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Biomedical subjects

L Cao

Publications and source records attributed to L Cao.

At least 19 recordsLinked to original sources
PubMed1992

HIV replication during the first weeks of life.

Diagnosis of HIV infection among children born to HIV-positive mothers can be made in the first 12 months, but few studies have examined HIV status during the first weeks of life. In a prospective longitudinal study of 50 infants born to HIV-1 seropositive women, blood samples were obtained at birth and at 4-9 weeks and 5-9 months of age, and were tested for HIV-1 by the polymerase chain reaction (PCR), viral culture, and p24 antigen measurements. 16 were diagnosed as HIV-infected by the age of 4-9 weeks according to both PCR and culture; by contrast, infection could be detected in only 5 children at birth. No changes in HIV status were observed between 4-9 weeks and 5-9 months in the 44 children who could be retested. Perinatal HIV-1 infection can therefore be diagnosed in the first 2 months of life, either by PCR or viral culture. Our inability to detect HIV-1 infection at birth in almost 70% of babies subsequently found infected suggests an active replication of HIV during the first weeks of life. Our results might favour the hypothesis that transmission of HIV-1 takes place either at the end of pregnancy or at delivery.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Independent binding of the retinoblastoma protein and p107 to the transcription factor E2F.

The cellular protein p107 and the retinoblastoma protein (pRB) have many features in common. Most strikingly, they contain homologous protein domains that mediate interaction with the oncoproteins of several small DNA tumour viruses, including adenovirus E1A and SV40 large-T antigen. In cells that do not contain these viral oncoproteins, pRB interacts with the cellular transcription factor E2F or a related protein termed DRTF1. E2F associates with a form of pRB that is found primarily in G1 cells. It seems that the E2F-pRB complex dissociates near the G1-S boundary before the initiation of S phase, releasing free E2F and apparently stimulating the ability of E2F to activate transcription. Cells that express E1A have no or little pRB-E2F complex, presumably because of the association of E1A with pRB. During S phase, E2F forms a second complex that contains cyclin A but apparently lacks pRB. Here, we report that p107 is found in the cyclin A/E2F complex and that this complex also contains p33cdk2. These observations suggest that p107 and pRB cooperate in the regulation of E2F activity, each affecting different stages of the cell cycle. Thus, by binding to pRB and p107, E1A and large-T antigen target two distinct aspects of E2F regulation.

Animals↗
PubMed1992

Hypoxia induces glucose transporter expression in endothelial cells.

Endothelial cells in various tissues of the body are often exposed to hypoxic conditions. To examine the effects of sustained hypoxia on energy metabolism in endothelial cells, we have maintained bovine aortic and human umbilical vein endothelial cells in an atmosphere containing low oxygen concentrations (14 mmHg) for up to 96 h. We report here that endothelial cells maintained under these conditions upregulate their glucose transport activity, consume more glucose, and produce greater amounts of lactic acid than normoxic cells. Upregulation of glucose transport activity by hypoxic endothelial cells required several hours to occur, was associated with increased expression of mRNA and protein for the erythroid/brain form of the facilitative glucose transporter, and was not due to depletion of glucose from the medium. Prolonged treatment of endothelial cells with inhibitors or uncouplers of oxidative phosphorylation (antimycin, azide, dinitrophenol) under normoxic conditions also upregulated glucose transporter expression. These results suggest that reduced rates of oxidative metabolism may represent an important signal for cells to adapt metabolically to hypoxia. Furthermore, in our examination of endothelial cell energy metabolism, we discovered that endothelial cells contain phosphocreatine and express both the brain and muscle isozymes of creatine kinase.

Animals↗
PubMed1991

Temporal comparison of recombination and synaptonemal complex formation during meiosis in S. cerevisiae.

In synchronous cultures of S. cerevisiae undergoing meiosis, an early event in the meiotic recombination pathway, site-specific double strand breaks (DSBs), occurs early in prophase, in some instances well before tripartite synaptonemal complex (SC) begins to form. This observation, together with previous results, supports the view that events involving DSBs are required for SC formation. We discuss the possibility that the mitotic pathway for recombinational repair of DSBs served as the primordial mechanism for connecting homologous chromosomes during the evolution of meiosis. DSBs disappear during the period when tripartite SC structure is forming and elongating (zygotene); presumably, they are converted to another type of recombination intermediate. Neither DSBs nor mature recombinant molecules are present when SCs are full length (pachytene). Mature reciprocally recombinant molecules arise at the end of or just after pachytene. We suggest that the SC might coordinate recombinant maturation with other events of meiosis.

Chromatin↗
PubMed1991

CD11c/CD18 on neutrophils recognizes a domain at the N terminus of the A alpha chain of fibrinogen.

Fibrinogen and fibrin serve as adhesive substrates for a variety of cells including platelets, endothelial cells, and leukocytes. Previously, we identified the C terminus of the gamma chain of fibrinogen as the region of the fibrinogen molecule that contains a ligand for CD11b/CD18 (complement receptor 3) on phorbol ester-stimulated polymorphonuclear leukocytes. In contrast, we report here that neutrophils stimulated with tumor necrosis factor adhere to fibrinogen-coated surfaces, but not to human serum albumin-coated surfaces, via the integrin CD11c/CD18 (p150/95). Monoclonal antibodies LeuM5 and 3.9, which are directed against the alpha subunit of CD11c/CD18, but not monoclonal antibodies OKM10 and OKM1, which are directed against the alpha subunit of CD11b/CD18, inhibit the adhesion of tumor necrosis factor-stimulated neutrophils to fibrinogen-coated surfaces. To identify the site on fibrinogen recognized by CD11c/CD18, we have examined the adhesion of tumor necrosis factor-stimulated neutrophils to surfaces coated with various fibrinogen fragments. Stimulated neutrophils adhere to surfaces coated with the N-terminal disulfide knot fragment of fibrinogen or fibrinogen fragment E. Moreover, peptides containing the sequence Gly-Pro-Arg (which corresponds to amino acids 17-19 of the N-terminal region of the A alpha chain of fibrinogen), and monoclonal antibody LeuM5, block tumor necrosis factor-stimulated neutrophil adhesion to fibrinogen and to the N-terminal disulfide knot fragment of fibrinogen. Thus, CD11c/CD18 on tumor necrosis factor-stimulated neutrophils functions as a fibrinogen receptor that recognizes the sequence Gly-Pro-Arg in the N-terminal domain of the A alpha chain of fibrinogen.

Amino Acid Sequence↗
PubMed1991

Clenbuterol plus acivicin decrease tumor growth and increase muscle mass in rats maintained on total parenteral nutrition.

Two problems associated with supplemental nutrition of tumor-bearing organisms are control of tumor growth and reduction of cachexia. To investigate these problems, rats bearing methylcholanthrene-induced sarcomas were maintained on total parenteral nutrition (TPN) for 10 to 12 days beginning 23 days after tumor inoculation. Combined treatment of one group of these rats with the glutamine antimetabolite, acivicin, and the beta 2-adrenergic agonist, clenbuterol, arrested tumor growth, increased skeletal muscle mass and protein content, increased gut mass, and decreased total plasma lipid levels. Resting energy expenditure and cardiac mass were increased by TPN and were increased further by acivicin plus clenbuterol. These results demonstrate that tumor growth and muscle wasting can be controlled during TPN of tumor-bearing organisms. Therefore, cachectic depletion of lean body tissue may not be obligatory in neoplastic disease.

Animals↗
PubMed1990

A pathway for generation and processing of double-strand breaks during meiotic recombination in S. cerevisiae.

We have identified and analyzed a meiotic reciprocal recombination hot spot in S. cerevisiae. We find that double-strand breaks occur at two specific sites associated with the hot spot and that occurrence of these breaks depends upon meiotic recombination functions RAD50 and SPO11. Furthermore, these breaks occur in a processed form in wild-type cells and in a discrete, unprocessed form in certain nonnull rad50 mutants, rad50S, which block meiotic prophase at an intermediate stage. The breaks observed in wild-type cells are similar to those identified independently at another recombination hot spot, ARG4. We show here that the breaks at ARG4 also occur in discrete form in rad50S mutants. Occurrence of breaks in rad50S mutants is also dependent upon SPO11 function. These observations provide additional evidence that double-strand breaks are a prominent feature of meiotic recombination in yeast. More importantly, these observations begin to define a pathway for the physical changes in DNA that lead to recombination and to define the roles of meiotic recombination functions in that pathway.

Blotting, Southern↗
PubMed1990

Threonine 1336 of the human insulin receptor is a major target for phosphorylation by protein kinase C.

The ability of tumor-promoting phorbol diesters to inhibit both insulin receptor tyrosine kinase activity and its intracellular signaling correlates with the phosphorylation of the insulin receptor beta subunit on serine and threonine residues. In the present studies, mouse 3T3 fibroblasts transfected with a human insulin receptor cDNA and expressing greater than one million of these receptors per cell were labeled with [32P]phosphate and treated with or without 100 nM 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA). Phosphorylated insulin receptors were immunoprecipitated and digested with trypsin. Alternatively, insulin receptors affinity purified from human term placenta were phosphorylated by protein kinase C prior to trypsin digestion of the 32P-labeled beta subunit. Analysis of the tryptic phosphopeptides from both the in vivo and in vitro labeled receptors by reversed-phase HPLC and two-dimensional thin-layer separation revealed that PMA and protein kinase C enhanced the phosphorylation of a peptide with identical chromatographic properties. Partial hydrolysis and radiosequence analysis of the phosphopeptide derived from insulin receptor phosphorylated by protein kinase C indicated that the phosphorylation of this tryptic peptide occurred specifically on a threonine, three amino acids from the amino terminus of the tryptic fragment. Comparison of these data with the known, deduced receptor sequence suggested that the receptor-derived tryptic phosphopeptide might be Ile-Leu-Thr(P)-Leu-Pro-Arg. Comigration of a phosphorylated synthetic peptide containing this sequence with the receptor-derived phosphopeptide confirmed the identity of the tryptic fragment. The phosphorylation site corresponds to threonine 1336 in the human insulin receptor beta subunit.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1990

Oxytocin- and vasopressin-binding sites in the rat uterus: competition binding and inhibitory pA2 studies with oxytocin and oxytocin antagonists.

Recent reports have presented evidence suggesting that there are distinct oxytocin (OT) and vasopressin (VP) receptors in the human and rabbit myometrium. In this study we have investigated whether OT and arginine vasopressin (AVP) activate the same or two different receptor systems in the rat uterus in producing their uterotonic action and whether the myometrial OT/VP receptors are similar to the V1 receptors in the vascular smooth muscle cells. We compared the dose-response characteristics of OT and AVP by the in vitro cumulative dose-response curve technique. We determined the ligand-receptor binding characteristics of [3H]OT and [3H]AVP on uterine membrane fractions from nonpregnant and pregnant rats. Specific OT antagonists were used in competition receptor binding assays and in antioxytocic pA2 bioassays against OT and AVP to determine whether OT antagonists can discriminate between OT- and AVP-binding sites in the myometrium. We also compared the in vitro antioxytocic (OT receptor-mediated action) and the in vivo antivasopressor (V1 receptor-mediated action) potencies of a series of six OT antagonists. Our results show that OT- and AVP-binding sites in the nonpregnant rat uterus have similar binding characteristics and cannot be distinguished by the dose-response study, radioligand receptor binding assays, or OT antagonists in the competition binding and pA2 assays. However, in the term pregnant parturient uterus, the two binding sites can be clearly differentiated. OT receptor density, but not AVP, was markedly increased at term pregnancy. All six OT antagonists studied in this investigation were more potent in antagonizing the uterotonic response to OT than the vasopressor response to AVP. The antioxytocic:antivasopressor potency ratios, however, were different between the antagonists, ranging from nearly equal (0.91) to low (0.1). The results above suggest that there are distinct OT- and AVP-binding sites in the rat myometrium. The myometrial OT/AVP receptors are similar to but not the same as the V1 receptors in the vascular smooth muscle cells.

Animals↗
PubMed1990

Effect of nephrectomy and of adrenergic receptor blockers on the cardiorenal actions of endothelin.

The cardiorenal actions of endothelin-1 (ET-1) were evaluated in rats following nephrectomy, in rats during alpha-adrenergic blockade with phentolamine, and in rats during beta-adrenergic blockade with propranolol. Female rats were anesthetized with pentobarbital and, following surgery, were allowed 60 min to stabilize before 3 x 20 min-control clearances were collected. ET-1 was then infused at a rate of 100 ng kg-1 min-1 for 30 min, the infusion was stopped, and three additional clearances were collected. Four groups of rats were studied: in Group 1 (n = 10), ET-1 was infused; in Group 2 (n = 5), a bilateral nephrectomy was performed 120 min before infusing ET-1; in Group 3 (n = 5), ET-1 was infused into rats treated with phentolamine (0.015 mg kg-1 min-1); and in Group 4 (n = 5), ET-1 was infused into rats treated with propranolol (0.015 mg kg-1 min-1). At 30 min during infusion of ET-1 into Group 1 rats, mean arterial blood pressure had increased (P less than 0.01) by 27 +/- 2% (SE) and the glomerular filtration rate had decreased (P less than 0.01) by 71 +/- 6% of baseline values. Nephrectomy potentiated and prolonged the ET-1-induced systemic vasoconstriction. Phentolamine had no effect on the cardiorenal actions of ET-1 whereas propranolol enhanced ET-1-induced changes in mean arterial blood pressure; mean arterial blood pressure increased 38 +/- 2% at 30 min during ET-1 + propranolol infusion (P less than 0.01 versus value with ET-1 alone). These data indicate that the kidney affects ET-1-induced systemic vasoconstriction and that beta-adrenergic (but not alpha-adrenergic) receptors are activated during infusion of ET-1 with a resultant attenuation of ET-1-induced changes in systemic blood pressure.

Animals↗
PubMed1990

[Preliminary studies of T lymphocyte subsets in patients with neurologic diseases].

With immunofluorescence assay a preliminary study of T-cell subsets in the peripheral blood (PB) and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS), viral encephalitis, Guillain-Barré syndrome (GBS), tuberculous meningitis, and other neurological diseases (OND) was carried out. The results revealed that the T4+ percentage and T4+/T8+ ratio of PB as well as CSF increased, T8+ decreased in cases of MS. The changes of CSF T subsets in cases of (GBS) were similar to those in cases of MS. There was no difference in PB T subsets between GBS and the normal controls. The T4+/T8+ ratio of PB and CSF reduced in cases of tuberculous meningitis, and such changes were also found in PB of viral encephalitis patients. Therefore, it was demonstrated that the immunoregulatory dysfunctions were present in these neurological disorders, and the characters of the changes were different between infectious and autoimmune diseases.

Adult↗
PubMed1989

Possible role of ammonia in experimental cancer anorexia.

Plasma concentrations of ammonia were elevated significantly in tumor-bearing rats prior to the onset of anorexia and continued to increase as the tumor grew and anorexia developed. Associated with this hyperammonemia were elevated levels of brain glutamine and large neutral amino acids (phenylalanine, tyrosine, tryptophan, methionine, histidine). Concentrations of the dopamine metabolites, DOPAC or HVA were elevated in the corpus striatum, nucleus accumbens, hypothalamus and amygdala of anorectic tumor-bearing rats only, while levels of the serotonin metabolite, 5-HIAA, were increased in these brain regions in both anorectic and non-anorectic tumor-bearing rats. Infusing ammonium salts into non-tumor-bearing rats elicited anorexia and alterations in brain amino acid profile and neurotransmitter metabolism that were similar to those observed in anorectic tumor-bearing rats. Therefore, we conclude that ammonia released by tumor tissue may have a direct role in the etiology of experimental cancer anorexia.

Amino Acids↗
PubMed1989

Brain 3-methyoxytyramine varies inversely with blood glucose in decapitated rats.

Concentrations of the dopamine metabolite, 3-methyoxytyramine, were decreased significantly in the corpus striatum and nucleus accumbens of rats 30 min after the IP injection of D-glucose (2 g/kg). Conversely, 90 min after the administration of regular insulin (6 U/kg), significant increases in the concentrations of 3-methoxytyramine were observed in these two brain regions. Brain levels of the major metabolites of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid, did not correlate well with blood glucose concentration. The significant negative correlation of blood glucose with striatal and accumbens 3-methoxytyramine suggests an inverse relationship between dopamine metabolism and blood glucose concentration, that may be secondary to decapitation-induced anoxia.

Animals↗
PubMed1988

Hyperammonemia in anorectic tumor-bearing rats.

Plasma ammonia concentrations were significantly elevated by 150% in anorectic rats bearing methylcholanthrene sarcomas. Assessment of ammonia levels in blood draining these sarcomas indicated nearly a 20-fold increase as compared with venous blood in control rats, suggesting the tumor mass as the source of this increase in ammonia. Infusing increasing concentrations of ammonium salts produced anorexia and alterations in brain amino acids in normal rats that were similar to those observed in anorectic tumor-bearing rats. Therefore, these results suggest that ammonia released by tumor tissue may be an important factor in the etiology of cancer anorexia.

Amino Acids↗
PubMed1988

Reduction of tumor growth following treatment with a glutamine antimetabolite.

Assessment of arterial-venous differences across transplanted methylcholanthrene-induced sarcomas in rats revealed significant decreases in plasma concentrations of glutamine, serine and glucose. Treatment with the glutamine antimetabolite, acivicin, significantly reduced tumor weights by 65% at the conclusion of the experiment 34 days after tumor induction. These results suggest that glutamine is an essential metabolic substrate for tumor growth and that blockade of glutamine utilization can inhibit the growth of these transplantable sarcomas.

Amino Acids↗
PubMed1988

Reversal of neurochemical aberrations after tumor resection in rats.

Assessment of biochemical parameters in methylcholanthrene sarcoma-bearing rats 2 days after the onset of anorexia revealed several biochemical aberrations in blood and brain. Plasma levels of glucose were decreased and lactate concentrations were increased. The plasma and brain amino acid profiles were also greatly altered in these rats, characterized by increased brain concentrations of glutamine and large neutral amino acids. Analysis of regional neurotransmitter and metabolite levels by high-performance liquid chromatography suggested increases in the neuronal activity of dopamine and serotonin in each brain region examined. Surgical removal of the tumors in another group of anorectic tumor-bearing rats was followed by the return of normal feeding within 6 days. Associated with the normalization of food intake was the reversal of these biochemical aberrations in blood and brain. It is hypothesized that the utilization of glutamine and excretion of ammonia by tumor tissue is the precursor of these alterations in brain amino acids and neurotransmitters, which may be causing anorexia.

Amino Acids↗
PubMed1988

Insulin and acivicin improve host nutrition and prevent tumor growth during total parenteral nutrition.

The effect that a 14-day treatment program of total parenteral nutrition (TPN) combined with the glutamine antimetabolite, acivicin, and anabolic hormone, insulin, has on carcass weight and muscle sparing was investigated in tumor-bearing rats. Although TPN resulted in increased carcass weight gain as compared to chow-fed tumor-bearing rats, no savings in gastrocnemius muscle could be demonstrated. The combination of TPN with daily insulin treatment elicited significant increases in both carcass weight and muscle savings, with no alteration in tumor growth. Although combining acivicin with TPN halted tumor growth and increased carcass weight, the change in carcass weight was less than that observed with the insulin-TPN combination. No muscle savings were observed in the acivicin-TPN-treated rats. Yet when acivicin and insulin were combined with TPN, tumor growth was stopped, carcass weight was gained, and muscle mass was saved. Therefore, these experiments suggest that it is possible to add lean body tissue and stabilize tumor growth in rats that receive TPN through anabolic hormone treatment combined with an inhibitor of tumor metabolism.

Animals↗