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Biomedical subjects

J Weiss

Publications and source records attributed to J Weiss.

At least 145 records · Page 8Linked to original sources
PubMed1997

Expression of ryanodine receptors in the pituitary gland: evidence for a role in gonadotropin-releasing hormone signaling.

GnRH elicits secretion of LH and FSH from gonadotropes by activating an array of intracellular signals including the generation of inositol triphosphate and the release of intracellular calcium. Given the important role of calcium in the secretory responses to GnRH, we examined the expression and function of the ryanodine receptors, which are known to modulate calcium release from intracellular stores. Using RT-PCR analysis, we found that ryanodine receptor (RyR) types 2 and 3, but not type 1, are expressed in rat pituitaries. Pulses of GnRH were administered to perifused primary rat pituitary cells in the presence or absence of a ryanodine receptor antagonist, ruthenium red, to assess effects on GnRH-mediated LH secretion. Treatment with ruthenium red resulted in a 40% decrease in the spike phase of GnRH-induced LH release and a 35% reduction in the plateau phase. Ruthenium red also inhibited GnRH-mediated transcription of a transfected alpha-LUC reporter plasmid. RyR messenger RNA (mRNA) expression varied during the rat estrous cycle with maximal levels following increases of progesterone. The effects of gonadal steroids on pituitary RyR mRNA levels were examined directly in ovariectomized rats that were treated with estrogen (E), or estrogen and progesterone (P). In this paradigm, E decreased, whereas E + P increased RyR3 mRNA levels. These results indicate that RyR is expressed and hormonally regulated in the rat pituitary and suggest that it might play a role in mediating GnRH-induced gonadotropin synthesis and secretion.

Animals↗
PubMed1997

Pituitary follistatin regulates activin-mediated production of follicle-stimulating hormone during the rat estrous cycle.

Follistatin, an activin-binding protein, plays a key role in the modulation of activin-dependent functions. In the anterior pituitary, activin stimulates the synthesis and secretion of FSH. In the current study, we assessed the roles of locally produced activin and follistatin in the control of FSH gene expression and secretion. The anterior pituitary gland follistatin content was measured at frequent intervals during the rat estrous cycle. Follistatin protein levels were high before the primary gonadotropin surges, decreased by 50% on proestrous evening, and rebounded to a peak at midnight on proestrus before returning to presurge levels on estrus morning. Changes in pituitary follistatin protein content were preceded by parallel changes in pituitary follistatin messenger RNA (mRNA). The trough in follistatin protein content on proestrus coincided with a peak in circulating levels of free activin A (not bound to follistatin) and a sharp rise in FSHbeta mRNA levels, suggesting that decreased pituitary follistatin leads to increased available activin. To quantitate the contribution of pituitary free activin to pituitary expression of FSHbeta mRNA and the primary and secondary serum FSH surges, rats were infused through carotid catheters with saline or recombinant human follistatin (288-amino acid isoform; rhFS-288) at different times during the estrous cycle. Infusion of rhFS-288 on diestrus did not affect FSH production. In contrast, infusion of rhFS-288 during the secondary FSH surge decreased the peaks in FSHbeta mRNA and serum FSH by 63% and 47%, respectively, relative to those in saline-infused control animals. Infusion of rhFS-288 during the primary FSH surge decreased serum FSH to a lesser degree (24%). These data indicate a physiological role for pituitary follistatin in the control of activin-mediated FSH synthesis and secretion during the rat estrous cycle.

Activins↗
PubMed1997

Ultraviolet light exposure, pigmentary traits and the development of melanocytic naevi and cutaneous melanoma. A case-control study of the German Central Malignant Melanoma Registry.

The present study firstly aimed at understanding the relationship between sun exposure, pigmentary traits and the history of sunburns. Secondly, the significance of UV-exposure for cutaneous melanoma and for melanocytic naevi was investigated. The case-controlled study comprised 513 patients with primary cutaneous melanoma and 498 controls matched by age and gender. Multivariate logistic regression analysis was used to study melanoma risk factors. The number of common melanocytic naevi was associated with age, gender, the history of sunburns and UV-exposure during holidays (odds-ratio = 1.9; 95% confidence interval = [1.1, 3.4]) for 3 weeks or more. The number of atypical melanocytic naevi was significantly related to age, gender, pigmentary traits, the history of sunburns and UV-exposure during holidays (odds-ratio = 3.5; 95% confidence interval = [1.4, 9.0]) for 2 months or more. The results of the present study showed that both the history of sunburn and intensive sun exposure during holidays were important for the development of melanocytic naevi and, therefore, indirectly for cutaneous melanoma. In addition, a particular type of pigmentation was found to be related to atypical melanocytic naevi.

Adolescent↗
PubMed1997

ECT treatment and cerebral perfusion in Catatonia.

A 40-yr-old woman with a diagnosis of schizoaffective disorder developed catatonia in the context of a depressive episode. A dramatic decrease in perfusion of the inferior frontal, posterior temporal and parietal lobes bilaterally and in posterior frontal lobes corresponding to the motor cortices was noted on the 99mTc-HMPAO SPECT scan obtained in the acute phase. The most dramatic decreases compared to normal control subjects were observed in the left parietal and left motor cortices. The patient was treated with a five-treatment course of electroconvulsive therapy (ECT), which resulted in a complete resolution of catatonia and some resolution of her symptoms of depression. The repeat HMPAO-SPECT scan showed improved perfusion in all areas. The most dramatic increases occurred in the left parietal and left motor cortices. Decreased perfusion in motor and parietal cortices could be state-specific to catatonia. Thus, SPECT imaging may be a useful method for monitoring catatonia treatment response.

Adult↗
PubMed1997

Alkaptonuric ochronosis: report of two affected brothers.

Alkaptonuric ochronosis is a rare inborn metabolic disorder. Because of the deficient activity of the enzyme homogentisic acid oxidase, homogentisic acid accumulates in plasma, is deposited in various tissues and is excreted in large amounts in urine. Dark brown discoloration of urine on exposure to air or after addition of alkaline solution is characteristic. We describe two brothers with typical alkaptonuric ochronosis with dark urine, blue pigmentation of auricles and axillae, focal brown hyperpigmentation of sclerae, and anthropathy.

Ear Diseases↗
PubMed1997

Antimicrobial peptides of phagocytes and epithelia.

Human and other vertebrate leukocytes contain multiple distinct antimicrobial (poly)peptides. Of these, BPI is a LPB protein active against gram-negative bacteria, PLA2 specifically cleaves bacterial phospholipids, while defensins and cathelicidins are broad spectrum antimicrobials that preferentially permeabilize microbial membranes. These and other polypeptides function in both phagocytic and extracellular killing of microbes, attacking multiple molecular targets to cooperatively penetrate and disrupt the microbial surfaces and membrane barriers. Such antimicrobial substances are of interest not only for students of phagocytic and epithelial host defenses but may lead to the development of novel pharmaceuticals for the treatment of infections and their sequellae.

Animals↗
PubMed1996

Evaluation of five QT correction formulas using a software-assisted method of continuous QT measurement from 24-hour Holter recordings.

To evaluate and compare QT correction formulas in healthy subjects, we used 24-hour Holter monitoring because it allows the assessment of QT intervals over a large range of rates. Computer-assisted QT-interval measurements were obtained from 21 subjects. QT-RR relations for individuals and the group were fitted by regression analysis to 5 QT prediction formulas: simple Bazett's, modified Bazett's, linear (Framingham), modified Fridericia's and exponential (Sarma's). There were no significant differences in mean squared residuals between formulas. When using individually calculated regression parameters, each formula gave good or acceptable QT correction over the entire range of RR intervals. Simple Bazett's formula (which uses no regression parameters) was unreliable at high rates. Akaike information criteria rank was: Sarma's, Framingham, modified Bazett's, Fridericia's, and simple Bazett's. When group-based regression parameters were applied to individuals, no formula had a clear advantage over simple Bazett's. We conclude that any formula that invokes regression parameters unique to each individual provides satisfactory QT correction. Determination of these parameters requires long-term recording to obtain an adequate range of rates. Group-based regression parameters give poor correction. When individual parameters cannot be determined, as in a 12-lead electrocardiogram, no formula provides an advantage over the familiar simple Bazett's.

Electrocardiography, Ambulatory↗
PubMed1996

Association between different psychotic disorders and the DRD4 polymorphism, but no differences in the main ligand binding region of the DRD4 receptor protein compared to controls.

The dopamine D4 receptor gene (DRD4 gene) is one of the important candidate genes for schizophrenia and other psychoses. In humans, several alleles with variable repeat numbers of a 48-base-pair element within the third exon are known. The corresponding receptor proteins differ in their pharmacological properties. It might be possible that specific alleles or genotypes predispose for schizophrenia and other psychoses. The aim of the present study was to investigate and compare the frequency of the DRD4 alleles and genotypes in healthy controls and patients suffering from schizophrenia, schizoaffective or affective disorders. The DRD4 subtypes of 92 controls, 91 patients with schizophrenia, 90 patients with affective and 20 with schizoaffective disorders were identified by a combination of Southern blot technique and PCR. Statistical analysis revealed several significant differences between controls and patients, e.g. an increased frequency of the D4.7 allele among patients with schizophrenia, schizoaffective or unipolar affective disorder. The results indicate a possible role of the DRD4 gene polymorphism in the pathophysiology of psychotic diseases. When a part of the DRD4 gene sequence containing the codons for the most important amino acids for dopamine binding in 9 controls, 9 patients with schizophrenia and 10 with affective disorders were compared, no differences could be found.

Adult↗
PubMed1996

Both N- and C-terminal regions of the bioactive N-terminal fragment of the neutrophil granule bactericidal/permeability-increasing protein are required for stability and function.

An N-terminal fragment (residues 1-199) of the 456-residue human bactericidal/permeability-increasing protein (BPI), isolated after limited proteolysis, exhibits antibacterial and LPS-neutralizing activities equal to or greater than those of holo-BPI. To assess minimal structural requirements for bioactivity, mutant species of BPI were expressed in vivo by transient transfection and in vitro by cellfree transcription/translation. BPI1-456 and BPI1-193 demonstrated the expected antibacterial and LPS-binding activities. Deletion of the N-terminal 12 residues did not diminish BPI function. However, further truncation either from the C-terminus to residue 169 (BPI1-169) or from the N-terminus (BPIdelta15-56) yielded in vitro products with little or no LPS-binding activity and in vivo products that could not be recovered from the culture medium or cellular acid extracts. The possible role of cysteine-175 (the three cysteines in human BPI are at residues 132, 135, and 175) in BPI stability/function was examined by substitution of Cys(175) with serine. Recovery of C175S BPI from extracellular medium was reduced 10-fold, and C175S BPI produced in vitro had little LPS-binding activity. Compared with wild-type holo-BPI and BPI1-193, BPI1-169, BPIdelta15-56, and C175S BPI showed increased susceptibility to cleavage by elastase in the region 1-193 (but not in the region 200-456), indicating conformational changes that may account for the loss of function. These findings suggest that the proteolytic N-terminal fragment of BPI corresponds closely to the minimum functional (antibacterial/anti-LPS) domain of BPI and that residues near both ends of this fragment are essential for structural stability and functional integrity.

Antimicrobial Cationic Peptides↗
PubMed1996

A new set of primers for the detection of Toxoplasma gondii in amniotic fluid using polymerase chain reaction.

A new PCR system including a pair of primers, a probe and an internal control were designed from the B1 gene of Toxoplasma gondii. The system described allowed the detection of less than 10 tachyzoites of the RH strain of T. gondii. Among 21 amniotic fluid samples, this system diagnosed the cases of congenital toxoplasmosis which were simultaneously diagnosed using mice inoculation, in vitro culture, and serology from both amniotic fluid and fetal blood. These results show that these new primers allow for a highly sensitive detection of T. gondii DNA.

Amniotic Fluid↗
PubMed1996

Effects of intraoperative irradiation and intraoperative hyperthermia on canine sciatic nerve: neurologic and electrophysiologic study.

PURPOSE: Late radiation injury to peripheral nerve may be the limiting factor in the clinical application of intraoperative radiation therapy (IORT). The combination of IORT with intraoperative hyperthermia (IOHT) raises specific concerns regarding the effects on certain normal tissues such as peripheral nerve, which might be included in the treatment field. The objective of this study was to compare the effect of IORT alone to the effect of IORT combined with IOHT on peripheral nerve in normal beagle dogs. METHODS AND MATERIALS: Young adult beagle dogs were randomized into five groups of three to five dogs each to receive IORT doses of 16, 20, 24, 28, or 32 Gy to 5 cm of surgically exposed right sciatic nerve using 6 MeV electrons and six groups of four to five dogs each received IORT doses of 0, 12,16, 20, 24, or 28 Gy simultaneously with 44 degrees C of IOHT for 60 min. IOHT was performed using a water circulating hyperthermia device with a multichannel thermometry system on the surgically exposed sciatic nerve. Neurologic and electrophysiologic examinations were done before and monthly after treatment for 24 months. Electrophysiologic studies included electromyographic (EMG) examinations of motor function, as well as motor nerve conduction velocities studies. RESULTS: Two years after treatment, the effective dose for 50% complication (ED50) for limb paresis in dogs exposed to IORT only was 22 Gy. The ED50 for paresis in dogs exposed to IORT combined with IOHT was 15 Gy. The thermal enhancement ratio (TER) was 1.5. Electrophysiologic studies showed more prominent changes such as EMG abnormalities, decrease in conduction velocity and amplitude of the action potential, and complete conduction block in dogs that received the combination of IORT and IOHT. The latency to development of peripheral neuropathies was shorter for dogs exposed to the combined treatment. CONCLUSION: The probability of developing peripheral neuropathies in a large animal model was higher for IORT combined with IOHT, than for IORT alone. The dose required to produce the same level of late radiation injury to the sciatic nerve was reduced by a factor of 1.5 (TER) if IORT was combined with 44 degrees C of IOHT for 60 min.

Animals↗
PubMed1996

The potent anti-Staphylococcus aureus activity of a sterile rabbit inflammatory fluid is due to a 14-kD phospholipase A2.

The cell-free fluid (ascitic fluid, AF) of a sterile inflammatory peritoneal exudate elicited in rabbits is potently bactericidal for complement-resistant gram-negative as well as gram-positive bacterial species. This activity is absent in plasma. We now show that essentially all activity in AF against Staphylococcus aureus is attributable to a group II 14-kD phospholipase A2 (PLA2), previously purified from AF in this laboratory. Antistaphylococcal activity of purified PLA2 and of whole AF containing a corresponding amount of PLA2 was comparable and blocked by anti-AF-PLA2 serum. At concentrations present in AF (approximately 10 nM), AF PLA2 kills > 2 logs of 10(6) S. aureus/ml, including methicillin-resistant clinical isolates, and other species of gram-positive bacteria. Human group II PLA2 displays similar bactericidal activity toward S. aureus (LD90 approximately 1-5 nM), whereas 14-kD PLA2 from pig pancreas and snake venom are inactive even at micromolar doses. Bacterial killing by PLA2 requires Ca2+ and catalytic activity and is accompanied by bacterial phospholipolysis and disruption of the bacterial cell membrane and cell wall. These findings reveal that group II extracellular PLA2, the function of which at inflammatory sites has been unclear, is an extraordinarily potent endogenous antibiotic against S. aureus and other gram-positive bacteria.

Animals↗
PubMed1996

[Erythema elevatum and diutinum in Crohn disease].

A 35-year-old woman suffering from Crohn's disease for 3 years developed painful erythematous nodular lesions predominantly on the dorsa of her hands and feet, as well as on her elbows and wrists. The clinical features and histopathological picture of leukocytoclastic vasculitis were both highly suggestive of erythema elevatum diutinum. No improvement of the skin lesions was observed during treatment with high doses of oral steroids. In contrast, treatment with dapsone resulted in a marked reduction of skin lesions. During a new attack of her Crohn's disease the erythema elevatum diutinum lesions flared again. The parallel clinical course of erythema elevatum diutinum and Crohn's disease, as well as the detection of immune complexes and neutrophilic granulocytes in lesions of both diseases, strongly suggest a common etiology. This hypothesis is discussed in context with this case and the recent literature.

Adult↗
PubMed1996

Diurnal pattern of QTc interval: how long is prolonged? Possible relation to circadian triggers of cardiovascular events.

OBJECTIVES: This study sought to evaluate the range and variability of the QT and corrected QT (QTc) intervals over 24 h and to assess their pattern and relation to heart rate variability. BACKGROUND: Recent Holter monitoring data have revealed a high degree of daily variability in the QTc interval. The pattern of this variability and its relation to heart rate variability remain poorly characterized. METHODS: We developed and validated a new method for continuous measurement of QT intervals from three-channel, 24-h Holter recordings. Average RR, QT, QTc and heart rate variability were measured from 5-min segments of data from 21 healthy subjects. RESULTS: Measurement of 6,048 segments showed mean (+/- SD) RR, QT and QTc intervals of 830 +/- 100, 407 +/- 23 and 445 +/- 16 ms, respectively (mean QTc interval for men 434 +/- 12 ms, 457 +/- 10 ms for women, p < 0.0001). The average maximal QTc interval was 495 +/- 21 ms and the average QTc range 95 +/- 20 ms. The maximal QTc interval was > or = 500 ms in 6 subjects and > or = 490 ms in 13. The 95% upper confidence limit for the mean 24-h QTc interval was 452 ms (men 439 ms, women 461 ms). The RR, QT and QTc intervals and the high frequency component of heart rate variability were greater during sleep. Both the QTc interval and the variability between hourly minimal and maximal QTc intervals reached their circadian peak shortly after awakening, before declining to daytime levels. CONCLUSIONS: The maximal QTc interval over 24 h in normal subjects is longer than heretofore thought. Both QT and QTc intervals are longer during sleep. The QTc interval and QTc variability reach a peak shortly after awakening, which may reflect increased autonomic instability during early waking hours, and the time of the peak value corresponds in time to the period of reported increased vulnerability to ventricular tachycardia and sudden cardiac death. These findings have implications regarding the definition of QT prolongation and its use in predicting arrhythmias and sudden death.

Adult↗