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Biomedical subjects

P Mack

Publications and source records attributed to P Mack.

At least 37 records · Page 2Linked to original sources
PubMed1997

Swimming-associated haemorrhagic colitis due to Escherichia coli O157:H7 infection: evidence of prolonged contamination of a fresh water lake.

We describe an Escherichia coli O157:H7 outbreak associated with a fresh water lake at a county park. Campers were surveyed for diarrhoeal illness within 10 days of their visit, and a case-control study of day visitors was conducted. A confirmed case was a symptomatic person with a stool culture positive for E. coli O157:H7 and a probable case was a person with bloody diarrhoea. Clinical isolates of E. coli O157 were subtyped by pulsed field gel electrophoresis (PFGE). In the camper survey, 12 (38%) of 32 swimmers had a diarrhoeal illness (relative risk [RR] = 12.4; 95% confidence interval [CI] = 1.7-89.7). For the case-control study, the 12 cases were more likely than controls to have purposefully ingested lake water (odds ratio [OR] = 6.9, 95% CI = 0.9-55.8). The PFGE patterns of six clinical isolates were indistinguishable. This report further demonstrates that contaminated fresh-water lakes can be the source of community outbreaks of E. coli O157:H7.

Adolescent↗
PubMed1997

Cyclosporin A modulation of early virologic and immunologic events during primary simian immunodeficiency virus infection in rhesus monkeys.

Virologic and immunologic effects of immunomodulation during primary simian immunodeficiency virus (SIV) infection were examined in monkeys treated with cyclosporin or vehicle for 32 days beginning 5 days before SIV inoculation. Duration of antigenemia decreased in 5 of 7 treated monkeys, 2 having delayed onset and peak of antigenemia. Although proviral DNA levels in blood and lymph nodes and infected cell numbers in lymph nodes were transiently decreased, levels were similar to those in controls by day 14. The CD4:CD8 ratio and percentage of CD4+ CD29+ cells decreased in controls 14 days after inoculation, but this decrease was delayed in treated monkeys. Two treated monkeys demonstrated rapid disease, with progressive antigenemia preceding early deaths 90-96 days after inoculation. Nevertheless, immunomodulation influenced the kinetics of primary SIV infection in some monkeys, supporting the rationale of careful exploration of the strategy of interference with the heightened state of cellular activation together with direct antiretroviral therapy in human immunodeficiency virus infection.

Animals↗
PubMed1996

Genistein, a tyrosine kinase inhibitor, reduces EGF-induced EGF receptor internalization and degradation in human hepatoma HepG2 cells.

In this work, using the ECL Western blotting assay system, it was found that genistein, a specific tyrosine kinase inhibitor, was able to inhibit EGF-induced EGF receptor degradation and tyrosine phosphorylation in human hepatoma HepG2 cells. This inhibition was increased with increasing genistein concentration. With treatment of HepG2 cells with genistein at 37 degrees C for 30 min, the amount of internalized EGF, which was measured by the detection of the sorting of 125I-EGF in the cells, was remarkably decreased. Under the same conditions, in cells untreated with genistein, the degradation of EGF was significantly increased. After preincubation of HepG2 cells with and without genistein for 120 min at 37 degrees C, the ratio between degraded and released EGF was 16 and 24, respectively. These results suggest that EGF-induced internalization and degradation of EGF-EGF receptor complexes in HepG2 cells depend on EGF receptor tyrosine kinase activity.

Carcinoma, Hepatocellular↗
PubMed1996

Detection of EGF-induced EGF receptor degradation and tyrosine phosphorylation in intact cells.

In this work, a simple, sensitive, and non-isotopic assay system for the detection of EGF-induced EGF receptor degradation and tyrosine phosphorylation in intact cells is described. In this system, boiling Laemmli sample buffer was directly added to cultured Chang liver cells to stop the reactions in the cells stimulated by EGF and to make whole-cell extracts. The effects of EGF concentration and incubation time on the EGF-induced degradation and tyrosine phosphorylation of EGF receptor were successfully determined using monoclonal anti-EGF receptor, recombinant anti-phosphotyrosine peroxidase conjugate, and enhanced chemiluminescence (ECL) Western blotting assay system. Unlike other assay systems, the use of radioisotopes was avoided in this determination. The assay system is linear up to 100 micrograms sample protein from whole-cell extracts for the detection of EGF receptor and EGF-induced autophosphorylation. This assay may be easily adopted for identification of other growth factor receptors and phosphotyrosine-containing proteins in intact cells, using appropriate anti-growth factor receptor antibodies.

Blotting, Western↗
PubMed1996

Intranasal monoclonal IgA antibody to respiratory syncytial virus protects rhesus monkeys against upper and lower respiratory tract infection.

Respiratory syncytial virus (RSV), the major cause of lower respiratory tract disease in infants, is thought to infect the upper airways before spreading to the lower respiratory tract. A rhesus monkey model of RSV infection after upper airway inoculation was used to test the protective effect of intranasal treatment with HNK20, a mouse monoclonal IgA antibody against RSV F glycoprotein. HNK20 was administered once daily for 2 days before RSV challenge and 4 days after challenge. Treatment with 0.5 mg/kg HNK20 reduced viral shedding in the nose, throat, and lungs by 3-4 log10/mL (P < or = .002). All monkeys developed RSV neutralizing antibody in serum, even in the absence of detectable viral replication. Neutralizing concentrations of monoclonal antibody remained in nasal secretions for > 1 day after treatment. These results suggest that nose-drop application of monoclonal antibody could provide convenient and effective protection against RSV infection in human infants at risk of severe lower respiratory tract disease.

Administration, Intranasal↗
PubMed1996

Efficacy of intra-arterial norcantharidin in suppressing tumour 14C-labelled glucose oxidative metabolism in rat Morris hepatoma.

Norcantharidin is the demethylated form of Cantharidin, which is the active ingredient of the blister beetle, Mylabris, a long used Chinese traditional medicine. Though not well publicized outside China, Norcantharidin is known to possess significant anti-hepatoma activity, and is relatively free from side effects. In the present study, glucose oxidation in tumour and liver tissue slices harvested from hepatoma-bearing animals was quantified by measuring the radioactivity of 14C-labelled CO2 released from 14C-glucose in oxygen-enriched incubation medium. Results were expressed as a tumour/liver ratio. For comparison, treatments with Norcantharidin, Adriamycin and with hepatic artery ligation were studied. The mean tumour/liver ratio was 4.2 +/- 2.2 in untreated controls, but dropped significantly to 2.3 +/- 0.5 (p < 0.05) with intra-arterial Norcantharidin (0.5 mg/kg) and to 2.3 +/- 0.7 (p < 0.05) with intra-arterial Adriamycin (2.4 mg/kg), and to 2.2 +/- 0.7 (p < 0.05) with hepatic artery ligation. However, with intravenous Adriamycin at 2.4 mg/kg, the mean tumour/liver ratio was reduced to only 3.5 +/- 2.0 and was not significantly different from untreated controls. It is concluded that intra-arterial Norcantharidin is as effective as intraarterial Adriamycin and hepatic artery ligation in suppressing tumour glucose oxidative metabolism. These result simply that Norcantharidin may have a role to play in the chemotherapy of primary liver cancer.

Animals↗
PubMed1996

EGF receptor in human Chang liver and hepatoma HepG2 cells.

Epidermal growth factor (EGF) receptor was detected in the human Chang liver and human hepatoma HepG2 cells. Both cell lines were found to be able to bind EGF. The expression of EGF receptor in Chang liver and HepG2 cells was 1.3 x 10(5) EGF receptors/cell and 1.8 x 10(5) EGF receptors/cell, respectively. In both cells, this receptor was identified by ECL Western blotting using monoclonal anti-EGF receptor antibody and by immunohistochemical assay using polyclonal anti-EGF receptor antibody. Some of internalized EGF was recycled in Chang liver cells, but not in HepG2 cells.

Carcinoma, Hepatocellular↗
PubMed1995

NGFI-C expression is affected by physiological stimulation and seizures in the somatosensory cortex.

NGFI-C is an early response gene which encodes a Cys2/His2 zinc finger protein. NGFI-C has previously been demonstrated to be inducible in PC12 cells after NGF stimulation. This study sought to localize this gene in somatosensory cortex, and investigate its possible induction by physiological and seizure stimuli. To determine if NGFI-C message levels are affected by stimulation, RT-PCR was performed on mRNA extracts from somatosensory cortex. NGFI-C mRNA levels were increased to levels four-fold over baseline after a seizure. In a paradigm used as a model of experience-dependent plasticity, vibrissae stimulation also increased the level of NGFI-C expression in the contralateral barrel cortex to 180% of control levels. In situ analysis using digoxigenin-labelled cRNA probes demonstrated NGFI-C containing neurons throughout layers 2 through 6 in somatosensory cortex. A higher cell density was seen after stimulation. Qualitatively, staining was more intense in post-seizure and post-stimulus cortex than in control cortex. Analysis of related zinc finger expression in serial sections revealed that NGFI-C is expressed in a distinct but overlapping cell populations relative to NGFI-A, Krox 20, and Egr-3. These studies demonstrate the inducible nature of NGFI-C message in response to a physiological vibrissae stimulus, as well as to seizures. However, the levels and pattern of expression differ between these two stimuli.

Animals↗
PubMed1995

Evaluation of thyroid nodules for malignancy using 99Tcm-sestamibi.

99Tcm-sestamibi (99Tcm-MIBI) is used for myocardial perfusion imaging but has also been reported to localize in tumours. The usual thyroid scanning radionuclide is 99Tcm-pertechnetate. Altogether, 161 patients with clinically solitary thyroid nodules had both 99Tcm-MIBI and 99Tcm-pertechnetate thyroid scans, with the nodules being reported as cold, warm or hot. Fine-needle aspiration cytology (FNAC) and surgery were performed in those patients who consented to these procedures. Of 131 patients who had FNAC, only 58 proceeded to surgery. In the surgically treated group, 14 of 58 (24%) were confirmed to have thyroid cancer, whereas 44 of 58 (76%) had benign lesions. The 14 cancerous nodules were cold on the 99Tcm-pertechnetate scan, whereas with 99Tcm-MIBI 11 were warm and 3 were either cold or hot nodules. Of the 44 benign lesions, 18 were cold, 9 were warm and 17 were hot nodules. In those 131 patients who had FNAC, the cytology was reported as benign in 120 of the nodules and malignant in 11. The three false-negative cytologies were reported as follicular adenomas. The benign lesions noted on FNAC and surgery were thyroiditis, adenomas and haemorrhagic or colloid cysts. The results from the 58 surgically treated patients suggest that the warm nodules would need surgery, whereas the cold and hot nodules are unlikely to be malignant. The overall sensitivity of the 99Tcm-MIBI scan was 79% and the specificity 80%, with the warm nodule on 99Tcm-MIBI scan having a positive predictive value of 55% and a negative predictive value of 92%.

Adenocarcinoma, Follicular↗
PubMed1995

A synthetic tumor necrosis factor-alpha agonist peptide enhances human polymorphonuclear leukocyte-mediated killing of Plasmodium falciparum in vitro and suppresses Plasmodium chabaudi infection in mice.

A peptide corresponding to residues 70-80 of the TNF-alpha polypeptide was synthesized and shown to enhance human PMN-mediated killing of Plasmodium falciparum in vitro and reduced the Plasmodium chabaudi parasitemia in mice. Studies of the mechanism of action showed that the peptide, TNF(70-80), stimulated and primed PMN for an increased respiratory burst and release of granule constituents in response to a second agonist. The PMN-stimulatory activity of the peptide was inhibited by mAbs against the p55 and p75 TNF receptors and a TNF-neutralizing mAb. Analysis of PMN receptor expression showed that CR3 (CD18/CD11b) and Fc gamma RIII were upregulated by TNF(70-80), which was consistent with the peptide's ability to enhance parasite killing by PMN. The peptide, unlike TNF, did not increase the expression of adhesion molecules on endothelial cells and failed to promote binding of P. falciparum-infected erythrocytes to endothelial cells. TNF(70-80) also inhibited the TNF-induced increase in adhesion of P. falciparum-infected erythrocytes to endothelial cells. The results demonstrate that the host-protective effects of TNF can be retained while toxic effects are eliminated using a selected, characterized subunit of the cytokine.

Animals↗
PubMed1995

A prospective comparative study between conventional and laparoscopic cholecystectomy.

A prospective, comparative study was made between 371 patients undergoing laparoscopic cholecystectomy and 100 patients undergoing conventional cholecystectomy. Post-operative pain was assessed subjectively by a single observer using a visual analog score and objectively by assessment of parenteral analgesic used. Patients who underwent laparoscopic cholecystectomy required significantly less analgesia (46.7 mg vs 223.9mg mean pethidine dose, p < 0.01) and were observed to have mobilised earlier and had a shorter mean post-operative stay (3.5 days vs 5.9 days, p < 0.01). Laparoscopic cholecystectomy objectively reduces post-operative pain significantly and should be the new standard for treatment of gallstones.

Adult↗
PubMed1994

Histamine degradative uptake by cultured human pulmonary vascular endothelial cells utilizes an inflammatory cell diamine oxidase.

Neutrophil-endothelial interactions, altered clearance properties of the lung toward vasoactive mediators, and damaging effects of histamine that target the lung represent prominent elements of the inflammatory response at the systemic level. The pulmonary vasculature is unusual in that, unlike other tissues and vascular beds, it normally does not metabolize circulating histamine in vivo, although histamine-metabolizing enzyme activities have been detected in disrupted lung tissue. We have therefore explored the capability of human pulmonary artery endothelial cells in culture to express the receptor-mediated histamine degradative uptake system we previously defined in systemic endothelial cells (Haddock, R. C., Mack, P., Leal, S., and Baenziger, N. L. (1990) J. Biol. Chem. 265, 14395-14401). Pulmonary endothelial cells display all components of this system: histamine methyltransferase generating the proximal cell-associated metabolite tele-methylhistamine and receptors binding diamine oxidase which generates the distal product methylimidazoleacetic acid that is accumulated by the cells. A diamine oxidase released from human neutrophil granules by activation with Ca2+ ionophore binds pulmonary and systemic endothelial cell and fibroblast diamine oxidase receptors and, thereby, participates in histamine degradative uptake. This enzyme utilizes cell-associated tele-methylhistamine as a substrate, preferentially generating methylimidazoleacetic acid in addition to reactive oxygen species. Thus the enzymatic and interactive cellular machinery for histamine clearance is inherently present as a functional unit in two major human pulmonary cell types. It interacts with products of inflammatory host defense cells, and pulmonary endothelial-neutrophil interactions via this pathway may influence the progression of inflammation.

Amine Oxidase (Copper-Containing)↗
PubMed1994

An environmentally regulated receptor for diamine oxidase modulates human endothelial cell/fibroblast histamine degradative uptake.

Human vascular endothelial cells and fibroblasts express a cell-surface degradative pathway for the multifunctional mediator histamine, which employs a receptor for the metabolic enzyme diamine oxidase (DAO) and results in cellular accumulation of the final metabolite methylimidazoleacetic acid. We demonstrate recognition and regulatory properties of DAO receptors as a function of cellular environmental conditions. Fast and slow ligand binding receptor populations bind DAO at 4 degrees C maximally in 1 and 7 h, respectively; upon warming cells to 37 degrees C both populations participate in degradative uptake of histamine accumulated as methylimidazoleacetic acid. Bound DAO is displaced by heparin with 24-fold greater potency than dextran sulfate, implicating structural specificity of heparin-like glycosaminoglycan moieties as a critical factor in initial receptor/enzyme interaction at fast and slow sites. Receptor-bound DAO is retained under mildly acidic conditions characteristic of early to mid endocytic intracellular compartments and thus could recycle to the plasma membrane intact after internalization. DAO initially bound to receptors in whole cells is retained through cell disruption/membrane fractionation procedures, but DAO binds poorly to isolated membrane fractions or presolubilized receptors, suggesting that the geometry of DAO binding components is not readily maintained upon cell disruption unless DAO is already bound. Cells down-regulate their complement of DAO receptors upon prolonged exposure to DAO. In cells plated at high density, half of the bound DAO becomes nondisplaceable by heparin within 15 min at 37 degrees C, a time consistent with receptor internalization, whereas cells plated at low density retain all bound DAO in a heparin-sensitive state. The protein kinase C activator phorbol 12-myristate 13-acetate modulates DAO receptor number by 35% and total histamine degradative uptake by > 2-fold. Thus this pathway is subject to regulation at the levels of DAO receptor numbers, their state of cell-surface display, and additional cellular elements of the degradative pathway with which the DAO receptors interface.

Amine Oxidase (Copper-Containing)↗
PubMed1994

5-fluorouracil and folinic acid-induced mucositis: no effect of oral glutamine supplementation.

In some clinical situations the endogenous production of glutamine may be insufficient to maintain optimal tissue structure and function such that glutamine becomes a conditionally essential amino acid. Studies in laboratory animals have demonstrated that glutamine supplementation can reduce the incidence and severity of cytotoxic-induced mucositis. This study examined the role of oral glutamine supplementation in the management of mucositis caused by 5-fluorouracil (5-FU) and folinic acid. Twenty-eight patients with gastrointestinal cancers were randomised to receive 16 g of glutamine per day for 8 days, or placebo, in a randomised double-blind trial before crossing over to the alternative supplement during the second treatment cycle. The supplement was well tolerated with no apparent adverse effects, but failed to have any significant effect on oral mucositis assessed by the patients or investigator. The possible reasons for this apparent lack of benefit are discussed.

Administration, Oral↗
PubMed1994

Thoracoscopic ganglionectomy for hyperhidrosis.

Thoracoscopic sympathectomy for the treatment of hyperhidrosis has been carried out with techniques that involve either monopolar coagulation or laser injury to the T2 ganglion. Although this has the advantage of being minimally invasive, it has not been established whether these techniques are superior to complete ganglion excision, as carried out during open surgery. A new technique of complete T2 ganglion excision for palmar hyperhidrosis (with T3 ganglionectomy for axillary sweating) was developed using thoracoscopic techniques. Sixteen patients were treated with thoracoscopic T2 ganglion excision on the right side, and simple coagulation (Nd-YAG laser or monopolar) on the left side. Results were excellent with no posttreatment differences between hands at 1 year follow-up. However, long-term follow-up of these patients will be carried out to determine whether differences exist between these two techniques.

Adult↗
PubMed1994

Video-assisted endoscopic thoracic sympathectomy in the management of intractable palmar hyperhydrosis.

Minimally invasive endoscopic surgical techniques have revolutionised patient management. We present our findings in our first 10 cases of bilateral video-assisted endoscopic thoracic sympathectomy in the management of intractable palmar hyperhydrosis including the first such procedure in Singapore. We have found the procedure to have minimal morbidity, good patient acceptance and all patients have remained with dry palms.

Adult↗