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Biomedical subjects

M L Johnson

Publications and source records attributed to M L Johnson.

At least 271 records · Page 15Linked to original sources
PubMed1984

Biologically active luteinizing hormone is secreted in episodic pulsations that vary in relation to stage of the menstrual cycle.

To characterize the physiological pattern(s) of bioactive LH secretion in normal women, serial blood samples were withdrawn at frequent intervals in each of six women at three different stages of the menstrual cycle. Plasma LH concentrations were quantitated in each sample by both rat interstitial cell testosterone ( RICT ) bioassay and immunoassay (RIA). When the resulting RICT and RIA LH profiles were systematically compared, we found that mean (and integrated) plasma concentrations of bioactive LH were approximately 2-fold higher than immunoactive LH levels at all stages of the menstrual cycle. In addition, unequivocal prominent pulsations of bioactive LH could be demonstrated in these women throughout the normal menstrual cycle. For all stages of the menstrual cycle, bioactive to immunoactive LH ratios within LH pulses were significantly (P less than 0.01) increased over these ratios in the interpulse periods. The frequency of bioactive LH pulses increased dramatically from 0.44 +/- 0.24 (+/- SD) pulses/h in the early follicular phase to 1.21 +/- 0.07 pulses/h in the late follicular phase (P less than 0.003), and then declined to only 0.25 pulses/h in the luteal phase (P less than 0.001). Notably, significant discordance existed between bioactive and immunoactive LH pulses, with 30% of immunoactive and 14% of bioactive LH pulses occurring alone. In conclusion, using the RICT , we demonstrated that biologically active LH is secreted in discrete episodic pulsations in normal women. Estimates of the bioactive to immunoactive LH ratio indicate that these pulses of LH are preferentially enriched in biologically active compared to immunoactive hormone. The properties of bioactive LH pulses are under physiological control, since the amplitude and frequency of bioactive LH pulses vary significantly in relation to phases of the menstrual cycle. Since significant discordance exists between immunoactive and bioactive LH pulsations in normal women, we suggest that estimates of the circulating concentrations of biologically active LH (rather than immunoactive LH alone) are necessary to characterize fully physiological patterns of LH secretion during the menstrual cycle.

Adult↗
PubMed1984

Intensified rates of venous sampling unmask the presence of spontaneous, high-frequency pulsations of luteinizing hormone in man.

To test the validity of venous sampling rates that are generally used to characterize pulsatile LH release in man (e.g. sampling every 15-20 min), we characterized apparent LH pulse frequency in blood withdrawn variously at 20- or 4-min intervals in 19 men, at 2-min intervals in 14 men, and at 1-min intervals in 6 men. In an effort to minimize detection bias, significant LH pulses were evaluated objectively using a computerized pulse-detection algorithm, which tended to maximize recognition of true-positive LH pulses, and minimize false-positive and false-negative pulses. Under these conditions, intensified rates of venous sampling at 4-, 2-, and 1-min intervals exposed approximately 3.6, 4.9, and 13.7-fold more LH pulses, respectively, than could be discerned at a 20-min sampling frequency. In addition, more rapid rates of venous sampling disclosed a previously unobserved pattern of LH pulses, in which higher frequency, lower amplitude LH pulsations were interposed among low frequency, high amplitude LH peaks. Quantitatively, LH pulses unmasked by intensified rates of venous sampling exhibited significantly lower pulse amplitudes, expressed either as a fractional (%) or absolute (mIU/ml) increment, than pulses identified at 20-min intervals. In conclusion, we demonstrated that intensified rates of venous sampling unmask a significant number of otherwise unrecognized LH pulses in the circulation of normal men. Moreover, because generally employed sampling rates overlooked these more rapid physiological fluctuations in LH concentrations, patterns of both high and low frequency LH pulsations must now be characterized in various states of health and disease using more rapid sampling paradigms.

Adult↗
PubMed1984

Mycotic aneurysm of the external iliac artery caused by migration of a total hip prosthesis.

A 77-year-old patient had a mycotic aneurysm of the left external iliac artery secondary to migration of a total hip prosthesis. Symptoms included pain, numbness, decreased hip motion, and a temperature of 38.5 degrees. The left leg was shortened, externally rotated, and swollen. There was anterior thigh hypoesthesia and quadriceps paralysis. A pulsatile mass in the lower left quadrant of the abdomen emitted a thrill and a loud bruit. A preoperative arteriogram facilitated diagnosis and planning of surgery. A transpubic femorofemoral bypass graft was used to reroute blood to the left lower limb, avoiding vascular reconstruction in the area of the aneurysm, a suspected site of infection. A false aneurysm was determined and was then isolated. The prosthesis was removed. During this operation, the acetabular component was found freely mobile within the false aneurysm. Cultures of the removed vascular tissue grew Staphylococcus epidermidis. An arteriogram should be obtained prior to operation for any medial intrapelvic displacement of a total hip prosthesis to diagnose the extent of vascular involvement. Physical examination may not reveal the aneurysm, but signs of neuropathy or venous thrombosis may suggest this diagnosis.

Acetabulum↗
PubMed1984

Role of coagulopathy in newborn intracranial hemorrhage.

Fifty newborn infants of less than 33 weeks' gestation were followed prospectively from birth with serial coagulation and real-time ultrasound studies. A significant association of hypocoagulability in the first four hours of life with subsequent onset or progression of intraventricular or other clinical hemorrhages was documented. Abnormalities included lower values for fibrinogen, platelet count, antithrombin III, and factor VIII with higher values for fibrin monomer and longer Laidlaw whole blood clotting times. These abnormalities tended to correct spontaneously in surviving infants. An association between gestational complications and incidence of hypocoagulability and intracranial hemorrhage (ICH) was noted. Babies of preeclamptic mothers had fewer abnormalities and babies born to mothers with premature rupture of membranes and suspected amnionitis manifested more hypocoagulability and more severe intracranial hemorrhages.

Blood Coagulation Disorders↗
PubMed1984

Timing and antecedents of intracranial hemorrhage in the newborn.

Fifty newborn infants of less than 33 weeks' gestation were followed prospectively from birth to evaluate the temporal relationships of various clinical factors to the onset and progression of intracranial hemorrhage (ICH) in an inborn population given maximal support. ICH was diagnosed and followed with bedside ultrasound every eight hours. The incidence of intraventricular hemorrhage was 30% and of any ICH was 40% with onset from less than 2 hours to 8 days of age. Grades 2, 3, and 4 ICH correlated with Apgar scores of less than 5 at five minutes, vaginal delivery, longer labors, and intrapartum hemorrhage. There was a significant correlation between ICH and both blood pressure fluctuations of greater than 100% and rapid colloid infusions. Slow transfusions of packed red cells did not appear to precipitate episodes of ICH. In a setting of optimal care, ICH appears to be more related to prenatal stresses than to specific postnatal complications.

Apgar Score↗
PubMed1983

Tissue- and cell-specific casein gene expression. II. Relationship to site-specific DNA methylation.

The relationship between DNA methylation and the expression of the gamma- and beta-casein genes was investigated in both expressing and nonexpressing tissues and in isolated tumor cell subpopulations displaying differential casein gene expression. MspI/HpaII digestions of DNA isolated from liver, a totally nonexpressing tissue, indicated that specific sites of hypermethylation existed in these genes as compared to the DNA isolated from casein-producing lactating mammary gland. The positions of these sites were mapped in the gamma-casein gene by comparing total genomic DNA Southern blots to the restriction digests of several overlapping phage clones constituting the gamma-casein gene. In contrast, the methylation status of the HhaI sites in the gamma-casein gene was found to be invariant regardless of the expression status of the gene. The inverse correlation between the hypermethylation of certain MspI/HpaII restriction sites in the casein genes and their potential expressibility was further substantiated by studies in 7,12-dimethylbenz(a)anthracene- and N-nitrosomethylurea-induced mammary carcinomas, which have an attenuated casein gene expression, and in cell subpopulations isolated from the 7,12-dimethylbenz(a)-anthracene tumor which were either depleted or enriched in casein-producing cells. Analysis of total tumor DNAs indicated that the casein genes were hypermethylated at the same sites observed in liver. However, a very faint hybridization signal was observed in the HpaII digests, suggesting cell-specific methylation differences. We have confirmed the hypomethylation of at least two of these MspI/HpaII sites within the subpopulation containing the casein-producing cells at a level consistent with the relative enrichment in that fraction. These results demonstrate differential site-specific casein gene methylation not only between tissues but also between cell subpopulations within a single tissue.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

The measurement of the kinetics of lipid phase transitions: a volume-perturbation kinetic calorimeter.

A volume-perturbation kinetic calorimeter to be used to study membrane phase transitions in lipid vesicles has been developed. In this instrument, the voltage-dependent extension of a stack of piezoelectric crystals is used to force the solution being studied to undergo a small adiabatic bidirectional volume change. This volume change induces a shift in the equilibrium position of the lipid gel to liquid-crystalline transition. The time course of the relaxation to the new equilibrium position is then monitored by observing the induced temperature and pressure changes as a function of time.

Calorimetry↗
PubMed1983

Role of computed tomography and ultrasound in neonatal brain imaging.

Neonatal brain imaging has had a tremendous impact on neonatal care with the introduction of computed tomography and ultrasound to noninvasive study of the neonatal brain. Improved obstetrical and neonatal care have saved many premature infants, resulting in an increased incidence of central nervous system hemorrhagic and hypoxic brain damage in those very-low-birthweight infants who are at greatest risk for intracranial hemorrhage. The evaluation of the neonatal brain can best be done by an understanding of the relative merits of computed tomography and ultrasound as imaging techniques. This report demonstrates the ability of each modality in specific lesions and recommends a basic approach to neonatal care based on the most likely lesion.

Brain↗
PubMed1983

Evaluation and propagation of confidence intervals in nonlinear, asymmetrical variance spaces. Analysis of ligand-binding data.

Two problems that are often overlooked in studies employing nonlinear least-squares techniques for parameter estimation are confidence-interval estimation and propagation. When the parameters are correlated, the variance space and consequently the confidence intervals are nonlinear and asymmetrical. The presented mathematical method for the evaluation of confidence intervals and error propagation addresses these problems. The examples employed to demonstrate these methods include linear least-squares and the nonlinear least-squares analysis of ligand-binding problems, such as hormone receptor interactions and oxygen binding to human hemoglobin. The mathematical procedures have proven very useful for analyzing the molecular mechanism of cooperativity in human hemoglobin (Johnson, M. L., and G. K. Ackers, 1982. Biochemistry 21:201-211).

Computers↗
PubMed1983

Endogenous opiates modulate the pulsatile secretion of biologically active luteinizing hormone in man.

We studied the secretion of physiological pools of immunoreactive and biologically active luteinizing hormone in response to endogenous pulses of gonadotropin-releasing hormone (GNRH) in eugonadal men. Concentrations of immunoactive and bioactive luteinizing hormone (LH) were determined in blood drawn at 20-min intervals for 8 h in eight normal men under two conditions: (a) after placebo, in order to evaluate spontaneous LH pulsations in the basal state, and (b) after administration of the opiate-receptor antagonist, naltrexone, which is believed to amplify the pulsatile release of endogenous GNRH. Spontaneous and naltrexone-stimulated secretion of LH occurred in pulses of high biological activity, as measured in the RICT (rat interstitial cell testosterone bioassay), i.e., bioactive:immunoactive LH ratios within both spontaneous and naltrexone-stimulated LH pulses were higher than corresponding interpulse ratios (P less than 0.001). Quantitative characterization of the pulsatile release of bioactive LH revealed the following specific effects of opiate-receptor blockade: increased 8-h mean and integrated serum concentrations of bioactive LH (P less than 0.002), enhanced pulse frequency of bioactive LH release (P less than 0.001), and augmented peak amplitude of bio-LH pulses (P less than 0.01). Moreover, this increase in episodic secretion of bioactive LH was associated with increased 8-h mean and integrated serum testosterone concentrations in these men (P less than 0.05). We conclude the following: (a) LH is normally released in spontaneous pulses of high biological activity in men; (b) when the endogenous GNRH signal is amplified by opiate-receptor blockade, the pituitary gland releases more frequent bioactive LH pulses, which are of high amplitude and contain a high bioactive:immunoactive LH ratio. This increase in pulsatile release of bioactive LH quantitated in the RICT assay in vitro is reflected by acutely increased serum testosterone concentrations in vivo. We infer that modulation of the episodic GNRH signal by endogenous opiates provides another significant mechanism by which the hypothalamus can alter the biological activity of circulating gonadotropic hormone in man. Moreover, observed alterations in the pulsatile pattern of bioactive LH release were associated in turn with significant changes in testosterone concentrations. Thus, we hypothesize that alterations in the properties of the bioactive LH pulse signal can provide an important mechanism for regulating target-cell function within the gonad in states of health or disease.

Adult↗
PubMed1983

Mode of secretion of bioactive luteinizing hormone in man.

The episodic nature of gonadotropin secretion was originally defined by RIA of circulating LH concentrations. We analyzed the pulsatile release of biologically active LH by measuring plasma LH concentrations in the rat interstitial cell testosterone bioassay. A computer algorithm to discriminate true biological signals (LH pulses) from background variation was applied to serially sampled LH data from seven men and seven postmenopausal women. Our results indicate the following. 1) In all subjects, mean bioactive LH values were considerably higher than immunoactive levels, (41.4 +/- 15.1 and 450 +/- 243 mIU/ml vs. 10.2 +/- 2.3 and 83 +/- 35 for men and postmenopausal women, respectively). There was a corresponding 4-fold increase in the total area under the bioactive LH secretion profile compared with that defined for the immunoactive hormone. 2) The absolute amplitude of the bioactive LH peaks was 0.5- to 11-fold higher than the immunoactive values. 3) Although the majority of the LH peaks were coincident by bioassay and RIA, significant dissociation occurred in 20% and 28% of the total LH peaks (rat interstitial cell testosterone bioassay and RIA) in men and postmenopausal women, respectively. 4) Significant increases in the bioactive to immunoactive ratio over interpulse bioactive to immunoactive levels occurred in 98% of the pulses in the men and 83% of those in postmenopausal women. Also, in two men, peaks of LH bioactivity exceeding 100 mIU were followed by major increases in serum testosterone concentrations. These findings demonstrate the value of bioactive LH determinations and indicate that LH is secreted in pulses of high biological activity. The in vitro LH bioassay provides a sensitive and appropriate estimate of functionally active LH in the circulation.

Adult↗
PubMed1983

Do alpha-adrenergic mechanisms regulate spontaneous or opiate-modulated pulsatile luteinizing hormone secretion in man?

Brain noradrenergic mechanisms participate in the excitatory control of episodic LH release in many experimental animals, including the nonhuman primate. In addition, augmentation of pulsatile LH release in the rodent in response to opiate receptor antagonists is dependent upon intact central noradrenergic pathways. The applicability of these tenets to humans is not known. We tested the excitatory influence of brain noradrenergic systems on pulsatile LH secretion in normal men by administering phenoxybenzamine (an irreversible, preferentially postsynaptic, alpha 1-receptor blocker) or alpha-methyldopa (an inhibitor of brain adrenergic transmission). Five normal men underwent repetitive (every 20 min) venous sampling for 8 h to characterize episodic LH release quantitatively under basal conditions and after the administration of naltrexone, a potent opiate receptor antagonist which stimulates puslatile LH release. Subjects received saline, phenoxybenzamine (1 mg/kg, iv, over 90 min), or alpha-methyldopa (250 mg, orally, every 6 h). The following parameters of spontaneous episodic LH secretion were not altered after phenoxybenzamine or alpha-methyldopa administration: mean and integrated serum LH concentrations, LH pulse frequency, LH pulse amplitude (percentage or milliinternational units per ml increment), and absolute peak serum LH values. In addition, the administration of adrenergic inhibitors did not impede the capacity of naltrexone to significantly augment pulsatile LH secretion in these subjects. We conclude that in the doses used, phenoxybenzamine and alpha-methyldopa do not alter spontaneous or opiate-modulated episodic LH release in normal men.

Adult↗
PubMed1983

A tissue-equivalent upper abdominal phantom.

The first prototypes of an abdominal phantom have been constructed. The phantom is intended for eventual use in training diagnostic ultrasound personnel and in demonstrating commercial equipment. It is constructed from plastics believed to be stable and approximately tissue-equivalent at room temperature. Abdominal structures are formed from a dispersion of a polystyrene butadiene plastic in mineral oil. Polyvinyl chloride particles are incorporated to provide the desired attenuation coefficients and scattering levels. B-scans of the phantom produced realistic images, although problems associated with scanning technique and somewhat high phantom attenuation were noted. Very useful phantoms should result from relatively simple improvements in construction techniques.

Abdomen↗
PubMed1983

Isolation and characterization of casein-producing and -nonproducing cell populations from 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinomas.

Previous studies from our laboratory have demonstrated that hormone-dependent 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinomas possess only a limited ability to synthesize the mammary gland-specific milk proteins, and this expression of normal differentiated function is limited to a small subpopulation of tumor cells (S. C. Supowit and J. M. Rosen, Cancer Res., 42: 1355-1360, 1982). In an effort to define the molecular defect in hormone-regulated casein gene expression in these tumors, a method has been developed which separates the 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinoma into two subpopulations of cells. Collagenase-dissociated tumor cell suspensions were fractionated by both continuous and discontinuous Percoll gradient centrifugation, and the separated cell populations were analyzed following plating on collagen-coated dishes. Two fractions of differing densities were isolated. The top fraction (rho = 1.05), containing approximately 75% of the dissociated tumor epithelial cells, is depleted in casein-producing cells, while the bottom fraction (rho = 1.07) is enriched 5- to 10-fold in casein-producing cells as assayed by both indirect immunofluorescence, using a specific anticasein antibody, and direct measurement of casein messenger RNA levels. These two subpopulations were further characterized by scanning and transmission electron microscopy, with respect to their cell morphology and ultrastructure, for the presence of hormone receptors; the arrangement of the epithelial cell marker, keratin; and their cell cycle distributions and ploidy. Prolactin, insulin, and estradiol binding were found to be uniform throughout each cell subpopulation and qualitatively similar between fractions. Both fractions appeared to be epithelial-like in morphology, containing numerous surface microvilli as assessed by scanning electron microscopy and containing numerous surface microvilli as assessed by scanning electron microscopy and contained keratin filaments as determined by indirect immunofluorescence. Furthermore, they had similar cell cycle distributions and ploidies of 2n. Differences in cell ultrastructure were observed between these two tumor epithelial cell fractions, reflecting an increased development of rough endoplasmic reticulum in the bottom fraction and a higher concentration of lipid-containing vesicles and free polysomes in the top fraction. The failure of the majority of the cells within the 7,12-dimethylbenz(a)anthracene-induced mammary tumors to produce casein in response to prolactin is not due to a receptor-negative phenotype or general cell type difference.

9,10-Dimethyl-1,2-benzanthracene↗