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Biomedical subjects

S Chan

Publications and source records attributed to S Chan.

At least 199 records · Page 11Linked to original sources

Dynamic cardiomyoplasty: clinical follow-up results.

From 1985 to April 1990, 78 clinical dynamic cardiomyoplasty procedures were performed using the latissimus dorsi muscle stimulated with the Medtronic Cardiomyoplasty System. Indications for surgery were mostly ischemic and idiopathic dilated cardiomyopathies with patients in severe cardiac insufficiency (NYHA Class III and IV). Results of this multicenter study (11 centers) indicate that the dynamic cardiomyoplasty procedure can be transferred and reproduced in many centers with low perioperative mortality and that it improves the functional status of patients who survive the procedure. The survival rate suggests a long-term benefit (average implant time: 11.7 months). Although clinical functional improvement was reported, actual hemodynamic augmentations could not be clearly demonstrated under the protocol. Further studies of functional and hemodynamic parameters are necessary to determine if dynamic cardiomyoplasty is efficacious for a well-defined group of congestive heart failure patients. These points will be addressed in forthcoming studies.

Adolescent↗

Characterization of in vivo expression of the human papillomavirus type 16 E4 protein in cervical biopsy tissues.

The role of human papillomavirus (HPV) proteins in the pathogenesis of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer is poorly understood. To characterize E4 protein expression in 49 paraffin-embedded cervical biopsies representing different histopathologic grades of disease, antibodies were elicited to a synthetic peptide corresponding to amino acids 20-34 of a protein predicted to be encoded by the HPV 16 E4 open reading frame. The E4 protein was detected throughout the spectrum of CIN, from CIN1 to CIN3. Expression was localized to the cell nucleus, primarily in the superficial layers of the squamous cervical epithelium. Ultrastructural studies showed that the E4 protein was organized into compact, intranuclear arrays 25-35 nm in diameter. E4 protein expression was also demonstrated in some histologically normal tissues containing HPV 16 DNA, but not in any of five cervical cancers containing HPV 16 DNA. These results suggest that E4 protein expression may precede development of light microscopic tissue abnormalities, that it may continue through the spectrum of CIN, and that expression of this protein may be reduced or terminated in invasive cancer. The function of this protein remains unknown, but its nuclear localization may be consistent with a role in viral maturation.

Amino Acid Sequence↗

Effects of prostaglandin E2 on production of new cancellous bone in the axial skeleton of ovariectomized rats.

The effects of prostaglandin E2 (PGE2) were histomorphometrically evaluated in cancellous bone of the axial skeleton of ovariectomized, osteopenic rats. Four months following bilateral ovariectomy (OVX) and sham-ovariectomy (SHAM) at 3 months of age, rats received daily subcutaneous injections of PGE2 at 0, 0.3, 1.0, 3.0 and 6.0 mg/kg/day for 30 days. The undecalcified fourth lumbar vertebral bodies (LVB) were processed for static and dynamic bone histomorphometry. The OVX rats possessed a slightly osteopenic LVB (17% vs. 24% cancellous bone mass). In rats given PGE2 at 3 and 6 mg/kg/day for 30 days, bone turnover, lamellar bone mass, and formation of new woven bone trabeculae were increased. Observations supported the conclusion that PGE2 activates bone modeling and remodeling, and shifts bone balance in favor of formation. In OVX rats given 6 mg PGE2/kg/day, cancellous bone mass and trabecular numbers were restored to levels found in untreated SHAM rats. Cancellous bone mass in the LVB of SHAM rats given 3 and 6 mg PGE2/kg/day increased by 16% and 30% over that of control rats. In addition, PGE2 stimulated longitudinal bone growth in both OVX and SHAM rats, a response that differed from male rats.

Aging↗

Prostaglandin E2 enhances cortical bone mass and activates intracortical bone remodeling in intact and ovariectomized female rats.

To assess the efficacy of prostaglandin E2 (PGE2) in augmenting cortical bone mass, graded doses of PGE2 were subcutaneously administered for 30 days to seven-month old sham-ovariectomized (SHAM) and ovariectomized (OVX) rats. Both groups were operated at three months of age. Histomorphometric analyses of double fluorescent labeled tibial shafts were performed on basal control, OVX, and SHAM rats treated with 0, 0.3, 1, 3, and 6 mg PGE2/kg/d for 30 days. Baseline aging data showed increased cortical tissue and cortical bone area and reduced bone formation parameters at the periosteal and endocortical bone envelopes between three and eight months of age. The tibial shafts of OVX rats compared to SHAM controls showed elevated periosteal mineral apposition rate and endocortical bone formation parameters. PGE2 administration to OVX and SHAM rats increased cortical bone by the addition of new circumferential bone on the endocortical and periosteal surfaces, as well as woven cancellous bone in the marrow region. Stimulated osteoblastic recruitment and activity enhanced bone formation at all bone surfaces. The new bone was both lamellar and woven in nature. PGE2 treatment also activated intracortical bone remodeling (not seen in untreated eight-month old rats), creating a porous cortex. Thus, PGE2 administration activated cortical bone modeling in the formation mode (A----F), as well as intracortical bone remodeling (A----R----F). PGE2 administration to OVX rats resulted in more intracortical bone remodeling, periosteal bone formation, and new cancellous bone production than observed in PGE2 treated controls. The findings that PGE2 administration to OVX and intact female rats increases cortical bone mass, coupled with observations that mouse, rat, dog, and man respond similarly to PGE2, suggest that PGE2 administration may be useful in the prevention and treatment of postmenopausal osteoporosis.

Aging↗

Percutaneous nephrostomy: its value in obstructive uropathy complicating carcinoma of cervix uterus.

Percutaneous nephrostomies (PCN) were performed in 25 patients with uterine cervical malignancy between November 1982 and December 1987 at the Christie Hospital and Holt Radium Institute. Group 1 consisted of eight patients with untreated disease; group 2 consisted of eight cases with recurrent tumour; and group 3 consisted of nine patients with obstructive uropathy related to previous treatment. Six patients in group 1 subsequently received radical radiotherapy, and two of them were alive and disease free (33%) ten months later. Further active treatment was only possible in two of the patients with recurrence and overall median survival was only 51 days. All patients in group 3 had normalization of their renal function post-nephrostomy and prior to definitive management of the obstruction. We conclude that the technique should be considered in patients who had no previous treatment and in patients with treatment-related complications. Its value in recurrent disease is limited.

Adult↗

Technical aspects of quantification of aluminum.

Aluminum has been implicated as a contributing factor to dialysis encephalopathy syndrome (DES) and osteomalacic osteodystrophy. Monitoring of its level together with i-PTH, desferoxamine infusion test, or bone biopsy gives the degree of intoxication. Specimens for aluminum must be collected in containers washed in nitric acid or disodium EDTA to avoid contamination. Determination is made with flameless atomic absorption spectrometry or neutron activation. Various experimental conditions for the former together with discussion on their merits and shortcomings are given. Included are protein precipitation, matrix modification, background correction, and sampling technique.

Aluminum↗

Medication compliance, antidepressant blood levels, and side effects in Southeast Asian patients.

A study of medication compliance, side effects, and clinical change with the use of antidepressants in 32 Southeast Asian refugee patients seen at an urban mental health center is reported. Patients met criteria for either major depressive episode, posttraumatic stress disorder, or both. Only five of the 32 patients who stated that they were taking their medications regularly had antidepressant blood levels in the therapeutic range. Another 10 patients had subtherapeutic levels and the remaining 17 had undetectable blood levels. Patients with therapeutic blood levels had fewer side effects (p = 0.049) than patients with undetectable blood levels. Blood levels tended (p = 0.070) to be correlated with clinical improvement. The authors discuss cultural attitudes of Southeast Asian refugee patients toward medication use and side effects that appear to influence medication compliance.

Adult↗

Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes.

We have identified and purified a novel cytokine, NK cell stimulatory factor (NKSF), from the cell-free supernatant fluid of the phorbol diester-induced EBV-transformed human B lymphoblastoid cell line RPMI 8866. NKSF activity is mostly associated to a 70-kD anionic glycoprotein. The purified 70-kD protein, isolated from an SDS-PAGE gel, yields upon reduction two small species of molecular masses of 40 and 35 kD, suggesting that this cytokine is a heterodimer. When added to human PBL, purified NKSF preparations induce IFN-gamma production and synergize with rIL-2 in this activity, augment the NK cell-mediated cytotoxicity of PBL preparations against both NK-sensitive and NK-resistant target cell lines, and enhance the mitogenic response of T cells to mitogenic lectins and phorbol diesters. The three activities remain associated through different purification steps resulting in a 9,200-fold purification, and purified NKSF mediates the three biological activities at concentrations in the range of 0.1-10 pM. These data strongly suggest that the same molecule mediates these three activities, although the presence of traces of contaminant peptides even in the most purified NKSF preparations does not allow us to exclude the possibility that distinct biologically active molecules have been co-purified. The absence of other known cytokines in the purified NKSF preparations, the unusual molecular conformation of NKSF, the high specific activity of the purified protein, and the spectrum of biological activities distinguish NKSF from other previously described cytokines.

Biological Factors↗

Reconstitution of a calcium-activated potassium channel in basolateral membranes of rabbit colonocytes into planar lipid bilayers.

A highly enriched preparation of basolateral membrane vesicles was isolated from rabbit distal colon surface epithelial cells employing the method described by Wiener, Turnheim and van Os (Weiner, H., Turnheim, K., van Os, C.H. (1989) J. Membrane Biol. 110:147-162) and incorporated into planar lipid bilayers. With very few exceptions, the channel activity observed was that of a high conductance. Ca2+-activated K+ channel. This channel is highly selective for K+ over Na+ and Cl-, displays voltage-gating similar to "maxi" K(Ca) channels found in other cell membranes, and kinetic analyses are consistent with the notion that K+ diffusion through the channel involves either the binding of a single K+ ion to a site within the channel or "single-filing" ("multi-ion occupancy"). Channel activity is inhibited by the venom from the scorpion Leiurus quinquestriatus, Ba2+, quinine, and trifluoperazine. The possible role of this channel in the function of these cells is discussed.

Analog-Digital Conversion↗

Depression and posttraumatic stress disorder in Southeast Asian refugees.

The authors report on 404 Southeast Asian refugees seen at a community clinic. Approximately three-quarters of these patients met DSM-III criteria for major depressive episode, and 14% had posttraumatic stress disorder. Complaints of pain and sleep disturbances were the predominant presenting symptoms. Most of the men were married, but more than 40% of the women were widowed. Between 15% and 30% of the patients reported specific traumatic experiences either in their homeland or during their escape. Widowhood and such traumatic experiences were positively correlated with more symptoms of depression and anxiety.

Acculturation↗

A comparative study of new cases seen at the Child Psychiatric Clinic in 1975 and 1985.

A comparative analysis of new cases seen at the Child Psychiatric Clinic in 1975 and 1985 is made in this study. There was a three and a half fold increase in the number of patients seen from 245 to 893. There was no significant change in sex ratio or ethnic groups. However, in 1985 more younger children (aged less than 6 years) were seen at the Clinic. The waiting time remained short with half the number of cases seen within one week of appointment. The commonest conditions besides Normal Variation were Adjustment Reaction, Mental Retardation, Conduct Disorder and Neurosis. Three-fifths of cases were discharged from follow-up within three months of therapy. Most cases (90%) did not require pharmacological therapy whilst family therapy was prescribed for a fifth of cases seen in 1985.

Adolescent↗

Effect of salivary proteins on binding curves of three radioimmunoassay kits: Amerlex-M progesterone, Amerlex cortisol, and Biodata testosterone.

Radioimmunoassay (RIA) is generally used to measure certain salivary hormones because of its high sensitivity. For speed and simplicity, it has been used in the form of "direct" assays, i.e., without first extracting the analyte from its matrix. Investigating the effect of the principal salivary proteins on the binding behavior of three commercial RIA kits, we found that the Amerlex-M [125I]progesterone binding was greatly reduced when alpha-amylase and mucins were added to the binding medium, whereas IgA and IgG were less effective. The Serono Biodata [125I]testosterone binding was unaffected by proteins, while the Amerlex [125I]cortisol binding was decreased by alpha-amylase and mucins. The protein influence was largely eliminated when an extraction step was incorporated. Thus, direct RIA of saliva may be subject to matrix effects, to extents that vary with the kit and that may adversely affect the quality of the assay results.

Humans↗

Histone H3 thiol reactivity and acetyltransferases in chicken erythrocyte nuclei.

Chicken erythrocyte nuclei previously incubated separately with two novel mercury compounds (N-chloromercuribenzoyl)-biocytin and bis(p-(chloromercuribenzoyl))-[3H]lysine diamide) were digested with micrococcal nuclease and the digest products fractionated according to their solubility in 0.15 M NaCl and molecular size. The identity and quantitation of the chromatin fractions and proteins containing covalently bound mercury were determined by Western blotting, autoradiography, and scintillation counting. The most highly acetylated species of histone H3 in the 0.15 M NaCl-soluble polynucleosome fraction also contained the highest proportion of bound mercury. This fraction contains hyperacetylated core histones, is depleted in linker histones, and enriched in nonhistone proteins. Histone H3 in the 0.15 M NaCl-soluble mononucleosomes, which are unacetylated and lack linker histones, was 45% less labeled than histone H3 in the 0.15 M NaCl-soluble polynucleosome fraction. In the 0.15 M NaCl-insoluble polynucleosomes, which contain unacetylated histones and molar proportions of linker histones, histone H3 was 63% less labeled. Allowing for the differential abundance of these subfractions in the nucleus, the relative H3 reactivities are 50, 7, and 1 for 0.15 M NaCl-soluble polynucleosomes, mononucleosomes, and 0.15 M NaCl-insoluble polynucleosomes, respectively. Thus a gradation of reactivities exists which correlates with increasing hyperacetylation and linker histone depletion. High mobility group proteins 1 and 2, found in subnucleosome particles in the 0.15 M NaCl-soluble fraction, are extensively mercury-labeled. Distribution of histone acetyltransferase activity among salt- and size-resolved micrococcal nuclease produced fractions was almost 5-fold greater in the 0.15 M NaCl-soluble supernatant than in the 0.15 M NaCl-insoluble pellet. Furthermore, the acetyltransferase activity, which is tightly bound to undigested chromatin, is rapidly released by both micrococcal nuclease and DNase I. For short digestion times the enzyme is associated with the salt-soluble polynucleosomes, but at longer times of digestion the enzyme appears to be free from intact nucleosomes. The enzyme may be localized in the globin domain in erythrocytes and maintains that region in a hyperacetylated state which results in an altered linker histone binding reflected in a change in the reactivity of the usually inaccessible H3 cysteine 110.

Acetyltransferases↗

Defective presentation to class I-restricted cytotoxic T lymphocytes in vaccinia-infected cells is overcome by enhanced degradation of antigen.

Vaccinia infection interferes with the presentation of influenza Haemagglutinin (HA) and Nucleoprotein (NP) to class I-restricted CTL. The inhibitory effect is selective for certain epitopes, and is more profound during the late phase of infection. For influenza A/NT/60/68 NP, the block is present during both early and late phases of infection, and is selective for the COOH-terminal epitope defined by peptide 366-379, having no detectable effect on the presentation of the NH2-terminal epitope 50-63. The presentation of HA is inhibited only during the late phase of vaccinia infection. For both proteins, presentation is partially (NP) or completely (HA) restored by expression of rapidly degraded protein fragments in the vaccinia infected target cell. For HA, deletion of the NH2-terminal signal sequence completely overcomes the block. For NP, either a large NH2-terminal deletion or the construction of a rapidly degraded ubiquitin-NP fusion protein partially restores presentation. These results illustrate the relationship between degradation of viral proteins in the cytoplasm of an infected cell and recognition of epitopes at the cell surface by class I-restricted T cells.

Animals↗

Histone accessibility determined by lysine-specific acetylation in chicken erythrocyte nuclei.

N-Hydroxysulfosuccinimidyl [3H]acetate was synthesized and, following the determination of the optimal reaction conditions, was used to acetylate histones in chicken erythrocyte nuclei at 4 degrees C, pH 8. The histones were extracted from the labelled nuclei and the distribution of the acetyl groups determined from the amount of tritiated acetate in isolated peptides. The relative degree of acetylation of molecules was H1 1.0, H5 0.81, H2B 0.48, H2A 0.24, H3 0.24, H4 0.16. Histone H1 is the most exposed histone followed by H5. The core histones are much less accessible to chemical modification than the linker histones by a factor of 4-5. Histones H2A, H2B and H5 appear to be labelled at random along the entire polypeptide chain, while histones H3 and H4 are labelled almost exclusively in the first 30 residues from the N terminus. Control and acetylated chicken erythrocyte nuclei were digested with DNase I and the resulting DNA hybridized to globin and ovalbumin cDNAs. Acetylation, at 14 molecules acetate/core nucleosome or 20 molecules acetate/chromatosome, increased the DNase I sensitivity of the ovalbumin gene to that of the globin sequences in the control sample, while the globin sequences became even more nuclease-sensitive. Our results suggest that increased sensitivity of chromatin towards nuclease digestion might be due to increased solubility of the chromatin fibre.

Acetylation↗

Noninvasive ventilatory support during sleep improves respiratory failure in kyphoscoliosis.

We investigated the effect on daytime respiratory function and quality of sleep, of providing adequate ventilation either by intermittent positive pressure ventilation (IPPV) or by continuous positive airways pressure (CPAP) both administered through a nose mask in a group of seven patients with severe thoracic kyphoscoliosis. All night control sleep studies were performed with and without ventilatory assistance. Patients underwent standard polysomnography including all night measurements of transcutaneous CO2 (tcCO2) and arterial oxyhemoglobin saturation (SaO2). Awake arterial blood gas tensions (ABGs), respiratory muscle strength (Pmus), and lung function tests were measured in the sitting position. Follow-up studies after three months of treatment showed normal sleep patterns, improvement in daytime ABGs, lung volumes, and respiratory muscle strength. We concluded that maintenance of nocturnal ventilation by either nasal CPAP or nasal IPPV in patients with nocturnal respiratory failure does significantly improve clinical measurements of respiratory function and quality of sleep.

Adolescent↗