[Ultrasonographic features and clinical pathological of liver metastasis in patients with melanoma].

Objective: To investigate the ultrasonographic features and clinical pathological of liver metastasis in patients with melanoma. Methods: Thirteen patients with liver metastasis from melanoma treated in Tianjin Medical University Cancer Institute and Hospital from 2013 to 2019 were selected, and their ultrasonographic and clinicopathological characteristics were analyzed retrospectively. Results: Eleven of the 13 patients had multiple liver lesions. The maximum diameter of the lesions was (5.89±2.73) cm. Five cases of lesions were mixed echo (3 cases with high melanin content), 4 cases of lesions were hyperechoic (3 cases with low melanin content), 3 cases of lesions were hypoechoic (all with high melanin content), 1 case of lesions were equal echo (with high melanin content). The lesions in 11 patients had clear boundaries, while other 2 patients lacked the clear borders. Cystic areas were present in the lesions of 3 patients. Six cases had irregular lesions (lobulated), and 7 cases had regular lesions (round, oval). There were acoustic halos around the lesion in 9 cases and smooth and uneven acoustic halos in 5 cases. The results of immunohistochemistry showed that 11 cases were positive for S-100, HMB45 and Melan-A. One patient was not tested for HMB45, while S-100 and Melan-A were positive. One patient did not undergo Melan-A test, while S-100 and HMB45 were positive. Conclusion: Most of the liver metastases of melanoma are mixed echo or hyperechoic, most of them are nodular with clear boundaries combined with vocal halo, and a few of the lesions have cystic areas.

[Prognostic value of international prognostic index, revised international prognostic index, enhanced international prognostic index and Grupo Español de Linfomas/trasplante autólogo de médula ósea-international prognostic index for diffuse large B-cell lymphoma].

Objective: To compare the prognostic values of international prognostic index (IPI), revised international prognostic index (R-IPI), enhanced international prognostic index (NCCN-IPI) and Grupo Español de Linfomas/trasplante autólogo de médula ósea-international prognostic index (GELTAMO-IPI) for diffuse large B-cell lymphoma (DLBCL). Methods: The clinical data of 238 DLBCL patients who were initially treated in Shanxi Cancer Hospital from September 2011 to March 2016 were collected retrospectively, the risk stratification and prognostic evaluation were conducted according to the IPI, R-IPI, NCCN-IPI and GELTAMO-IPI. Survival analysis was performed by the Kaplan-Meier method, COX regression analysis was used to compare the risks of death and progress in each group. Harrell's C statistics was used to compare the prediction accuracy of each hazard stratification model. Results: The 3-years progression-free survival rates of low risk, middle-low risk, middle-high risk and high risk group stratified according to IPI were 90.9%, 67.5%, 54.0% and 52.4%, respectively. The 3-years overall survival rates of each group were 93.9%, 72.5%, 58.0% and 53.7%, respectively. The 3-years progression-free survival rates of patients with very good prognosis, good prognosis and poor prognosis were 90.9%, 79.8% and 53.0%, respectively, the 3-years overall survival rates were 95.5%, 83.3% and 55.3%, respectively. The 3-years of progression-free survival of low risk group, middle-low risk group, middle-high risk group and high risk group stratified according to NCCN-IPI were 91.7%, 76.5%, 66.7% and 41.1%, respectively. The 3-years overall survival rates of each group were 95.8%, 79.4%, 70.0% and 42.9%, respectively. The 3-years progression-free survival rates of low risk, middle-low risk, middle-high risk and high risk group stratified according to GELTAMO-IPI were 91.3%, 76.3%, 67.4% and 32.7%, respectively. The 3-years overall survival rates of each group were 95.7%, 80.7%, 67.4% and 34.5%, respectively. Cox regression analysis showed that the risks of progression and death were significantly different between the middle-low risk group and low risk group of IPI (HR=4.144 and 5.085). The risks of progression and death were significantly different between the poor prognosis group and good prognosis group of R-IPI (HR=2.752 and 3.171), but both of which were significantly lower than the IPI groups. The risk stratification showed that the risks of progression and death were significantly different between the high risk group and middle-high risk group of NCCN-IPI and GELTAMO-IPI. However, the screening ability of high risk patients in GELTAMO-IPI group was better than that of NCCN-IPI group (NCCN-IPI HR=2.290 and 2.309, GELTAMO-IPI HR=3.084 and 2.966). Harrell's C-index analysis showed that the C-indexes of 3-years progression-free survival prediction in IPI, R-IPI, NCCN-IPI and GELTAM0-IPI were 0.672, 0.641, 0.664 and 0.700, respectively (P<0.001). The C-indexes of 3-years overall survival prediction were 0.687, 0.653, 0.671 and 0.721, respectively (P<0.001). The C-index of GETAMO-IPI was highest, superior to other prediction models. Conclusions: The screening abilities of GELTAMO-IPI and NCCN-IPI for high-risk DLBCL patients are better than those of IPI and R-IPI. The prediction accuracy of GELTAMO-IPI is significantly better than other prognostic stratified models.

Pharmacological inhibition of ß-catenin/BCL9 interaction overcomes resistance to immune checkpoint blockades by modulating Treg cells.

The Wnt/ß-catenin (ß-cat) pathway plays a critical role in cancer. Using hydrocarbon-stapled peptide technologies, we aim to develop potent, selective inhibitors targeting this pathway by disrupting the interaction of ß-cat with its coactivators B-cell lymphoma 9 (BCL9) and B-cell lymphoma 9-like (B9L). We identified a set of peptides, including hsBCL9CT-24, that robustly inhibits the activity of ß-cat and suppresses cancer cell growth. In animal models, these peptides exhibit potent anti-tumor effects, favorable pharmacokinetic profiles, and minimal toxicities. Markedly, these peptides promote intratumoral infiltration of cytotoxic T cells by reducing regulatory T cells (Treg) and increasing dendritic cells (DCs), therefore sensitizing cancer cells to PD-1 inhibitors. Given the strong correlation between Treg infiltration and APC mutation in colorectal cancers, it indicates our peptides can reactivate anti-cancer immune response suppressed by the oncogenic Wnt pathway. In summary, we report a promising strategy for cancer therapy by pharmacological inhibition of the Wnt/ß-cat signaling.

Loss of function of NF1 is a mechanism of acquired resistance to endocrine therapy in lobular breast cancer.

Background: Invasive lobular carcinoma (ILC) as a disease entity distinct from invasive ductal carcinoma (IDC) has merited focused studies of the genomic landscape, but those to date are largely limited to the assessment of early-stage cancers. Given that genomic alterations develop as acquired resistance to endocrine therapy, studies on refractory ILC are needed. Patients and methods: Tissue from 336 primary-enriched, breast-biopsied ILC and 485 estrogen receptor (ER)-positive IDC and metastatic biopsy specimens from 180 ILC and 191 ER-positive IDC patients was assayed with hybrid-capture-based comprehensive genomic profiling for short variant, indel, copy number variants, and rearrangements in up to 395 cancer-related genes. Results: Whereas ESR1 alterations are enriched in the metastases of both ILC and IDC compared with breast specimens, NF1 alterations are enriched only in ILC metastases (mILC). NF1 alterations are predominantly under loss of heterozygosity (11/14, 79%), are mutually exclusive with ESR1 mutations [odds ratio = 0.24, P < 0.027] and are frequently polyclonal in ctDNA assays. Assessment of paired specimens shows that NF1 alterations arise in the setting of acquired resistance. An in vitro model of CDH1 mutated ER-positive breast cancer demonstrates that NF1 knockdown confers a growth advantage in the presence of 4-hydroxy tamoxifen. Our study further identified a significant increase in tumor mutational burden (TMB) in mILCs relative to breast ILCs or metastatic IDCs (8.9% >20 mutations/mb; P < 0.001). Most TMB-high mILCs harbor an APOBEC trinucleotide signature (14/16; 88%). Conclusions: This study identifies alteration of NF1 as enriched specifically in mILC. Mutual exclusivity with ESR1 alterations, polyclonality in relapsed ctDNA, and de novo acquisition suggest a role for NF1 loss in endocrine therapy resistance. Since NF1 loss leads to RAS/RAF kinase activation, patients may benefit from a matched inhibitor. Moreover, for an independent subset of mILC, TMB was elevated relative to breast ILC, suggesting possible benefit from immune checkpoint inhibitors.

[Contrastive analysis of ultrasonographic features of synchronous and heterochronic liver metastasis in patients with stromal tumor].

Objective: To investigate the ultrasonographic features of synchronous and heterochronic liver metastasis in patients with stromal tumors, and to elucidate the value of ultrasonic examination in follow-up surgery. Methods: A total of 1 516 patients with pathologically confirmed gastrointestinal stromal tumors (GISTs) and extra-gastrointestinal stromal tumors (EGISTs) were enrolled. The ultrasonographic features of primary lesions and liver metastases in a total of 46 cases with 95 liver metastases were analyzed. Results: 24 out of 46 cases had primary lesion in the small intestine, 14 in the stomach, 4 in the abdominal cavity, 1 in the colon, 2 in the esophagus, and 1 in the mesentery. The expression of CD117, Dog-1 and CD34were detected by immunohistochemical staining. The positive rate of CD117 was 100%, the Dog-1 was 95.7% and the CD34 was 69.6%. There were statistically significant differences in the maximum diameter, boundary and blood flow of primary tumors in 28 patients with synchronous liver metastasis and 18 patients with heterochronic liver metastasis (P=0.001, 0.022 and 0.036, respectively). Of the 95 liver metastases, 86 (90.5%) were located in the right lobe of the liver, 79 (83.2%) had clear boundaries, 75 (78.9%) were hypoechoic or isoechoic, 55 (57.9%) showed colored patterns, and 68 (71.6%) had no halo.11 liver metastases were cystic masses, 59 were solid masses, and 25 were mixed masses. There was a statistically significant difference in blood flow between 65 synchronous hepatic metastases and 30 heterochronic liver metastases (P=0.017). Conclusions: There were differences of the primary tumor ultrasonographic features between the synchronous metastasis group and heterochronic metastasis group. The ultrasonographic features of primary tumors and liver metastases have important clinical significance for the diagnosis, follow-up and treatment of malignant mesenchymal tumors.

Characterisation of a novel cell line (CSQT-2) with high metastatic activity derived from portal vein tumour thrombus of hepatocellular carcinoma.

BACKGROUND: Portal vein tumour thrombus (PVTT) is highly associated with the progression and metastasis of hepatocellular carcinoma (HCC). However, there are no appropriate cell models of PVTT with which to study the biological and physiological characteristics of PVTT. METHODS: Primary cell culture was performed by the use of a successive xenograft line called PVTT-#1, which was obtained from a 60-year-old male HCC patient accompanied by PVTT. RESULTS: A successive cell line named CSQT-2 was established. The cell line showed aggressive phenotypes in terms of cell growth, survival, migration, xenograft and metastasis. Moreover, an orthotopic transplantation assay showed that PVTT can be generated in nude mice when CSQT-2 cells were inoculated in the liver and that it shows a typical migratory tendency in the vascular branches of portal vein. Moreover, the established CSQT-2 cells also showed varied expression of tumour-initiating cell (TIC) markers such as CD133, CD90 and EpCAM. CONCLUSION: Establishment of CSQT-2 may provide a suitable model with which to investigate the molecular mechanisms of PVTT-related HCC.

A ropivacaine-lidocaine combination for caudal blockade in haemorrhoidectomy.

A single dose of caudal lidocaine does not provide a sufficiently long anaesthetic duration and is not generally used for complicated anorectal surgery. This study evaluated the safety and efficacy of a ropivacaine-lidocaine combination for caudal anaesthesia in patients undergoing haemorrhoidectomy. A total of 287 haemorrhoid patients with successful initial caudal anaesthesia were randomized to receive either a mixture of 0.375% ropivacaine and 1.0% lidocaine (ropi-lido group; n=146) or 1.0% lidocaine alone (placebo-lido group; n=141). Significantly fewer patients in the ropi-lido group required intra-operative supplemental anaesthesia than in the placebo-lido group. Patients treated with the ropivacaine-lidocaine combination had significantly lower scores for pain at each post-operative time point, and a longer mean time to the first requirement for post-operative analgesic than patients in the placebo-lido group. These results suggest that caudal anaesthesia with a combination of ropivacaine and lidocaine is a safe and effective method of inducing anaesthesia during haemorrhoidectomy.

Serum- and glucocorticoid-dependent kinase, cell volume, and the regulation of epithelial transport.

Ample pharmacological evidence points to a role of kinases in the regulation of cell volume. Given the limited selectivity of most inhibitors, however, the specific molecules involved have remained largely elusive. The search for cell volume regulated genes in liver HepG2 cells led to the discovery of the human serum- and glucocorticoid-dependent serine/threonine kinase hsgk1. Transcription and expression of hsgk1 is markedly and rapidly upregulated by osmotic and isotonic cell shrinkage. The effect of osmotic cell shrinkage on hsgk1 is mediated by p38 kinase. Further stimuli of hsgk1 transcription include glucocorticoids, aldosterone, TGF-beta1, serum, increase of intracellular Ca2+ and phorbolesters, whereas cAMP downregulates hsgk1 transcription. The hsgk1 protein is expressed in several epithelial tissues including human pancreas, intestine, kidney, and shark rectal gland. Co-expression of hsgk1 with the renal epithelial Na+-channel ENaC or the Na+/K+/2Cl(-)-cotransporter NKCC2 (BSC1) in Xenopus oocytes, accelerates insertion of the transport proteins into the cell membrane and thus, stimulates channel or transport activity. Thus, hsgk1 participates in the regulation of transport by steroids and secretagogues increasing intracellular Ca2+-activity. The stimulation of hsgk1 transcription by TGF-beta1 may further bear pathophysiological relevance.

The genomic RNA in Ty1 virus-like particles is dimeric.

The yeast retrotransposon Ty1 resembles retroviruses in a number of important respects but also shows several fundamental differences from them. We now report that, as in retroviruses, the genomic RNA in Ty1 virus-like particles is dimeric. The Ty1 dimers also resemble retroviral dimers in that they are stabilized during the proteolytic maturation of the particle. The stabilization of the dimer suggests that one of the cleavage products of TyA1 possesses nucleic acid chaperone activity.

The human immunodeficiency virus type 1 Gag polyprotein has nucleic acid chaperone activity: possible role in dimerization of genomic RNA and placement of tRNA on the primer binding site.

The formation of an infectious retrovirus particle requires several RNA-RNA interaction events. In particular, the genomic RNA molecules form a dimeric structure, and a cellular tRNA molecule is annealed to an 18-base complementary region (the primer binding site, or PBS) on the genomic RNA, where it will serve as primer for reverse transcription. tRNAs normally possess a highly stable secondary and tertiary structure; it seems unlikely that annealing of a tRNA molecule to the PBS, which involves unwinding of this structure, could occur efficiently at physiological temperatures without the assistance of a cofactor. Many prior studies have shown that the viral nucleocapsid (NC) protein can act as a nucleic acid chaperone (i.e., facilitate annealing events between nucleic acids), and the assays used to demonstrate this activity include its ability to catalyze dimerization of transcripts representing retroviral genomes and the annealing of tRNA to the PBS in vitro. However, mature NC is not required for these events in vivo, since protease-deficient viral mutants, in which NC is not cleaved from the parental Gag polyprotein, are known to contain dimeric RNAs with tRNA annealed to the PBS. In the present experiments, we have tested recombinant human immunodeficiency virus type 1 Gag polyprotein for nucleic acid chaperone activity. The protein was positive by all of our assays, including the ability to stimulate dimerization and to anneal tRNA to the PBS in vitro. In quantitative experiments, its activity was approximately equivalent on a molar basis to that of NC. Based on these results, we suggest that the Gag polyprotein (presumably by its NC domain) catalyzes the annealing of tRNA to the PBS during (or before) retrovirus assembly in vivo.

HIV-1 nucleocapsid protein induces "maturation" of dimeric retroviral RNA in vitro.

After a retrovirus particle is released from the cell, the dimeric genomic RNA undergoes a change in conformation. We have previously proposed that this change, termed maturation of the dimer, is due to the action of nucleocapsid (NC) protein on the RNA within the virus particle. We now report that treatment of a 345-base synthetic fragment of Harvey sarcoma virus RNA with recombinant or synthetic HIV-1 NC protein converts a less stable form of dimeric RNA to a more stable form. This phenomenon thus appears to reproduce the maturation of dimeric retroviral RNA in a completely defined system in vitro. To our knowledge, maturation of dimeric RNA within a retrovirus particle is the first example of action of an "RNA chaperone" protein in vivo. Studies with mutant NC proteins suggest that the activity depends upon basic amino acid residues flanking the N-terminal zinc finger and upon residues within the N-terminal finger, including an aromatic amino acid, but do not require the zinc finger structures themselves.

Multiple regions of Harvey sarcoma virus RNA can dimerize in vitro.

Retroviruses contain a dimeric RNA consisting of two identical molecules of plus-strand genomic RNA. The structure of the linkage between the two monomers is not known, but they are believed to be joined near their 5' ends. Darlix and coworkers have reported that transcripts of retroviral RNA sequences can dimerize spontaneously in vitro (see, for example, E. Bieth, C. Gabus, and J. L. Darlix, Nucleic Acids Res. 18:119-127, 1990). As one approach to identification of sequences which might participate in the linkage, we have mapped sequences derived from the 5' 378 bases of Harvey sarcoma virus (HaSV) RNA which can dimerize in vitro. We found that at least three distinct regions, consisting of nucleotides 37 to 229, 205 to 272, and 271 to 378, can form these dimers. Two of these regions contain nucleotides 205 to 226; computer analysis suggests that this region can form a stem-loop with an inverted repeat in the loop. We propose that this hypothetical structure is involved in dimer formation by these two transcripts. We also compared the thermal stabilities of each of these dimers with that of HaSV viral RNA. Dimers of nucleotides 37 to 229 and 205 to 272 both exhibited melting temperatures near that of viral RNA, while dimers of nucleotides 271 to 378 are quite unstable. We also found that dimers of nucleotides 37 to 378 formed at 37 degrees C are less thermostable than dimers of the same RNA formed at 55 degrees C. It seems possible that bases from all of these regions participate in the dimer linkage present in viral RNA.

[Comparison of morphological and microscopical diagnostic characters of Hawthorn fruits (Crataegus species)].

This paper deals with studies on morphological and microscopical diagnostic characters of Chinese Hawthorn fruits. Their similarities and differences in morphological and microscopical characters among eight species of Crataegus (C. pinnatifida Bge., C. pinnatifida var. major NE Br., C. cuneata sieb. & Zuce., C. scabrifolia (Franch.) Rehd., C. hupehensis Sarg., C. kansuensis Wils, C. maximowiczii Schneid. and C. sanguinea Pall.) fruits are compared and illustrated with diagrams.

[Suppressive effects of adenosine on nonspecific and humoral immunities in mice].

Adenosine (Ade) 1.3, 13, 130 mg.kg-1 ip inhibited the ability of peripheral leukocytes and peritoneal macrophages in phagocytosing the Staphylococcus albus with [3H]TdR incorporation in mice, declined the hemolytic ability of plaque-forming cells and the production of antibody in mice immunized by sheep erythrocytes. Ade 13, 130 mg.kg-1 ip decreased the mouse serum muramidase (lysozyme) concentration. Dipyridamole (Dip) 10 mg.kg-1 ip attenuated the effects of Ade 130 mg.kg-1 on humoral immunity reaction, but the nonspecific immunity was not attenuated. These results showed that the uptake of Ade may play an important role in the effects of Ade on humoral immunity reaction. Aminophylline (Ami) 100 mg.kg-1 ip attenuated the effects of Ade 130 mg.kg-1 on hemolytic ability of plaque-forming cells and the ability of peripheral leukocytes in phagocytosing Staphylococcus albus. These results suggested that the effects of Ade on murine humoral and nonspecific immunity reaction were mediated by Ade A2 receptor (A2DR).

[A clinical and basic study on the relationship between acute myocardial infarction and endothelin].

The level of plasma endothelin (ET) was studied in 40 cases with acute myocardial infarction (AMI) with radioimmunoassay. The results showed that plasma ET level reached its peak value (46.01 +/- 1.64 pg/ml) immediately after AMI attack and dropped down (39.37 +/- 0.47 pg/ml) on the first day; The value was still high (15.56 +/- 1.40 pg/ml) on the twenty-eight day: this was significant higher than that in control group (6.35 +/- 0.44 pg/ml, P < 0.001). It was found that height of plasma ET level was closely correlated with severity of myocardial damage and degree of cardiac insufficiency. In order to evaluate the pathogenic role of ET in AMI, the effect of ET-antiserum on myocardial infarction (MI) was investigated on infarct model produced by ligature of left anterior descending coronary artery in rats. The results showed that plasma ET levels elevated significantly in rats with MI (8.4 +/- 1.0, sham 3.1 +/- 0.2 pg/ml, P < 0.01) and ET-antiserum administration dramatically decreased plasma ET level 65% (P < 0.01), lowered plasma content of lipid peroxide 27% (P < 0.01) and reduced infarct size 48% (P < 0.01). It is suggested that ET is an important factor which contributes to the pathogenesis of MI. Limb ischemia and reperfusion study was carried out in rats also. Metallothionein (MT) was found to antagonize markedly ET-induced vasoconstriction and lower the release of ET stimulated by angiotensin II in a dose-dependent manner. It is suggested that under certain pathological conditions MT may exert its injury--resistant and cell protective action.

Surgical treatment of atherosclerotic infrarenal abdominal aortic aneurysms. A review of 30 years' experience.

During the 30 years from 1960 to 1989, 100 sequential patients with atherosclerotic infrarenal abdominal aortic aneurysm (AAA) were admitted to Zhongshan Hospital. Twenty-eight were not treated surgically and 72 underwent resection of the AAA with prosthesis replacement. Nineteen non-surgical patient were followed up, and 8 died from ruptures with a five-year survival rate of 41.3 +/- 13%. In 72 surgically treated patients, the operative mortality was 2.8%. The five-year survival rate is 77.5 +/- 6.2%, which is higher in comparison with the non-surgical group (P < 0.01). The data show that the operation for AAA is safe and the postoperative long-term results are satisfactory.

[Constituents in volatile oil of peilan and 3 plants of the same genus].

A study hes been made on the essential oil from the crude drug Peilan (Eupatorium fortunei) and the plants E. japonicum, E. chinense and E. cannabinum. 71 constituents have been identified by GC-MS. Quantitative analysis has been carried out by GC. The study provides scientific methods for the identification of the crude drug "Peilan" and the quality control of the fresh and dried "Peilan".

Bipartite signal for read-through suppression in murine leukemia virus mRNA: an eight-nucleotide purine-rich sequence immediately downstream of the gag termination codon followed by an RNA pseudoknot.

The pol gene of murine leukemia virus and other mammalian type C retroviruses is expressed by read-through suppression of an in-frame UAG codon which separates the gag and pol coding regions. In this study, we have analyzed the sequence requirements for read-through suppression by placing different portions of wild-type and mutant viral sequences from the gag-pol junction between reporter genes and testing transcripts of these constructs for suppression in reticulocyte lysates. We find that the read-through signal is contained within the first 57 nucleotides on the 3' side of the UAG codon. Our results indicate that the identities of six conserved bases in the eight-nucleotide, purine-rich sequence immediately downstream of the UAG codon are critical for suppression, as is the existence of a pseudoknot structure spanning the next 49 nucleotides. Thus, read-through suppression depends on a complex, bipartite signal in the mRNA.

Identification of amino acids inserted during suppression of UAA and UGA termination codons at the gag-pol junction of Moloney murine leukemia virus.

Expression of the murine leukemia virus pol gene occurs by translational readthrough of an in-frame UAG codon between the gag and pol coding regions. In a previous study, we mutated the UAG codon to UAA or UGA and demonstrated that both of these termination codons could be suppressed in reticulocyte lysates and in infected cells with the same efficiency as UAG. We now report the identity of the amino acids inserted in vitro in response to UAA and UGA in fusion products containing the gag-pol junction region. The results show that UAA, like UAG, directs the incorporation of glutamine, whereas UGA directs the incorporation of three amino acids, arginine, cysteine, and tryptophan. To our knowledge, this is the first report indicating misreading of UAA as glutamine and UGA as arginine and cysteine in higher eukaryotes. Interestingly, although our protein synthesis system presumably contains other known UAG and UGA suppressors, these tRNAs did not suppress the termination codons in our experiments. Thus, it seems possible that the sequence surrounding the gag-pol junction not only promotes suppression but also helps determine which tRNAs function in suppression.

Chromatographic analysis of the aminoacyl-tRNAs which are required for translation of codons at and around the ribosomal frameshift sites of HIV, HTLV-1, and BLV.

An examination of the frameshift signals or proposed signals within published sequences of retroviruses and other genetic elements from higher animals shows that each site utilizes a tRNA which normally contains Wybutoxine (Wye) base or Queuine (Q) base in the anticodon loop. We find experimentally that most of the Phe-tRNA present in HIV-1 infected cells lacks the highly modified Wye base in its anticodon loop and most of the Asn-tRNA in HTLV-1 and BLV infected cells lacks the highly modified Q base in its anticodon loop. Interestingly, Phe-tRNA translates a UUU codon within the ribosomal frameshift signal in HIV and Asn-tRNA translates a AAC codon within the proposed frameshift signals in HTLV-1 and BLV. Thus, the lack of a highly modified base in the anticodon loop of tRNAs in retroviral infected cells is correlated with the participation of these undermodified tRNAs in the corresponding frameshift event. This suggests that the "shifty" tRNAs proposed by Jacks et al. (Cell 55, 447-458, 1988) to carry out frameshifting may be hypomodified isoacceptors.