The kinetic of changes in plasma concentrations and pituitary contents of FSH, LH, prolactin after hysterectomy and treatment with steroid-free uterine extracts were studied in adult, non-pregnant female rats. The post-castration rise of plasma and pituitary FSH and plasma LH was inhibited but the plasma prolactin was elevated by hysterectomy. Steroid-free uterine extracts from previously castrated animals increased the plasma FSH, LH and prolactin concentrations in hysterectomized females 48 hours after administration. Uterine extracts from intact and oestradiol-substituted-castrated animals decreased the pituitary prolactin content 48 h after single i.p. injection. Pituitary FSH and LH contents were not affected by single dose of uterine extracts at any time which were examined. It is concluded that the uterus may play some role in the synthesis and release of pituitary gonadotropins and prolactin.

Smart antennas promise to provide range extension and capacity enhancements crucial to the successful deployment of Universal Mobile Telecommunications System (UMTS) networks. The frequency offset between the uplink and downlink in the Frequency Division Duplex (FDD) air interface gives rise to a frequency dependency in the channel responses and potential problems in downlink beamforming. In order to investigate this, a highly novel dual-band, dual- polarised channel sounding trial was performed in the UMTS FDD bands by the University of Bristol. The wideband measurements were conducted in the City of Bristol, encompassing urban city and sub-urban residential scenarios and subsequent post processing was performed to extract channel parameters across the two bands. This paper presents the results and analysis done so far. It was observed that there was generally a higher degree of scattering in the higher frequency band, resulting in larger angular spreads and delay spreads in most locations. The channels also exhibited a strong degree of de-correlation when viewed from the spatial and temporal domains.

The drug disulfiram is a thiol-reacting drug that is relatively nontoxic when used alone and has been used in the therapy of alcohol abuse for more than 40 years. Several effects of this drug have been reported for DNA synthesis and cell proliferation. In this study, the inhibitory effect of disulfiram on topoisomerase I and II activity was investigated by measuring the relaxation of superhelical plasmid pBR322 DNA. Disulfiram (1-100 microM) inhibited topoisomerase I and II in a concentration-dependent manner (IC(50) congruent with 42 +/- 8 and 30 +/- 9 microM, respectively). Consistent with the assumption that a thiol residue is involved, dithiothreitol (1 mM) markedly prevented the inhibitory effect of disulfiram on the activity of both classes of topoisomerases. These findings might explain certain aspects of disulfiram toxicity and encourage new studies to determine the usefulness of this drug and its analogues as antineoplastic agent.

Teleconferencing systems employ acoustic echo cancelers to reduce echoes that result from the coupling between loudspeaker and microphone. To enhance the sound realism, two-channel audio is necessary. However, stereophonic acoustic echo cancellation (SAEC) is more difficult to solve because of the necessity to uniquely identify two acoustic paths, which becomes problematic since the two excitation signals are highly correlated. In this paper, a wideband stereophonic acoustic echo canceler is presented. The fundamental difficulty of stereophonic acoustic echo cancellation is described and an echo canceler based on a fast recursive least squares (FRLS) algorithm in a subband structure, with equidistant frequency bands, is proposed. The structure has been used in a real-time implementation, with which experiments have been performed. In this paper, simulation results of this implementation on real life recordings, with 8 kHz bandwidth, are studied. The results clearly verify that the theoretic fundamental problem of SAEC also applies in real-life situations. They also show that more sophisticated adaptive algorithms are needed in the lower frequency regions than in the higher regions

Studies have shown evidence of production of nitric oxide (NO) in adipose tissue, as well as inhibition of lipolysis by NO. We have analyzed nitric oxide synthase (NOS) expression in subcutaneous adipose tissue from 13 nonobese and 18 obese male subjects. Using a competitive reverse transcription polymerase chain reaction method, endothelial (eNOS) and inducible (iNOS), but not neuronal (nNOS), nitric oxide synthase mRNA expression was detected in isolated fat cells and pieces of adipose tissue. Tissue mRNA levels for eNOS were 3,814 +/- 825 and 5,956 +/- 476 amol/mg RNA (P = 0.043), and for iNOS 306 +/- 38 and 332 +/- 48 amol/mg RNA, for nonobese and obese individuals, respectively. Western blotting revealed similar eNOS protein levels in isolated fat cells and adipose tissue pieces. Protein levels for eNOS in nonobese and obese individuals, respectively, were (in optical density [OD] units per mm(2) per 100 microgram of total protein) 0.11 +/- 0.08 and 2.80 +/- 1.30 (P = 0.043). iNOS protein was detectable, but not measurable, at low levels in a subset of obese patients (3 of 10). iNOS protein levels could not be detected in nonobese individuals. Hormone-sensitive lipase (HSL), the key regulating enzyme in lipolysis, is reduced in obesity. The expression of HSL protein in subcutaneous adipose tissue was studied in the same subset of patients; in agreement with previous results, HSL levels were reduced in obese subjects: 4.64 +/- 1.10 and 1.27 +/- 0.35 (P = 0.012) in nonobese and obese subjects, respectively. In conclusion, this study shows that eNOS and iNOS, but not nNOS, are present in human subcutaneous adipose tissue. Gene expression and protein levels of eNOS are increased, whereas HSL protein levels are decreased in obesity. It is speculated that increased NO production, preferably by eNOS, and decreased HSL levels may cause decreased subcutaneous adipose tissue lipolysis in obesity. synthases in subcutaneous adipose tissue of nonobese and obese humans.

In this paper a wideband stereophonic acoustic echo canceler is presented. The fundamental difficulty of stereophonic acoustic echo cancellation (SAEC) is described and an echo canceler based on a fast recursive least squares algorithm in a subband structure is proposed. This structure have been used in a real-time implementation, on which experiments have been performed. In the paper, simulation results of this implementation on real life recordings, with 8 kHz bandwidth, are studied. The results clearly verify that the theoretic fundamental problem of SAEC also applies in real-life situations. They also show that more sophisticated adaptive algorithms are needed in the lower frequency regions than in the higher regions.

Teleconferencing systems employ acoustic echo cancelers to reduce echoes that results from the coupling between loudspeaker and microphone. To enhance the sound realism, two-channel audio is necessary. However, stereophonic acoustic echo cancellation is more difficult to solve because of the necessity to uniquely identify two acoustic paths, which becomes problematic since the two excitation signals are highly correlated. In this paper a wideband stereophonic acoustic echo canceler is presented. The fundamental difficulty of stereophonic acoustic echo cancellation (SAEC) is described and an echo canceler based on a fast recursive least squares algorithm in a subband structure is proposed. The structure has been used in a real-time implementation, with which experiments have been performed. In the paper, simulation results of this implementation on real life recordings, with 8 kHz bandwidth, are studied. The results clearly verify that the theoretic fundamental problem of SAEC also applies in real-life situations. They also show that more sophisticated adaptive algorithms are needed in the lower frequency regions than in the higher regions.

By using tissue miniunits, protein kinase modulators, and topoisomerase inhibitors in short-term incubation (0–90 min) we studied (1) the role of protein phosphorylation in the immediate control of DNA replication in the developing rat cerebral cortex and (2) the mechanism of action for genistein-mediated DNA synthesis inhibition. Genistein decreased the DNA synthesis within less than 30 min. None of the other protein kinase inhibitors examined (herbimycin A, staurosporine, calphostin-C) or the protein phosphatase inhibitor sodium orthovanadate inhibited DNA synthesis and they did not affect the genistein-mediated inhibition. The selective topoisomerase inhibitors camptothecin and etoposide decreased the DNA synthesis to an extent similar to that of genistein and within less than 30 min. In addition, the effects of these substances on topoisomerase I and II were studied. Etoposide and genistein but not herbimycin A, staurosporine, or calphostin-C strongly inhibited the activity of topoisomerase II. Our results (1) strongly suggest that the net rate of DNA replication during the S phase of the cell cycle is independent of protein phosphorylation and (2) indicate that the early inhibitory effect of genistein on DNA synthesis is mediated by topoisomerase II inhibition rather than protein tyrosine kinase inhibition.

Four main dammarane-type aglycones of gypenosides, extracted from the aerial parts of Gynostemma pentaphyllum were identified by gas chromatography–mass spectrometry. By detecting these aglycones as well as the aglycones of ginsenosides, a difference in sapogenin composition between Gynostemma pentaphyllum and Panax species was observed, which can be used in the differentiation of these plant drugs.

Stereophonic acoustic echo cancellation has been found more difficult than echo cancellation in mono due to a high correlation between the two audio channels. Different methods to decorrelate the channels have been proposed so that the stereophonic echo canceller identifies the true echo paths and its convergence rate increases. It is shown that the use of a perceptual audio coder effectively reduces the correlation between the channels and thus convergence to the true echo paths is insured. Furthermore, in those frequency regions where the encoder introduced quantization noise which is below the global perceptual masking threshold, an extra amount of inaudible noise can be added to the channels. Thereby the channel correlation is further decreased and the solution is stabilized. In subband audio coders with high frequency resolution only minor modifications are needed in the decoder

A proliferation assay based on the production of mini-units of tissue was adopted and modified for the simultaneous determination of cell proliferation rate and the effect of genistein in rat cerebral cortex. Mini-units of tissue were produced from rat cerebral cortex immediately after killing the animal and incubated with culture medium containing 3H-methyl-thymidine during 90 min. The proliferation rate was assessed by measurement of 3H-methyl-thymidine incorporation into trichloroacetic acid insoluble material/mg of protein/min. The mini-unit method preserves the neural-cell topological relation existing in vivo and, in addition, has several additional advantages: (1) the short incubation time required limits the metabolic changes, (2) the sensitivity to drugs can be assessed simultaneously with the cell proliferation rate, (3) the complete procedure can be performed within 4-6 h, and (4) many experiments can be performed with the tissue from one animal. Genistein in doses from 10 to 100 microM inhibited cell proliferation in a concentration-dependent manner. The percentage of inhibition was highest in young animals and decreased with increasing age. This method is a powerful tool for the study of drugs with short-time onset mechanisms of action and can be useful for the screening of new drugs.

The effects of the cyclin-dependent kinase (CDK) inhibitors olomoucine and roscovitine on DNA synthesis were studied using short time incubation (30-90 minutes). Both purine analogues at concentrations from 1-100 μM decreased the DNA synthesis of rat brain cortex in a dose-dependent manner and the maximum effect occurred within 30 min of incubation. Staurosporine, another potent CDK inhibitor did not affect the DNA synthesis in the concentration range 1-250 nM. These results indicate that olomoucine and roscovitine block DNA synthesis by a mechanism independent of CDK inhibition. We propose that the cellullar effects of olomuocine and roscovitine on the cell cycle are at least in part due to this early inhibitory effect on DNA synthesis.

Objective: To evaluate 24-h ambulatory blood pressure (24 h amb BP) and its relation to the menstrual cycle in women with previous preeclampsia (PE).Study Design: A case-control study, 2 x 2 factorial (group x phase), was undertaken at Karolinska Hospital, Stockholm, Sweden. The subjects, 25 women with a history of moderate to severe PE, were included 2-5 years after pregnancy. Twenty-four women with normal pregnancies matched for age, parity at index pregnancy, and time of delivery served as controls. Half of the subjects started recordings in the follicular phase and the other half in the luteal phase of the menstrual cycle.Main Outcome Measures: Diurnal blood pressure (BP) recording in the early follicular and the late luteal phases of the menstrual cycle. Blood samples were drawn for determination of estradiol, progesterone, aldosterone, plasma renin activity, plasma angiotensin II, and angiotensin-converting enzyme.Results: The BP values were significantly higher in women with previous PE, including 24 h amb BP, mean day BP, mean night BP (p < 0.01). There were no phase differences in mean 24 h amb BP. Mean diastolic BP (DBP) and mean arterial pressure (MAP) recordings at night in the luteal phase were lower than in the follicular phase in both groups (p < 0.05). In a group of PE patients with one or more BP readings greater than or equal to 140/90 mm Hg at night (n = 11), the mean 24 h amb BP, MAP, angiotensin II, and renin activity were significantly higher compared to the group with no BP readings greater than or equal to 140/90 mm Hg at night.Conclusion: Two to five years after pregnancy, women with a diagnosis of PE have a significantly higher 24 h amb BP compared to women with normal pregnancies. A blunted diurnal BP reaction at night in the follicular phase compared to the luteal phase was seen mainly in the group of women with previous PE.

Five dammarane-type aglycones, released from gypenosides following an alkaline cleavage procedure previously developed for ginsenosides, were separated and characterized by gas chromatography-mass spectrometry (GC-MS) after trimethylsilylation. A satisfactory identification among isomers of 20(S)-protopanaxadiol or 20(S)-protopanaxatriol was obtained. (C) 1998 John Wiley & Sons, Ltd.

Levels of substance P were determined in the cerebrospinal fluid (CSF) in 15 patients with chronic fatigue syndrome (CFS). All values were within normal range. This is in contrast to fibromyalgia (FM). The majority of patients with FM have increased substance P values in the CSF. The results support the notion that FM and CFS are different disorders in spite of overlapping symptomatology.

An improved gas chromatographic-mass spectrometric method (GC-MS) with a fast solid-phase extraction on a newly introduced C18 microcolumn, was applied to study the urinary excretion of 20(S)-protopanaxadiol and 20(S)-protopanaxatriol glycosides in man after oral administration of ginseng preparations. Using panaxatriol as internal standard, 20(S)-protopanaxadiol and 20(S)-protopanaxatriol (the aglucones of ginesenosides) could be determined at a detection level of a few ng per ml urine by GC-MS with selected-ion monitoring after their release from glycosides which occur in urine. The extraction recovery of ginsenosides from urine was more than 80% and the intra-assay coefficient of variation was less than 5.0%. The results after intake of single doses of ginseng preparations demonstrated a linear relation between the amounts of ginsenosides consumed and the 20(S)-protopanaxatriol glycosides excreted in urine. About 1.2% of the dose was recovered in five days.

We have previously shown that p-aminobenzoic acid (PABA) is acetylated by several cell lines and most peripheral blood cells, including platelets, to p-acetamidobenzoic acid (PACBA). The structural similarity of PABA and PACBA to local anesthetics and some non steroidal anti inflammatory drugs urged us to perform the present investigation.When human platelets were stimulated with thrombin to liberate AA, we found that PABA inhibited the production of thromboxane (TxB(2)) as measured with enzyme-linked immunosorbent assay. The inhibition was reversible and observed at PABA concentrations ranging between 55 and 1000 mu M. At 328 mu M PABA the production of TxB(2) diminished by 87% (p=0.013). PACBA in the same doses did not affect the production of TxB(2). When platelets were incubated with [1-C-14]AA, in the presence of PABA, the production of [1-C-14]TxB(2) was only slightly inhibited, according to analysis by high pressure liquid chromatography.Obviously PABA is not mainly acting as a prostaglandin H (cyclooxygenase) or Tx synthase inhibitor. It is rather affecting a step prior to thromboxane production, most likely the liberation of the precursor AA. In conclusion, our results demonstrate for the first time that PABA, a substance occurring in nature, inhibits endogenous TxB(2) synthesis in human platelets and might thus exert profound effects on platelet AA metabolism. (C) 1997 Elsevier Science Ltd.

The commonly used antidepressants imipramine, amitriptyline, and nortriptyline were found to significantly inhibit human natural killer (NK) cell-mediated cytolysis in vitro and suppress the stimulation of NK cells by IFN-gamma. This is a previously unrecognized biologic property of these drugs with psychotropic activity. Tricyclic antidepressants did not decrease effector-target cell conjugation formation, nor did they induce target cell resistance to NK lysis, indicating that the drugs might interfere with the killing mechanism of the effector cells. Kinetic data reveal that the drug interference is related to an early postbinding event in the activation of NK cells. Results also showed that the inhibitory effect of tricyclic antidepressants on human NK cell activity occurred in parallel to an increase in intracellular cyclic GMP concentration. However, the attenuation in the cyclic GMP formation by methylene blue, a selective inhibitor of soluble guanylate cyclase, was not accompanied by a corresponding increase in NK cell cytolytic activity. It is suggested that the stimulation of cyclic GMP was not directly involved in the inhibitory effect of antidepressants on NK cells and perhaps was a secondary phenomenon. This immune cell modulatory property of tricyclic antidepressants seems to indirectly provide evidence for the concept that human brain neurons and NK cells might share regulatory system(s).