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Biomedical subjects

M T Tseng

Publications and source records attributed to M T Tseng.

At least 37 records · Page 2Linked to original sources
PubMed1991

Differentiation induction of human promyelocytic leukemia cells by 10-hydroxycamptothecin, a DNA topoisomerase I inhibitor.

The cytotoxic and differentiating effects of 10-hydroxycamptothecin (HCPT) in the human promyelocytic leukemia cell line HL-60 were examined. By trypan blue dye exclusion, a 24-h exposure of the cells to 0.1 microM of the drug was found to be cytotoxic. Exposure of the cells to lower concentrations (0.001-0.01 microM) for 3 days reduced cell proliferation and induced cell differentiation. As determined by Wright-Giemsa staining, approximately 25% of promyelocytic cells became metamyelocytes, banded and segmented neutrophils. Electron microscopy demonstrated alterations in the ultrastructure of HCPT-induced HL-60 cells that included the formation of lobulated nuclei and the accumulation of large vesicles and small myelin bodies as well as glycogen-like particles in the cell periphery. Qualitatively similar results were obtained in a subline of HL-60 that is resistant to 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA); however, the rate and extent of induced nitroblue tetrazolium-positive cells by HCPT and several other agents were greater in the resistant cell line. Under conditions that induced cell differentiation, HCPT sharply inhibited [3H]thymidine incorporation into DNA and increased the rate of protein synthesis without an effect on the rate of RNA synthesis. The measurement of DNA topoisomerase I activity in nuclear extracts from both HCPT- and DMSO-treated cells demonstrated that the enzyme was decreased in mature cells compared to nondifferentiated controls. The data suggest that progressive reduction of DNA topoisomerase I activity may be associated with cell differentiation, but whether HCPT-induced differentiation is mediated by inhibition of the enzyme is inconclusive.

Antineoplastic Agents, Phytogenic↗
PubMed1990

Facilitated ERG recovery in taurine-treated bovine eyes, an ex vivo study.

Excorporal bovine eye with stable ERG patterns were used in this study to examine the possible antihypoxic property of the taurine. Taurine (1 mM) given prior to or after the on-set of hypoxia facilitated the retinal recovery as indicated by the B-wave amplitude changes. This observation is consistent with previous observations in hippocampal slice and other tissues which suggests an antihypoxic function of this sulfur-containing amino acid.

Animals↗
PubMed1990

Effects of trifluoroacetic acid, a halothane metabolite, on C6 glioma cells.

Effects of trifluoroacetic acid (TFA) on cell growth, DNA, glycoprotein, and dolichol-linked oligosaccharides synthesis and ribonucleotide triphosphate concentrations were examined in exponentially growing C6 murine glioma cells. One day of treatment with TFA caused a slight concentration-dependent enhancement of cell growth and [3H]thymidine incorporation. Exposure for 1 or 5 d to TFA (0.5-7.0 mM) elevated the [3H]leucine incorporation in a dose- and time-dependent manner. The results suggested that TFA stimulated cell growth and enhanced protein synthesis. TFA also affected [3H]mannose incorporation into glycoproteins and dolichol-linked oligosaccharides in a dose-dependent fashion. In addition, it was found that TFA accelerated lectin-induced cell agglutination. These data suggest that TFA, the principle halothane metabolite, alters plasmalemmal glycoprotein synthesis. These findings should form a basis for further understanding on the mechanism underlying halothane-associated neurotoxicity.

Animals↗
PubMed1989

Effects of homoharringtonine on protein glycosylation in human bladder carcinoma cell T-24.

Rates of [3H]glucosamine and mannose incorporation into glycoproteins and dolichol-linked oligosaccharides in exponentially growing T-24 bladder cancer cells were examined after exposure to homoharringtonine (HHT). Two-h treatment of HHT (10 ng/ml) reduced [3H]glucosamine and mannose incorporation into the glycoproteins to 61% and 32% of controls. Concomitantly, respective sugar incorporation into dolichol-linked oligosaccharides was elevated 29% and 30% above control. The maximal inhibition of glycoprotein biosynthesis and stimulation of the lipid-linked oligosaccharides occurred within 2 to 4 h after exposure to 50 ng/ml of the drug. Prolonged drug exposure (greater than 8 h) resulted in generalized suppression of glycoprotein biosynthesis and lipid-linked oligosaccharide formation. The kinetic study indicated that the time course on reduction of glycoprotein biosynthesis and accumulation of dolichol-linked oligosaccharides paralleled the decline in protein synthesis. Further, the inhibition of glycoprotein synthesis and stimulation of dolichol-linked oligosaccharides were reversible 4 h after drug withdrawal. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiographic analysis of the [3H]mannose-labeled glycoprotein revealed no pronounced difference between HHT-treated and control cells. These data suggest that the inhibition of glycosylation results from combined decrease of acceptors for glycoprotein biosynthesis with a simultaneous accumulation of the dolichol-linked oligosaccharides. Collectively these data may account for many of the HHT-induced bioresponses.

Alkaloids↗
PubMed1989

Complications of whole bladder dihematoporphyrin ether photodynamic therapy.

Photodynamic therapy with dihematoporphyrin ether was used to treat superficial bladder tumors in 7 patients with a followup of at least 1 year. Each patient received treatment to the whole bladder and those with papillary lesions received additional focal treatment. At 3 months 4 of the 5 patients with papillary tumors (stages Ta and T1) and 1 of the 2 with diffuse carcinoma in situ (Tis) were free of disease. However, at 1 year only 3 patients remained free of disease. Of 5 patients with an increase in irritative bladder symptoms 4 had a contracted bladder, hydroureteronephrosis and vesicoureteral reflux. Deep bladder biopsies showed replacement of smooth muscle by fibrous tissue. Six patients had mild to moderate skin phototoxicity. We conclude that although photodynamic therapy is an attractive and exciting method to treat cancer, its use with dihematoporphyrin ether in cases of bladder carcinoma can be associated with significant complications. The correct treatment parameters for safe, effective therapy are not known to date.

Adult↗
PubMed1989

Isolated, perfused bovine eye a model for acute retinal toxicity screening.

Excorporal bovine eye has been resuscitated and sustained with an aim of its development as an alternative to whole animal in evaluating acute retinal toxicity of xenobiotics. As indicated by the stable ERG response, such preparation is functionally reactive to photic stimuli over a span of 6-12 h. Moreover, after experienced a 20 min hypoxia the reperfused eyes recovered fully. This functionally responsive preparation was used to evaluate the influence of a highly purified bacterial collagenase (Nucleolysin) on the integrity of vitreoretinal junction. Nucleolysin at concentrations between 120-600 U/ml was injected into the posterior chamber for 15 min. Retinal surfaces were irrigated and eyes were perfusion fixed with glutaraldehyde. Ultrastructural analysis indicated that thinning of the internal limiting membrane occurred when enzyme exceeded 480 U. At 600 U concentration, the principle subcellular change involved the end-foot region of the Muller cells. These studies suggest that the isolated, perfused bovine eye is a suitable model for evaluating acute retinal toxicity of xenobiotics.

Animal Testing Alternatives↗
PubMed1989

A comparison of the effects of photodynamic therapy on normal and tumor blood vessels in the rat microcirculation.

The effects of light activation of the tumor photosensitizer dihematoporphyrin ether (DHE) were studied in the microcirculation of the rat cremaster muscle. Arterioles and venules in an implanted chondrosarcoma were studied by in vivo television microscopy and were compared to normal vessels of the same size elsewhere in the preparation and in control preparations. Activation with green light (530-560 nm, 200 mW/cm2, 120 J/cm2) 48 h after intraperitoneal injection of DHE (10 mg/kg body wt) resulted in significant narrowing of diameters of red blood cell columns in tumor arterioles and venules. The response in normal and control arterioles and venules was not significantly different from that seen in the tumor vessels except that the control arterioles did not remain significantly constricted during the treatment period. Treatment resulted in stasis of blood flow in 90% of tumor and normal arterioles at the completion of light activation. In venules, stasis of blood flow was observed in 75% of tumor and 70% of normal vessels. Vasoconstriction was the primary response in arterioles, while thrombosis predominated in venules. Morphologic assessment of light-activated vessels in the cremaster preparation by transmission electron microscopy revealed platelet aggregation with damage to endothelial cells and smooth muscle cells. Perivascular effects observed included interstitial edema and damage to skeletal muscle cells. In the tumor-bearing preparation, no direct cytotoxic effect on the tumor cells was shown. The surrounding vessels exhibited similar vascular stasis, but the lining cells appeared minimally affected. Photoactivation of DHE results in significant changes in the microcirculation which lead to stasis of blood flow. In this model, the response was similar for the normal microvasculature and for the microcirculation of an implanted chondrosarcoma. These effects may account, in part, for the mechanism of action of photodynamic therapy.

Animals↗
PubMed1988

The effect of photodynamic therapy on the microcirculation.

Photodynamic therapy (PDT) is a new form of cancer therapy involving tumor localization by photosensitizing drugs such as dihematoporphyrin ether (DHE). Light irradiation of drug-sensitized tissue results in photoactivation of DHE and tumor necrosis. The mechanism of action is incompletely understood but involves the generation of singlet oxygen which produces cytotoxic effects on tissues containing the compound. In addition, microcirculatory aberrations have been described during PDT. We have studied the acute effects of PDT on the microcirculation using in vivo television microscopy of the rat cremaster. This has enabled us to observe the effects of PDT on both paired and unpaired arterioles and venules using two different wavelengths of activating light (blue, 450-490 nm, and green, 530-560 nm). For both wavelengths of activating light, significant reduction in blood flow of all vessels was seen during PDT. This, in combination with the formation and embolization of platelet thrombi, resulted in stasis of blood flow in 80% of arterioles and 90% of venules. Observation for 2 hr after the completion of photoactivation revealed reperfusion in 20% of the arterioles but none of the venules. Blood flow was reduced by a combination of vasoconstriction and platelet thrombus formation. Reducing the total activating energy from 120J/cm2 to 24J/cm2 significantly reduced the response in venules and the incidence of stasis in both arterioles and venules. We conclude that the photoactivation of DHE results in significant vasoconstriction and thrombosis of normal vessels and that if these effects are seen at later times after DHE administration and in tumor neovasculature they may contribute to the mechanism by which PDT results in tumor necrosis.

Animals↗
PubMed1988

Pitfalls in the use of brain slices.

In vitro brain slices are the preparation of choice for the detailed examination of local circuit properties in mammalian brain. However it is the investigator's responsibility to verify that the circuits under investigation are indeed confined within the boundaries of the functional region of the slice used. The medium in which the slice is maintained is under the full control of the investigator. This places the burden on the investigator to ensure that: (1) the properties of the medium are fully under control; (2) the effects of the medium on the slice are known; (3) the conditions under which the slice is being maintained bear some reasonable relation to those it enjoys (or endures) in vivo. Generalizations to in vivo conditions must be made with caution. If at all possible, similar studies (perhaps less extensive, due to the greater technical difficulties) should be done in vivo to provide a basis for comparison. Investigators using drugs should be aware of, and respect, the basic pharmacological principles cited in the text. In particular, the substantial freedom the investigator has in defining the extracellular medium should not be abused.

Animals↗
PubMed1987

Increased glucose improves recovery of neuronal function after cerebral hypoxia in vitro.

The rat hippocampal slice preparation was used to evaluate the effect of increasing glucose levels in the perfusion medium on the recovery of synaptic function after a standardized hypoxic insult. Slices exposed to low glucose (5 mM) did not recover from a standard hypoxic insult (10 min of 95% N2/5% CO2 atmosphere). Following the same insult, 39% of the control (10 mM glucose) slices recovered their synaptic function, while 93% of the slices provided with high glucose level (20 mM) exhibited recovery of synaptic function. Thus, a dose-dependent effect of glucose on recovery of neuronal function following an intermediate period (10 min) of oxygen deprivation was found. The high-glucose-treated slices could tolerate a severe hypoxic insult of 15 min or even 20 min from which 94% and 81% of them recovered, respectively. Only 21% of the control (10 mM glucose) slices recovered their synaptic activity following 15 min of hypoxia, and none survived 20 min of that insult. The adverse effects of hyperglycemia reported in vivo were not seen in our study. This may be due to the sustained perfusion of the brain slice preparation, which could limit accumulation of lactic acid during hypoxia. However, treatment of slices with lactic acid prior to and during the hypoxic insult did not worsen the outcome. Alternatively, glucose may protect against the damaging effects of oxygen free radicals formed during reoxygenation. Nevertheless, the antihypoxic effect of glucose appears to be a metabolic one, since L-glucose (the non-metabolic analog of D-glucose) was innocuous in this respect.

Animals↗
PubMed1987

Taurine improves the recovery of neuronal function following cerebral hypoxia: an in vitro study.

Rat hippocampal slices were used in the present study to assess the effect of a pretreatment with the amino acid taurine on their ability to recover synaptic function following a standardized hypoxic insult. After 10 min hypoxia, 47% of all control (untreated) slices exhibited recovery of synaptic function (orthodromically evoked CA1 population spike). Of slices pretreated with 0.5, 1.0 or 2.0 mM taurine, 63, 88 and 97% recovered from the same hypoxic insult. This dose-dependent protective effect was biphasic, as 5.0 mM taurine produced no protection. When hypoxia was extended to 15 min, only 20% of the untreated slices recovered, while 88% of slices treated with 1.0 mM taurine recovered their population spike. The same pretreatment attenuated the fall in the population spike amplitude upon Ca2+ depletion. We hypothesize that taurine plays an important role in an endogenous antihypoxic mechanism through the attenuation of Ca2+ movement across the neuronal membrane.

Animals↗
PubMed1987

Ultrastructure of the pineal gland of the tropical bat Rousettus leschenaulti.

The ultrastructure of the pineal organ was studied in the tropical megachiropteran Rousettus leschenaulti. The pineal lies deep beneath the hemispheres adjacent to the third ventricle and is traversed by the habenular commissure anteriorly. Its parenchyma consists of a uniform population of light and occasional dark pinealocytes which appear to differ only in the degree of cytoplasmic staining. Pinealocytes are characterized by well developed Golgi bodies associated with numerous small vesicles, many mitochondria and polyribosomes, and frequent subsurface cisternae. Lipid droplets and elements of smooth endoplasmic reticulum are scant. Cisternae of granular endoplasmic reticulum are occasionally dilated. A distinct feature is the abundance of clear vesicles in the pinealocyte pericapillary terminals, which also frequently contain granular vesicles and a very large vacuole. The pineal is further characterized by the presence of a small number of glial cells and myelinated nerve fibers. A broad perivascular space investing numerous capillaries contains glial-cell and pinealocyte processes, collagen fibrils and abundant unmyelinated nerve fibers. Tortuous extensions of the perivascular space enter the pineal parenchyma where they come in close proximity to branched intercellular channels or canaliculi characterized by specialized junctions and microvilli. Differences between the pineal of the non-hibernating megachiropteran Rousettus and that of the hibernating microchiropteran bats, and structural similarities to the pineal of tropical rodents are discussed.

Animals↗
PubMed1986

Adaptation of adult brain tissue to anoxia and hypoxia in vitro.

The rat hippocampal slice preparation was used in the present study to demonstrate the ability of adult brain tissue to adapt to anoxic and hypoxic conditions. Adaptation was induced by pre-exposure of hippocampal slices to a short (5 min) anoxic episode. The evoked electrical activity of pre-exposed slices recovered from a subsequent, longer anoxic insult, while that of controls (without pre-exposure), receiving the same insult, did not. The adaptation process is time-dependent; an interval of 0.5 h between the pre-exposure and the subsequent anoxic insult allowed slices to resist anoxic periods of 13 +/- 2 min while after an interval of 2 h an anoxic period of 16 +/- 2 min could be tolerated. Evoked electrical activity persisted in adapted slices during exposure to hypoxia while their non-adapted controls exhibited synaptic silence under hypoxic conditions.

Adaptation, Physiological↗
PubMed1986

Induction and growth of mammary tumors after superior cervical ganglionectomy in sighted and blinded-anosmic rats.

Female rats were subjected to superior cervical ganglionectomy (Gx), blinding and anosmia (BAs) or combined procedures (BAsGx). Onset and growth of dimethylbenz(a)anthracene (DBMA)-induced mammary tumors was studied in these animals and compared to tumorigenesis in intact control rats. Carcinostatic effects were present in all surgically altered animals, as evidenced by a trend toward reduced tumor incidence, reduced final tumor mass, and a significant reduction in mean number of tumors in Gx and BAsGx rats, and increased regression of tumors in BAs rats compared to intact group. Reduced tumorigenesis was paralleled by a trend toward either an increase (BAs) or a decrease (Gx and BAsGx) in the activity of pineal hydroxyindole-O-methyltransferase (HIOMT) compared to intact group. In addition, BAs and BAsGx animals showed a significant reduction in body weight. These results suggest that Gx reduces mammary tumorigenesis in both sighted and BAs rats. They further confirm the findings of others on reduced mammary tumorigenesis in BAs rats. Possible involvement of multiple carcinostatic mechanisms in different animal models is discussed.

9,10-Dimethyl-1,2-benzanthracene↗