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Biomedical subjects

C Branch

Publications and source records attributed to C Branch.

At least 19 recordsLinked to original sources
PubMed2000

Tumor-suppressive effects by adenovirus-mediated mda-7 gene transfer in non-small cell lung cancer cell in vitro.

The melanoma differentiation-associated gene-7 (mda-7), cloned from a human melanoma cell line H0-1, is known to induce tumor cell-selective growth inhibition in breast cancer cells in vitro and loss of tumorigenicity ex vivo. Yet, the mechanisms underlying these effects are still unknown. Therefore, we investigated these mechanisms on the molecular level in human non-small cell lung carcinoma (NSCLC) cells in vitro. Overexpression of mda-7 protein by Ad-mda-7 significantly suppressed proliferation and induced G2/M cell cycle arrest in wild-type p53 (A549, H460), and p53-null (H1299) non-small cell lung cancer cell lines, but not in normal human lung fibroblast (NHLF) cells. p53, Bax, and Bak protein expression was up-regulated in wild-type p53 tumor cell lines, but not in p53-null cells, suggesting that an intact p53 pathway was required for Bax and Bak induction. However, in all three cancer cell lines tested, activation of the caspase cascade and cleavage of poly(ADP-ribose) polymerase (PARP) appeared to be independent of the p53 mutational status. Together, these results suggest that apoptosis may be induced via multiple pathways by Ad-mda-7 in lung cancer cells and that Ad-mda-7 has the potential to become a novel therapeutic for clinical cancer gene therapy. Gene Therapy (2000) 7, 2051-2057.

Adenoviridae↗
PubMed1999

MR perfusion imaging in human brain using the UNFAIR technique. Un-inverted flow-sensitive alternating inversion recovery.

Pulsed arterial spin labeling magnetic resonance techniques have been developed recently to estimate cerebral blood flow (CBF). Flow-sensitive alternating inversion recovery (FAIR) is one such technique that has been implemented successfully in humans. Un-inverted FAIR (UNFAIR) is an alternative technique in which the flow-sensitive image is acquired following inversion of all spins outside the slice of interest, and the control image is acquired without any spin labeling. This approach is potentially more efficient than FAIR since the UNFAIR control image is entirely flow independent and need only be acquired once. Here, we describe implementation of the sequence on a clinical 1.5 T magnetic resonance system. Both FAIR and UNFAIR perfusion-weighted images were obtained from six normal volunteers. Wash-in/wash-out curves measured in cortical gray and white matter were practically identical for the two techniques, as predicted by our model.

Adult↗
PubMed1998

Coronary arterial lesions in dogs treated with an endothelin receptor antagonist.

Structurally and pharmacologically diverse vasodilators are known to lower blood pressure, increase heart rate, and produce acute injury to right coronary arteries in the dog. Administration of low concentrations of endothelin-1 (ET-1) to anesthetized dogs causes coronary vasoconstriction and reductions in coronary blood flow. Therefore, pharmacologic blockade of endothelin receptors (ETA and ETB) with the mixed ET receptor antagonist SB 209670 could lead to coronary vasodilatation. In toxicology studies, continuous administration of SB 209670 to dogs for 5 days at 50 micrograms/kg/min was associated with minor but sustained increases in heart rate (10-30 beats/min), slight decreases in mean arterial pressure (10-15 mm Hg), and medial hemorrhage and necrosis of extramural coronary arteries in the right atria. Doses of 10 micrograms/kg/min had no effect. The lesions in the right atrium were associated with the highest density of ET receptors, approximately 470 fmol/mg compared to 170-200 fmol/mg in the ventricles and septum. Because changes in systemic cardiovascular parameters are minimal, the coronary arterial lesion is most likely due to a local vasodilatory effect in the coronary bed.

Animals↗
PubMed1998

Transcranial 3D B-mode imaging in a case of cerebral hemorrhage.

The case of a patient with temporal lobe hemorrhage is presented. This is the first report of use of a new three-dimensional data acquisition system that entails free-hand scanning with three-dimensional transcranial duplex sonography. Three-dimensional image reconstruction reduced the spatial asymmetry inherent in oblique two-dimensional ultrasonography, making evaluation of the precise location, size, and anatomic relations of intracranial hemorrhage easier.

Adult↗
PubMed1996

Tumor retention of 5-fluorouracil following irradiation observed using 19F nuclear magnetic resonance spectroscopy.

PURPOSE: The combination of 5-fluorouracil (5FU) and radiation results in improved tumor control in a variety of gastrointestinal cancers. We propose the enhancement is related to radiation potentiating the antitumor effects of 5FU. To better understand the mechanism of the 5FU-radiation interaction, 19F nuclear magnetic resonance (NMR) spectroscopy experiments were performed to observed the tumor clearance and metabolism of 5FU. METHODS AND MATERIALS: Experiments were performed on 10 3-6-week-old female (Nu/Nu) athymic nude mice. Flank tumors measuring approximately 1.0 cm in diameter 3 weeks following a subcutaneous injection of 1 x 10(6) human colon adenocarcinoma (HT-29) cells were studied. In our first group, all animals received an intravenous bolus injection of 5FU (100 mg/kg) immediately before spectroscopic analysis. Animals in the second group were first treated with a single tumor radiation dose of 10 Gy just before the 5FU injection and subsequent spectroscopy. Spectroscopic analysis was performed with a 2.0-T NMR spectroscopy system. RESULTS: The tumor retention of 5FU was prolonged in animals receiving radiation before the drug infusion. The tumor clearance rate of the 5FU for nonirradiated animals was 0.0178 +/- 0.0082/min vs. 0.0055 +/- 0.0027/min for irradiated animals, reflecting a threefold reduction in drug clearance in the irradiated tumors. The difference was significant at p < 0.005. CONCLUSION: Our preliminary experiments suggest the enhanced cytotoxicity seen with concurrent 5FU and radiation is related to prolonged tumor retention of 5FU induced by radiation. This is consistent with the hypothesis that radiation is potentiating the cytotoxic effects of 5FU.

Animals↗
PubMed1996

Improving analgesic prescribing in a general teaching hospital.

Patients suffering from cancer and human immunodeficiency virus (HIV) disease at a teaching hospital were found to have poorly controlled pain. Many were prescribed inappropriate analgesia. A palliative care service was established to provide symptom control for patients and education for staff. Educational materials were developed, didactic teaching organized, and one-to-one education by case discussion provided to improve patient management. A repeat survey to evaluate the service showed an increase in the use of appropriate opioids, such as morphine and diamorphine, and a decrease in the use of buprenorphine and papaveretum, which are less suitable for use in chronic cancer pain. The acceptability of the guidelines and rapid availability of a palliative care opinion has improved analgesic prescribing.

Adolescent↗
PubMed1996

The provision of a palliative care service in a teaching hospital and subsequent evaluation of that service.

A survey at a large tertiary referral hospital showed that patients with cancer and HIV disease had poorly controlled symptoms. A palliative care service was introduced, employing a doctor and part-time pharmacist. The doctor was available to see and advise about terminally ill patients. With the pharmacists, an educational programme of meetings, teaching sessions and information leaflets was developed. One year after the introduction of the service a repeat survey all patients with cancer or HIV disease was carried out. Problems on admission were similar in both surveys, but fewer patients' symptom scores deteriorated during their hospital stay. There was a significantly increased use of appropriate opioid analgesics and NSAIDs. Staff were satisfied with the service.

Attitude of Health Personnel↗
PubMed1995

Higher lung cancer risk for younger African-Americans with the Pro/Pro p53 genotype.

A restriction fragment length polymorphism in codon 72 of the p53 gene has been implicated in lung cancer risk, although the functional significance of the polymorphism has not been determined. This association was examined in 109 lung cancer cases (67 African-American and 42 Mexican-American) and 114 controls (74 African-American and 40 Mexican-American) identified from a molecular epidemiological study of lung cancer. The susceptible Pro/Pro genotype was associated with a 1.56-fold higher risk of lung cancer in African-Americans and a 1.95-fold in Mexican-Americans, although neither estimate was statistically significant. In fact, the prevalence of the Pro/Pro genotype was only 2.5% in Mexican-American controls, compared with 20.3% for African-American controls. Patients with the susceptible genotype appeared to have earlier age at diagnosis and lower mean cigarette pack-year exposures than did patients with the Arg/Arg or Arg/Pro genotypes. Risk estimates for the susceptible genotype were 11.29 (1.1, 111.3) for patients < 53 years of age and 14.1 (1.5, 130.6) for patients who reported < 30 pack-years of smoking. The Pro/Pro genotype was not associated with elevated risk in older patients, nor with heavier smokers. If Pro/Pro is a susceptible genotype, the lower prevalence evident in Mexican-Americans may partly explain their lower rates of lung cancer.

Aged↗
PubMed1994

Loss of alpha 1 beta 1 and reduced expression of other beta 1 integrins and CAM in lung adenocarcinoma compared with pneumocytes.

Alterations in expression of various cell-adhesion molecules have been reported in a variety of malignant tissues. However, little is known about how lung adenocarcinomas differ in CAM expression from the normal lung. We analyzed the expression of integrins alpha 1 beta 1 through alpha 6 beta 1, intercellular adhesion molecule (ICAM)-1, neural cell adhesion molecule (NCAM), and lymphocyte function antigen (LFA)-3, CD44, and the two carbohydrate antigens, Lewisx (Le(x)) and sialosyl-Le-Le(x) of lung adenocarcinoma cells, and compared them with autologous pneumocytes. CAM expression was studied by an immunohistochemical method using monoclonal antibodies, and computerized image analysis was used to quantify the immunoperoxidase-staining intensity. The normal lung alveolar cells strongly expressed the integrins alpha 1 beta 1 and alpha 3 beta 1, and fairly expressed alpha 2 beta 1, alpha 4 beta 1, alpha 5 beta 1, and alpha 6 beta 1. ICAM-1, LFA-3, and CD44 were strongly expressed, whereas NCAM, the Le(x) and sialosyl-Le-Le(x) antigens, were expressed weakly. In contrast, we did not detect expression of the alpha 1 beta 1 integrin on any autologous lung adenocarcinoma cells, and they showed on average a 50% reduction in labeling relative intensity units for the integrin common chain marker beta 1, the specific integrins alpha 3 beta 1, alpha 5 beta 1, and alpha 6 beta 1, and ICAM-1, and LFA-3. Examination of the adjacent small blood vessel endothelium in malignant lung tissues did not reveal any major alterations in CAM expression, the small vessel endothelium of the normal and malignant lung tissues appeared with a similar CAM profile. These results suggest that lung adenocarcioma cells have a lack of alpha 1 beta 1 expression and significant reduction in some other integrin beta 1 and CAM expression in comparison with their autologous pneumocytes. This aberration in CAM expression by the lung adenocarcinoma cells may be involved in their loss of proliferation control and may interfere with leukocyte adhesion to tumor cells, enabling the tumor to escape immunodestruction.

Adenocarcinoma↗
PubMed1994

The relationship of intracranial venous pressure to hydrocephalus.

Little is known about intracranial venous pressure in hydrocephalus. Recently, we reported that naturally occurring hydrocephalus in Beagle dogs was associated with an elevation in cortical venous pressure. We proposed that the normal pathway for cerebrospinal fluid (CSF) absorption includes transcapillary or transvenular absorption of CSF from the interstitial space and that the increase in cortical venous pressure is an initial event resulting in decreased absorption and subsequent hydrocephalus. Further analysis, however, suggests that increased cortical venous pressure reflects the effect of the failure of transvillus absorption with increase in CSF pressure on the venous pressure gradient between ventricle and cortex. Normally, the cortical venous pressure is maintained above CSF pressure by the Starling resistor effect of the lateral lacunae. A similar mechanism is absent in the deep venous system, and thus the pressure in the deep veins is similar to that in the dural sinuses. Decreased CSF absorption causes an increase in CSF pressure followed by an increase in cortical venous pressure without a similar increase in periventricular venous pressure. The periventricular CSF to venous (transparenchymal) pressure (TPP) gradient increases. In contrast, cortical vein pressure remains greater than CSF pressure (negative TPP). The elevated periventricular TPP gradient causes ventricular dilatation and decreased periventricular cerebral blood flow (CBF), a condition that persists even if the CSF pressure returns to normal, particularly if tissue elastance is lessened by tissue damage. If deep CBF is to be maintained, periventricular venous pressure must increase. Since the veins are in a continuum, cortical venous pressure will further increase above the CSF pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1987

Intracranial compliance is time-dependent.

Compliance is considered a fundamental characteristic of the intracranial system, is measured by the volume pressure test (VPT), and is considered to be related to the cerebrospinal fluid (CSF) pulse pressure (delta Pcsf). This study was carried out to determine the time-dependent relationship of intracranial compliance and the relationship between intracranial pulse pressure and compliance. In nine dogs divided into two groups, the rate of injection of a test volume and the physical compliance of the intracranial system was altered by opening or closing the skull without altering the base line intracranial pressure. The VPT was carried out by three methods: slow infusion--infusion of 0.3 ml at 1.5 to 0.2 ml/second, fast infusion--infusion of 0.2 ml in 0.5 second, and bolus injection--injection of 0.05 ml as rapidly as possible. With the skull closed, there were linear relationships between diastolic CSF pressure (Pcsf-d) and delta Pcsf; Pcsf-d and slow infusion, fast infusion, or bolus injection; and Pcsf-d and CSF respiratory wave amplitude. With the skull open, the linear relationship was retained only for Pcsf-d vs. delta Pcsf and Pcsf-d vs. bolus injection. Furthermore, delta Pcsf amplitude at any level of Pcsf-d was the same whether the skull was open or closed. It is concluded that intracranial compliance can be divided into two components based on the time constant of the injected volume: physical compliance, which has a short time constant and is related to delta Pcsf, and physiological compliance, which has a longer time constant and is related to the VPT.

Animals↗
PubMed1985

The CSF pulse wave in hydrocephalus.

Twenty-one dogs were rendered hydrocephalic by the intracisternal injection of kaolin. After various intervals between 1 and 44 days the animals were anesthetized for the measurement of arterial (lingual), ventricular, and sagittal sinus pressures. Following the recordings the animals were sacrificed by formalin infusion, the brains sectioned serially, and ventricular size measured. In general, the longer the period of incubation the larger the ventricles. There was no correlation between the degree of hydrocephalus and mean or pulsatile ventricular pressure. All animals with a pressure of less than 9 torr demonstrated non-linear transmission of the arterial wave into the CSF (which is the same as the pulse in the venous bed). All animals with a pressure greater than 12 torr had linear transmission of the wave. These findings in the hydrocephalic animals are the same as those found in nonhydrocephalic animals with similar pressures. It is concluded that the CSF pulse wave seen in hydrocephalic dogs is a result of how the cerebrovascular bed processes the cardiac pulse wave and is independent of the hydrocephalic process. There is no evidence that the pulse wave produces hydrocephalus.

Animals↗
PubMed1984

Headaches after childbirth.

71 women were examined daily for the presence of headache in their first post partum week. Post natal headache (PNH) occurred in 27, (39%) of the women and was most frequent on days 4-6 post partum. PNH was significantly associated with a previous or family history of migraine and pre-menstrual migraine. Although 83% of those with PNH had a migraine diathesis, they did not describe their headache as one of their usual migraines as it was considerably milder. Headaches were more frequent among multigravida but as rather more multigravida had a previous migraine diathesis this may reflect a sampling bias. PNH subjects had significantly more tension and depression suggesting that at least some PNH may be tension headache. Around 3 or 4 days post partum, women began to lose weight and the onset of headache often coincided with the start of this weight loss. 12 women with, and 12 without PNH took part in a metabolic study, and collected sequential 24 h urine samples from days 2-7 post partum. Potassium and oestrogen excretion were increased on day 3, and progesterone on days 3, 4 and 5. Differences in the excretion pattern of these hormones might reflect small changes in renal function and further work measuring plasma hormone levels could help to clarify this. PNH, like pre-menstrual headache and pill withdrawal headache may represent a further example of the triggering effect that a fall in sex hormone level has on the migraine diathesis.

Adolescent↗
PubMed1983

Hydraulic model of the cerebrovascular bed: an aid to understanding the volume-pressure test.

A hydraulic model of the cerebrovascular bed is presented. The model consists of a Starling resistor in series with an upstream resistance. Volume-pressure tests were performed on the model by injecting fluid into the rigid shell of the Starling resistor. An exponential pressure response to the increase in fluid volume was observed, which supports the hypothesis that the origin of the in vivo exponential pressure response to a transient increase in cerebrospinal fluid (CSF) volume can be attributed to compression of the cerebral vessels, most probably the veins. Mathematical expressions for the dependence of pressure on volume change were derived from the model and applied to in vivo volume-pressure data. The correlation between the model and in vivo experiments suggests that the CSF pressure is coupled to cerebral venous pressure and that the volume-pressure test is an indirect measure of the cerebral venous volume and is not a measure of intracranial elastance. The physical basis for the volume-pressure test is clarified, and expressions are derived to improve the utility of the test.

Blood Pressure↗
PubMed1983

Hydraulic model of myogenic autoregulation and the cerebrovascular bed: the effects of altering systemic arterial pressure.

Systemic arterial (Ps), cerebrospinal fluid (Pcsf), and sagittal sinus (Pss) pressures were measured in 39 dogs divided into eight groups in which Ps was altered pharmacologically or by bleeding. The pharmaceuticals used were norepinephrine (N-EP), dopamine (DOP), sodium nitroprusside (SNP), and nitroglycerin (NTG). SNP and NTG were examined with and without methohexital (MHX) anesthesia and during chronic infusion and bolus injection. The various pressures were subjected to systems analysis in accordance with a previously published model of myogenic autoregulation. Myogenic autoregulation seemed to be impaired only during infusions of N-EP, DOP, and SNP without MHX and during hypovolemic hypotension. The various observed changes in Pcsf are explained by using a hydraulic model of the cerebrovascular bed in which Pcsf represents the pressure drop across the outflow resistance of the bridging veins and lateral lacunae and myogenic autoregulation at the arteries and arterioles represents the major inflow resistance. Impaired myogenic autoregulation is associated with a rise in Pcsf. In addition, variation in pulse pressure is demonstrated to be related to the arterial pulse pressure and the degree of arterial and arteriolar vasodilation.

Animals↗
PubMed1982

Cerebrospinal fluid pulse waveform as an indicator of cerebral autoregulation.

Systems analysis of the systemic arterial (SAPW), cerebrospinal fluid (CSFPW), and sagittal sinus (SSPW) pulse waves was carried out in 13 dogs during hypercapnia (5% CO2), intracranial normotension (inhalation of 100% O2), and intracranial hypertension (inhalation of 100% O2 plus an intraventricular infusion). Power amplitude and phase spectra were determined for each wave, and the power amplitude and phase transfer functions calculated between the cerebrospinal fluid (CSF) pressure and systemic arterial pressures, and between the sagittal sinus pressure and CSF pressure. The study indicates that the CSFPW and SSPW were virtually identical when impedance between the cerebral veins and sagittal sinus was minimal, which argues that the CSF pulse was derived from the cerebral venous bed. During inhalation of 100% O2, transmission of the SAPW across the precapillary resistance vessels into the cerebral venous pulse (as represented by the CSFPW) was nonlinear, while transmission across the lateral lacunae into the sagittal sinus was linear. During intracranial hypertension, wave transmission across the precapillary resistance vessels was linear, and across the lateral lacunae was nonlinear. During hypercapnia, wave transmission across the precapillary resistance vessels and the lateral lacunae was linear. When the wave transmission was nonlinear, there was also suppression in transmission of the lower harmonics, particularly the fundamental frequency, and a more positive phase transfer function, suggesting an inertial effect or decrease in acceleration of the pulse. Conversion from a nonlinear to linear transmission across the precapillary resistance vessels is evidence of loss of vasomotor tone, and is accompanied by rounding of the CSFPW. A vascular model which encompasses the above data and is based on flow in collapsible tubes and changes in vasomotor tone is posited to explain control of pulsatile flow and pulse waveform changes in the cerebrovascular bed. The model helps to clarify the strong interrelationship between intracranial pressure, cerebral blood flow, and cerebral autoregulation.

Animals↗