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Biomedical subjects

C Hu

Publications and source records attributed to C Hu.

At least 127 records · Page 7Linked to original sources
PubMed1996

Milk carnitine affects organ carnitine concentration in newborn rats.

Previous studies suggest that exogenous milk carnitine may be necessary during the suckling period to maintain normal fat metabolism. To characterize the relationship between milk carnitine and carnitine in body organs, newborn rats were fed from birth a rat milk substitute with or without 300 micromol/L L-carnitine, corresponding to the concentration present in rat milk, for either 2 or 4 d. Carnitine concentrations in heart, skeletal muscle, liver and small intestine were compared with levels in rat pups that were never fed (d 0) and those that were nursed by their mothers for 4 d. Carnitine supplementation resulted in significantly higher concentrations of carnitine in all organs studied after 4 d compared with nursed controls. Relative intestinal carnitine pool size was 38.1 +/- 3.0, 22.6 +/- 1.0, 7.9 +/- 0.5 and 2.3 +/- 0.7 micromol/g body wt in supplemented, nursed, unsupplemented and never fed pups, respectively (P < 0.05, compared with one another). These results indicate that carnitine organ concentrations are related to dietary intake during the early suckling period and that the small intestine is a considerable and previously unrecognized proportion of the carnitine pool of suckling animals.

Animals↗
PubMed1996

In vitro effects of IL-2 on NK-activity, clonogenic potential, blast cell proliferation and cytokine release of MDS bone marrow patients.

To evaluate the clinical usefulness of IL-2 in myelodysplastic syndromes (MDS) the in vitro effects of interleukin-2 (IL-2) on blast cell proliferation, clonogenic activity, cytokine release and cell mediated cytotoxicity were examined in 49 MDS patients. Morphological analyses of bone marrow (BM) cytospin preparations showed a significant decrease in the number of blast cells in MDS after incubation with IL-2. Incubation of bone marrow mononuclear cells (BMMNCs) with IL-2 induced a significant increase in the number of CFU-GM in comparison with untreated controls. gamma-IFN and GM-CSF, but not alpha-TNF were found to be released in significant amounts by the BMMNCs cultured with IL-2. No significant differences in the surface phenotypes of fresh lymphocytes were observed between the normal and MDS subjects. After incubation with IL-2, we observed a significant increase in the number of CD3-/CD56+ cells in both normal and MDS subjects. Peripheral blood (PB) and BM NK activity against K562 was significantly greater in MDS after stimulation with IL-2. These data suggest the clinical usefulness of IL-2 in a large subgroup of patients as it may reduce the percentage of blasts and increase clonogenic capacity and cell-mediated cytotoxicity.

Adult↗
PubMed1996

Posterior stabilized knee prosthesis for total knee replacement in patients with prior patellectomy.

OBJECTIVE: To determine the outcome of total knee replacement using a posterior cruciate-substituting knee prosthesis in patients who have undergone previous patellectomy. DESIGN: A cohort study, with a follow-up ranging from 2 to 9 years. SETTING: A university-affiliated institution specializing in elective orthopedic surgery. PARTICIPANTS: Sixteen patients with arthritis of the knee who had had patellectomy. All agreed preoperatively to a prolonged postoperative follow-up. INTERVENTION: A cemented posterior cruciate-substituting knee replacement. MAIN OUTCOME MEASURES: Stair climbing ability, the Hospital for Special Surgery knee rating system for clinical results and a radiologic rating using a zonal system. RESULTS: Clinical rating was 69% good or excellent. Eighty-one percent of patients could use the replaced knee as the lead leg on stair climbing. Minor radiolucency, mostly single zone only, was found. Two patients required revision because of pain, but no obvious reasons for this pain were found at operation. CONCLUSION: In the absence of a patella, a posterior cruciate-substituting prosthesis gives reasonable results.

Aged↗
PubMed1996

Cataract free zone and primary health care approach to prevention of blindness in Shunyi county of Beijing.

OBJECTIVE: To establish a three-level eye care network, together with a referral and monitor system for the prevention of blindness, with the aim of creating a cataract free zone. SUBJECTS AND METHODS: Shunyi County with a population of 548364 was chosen as the target site. Our activities included (1) establishment of a County Guiding Committee for the prevention of blindness: (2) training local ophthalmologists and primary eye care personnel: (3) extensive publicity of knowledge for the prevention of blindness: (4) screening for blindness and low vision, (5) cataract surgery as the chief measure for creating a cataract free zone. RESULTS: A referral and monitor system for cataract blindness was established in 1987. Seven local ophthalmologists, 449 primary eye care health workers and six optometrists were trained. 815 cataract-blind patients were identified. Up to December 1991, 667 patients (737 eyes), accounting for 81.84% of the total, were treated with cataract surgery, 90.64% of these eyes had their sight restored, and 59.66% patients resumed work. A cataract free zone has been created in Shunyi County. CONCLUSIONS: The prevention of blindness with cataract surgery as the chief measure can dramatically decrease the prevalence of blindness in a relatively short period of time.

Blindness↗
PubMed1996

[Reconstruction of TMJ condyle cartilage defects with autogenous free periosteal grafts].

How to reconstruct the damaged articular cartilage has been one of the main subjects in treatment of articular disease for a long time. In this experimental study, fullthickness cartilage defects of 4 mm x 5 mm in size were created in rabbit's TMJ condyle cartiage on the left sides. The autogenous free periosteum were transplanted to the defects by using biological gelatin. Postoperatively, the animals were killed at intervals of 1, 2, 4, 8, 12 and 16 weeks. The regenerative cartilage in the defects were examined by gross appearance and histology. The result showed that mesenchymal cells in the cambium layer of periostum can transform into chondroblasts under the mechanical stress.

Animals↗
PubMed1995

Amifostine improves the antileukemic therapeutic index of mafosfamide: implications for bone marrow purging.

One of the principal challenges of cancer chemotherapy is the relative inability of most anticancer drugs to distinguish between normal and neoplastic tissues. Consequently, a broad range of toxicities are experienced by patients, especially myelosuppression. Amifostine, a phosphorylated aminothiol, increases the selectivity of specific anticancer drugs for neoplastic cells by protecting normal tissues. One potential application of this protector is during bone marrow purging to selectively remove contaminating cancer cells. This study took normal or leukemic marrow from human subjects and evaluated the ability of amifostine to selectively protect normal bone marrow progenitor cells versus leukemic progenitor cells from the cytotoxic effect of mafosfamide. The dose response of mafosfamide amifostine on leukemia colony-forming units or normal marrow progenitor cells was determined and the LD95 was calculated. Amifostine pretreatment resulted in a statistically significant protection of granulocyte-macrophage colony-forming units and erythroid blast-forming units from the toxicity of mafosfamide (P = .031). Thus, amifostine protection of normal marrow progenitor cells allows a higher LD95 concentration of mafosfamide to be used in ex vivo purging. In contrast, amifostine pretreatment increased the cytotoxicity of mafosfamide on the fresh human leukemia progenitor cells (P = .006). The dual effect of amifostine protection of normal marrow progenitor cells coupled with amifostine-induced sensitization of the leukemia cells increases the possible cell-kill of leukemic stem cells. With amifostine pretreatment, at the LD95 concentrations of mafosfamide for marrow progenitor cells, there was an estimated 6 log increase in cell-kill of the leukemia cells. This selective cell-kill offers the potential for lowering the incidence of leukemic relapse, while preserving more normal stem cells for autologous transplantation.

Amifostine↗
PubMed1995

Amifostine (WR-2721) protects normal haematopoietic stem cells against cyclophosphamide derivatives' toxicity without compromising their antileukaemic effects.

We compared the effects of amifostine (WR-2721) on the cytotoxicity of mafosfamide or 4-hydroperoxycyclophosphamide (4-HC) in normal marrow progenitor cells (CFU-GM) and leukaemic progenitor cells (CFU-L) during ex vivo purging for autologous bone marrow transplantation (ABMT). Mononuclear cells (MNC) were incubated with amifostine 3 mg/ml for 15 min, washed, and subsequently tested for their sensitivity to mafosfamide or 4-HC (20-200 micrograms/ 10(7) MNC/ml). The LD95 was significantly higher among amifostine-treated cells for PCM-CFU-GM in 6 of 13 patients and for 5R-CFU-GM in 4 of 10 patients (P < 0.05). In contrast, amifostine exhibited no protective effects upon CFU-L. The results of this study will show that amifostine protects normal late and early progenitor cells for the toxic effects of cyclophosphamide derivatives while preserving their antileukaemic effects. These results suggest that amifostine has therapeutic value as a protective agent for normal marrow progenitor cells during ex-vivo purging of bone marrow for ABMT.

Amifostine↗
PubMed1995

[An experimental study on the effect of operation at one side of the temporomandibular joint on the opposite side].

Condylectomy and menisectomy were performed in left TMJ of 14 rabbits, of them, 7 were treated with periosteal interposition and 7 without. Sixteen weeks after operation, condylar cartilage of the right side were studied and compared with 7 normal rabbits by means of histology and histochemistry. The results show that an operation of high condylectomy and menisectomy with or without interposition on one side of TMJ will result in degenerative changes in the other side (non-operated side). The degenerative changes in the rabbits without any interposition are more serious than those with periosteal interposition.

Animals↗
PubMed1994

Phosphorylation of PHAS-I by mitogen-activated protein (MAP) kinase. Identification of a site phosphorylated by MAP kinase in vitro and in response to insulin in rat adipocytes.

PHAS-I is a heat- and acid-stable protein that is phosphorylated on Ser/Thr residues in response to insulin and growth factors. To investigate the phosphorylation of PHAS-I, the protein was expressed in bacteria and purified for use as substrate in protein kinase reactions in vitro. Recombinant PHAS-I was rapidly and stoichiometrically phosphorylated by mitogen-activated protein (MAP) kinase. At saturating MgATP, the Km and Vmax observed with PHAS-I were almost identical to those obtained with myelin basic protein, one of the best MAP kinase substrates. PHAS-I was also phosphorylated at a significant rate by casein kinase II and protein kinase C. To investigate sites of phosphorylation, PHAS-I was digested with collagenase and phosphopeptides were resolved by reverse phase high performance liquid chromatography. Almost all of the phosphate introduced by MAP kinase was recovered in the peptide, Leu-Met-Glu-Cys-Arg-Asn-Ser-Pro-Val-Ala-Lys-Thr. 32P was released in the seventh cycle of Edman degradation, identifying the Ser (Ser64) as the phosphorylated residue. Ser64 was also phosphorylated in response to insulin in rat adipocytes. We conclude that PHAS-I is a substrate for MAP kinase both in vivo and in vitro. As PHAS-I is one of the most prominent insulin-stimulated phosphoproteins in adipocytes, it may qualify as the major MAP kinase substrate in these cells.

Adipocytes↗
PubMed1994

Molecular cloning and tissue distribution of PHAS-I, an intracellular target for insulin and growth factors.

Although the actions of insulin and a number of growth factors that signal via protein-tyrosine kinase receptors are believed to involve increased phosphorylation of key intracellular proteins, relatively few of the downstream phosphoproteins have been identified. In this report we describe a cDNA encoding one of the most prominent insulin-stimulated phosphoproteins in rat adipocytes. The cDNA encodes a protein, designated PHAS-I, which has 117 amino acids and a M(r) of 12,400. When translated in vitro and subjected to SDS/PAGE, PHAS-I migrates anomalously, having an apparent M(r) of 21,000. The predicted amino acid composition is interesting in that approximately 45% of the PHAS-I protein is accounted for by only four amino acids--serine, threonine, proline, and glycine. The PHAS-I gene is expressed in a variety of tissues, although the highest levels of mRNA are present in fat and skeletal muscle, two of the most insulin-responsive tissues. The nucleotide and deduced amino acid sequences of PHAS-I differ from any that have been reported, and homology screening provided no clues concerning the function of the protein. However, in view of its tissue distribution and the fact that the protein is phosphorylated in response to insulin, we speculate that PHAS-I is important in insulin action.

Amino Acid Sequence↗
PubMed1994

Cytomegalovirus DNA in arterial walls of patients with atherosclerosis.

The biological properties of cytomegalovirus (CMV) are consistent with a potential role in the pathogenesis of atherosclerosis. The evidence of such a role has so far been circumstantial, but CMV nucleic acid is beginning to be reported with increasing frequency in the arterial wall. Arterial specimens from 135 patients who underwent vascular surgery for symptomatic atherosclerotic vessel disease were analyzed by PCR for the presence of CMV nucleic acid. Samples were studied from the atheromatous plaque area and from uninvolved aortic tissues of patients undergoing surgery for vascular disease. One primer pair (LA) was used for detection of a late gene, and two other primer pairs (E1 and E2) were used for the immediate early gene region. Serum antibody to CMV was measured by radioimmunoassay. With the late gene primer, CMV nucleic acid was found in 76% of the tissue specimens tested, whereas the E2 gene primer complementary to the transforming mtr2 region was reactive in 90% of the arterial samples. There was no significant difference in the prevalence of CMV DNA in atherosclerotic plaque tissue and in uninvolved aortic tissue from the patients. A second early gene primer was not reactive with the tissue specimens, although it gave positive results with the positive control of infectious virus. Serum antibody to CMV was detected in 86% of the patients in whose tissue CMV DNA was demonstrated. CMV DNA was detected in a high proportion of atherosclerotic plaque tissues as well as in uninvolved aortic tissue of surgical patients, suggesting that latent CMV infection of the arterial wall may be a common occurrence in patients with atherosclerosis.

Adult↗
PubMed1994

An efficient control strategy for dosage regimens.

In medical drug therapy, efficient dosage strategies are needed to maintain target drug concentrations. The relationship between the concentration of a drug and the dosages is often described by compartment models in which the parameters are unknown, although prior knowledge may be available and can be updated after blood samples are taken during the therapy. Currently MAP (maximum a posteriori) Bayesian is the most often used control strategy in this setting. We show by simulation in a one-compartment context that the performance of the MAP Bayesian strategy depends on the assumptions in prior distribution of the parameters as well as the cost function. We propose an alternative control strategy, VU, that outperforms and is more robust than the MAP Bayesian strategy in a variety of problem settings.

Bayes Theorem↗
PubMed1994

Comparison of some control strategies for three-compartment PK/PD models.

In drug therapy, effective dosage strategies are needed to maintain target drug effects. The relationship between drug dose and drug effect is often described by pharmacokinetic/pharmacodynamic (PK/PD) models where typically the PK model has a multicompartment form and the PD model is the sigmoidal Emax model. The parameters in the PK/PD model are generally unknown in the individual patient, although prior knowledge may be available and can be updated after measurements of drug effect are taken during the therapy. This fact, together with the complexity of the PK/PD model, makes the control problem complex. This paper investigates several control strategies in the framework of a three-compartment PK model plus an effect site with a PD model. Using computer simulations under different assumptions, we show that a MAP (maximum a posteriori) Bayesian type of strategy is effective, nevertheless in high-risk situations a stochastic control strategy hedging against estimation errors provides better performance at computational cost.

Bayes Theorem↗