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Biomedical subjects

C Lee

Publications and source records attributed to C Lee.

At least 505 records · Page 28Linked to original sources

Thymoma and agranulocytosis: two case reports and literature review.

Thymoma with agranulocytosis is a rare association. We describe two cases of agranulocytosis presenting with sepsis which were both found to have coincident benign spindle cell thymomas. One case, associated with promyelocyte arrest and hypogammaglobulinaemia, was treated successfully with granulocyte colony-stimulating factor (G-CSF). Thymectomy had no effect. The other case, associated with complete myeloid aplasia, proceeded to a fatal outcome after failure of treatment with granulocyte-macrophage colony stimulating factor (GM-CSF), plasmapheresis, thymectomy, intravenous immunoglobulin, cyclophosphamide and methylprednisolone. We also review the literature of thymoma in association with agranulocytosis.

Agranulocytosis↗

Influence of heat on Na(+)-dependent HCO3-/Cl- exchanger function in a thermoresistant cell line.

During previous studies on the relationship between thermosensitivity and intracellular pH (pHi) regulation in mammalian cells, we observed that the thermoresistant TR-4 cells appeared to be resistant to manipulations of the Na+/H+ antiport, one of the two primary membrane regulators of pHi. We hypothesized that this might be due to up-regulation of the alternate pHi regulator, the Na(+)-dependent HCO3-/Cl- exchanger, in the TR-4 cells. We have now evaluated the effect of heat exposure on the function of the Na(+)-dependent HCO3-/Cl- exchanger in both the parent RIF-1 and the thermoresistant variant TR-4 cells. We also assessed thermosensitivity of the cell lines under conditions of either pHe 7.2 or 6.8, with NaHCO3, with or without the addition of DIDS, an inhibitor of HCO3-/Cl- exchanger function. After 2h of heating at 43 degrees C, relative exchanger function declined to around 50% for the TR-4 cells and 10% for the RIF-1 cells. DIDS (0.2 mM) enhanced thermal cytotoxicity in both cells lines, by around 1 log when the cells were heated at neutral conditions, and by around 1.5 log when the condition became acidic. Results from pHi measurements during heating reflected the clonogenic survival data in that lower pHi levels were associated with the conditions when DIDS was present. We conclude that in the TR-4 cells, the Na(+)-dependent HCO3-/Cl- exchanger appears to be a more important regulator of pHi than the Na+/H+ antiport.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

Increased frequency of TCR gamma delta + T cells in disease-free survivors following T cell-depleted, partially mismatched, related donor bone marrow transplantation for leukemia.

Recent interest has focused on the function of gamma delta + T cells in immune responses. However, their role in allogeneic bone marrow transplantation (BMT) remains undefined. We report on a group of 43 leukemia patients who survived for at least 100 days following transplantation using partially HLA-mismatched grafts from related donors that were T cell depleted with the anti-TCR alpha beta monoclonal antibody T10B9.1A-31 and complement. Ten patients (23.2%) were found to have an increased (> or = 10%) proportion of gamma delta + T cells in the peripheral blood at 60-270 days after BMT. All of these patients remain alive, and 9 (90% of patients with > or = 10% gamma delta + cells) are free of disease at 2.5 years compared with a disease-free survival probability of 31% among patients with a normal proportion and concentration of gamma delta + T cells. No other factor was found to be independently associated with improved survival in these patients. These data suggest a possible association between an increase in the percentage and number of gamma delta + T cells and improved disease-free survival following transplantation from a partially mismatched related donor.

Bone Marrow Transplantation↗

Electromyographic and mechanomyographic characteristics of neuromuscular block by magnesium sulphate in the pig.

In spite of its well known propensity to cause accidental paralysis by a specific mechanism of action, Mg(2+)-induced neuromuscular block has not been examined systematically for its characteristics of muscle response to nerve stimulation. We examined in seven anaesthetized domestic pigs the mechanomyographic (MMG) and neurally evoked compound electromyographic (ncEMG, EMG) responses of the tibialis anterior muscle to stimulation of its motor nerve, at baseline and during three levels of neuromuscular block induced by infusion of MgSO4 (at approximately 25%, 50% and 75% depression of the 0.1-Hz EMG). We observed that: at 0.1 Hz, the MMG tended to be more depressed than the EMG; the train-of-four (2 Hz) was essentially non-fading; the tetanic force (50 Hz) showed tetanic ascent instead of tetanic fade and reached its baseline control value at 5 s in spite of depression of the twitch; the EMG counterpart of the tetanus showed escalation of the train of ncEMG, so that the fourth ncEMG was much greater than the first; and the post-tetanic twitch was also relatively spared from Mg(2+)-induced neuromuscular block. Sparing of the tetanus and post-tetanic twitch resulted in large gains in the tetanus:twitch ratio and the post-:pre-tetanic twitch ratio, which increased at the 75% level of depression from 2.8 (SD 0.7) to 11.5 (4.0), and from 1.5 (0.3) to 4.6 (1.4) (P < 0.01), respectively. These characteristics of neuromuscular block by Mg2+ reflect its prejunctional mechanism of action by depression of transmitter release.

Animals↗

Endoscopic-assisted repair of a malar fracture.

Although the zygomatic arch can be employed as a key landmark to the accurate alignment of a displaced malar fracture, it has been traditionally avoided because of the need for a bicoronal incision. Exposure of the zygomatic arch by means of the conventional bicoronal incision has several possible disadvantages, including an increased risk of blood loss, alopecia, loss of sensation posterior to the incision, and traction palsy of the facial nerve. Endoscopic-assisted exposure of a zygomatic arch can largely obviate the disadvantages of a bicoronal incision and yield this site accessible to reduction and fixation in the routine treatment of displaced malar fractures. A case of endoscopic-assisted open reduction and internal fixation of a moderately displaced malar fracture is presented. In particular, exposure and fracture fixation of the zygomatic arch were performed without the need for a bicoronal incision.

Adult↗

The use of gadolinium-BOPTA on magnetic resonance imaging in brain infection.

RATIONALE AND OBJECTIVES: The use of gadolinium (Gd)-BOPTA as a magnetic resonance contrast agent for central nervous system disease was studied in a canine brain abscess model. METHODS: A Streptococcus faecalis brain abscess was evaluated in five dogs at 1.5T. Imaging was performed during the late cerebritis stage, at 5 to 7 days after surgery. Magnetic resonance scans were acquired before and at 1, 5, 15, 30, 45, and 60 minutes after contrast administration, using a dose of 0.1 mmol/kg. Scans also were acquired both before and after contrast injection with the implementation of magnetization transfer. RESULTS: Lesion enhancement, quantified by region-of-interest measurement, peaked at 5 minutes after contrast injection. Both the increase in lesion enhancement from 1 to 5 minutes after injection and the decrease from 5 to 15 minutes after injection, although small, were statistically significant (P < 0.004 and P < 0.03, respectively). The application of magnetization transfer improved lesion enhancement, as measured by signal difference/noise, by 39%. This result also was statistically significant (P < 0.001). CONCLUSIONS: In intraparenchymal brain infection, Gd-BOPTA provides effective lesion enhancement when used at a dose of 0.1 mmol/kg. Further research is needed to compare the magnitude of enhancement achieved with Gd-BOPTA, which has weak protein binding and both hepatobiliary and renal excretion, with that with Gd chelates, which have pure renal excretion.

Animals↗

Observation of metabolic changes in chronic schizophrenia after neuroleptic treatment by in vivo hydrogen magnetic resonance spectroscopy.

RATIONALE AND OBJECTIVES: The authors investigate: (1) whether there is a lateral effect of hydrogen (1H) magnetic resonance (MR) spectroscopy observable metabolite ratios between the right and the left prefrontal lobe in chronic schizophrenia; (2) whether there is a change of proton metabolite ratios in chronic schizophrenia after neuroleptic treatment; (3) whether there is a relation between changes in 1H MR spectra and the clinical assessment of Brief Psychiatric Rating Scale (BPRS); and (4) to investigate a hypofrontality hypothesis in schizophrenia in terms of neurochemical aspects. METHODS: Localized in vivo 1H MR spectroscopy was used to measure the metabolite levels in the prefrontal lobes of control persons (n = 20) and of chronic patients before and after neuroleptic treatment (n = 34). The MR spectra of 8 cm3 voxels were compared with clinical assessment of BPRS in each subject. RESULTS: No significant metabolic lateral effect was established in both schizophrenia and control groups (P > 0.05). After neuroleptic treatment, chronic schizophrenic patients generally demonstrated a decrease of the complex of gamma-aminobutyric acid (GABA) and glutamate (Glu) containing (GABA + Glu)/creatine (Cr) ratio. CONCLUSIONS: The current follow-up 1H MR spectroscopy study shows a significant correlation between alterations of (GABA + Glu)/Cr ratio and BPRS, and supports a hypofrontality hypothesis in chronic schizophrenia. The reduction of (GABA + Glu)/Cr ratio after neuroleptic treatment may implicate the recovery of normal neuronal function in neurotransmitters. In vivo 1H MR spectroscopy may be a useful modality in follow-up evaluation of neuroleptic treatment in chronic schizophrenia.

Adolescent↗

Angiotensin II and basic fibroblast growth factor induce neonatal bladder stromal cell mitogenesis.

PURPOSE: Our aims were to establish primary stromal cell cultures from the neonatal rabbit bladder and investigate the potential mitogenic effects of angiotensin II and basic fibroblast growth factor on these cells. MATERIALS AND METHODS: Primary bladder stromal cell cultures were obtained from 3-day-old rabbits, plated at a density of 3 x 10(4) cells per ml. and allowed to grow for 24 hours. Subconfluent cells were growth arrested in serum deficient (0.25% newborn calf serum) or serum-free media for 24 hours and then stimulated with 10(-7) M. angiotensin II or 10 ng./ml. basic fibroblast growth factor for an additional 48 hours. Cell counts and [3H] thymidine incorporation were done to measure cellular proliferation and deoxyribonucleic acid synthesis. RESULTS: Angiotensin II and basic fibroblast growth factor each stimulated neonatal bladder stromal cell proliferation and [3H] thymidine incorporation under serum deficient conditions. Angiotensin II provoked an average 26% increase in cell number (p < 0.01) and 35% increase in [3H] thymidine incorporation (p < 0.01) compared to control values. Basic fibroblast growth factor was an even more potent mitogen with a 47% increase in cell number (p < 0.01) and 180% increase in [3H] thymidine incorporation (p < 0.01) compared to controls. In contrast, angiotensin II and basic fibroblast growth factor each failed to have significant stimulatory effects under serum-free conditions. CONCLUSIONS: Angiotensin II and basic fibroblast growth factor induce a mitogenic response to neonatal bladder stromal cells in vitro. These mitogenic effects require the presence of serum factors. Whether angiotensin II and basic fibroblast growth factor are involved in the in vivo regulation of bladder growth associated with obstructive uropathy requires further investigation.

Angiotensin II↗

Longitudinal genotype analysis and quantification of hepatitis C virus in haemophilic patients receiving interferon-alpha therapy.

Haemophilic patients have a high prevalence of hepatitis C virus (HCV) infection because of the use of unsterilized clotting factor concentrates. Six major genotypes of HCV have been distinguished so far, with epidemiological evidence suggesting that genotypes 1-3 are common in the indigenous UK and US populations. The aim of this study was to analyse the changes in viral load and composition of the HCV quasispecies in haemophilic patients receiving therapy with interferon-alpha (IFN-alpha) using the four major methods currently available for HCV genotyping. The most consistent genotype results were obtained using restriction fragment-length polymorphism (RFLP) analysis when compared with the DNA sequence analysis, and showed that the dominant genotype can change in patients with mixed genotype infections treated with IFN-alpha. This study indicates the difficulties in studying this group of patients with mixed HCV genotype infections, and that frequent sampling is necessary, together with viral load measurement to monitor response to IFN-alpha therapy.

Adult↗

The influence of psychological debriefing on emotional adaptation in women following early miscarriage: a preliminary study.

About a fifth of pregnancies end in miscarriage, leading to emotional consequences, such as anxiety and depression, which may last for a number of months. Despite this, women are not routinely provided with follow-up care. Anecdotal evidence suggests that follow-up focusing on emotional experiences may have beneficial effects. This study tests the hypothesis that the psychological debriefing process has a positive influence on emotional adaptation. Women were assessed, using the Hospital Anxiety and Depression Scale and Impact of Events Scale, at one week and four months post-miscarriage. Half the women also received psychological debriefing at two weeks. Intrusion and avoidance scores were initially as high as those of post-trauma victims, but had significantly decreased by four months. Depression was not detected at any time point, but anxiety was significantly higher than community sample estimates at one week and four months. Psychological debriefing was perceived to be helpful, but did not influence emotional adaptation. A number of hypotheses are provided to explain these results. Outcome scores at one week significantly predicted outcome at four months, suggesting that early assessment would be important in determining which women should be offered intervention.

Abortion, Spontaneous↗

The activity of the high-affinity K+ uptake system Kdp sensitizes cells of Escherichia coli to methylglyoxal.

Expression of the Kdp system sensitizes cells to methylglyoxal (MG) whether this electrophile is added externally or is synthesized endogenously. The basis of this enhanced sensitivity is the maintenance of a higher cytoplasmic pH (pHi) in cells expressing Kdp. In such cells, MG elicits rapid cytoplasmic acidification via KefB and KefC, but the steady-state pHi attained is still too high to confer protection Lowering pHi further by incubation with acetate increases the sensitivity of cells to MG.

Adenosine Triphosphatases↗

Effects of theophylline on inflammatory cells and cytokines in asthmatic subjects: a placebo-controlled parallel group study.

The anti-inflammatory effects of oral theophylline on cells in bronchial biopsies of symptomatic atopic asthmatic subjects were investigated. Following a 2 week run-in period, asthmatic subjects were randomly assigned to either placebo (n=11) or theophylline (n=15). Bronchial biopsies were taken at fibre-optic bronchoscopy at the beginning and end of a 6 week period, during which subjects took placebo or theophylline medication at a dose intended to produce therapeutic concentrations. Nine of the placebo subjects and 12 of the theophylline subjects completed the study. Improvement in asthma control was seen in the theophylline-treated group. The mean (SD) theophylline blood level at the end of the study was 10.9 (6.0) microg x mL-1. A significant decrease in interleukin (IL)4 expression from 1.38 to 1.04 cells x mm-2 (<0.05) and a trend to a reduction in IL-5 from 1.29 to 0.48 cells x mm-2 (NS) were seen in biopsies from the theophylline-treated group compared with placebo, although there was no change in mast cell numbers (judged by tryptase expression). A decrease in epithelial CD8+ cells from 2.60 to 0.53 cells x mm-1 of surface (<0.05) was noted. This study shows an anti-inflammatory effect of theophylline in asthmatic bronchi, both in cell numbers and in the expression of IL-4, believed to be an important cytokine in the pathophysiology of asthmatic inflammation. We speculate that theophylline induces downregulation in vivo of cytokine production, accounting for the known inhibitory effect of theophylline on the late asthmatic reaction.

Administration, Inhalation↗

Hormone replacement therapy: knowledge, attitudes, and well-being among middle-aged Australian women.

Use of hormone replacement therapy (HRT) is increasing, yet little is known of women's perceptions of HRT. A telephone survey examined relevant knowledge and attitudes, and psychological well-being, in 258 women aged 51 to 60 (111 HRT users, 47 previous users, and 100 never-users). Although HRT users were better informed than nonusers, knowledge was generally low. Half the HRT users could not name any hormone used in HRT, and one third could not give any reason for using HRT. Current users, however, had more positive attitudes to HRT. Groups defined by HRT usage did not differ on well-being or current symptomatology, although current and previous HRT users reported having previously experienced a higher level of symptomatology than never-users, suggesting that HRT may have provided symptom relief for those women who chose to use it. In contrast to previous research, women with a history of hysterectomy did not show more emotional distress than others. Results suggest that Australian women frequently make choices concerning HRT without adequate knowledge, and that HRT may reduce symptoms but may have little impact on psychological well-being. Optimal usage of HRT by middle-aged women will rely on a clearer understanding, both of its effects and of women's attitudes toward its use.

Journal Article↗

Transforming growth factor-beta1 is a mediator of androgen-regulated growth arrest in an androgen-responsive prostatic cancer cell line, LNCaP.

LNCaP is an androgen-responsive prostatic cancer cell line that exhibits a bell-shaped growth response to increasing doses of dihydrotestosterone (DHT) in culture. Although the precise mechanism responsible for this growth response to androgen stimulation remains unclear, many studies have suggested that androgen modulates the level of various growth factors. In the present study, the role of transforming growth factor-beta (TGF-beta) in mediating the androgen-regulated growth arrest of LNCaP cells was investigated. The following concentrations of DHT were used: 0, 10(-12), 10(-10), and 10 (-7) M. These concentrations were selected because they represent the zero DHT control, the low-proliferative dose, the high-proliferative dose, and the growth arrest dose, respectively. Results of RT-PCR showed that LNCaP cells express TGF-beta1 but not -beta2 and -beta3 messenger RNA. Competitive quantitative RT-PCR demonstrated that the level of TGF-beta1 messenger RNA increased approximately 7-fold when cells were treated with 10(-7) M DHT. Results of Western blot analysis showed a dramatic increase in the level of latent TGF-beta1 protein in cell lysates with increasing concentrations of DHT. In addition, results of enzyme-linked immunoadsorbent assay for TGF-beta1 indicated that treatment of LNCaP cells with DHT led to a dose-dependent increase in both total and biologically active TGF-beta1 in the conditioned media. To determine the role of TGF-beta1 in regulating LNCaP proliferation, the action of TGF-beta1 was blocked by two different but complementary approaches. First, TGF-beta1 neutralizing antibody was added to the culture medium with varying concentrations of DHT. Second, mannose-6-phosphate, which has been demonstrated to inhibit the activation of latent TGF-beta1, was added in a similar manner to the culture. Results demonstrated that the characteristic bell- shaped growth response following treatment with increasing doses of DHT was converted to a linear dose-response curve as the growth of inhibition seen at the high dose by DHT was abolished. These observations, taken together, indicate that TGF-beta1 mediates at least in part the growth arrest observed at the high concentration of DHT in LNCaP cells.

Androgens↗

Expression and localization of transforming growth factor-beta receptors type I and type II in the rat ventral prostate during regression.

Of the three ubiquitously expressed transforming growth factor-beta (TGF beta) receptors, only type I and type II receptors contain serine/threonine kinase activity and have a direct role in TGF beta signal transduction. In the prostate, it has been reported that the level of type III receptor expression increases transiently after castration. However, the relationship between the TGF beta signaling receptors, type I and type II, and androgen is currently unclear. Thus, in the present study, we made an initial attempt to elucidate the effect of androgen on type I and type II receptor expression in the rat ventral prostate by measuring the levels of messenger RNA (mRNA) and protein at specific time points after castration up to 10 days. Within 3 days after castration, an increase in type II receptor mRNA was observed in the prostate, and the level continued to rise until 7 days postcastration (approximately 8-fold increase). Between days 7-10 postcastration, no significant change in the level of type II receptor mRNA was observed. Testosterone administration immediately after castration abolished the induction of type II receptor mRNA during the same 10-day period. Western blot analysis performed for type II receptor showed a similar result, in that the level of type II receptor protein increased approximately 5-fold by day 10 postcastration. In a similar manner to the expression of type II receptor mRNA, the level of type I receptor mRNA increased steadily until day 7 postcastration (approximately 6-fold increase). Between days 7-10 postcastration, the level of type I receptor mRNA did not change significantly. As with type II receptor mRNA, the induction of type I receptor mRNA was suppressed when testosterone was administered immediately after castration. To localize the expression of TGF beta receptor type II, immunohistochemical studies were performed. The results of these studies demonstrated a preferential localization of type II receptor in the prostatic epithelial cells and an increased staining intensity for the receptor after castration. Taken together, these data indicate that TGF beta signaling receptors, type I and type II, are under negative androgenic regulation at the transcriptional level and that TGF beta may be an important regulator of a stromal-epithelial interaction in the rat ventral prostate.

Animals↗

[Measurement of reactive oxygen species in a biological system and its perspectives].

In recent years, reactive oxygen species have been implicated in the pathogenesis of a wide variety of disorders. Although the existence of reactive oxygen intermediates in drug metabolism can be inferred from end product analysis or from the effects of antioxidants or enzymes such as superoxide dismutase, only the technique of electron spin resonance (ESR) allows the direct detection of these highly reactive species. However, some free radical species cannot be detected by ESR due to their extremely short half-lives, which result in low steady-state concentrations of the radicals or to short radical relaxation times, which lead to a very broad line. These facts made recent development of spin-trapping and chemiluminescence techniques are widely used to detect free radicals. The goal of this paper is to introduce the various assays available for measurement of reactive oxygen species in biological models. This paper will focus on two topics: (1) the spin-trapping/ESR technique in vitro and vivo and (2) the chemiluminescence-optical biosensor application of this technique, a very sensitive method that has the advantage of being able to provide continuous, online, nondestructive monitoring of reactive oxygen species.

Animals↗