Hypogonadism caused by a single amino acid substitution in the beta subunit of luteinizing hormone.
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Adult↗
Biomedical subjects
J Weiss
Publications and source records attributed to J Weiss.
Bio-effects of high magnetic fields: a study using a simple animal model.
The desire to do clinical imaging and spectroscopy at magnetic field strengths greater than 2 Tesla (T) necessitates investigation of possible bioeffects at these high fields. A simple T-maze was utilized to evaluate the aversive effects of exposure to three levels of static magnetic field (0, 1.5, and 4 T). The right arm of the maze extended into the center of a 30-cm horizontal bore magnet, while the left arm extended into a mock magnet bore with the same dimensions. The self-shielded design of the magnet reduces the fringe field to zero within 1 m of the bore, placing the start box of the maze outside the 5-G line of the magnet. Each rat performed a total of ten trials at each level of magnetic field strength. A follow-up subset was run at 4 T with the maze reversed. At 0 T, the rats entered the magnet freely. No significant differences from the control were observed at 1.5 T. At 4 T, however, in 97% of the trials the rats would not enter the magnet. In the maze-reversed subset a majority of the rats turned toward the magnet, indicating that they had learned an aversive response from the previous trials at 4 T. However, in only 4 decisions out of 58 did the rats actually enter the magnet. Eighteen decisions to turn around were made at the edge of the magnet in a region of strong field gradients (up to 13 T/m) and a field strength up to 1.75 T.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Antitumour effect and symptomatic control with interferon alpha 2b in patients with endocrine active tumours.
26 patients with progressive neuroendocrine tumours received 3 x 10(6)U/m2 interferon alfa (IFN-alpha 2b) subcutaneously thrice weekly, until progression, as outpatients with moderate toxicity. 4/16 carcinoids and none out of 10 endocrine pancreatic tumours showed objective regression. Another 17 patients (68%) had no change. For a median of 34 weeks symptom control was excellent: 9 of 17 patients had major relief from pain, 11 of 13 from diarrhoea, and 7 of 7 from flushing. Thus, low-dose INF-alpha 2b given thrice weekly might be as effective as daily treatment with higher dosages. Treatment was only administered to patients with progression or major symptoms and this did not seem to adversely affect remission quality and survival.
Adult↗
[Histochemical investigations on the localization of acetylcholinesterase in the kidney of selected vertebrates].
The light and electron microscopical localization of AChE activity in the kidney of selected vertebrates was studied using the method of Karnovsky and Roots (1964) for light microscopy and the modification of the Koelle and Friedenwald's technique according to Tsuji (1974, 1984) for electron microscopy. AChE activity could be demonstrated light microscopically mainly within the glomeruli of some mammals (golden hamster, mouse, rat) and non-mammalian vertebrates (carp, frog). No activity was found in the glomeruli of guinea pig, of chicken and tortoise. In the mammalians, the strongest AChE activity could be demonstrated in the guinea pig, the lowest in the rat. A strong AChE enzyme activity was also detected within the interlobular arteries and the cells of Bowman's capsule. With the electron microscopical method AChE activity was demonstrated in mesangial cells and endothelial cells of the glomeruli (golden hamster and carp) and in the cells of Bowman's capsule (carp). Reaction product was localized within the cisterns of endoplasmic reticulum and the perinuclear space (nuclear envelope). A high amount of electron opaque material could be observed in the cells of Bowman's capsule and their lamina basalis. The functional significance of the localization of AChE activity in the glomeruli will be discussed.
Acetylcholinesterase↗
Multiple sclerosis: will it come between us? Sexual concerns of clients and their partners.
Multiple sclerosis (MS), an unpredictable neurologic disease, is sometimes called the crippler of young adults. This crippling effect often involves sexual functioning. Sexuality is an issue that is frequently difficult for clients, their partners and health care providers to discuss. To address this difficulty, a teaching pamphlet entitled, MS ... Will it Come Between Us? was produced. Open communication and creativity are helpful in dealing with problems frequently encountered by clients with MS: fatigue, impotence, decreased vaginal lubrication, bladder and bowel dysfunction. The pamphlet helps clients with these issues as well as the basics of sexuality as a whole.
Adaptation, Psychological↗
High-affinity binding of the bactericidal/permeability-increasing protein and a recombinant amino-terminal fragment to the lipid A region of lipopolysaccharide.
Bactericidal/permeability-increasing protein (BPI) is a 55-kDa cationic protein (nBPI55) elaborated by polymorphonuclear neutrophils (PMN). BPI has potent bactericidal activity against a wide variety of gram-negative organisms and neutralizes endotoxin activities. An N-terminal fragment of nBPI55 exhibits the bactericidal and antiendotoxin properties of the holoprotein. To further characterize the biological activities of the N-terminal fragment, a recombinant protein (rBPI23) corresponding to the first 199 amino acids of human BPI was produced and purified. rBPI23 had antibacterial activity equivalent to that of nBPI55 against Escherichia coli J5. Furthermore, both rBPI23 and nBPI55 bound identically to a broad range of R- and S-form lipopolysaccharides (LPS) and to natural and synthetic lipid A. Binding of radiolabeled nBPI55 to LPS was inhibited in an identical fashion by either nBPI55 or rBPI23. The binding of both proteins to immobilized E. coli J5 lipid A was inhibited in a comparable fashion by long- or short-chain LPS or lipid A. The binding of both rBPI23 and nBPI55 was specific, saturable, and of high affinity, with an apparent Kd of approximately 2 to 5 nM for all ligands tested. These results demonstrate that BPI recognizes the highly conserved lipid A region of bacterial LPS via residues contained within the amino-terminal portion of the BPI molecule.
Antimicrobial Cationic Peptides↗
Human bactericidal/permeability-increasing protein and a recombinant NH2-terminal fragment cause killing of serum-resistant gram-negative bacteria in whole blood and inhibit tumor necrosis factor release induced by the bacteria.
The bactericidal/permeability-increasing protein (BPI) of neutrophils and BPI fragments neutralize the effects of isolated Gram-negative bacterial lipopolysaccharides both in vitro and in vivo. Since endotoxin most commonly enters the host as constituents of invading Gram-negative bacteria, we raised the question: Can BPI and its bioactive fragments also protect against whole bacteria? To determine whether the bactericidal and endotoxin-neutralizing activities of BPI/fragments are expressed when Gram-negative bacteria are introduced to the complex environment of whole blood we examined the effects of added BPI and proteolytically prepared and recombinant NH2-terminal fragments on: (a) the fate of serum-resistant encapsulated Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa that survive the antibacterial actions of whole blood and (b) the ability of these bacteria to trigger cytokine release. Added BPI in nanomolar concentrations killed each of three encapsulated strains of E. coli and in closely parallel fashion inhibited tumor necrosis factor (TNF) release. Holo-BPI and its NH2-terminal fragment were equipotent toward a rough LPS chemotype K1-encapsulated strain, but the fragment was substantially more potent than holo-BPI toward two encapsulated smooth LPS chemotype strains. TNF release induced by K. pneumoniae and P. aeruginosa was also inhibited by both holo-BPI and fragment but, at the protein concentrations tested, P. aeruginosa was killed only by the fragment and K. pneumoniae was not killed by either protein. The bactericidal action of BPI/fragment toward E. coli is inhibited by C7-depleted serum, but accelerated by normal serum, indicating that BPI, acting in synergy with late complement components, enhances extracellular killing of serum-resistant bacteria. Thus, BPI and an even more potent NH2-terminal fragment may protect against Gram-negative bacteria in the host by blocking bacterial proliferation as well as endotoxin-mediated effects, not only as components of the intracellular antibacterial arsenal of the neutrophil, but also as potentially therapeutic extracellular agents.
Antimicrobial Cationic Peptides↗
Quantitative determination of morphometric indices of the total and perfused capillary network of the newborn pig brain.
The purpose of this study was to determine if the newborn pig brain had a reserve of unperfused capillaries during normoxia. To accomplish this, a method was developed to determine the volume fraction, surface area, and number of both total and perfused capillaries in the newborn pig brain. Newborn pigs of either sex, 2-7 d old, were used. FITC-dextran, molecular weight 147,000, was used as a plasma marker to visualize the perfused capillaries. Alkaline phosphatase staining was used to stain the total capillary bed of the brain. Our results showed that FITC-dextran stayed within the vascular compartment, as it was not seen in areas that were not subsequently visualized with alkaline phosphatase staining. Eighty-four to 86% of the alkaline phosphatase-stained capillaries could be visualized with perfusion markers (india ink or FITC-dextran) in different brain regions. Similar results were obtained in two animals using a basement membrane stain, silver methenamine. The total volume fraction of capillaries (mm3/mm3) was cortex 0.055 +/- 0.012, cerebellum 0.062 +/- 0.011, and medulla 0.039 +/- 0.012. Capillary surface area (mm2/mm3) of different brain regions averaged cortex 23.2 +/- 1.8, cerebellum 24.8 +/- 2.5, and medulla 15.8 +/- 2.9. The total number of capillaries (per mm2) was cortex 375 +/- 37, cerebellum 329 +/- 37, and medulla 216 +/- 32. The time course of filling of the capillaries indicated that approximately 50% were perfused at 6 s, which increased to over 80% at 12 s and remained unchanged thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Pulsatile gonadotropin-releasing hormone modifies polyadenylation of gonadotropin subunit messenger ribonucleic acids.
Gonadotropin subunit mRNA levels rise after castration, coincident with a period of increased GnRH input to the pituitary. In addition to increased levels of gonadotropin mRNAs, we observed that the sizes of the alpha and LH beta mRNAs were increased after ovariectomy (OVX) of rats. To determine whether these changes occurred in the 5' (alternate transcriptional start site or splicing)- or 3' (altered polyadenylation)-end of the molecules, mRNAs were cleaved using oligonucleotide-directed RNase-H digestion, and the fragments were analyzed by Northern blot, using probes specific to the 5'- and 3'-segments of each transcript. After OVX, there was no change in the sizes of the 5'-segments of LH beta, FSH beta, and alpha-subunit mRNAs. However, the LH beta and alpha-subunit 3'-fragments were increased in size, indicating a shift to more adenylated forms of the LH beta and alpha transcripts. For FSH beta, the 3'-fragment bands were more diffuse than for LH beta or alpha-subunit, and no alteration in the lengths of FSH beta poly(A) tails were detected. A perifused pituitary cell system was used to determine whether pulses of GnRH were sufficient to cause modifications of polyadenylation. GnRH was administered as hourly 10-nM pulses for 4-12 h. Time-dependent increases in the sizes of LH beta and alpha-subunit mRNAs were observed in GnRH-treated cells compared to cells receiving no GnRH. Changes in the lengths of LH beta and alpha-subunit mRNAs were shown to be due to increased polyadenylation, and there was no observable change in polyadenylation of FSH beta mRNA. In addition, no changes were observed in the size of the 3'-fragments of PRL or beta-actin mRNAs. These data demonstrate that pulsatile GnRH administered in vitro elicits specific increases in the lengths of the LH beta and alpha-subunit mRNA poly(A) tails. Similar changes occur after OVX. Thus, in addition to transcriptional stimulation of the gonadotropin gene, GnRH modifies gonadotropin mRNAs at a posttranscriptional level.
Animals↗
Dynamic regulation of follicle-stimulating hormone-beta messenger ribonucleic acid levels by activin and gonadotropin-releasing hormone in perifused rat pituitary cells.
Maintenance of FSH biosynthesis requires ongoing exposure to pulsatile GnRH. Recent data demonstrate that activin also stimulates FSH biosynthesis. We used a perifused pituitary system to examine regulation of FSH beta mRNA levels by pulsatile GnRH and activin. Hourly pulses of 10 nM GnRH increased FSH beta mRNA levels by 3-fold. In the same experiment, continuous infusion of 50 ng/ml activin elicited a 50-fold increase in FSH beta mRNA. This magnitude of response to activin in perifusion was unexpected, as only a 2.7-fold increase in FSH beta mRNA was observed when activin was administered to pituitary cells that were cultured in dishes. Since perifusion columns, unlike culture dishes, are exposed to a continuous supply of fresh medium, we examined the possibility that endogenous factors produced by pituitary cells cultured in dishes were stimulating the cells in a paracrine fashion, thereby precluding the full response to exogenously added activin. The kinetics of FSH beta mRNA expression were examined immediately after pituitary dispersion and at different times after culturing the cells in plates. FSH beta mRNA levels fell rapidly after dispersion to 8% of initial levels and remained low over 8 h. Thereafter, FSH beta mRNA levels increased slowly and exceeded initial levels by the second day of culture. In a parallel set of experiments, when medium conditioned by exposure to plated cells was applied to the perifusion system, FSH beta mRNA levels were selectively stimulated (6-fold). These data suggest the removal during dispersion and subsequent accumulation in culture of pituitary-derived factors that are important for the maintenance of FSH beta mRNA levels. We conclude that activin plays a greater role in the regulation of FSH beta mRNA levels than was suggested by previous experiments employing static culture systems in which autocrine or paracrine stimulation may have obscured the effects of exogenously added activin.
Actins↗
Glycoprotein hormone alpha-subunit-producing pituitary adenomas in rats treated for one year with calcitonin.
Calcitonin, a calcium-lowering hormone, has been associated with an increased incidence of nonfunctioning pituitary tumors in rats. In this study, rats were treated with calcitonin (80 IU/kg/d) for 52 weeks. After treatment with calcitonin, immunohistochemistry and in situ hybridization analyses demonstrated that most pituitary tumors expressed the glycoprotein hormone alpha-subunit. Expression of the alpha-subunit was identified rarely in hyperplastic lesions of control animals. Serum levels of GH, PRL, ACTH, LH, and FSH were unchanged in calcitonin-treated rats relative to controls. However, TSH levels were increased 2.1 fold after chronic treatment with calcitonin in both male and female rats (P less than 0.001). The level of glycoprotein hormone alpha-subunit was markedly increased (20-fold) in male rats with smaller elevations in female rats. Time course studies demonstrated that increases in serum alpha-subunit levels could be detected by 24 weeks of treatment and that elevations in alpha-subunit were present in the majority of animals by 40 weeks of treatment with calcitonin. The authors conclude that high doses of calcitonin, administered to rats for 6 months or longer, increases the incidence of alpha-subunit-producing pituitary tumors.
Adenoma↗
[Analysis of the place of regulation of C-11 transmitters at the Tele-electronic Works "Telkom-Telfa" in Bydgoszcz from the point of view of visual hygiene].
The authors performed a detailed analysis of 100 positions of regulation of the C-11 transmitters in the "Telcom-Telfa" ++Tele-electronic Works in Bydgoszcz. It was determined that the requirements for the condition of the eyes and the lighting at this workstand are considerable. Conclusions and recommendations tending to improvement of the working conditions are drawn up. Proposed is eventual rationale leading to the reduction of the eyestrain and facilitation of the work.
Asthenopia↗
Substance abuse during pregnancy. Legal & health policy issues.
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Child↗
[Repeated treatment of subtotal vertebrobasilar stenosis with tissue plasminogen activator (tPA)].
We report on the successful repeated treatment of a patient with rapidly progressive severe brain-stem stroke by application of I.V. tissue plasminogen activator (tPA). This treatment twice led to a prompt remission of severe brain-stem symptoms, although a permanent therapeutic success could not be achieved. Unfortunately, the patient died a few days later from pneumonia and sepsis. Necropsy revealed bilateral partial brain-stem infarctions and a subtotal stenosis of the vertebrobasilar junction with superimposed fresh thrombus. The clinically dramatic response to tPA indicates that this type of treatment is potentially successful in high-grade subtotal basal cerebral artery stenosis with progressive stroke symptoms. In particular, application of tPA should be considered if stroke progression cannot stopped by therapeutic heprinization. A prospective randomized oligocentric study is advocated.
Aged↗
Heart rate variability. Frequency domain analysis.
Experience with frequency domain analysis over the past two decades strongly suggests that it represents a unique, noninvasive tool for achieving a more precise assessment of autonomic function in both the experimental and clinical settings. Available studies indicate that the significance of the HF component is far better understood than that of the lower frequency components. In general, it is considered to reflect vagal activity, and because it is readily manipulated pharmacologically, is used as a an index of that activity. However, some caution is required because this parameter also is strongly influenced by the degree of coupling between respiration and heart rate, which, in turn, reflects the intensity of the respiratory effort as well as of parasympathetic activity. Respiratory pattern also can significantly influence HF power. The use of controlled breathing minimizes these problems, improves reproducibility of test findings, and also facilitates quantitative comparisons. The situation with respect to LF power is more complicated because it is modulated by both sympathetic and parasympathetic outflows (see previous discussion) as well as by other factors, including baroreceptor activity. Therefore, LF analysis per se cannot afford a precise delineation of the state of sympathetic activation. Determinations of the LF/HF ratio, an index of sympathovagal balance both under control conditions and in conjunction with interventions that maximize sympathetic and parasympathetic activity, provide additional insights, as do correlations between spectral activity and direct nerve recordings, plasma norepinephrine concentrations, and radionuclide imaging of adrenergic nerves. Renewed interest has recently been evinced in frequencies lower than 0.04 Hz in view of reports that the VLF portion of the spectrum (0.01-0.04 Hz) reflects a purer form of sympathetic activity than does the LF band. Despite the potential applicability to clinical problems, only very little is known about the physiologic basis of the VLF and ULF bands. Further study is required. However, it is important to note that meaningful determinations of VLF and ULF power may be difficult because decreases in frequency to such low levels are associated with an increasing propensity to violate the rules governing power spectral determinations (see previous discussion and appendix), violations that diminish reliability despite the most sophisticated preprocessing. It is also noteworthy that the reliability of spectral power determinations diminishes with decreases in the power of the signal and of the signal-to-noise ratio.(ABSTRACT TRUNCATED AT 400 WORDS)
Aging↗
Race, family income, and low birth weight.
The relations among race, family income, and low birth weight were examined using information obtained from the National Longitudinal Survey of Youth, which conducted yearly interviews with a nationally representative sample of young women identified in the late 1970s. Data were available for these women and their offspring from 1979 through 1988. Maternal education, maternal age, age/parity risk, marital status, and smoking during pregnancy served as covariates in cross-sectional and longitudinal analyses. The risk of low birth weight among births to black women and white women who were poor was at similarly high levels regardless of whether poverty was determined prior to study entrance or during the study period. Longitudinal analyses showed an exceptionally large increase in risk of low birth weight among children born to women whose prior pregnancy ended in a low-birth-weight infant. These two findings emphasize the importance of factors antecedent to the pregnancy in the genesis of low birth weight.
Adolescent↗
Endotoxin-neutralizing properties of the 25 kD N-terminal fragment and a newly isolated 30 kD C-terminal fragment of the 55-60 kD bactericidal/permeability-increasing protein of human neutrophils.
The bactericidal/permeability-increasing protein (BPI) of polymorphonuclear leukocytes (PMN) is a potent cytotoxin, specific for Gram-negative bacteria, that also inhibits endotoxin activity by neutralizing isolated bacterial lipopolysaccharides (LPS). We have previously shown that an isolated 25 kD N-terminal fragment of human BPI carries all the antibacterial activities of the parent 55-60 kD molecule. In this study we have compared the LPS-neutralizing activities of human holo-BPI, the N-terminal fragment and a 30 kD C-terminal fragment that we have now isolated. We show that the N-terminal fragment also has LPS-neutralizing activity as detected by inhibition (up to 95%) of (a) activation by LPS of procoagulant proteases in Limulus amebocyte lysates, (b) LPS "priming" of PMN, and (c) LPS-mediated production of tumor necrosis factor in whole human blood. Holo-BPI and the 25 kD fragment have similar neutralizing potency (in nanomolar range) in all assays toward "smooth" LPS from Escherichia coli O111:B4 and O55:B5 (possessing long chain polysaccharide or O-antigen), and "deep rough" LPS from Salmonella minnesota Re595 mutant (possessing no O-antigen). The C-terminal fragment of BPI is devoid of antibacterial activity when tested against BPI-sensitive E. coli J5, but does have endotoxin-neutralizing activity. This activity is weak relative to holo-BPI and the 25 kD N-terminal fragment in the Limulus and PMN-priming assay, but is comparable for inhibition of TNF production in whole blood. We conclude that the principal determinants for LPS recognition and neutralization, like those for antibacterial action, reside in the N-terminal half of the BPI molecule, but that sites within the C-terminal half can also contribute to BPI-LPS interaction once LPS is detached from the bacterial envelope.
Antimicrobial Cationic Peptides↗
Conversion of pig pancreas phospholipase A2 by protein engineering into enzyme active against Escherichia coli treated with the bactericidal/permeability-increasing protein.
Phospholipases A2 (PLA-2) are conserved enzymes that can vary widely in their activity toward certain biological targets. Activity of PLA-2 toward Escherichia coli treated with the bactericidal/permeability-increasing protein (BPI) of granulocytes has been detected only in "Group II" PLA-2 (lacking Cys11-Cys77) and correlates with overall basicity and the presence of a cluster of basic amino acids within a variable surface region near the NH2 terminus (including residues 6, 7, 10, 11, and 15). We now show that of five pancreatic PLA-2 ("Group I" enzymes) tested from different species of mammals, the human enzyme that is most basic both globally (pI 8.7) and locally (Arg-6, Lys-7, and Lys-10) is active toward BPI-treated E. coli (approximately 1-2% activity of the most active Group II PLA-2) whereas the other four PLA-2 are essentially inactive (less than 0.1%). The cDNA of the pig pancreatic PLA-2 (pI 6.4; Arg-6, Ser-7, Lys-10) has been modified by site-specific mutagenesis and the wild-type and mutant PLA-2 have been expressed in and purified from either E. coli or Saccharomyces cerevisiae to determine more precisely the structural determinants of PLA-2 activity toward BPI-treated E. coli. The single substitution of lysine (or arginine) for Ser-7 transformed the pig pancreatic PLA-2 into an active enzyme toward BPI-treated E. coli possessing 25-50% the activity of the human PLA-2. Additional modifications to increase global basicity (increase in net charge up to +4) caused a further (up to 2-fold) increase in activity. All mutant PLA-2 still containing Ser-7 possessed little or no activity toward BPI-treated E. coli. Changes in activity toward BPI-treated E. coli were accompanied by parallel changes in enzyme binding to this target. In contrast, substitution of lysine (or arginine) for Ser-7 caused little or no alteration of enzyme activity toward either autoclaved E. coli or egg yolk lipoproteins indicating no major effects on the catalytic properties of the PLA-2. This study demonstrates directly the role of NH2-terminal basic residues in the action of PLA-2 on BPI-treated E. coli and suggests that these properties mainly facilitate PLA-2 binding to this biological target.
Animals↗