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Biomedical subjects

C L Huang

Publications and source records attributed to C L Huang.

At least 19 recordsLinked to original sources
PubMed1996

Correlation of KAI1/CD82 gene expression with good prognosis in patients with non-small cell lung cancer.

As part of our evaluation of members of the transmembrane 4 super-family as possible prognostic predictors, we performed a retrospective study on the expression of the recently identified KAI1 gene by tumors of the lung. This gene, which is identical to CD82, suppresses tumor metastasis of prostate cancer, and its decreased expression may be involved in malignant progression. We used reverse transcription-PCR to analyze tumor tissues from 151 lung cancer patients; 74 tumors were stage I, 17 were stage II, and 60 were stage III. Our results indicate that while 35 patients had tumors in which the KAI1/CD82 gene was conserved (positive), 116 patients had tumors with reduced gene expression (negative). The overall survival rate of patients with KAI1/CD82-positive tumors was significantly higher than that of patients with KAI1/CD82-negative tumors (77.4% versus 38.5%; P=0.002). Furthermore, the overall survival rate of patients with KAI1/CD82-positive adenocarcinoma was also much higher than that of individuals whose adenocarcinoma had reduced KAI1/CD82 expression (73.4% versus 27.1%;P=0.009). Multivariate analysis with the Cox regression model indicated that KAII/CD82 positivity correlated best with the overall survival rate, except for lymph node status. Our data suggest that high KAII/CD82 gene expression by tumors of the lung may be associated with a good prognosis. These findings complement our earlier studies on MRP-1/CD9, another member of the transmembrane 4 superfamily, whose reduced expression in non-small cell lung cancer appears to be a factor of poor prognosis. This set of observations suggests that assessment of the expression status of KAI1/CD82 and MRP-1/CD9 by tumors may provide prognostic information on the clinical behavior of lung cancer.

Age Factors↗
PubMed1995

Reduced motility related protein-1 (MRP-1/CD9) gene expression as a factor of poor prognosis in non-small cell lung cancer.

Motility related protein-1 (MRP-1) is a transmembrane glycoprotein that is identical to the CD9 antigen. In previous studies, we showed that various types of cultured tumor cells transfected with MRP-1/CD9 cDNA have low motility and diminished metastatic potential to the lung. More recently we used immunohistochemical procedures, immunoblotting, and reverse transcription-PCR to demonstrate that the level of MRP-1/CD9 expression was inversely related to the clinical stage of a given carcinoma of the breast. In addition, we found that the primary tumors of almost 50% of the patients had higher MRP-1/CD9 levels than their respective metastatic lymph nodes. In consideration of these findings, we have now applied reverse transcription-PCR to determine MRP-1/CD9 gene expression in lung cancer. We analyzed tumor tissues of 109 patients: 49 tumors were stage I; 15 were stage II; and 45 were stage III. We found that 67 patients had MRP-1/CD9-positive tumors, and that gene expression was reduced in the tumors of the remaining 42 individuals. The overall rate of survival was strikingly higher among patients with positive tumors than in those whose tumors had reduced gene expression (62.3 versus 34.9%; P < 0.001). This also pertained to patients with adenocarcinomas of the lung (55.4 versus 26.0%; P < 0.001). Multivariate analysis with the Cox regression model indicated that MRP-1/CD9 positivity correlated better with overall survival rate than did other variables, except lymph node status. Our data suggest that low MRP-1/CD9 expression by tumors of the lung may be associated with poor prognosis. It is conceivable that testing for MRP-1/CD9 may identify node-negative lung cancer patients and patients with adenocarcinomas who are at high risk for early disease recurrence.

Antigens, CD↗
PubMed1995

Motility related protein 1 (MRP-1/CD9) expression: inverse correlation with metastases in breast cancer.

In our previous studies we showed that motility related protein 1 (MRP-1) is a glycoprotein recognized by mAb M31-15, and that the sequence of MRP-1 is identical to that of CD9, a WBC differentiation antigen. Transfection of MRP-1/CD9 cDNA into cultured nonhematopoietic cells suppresses cell motility. The extent of suppression is directly related to the level of MRP-1/CD9 expression. In addition, the metastatic potential of MRP-1/CD9-transfected melanoma BL6 cells is lower than that of control BL6 cells. To determine whether these experimental results are of relevance with respect to actual human tumors, we investigated MRP-1/CD9 expression in 143 invasive ductal carcinomas of the breast. Of 97 patients with MRP-1/CD9-positive tumors, only 36 (37.1%) had lymph node involvement. In contrast, 21 of 39 (53.8%) patients whose tumors had reduced MRP-1/CD9 immunoreactivity and 5 of 7 patients whose primary carcinomas were not stained by the anti-MRP-1/CD9 MAb had lymph node metastases. The comparison of protein expression by 62 primary tumors and their respective metastatic lymph nodes revealed that in almost 50% of the cases, the latter had lower MRP-1/CD9 levels than the former. Moreover, reverse transcriptase-PCR-based analysis disclosed that MRP-1/CD9 gene expression in the metastatic lymph nodes of 17 of 32 patients was strikingly lower than in the primary invasive ductal carcinomas. Gene overexpression was not observed in any of the samples studied. Our data suggest that low MRP-1/CD9 expression may be associated with the metastatic potential of certain human tumors.

Adult↗
PubMed1995

Effect of membrane potential on surface Ca2+ receptor activation in rat osteoclasts.

Osteoclasts are known to possess a divalent cation-sensitive receptor, the Ca2+ receptor (CaR). The latter monitors changes in the local Ca2+ concentration generated as a result of hydroxyapatite dissolution. CaR activation elevates cytosolic [Ca2+] and thereby inhibits osteoclastic bone resorption. Recent studies have used Ni2+ as a surrogate CaR agonist to elicit changes in cytosolic [Ca2+]. This article examines the effects of membrane potential changes on the kinetics of the cytosolic [Ca2+] signal resulting from such Ni(2+)-induced CaR activation. Membrane potential was altered through variations in the extracellular [K] in combination with applications of the K+ ionophore, valinomycin. Membrane potential changes were confirmed by independent electrophysiological patch clamp studies of whole osteoclasts. The application of valinomycin produced a distinct, sustained elevation of cytosolic [Ca2+] in single fura 2-loaded cells, a "primary" response. This response was independent of valinomycin concentration (between 5 nM to 5 microM) and persisted in Ca(2+)-free, EGTA-containing solutions. It also persisted both in high (105 mM) and low (5 mM) extracellular [K+]. A gradual "secondary" elevation of cytosolic [Ca2+] then followed with the continued application of valinomycin, but this was eliminated by sequestering the extracellular [Ca2+] or by increasing extracellular [K+] from 5 to 105 mM. In a separate set of experiments, the presence of 5 microM [valinomycin]-([K+] = 5 mM) prolonged the cytosolic [Ca2+] signal elicited by 50 microM-[Ni2+] application. These prolonged kinetics persisted in low extracellular [Ca2+] (zero-added Ca2+), but reverted to a rapid time-course in the presence of 105 mM-[K+] or at higher [Ni2+] (500 microM and 5 mM). The experiments thus indicate that membrane voltage modifies the kinetics of CaR activation by Ni2+ and therefore suggests that the CaR is an integral protein in the osteoclast surface membrane.

Animals↗
PubMed1995

The afterdepolarization in Rana temporaria muscle fibres following osmotic shock.

Rana temporaria sartorius muscle fibres were exposed to varied sequences of solution and temperature changes that have been employed hitherto in procedures that sought to decouple the transverse tubules from the surface membrane. The incidence of such detubulation was assessed in large numbers of fibres through demonstrating a loss or otherwise of the after-depolarization that normally reflects successful tubular propagation of the surface action potential. This criterion yielded assessments of the existing detubulation techniques in agreement with earlier results. The experiments then developed an improved detubulation procedure that required only brief (15 min) exposures to glycerol, its replacement in a single step by a Ca2+/Mg(2+)-Ringer solution for 30 min, and rapid cooling from room temperature (19-21 degrees C) to 6-10 degrees C prior to final restoration of the normal Ringer solution. This sequence of steps yielded an optimal incidence (98%) of detubulation in viable surface fibres that were amenable to electrophysiological studies. Studies that systematically modified the detubulation procedure demonstrated that the omission of any one step in the protocol significantly reduced the incidence of detubulation with or without accompanying deteriorations in fibre resting potentials. Successful detubulation accordingly required an initial exposure to an optimal glycerol concentration that lasted for a minimal duration and for its abrupt withdrawal. Inclusion of a cooling step within 30 min after glycerol withdrawal was coincident with, and critical to, optimal tubular isolation. Thus, cooling steps that either preceded, or that followed the glycerol withdrawal step by more than 60 min, resulted in a sharp reduction in the incidence of detubulation. Similarly, a critical period of exposure to Ca2+/Mg2+ Ringer solution also promoted detubulation without compromising the recovery of stable and satisfactory resting potentials. The findings reported here remain consistent with a primarily osmotic mechanism for detubulation. However, they demonstrated additional and important influences of temperature and of divalent cation concentration on the extent of tubular detachment when such factors were modified during the time course of the expected volume changes that followed each adjustment in osmotic condition.

Action Potentials↗
PubMed1995

Systemic artery-to-pulmonary artery shunt after using an omental pedicle flap.

A 66-year-old man was hospitalized because of hemoptysis. Four years earlier, he had undergone an operation involving the use of an omental pedicle flap that was supplied by the right gastroepiploic artery for the treatment of empyema. Arteriography revealed that the right gastroepiploic artery communicated with the periphery of the right pulmonary artery. The right gastroepiploic artery was divided surgically.

Abdominal Muscles↗
PubMed1995

Clear cell papulosis: report of three cases of a newly recognized disease.

BACKGROUND: Clear cell papulosis is a newly described disease. Since the first report in 1987, no other cases have been reported. OBJECTIVE: Our purpose was to describe three more newly identified cases that further characterize this disease. METHODS: Formalin-fixed and paraffin-embedded biopsy specimens were used for histochemical and immunohistochemical studies. RESULTS: The three patients included two boys and, for the first time, a girl. All three had multiple white papules on the lower part of the abdomen, with or without scattered lesions along the milk lines bilaterally. The main histopathologic finding was the presence of clear cells scattered mainly among the basal cells of the acanthotic epidermis. The clear cells were variably stained by mucicarmine, colloidal iron, alcian blue (pH 2.5), periodic acid-Schiff, the anticytokeratin antibody AE1, carcinoembryonic antigen, epithelial membrane antigen, and gross cystic disease fluid protein-15. CONCLUSION: Clear cell papulosis is a unique clinicopathologic entity. The clear cells were confirmed to be sweat gland secretory cells by their positive immunostaining with gross cystic disease fluid protein-15. The latter was also present in eccrine sweat gland coil cells. However, whether the clear cells were eccrine or apocrine secretory cells could not be determined.

Biopsy↗
PubMed1995

Evidence that direct binding of G beta gamma to the GIRK1 G protein-gated inwardly rectifying K+ channel is important for channel activation.

Activation of G protein-gated K+ channels by G protein-coupled receptors contributes to parasympathetic regulation of heart rate in the atrium and inhibitory postsynaptic potentials in the peripheral and central nervous system. Having found that G beta gamma activates the cloned GIRK1 channel, we now report evidence for direct binding of G beta gamma to both the N-terminal hydrophilic domain and amino acids 273-462 of the C-terminal domain of GIRK1. These direct interactions are physiologically important because synthetic peptides derived from either domain reduce the G beta gamma binding as well as the G beta gamma activation of the channel. Moreover, the N-terminal domain may also bind trimeric G alpha beta gamma, raising the possibility that physical association of G protein-coupled receptors, G proteins, and K+ channels partially accounts for their compartmentalization and hence rapid and specific channel activation by receptors.

Amino Acid Sequence↗
PubMed1995

The effect of cerebrospinal fluid dilution of isobaric 0.5% bupivacaine used for spinal anaesthesia.

A prospective study was conducted to see the effect on spinal anaesthesia of the dilution of isobaric 0.5% bupivacaine with cerebrospinal fluid. Sixty patients were randomly allocated to three groups. In group 1, patients received 3 ml isobaric 0.5% bupivacaine intrathecally without aspirating cerebrospinal fluid. In groups 2 and 3, cerebrospinal fluid 1 ml and 2 ml was aspirated respectively and mixed with 3 ml isobaric 0.5% bupivacaine. A total volume of 4 ml in group 2 and 5 ml in group 3 was administered. Thus, the volume of cerebrospinal fluid remained unchanged. Pinprick analgesia and motor block was evaluated from induction until recovery. No differences in onset time, duration and 'two segments regression' were noticed. The only statistical difference was the time to reach complete motor block, which was shorter in group 1 as compared to groups 2 and 3 (6.9 SD 1.4 min versus 11.3 SD 3.0 and 13.5 SD 3.9 min respectively). The mean value of maximum decrease in systolic blood pressure was small, being less than 15% of the pre-operative value for each group. In conclusion, the effect of diluting isobaric 0.5% bupivacaine with cerebrospinal fluid, 1 ml and 2 ml, is minimal and it is an unnecessary procedure with limited clinical effect.

Adult↗
PubMed1995

Caffeine modulates Ca2+ receptor activation in isolated rat osteoclasts and induces intracellular Ca2+ release.

A ryanodine-sensitive pathway is involved in intracellular Ca2+ release in response to activation of the osteoclast cell surface Ca2+ receptor. We now report that the ryanodine-receptor modulator, caffeine itself released intracellularly stored Ca2+ and, strongly inhibited Ca2+ release triggered in response to Ca(2+)-receptor activation by Ni2+, a surrogate cation agonist. Caffeine yielded a bell-shaped concentration-response curve (0.005-2 mM) and displayed use-dependent inactivation. Furthermore, responses to caffeine were abolished on prior application of Ni2+ (5 mM). Subthreshold (0.005 mM) caffeine concentrations abolished Ni(2+)-induced elevations in the cytosolic Ca2+ concentration ([Ca2+]). However, in a Ca(2+)-free, ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid-containing solution (extracellular [Ca2+] < 10 nM), caffeine (0.5 mM) neither elevated [Ca2+] nor inhibited the response to Ni2+. Finally, when caffeine was applied to intercept the plateau phase of the cytosolic Ca2+ signal triggered by extracellular Ca2+ elevation (10 mM), a rapid but reversible inactivation followed. These studies strongly indicate the existence of a caffeine-sensitive mechanism for the release of intracellularly stored Ca2+ in the osteoclast.

Animals↗
PubMed1994

Kinetic separation of charge movement components in intact frog skeletal muscle.

1. Procedures for a complete charge movement separation employed a combination of its steady-state inactivation and activation properties in intact frog skeletal muscle fibres in gluconate-containing solutions. 2. Holding potential shifts from -70 to -50 mV reduced the total charge available between -90 and -20 mV from 16.76 +/- 1.70 nC microF-1 (mean +/- S.E.M.; n = 4 fibres) to 9.25 +/- 1.43 nC microF-1 without significant loss of tetracaine-resistant charge (q beta). 3. The steady-state and kinetic properties of tetracaine-sensitive charge (q gamma) persisted through holding potential changes from -90 to -70 mV in the presence of gluconate and generally resembled activation properties established hitherto in sulphate-containing solutions. 4. Further holding potential displacement to -50 mV abolished q gamma charge movements and depressed the charge-voltage curve. 5. Test voltage steps applied from a -70 mV prepulse level gave rapid monotonic q beta decays and similarly depressed activation functions in 2 mM tetracaine unchanged by holding potential shifts between -70 and -50 mV. 6. The isolated 'on' q gamma charge movements, I(t), always included early transients that preceded any prolonged charging phases and which increased with depolarization. They decayed to stable baselines in the absence of prolonged time-dependent or inward-current phases and yielded integrals, Q(t), that monotonically increased with test voltage. 7. 'Off' steps always elicited rapid monotonic q gamma decays that fully returned the 'on' charge. 8. 'On' and 'off' q gamma currents, I(t), following voltage steps from fixed conditioning to varying test levels mapped onto topologically distinct higher-order phase-plane trajectories, I(Q), that steeply varied with test voltage. 9. In contrast, voltage steps to fixed test potentials of either -70 or -20 mV elicited identical q gamma phase-plane trajectories independent of prepulse history. 10. The q gamma current thus reflects an independent, capacitative process driven uniquely by higher-order dependences upon charge distribution, Q(t), and test voltage, V(t), autonomous of prepulse history or time, t.

Animals↗
PubMed1994

IL-10 inhibits HIV-1 replication and is induced by tat.

Interleukin 10 (IL-10) is produced by TH2 lymphocytes and regulates both lymphoid and myeloid cells. In the present study we demonstrate that IL-10 is expressed and produced spontaneously in the peripheral blood mononuclear cells (PBMCs) of all HIV-1 infected individuals tested, 3 of 19 cases of HIV-negative lymphoma and none of five healthy controls. IL-10 mRNA was detectable in both monocytes/macrophages and T lymphocytes isolated from PBMCs of HIV infected patients. We have also shown that infection of promonocytic (U937) and T (H9) cell lines with HIV stimulates IL-10 secretion. Furthermore, a T cell line (H9) stably transfected with a HIV tat expression-vector secreted higher levels of IL-10. We have also demonstrated that rhIL-10 inhibited HIV-1 replication in infected monocytes and PBMCs in a dose dependent manner. IL-10 may thus participate in long latency between HIV-1 infection and development of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Modulation of the osteoclast Ca2+ receptor by extracellular protons: possible linkage between Ca2+ sensing and extracellular acidification.

We report a sensitivity of the osteoclast cell surface Ca2+ receptor to extracellular protons. Freshly isolated rat osteoclasts were exposed to the known agonists of the Ca2+ receptor, Ca2+ and Ni2+, in extracellular solutions set at different pH values. Decreasing the extracellular pH from 7.8 to 4.0 units markedly potentiated the cytosolic Ca2+ signals elicited in response to Ca2+ receptor activation by either Ni2+ (50 microM, 500 microM or 5 mM) or Ca2+ (5 mM). Each response consisted of a rapid and usually transient elevation of cytosolic [Ca2+]. Maximal cytosolic [Ca2+] responses were obtained at pH values of 6.6 (for 5 mM-[Ni2+]) and 4.0 units (for 5 mM-[Ca2+]). Finally, the effects of extracellular pH persisted in Ca(2+)-free, EGTA-containing solutions, suggesting a modulation of intracellular Ca2+ release.

Animals↗
PubMed1994

Elevated cytosolic calcium levels in human lymphocytes during surface virus infections.

Generalised metabolic and electrolyte disturbances are known to accompany both plasma and surface virus infections. We have investigated whether these infections could impair the transport of Ca2+ from cells under conditions of controlled concentrations of the energy substrate glucose. Thus, cytosolic calcium levels ([Ca2+]i) were measured in single isolated lymphocytes obtained from healthy volunteers or those suffering from coryza. Before making measurements using a Ca(2+)-sensitive fluorescent dye indo 1, we incubated lymphocytes in buffers containing 0 mM-, 5.6 mM- or 11.2 mM-[glucose]. We found that [Ca2+]i of lymphocytes obtained from the sick were significantly higher than those from healthy controls both at 0 mM and 5.6 mM-[glucose], and that [Ca2+]i was inversely related to the media glucose concentration for both groups. These results suggest a diminished capacity of cation pumping in viral infections, such as coryza, in relationship to the available glucose as energy substrate.

Calcium↗
PubMed1994

Charge conservation in intact frog skeletal muscle fibres in gluconate-containing solutions.

1. The conservation of intramembrane charge was investigated in intact voltage-clamped frog skeletal muscle fibres under conditions that minimized time-dependent ionic currents and so facilitated precise determination of capacitative charge. 2. Prolonged (q gamma) transients were demonstrated in 3,4-diaminopyridine and tetraethyl-ammonium gluconate-containing low [Ca2+] solutions in response to 125 ms pulses that explored the voltage range -90 to -20 mV. The tetracaine-sensitive, q gamma, component then accounted for a significant proportion (over 50%) of available charge. 3. Both delayed 'on' q gamma currents and 'off' current tails decayed to steady direct current (DC) baselines without significant residual ionic current slopes in the chosen extracellular solutions. This suggested that the current transients represented capacitative decays. It was also compatible with the precise determination of effective charge by integration. 4. The advent of 'on' q gamma current was accompanied by increased 'off' charge. Thus, charge was conserved through all 'on' and 'off' steps and through test voltages that extended from the threshold appearance of q gamma as a slow transient to its full merger with the earlier q beta decay at stronger depolarizations. 5. Charge conservation persisted through a wide range of 'on' pulse durations between 60 and 370 ms and was therefore independent of the interval following the q gamma decay. 6. The quantity of q gamma charge remained a monotonic single-valued function of test voltage, whether this potential was reached directly from the -90 mV holding potential or following a prepulse to -10 mV. 7. These findings suggest that the q gamma charge movement represents the electrical signature of an intramembrane entity whose transitions are primarily driven by, and therefore conserved with, the steady-state potential.

Animals↗
PubMed1994

Dimensional analysis of osteoclastic bone resorption and the measurement of biologically active calcitonin.

Calcitonin inhibits bone resorption through a direct action on the osteoclast. We report a quantitative analysis of bone resorption by disaggregated rat osteoclasts. We then used our findings to develop a formal bioassay for calcitonin. Osteoclasts were mechanically disaggregated from neonatal rat long bones and dispersed at low densities on slices of devitalized bovine cortical bone. The resulting areas of bone excavation were quantified to micrometric precision by scanning electron microscopy together with computer-assisted image analysis. These findings were correlated with the volumes of bone resorption in the same slices measured by confocal scanning microscopy for the first time. The total planar areas of bone resorption per slice correlated linearly (r = 0.78) with the confocal microscopic measurements of total volume resorbed, provided that volume was expressed to its two-thirds power. The latter transformation resulted in representations of the determined areas ([length]2) and volumes ([length]3) which were dimensionally consistent. These findings thus demonstrate that osteoclastic bone excavations show a consistent relationship between area and volume and that assessments of the area of excavations accordingly provide an empirical representation of the volume of bone resorbed. Furthermore, in view of the skewed nature of the distributions of area measurements, we assessed the effect of transforming the response variable to derive a metameter, (planar area of resorption)1/2. Such transformed data points, which expressed the data in the dimensions of [length], were more normally distributed than the raw data points and had more stable variances over a wider concentration range. We accordingly determined relative potencies using parallel line analyses on the transformed data. The latter offered a consistent correlation to the volume measurements when these were also converted to dimensions of [length] (r = 0.805). It was confirmed that the inhibition of bone resorption by calcitonins from various species, namely, pig, salmon and eel, was quantitatively dependent upon concentration of the respective peptides. The resulting assay was also found to be sufficiently sensitive to measure picomolar peptide concentrations with a precision, lambda (standard deviation/slope), ranging between 0.3 and 0.8. Finally, we identified factors affecting assay precision and sensitivity.

Animals↗