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Biomedical subjects

T Liu

Publications and source records attributed to T Liu.

At least 433 records · Page 24Linked to original sources

Response to transcatheter oily chemoembolization in hepatocellular carcinoma 3 cm or less: a study in 50 patients who underwent surgery.

The response of 50 patients who underwent hepatectomy for hepatocellular carcinoma measuring 3 cm or less (at the time of surgery) to transcatheter oily chemoembolization was evaluated. The response was assessed in 5 categories, A: complete necrosis (100%), B: necrosis of at least 95%, C: at least 80%, but less than 95%, D: at least 50% but less than 80%, and E: less than 50% of the tumor cells. Response A was observed in 19 patients (38%), B in 7 (14%), C in 9 (18%), D in 7 (14%), and E in 8 (16%). These results were classified with respect to the histological degree of tumor differentiation, the WHO histological classification, the microscopic patterns of tumor growth, and macroscopic classification. The response was evaluated in relation to the histological grade of tumor differentiation and the WHO histological classification in all categories of response except response A, and there was no significant difference between the categories. The response was obviously better with the expansive type than with the replacing type. Single nodular type lesions were more responsive than the single nodular type lesions with extranodular growth and the contiguous multinodular type. Pretreatment estimation of the microscopic patterns of tumor growth and macroscopic classification appears to be valuable in predicting prognosis.

Adult↗

Phase I trial of the murine monoclonal anti-GD2 antibody 14G2a in metastatic melanoma.

In a phase I trial, 12 patients with GD2 antigen-positive metastatic melanoma received the murine anti-GD2 monoclonal antibody 14G2a. The monoclonal antibody was administered in four doses over an 8-day period with total dose ranging from 10 to 120 mg. All patients receiving greater than 10 mg of 14G2a experienced transient abdominal/pelvic pain during the antibody infusion. Five patients had a delayed extremity pain syndrome following the third and fourth antibody infusion. Four of the five patients developed neurological toxicity, including two patients with significant although reversible motor neuropathy. Two of the patients developed hyponatremia secondary to a syndrome of inappropriate antidiuretic hormone. All 12 patients developed high levels of human anti-14G2a antibody. The plasma half-life of 14G2a was 42 +/- 6 (SD) h. One patient each had a partial response, mixed response, and stable disease, respectively. The very modest antitumor activity accompanied by dose-limiting neurological toxicity at total doses greater than 80 mg may restrict the clinical utility of murine 14G2a.

Antibodies, Monoclonal↗

Use of radiation with or without WR-2721 in advanced rectal cancer.

One hundred patients with inoperable, unresectable, or recurrent adenocarcinoma of the rectum were stratified and randomized to WR-2721 plus radiation therapy (WR + RT) or radiation therapy (RT) only treatment arms. The protector, WR-2721, was administered at a dose of 340 mg/m2 15 minutes before RT, 4 days a week for 5 weeks. The entire pelvis received 225 cGy per fraction for a total of 4500 cGy. The RT only group received the same treatment schedule. After this, both groups received a conedown of 720 cGy in 4 fractions. Inoperable and unresectable cases received a second conedown of 720 cGy. No moderate or severe pelvic normal tissue late effects were seen in the 34 evaluable patients in the combination group. However, in the RT only group, 5 of 37 evaluable patients exhibited late effects of moderate or severe degree. This difference was statistically significant (P = 0.03). There was no evidence of tumor protection by WR-2721. Sixteen percent of patients randomized to the WR + RT group had a complete response compared with 10% in the RT only group. The conditions of 12 patients of 100 became operable and 8 were resected. Seven of these patients remain free of recurrence.

Adult↗

Expression of human alpha 1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes.

The liver represents an excellent organ for gene therapy since many genetic disorders result from the deficiency of liver-specific gene products. We have previously demonstrated that transgenic mouse hepatocytes can be heterologously transplanted into congenic recipients where they survived indefinitely and continued to function as hepatocytes. Here we demonstrate the autologous transplantation of retrovirally transduced canine hepatocytes. At least 1 x 10(9) hepatocytes or 5% of the liver mass can be transplanted by the portal vasculature. In two animals we have transplanted hepatocytes transduced with a retroviral vector containing the human alpha 1-antitrypsin cDNA under transcriptional control of the cytomegalovirus promoter. Both animals had significant human alpha 1-antitrypsin in the serum for 1 month. Although the serum levels of human alpha 1-antitrypsin eventually fell due to inactivation of the cytomegalovirus promoter, PCR analysis demonstrated that a significant fraction of transduced hepatocytes migrated to the liver and continued to survive in vivo. The results suggest that gene therapy of hepatic deficiencies may be achieved by hepatocellular transplantation after genetic reconstitution with the use of promoters of cellular genes that are active in the normal liver.

Animals↗

Frequent anti-V-region immune response to mouse B72.3 monoclonal antibody.

The immune response of 56 colorectal cancer patients to a single infusion of 1 mg of radiolabeled (111In) mouse B72.3-GYK-DTPA immunoconjugate was examined using a double-antigen radiometric assay system. The incidence of antibody response was 48% to polyclonal mouse IgG, 71% to mouse B72.3, and 62% to chimeric B72.3. Twelve patients (23%) had an antibody response to B72.3 V region in the absence of binding to polyclonal mouse IgG. An antiidiotype response was demonstrated in sera from 36% of 25 patients examined and correlated well with chimeric B72.3-GYK-DTPA immunoconjugate binding (r = 0.72, moderately well with mouse B72.3 binding (r = 0.56), and not at all with polyclonal mouse IgG binding (r = 0.28). The peak antibody response occurred most frequently 2 weeks postinfusion, although a "delayed" peak response to chimeric B72.2 occurred in 29% of patients. This study suggests that mouse B72.3 causes an immune response in the majority of patients and that antibody response to the V region is common. Understanding the physiological significance of these antibody responses will require correlation with the kinetics and tumor localization of repeat infusions of such immunoconjugates.

Animals↗

An improved technique for isolated perfusion of rat livers and an evaluation of perfusates.

We have modified the apparatus for isolated rat liver perfusion (IPRL) in order to be able to perform two perfusions simultaneously. In addition, we studied the quality and stability of livers by comparison of five different perfusates: Blood (Group A), Original Krebs Henseleit buffer (Group B), Krebs buffer with glucose (Group C) or bovine serum albumin (BSA) added, (Group D). In a last group (E) albumin, glucose, and taurocholic acid were added to Krebs. After 180 min of perfusion, livers perfused with solutions including 2% albumin (Group D, E) had a significantly higher release of hepatocellular and endothelial cell (purine nucleoside phosphorylase) enzymes and lower bile production as compared to Groups A, B, and C (P less than 0.0001). Increasing levels of purine nucleoside phosphorylase (PNP), a reflection of damage to the microvascular endothelium preceded the increases in hepatocellular enzymes. Histologically, damages of sinusoidal endothelial cells and hepatocytes are appreciated moderate to severe in Groups D and E, slight to mild in Groups A and B, and not significant in Group C. These results suggest that BSA may have toxic effects to the perfused rat liver. These data also confirm that the IPRL modified for simultaneous perfusion of two livers is efficient, and that with this technique the rat liver can be optimally perfused for up to 3 hr with oxygenated Krebs Henseleit buffer without additives (Group B) and without blood. These two improvements should allow those performing studies with perfused rat livers to obtain data in a more efficient, accurate, and inexpensive fashion.

Animals↗

Interim analysis of a randomized trial of radiation therapy of rectal cancer with/without WR-2721.

The objectives of this randomized trial are to define the maximum tolerated dose of radiation therapy, at curative dose levels, that can be delivered following WR-2721, and to observe the anti-tumor effects and normal tissue responses. One hundred patients with inoperable, unresectable, or recurrent rectal cancer were stratified and randomized to radiation only, or WR-2721 and radiation. The entire pelvis is treated with 4 portals 4 times a week to a total of 4500 cGy (first level dose) in 5 weeks. WR-2721, 340 mg/m2 was given 15 minutes before radiation to the combination group. Subsequently, both groups received a conedown of 720 cGy in 4 days to 144(2) cm portals APPA, and if originally inoperable or unresectable 720 cGy in four days to second conedown of 64(2) cm. Patients were observed from 3 to 18 months (median = 12 months). No significant hypotension or hematologic toxicity occurred in the WR-2721 treated group. Mild to moderate emesis occurred in 80% of the courses. (No antiemetics were used.) Moderate or severe acute toxicities to normal tissues were observed less frequently in the WR-2721 arm. No moderate or severe late toxicities to the skin, mucous membrane, urinary bladder or intestine was observed in the WR-2721 group, however, 5 patients treated with radiation alone experienced moderate or severe late toxicity to these organs. No evidence of tumor protection was observed.

Adenocarcinoma↗

Inducible expression of calmodulin antisense RNA in Dictyostelium cells inhibits the completion of cytokinesis.

The single gene encoding calmodulin in the eukaryotic microorganism Dictyostelium discoideum was cloned and sequenced. The gene was found to contain three introns, one lying immediately after the translation initiation codon. The deduced amino acid sequence indicated that Dictyostelium calmodulin contains 19 amino acid differences from vertebrate calmodulin, including extensions at both termini. Northern blot analysis showed that similar levels of calmodulin mRNA are present throughout growth and development of wild-type cells. A complete copy of the calmodulin cDNA was prepared, and an 87-base pair fragment complementary to the 5'-end of the calmodulin mRNA was subcloned into the Dictyostelium transformation vector pVEII, such that expression of the antisense transcript was driven by the discoidin I gamma promoter. Transformed cells were selected and maintained at low cell density, a condition resulting in minimal activity of the discoidin I promoter. High level expression was induced by allowing the transformants to reach high cell density or by growing them in the presence of medium conditioned by high density cells. Under these conditions, in which calmodulin mRNA and protein levels were reduced about twofold, the calmodulin antisense transformants lost the ability to complete cytokinesis. A contractile ring formed and constricted, but the midbody linking daughter cells failed to break. The resulting cell population contained multinucleated cells and networks of cells connected by cytoplasmic bridges. Normal cell division was restored when the cells were diluted to low density. These observations have identified a new point at which calmodulin may regulate cell cleavage.

Amino Acid Sequence↗

Evaluation of three nutritional assessment methods in a group of women.

We conducted a reproducibility study of four 24-hour dietary recalls (N = 224) and four biochemical assessments of nutritional status (N = 265) in a group of women in Alabama. For 24-hour recalls, the variance component ratios were all greater than 1, and the intraclass correlation coefficients ranged from 0.16 to 0.27 for macronutrients, and from 0.09 to 0.37 for vitamins and minerals. The intraclass correlation coefficients for biochemical assessments ranged between 0.39 and 0.74 with corresponding variance component ratios of 1 or below for most nutrients. The correlation coefficients between the food frequency questionnaire on the usual dietary intake during the year preceding the beginning of study and the mean values of four 24-hour dietary recalls administered at the initial visit and again after 2, 4, and 6 months ranged from 0.3 to 0.4 for most nutrients. We found plasma beta-carotene levels to be moderately correlated with dietary vitamin A (r = 0.20) and beta-carotene (r = 0.22).

Adult↗

Ontogeny of intestinal lactase: posttranslational regulation by thyroxine.

To assess the molecular mechanisms underlying the regulation of lactase ontogeny by thyroxine (T4), we performed an in vivo study of lactase catalytic activity, synthesis, subunit structure, degradation, and enterocyte migration rates in propylthiouracil-induced hypothyroid rat pups, hypothyroid pups injected with T4, and normally weaned rats. Although lactase catalytic activity remained elevated in the hypothyroid rats and declined normally in the other two groups, lactase synthesis was constant among the groups. Lactase subunit structure was identical in normally weaned and T4-injected animals, but the 100-kDa moiety, characteristic of weaned rats, was absent in the hypothyroid pups. The turnover of lactase enzyme was more rapid in euthyroid and T4-injected rats than in hypothyroid animals (t1/2 = 17, 20, and 30 h, respectively). In addition, enterocyte migration was accelerated in the T4-injected rats and reduced in the hypothyroid group compared with controls. However, transit rate was not directly related to lactase activity. Our results suggest that T4 regulates lactase ontogeny by posttranslational mechanisms that include altered processing and increased degradation of the lactase enzyme.

Animals↗

[Experimental study of tumor directed therapy with gastric cancer monoclonal antibody-mitomycin conjugate combined with propranolol or angiotensin II].

The effects of vasoactive agents propranolol hydrochloride and angiotensin (AT-II) on improving the directed therapy of cancer with the use of conjugate of gastric cancer monoclonal antibody (3H11) and mitomycin C (MMC) were studied. The antibody activity of the conjugate (3H11-HSA-MMC) was retained with the molecular ratio of 1:2:60. In tests with tumor-bearing nude mice, the tumor inhibitory rate of the conjugate alone was found to be 50%, while in conjugate treated mice that also received propranolol or AT-II the tumor inhibitory rate were 79% and 60%, respectively. In tumor-bearing nude mice given 131I-3H11 both propranolol and AT-II increased the tumor uptake of 131I-3H11. These results indicate that these vasoactive agents can change the tissue perfusion ratio via the effect on tumor blood vessels and increase the access of the conjugate to tumor, thereby, enhancing the effectiveness of tumor directed therapy with the use of conjugates.

Angiotensin II↗

[The antitumor effect of adriamycin conjugated with monoclonal antibody against gastric cancer in vitro and in vivo].

Adriamycin (ADM), an anthracycline cytotoxic agent, was conjugated with monoclonal antibody 3H11 against gastric cancer via the dextran bridge method. The conjugate 3H11-DEX-ADM, with molar ratio of 3H11 to ADM being 1:73, retained antibody activity to 86%. In the cytotoxicity assay, 3H11-DEX-ADM was shown to exhibit increased cytotoxicity against the target cell line BGC 823. Its IC50 was 3.75 fold less than that of free ADM. The antitumor effect of the conjugate was evaluated in tumor-bearing nude mice. The results indicate that the specific antibody conjugate 3H11-DEX-ADM can significantly inhibit the tumor growth. At the dosage level used in the present study (5 micrograms/mouse x 6), 3H11-DEX-ADM showed an inhibition rate of 51.5%, whereas only moderate inhibition rates were observed with free ADM and the control conjugate NIgG-DEX-ADM. In addition, experiment was performed to evaluate the combined cytotoxicity of 3H11-DEX-ADM and the conjugate of mitomycin C (3H11-HSA-MMC) at different ratios. It was shown that the combination has no synergistic effect when their IC50 was compared with that of the two conjugates used alone. The same result was observed on combinations of the two corresponding free drugs.

Animals↗

Dose fractionation of radiolabeled antibodies in patients with metastatic colon cancer.

Twelve patients with metastatic colon cancer were treated with 131I-chimeric B72.3 (IgG-4) at total doses of 28 or 36 mCi/m2 in two or three weekly fractions. Bone marrow suppression was the only significant side effect. The degree of bone marrow suppression adjusted for whole-body dose was modestly but statistically significantly (p = 0.04) less than that seen with identical doses given as a single infusion for the total dose of 36 mCi/m2. Nine of twelve patients developed an antibody response to ch B72.3, which altered the kinetics of radiolabeled antibody in four patients given a second course of therapy. One patient had a minor response that lasted 4 mo. Fractionation of this particular radiolabeled antibody at the dose schedule used produced a modest increase in the therapeutic window in regard to administered dose.

Adult↗

[Endothelium contributes to the decreased aortic contractility in response to norepinephrine in experimental septic rats].

The responses to norepinephrine of thoracic aortic rings from septic and sham operated rats were compared. Rings with endothelium taken from septic rats manifested significantly lower maximal contractile response to norepinephrine (575 +/- 46.1 mg) in comparison with sham operated tissues (775 +/- 54.7 mg). Tissues without endothelium showed no significant difference. The results suggest that the diminished responsiveness to norepinephrine of the thoracic aorta in septic rats is mediated, at least in part, by vascular endothelium.

Animals↗

[Study on relativity of sudden death from CHD to risk factor of cardiovascular disease].

The relativity of the incidence rate of sudden death from coronary heart disease (CHD) among 2,990,816 people from 1985 to 1989 and the risk factor of cardiovascular disease was studied. The result showed that the crude incidence rate of sudden death from CHD was 12/100,000, standardized incidence rate 11.1/100,000 (according to the population in 1982), 9.5/100,000 (according to the population in 1964), was positive correlation with the mean level of blood pressure, prevalence rate of hypertension, total cholesterol in serum, Quetiele index of weight, rate of smoking, finding rate of abnormal ECG and prevalence rate of cardiovascular disease (r = 0.79-0.99, P less than 0.01); and was negative correlation with the level of HDL-TC (r = -0.81, P less than 0.01).

Adult↗

[Anorexia nervosa with bulimia and self-provoked-vomiting (a case report)].

A young female anorexia nervosa patient reported who was undigested with food, weight dropped to half of the normal standard. She manifested not only episodic bulimia, impulsive self-injury, suicidal attempt, and obvious depressive emotion; but also self-provoked-vomiting, wandering, stealing and lying. The course of disease lasted already three years, she got 37 points on Hamilton Depressive Scale. Positive DST and normal EEG were exhibited in lab tests. The patient was improved after comprehensive therapy for about 5 months and then discharged. The recent literatures were reviewed on epidemiology, etiology, clinic features, therapy, prognosis and its relationship with depression.

Adult↗