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PubMed2001

Airflow resistance of airflow-regulating devices described by independent coefficients.

Rehabilitation after laryngectomy includes more and more the use of airflow-regulating devices such as shunt valves (SVs), tracheostoma valves (TSVs), and heat and moisture exchange (HME) filters. In determining the quality of those devices, airflow resistance is a very important factor. It is currently defined as pressure drop divided by airflow. However, for most applications, this definition does not result in a pressure- and airflow-independent parameter. Therefore, a new set of parameters is defined and applied to pressure-airflow curves of airflow-regulating devices. Pressure drop over TSVs and HME filters appears to have a squared relationship with flow. In SVs, it has a linear relationship. The new set of parameters describes the pressure-airflow relationship properly for all considered devices. In conclusion, theoretical predictions of flow mechanics appear to be valid for SVs, TSVs, and HME filters. Only 2 coefficients are necessary to describe the pressure-flow characteristics of these airflow-regulating devices, independent of pressure drop over and flow through the device.

Airway Resistance↗

PubMed2026

Molecular residual disease assessment in colorectal and bladder cancer by somatic structural variant analysis of cell-free DNA whole-genome sequencing data.

BACKGROUND: Whole-genome sequencing (WGS)-based methods for circulating tumor DNA (ctDNA) detection typically rely on tumor-informed identification of somatic single nucleotide variants (SNVs). Somatic structural variants (SVs) are another type of cancer-specific genomic alteration, which owing to their larger genomic footprint and unique breakpoint junctions, are easier to distinguish from sequencing noise than SNVs. They are, however, rarely used for ctDNA detection because of (1) artifacts from WGS procedures that SV callers may falsely interpret as genuine SVs. This makes it difficult to establish high-confidence SV catalogos from short-read tumor WGS and can cause false-positive ctDNA detections. (2) Lack of robust strategies to quantify SV-supporting reads in plasma WGS. To address these barriers and enable integration of SV biomarkers into WGS-based ctDNA detection, we present a bioinformatic framework for algorithmic curation of somatic SV calls from fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tumors, coupled with a novel approach for sensitive, accurate mapping and quantification of SV breakpoint-supporting reads in plasma WGS. METHODS: Tumor, normal and plasma WGS data from 144 patients with stage III colorectal cancer was used to establish the bioinformatic framework. This included ~30x WGS data from 1564 serially collected plasma samples. The framework was validated using tumor/normal/plasma WGS data from 32 patients with muscle-invasive bladder cancer. SV-based ctDNA detection was benchmarked against previously published SNV-based ctDNA results for the same samples. RESULTS: After curation of SV calls and quantification in plasma WGS, our SV-based approach enabled robust ctDNA detection with overall specificity exceeding 99% in plasma samples. Furthermore, we observed strong concordance (Pearson’s r > 0.93, p < 2.2 × 10− 16) between ctDNA-positive samples identified by our SV-based method and previous SNV-based analyses, validating the reliability of our approach. Finally, we demonstrated application of the method in an independent bladder cancer cohort, highlighting its generalizability and potential clinical use. CONCLUSIONS: We provide a bioinformatic framework that establishes somatic SVs as ultra-specific biomarkers for WGS-based, tumor-informed ctDNA detection. The approach delivers specific detection even when the SV catalogos are established from FFPE samples. The SV framework can stand alone or enhance SNV-based analysis pipelines.

Humans↗

PubMed2025

The causal relationship between steroid hormones and risk of stroke: evidence from a two-sample Mendelian randomization study.

It is unclear how steroid hormones contribute to stroke, and conducting randomized controlled trials to obtain related evidence is challenging. Therefore, Mendelian randomization (MR) technique was employed in this study to examine this association. Through genome-wide association meta-analysis, the genetic variants of steroid hormones, including testosterone/17β-estradiol (T/E2) ratio, aldosterone, androstenedione, progesterone, and hydroxyprogesterone, were acquired as instrumental variables. Analysis was done on the impact of these steroid hormones on the risk of stroke subtypes. The T/E2 ratio was associated to an elevated risk of small vessel stroke (SVS) according to the inverse variance weighted approach which was the main MR analytic technique (OR, 1.23, 95% CI: 1.05-1.44, p = 0.009). These findings were solid since no heterogeneity nor horizontal pleiotropy were found. The causal association between T/E2 and SVS was also confirmed in the replication study (p = 0.009). Nevertheless, there was no proof that other steroid hormones increased the risk of stroke. According to this study, T/E2 ratio and SVS are causally related. However, strong evidence for the impact of other steroid hormones on stroke subtypes is still lacking. These findings may be beneficial for developing stroke prevention strategies from steroid hormones levels.

Mendelian Randomization Analysis↗

PubMed2002

Direct response of the murine prostate gland and seminal vesicles to estradiol.

In the prostate, testosterone action depends on conversion to bioactive metabolites dihydrotestosterone and 17beta-estradiol (E2) via the 5alpha-reductase and aromatase enzymes, respectively. Exogenous estrogen inhibits prostate growth by indirect effects caused by suppression of pituitary gonadotropins and testicular testosterone output, but direct effects are less well known. Direct effects of estrogens were evaluated using the hypogonadal (hpg) mouse model, which has postnatal deficiency in gonadotropins and testosterone but remains hormone sensitive. Mature hpg mice were implanted sc with implants filled with E2. After 6 wk, prostate lobe [anterior prostate (AP) and ventral prostate (VP)] and seminal vesicle (SV) organ volumes were significantly increased (P < 0.05) but remained smaller than wild-type mice. Analysis of the relative volumes (the proportional composition) of each tissue compartment in these organs showed significant increases in cellular and luminal volumes (P < 0.05) in AP (but not VP) and in SVs. Stromal fibroblasts proliferated, whereas smooth muscle cells were reduced in the AP and SVs. In the epithelia, basal cells proliferated and became metaplastic in the AP and VP. In the AP, luminal debris accumulated, together with an inflammatory response, but there was no evidence of malignant changes. The current study unequivocally demonstrates direct proliferative responses to E2 in the hpg mouse AP and VP lobes and SVs, characterized by discrete lobe-specific changes, including smooth-muscle regression, fibroblast proliferation, inflammation, and basal epithelial cell proliferation and metaplasia.

Animals↗

PubMed2005

Expression of constitutive androstane receptor splice variants in rat liver and lung and their functional properties.

The mammalian constitutive androstane receptor (CAR) is a transcription factor that participates in controlling the expression of xenobiotic metabolizing and transporting genes in response to xenobiotics in an organ-specific manner. In addition to the wild-type CAR (CAR WT) mRNA, mRNAs for five splice variants (SVs) could be detected in the liver of 7-week-old male Wistar rats by RT-PCR using primer pairs covering a full-length mRNA derived from 9 exons; insertion of 18 bp at the 5'-end of intron 8 with or without deletion of 3 bp from the 5'-end of exon 7 (CAR SV1 or SV2), deletion of 4 bp from the 5'-end of exon 8 (CAR SV3), insertion of 195 bp intron 7 (CAR SV4), and insertion of 91 bp intron 6 (CAR SV5). In contrast, only CAR SV5 was detected in lung. Due to the introduction of novel stop codons, all the SVs were considered to code for premature proteins. The liver homogenate gave two protein bands in the vicinity of 37 kDa on Western blotting. They were attributable to CAR WT and SV-complex, respectively, based on their putative molecular weights in descending order. Upon cotransfection with the reporter plasmid, only the cells transfected with the CAR SV4-expression plasmid showed enhanced luciferase activity similar to the WT-transfected cells, for which the further splicing of the remaining intron 7 seemed to be responsible. The transactivation-defective SVs downregulated CAR WT-induced luciferase activity to some extent in the cotransfection experiments.

Alternative Splicing↗

PubMed1999

[Development of new anti-atherosclerotic drugs based on the phenotypic modulation of vascular smooth muscle cells].

We have established a novel smooth muscle cell line (SVS) which retains the expression of specific markers for smooth muscle cells, such as smooth muscle myosin-1, calponin and SM22 alpha, from temperature-sensitive SV40 large T-antigen transgenic mice. SVS cells showed temperature-dependent growth and the expression of smooth muscle markers, showing that the differentiation stage can be controlled in this cell line by culture temperature. We have constructed luciferase-reporter cell lines for calponin and SM22 alpha genes by using SVS cells. We detected some compounds including ascorbic acid, which stimulated the expression of smooth muscle markers by the reporter assay. Ascorbic acid and its long lasting derivatives stimulated the expression of markers continuously. Moreover, ascorbic acid activated the expression of markers in synthetic SMCs seen in the intima of a rat balloon injury model. Thus, this reporter system should be useful for discovery of new antiatherosclerotic drugs.

Animals↗

PubMed2005

Developmental transformation of the release modality at the calyx of Held synapse.

Ca(2+) influx through voltage-gated Ca(2+) channels (VGCCs) into nerve terminals triggers vesicular fusion and neurotransmitter release. However, it is unknown whether the coupling between VGCCs and synaptic vesicles (SVs) is developmentally regulated. By paired patch-clamp recordings from the mouse calyx of Held synapse, we show here that injection of a Ca(2+) buffer with slow binding kinetics (EGTA; 10 mm) potently attenuated transmitter release in young terminals [postnatal day 8 (P8)-P12] but produced little effect in older ones (P16-P18), suggesting that SVs in young synapses are loosely coupled to VGCCs, but the coupling tightens spatially during maturation. Using voltage paradigms that specifically recruit different numbers of VGCCs without changing the driving force for Ca(2+), we found that the Ca(2+) cooperativity (m), estimated from graded presynaptic Ca(2+) currents and transmitter release, was much higher in P8-P12 synapses (m = 4.8-5.5) than that in P16-P18 synapses (m = 2.8-3.0; 1 mm [Ca(2+)](o)), implying that the number of VGCCs or Ca(2+) domains required for release of single SVs decreases with maturation. The m value remained significantly different between two age groups at 35 degrees C or in 2 mm [Ca(2+)](o) and was independent of postsynaptic receptor desensitization. We demonstrated that release from P8-P12 terminals involved both N- and P/Q-type VGCCs, but P/Q-type-associated release sites specifically displayed low m values. These results suggest a developmental transformation of the release modality from "microdomain," involving cooperative action of many loosely coupled N- and P/Q-type VGCCs, to "nanodomain," in which opening of fewer tightly coupled P/Q-type VGCCs effectively induce a fusion event. Spatial tightening improves the release efficiency and is likely a critical step for the development of high-fidelity neurotransmission in this and other central synapses.

Age Factors↗

PubMed2001

Localization of parathyroid tumours in the minimally invasive era: which technique should be chosen? Population-based analysis of 253 patients undergoing parathyroidectomy and factors affecting parathyroid gland detection.

A series of 253 consecutive patients with proved primary hyperparathyroidism due to parathyroid tumours was reviewed. There were 68 (26.9%) men and 185 (73.1%) women, with a median age of 57 years (range 13-82 years). All patients, prior to successful parathyroidectomy, underwent one or more preoperative localization procedures such as: neck ultrasonography (US) in 191 (75.5%), (201)Tl/(99m)Tc-pertechnetate subtraction scintigraphy (TPS) in 144 (56.9%), CT scan in 92 (36.4%), (99m)Tc-sestamibi/(99m)Tc-pertechnetate subtraction scintigraphy (MPS) in 90 (35.6%), selective venous sampling (SVS) with parathyroid hormone (PTH) assay in 30 (11.9%), and magnetic resonance imaging (MRI) in 6 (2.4%) patients. The results were compared with operative and histological findings that showed 235 (92.9%) solitary parathyroid adenomas, 13 (5.1%) carcinomas and 5 (2.0%) double adenomas. Sensitivity and positive predictive value were 82.9% and 93.8% for US, 83.6% and 91.8% for TPS, 81.3% and 98.7% for CT scan, 85.1% and 96.1% for MPS, 65.4% and 80.9% for SVS, and 80.0% and 80.0% for MRI respectively. No different results (P=NS) were found using US, TPS, MPS or CT scan, whereas SVS and MRI sensitivity was lower (P<0.05). The combination of MPS and US was 94.0% sensitive (P<0.05) but when TPS, CT scan or MRI were also used overall sensitivity did not improve significantly (P=NS). In conclusion, MPS should be used as the starting preoperative localization procedure, while US and MPS together represent the most reliable noninvasive localization tool. If MPS and US are negative or not in agreement, further studies are not cost-effective and the patient should undergo bilateral neck exploration.

Adolescent↗

PubMed1998

Ventricular shunt removal: the ultimate treatment of the slit ventricle syndrome.

OBJECT: The aim of this study was to assess the effectiveness of an algorithm used to evaluate and prescribe treatment for patients having slit ventricle syndrome (SVS). METHODS: All patients included in this protocol underwent fiberoptic intracranial pressure monitoring after removal or externalization of their ventricular shunt systems. A significant number of patients did not need extracranial cerebrospinal fluid (CSF) diversion and tolerated removal of their shunt systems without requiring further intervention. Patients who demonstrated a need for CSF drainage underwent an endoscopic third ventriculostomy, regardless of the putative cause of their hydrocephalus. Sixteen (72.7%) of 22 patients experienced resolution of or significant improvement in their SVS complaints after their inclusion in the protocol. Concomitantly, 14 (64%) of 22 patients were no longer shunt dependent after a mean follow-up period of 21.4 months. CONCLUSIONS: A significant number of patients debilitated by SVS may experience improvement in their symptoms and undergo shunt removal according to this protocol, improving their quality of life and simplifying their medical follow up.

Adolescent↗

PubMed2005

The role of lumbar shunts in the management of slit ventricles: does the slit-ventricle syndrome exist?

OBJECT: Slit-ventricle syndrome (SVS) is a confusing description of presentations in patients with chronic shunt-treated hydrocephalus. These patients are prone to acute deterioration with recurrent malfunction. The authors describe the clinical profile and management outcome of using lumboperitoneal (LP) shunts in this population of patients. METHODS: Thirty-three patients with slit ventricles and recurrent malfunctions were converted to LP shunts (mean age 12 years). The initial ventricular shunt was placed at a mean age of 16.5 months. Ten patients had failed endoscopic third ventriculostomies prior to placement of their LP shunt. At a previous presentation, in 11 patients suspected to have SVS following revision of the shunt, intracranial pressure normalized after insertion of a contralateral shunt, suggesting that their ventricles were isolated. The rate of infection and malfunction was compared before and after conversion to an LP shunt. Twenty-seven patients were successfully converted to LP shunts. Four of the 11 patients with isolated ventricles required ventricular shunts in addition to the LP shunt. During a mean follow-up period of 16.7 months, the malfunction rate per patient decreased from 4.81 for ventriculoperitoneal shunts, prior to conversion to 1.48 after conversion to LP shunts, a statistically significant reduction (p < 0.000). No significant difference was found in the rate of shunt infections (7.1% for VP shunts and 9.6% for LP shunts, p = 0.44). No patient presented with acute symptoms following malfunction of an LP shunt or suffered from a Chiari I malformation. CONCLUSIONS: Conversion to an LP shunt is a safe and effective procedure in patients prone to rapid decompensation and recurrent shunt malfunctions from small, slitlike ventricles. The term SVS is confusing. The condition is a manifestation of an unrecognized slitlike isolated ventricle and should be abandoned.

Adolescent↗

PubMed1999

Zone I retroperitoneal hematoma identified by computed tomography scan as an indicator of significant abdominal injury.

OBJECTIVE: All zone I retroperitoneal hematomas (Z1RPHs) identified at laparotomy for blunt trauma traditionally require exploration. The purpose of this study was to correlate patient outcome after blunt abdominal trauma with the presence of Z1RPH diagnosed on admission computed tomography (CT) scan. METHODS: This is a retrospective review of patients with blunt trauma who were admitted to a Level 1 trauma center and who underwent CT scan during a 40-month period. All scans with a traumatic injury were reviewed to identify and grade Z1RPH as mild, moderate, or severe. Patients requiring operative treatment were compared with those who were observed. Statistical analysis was performed with Student's t test and chi-square test, with P < .05 considered significant. RESULTS: Eighty-five (15.5%) of the CT scans were positive for Z1RPH. None of the 50 patients with a mild Z1RPH had their treatment altered. Of the 29 patients with a moderate or severe Z1RPH, 8 required celiotomy. The patients requiring celiotomy had significant elevations of solid viscus score (SVS) (4.9 +/- 1.6 versus 1.8 +/- 0.3), abdominal Abbreviated Injury Scale (3.8 +/- 0.3 versus 2.6 +/- 0.3), and transfusion requirements (13 +/- 4 versus 2 +/- 1). All patients (N = 4) with an SVS >4 required operative treatment. Seventy-two percent of patients with more than 1 intra-abdominal injury required abdominal exploration. CONCLUSIONS: The presence of a moderate or severe Z1RPH and more than 1 intra-abdominal injury or an SVS >4 on admission CT scan is an important radiographic finding. This injury pattern should be considered a contraindication for nonoperative treatment of the associated solid organ injury.

Abdominal Injuries↗

PubMed2001

Structure-based virtual screening protocols.

Virtual screening techniques continue to play an important role within the pharmaceutical industry lead discovery process. A core element of these technologies encompasses the ability to virtually screen compound databases in three-dimensional (3-D) target active sites (structure-based virtual screening (SVS)). Reviewed are the latest developments within SVS, with particular emphasis on new technology and validation experiments. Examples of successful SVS application are highlighted, together with studies illustrating current technology limitations. New methods for scoring ligand-protein binding interactions are discussed, including the latest developments in ligand interaction sampling technology.

Computer Graphics↗

PubMedDate not supplied

[Proton magnetic resonance spectroscopy in the diagnosis of brain diseases].

The role and position of proton magnetic resonance spectroscopy have been studied in diagnosis of brain diseases. 114 patients with various diseases of the brain have been examined (multiple sclerosis--41, insults of different etiology--17, encephalopathy--12, AIDS infection--23, epilepsy--12, reduction of the intellectual ability of various etiology--9). MR tomography and 1HMR Spectroscopy have been done with Magnetom "Vision", 1.5 T (Siemens) in the CRIRR, St. Petersburg. To get a proton magnetic-resonance specter, SVS_STEAM, SVS_STEAM-20 and SVS_SE-135 sequences have been used with the following parameters: TR 5000 ms, TE 10, 20 and 135 ms respectively, number of acquisitions--100. Typical changes of metabolities in every group have been revealed. The performed examinations have shown that proton magnetic resonance spectroscopy enables to widen our know-ledge about the nature of pathologic changes, that grow with different diseases of the brain.

Adolescent↗

PubMed2004

Surgical video systems.

A surgical video system (SVS) is an integration of components used to perform minimally invasive surgery (MIS). In the operating room, an SVS consists of an endoscope, an attached video camera, a light source, a video processor, and one or more video displays. A single SVS can generally be used in any type of MIS procedure (e.g., general, orthopedic, urologic), provided that it is equipped with the appropriate type of endoscope. In this Evaluation, we tested seven systems from six manufacturers. We found that, on average, three-chip systems provide better overall image quality than one-chip systems. Three systems were judged as providing image quality slightly superior to that of all the other systems; however, the level of subjectivity involved in judging performance suggests that users should perform in-house trials before purchase. All the evaluated systems performed relatively well in performance testing, but most systems were rated Fair or Poor in several human factors and safety tests. In fact, only two systems did not receive any Poor ratings in the Light Source Safety Features tests. Although users bear much of the responsibility for ensuring that light sources are used safely, most manufacturers have not made simple design changes that would make unintentional misuse less likely. We would be more likely to rate systems that still exhibit these safety issues in the future as Not Recommended or Unacceptable.

Costs and Cost Analysis↗

PubMedDate not supplied

Using data linkage to identify First Nations Manitobans: technical, ethical, and political issues.

BACKGROUND: The Manitoba Health Registry does not fully identify First Nations Manitobans, impacting the ability to adequately describe their health status and use of health services using this data source alone. This paper describes the processes in producing a valid database for use in a population-based report by the Manitoba Centre for Health Policy (MCHP). METHODS: The Indian Registry's Status Verification System (SVS) file is a national database containing a complete list of Registered First Nations eligible for benefits through the Indian Act. Through negotiations with the Assembly of Manitoba Chiefs' Health Information Research Committee, Indian and Northern Affairs Canada, FNIHB, Manitoba Health, and MCHP, a linkage of the SVS files and Manitoba Health's Registry was accomplished. Of the 116,177 SVS records and 5,803 deceased records, 97,635 individuals linked to the Manitoba Health Registry. RESULTS: There was a 99% match on gender, 70% match on surname, 94% match on given name, and 96% match on birth year. The total represents a 20% decrease in records from the Indian Registry. The decrease was greater for females, older people and those from southern areas. CONCLUSION: The linkage resulted in a 20% increase over Manitoba Health data alone. Our inability to link all of the records may be due to several factors. Individuals with a Manitoba Band affiliation living outside of the province could not be linked to the Manitoba Health Registry. First Nations living in Manitoba but affiliated with a non-Manitoba Band would not have been in the file obtained. Finally, births, deaths and surname change after marriage may be under-reported to the Indian Registry. This linkage enabled MCHP to provide a more accurate picture of First Nations health status and use of health care services than otherwise would have been available. Ongoing linkages with Manitoba Health data, as well as similar linkages elsewhere in Canada, are encouraged.

Adolescent↗

PubMed2005

Diagnostic and prognostic value of early MR Imaging vessel signs in hyperacute stroke patients imaged <3 hours and treated with recombinant tissue plasminogen activator.

BACKGROUND AND PURPOSE: Analogous to the CT hyperattenuated vessel sign (HMCAS), MR imaging may show hypo- or hyperintense vessels in acute ischemic stroke (AIS) patients. We assessed the diagnostic and prognostic strength of early MR imaging vessel signs in AIS patients treated with intravenous thrombolysis (IVT) within 3 hours of the onset of symptoms. METHODS: We studied AIS patients both treated with IVT and stroke MR imaged within 3 hours of the onset of symptoms and at 2 hours and 24 hours after treatment. We assessed the presence or absence of early vessel signs (hyperintense fluid-attenuated inversion recovery sign [FLAIR HVS]; gradient-echo susceptibility vessel sign [GRE SVS]) compared with a combined MR angiography/perfusion-weighted imaging reference and their strength for predicting clinical outcome (favorable vs. poor, independent vs. dependent, or dead, death), recanalization (by clot composition and flow), and hemorrhage in uni- and multivariate analysis. RESULTS: Fifty-six patients (age range, 76 years +/- 13 years; median National Institutes of Health stroke scale score [NIHSSS], 11) met the inclusion criteria. Forty-four patients (78.6%) had a vessel occlusion at baseline; 22 of them (50%) recanalized. Nineteen patients (33.9%) suffered some form of intracranial hemorrhage (ICH), 24 patients (42.9%) had an independent outcome, 18 patients (32.1%) a favorable outcome, and 14 patients died. Compared with our combined reference for vessel status PWI/MRA, the sensitivities of CT HMCAS, FLAIR HVS, and GRE SVS were 40%, 66%, and 34%, respectively, and improved during the hours that followed. Localization was accurately reflected by FLAIR HVS but not by GRE SVS. Only NIHSSS and age were independent predictors for recanalization and all clinical outcomes in multiple logistic regression analysis. CONCLUSION: Although early vessel signs can be helpful in the diagnosis of intravascular disease, they do not independently predict recanalization, ICH, or any of the three clinical outcomes in a multivariate logistic regression model. Thrombus composition as reflected by signal intensity characteristics on GRE and FLAIR does not predict the therapeutic effect of IVT.

Aged↗

PubMed2006

Characterization of receptors for growth hormone-releasing hormone in human osteosarcomas and Ewing's sarcomas.

Antagonists of growth hormone-releasing hormone (GH-RH) inhibit growth of various human cancers including osteosarcomas and Ewing's sarcomas, xenografted into nude mice or cultured in vitro. The antiproliferative effect of GH-RH antagonists could be mediated, in part, through the splice variants (SVs) of receptors for GH-RH which have been found in several human cancers and cancer cell lines. In this study we investigated the expression of SVs of GH-RH receptors and the binding characteristics of these receptor isoforms in MNNG/HOS human osteosarcoma and SK-ES-1 human Ewing's sarcoma grown in nude mice. RT-PCR revealed the presence of mRNA for SVs of GH-RH receptors in both human malignant bone cancer models. Using ligand competition assays with 125I-labeled GH-RH antagonist JV-1-42, we demonstrated in MNNG/HOS and SK-ES-1 tumors the presence of specific high affinity binding sites for GH-RH (Kd=5.83 nM and Kd=2.76 nM) with a maximal binding capacity (Bmax) of 552.1 fmol/mg protein and 371.9 fmol/mg protein, respectively. We also investigated the effect of GH-RH antagonist JV-1-38, administered s.c. at a dose of 20 microg twice daily for 4 weeks on the gene expression, affinity and concentration of receptors for GH-RH in MNNG/HOS human osteosarcomas xenografted into nude mice. Treatment with JV-1-38 did not affect the expression and binding characteristics of GH-RH receptors. High affinity binding of JV-1-38 to GH-RH receptors on MNNG/HOS tumors was characterized by an IC50 value of 1.04 nM. The presence of GH-RH receptors in human bone tumors provides a rationale for new approaches to the therapy of this malignancy based on GH-RH antagonists.

Animals↗

PubMed1988

Prostacyclin and thromboxane A2 formation by atherosclerotic carotid artery: comparison with normal aorta, saphenous vein, and platelets.

Prostacyclin (PGI2) and thromboxane A2 (TxA2) formation by whole-tissue segments of nine carotid endarterectomy specimens (CES), five normal aortic specimens (NAS), six saphenous vein specimens (SVS), and four platelet samples were determined by incubation with 10 mumol/L 1-14C-radiolabeled prostaglandin endoperoxide H2 (PGH2), and in other experiments with and without 10 mumol/L of CGS 13080, a TxA2 synthase inhibitor. PGI2 formation (expressed as picomoles 6-keto-PGF1 alpha/2-min incubation per sample) by nonatheromatous proximal intima of CES (307 +/- 23, mean +/- standard error) and distal intima of CES (260 +/- 22) was not statistically different; however, it was greater than atheromatous transitional plaque (159 +/- 13 pmol) (p less than 0.01) and ulceration regions (140 +/- 15 pmol) (p less than 0.01) of CES, NAS (204 +/- 16 pmol) (p less than 0.01), and SVS (165 +/- 9 pmol) (p less than 0.01). TxA2 formation (expressed as picomoles TxB2/2-min incubation per sample) by CES ulceration (51 +/- 2 pmol) was low but greater than proximal (17 +/- 2 pmol) (p less than 0.01), distal (19 +/- 3 pmol) (p less than 0.01), and transitional (23 +/- 3 pmol) (p less than 0.01) regions. TxA2 formation by NAS and SVS was not detected (less than 10 pmol). CGS 13080 inhibited TxA2 formation by CES below the limits of detection. Incubation of 1.9 x 10(5) intact platelets with 10 mumol/L of PGH2 formed a quantity of TxA2 equal to that of CES ulceration.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗