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Biomedical subjects

J M Weiss

Publications and source records attributed to J M Weiss.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of chronic antidepressant drug administration and electroconvulsive shock on locus coeruleus electrophysiologic activity.

BACKGROUND: The locus coeruleus (LC) is the major noradrenergic cell body group in the brain. Although previous studies have examined changes in electrophysiologic activity of LC neurons produced by antidepressant drugs, only a small number have examined changes that occur with chronic drug administration, which is the therapeutically effective regimen, and only one group of investigators has assessed effects on activated (or "burst") firing of LC neurons under such treatment conditions. The present study assessed changes produced in rats by effective antidepressant treatments-several drugs given chronically (two tricyclic antidepressants, two selective serotonin reuptake inhibitors, and a monoamine oxidase inhibitor) as well as a series of electroconvulsive shocks (ECSs)-in single-unit electrophysiologic activity of LC neurons, measuring effects on spontaneous depolarization rate and also on sensory-evoked burst firing. METHODS: Drugs were administered via osmotic minipumps for either 14 or 30 days; ECSs were administered five times, with a 72-hour interval between each administration. Electrophysiologic recording of LC activity took place under halothane anesthesia on the last day of drug treatment or following a delay of 1 or 5 days after the final ECS. RESULTS: A common effect of all drugs tested and ECS treatment was to decrease LC spontaneous and sensory-evoked burst firing. CONCLUSIONS: The clinical efficacy of antidepressant medication and ECS may be mediated, in part, through reduction of LC neural activity. The findings reported here are consistent with recent indications that LC neurons are hyperactive in depressed individuals and with suggestions that some behavioral changes seen in depression can arise from consequences of rapidly depolarizing LC terminals, such as release of peptides.

Animals↗
PubMed2001

[Reproducible drug exanthema to terbinafine with characteristic distribution of baboon syndrome].

A 26 year old patient developed a fixed drug eruption located on his hands, inguinal and gluteal areas following oral treatment of onychomycosis with terbinafine. The rash showed the characteristic distribution of the "baboon-syndrome", so-named because of the red perianal region of the baboon. Although epicutaneous testing revealed no positive reaction, the rash could be induced in identical sites by oral administration of terbinafine. As the underlying pathomechanism for the "baboon-syndrome" a systemically induced allergic contact dermatitis has been suggested. In addition to the described substances, e.g. mercury, amoxicillin, ampicillin, heparin and nickel, this is the first report of "baboon syndrome" induced by terbinafine.

Administration, Oral↗
PubMed2001

Pelvic floor myofascial trigger points: manual therapy for interstitial cystitis and the urgency-frequency syndrome.

PURPOSE: The effectiveness of manual physical therapy was evaluated in patients with interstitial cystitis and the urethral syndrome, that is urgency-frequency with or without pelvic pain. The rationale was based on the hypothesis that pelvic floor myofascial trigger points are not only a source of pain and voiding symptoms, but also a trigger for neurogenic bladder inflammation via antidromic reflexes. MATERIALS AND METHODS: From September 1995 to November 2000, 45 women and 7 men, including 10 with interstitial cystitis and 42 with the urgency-frequency syndrome, underwent manual physical therapy to the pelvic floor for 1 to 2 visits weekly for 8 to 12 weeks. Results were determined by patient completed symptom score sheets indicating the rate of improvement according to outcome parameters, including 25% to 50%-mild, 51% to 75%-moderate, 76% to 99%-marked and 100%-complete resolution. In 10 cases these subjective results were confirmed by measuring resting pelvic floor tension by electromyography before and after the treatment course. RESULTS: Of the 42 patients with the urgency-frequency syndrome with or without pain 35 (83%) had moderate to marked improvement or complete resolution, while 7 of the 10 (70%) with interstitial cystitis had moderate to marked improvement. The mean duration of symptoms before treatment in those with interstitial cystitis and the urgency-frequency syndrome was 14 (median 12) and 6 years (median 2.5), respectively. In patients with no symptoms or brief, low intensity flares mean followup was 1.5 years. In 10 patients who underwent electromyography mean resting pelvic floor tension decreased from 9.73 to 3.61 microV., which was a 65% improvement. CONCLUSIONS: Pelvic floor manual therapy for decreasing pelvic floor hypertonus effectively ameliorates the symptoms of the urgency/frequency syndrome and interstitial cystitis.

Adult↗
PubMed2001

Embryo implantation and GnRH antagonists: ovarian actions of GnRH antagonists.

The gonadotrophin-releasing hormone (GnRH) antagonists, cetrorelix and ganirelix, have both been approved for ovarian stimulation to prevent a premature LH surge. Since GnRH receptors and their gene expression have been detected in human ovary, concern has risen over whether GnRH antagonists might affect ovarian function. Three large trials which compared GnRH agonists (used in the standard protocol worldwide), with the new antagonist treatment found no significant differences concerning the most important goals, e.g. pregnancy rate, fertilization and quality of oocytes. However, the concentration of oestradiol, and the pregnancy and implantation rates were lower in GnRH antagonist-treated patients. These findings again fuelled the debate about the possible extrapituitary effects of GnRH antagonists. Here, we review the conflicting data in the literature on the ovarian effects of GnRH antagonists and discuss our own results. In our view, it is unlikely that GnRH antagonists have a relevant impact on ovarian steroidogenesis and function; however, GnRH antagonists may exert other effects on the ovary.

Animals↗
PubMed2001

Interactions of insulin-like growth factor-I, insulin and estradiol with GnRH-stimulated luteinizing hormone release from female rat gonadotrophs.

BACKGROUND: It is well established that ovarian steroids modulate gonadotropin secretion from anterior pituitary cells. It has been speculated that insulin and IGF-I might influence gonadotropin secretion. OBJECTIVE: To investigate the effects of IGF-I and estradiol alone, or combinations of IGF-I with insulin and estradiol on GnRH-stimulated LH release from female rat pituitary cells in serum-supplemented and serum-free culture conditions. METHODS: Pituitary cells were incubated for 24 h or 48 h with a series of increasing concentrations of IGF-I or estradiol and stimulated with 1 nmol/l GnRH for 3 h. To determine the interaction of IGF-I and estradiol on GnRH-stimulated LH secretion, cells were exposed to increasing concentrations of IGF-I and 100 pmol/l estradiol for 24 h. We also investigated the effects of combined treatment with IGF-I and insulin on GnRH-stimulated LH secretion. RESULTS: Our findings indicate that long-term IGF-I treatment (24 h) alone has a significant augmenting effect on GnRH-stimulated LH release in serum-free medium only, with a maximum at low concentrations (10 and 100 pmol/l). Estradiol significantly increased GnRH-induced LH release in a dose-dependent manner. The extent of GnRH-stimulated LH secretion by long-term estradiol treatment (24 h) was significantly greater in serum-supplemented (+42%) medium than in serum-free medium. Estradiol facilitated IGF-I-primed LH responses to GnRH in serum-free medium. In contrast, in serum-supplemented medium, the facilitating potential of estradiol was lower. We also found that, in GnRH-stimulated cells, LH release was augmented by insulin treatment, in contrast to quiescent cells that had been pretreated with 100 pmol/l IGF-I alone and 1 nmol/l insulin alone. CONCLUSIONS: IGF-I and to a lesser extent insulin stimulate GnRH-induced LH secretion from pituitary gonadotrophs. This action is enhanced by estradiol treatment of the cells. However, the well known stimulatory action of estradiol on LH secretion is dependent on the presence of growth factors.

Animals↗
PubMed2001

Actions of gonadotropin-releasing hormone antagonists on steroidogenesis in human granulosa lutein cells.

OBJECTIVE: GnRH antagonists have recently been introduced for the prevention of premature LH surges during controlled ovarian hyperstimulation (COH). We have here investigated whether the GnRH antagonists cetrorelix and ganirelix exert effects on ovarian steroidogenesis. Since there is some controversy about the action of GnRH agonists in the human ovary we also tested the effect of triptorelin on steroid production in cultured human granulosa lutein cells. METHODS: Cells were obtained from patients treated with different protocols of COH. In addition to gonadotropins they received triptorelin, cetrorelix, ganirelix or no GnRH analogue. RESULTS: Such in vivo treatment did not result in significant effects of triptorelin or the two GnRH antagonists on spontaneous or human chorionic gonadotropin (hCG)-stimulated steroidogenesis. To exclude the possibility that the in vivo treatment might not affect in vitro steroid production because of low or absent peptide activity, we performed in vitro treatments with triptorelin, cetrorelix and ganirelix for up to 96 h. However, these treatment paradigms did not influence basal or hCG-stimulated steroid production. CONCLUSIONS: We conclude that GnRH antagonists do not exert any significant effects on ovarian steroidogenesis in vitro and therefore their introduction into protocols of COH is unlikely to impair ovarian function.

Cells, Cultured↗
PubMed2001

The role of CD44 during CD40 ligand-induced dendritic cell clustering and maturation.

The interaction between CD40 on dendritic cells (DC) and its ligand CD154 has been recognized to be an important feature in the maturation of DC. Here, we were interested in the role of CD44 a surface receptor shown to mediate cell-cell adhesion and binding to Hyaluronic acid (HA). Western blot analysis of human DC stimulated for 3-12 h with CD154 revealed the rapid induction of the 85 kDa standard form of CD44 and an increased HA-binding affinity. Time-lapse video-imaging microscopy of human DC co-cultured on CD154-transfected murine fibroblasts showed that the CD44 up-regulation coincided with the rapid induction of homotypic DC clustering, which did not occur on empty vector-transfected fibroblasts. In this system, addition of anti-CD44s mAbs abrogated DC-cluster formation, thereby inhibiting further maturation, as shown by a reduced TNF-alpha production and inhibition of CD154-induced MHC class II up-regulation. However, co-incubation with HA-degrading enzymes induced no changes in the CD154-mediated DC clustering and maturation.

Animals↗
PubMed2000

Depletion of brain norepinephrine does not reduce spontaneous ambulatory activity of rats in the home cage.

6-Hydroxydopamine (6-OHDA) lesions of brain noradrenergic neurons and terminals were made in rats to assess the importance of forebrain norepinephrine (NE) for mediating circadian patterns of spontaneous ambulatory activity that rats show in the home cage. 6-OHDA was injected intracranially into the fibers of the ascending noradrenergic dorsal and ventral bundle pathways or infused into the lateral ventricle or both. Rats living in a 12/12 h light/dark cycle exhibit a marked increase in ambulatory activity during the dark period in comparison to the light period and a 'W-shaped' pattern of activity during the 12 h of the dark phase. Results showed that near-total depletion of brain NE did not impair the capacity to generate normal patterns of spontaneous ambulatory activity that occur in the home cage. In the animals that sustained the most complete NE lesions, the amounts of activity generated at times of peak activity were exaggerated in comparison to the control animals, which is consistent with the possibility that NE in the brain exerts a moderating influence on behavior.

Animals↗
PubMed2000

Oligosaccharides of hyaluronan are potent activators of dendritic cells.

The extracellular matrix component hyaluronan (HA) exists physiologically as a high m.w. polymer but is cleaved at sites of inflammation, where it will be contacted by dendritic cells (DC). To determine the effects of HA on DC, HA fragments of different size were established. Only small HA fragments of tetra- and hexasaccharide size (sHA), but not of intermediate size (m.w. 80, 000-200,000) or high m.w. HA (m.w. 1,000,000-600,000) induced immunophenotypic maturation of human monocyte-derived DC (up-regulation of HLA-DR, B7-1/2, CD83, down-regulation of CD115). Likewise, only sHA increased DC production of the cytokines IL-1beta, TNF-alpha, and IL-12 as well as their allostimulatory capacity. These effects were highly specific for sHA, because they were not induced by other glycosaminoglycans such as chondroitin sulfate or heparan sulfate or their fragmentation products. Interestingly, sHA-induced DC maturation does not involve the HA receptors CD44 or the receptor for hyaluronan-mediated motility, because DC from CD44-deficient mice and wild-type mice both responded similarly to sHA stimulation, whereas the receptor for hyaluronan-mediated motility is not detectable in DC. However, TNF-alpha is an essential mediator of sHA-induced DC maturation as shown by blocking studies with a soluble TNFR1. These findings suggest that during inflammation, interaction of DC with small HA fragments induce DC maturation.

Adjuvants, Immunologic↗
PubMed2000

Effect of the gonadotropin-releasing hormone antagonist ganirelix on cyclic adenosine monophosphate accumulation of human granulosa-lutein cells.

OBJECTIVE: To evaluate whether the GnRH antagonist ganirelix exerts an effect on cyclic adenosine monophosphate (cAMP) production of human granulosa-lutein (GL) cells in vitro. DESIGN: In vitro cell culture study. SETTING: Research laboratory of a university hospital. PATIENT(S): Mural GL and cumulus cells were obtained from 15 patients on whom controlled ovarian hyperstimulation was being performed for intracytoplasmic sperm injection treatment. INTERVENTION(S): Mural GL and cumulus cells were cultured for 48 hours with and without 1 nM ganirelix or triptorelin. For the last 6 hours, the cells were either exposed to 1-5 IU hCG or left unstimulated. MAIN OUTCOME MEASURE(S): At the end of the culturing period, the intracellular and extracellular cAMP accumulations were measured by an (125)I-scintillation proximity assay. RESULT(S): hCG induced dose-dependent increases in total cAMP accumulation. Stimulation with 1 IU/mL hCG resulted in 9-fold and 13-fold increases, and 5 IU/mL hCG resulted in 19-fold and 14-fold increases in total cAMP release from cumulus and mural GL cells, respectively. On the other hand, treatments with 1 nM GnRH antagonist ganirelix and 1 nM GnRH agonist triptorelin did not exert any significant changes on the basal and hCG-stimulated cAMP accumulation of mural GL cells and cumulus cells as compared with controls. CONCLUSION(S): Ganirelix does not influence basal and hCG-stimulated cAMP accumulation of human GL cells in vitro. cAMP is apparently not involved in the mechanism of action of GnRH analogs in human ovary.

Adenosine Monophosphate↗
PubMed2000

Blood level of B and CD4+ lymphocytes measured before induction of an experimental tumor in rats predicts tumor progression and survival.

After an initial series of experiments indicated that early responses of B lymphocytes were important in controlling tumor metastases in two rat models of cancer (N. Quan et al., Cancer Res., 59: 1080-1089, 1999), the present study assessed whether differences in the number of B lymphocytes that are normally present in different individual rats before any tumor development could predict tumor growth, metastases, and length of survival when tumor challenge subsequently occurred. Repeated baseline measures of several circulating lymphocyte subtypes (i.e., natural killer, B, CD4+, CD8+ lymphocytes) were made in individual inbred WAG rats before any introduction of tumor cells, and stable baselines for these subtypes were found. Animals were then injected with 2 x 10(6) CC531 tumor cells (a syngeneic tumor) into the leg, and the size of the resulting primary tumor measured. Primary tumors were surgically removed 6-7 weeks after tumor-cell injection, and animals then followed until death from metastases. In two experiments, the size of the primary tumor as well as the length of time that animals survived correlated with the pretumor percentage of certain lymphocyte subtypes in peripheral blood before tumor-cell injection. Baseline percentage of B lymphocytes was significantly negatively correlated with the size of the primary tumor and was positively correlated with the duration of survival. Baseline percentage of CD4+ lymphocytes showed the opposite relationship, being positively correlated with tumor size and negatively correlated with survival time, although these correlations were lower than those for B lymphocytes. Percent B lymphocytes in circulation also declined during tumor development. In summary, a high percentage of endogenous peripheral blood B lymphocytes predicted growth of smaller primary tumors and longer survival after experimental tumor induction in a rat model, further suggesting that B lymphocytes are involved in protection against development of certain tumors.

Adenocarcinoma↗
PubMed2000

Mechanisms of leukocyte trafficking into the CNS.

HIV-1 encephalitis occurs in up to one-third of HIV-1-infected individuals. The mechanisms through which this pathology develops are thought to involve viral passage across the blood-brain barrier (BBB), as well as entry of HIV-infected and/or uninfected inflammatory cells into the central nervous system (CNS). Viral proteins and cytokines may also contribute to the pathogenesis of encephalitis. We show that the chemokines SDF-1 and MCP-1 induce transmigration of uninfected human lymphocytes and monocytes across our model of the BBB, a co-culture of human fetal astrocytes and endothelial cells. We also demonstrate that the HIV-1 protein Tat induces adhesion molecule expression and chemokine production by human fetal astrocytes and microglia, which could further contribute to leukocyte entry into the CNS. Finally, our data indicate that inflammatory cytokines modulate the expression of CXCR4, a co-receptor for HIV-1, on human fetal astrocytes, suggesting that these cytokines may potentially modulate the infectability of astrocytes by HIV-1. These findings support the hypothesis that there may be several different mechanisms that contribute to the development and progression of HIV-1 encephalitis.

Adult↗
PubMed1999

HIV-1 Tat induces monocyte chemoattractant protein-1-mediated monocyte transmigration across a model of the human blood-brain barrier and up-regulates CCR5 expression on human monocytes.

AIDS dementia is characterized by neuronal loss in association with synaptic damage. A central predictor for clinical onset of these symptoms is the infiltration of monocytes and macrophages into CNS parenchyma. Chronic HIV-1 infection of monocytes also allows these cells to serve as reservoirs for persistent viral infection. Using a coculture of endothelial cells and astrocytes that models several aspects of the human blood-brain barrier, we examined the mechanism whereby the HIV-derived factor Tat may facilitate monocyte transmigration. We demonstrate that treatment of cocultures on the astrocyte side with HIV-1 Tat induced significant monocyte chemoattractant protein (MCP)-1 protein. Astrocytes, but not endothelial cells, were the source of this MCP-1 expression. Supernatants from Tat-treated cocultures induced significant monocyte transmigration, which was detected by 2.5 h after the addition of PBMC. Pretreatment of the supernatants from Tat-stimulated cocultures with an Ab to MCP-1 completely blocked monocyte transmigration. Flow cytometric analysis of Tat-stimulated PBMC demonstrated that Tat up-regulated expression of the chemokine receptor, CCR5, on monocytes in a time-dependent manner. Taken together, our data indicate that HIV-1 Tat may facilitate the recruitment of monocytes into the CNS by inducing MCP-1 expression in astrocytes. These recruited monocytes may contribute to the pathogenesis of HIV-1-associated AIDS encephalitis and dementia.

Blood-Brain Barrier↗
PubMed1999

Evidence for involvement of B lymphocytes in the surveillance of lung metastasis in the rat.

These studies examined the composition of lymphocytes within the lung after the introduction of tumor cells that metastasize to the lung in rats. i.v. delivery of MADB106 tumor cells into syngeneic Fischer 344 rats caused dose- and time-dependent development of lung tumors, with surface metastases evident 7 days after injection and markedly increased 11 days after injection. The total number of lymphocytes recovered from the lung was increased 11 days after injection but not 7 days after injection. When lymphocytes from the lung, spleen, and blood were subjected to fluorescence-activated cell sorting analysis, the most conspicuous change was an increase in the percentage of CD45RA+ cells (i.e., B lymphocytes in the rat) in the lung, with no changes seen in the percentage of natural killer (NKR-P1+), CD4+, or CD8+ cells in the lung. Analysis of the time course showed that B lymphocytes increased in the lung soon after i.v. tumor injection, with an initial peak seen 6 h after injection. Rapid influx of B lymphocytes into lung after i.v. tumor cell injection was also observed in another syngeneic tumor model, i.e., after injection of CC531 cells into WAG rats. To determine whether the influx of B lymphocytes into the lung might participate in tumor surveillance, a high dose of antibody (100 microg) to rat B lymphocytes was given to immunoneutralize these cells; this produced an increase in lung tumors in both models. Finally, Fischer 344 rats were given a s.c. injection of MADB106 tumor cells that made them resistant to lung tumors when given a later i.v. injection of these tumor cells. These animals were found to have an elevated level of B lymphocytes residing in the lung associated with the resistance to lung tumor. These findings suggest that early responses of B lymphocytes are important in protection against tumor development in two rat models of cancer.

Adenocarcinoma↗
PubMed1999

Rats selectively bred for high and low swim-test activity show differential responses to dopaminergic drugs.

RATIONALE: Selective breeding of Sprague-Dawley rats has been used to generate a line of animals with very low swim-test activity (SwLo) in an attempt to model certain characteristics of depression. For comparison with the SwLo animals, a line bred for high swim-test activity (SwHi) and a non-selectively bred line (SwNS) have been generated. Previous studies using these lines suggested an inverse relationship between dopamine (DA) function in the brain and inactivity in the swim test. OBJECTIVES: The current experiments investigated the possibility that SwLo and SwHi rats show differences in central DA processes, as suggested by responsiveness to DA agonists. RESULTS: The increase in ambulation produced by d-amphetamine (0.25-1.0 mg/kg) was largest in SwHi rats and smallest in SwLo rats, with SwNS rats showing an intermediate response. Amphetamine levels in plasma and brain tissue were similar in SwHi and SwLo rats, indicating that pharmacokinetic differences were not responsible for the behavioral differences. Repeated amphetamine administration produced enhancement in the ambulation-increasing effects of this drug (i.e., sensitization), with significant enhancement seen in all three lines. Apomorphine in doses that stimulate postsynaptic receptors (0.25-4.0 mg/kg) produced mainly increased sniffing behaviors in SwHi and SwNS rats and oral behaviors in SwLo rats, suggesting that the lines differ in proportions of D1, D2, and D3 postsynaptic receptors. CONCLUSIONS: The findings suggest that DA function differs in lines of rats selectively bred for differences in swim behavior, a feature that may make these lines useful for studying certain depressive symptoms that might be related to DA function.

Amphetamine↗
PubMed1999

Motor activation by amphetamine infusion into nucleus accumbens core and shell subregions of rats differentially sensitive to dopaminergic drugs.

Selective breeding based on activity in a swim test has been used to produce lines of rats that show a high level of activity in the swim test (Swim High-active (SwHi) rats) and a low level of activity in the swim test (Swim Low-active (SwLo) rats). Previous studies have indicated that dopamine (DA) function is enhanced in SwHi rats and reduced in SwLo rats; a principal finding was that SwLo rats showed much smaller increases in ambulatory activity after systemic administration of amphetamine than did SwHi or non-selected rats. In light of the importance of the nucleus accumbens (NAC) in amphetamine-induced activity, the present study investigated whether DA function in NAC differs in SwHi and SwLo rats. Amphetamine was infused bilaterally into either the core or shell subregion of NAC, and ambulation or swim test activity was then measured. In SwLo rats, infusion of amphetamine (0.2-2.0 microg) into either NAC core or shell produced moderate increases in ambulation. In SwHi rats, infusion of amphetamine into NAC shell produced similar moderate increases in ambulation, but infusion into the core produced markedly larger dose-related increases in ambulation. In the swim test, infusion of amphetamine (1.0 microg) increased activity by affecting the dominant behavior of each line; i.e. struggling increased in SwHi rats and floating decreased in SwLo rats, with large effects seen in both lines with infusion into either NAC core or shell. These results support the idea that the distinct behavioral characteristics of SwHi and SwLo rats are mediated in part by differences in NAC-DA function.

Animals↗
PubMed1999

Colocalization of basic fibroblast growth factor and CD44 isoforms containing the variably spliced exon v3 (CD44v3) in normal skin and in epidermal skin cancers.

Previous in vitro studies have shown CD44 isoforms containing the alternatively spliced exon v3 (CD44v3) to be modified with heparan sulphate (HS) and to bind HS-binding basic fibroblast growth factor (bFGF). Here, we demonstrate that exogenously added bFGF is also bound in vivo by CD44v3-positive keratinocytes in normal skin and by tumour cells in basal cell carcinoma and squamous cell carcinoma (SCC), two skin cancers of keratinocyte origin. bFGF binding and CD44v3 expression were colocalized in cultured human normal keratinocytes (HNK) and on the SCC cell line A431. By contrast, benign or malignant tumours of melanocyte origin failed to express CD44v3 and bound no bFGF. The bFGF binding to normal or transformed keratinocytes in vivo and in vitro was dependent on HS modification, as it was completely eliminated by pretreatment with heparitinase or by blocking with free heparin, whereas chondroitinase had no effect. In addition, specific removal of CD44v3 by antibody-induced shedding also diminished bFGF binding to keratinocytes. Furthermore, bFGF stimulated the proliferation of CD44v3-positive HNK and A431 in a dose-dependent fashion. This bFGF effect was again completely abolished by heparitinase or free heparin, but not by chondroitinase. In aggregate, our results suggest that a function of HS-modified CD44 isoforms such as CD44v3 in skin is to present the HS-binding growth factor bFGF, thereby stimulating the proliferation of normal or transformed keratinocytes.

Antigens, Neoplasm↗