Biomedical subjects

M T Lin

Publications and source records attributed to M T Lin.

At least 109 records · Page 6Linked to original sources

PubMed1997

Kinetics of cytokine mRNA expression in the central nervous system following lethal and nonlethal coronavirus-induced acute encephalomyelitis.

The potential role(s) of cytokines in the reduction of infectious virus and persistent viral infection in the central nervous system was examined by determining the kinetics of cytokine mRNA expression following infection with the neurotropic JHM strain of mouse hepatitis virus. Mice were infected with an antibody escape variant which produces a nonlethal encephalomyelitis and compared to a clonal virus population which produces a fulminant fatal encephalomyelitis. Infection with both viruses induced the accumulation of mRNAs associated with Th1- and Th2-type cytokines, including IFN-gamma, IL-4, and IL-10. Peak mRNA accumulations were coincident with the clearance of virus and there was no obvious differences between lethally and nonlethally infected mice. TNF-alpha mRNA was induced more rapidly in lethally infected mice compared to mice undergoing a nonfatal encephalomyelitis. Rapid transient increases in the mRNAs encoding IL-12, iNOS, IL-1alpha, IL-1beta, and IL-6 occurred following infection. Nonlethal infections were associated with increased IL-12, IL-1beta, and earlier expression of IL-6, while lethal infections were associated with increased iNOS and IL-1alpha mRNA. These data suggest a rapid but differential response within the central nervous system cells to infection by different JHMV variants. However, neither the accumulation nor kinetics of induction provide evidence to distinguish lethal infections from nonlethal infections leading to a persistent infection. Accumulation of both Th1 and Th2 cytokines in the central nervous system of JHMV-infected mice is consistent with the participation of both cytokines and cell immune effectors during resolution of acute viral-induced encephalomyelitis.

Acute Disease↗

PubMed1997

Ultrasonic analysis of tremorine and cold tremor activity in unanesthetized rats.

In order to quantify the tremorine and cold tremor activity in unanesthetized rats, a new ultrasonic motion transducer method was used. Both kinds of activity are reported as vibratory body motion that occurred between 18-32 Hz as determined by spectral analysis. The recorded signal was analyzed and its power spectrum was obtained through a fast Fourier transform operation. It was found that a negative linear relation occurs between shiver amplitude and ambient temperature (r = 0.999). A negative linear relation also occurs between metabolic rate and ambient temperature (r = 0.997). In addition, a positive linear relation between metabolic rate and cold shiver exists (r = 0.999). Both tremorine (30 mg/kg, i.p.) and cold tremor (Ta = 2-22 degrees C) activity monitored by the ultrasonic method were completely abolished by premedication with 1 mg/kg atropine. Thus, it appears that the advantages of this tremor detection method are that is non-invasive and non-contact. Therefore, the ultrasonic method provides a good choice for quantifying tremorine and cold tremor activity in unanesthetized animals during studies of thermoregulatory physiology or motor disorders.

Animals↗

PubMed1997

Heatstroke-induced cerebral ischemia and neuronal damage. Involvement of cytokines and monoamines.

Experiments were carried out to ascertain whether the levels of brain monoamines and cytokines are involved in the heatstroke-induced cerebral ischemia and neuronal damage. Heatstroke was induced by exposing anesthetized rats to a high ambient temperature of 42 degrees C; the moment at which the mean arterial pressure began to decrease from its peak level was taken as the onset of heatstroke. It was found that, during the heatstroke-induced cerebral ischemia and neuronal damage, the extracellular concentration of either dopamine, serotonin or norepinephrine were increased in the hypothalamus, the corpus striatum and other brain regions. In addition, the concentration of interleukin-1 (IL-1), IL-6 and tumor necrosis factor in both the plasma and brain was also increased during heatstroke-induced cerebral ischemia and neuronal damage. Heatstroke-induced cerebral ischemia and neuronal damage were attenuated by depletion of brain dopamine or serotonin produced by intracerebral injection of 6-hydroxydopamine or 5,7-dihydroxytryptamine, respectively. Accordingly, the survival of these heatstroke rats was increased after brain dopamine or serotonin depletion. Furthermore, heatstroke-induced cerebral ischemia, neuronal damage and monoamine accumulation were attenuated by blockade of IL-1 receptor produced by treatment with an IL-1 receptor antagonist. The survival of the heatstroke rats was also increased after induction of heat shock protein. The results suggest that marked accumulation of either dopamine, serotonin or IL-1 in brain is important for the occurrence of heatstroke-induced cerebral ischemia and neuronal damage in rats. The survival of these heatstroke rats can be increased by inhibition of IL-1 receptors or monoamine system in brain as well as by induction of heat shock protein.

Animals↗

PubMed1997

Nitric oxide inhibition decreases neutrophil adhesion at the inflammatory site, while increasing adhesion in remote organs in peritonitis.

Nitric oxide (NO) is a regulator of leukocyte adhesion in the microcirculation. This study was designed to examine the effects of a NO synthase inhibitor on neutrophil adhesion in the peritoneum, lung, liver, and kidney in a rat peritonitis model using a fluorescence microscopic method. Sprague-Dawley rats were given normal saline (control) or N omega-nitro-L-arginine methyl ester (L-NAME) at dosages of 10 mg/kg (N10) or 100 mg/kg (N100) (n = 66) intraperitoneally. One hour after pretreatment fluorescein-labeled neutrophils were infused without bacterial challenge (0 hr). Other rats received an injection of 10(7) Escherichia coli into the peritoneal cavity 1 hr after pretreatment. Labeled neutrophils were infused 1 and 5 hr after bacterial challenge. Just 2 min after neutrophil injection, blood samples were obtained and the animals were killed. Five peritoneal samples (omentum, mesentery, parietal peritoneum, colon, and ileum), both lungs, the liver, and the right kidney were harvested for counting of labeled neutrophils under epifluorescent microscopy. Combined plasma nitrite/nitrate levels were determined. In another set of rats (n = 36), an arterial catheter was inserted after L-NAME treatment and bacterial challenge. At 0, 1, 5, and 12 hr after challenge, blood pressure, heart rate, and arterial blood gas data were measured. One hour after E. coli challenge, the number of neutrophils in the peritoneum was significantly lower in both L-NAME-treated groups than in the control group. In contrast, the number of labeled neutrophils in the lungs was significantly higher in the N100 group than in the control group. Neutrophil accumulation in the lungs and peritoneum at 0 and 5 hr and in the liver and kidney at 0, 1, and 5 hr did not differ among groups, nor did combined plasma nitrite/nitrate levels. L-NAME treatment had no influence on either hemodynamic or blood gas data. In conclusion, administration of L-NAME increases neutrophil adhesion in the lung, while decreasing that in the peritoneum. NO plays an important role in neutrophil adhesion at the inflammatory site, as well as in remote organs, during peritonitis. NO inhibition may be detrimental, due to neutrophil sequestration, in this peritonitis model.

Animals↗

PubMed1997

Hypoxia-induced differential electrophysiological changes in rat locus coeruleus neurons.

The effects of hypoxia on rat locus coeruleus (LC) neurons were investigated by intracellular recording from in vitro brain slices. In response to a brief exposure to hypoxic medium (2-5 min), equilibrated with 95% N2 - 5% CO2, two populations of cells could be distinguished, type 1 neurons (61%), showing hyperpolarization (9.3 +/- 0.4 mV, n = 125) and cessation of spontaneous action potentials, and type 2 neurons (39%), displaying gradual pure depolarization (6.0 +/- 0.3 mV, n = 80), instead of hypoxic hyperpolarization. Both types of response were associated with a reduction in membrane input resistance (34 +/- 1% for type 1 cells, n = 125, and 21 +/- 2% for type 2 cells, n = 68). While both types of neurons share similar electrophysiological properties, their membrane input resistance differ significantly (type 1 cells: 144 +/- 5 M omega, n = 125; type 2 cells: 183 +/- 9 M omega, n = 80, p < 0.001). These responses were compared to cyanide-induced chemical hypoxia. Cyanide (2 mM) induced the identical membrane response as effected by nitrogen hypoxia. All cells which responded to nitrogen-saturated hypoxic medium with a pure depolarizing response gave a similar response to cyanide and all neurons hyperpolarized by cyanide were also hyperpolarized by hypoxic medium. Moreover, the K(ATP) channel opener, diazoxide (1 mM), could mimic the hypoxia-induced hyperpolarization in type 1 neurons (10.6 +/- 0.9 mV, n = 18), but was unable to induce hyperpolarization in type 2 cells (n = 13). In addition, the N2-hypoxia-induced hyperpolarization was completely blocked by tolbutamide (200 microM, n = 8) or glibenclamide (3 microM, n = 9). These results indicate that a brief period of hypoxia evokes two different responses in LC neurons and this may be due to the heterogeneous distribution of K(ATP) channels among different LC neurons.

Animals↗

PubMed1997

Glutamine-enhanced bacterial killing by neutrophils from postoperative patients.

Neutrophils play an important role in host defense by phagocytosing and destroying invading bacteria. A recent investigation revealed that glutamine (Gln) augmented the in vitro bactericidal activity of neutrophils from burn patients. However, it is unclear whether Gln enhances the function of neutrophils in postoperative patients. This study was designed to investigate the effect of Gln on the in vitro Escherichia coli-killing activity of neutrophils from postoperative patients. Nine randomly selected patients were included in this study. On the morning of the first postoperative day, blood was drawn and neutrophils were isolated. Eight healthy volunteers served as controls. E. coli was opsonized with pooled normal serum. Neutrophils (5 x 10(6)), together with opsonized E. coli (5 x 10(5)), were incubated for 2 h at 37 degrees C in Hanks' balanced salt solution supplemented with 0, 100, 500, or 1000 nmol/mL of Gln. The bactericidal function of neutrophils was determined by counting the number of viable bacteria. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-8, and granulocyte elastase levels in the cell culture supernatant were measured. Plasma C-reactive protein (CRP), cortisol, and amino acids were also analyzed. The plasma concentration of Gln was significantly lower in the postoperative patients than in the controls. Following culture with patient neutrophils, the number of viable E. coli decreased by 26% as the in vitro Gln concentration was increased from 500 to 1000 nmol/mL (P < 0.01). We defined the Gln 1000/Gln 500 ratio of the number of viable bacteria as the number of viable E. coli at an in vitro Gln concentration of 1000 nmol/mL divided by the number of viable E. coli at an in vitro Gln concentration of 500 nmol/mL. A positive correlation was thus demonstrated between the plasma Gln level and the Gln 1000/Gln 500 ratio of the number of viable bacteria in the patients (r = 0.69, P = 0.04). This finding indicated that as plasma Gln fell, there was an enhancement of neutrophil E. coli-killing activity by neutrophils in in vitro tests when the Gln concentration was increased from 500 to 1000 nmol/mL. Gln supplementation caused no appreciable changes in TNF-alpha, IL-1 beta, IL-8, or granulocyte elastase levels in cell culture supernatants. A negative correlation was recognized between the patient plasma Gln level and the Gln 1000/Gln 500 ratio of the cell culture supernatant IL-8 level (r = -0.73, P = 0.025). In conclusion, Gln supplementation enhanced the in vitro bactericidal function of neutrophils from postoperative patients.

Adult↗

PubMed1997

Preoperative total parenteral nutrition influences postoperative systemic cytokine responses after colorectal surgery.

Previous human studies have investigated the influences of nutritional routes on the serum kinetics of cytokines following intravenous administration of lipopolysaccharide. However, it is unclear whether preoperative nutritional routes influence responses of systemic cytokines in patients after surgery. This study was designed to investigate whether preoperative total parental nutrition (TPN) influences systemic interleukin-6 (IL-6) and interleukin-8 (IL-8) responses in patients following surgery for colorectal cancer. Patients with colorectal cancer received TPN (TPN group, n = 6) or an oral diet (oral group n = 6) for more than 7 d before the operation. Patients in the TPN group received standard TPN. Patients in the oral group received an ordinary hospital diet. Blood samples were collected before the operation, on postoperative day 1 (POD1), POD3, and POD7. Levels of IL-6, IL-8, and C-reactive protein (CRP) in plasma were determined. The characteristics of patients in the TPN and oral groups were comparable. Mean carbohydrate intake was greater (28 versus 19 kCal/kg), and lipid intake was smaller (0 versus 7 kCal/kg) in the TPN group than in the oral group. Plasma CRP levels did not differ between the two groups. Plasma IL-6 and IL-8 levels were marginally higher before the operation and were significantly higher on POD1 in the TPN group than in the oral group. The IL-6 levels showed a positive regression relation with the amounts of blood loss only in the TPN group (P < 0.05, r = 0.881). The slope of the regression line was steeper in the TPN group than in the total enteral nutrition (TEN) group (P < 0.01). In conclusion, routes of nutritional supply have an impact on the production of systemic cytokines after insult. The postoperative systemic IL-6 and IL-8 responses in patients who received standard TPN preoperatively were greater than in patients who received an oral diet. Preoperative nutrition via the enteral route may provide better regulation of cytokine responses after surgery than parenteral nutrition.

Colorectal Neoplasms↗

PubMed1997

Clinical and biological characteristics of acute promyelocytic leukemia in Taiwan: a high relapse rate in patients with high initial and peak white blood cell counts during all-trans retinoic acid treatment.

Acute promyelocytic leukemia (APL) patients treated with all-trans retinoic acid (ATRA) and chemotherapy have been shown to have better outcome than those treated with conventional chemotherapy alone. However, the biological characteristics of leukemic cells and their clinical implications in patients treated with ATRA have not been well established. In this study, the biological and clinical features of 30 APL patients were reported. The risk factors for relapse and for occurrence of retinoic acid (RA) syndrome, which might cause morbidity or mortality of patients after ATRA treatment, were also analyzed. All patients showed 15;17 translocation by cytogenetic and/or gene analysis. Patients in this study had higher white blood cell (WBC) counts and a higher incidence of additional abnormalities than those from other areas. The ratio of long (L) form to short (S) form PML-RAR alpha fusion transcript was 1.8:1, a value lower than that of Latino patients but higher than that of Italians. Leukemic cells from four patients showed coexpression of T cell-associated antigen CD2 which was highly correlated with S form fusion transcript. Nine (36%) of the 25 patients treated with ATRA developed RA syndrome; all but one were successfully controlled by corticosteroid. Complete remission (CR) rate was 84%. Patients with high WBC counts tended to develop RA syndrome and had increased risk of relapse. Isochromosome for the long arm of the derivative chromosome 17, ider(17q), as an additional chromosomal abnormality was also associated with poor outcome in this study. In conclusion, APL in this study showed some different biological characteristics compared with those reported in other areas. High WBC count was a risk factor for relapse and development of RA syndrome after ATRA treatment. The prognostic implication of the presence of ider(17q) needs further clarification.

Adolescent↗

PubMed1997

The inducible lactose operator-repressor system is functional in the whole animal.

Mouse liver cell lines that bear a stably integrated lactose operon repressor (lacI) gene and a Ha-ras gene linked to a lactose operator-containing SV40 early promoter were generated. When grown in medium containing more than 0.1 mM isopropyl beta-D-thiogalactoside (IPTG), the Ha-ras gene was induced up to 20-fold. Maximum induction of Ha-ras gene expression occurred after 12 h of exposure. The tumorigenicity of these cell lines in syngeneic mice was enhanced when the mice were maintained on drinking water containing 12.5 mM IPTG. Ha-ras gene expression in tumors was strongly induced in the presence of IPTG in vivo. Induction of Ha-ras gene expression in mice was consistently observed after 48 hr of exposure to drinking water containing IPTG. This system provides an approach for studying the function of oncogene in vivo as well as other genes of interest.

Animals↗

PubMed1997

Alanylglutamine-enriched total parenteral nutrition improves protein metabolism more than branched chain amino acid-enriched total parenteral nutrition in protracted peritonitis.

Branched chain amino acids (BCAAs) and glutamine are both recommended in catabolic states. The object of this study was to compare the efficacies of alanylglutamine (Ala-Gln)-enriched and BCAA-enriched total parenteral nutrition (TPN) on the protein kinetics in peritonitis. Rats were divided into Ala-Gln and BCAA groups after intraperitoneal implantation of an osmotic pump, delivering a continuous infusion of Escherichia coli. Glutamine composed 30.0% (w/v) of the total amino acids in the Ala-Gln group, and BCAA composed 30.5% (w/v) of the total amino acids in the BCAA group. The two solutions were isocaloric and isonitrogenous. Whole body protein turnover and organ fractional protein synthetic rates (FSR) were measured on days 3 and 5. Serum amino acid levels and mucosal morphology were determined. Ala-Gln group had higher rates of whole body protein turnover, and hepatic FSR on both days. Serum glutamine levels correlated with hepatic and muscle FSR. Ala-Gln TPN group had greater mucosal thickness, numbers of mitoses per crypt, and FSR in distal intestine. Ala-Gln-enriched TPN may be a useful nutritional treatment modality in sepsis.

Amino Acids↗

PubMed1997

Interleukin-1 and tumor necrosis factor alter plasma concentration and interorgan fluxes of taurine in dogs.

We examined the effects of interleukin-1 beta (IL-1), tumor necrosis factor (TNF), and alanylglutamine (Ala-Gln) infusion on the plasma concentrations and interorgan fluxes of taurine and taurine precursors, including methionine and serine, using chronically catheterized awake dogs. In the first study, the dogs received 5 micrograms/kg/h of either human recombinant IL-1 or TNF intravenously for 2 h. Taurine fluxes in the liver and gut were calculated by blood flows and arteriovenous differences during infusion and for 2 h after discontinuation of the cytokine infusions. The 2 h continuous infusions of TNF and IL-1 resulted in 60 and 90% increases, respectively, in the arterial plasma taurine concentration. Hepatic taurine flux changed from uptake to release after 2 h of continuous IL-1 infusion. In the second study, we investigated whether Ala-Gln infusion affects taurine metabolism under normal and stress conditions. The dogs were given a constant 2 h intravenous infusion of IL-1 or saline. Ala-Gln (6 mumol/kg/min) was infused simultaneously during the second hour. Plasma concentrations and fluxes, across the liver, gut, and lung, of taurine and taurine precursors were studied. IL-1 administration increased the plasma concentration, hepatic release, and lung uptake of taurine. Ala-Gln infusion did not affect either plasma concentrations or organ fluxes of taurine. These data suggest that cytokines play a role in taurine metabolism under stress conditions.

Alanine↗

PubMed1997

Staphylococcal enterotoxin A-induced fever is associated with increased circulating levels of cytokines in rabbits.

Rabbits were injected intravenously with 10 to 100 ng of staphylococcal enterotoxin A (SEA) per kg, and colonic temperatures were monitored. The febrile responses were compared with circulating levels of interferon (IFN), tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-2, and IL-6 just before the injection of SEA. Both colonic temperatures and circulating levels of IFN, TNF, and IL-2 started to rise at 1 to 2 h and reached their peak levels at 3 to 5 h after SEA injection. Both the fever and the increased circulating levels of IFN, TNF, and IL-2 produced by SEA were decreased by pretreatment with indomethacin (a cyclo-oxygenase inhibitor) (15 mg/kg, intraperitoneally), anisomycin (a protein synthesis inhibitor) (15 mg/kg, subcutaneously), or dexamethasone (an effective anti-inflammatory and immunosuppressive agent) (4 mg/kg, intravenously) in rabbits. Rabbits were injected intravenously with 30 ng of SEA per kg on four consecutive days, and colonic temperatures were monitored. Compared to rabbits that received the single injection of SEA, rabbits that received four consecutive injections of SEA showed a lesser increase in circulating levels of IFN, TNF, and IL-2 as well as colonic temperatures in response to an intravenous dose of SEA (30 ng/kg). The data suggest that the prevention of the febrile response elicited by SEA by indomethacin, anisomycin, or dexamethasone is due to prevention by these compounds of the increase in the circulating levels of IFN, TNF, and IL-2. The pyrogenic hyporesponsiveness to repeated injection of SEA is associated with decreased production of these circulating cytokines.

Animals↗

PubMed1997

Mouse hepatitis virus is cleared from the central nervous systems of mice lacking perforin-mediated cytolysis.

Perforin-deficient [perforin (-/-)] mice were infected with two strains of JHM virus (JHMV) to analyze the role of perforin-mediated cytotoxicity in acute lethal and subacute central nervous system (CNS) infections. During both acute and subacute infections, the overall mortality of the perforin (-/-) mice was not different from that of the controls. Perforin (-/-) mice survived longer than the controls, consistent with reduced morbidity. Both strains of virus were cleared from the perforin (-/-) mice as in the controls; however, the rate of clearance was delayed in the perforin (-/-) mice, indicating that perforin-mediated cytolysis is involved in viral clearance. The absence of perforin-mediated cytolysis did not prevent encephalomyelitis or extensive demyelination. Cells undergoing apoptosis were detected in the CNS of both the perforin (-/-) and control groups, indicating that perforin is not essential for programmed cell death. Neutralizing antibodies were not detected in either group of mice until day 9 postinfection, when the majority of the virus had been cleared. These data further confirm the importance of cell-mediated cytotoxicity and suggest that additional components of the immune response contribute to the clearance of JHMV from the CNS.

Animals↗

PubMed1997

Involvement of interleukin-1 receptor mechanisms in development of arterial hypotension in rat heatstroke.

Rats, under urethan anesthesia, were exposed to a high ambient temperature (42 degrees C) to induce heatstroke and to assess the hemodynamic changes associated with heatstroke. Compared with normothermic controls, rats with heatstroke showed higher values of colonic temperature, heart rate, and plasma levels of interleukin (IL)-1 but lower values of R wave amplitude, P-R and Q-T intervals, systolic wave amplitude, diastolic and dicrotic wave duration, mean arterial pressure, stroke volume, and cardiac output. Animals injected intravenously with an IL-1-receptor antagonist at the time of heatstroke induction were protected from some of the cardiovascular effects of heatstroke, such as depressed ventricular depolarization, decreased stroke volume, decreased cardiac output, and arterial hypotension. The hemodynamic changes associated with heatstroke could be mimicked by IL-1beta administration. Other cardiovascular parameters such as total peripheral vascular resistance were unaffected by heatstroke induction or IL-1beta treatment. The results indicate that a selective decline in stroke volume or ventricular depolarization resulting from increased plasma levels of IL-1 may be an important mechanism signaling arterial hypotension or circulatory failure in rat heatstroke.

Animals↗

PubMed1997

Molecular subtyping of human T-lymphotropic virus type I (HTLV-I) by a nested polymerase chain reaction-restriction fragment length polymorphism analysis of the envelope gene: two distinct lineages of HTLV-I in Taiwan.

The major type of human T-lymphotropic virus type I (HTLV-I), generally referred to as the cosmopolitan type, has been grouped into three subtypes (A, B, and C) by phylogenetic analysis of the long terminal repeat sequences of the viral genome. Twelve subtype-specific nucleotide variations have been deduced by comparison between the envelope (env) sequences of 16 HTLV-I strains with defined subtypes and 9 Taiwanese HTLV-I strains. To gain further insights into the molecular epidemiology of HTLV-I and the origin of this virus in Taiwan, a rapid method of identification for the cosmopolitan subtypes was developed by using a nested polymerase chain reaction (PCR) and subsequent restriction fragment length polymorphism (RFLP) studies using the two subtype B-specific and four subtype C-specific nucleotides located within the positions 5708 to 6320 of the envgene. The nested PCR-RFLP method was used to subtype HTLV-I from four virus-positive cell lines derived from 1 Japanese and 3 North American patients, as well as 41 blood-unrelated Taiwan Chinese. The sequences of PCR products were determined and the six positions of subtype-specific nucleotide variations were examined. The sequence data completely supported the subtyping data via the nested PCR-RFLP method. The results demonstrated that, as is the case in Japan, at least two distinct cosmopolitan subtypes (A and B) of HTLV-I were present in Taiwan, but the more prevalent subtype in Taiwan is A in contrast to subtype B in Japan. Furthermore, rapid subtyping could facilitate molecular epidemiological studies of HTLV-I infection and linkage between HTLV-I subtypes and virus-associated diseases.

Base Sequence↗

PubMed1997

MVP (mitomycin-C, vinblastine, cisplatin) salvage chemotherapy for relapsed and refractory metastatic breast cancer.

Salvage chemotherapy for relapsed and refractory metastatic breast cancer is a challenging issue for oncologists. At our institution, the combination of mitomycin-C, vinblastine and cisplatin (MVP) is used for treatment. The records of 19 consecutive patients with refractory metastatic breast cancer treated with MVP between April 1992 and October 1995 were reviewed. The regimen consisted of mitomycin-C 6 mg/m2, vinblastine 6 mg/m2 and cisplatin 60 mg/m2, repeated every 3 to 4 weeks. The median age of patients was 49 years (range, 35-71 yr). All patients had clinically measurable or evaluable disease and a Karnofsky's performance status greater than or equal to 50%. The median number of prior chemotherapy regimens was two (range, 1-4). Eighteen (94.7%) patients had previously received an anthracycline/anthracenedione-containing regimen, and seven (36.9%) had progression of disease during these therapies. Sixteen patients had two or more sites of metastasis and 17 patients had visceral disease. The median duration of follow-up was 26 months. A mean of 3.5 courses (range, 1-7) was administered. One patient was lost to follow-up after one course of treatment. Of the remaining 18 patients, two complete and five partial responses were observed, for a total response rate of 37% (range, 17-61%, 95% CI). One of the partial responders had disease progression during anthracycline treatment. Treatment-related toxicities were relatively well tolerated. There were no treatment-related deaths. The median duration of response was 3 months (range, 2-11 mo). The median overall survival was 7 months (range, 1-32 mo). Our data suggest that the MVP regimen is an effective palliative treatment for patients with refractory metastatic breast cancer.

Adult↗

PubMed1997

Human T-lymphotropic virus type II infection in Vietnamese thalassemic patients.

Anti-human T-lymphotropic virus type I/II (HTLV-I/II) antibodies were screened by particle agglutination test in a total of 66 patients with thalassemia major who received multiple transfusion from paid donors at the Blood Transfusion Hematology Center of Ho Chi Minh City in South Vietnam. HTLV-II infection was confirmed in 6 patients (9.1%) by Western blot analysis and/or polymerase chain reaction. Phylogenetic analysis revealed that long terminal repeat sequences of HTLV-II proviruses from 5 thalassemic patients in Vietnam belonged to the same phylogenetic subgroup of HTLV-IIb as those from intravenous drug abusers in North America and Europe. These data shed light on the route of introducing HTLV-II into Vietnam.

Adolescent↗

PubMed1996

Picrotoxin induces both hypertension and dopamine release in the rat amygdala.

The effects of the epileptogenic agent, picrotoxin, on both the cardiovascular responses and the dopamine (DA) release in the amygdala were studied in anesthetized rats. In vivo voltammetry was used to measure change in extracellular concentrations of DA and its metabolites in the amygdala. Intravenous administration of picrotoxin produced hypertension, increased amygdaloid DA release and behavioral syndromes (such as increased masticatory movements, salivation, and forepaw tremors). Direct administration of picrotoxin into the amygdala also induced the same effects. The picrotoxin-induced effects were suppressed by activation of gamma-aminobutyric acid (GABA) receptors with diazepam or depleting brain DA with 6-hydroxydopamine. Blockade of central DA receptors with haloperidol also attenuated the picrotoxin-induced hypertension. These results indicate that picrotoxin affects interactions between GABA neurons and DA system in rat brain to induce hypertension during an epileptic attack.

Amygdala↗