission (P < 0.05). For patients with diabetes and heart failure, decreased readiness-for-discharge adherence scores correlated with increased risk for readmission (P = 0.001 and P = 0.016, respectively). In patients with obstructive lung disease, decreased admission-workup scores correlated with increased risk for readmission (P = 0.013). One of 7 readmissions in patients with diabetes, 1 of 5 readmissions in patients with heart failure, and 1 of 12 readmissions in patients with obstructive lung disease were attributable to substandard care. CONCLUSIONS: Lower quality of inpatient care increases the risk for unplanned early readmission in patients with heart failure, diabetes, or obstructive lung disease. Under certain circumstances, readmission is associated with remediable deficiencies in the process of inpatient care.

APACHE↗
PubMed1995

Vitamin D receptor gene polymorphism, bone mass, body size, and vitamin D receptor density.

We determined vitamin D receptor (VDR) gene alleles (based on the BsmI restriction site polymorphism), duodenal mucosal receptor density, bone mass at spine and total body, and body size in 32 healthy premenopausal females. While we found no relationship between allele and receptor density in duodenal mucosa, bone mineral content (BMC) at both spine and total body was significantly associated with VDR gene alleles. BMC was highest for the bb allele, lowest for BB, and intermediate for Bb. A similar association was noted between allele and body size variables, particularly weight. When BMC was adjusted for body weight, the association with VDR polymorphism disappeared. The VDR gene polymorphism may be affecting bone mass not through classical nutritional mechanisms (e.g., intestinal calcium absorption), but through an influence on body size.

Adult↗
PubMed1995

In-hospital complications among survivors of admission for congestive heart failure, chronic obstructive pulmonary disease, or diabetes mellitus.

OBJECTIVE: To determine the frequency of hospital complications among survivors of inpatient treatment for congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), or diabetes mellitus (DM). DESIGN: Retrospective cohort study. SETTING: Nine Veterans Affairs hospitals in the southern United States. PATIENTS: 1,837 men veterans discharged alive following hospitalization for CHF, COPD, or DM between January 1987 and December 1989. This patient population represents a subset of cases gathered to study the process of care in the hospital and subsequent early readmission; thus, veterans who died in the hospital were not included. MEASUREMENTS: Medical record review to record the occurrence of any of 30 in-hospital complications such as cardiac arrest, nosocomial infections, or delirium (overall agreement between two reviewers = 84%, kappa = 0.37). RESULTS: Complications occurred in 15.7% of the CHF cases, 13.1% of the COPD cases, and 14.8% of the DM cases. Hypoglycemic reactions were the most frequent individual adverse events in the CHF and DM cases (3.6% and 11.4% of the cases, respectively), and theophylline toxicity was most frequent among the COPD cases (4.9%). Patient age, the presence of comorbid diseases, and the Acute Physiology Score (APS) of APACHE II were associated with complication occurrence. For each disease, the patients who had a complication had significantly longer mean hospital stays than did the patients who did not have complications (14.6 to 14.9 days vs 7.2 to 8.2 days, p < 0.01). CONCLUSIONS: Complications are frequent among patients discharged alive with CHF, COPD, or DM. The patients who experienced complications were more ill on admission and had longer hospital stays.

APACHE↗
PubMed1995

Steroid sulfatase and the Y chromosome hypertensive locus of the spontaneously hypertensive rat.

The spontaneously hypertensive rat (SHR) has a Y chromosome locus that increases blood pressure. This locus requires an androgen receptor and testosterone for maximum expression. Steroid sulfatase (STS) catalyzes the conversion of steroid sulfates to their active nonconjugated form. In some mammals the steroid sulfatase locus (Sts) is on the Y chromosome, although the rat Sts is on the X chromosome. We measured STS activity levels in SHR and normotensive Wistar Kyoto (WKY) males. SHR had significantly higher STS activity in testes, adrenal gland, liver, and hypothalamus. The Km values for STS in the two strains were not significantly different; thus, activity differences were likely due to differences in enzyme amounts. STS activity was measured in the backcross strains SHR/y and SHR/a to test and/or confirm a Y chromosome influence on STS. STS activity levels in these strains were intermediate between those of SHR and WKY. Because the blood pressures of SHR/y and SHR/a were also intermediate between SHR and WKY, the STS activity could be a secondary response to the hypertension. An alternative hypotheses is that a regulatory locus in addition to the structural locus is responsible for STS activity levels, and this regulatory locus is on the rat Y chromosome. Further study is needed to discriminate between these possibilities, and until the second hypothesis can be eliminated, the Sts locus or its modifier loci remain a potential component of the Y chromosome hypertensive locus.

Adrenal Glands↗
PubMed1995

Administrative databases, case-mix adjustments and hospital resource use: the appropriateness of controlling patient characteristics.

Hospital administrative databases are used for studying resource use and medical outcomes. The ability to use administrative data to make comparisons among providers requires accurate adjustment of rates based on case mix. Adjustment for case mix often incorporates pre-existing patient conditions such as comorbidities. We tested the hypothesis that some circulatory comorbidities can appear positively or negatively associated with percutaneous transluminal coronary angioplasty (PTCA), not for clinical reasons, but because of the population used for modeling. When statistical models included all discharges with a principal or primary diagnosis of coronary atherosclerosis, or angina with coronary atherosclerosis, multivariate analysis revealed that discharges with dysrhythmias and the more severely ill were less likely to receive PTCA. However, when analysis excluded discharges treated with options (e.g. bypass) reserved for patients with more severe conditions, the presence of dysrhythmias and more severe illness increased the odds of receiving PTCA. Variability involving the direction of association between patient characteristics and a specific intervention illustrates that rates adjusted for patient characteristics cannot be properly interpreted without a clear understanding of the rationale underlying strategies for case-mix adjustment.

Adolescent↗
PubMed1995

Expected source of payment and use of hospital services for coronary atherosclerosis.

To study associations between payer and provision of services for patients hospitalized for coronary atherosclerosis, the authors analyzed abstracts of 24,424 discharges from California acute care hospitals during 1989. Services examined included receipt of coronary artery bypass surgery, percutaneous transluminal coronary angioplasty (PTCA), long length of stay (LOS) without revascularization, and overall LOS. Regression techniques controlled demographic factors and comorbidities. The privately insured were 96% more likely to undergo revascularization (either bypass or PTCA) than Medicaid discharges and 117% more likely than the uninsured. Odds of revascularization for Medicare and health maintenance organization discharges resembled those for the privately insured. Analyzed separately, PTCA was far more likely among the privately insured than Medicaid beneficiaries and the uninsured. In addition, the adjusted odds for PTCA were 52% greater for the privately insured than for health maintenance organization discharges. The greatest likelihood of long LOS without revascularization and the greatest overall LOS was observed for Medicaid discharges. Strong associations, consistent with financial incentives to provide care, exist between payer and provision of services. Future studies need to address whether variations in process result from differences in thresholds for procedure performance, differences in admission practices, or both.

Adolescent↗
PubMed1995

Testosterone regulation of renal alpha 2B-adrenergic receptor mRNA levels.

Androgens regulate blood pressure and renal alpha 2-adrenergic receptors in a parallel fashion in the spontaneously hypertensive rat (SHR). The present studies investigated whether this regulation of renal alpha 2B-adrenergic receptors occurs at the mRNA level. Male and female SHR were gonadectomized at 4 weeks of age. The gonadectomized rats were implanted with or without testosterone propionate. Sham-gonadectomized rats served as controls. Total kidney RNA was purified, and alpha 2B-adrenergic receptor mRNA was quantified with a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. The assay uses a mimic RNA added at known concentrations to the sample RNA. The mimic was constructed from the target sequence in the alpha 2B-adrenergic receptor mRNA plus a 20-bp insertion of a random nucleotide sequence. The amount of alpha 2B-adrenergic receptor mRNA present in each sample was obtained by determining the equivalence point between the amount of RT-PCR product formed in the target band versus the mimic band, which were resolved by gel electrophoresis. Intact males had more than two times as much alpha 2B-adrenergic receptor mRNA as intact females. Castration of males reduced the male-female difference by more than 60%. Ovariectomy slightly increased the alpha 2B-adrenergic receptor mRNA level compared with that of intact females. Treatment with testosterone elevated alpha 2B-adrenergic receptor mRNA levels of gonadectomized males and females to the level of intact males. The alpha 2B-adrenergic receptor mRNA levels correlated remarkably well with renal alpha 2-adrenergic receptor density. We conclude that testosterone regulates renal alpha 2B-adrenergic receptor gene expression at the mRNA level in the SHR.

Animals↗
PubMed1995

Somatic mutation and CDR3 lengths of immunoglobulin kappa light chains expressed in patients with rheumatoid arthritis and in normal individuals.

Immunoglobulin secretion by plasma cells infiltrating synovial membranes is a prominent feature of RA. Previous analyses of a cDNA library generated from synovium of RA patient BC revealed immunoglobulin kappa light chain transcripts with extensive somatic mutation, frequent N region addition, and unexpected variation in the lengths of CDR3 regions which form the center of the antigen binding site. To determine if these characteristics are present in other individuals, we performed reverse transcription-polymerase chain reaction amplification and sequenced > or = 10 V kappa-containing amplicons from nine tissue samples: synovia of three individuals with long-standing RA (including patient BC), PBLs of two of these individuals, and PBLs or splenocytes of four normal individuals. Increased levels of somatic mutation in PBLs appeared to correlate with increased age, which may reflect accumulation of circulating memory cells and/or decreased bone marrow production of naive B lymphocytes. Two of three RA synovial samples and both RA PBL samples exhibited increased proportions of clones with unusual CDR3 lengths. Enrichment for these antibody binding sites could be due to abnormal regulation of the emerging repertoire or to selection for B lymphocytes bearing antibodies of unusual specificity, and may play a role in the pathogenesis of RA.

Adult↗
PubMed1995

Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay.

A chemiluminescence-based GH assay with 30- to 100-fold increased sensitivity recently disclosed combined basal and pulsatile GH secretion in men. However, how age, sex steroid hormones, and obesity singly and jointly influence the basal vs. pulsatile modes of GH release is not known. We used the foregoing assay (detection threshold, 0.002-0.005 microgram/L) and high sensitivity and specificity (> or = 90% each) deconvolution analysis to quantitate basal and pulsatile GH secretion from 24-h serum GH concentration profiles in 26 healthy lean and obese men, whose ages spanned 18-63 yr and whose percentage body fat ranged from 12-47%. Concentrations of serum insulin-like growth factor I (IGF-I), IGF-I-binding protein-1 (IGFBP-1), and IGFBP-3 were related to specific measures of basal or pulsatile GH release. We observed that mean (24-h) serum GH concentrations embraced a 140-fold range from 0.013-1.8 micrograms/L and were related negatively to age (r = -0.50; P < 0.01), percentage body fat (r = -0.620; P < 0.01), and their interaction (r = -0.610; P < 0.01). In contrast, testosterone was a robustly positive statistical determinant of mean serum GH values (r = 0.628; P = 0.0006). Stepwise multivariate regression analysis disclosed that percentage body fat alone and jointly with the serum testosterone concentration controlled, respectively, 38% and 50% of the total variability in GH levels (P = 0.0013 and P = 0.0008). As assessed by deconvolution analysis, GH secretory burst mass was negatively related to percentage body fat (r = -0.621; P < 0.01) and positively to serum testosterone (r = 0.529; P = 0.0054). The calculated half-life of GH correlated positively with serum estradiol (r = 0.447; P = 0.032), and negatively with percentage body fat (r = -0.437; P = 0.048). Basal GH secretion rates were negatively related to serum estradiol (r = -0.485; P = 0.016). In contrast, GH secretory burst frequency and duration were unrelated to age, percentage body fat, or sex steroids. The fraction of total GH secreted in bursts was negatively correlated with the body mass index (r = -0.540; P < 0.01). Serum IGF-I concentrations were positively related to total pulsatile GH secretion (r = 0.690; P = 0.0011) and negatively to age (r = -0.597; P = 0.007) and percentage body fat (r = -0.611; P = 0.009).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1995

Worth remembering: the process and products of oral history.

This paper documents the process of an oral history study that involved interviews with 18 women who graduated from the Illinois Training School near the turn of the century. It described oral history as a methodology, the process of data collection as it related to working with a specific population, the significance of the findings as they relate to self care, and a summary of the efforts with recommendations for future endeavours.

Education, Nursing↗
PubMed1995

Identifying complications and low provider adherence to normative practices using administrative data.

OBJECTIVE: This study investigated whether unexpected length of stay (LOS) could be used as an indicator to identify hospital patients who experienced complications or whose care exhibited low adherence to normative practices. DATA SOURCES AND STUDY SETTING: We analyzed 1,477 cases admitted for one of three medical conditions. All cases were discharged from one of nine participating Department of Veterans Affairs (VA) hospitals from October 1987 through September 1989. Analyses used administrative data and information abstracted through chart reviews that included severity of illness indicators, complications, and explicit process of care criteria reflecting adherence to normative practices. STUDY DESIGN: We developed separate multiple linear regression models for each disease using LOS as the dependent measure and variables that could be assumed present at the time of admission as explanatory variables. Unexpectedly long LOS (i.e., discharges with high residuals) was used to target complications and unexpectedly short LOS was used to target cases whose care might have exhibited low adherence to normative practices. Information gleaned from chart reviews served as the gold standard for determining actual complications and low adherence. PRINCIPAL FINDINGS: Analyses of administrative data showed that unexpectedly long LOS identified complications with sensitivities ranging from 40 through 62 percent across the three conditions. Positive predictive values all were at greater than chance levels (p < .05). This represented substantial improvement over identification of complications using ICD-9-CM codes contained in the administrative database where sensitivities were from 26 through 39 percent. Unexpectedly short LOS identified low provider adherence with sensitivities ranging from 33 through 45 percent with positive predictive values all above chance levels (p < .05). The addition to the LOS models of chart-based severity of illness information helped explain LOS, but failed to facilitate identification of complications or low adherence beyond what was accomplished using administrative data. CONCLUSIONS: Administrative data can be used to target cases when seeking to identify complications or low provider adherence to normative practices. Targeting can be accomplished through the creation of indirect measures based on unexpected LOS. Future efforts should be devoted to validating unexpected LOS as a hospital-level quality indicator. RELEVANCE/IMPACT: Scrutiny of unexpected LOS holds promise for enhancing the usefulness of administrative data as a resource for quality initiatives.

Diabetes Mellitus, Type 1↗