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Biomedical subjects

R C Lee

Publications and source records attributed to R C Lee.

At least 73 records · Page 4Linked to original sources

Swallowing difficulty in Parkinson's disease.

Dysphagia is a frequent and potentially serious complication of Parkinson's disease (PD). We examined the oropharyngeal swallowing ability in 19 PD patients (15 men and 4 women, mean age 68.42 years, mean Hoehn and Yahr stage 1.8) using modified barium swallow before and after administering oral levodopa (in combination with benserazide). Twelve (63.2%) patients demonstrated objective evidence of swallowing abnormalities; although only six patients (31.6%) had subjective complaints. Vallecula sinus and pyriform sinus residues were the most frequent abnormalities (47.4% and 42.1%); followed by delayed swallowing reflex (26.3%). Three patients demonstrated silent aspiration. In the 12 patients with abnormal swallowing, six (50%) showed objective improvement after levodopa treatment, while the remaining six showed no change. Of the former group of six, one patient showed improvement in the oral phase, but deterioration in the pharyngeal phase. We concluded that PD patients had a high percentage of objective swallowing abnormalities which could be reduced in half of the patients through the administration of levodopa treatment.

Adult↗

The techniques of nonmuscular closure of hypopharyngeal defect following total laryngectomy: the assessment of complication and pharyngoesophageal segment.

The usual method of reconstructing a hypopharyngeal defect during total laryngectomy includes pharyngeal muscle layer closure, which may result in high pharyngoesophageal pressure. We hypothesize that nonclosure of the pharyngeal muscle can reduce the pressure of the pharyngoesophageal segment which can reduce the chances of the formation of pharyngocutaneous fistulae. A technique of nonmuscular closure of a hypopharyngeal defect is presented. The differences in the rate of fistula formation and swallowing function between patients with usual and nonmuscular closure were also studied. Sixty consecutive laryngectomees were enrolled in this study. Thirty patients received usual closure after total laryngectomy, whereas the other 30 patients underwent non closure of their pharyngeal muscles. One patient (3.3 per cent) in the nonmuscular closure group and three patients (10 per cent) in the usual closure group developed a pharyngocutaneous fistula. The pharyngoesophageal pressures of the nonmuscular closure group were significantly lower than those of the usual closure group. We conclude that the technique of nonclosure of the pharyngeal constrictor muscle after total laryngectomy is relatively more simple and is not associated with a higher rate of fistula formation. Furthermore, nonclosure of the pharyngeal constrictor muscle is preferable to muscular closure because it reduces the spasm of the pharyngoesophageal segment which limits voice rehabilitation.

Cutaneous Fistula↗

Plastic surgery.

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Culture Techniques↗

Protein kinase C activity is altered in HL60 cells exposed to 60 Hz AC electric fields.

We examined the effects of electric fields (EFs) on the activity and subcellular distribution of protein kinase C (PKC) of living HL60 cells. Sixty Hertz AC sinusoidal EFs (1.5-1,000 mV/cm p-p) were applied for 1 h to cells (10(7)/ml) in Teflon chambers at 37 degrees C in the presence or absence of 2 microM phorbol 12-myristate 13-acetate (PMA). PMA stimulation alone evoked intracellular translocation of PKC from the cytosolic to particulate fractions. In cells that were exposed to EFs (100-1,000 mV/cm) without PMA, a loss of PKC activity from the cytosol, but no concomitant rise in particulate PKC activity, was observed. In the presence of PMA, EFs (33-330 mV/cm) also accentuated the expected loss of PKC activity from the cytosol and augmented the rise in PKC activity in the particulate fraction. These data show that EFs alone or combined with PMA promote down-regulation of cytosolic PKC activity similar to that evoked by mitogens and tumor promoters but that it does not elicit the concomitant rise in particulate activity seen with those agents.

Carcinogens↗

The physicochemical basis for thermal and non-thermal 'burn' injuries.

One of the most basic problems of burn science may well be the confusing nomenclature we use. The word 'burn' is used to identify several different mechanisms of tissue injury. This article describes the problem of accurately characterizing and defining the various burn injuries on the basis of molecular events. The most important objective is to distinguish between the various physicochemical injuries on the basis of differences in their fundamental physicochemical mechanisms and physiological consequences. Also, pathophysiologically important biophysical processes such as the central importance of cell membrane permeabilization in acute cellular necrosis, which different types of burn injury have in common, are emphasized. The biophysics of membrane formation and permeabilization is presented to clarify the conditions for membrane damage as well as to discuss the potential for therapeutic intervention. Where feasible, plausible new strategies to reverse the molecular alterations caused by injury are hypothesized.

Biophysical Phenomena↗

Design, synthesis and in vitro evaluation of pyridinium ion based cyclase inhibitors and antifungal agents.

The design, synthesis and in vitro biological evaluation of pyridinium ion based inhibitors of oxidosqualene cyclase enzymes are reported. N-Alkyl- and N-prenylpyridinium ions have been found to be potent and specific inhibitors of Candida albicans oxidosqualene-lanosterol cyclase and to exhibit antifungal activity. The ability of pyridinium ions to inhibit the C. albicans cyclase increases with increasing structural resemblance to a putative monocyclized species formed during the course of the cyclization process. The N-(4E,8E)-5,9,13-trimethyl-4,8,12-tetradecatrien-1- ylpyridinium cation 1 inhibits the C. albicans enzyme at concentrations more than 100-fold lower than does the directly analogous piperidinium derivative 4.

Antifungal Agents↗

Alteration in sensory nerve function following electrical shock.

A study of the effects of electrical shock on peripheral nerve fibres is presented. Strength and duration of the applied shocks were similar to those encountered in a typical industrial electrical accident. The purpose of this study is: (i) to identify the electrophysiological and morphological change in nerve fibres after the application of electrical current shocks; (ii) to examine the ability of the peripheral nerve fibres to spontaneously regain function and; (iii) to demonstrate the usefulness of the sensory refractory spectrum as an additional technique in assessing the damage. Three groups of animals received twelve 4-ms electric field pulses of approximately 37 V/cm (n = 5), 75 V/cm (n = 9) and 150 V/cm (n = 6), respectively. Group 4 was a control group and received a direct application of 2 per cent lidocaine over the sciatic nerve for 30 min. Thermal effects of the shocks were negligible. The sensory refractory spectrum shows that electrical shock damage was mainly to the large, fast myelinated fibres and that higher field strengths do more damage. Also in a histological examination it was found that the more heavily shocked myelinated fibres had sustained more damage.

Action Potentials↗

Reorganization of microfilament structure induced by ac electric fields.

AC electric fields induce redistribution of integral membrane proteins. Cell-surface receptor redistribution does not consistently follow electric field lines and depends critically on the frequency of the applied ac electric fields, suggesting that mechanisms other than electroosmosis are involved. We hypothesized that cytoskeletal reorganization is responsible for electric field-induced cell-surface receptor redistribution, and used fluorescence video microscopy to study the reorganization of microfilaments in human hepatoma (Hep3B) cells exposed to low-frequency electric fields ranging in strength from 25 mV/cm to 20 V/cm (peak to peak). The frequency of the applied electric field was varied from 1 to 120 Hz and the field exposure duration from 1 to 60 min. In control cells, cytoplasmic microfilaments were aligned in the form of continuous parallel cables along the longitudinal axis of the cell. Exposure of cells to ac electric fields induced alterations in microfilament structure in a manner that depended on the frequency of the applied field. A 1 or 10 Hz ac field caused microfilament reorganization from continuous, aligned cable structures to discontinuous globular patches. In contrast, the structure of microfilaments in cells exposed to 20-120 Hz electric fields did not differ from that in control cells. The extent of microfilament reorganization increased nonlinearly with the electric field strength. The characteristic time for microfilament reorganization in cells exposed to a 1 Hz, 20 V/cm electric field was approximately 5 min. Applied ac electric fields could initiate signal transduction cascades, which in turn cause reorganization of cytoskeletal structures.

Actin Cytoskeleton↗

Malakoplakia of the prostate forming a fistulous tract to rectum: a case report.

Malakoplakia is a rare lesion of granulomatous inflammation which mainly affects urinary bladder but may involve other parts of the body. Differentiation from neoplastic process is often difficult due to its tumorous gross appearance and similarity to carcinoma microscopically. Malakoplakia of the prostate is even rare. We present a case of prostatic malakoplakia masquerading as a rectal tumor due to formation of a fistulous tract to the rectal muscular layers accompanied with ulceration of the rectal mucosa. Its clinical course is different from those of most reported cases, while the outcome is as satisfactory as in usual cases.

Diagnosis, Differential↗

Dynamics of cell membrane permeability changes at supraphysiological temperatures.

A quantitative fluorescent microscopy system was developed to characterize, in real time, the effects of supraphysiological temperatures between 37 degrees and 70 degrees C on the plasma membrane of mouse 3T3 fibroblasts and isolated rat skeletal muscle cells. Membrane permeability was assessed by monitoring the leakage as a function of time of the fluorescent membrane integrity probe calcein. The kinetics of dye leakage increased with increasing temperature in both the 3T3 fibroblasts and the skeletal muscle cells. Analytical solutions derived from a two-compartment transport model showed that, for both cell types, a time-dependent permeability assumption provided a statistically better fit of the model predictions to the data than a constant permeability assumption. This finding suggests that the plasma membrane integrity is continuously being compromised while cells are subjected to supraphysiological temperatures.

3T3 Cells↗

Chemoprotective effects of capsaicin and diallyl sulfide against mutagenesis or tumorigenesis by vinyl carbamate and N-nitrosodimethylamine.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a major pungent and irritating ingredient of hot chilli peppers, which are frequently consumed as spices. This dietary phytochemical has been found to interact with microsomal xenobiotic metabolizing enzymes in rodents. Capsaicin and its saturated analog dihydrocapsaicin (trans-8-methyl-N-vanillyl-6-nonanamide) have been proposed to inactivate cytochrome P-450 HE1 by irreversibly binding to the active sites of the enzyme. Besides cytochrome P-450 HE1, other isoforms of the P-450 superfamily were also reported to be inhibited by capsaicin. The inhibition by capsaicin of microsomal monooxygenases involved in carcinogen activation implies its chemopreventive potential. As part of a program to investigate chemoprotective properties of capsaicin we initially determined the effect of capsaicin on vinyl carbamate (VC)- and N-nitrosodimethylamine (NDMA)-induced mutagenesis in Salmonella typhimurium TA100. Capsaicin (0.42 mM) attenuated the bacterial mutagenicity of VC and NDMA by 50% and 42% respectively. Diallyl sulfide, a thioether found in garlic with selective P-450 HE1 inhibitory activity, also lessened the mutagenicity of the above carcinogens in a concentration-dependent manner. The suppression of VC- and NDMA-induced mutagenesis by capsaicin and diallyl sulfide correlated with their inhibition of P-450 IIE1-mediated p-nitrophenol hydroxylation and NDMA N-demethylation. Pretreatment of female ICR mice with a topical dose of capsaicin lowered the average number of VC-induced skin tumors by 62% at 22 weeks after promotion. A similar degree of protection was attained with oral administration of diallyl sulfide before carcinogen treatment. The results of this study suggest that capsaicin and diallyl sulfide suppress VC- and NDMA-induced mutagenesis or tumorigenesis in part through inhibition of the cytochrome P-450 IIE1 isoform responsible for activation of these carcinogens.

Allyl Compounds↗