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Biomedical subjects

T T Wu

Publications and source records attributed to T T Wu.

At least 127 records · Page 7Linked to original sources

Evolution of expression of hepatitis B surface and core antigens (HBsAg, HBcAg) in resected primary and recurrent hepatocellular carcinoma in HBsAg carriers in Taiwan. Correlation with local host immune response.

Studies were conducted on the evolution of hepatitis B virus (HBV) surface and core antigens (HBsAg and HBcAg) in the tumors of both primary and recurrent hepatocellular carcinoma (HCC) in 27 HBsAg carriers; these were followed for up to 8 years after the resection of the primary tumor. Twenty-seven primary and 34 recurrent tumors were included. HBV antigens were detected in the tumor of the primary HCC in ten cases (37%): six (22.2%) had both antigens (Group I) and four (14.8%) had HBsAg alone (Group II). The remaining 17 cases were negative for both antigens (Group III). Intrahepatic tumor recurrence occurred in 17 cases; both HBcAg and HBsAg were found in the recurrent HCC in four of five HBcAg-positive cases (Group I). In contrast, HBcAg was detected in none of the other 12 cases (Group II, 0 of one; Group III, 0 of 11), and HBsAg in only one (Group II, 0 of one; Group III, one of 11), P less than 0.03 and P less than 0.02, respectively. Groups I, II, and III had extrahepatic recurrence in two, four, and seven cases, respectively. HBcAg was detected in none, while HBsAg was found in only one case (7.7%). The frequent detection of both antigens in the primary HCC and even in the intrahepatic recurrences suggests that HBV replication in HCC may occur more commonly than previously perceived, especially in the small HCC. Failure to detect HBV antigens in the extrahepatic recurrences suggests that the switch-off of the viral gene expression, particularly the core gene, may be an event related to the extrahepatic growth of HCC. HBV antigen expression in HCC is associated with more evident lymphocyte infiltration; this local host immune response may in turn result in a negative selection and expansion of the antigen-negative HCC cell clones. This suggestion is in accord with the fact that HBV antigens, particularly HBcAg, are rarely detected in advanced HCC.

Carcinoma, Hepatocellular↗

Tumor invasiveness and prognosis in resected hepatocellular carcinoma. Clinical and pathogenetic implications.

In order to elucidate the biologic behavior of hepatocellular carcinoma (HCC), the long-term prognostic impact of the pathologic features of 143 surgically resected HCC were studied. Seventy-four were smaller than 5 cm in diameter (small HCC), and 69 were larger (large HCC). This study confirmed that tumor size was an important but not the only determining prognostic factor in HCC. Although cirrhosis could cause hepatic failure, patient mortality was mainly attributable to tumor recurrence, which, in turn, was strongly correlated with the invasive nature of HCC. Tumor invasion to the liver and the intraportal spread were very frequent and particularly extensive in large HCC. In both small and large HCC the noninvasive groups not only had high 4-year actuarial survival (84.6% and 90%, respectively), but there was also no patient mortality from intrahepatic tumor recurrence. Therefore, it was concluded that invasiveness of an HCC is the most crucial factor in determining the long-term outcome for the patient, and that the clinical course of resected HCC is predictable in a great majority of the cases. In our small HCC series only 2.4% of HCC were regarded as having true multicentric origin. These findings suggest that the majority of HCC occur unicentrically, and that multiplicity and tumor recurrence result mostly from intrahepatic dissemination. In both small and large HCCs invasive tumors were accompanied by high patient mortality from tumor recurrence even when the tumor was small, indicating that intrahepatic spread may start very early during the growth of HCC.

Carcinoma, Hepatocellular↗

Matching nucleotide sequences of human antibodies with other known sequences.

From an evolutionary point of view, the complementarity-determining regions of antibodies are distinct from other proteins including the framework regions of antibodies. A search for identical nucleotide sequences of eighty-four 15 consecutive bp in the complementary-determining regions of human antibody heavy chains with other known sequences yielded four matches: two sequential 15-bp matches, or one 16-bp match, with the coding region of a sea-urchin testis histone H2b-2, one 15-bp match with the promotor region of a cauliflower mosaic virus inclusion body protein, and a 15-bp match with an intron between exons 1 and 2 of human factor IX. As a control, an identical search of eighty-four 15 consecutive bp in the framework regions of human antibody heavy chains yielded no matches with other sequences except those from other antibody framework regions. Since the currently available nucleotide sequence database used in the search consisted of about 1 x 10(7) bp, finding such matches in the complementarity-determining regions might not be random.

Antibodies↗

Clearance of hepatitis B surface antigen (HBsAg) after surgical resection of hepatocellular carcinoma.

The serum HBsAg in 4 chronic HBsAg carrier patients with hepatocellular carcinoma (HCC) cleared within 4-38 months after surgical resection of their hepatic tumors. Two patients developed anti-HBs. During the follow-up period from 21 to 28 months after HBsAg clearance, none of the patients regained positive serum HBsAg. Two patients who had had tissue HBsAg present, exclusively in the tumor, showed quick HBsAg clearance after resection. The other 2 patients had a delayed HBsAg clearance. One had tissue HBsAg in both the tumor and nontumoral liver. Only 1 patient had tissue HBsAg in the liver, but not in the tumor. During the same period of observation of 323 chronic HBsAg carriers, who had a variety of histologically-verified chronic liver diseases and were followed for more than 6 months, only 1 cleared the antigen. The spontaneous HBsAg clearance in our HBsAg carriers (1/323) was significantly lower than that (4/64) of HBsAg-positive HCC patients with tumor resection, P less than 0.004. The mechanisms of HBsAg clearance in HCC patients after surgical resection of tumors are discussed.

Aged↗

Subgroups of variable region genes of beta chains of T-cell receptors for antigen.

The beta-chain variable regions of 6 human, 21 mouse, and 1 rabbit T-cell receptors for antigen, including two pairs of duplicates, have been classified into two subgroups. Subgroup I has an invariant Phe at residue 65 and a salt bridge can be formed between the Asp at position 86 and the 11 Arg, 2 Lys, and 1 His residues at position 64. In one instance Tyr replaces Asp at position 86 so that a salt bridge cannot be formed with the Lys at position 64. Subgroup II has an invariant Tyr at residue 65; 8 chains have Gly and 3 have Ala at position 63. These 3 have Asp at position 64. Those with Gly-63 cannot form a salt bridge in this region of the beta chain. The 3 with Asp-64 have Arg at position 86, can form a reverse salt bridge, and could constitute a third subgroup. The relation of these findings to functional parameters in beta chains of the T-cell receptors for antigen deserves further study. The use of variability plots on the assumption that the beta chains are a single population may be misleading for the variable region. Most of the variability in the expressed beta chains would be created by variable-diversity-joining assortment, junctional diversity, and the possible insertion of N sequences.

Amino Acid Sequence↗

Possible involvement of human D minigenes in the first complementarity-determining region of kappa light chains.

The nucleotide sequences of the complementary strands of two human diversity region (D) minigenes, D2 and D4, show stretches of homology with two human variable region kappa chain (V kappa) genes, NG9 and HK101, respectively, in the first complementarity-determining region. In one V kappa sequence, the homology includes the 5' flanking region of D minigenes, which may comprise a recombinase recognition signal. It is thus conceivable that gene conversions involving D minigenes may contribute to V kappa diversity.

Antibody Diversity↗

[Hyperdynamic state induced by continuous infusion of E. coli endotoxin in dogs].

It is well established that septic shock is caused by Gram-negative endotoxemia, and is characterized by hyperdynamic state being observed in the early stage of shock. This study is designed to elucidate the hemodynamic and metabolic changes induced by continuous infusion of small amount of endotoxin in the dog, with special reference to the existence of hyperdynamic state. Seven mongrel dogs were continuously infused with 10 micrograms/kg/day of E.coli endotoxin for 4 days under fasted, awake condition. All animals revealed mild hypodynamic state with severe catabolic responses in protein-energy metabolism. In contrast, 11 dogs infused with 36kcal/kg/day of glucose and 10 micrograms/kg/day of endotoxin showed marked increase (+30%) in cardiac index, and decrease in mean arterial pressure as well as total peripheral resistance, indicating the presence of hyperdynamic state. Metabolic studies indicate mild catabolic response. Administration of fat emulsion instead of isocaloric glucose has resulted transient hyperdynamic state, but failed to maintain this condition. In conclusion, it is possible to produce hyperdynamic state similar to that seen in septic shock by continuous administration of small amount of endotoxin in the dog, provided proper amount of glucose is supplied.

Amino Acids↗

Long identical repeats in the mouse gamma 2b switch region and their implications for the mechanism of class switching.

A computer sorting method was used to construct a dictionary by which long identical repeats of nucleotides could be identified and all available sequences of immunoglobulin switch regions were examined. The genomic mouse gamma 2b switch region contains two sets of four long identical repeats comprising 102, 72, 98 and 109 nucleotides respectively. The first is separated from the second by 347 nucleotides which contain the first 46 nucleotides of the 98 nucleotide set as a third partial repeat. These sets overlap the 49-bp separation between identical five nucleotide repeats GAGCT, GGGGT, ACCAG and CGAGC. Switches from S mu to S gamma 2b in and between these sets involve deletions of all or part of a set. Frequencies and locations of short repeats show differences between S mu, S epsilon, and S alpha and the other switch regions; these could determine specificity and locations of switches.

Animals↗

Identification of amino acid residues implicated in the cross-reaction between immunoglobulin VH and a T cell receptor molecule.

The problem of the relationship between the immunoglobulin-related T cell receptor (IgT) and classical immunoglobulin heavy chain variable regions (VH) was approached by determining the capacity of a xenoantiserum made against the immune affinity purified product of a permanent in vitro T cell line of mature, amplifier phenotype to react with human and murine monoclonal immunoglobulins with completely sequenced VH regions. Most of the amino acid residues identified as critical for the observed serological cross-reaction were localized within the disulfide-bonded loop and all of these occur on the surface of the 3-dimensional structure of the VH molecule. The most strongly correlated residues were restricted to the second complementarity determining region and the third framework region. This suggests that IgT need not contain complete VH regions, but that the serological cross-reaction might result from the insertion of 'minigenes' into a non-immunoglobulin framework or from short stretches of shared sequence between VH and the products of separate VT gene cluster.

Amino Acid Sequence↗

Fourteen nucleotides in the second complementarity-determining region of a human heavy-chain variable region gene are identical with a sequence in a human D minigene.

A sequence of 14 nucleotides in one human diversity (D) minigene (D2) is identical with a sequence in complementarity-determining region 2 (CDR2) of one human gene for the variable region of the heavy chain of immunoglobulin. The finding that nucleotide segments present in a D minigene can appear in CDR2 raises the possibility that other minigene segments may be involved in the generation of antibody diversity and complementarity or that nucleotide segments may move from one CDR to another by a gene conversion mechanism.

Antibody Diversity↗

Fractionation of calf thymus DNA by DEAE cellulose column chromatography.

Commercially available calf thymus DNA could be fractionated into different populations by DEAE-cellulose column chromatography, presumably due to the tertiary folding of the solid fibrous form of DNA which opened up gradually in solution. Depending on the duration in solution or the concentration of the solution, various peaks could be obtained by eluting the DEAE column with 0.01 M sodium phosphate buffer at pH 7.0 and 0.01, 0.4, 0.5, 0.6 and 1.0 M NaCl in the same buffer. The DNA fraction in each peak gave very narrow bands on 1% agarose gel electrophoresis, probably reflecting the folding and thus shielding of charges rather than molecular weight. The present fractionation procedure might be useful in characterizing the complicated network structure of calf thymus DNA and in studying the unfolding of DNA tertiary structure.

Animals↗