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Biomedical subjects

C Y Su

Publications and source records attributed to C Y Su.

At least 91 records · Page 5Linked to original sources

In vivo stimulation of myelopoiesis in cyclophosphamide-treated mice by purified human GM-CSF.

Human granulocyte-macrophage colony-stimulating factor (hGM-CSF) secreted by a hepatoma cell line, HA22T/GVH, was purified and assessed for its effects in vivo on blood leukocytes and bone marrow granulocyte-macrophage progenitor cells (CFU-GM) in ICR mice pretreated with a sublethal dose of cyclophosphamide (cytoxan). The hGM-CSF preparations were natural and had no detectable endotoxin. Five days after the administration of 300 mg/kg cytoxan, severe leukopenia with marked myelopoietic suppression was induced. The cytoxan-treated mice were then injected intraperitoneally with 10,000 units of purified hGM-CSF/mouse daily for three days. Leukopenia was totally abrogated and the leukocyte number greatly increased to a level 2- to 3-fold higher than in GM-CSF-uninjected mice. Differential white cell count showed that the subpopulations of leukocytes responsive to hGM-CSF stimulation were mainly of neutrophils and monocytes, while the lymphocytes remained unaffected. Meanwhile, in the bone marrow, hGM-CSF administration induced an apparent (3-fold) increase in the number of myeloid progenitor cells, CFU-GM. However, the effect in vivo of a single hGM-CSF injection could only maintain for 48 hrs. In addition, the loss in body weight caused by cytoxan was less in the mice with subsequent hGM-CSF than those without CSF. These results suggest that injection of GM-CSF can effectively reconstitute the cytotoxic drug-damaged myelopoiesis without apparent in vivo toxic reaction.

Animals↗

[Chronic myelocytic leukemia induced into remission by interferon-alpha associated with early esophageal cancer].

A fifty-one-year-old male patient visited the Department of Dermatology of Toho University Ohashi Hospital with a complaint of generalized exanthema, which was diagnosed assyringoma; at that time his leukocytosis was recognized. He was admitted to our department on August 8, 1988. Physical examination on admission revealed slight hepatosplenomegaly. WBC count was elevated (50,700/microliters). He was diagnosed as having Ph1-positive CML in the chronic phase and was treated with IFN-alpha (HLBI, Sumitomo, 3 x 10(6) units/day, daily, I. M.) from August 12, but an elevated lesion was detected at the lower part of his esophagus by endoscopy, and it was diagnosed by biopsy as squamous cell carcinoma. Radical operation for esophageal cancer was performed on September 26; at that time his WBC count was 17,400/microliters. After discharge, his WBC level was maintained within normal range by IFN-alpha. On August 2, 1989, he was readmitted to our hospital because of lymphoblastic crisis. Although he attained transient complete remission, he died of pneumonia after the relapse on January 10, 1990. IFN-alpha therapy is suggested to be useful for the treatment of CML associated with gastrointestinal cancer because of its possible parenteral administration and mild toxicity.

Carcinoma, Squamous Cell↗

Ultrastructural studies on splenic microcirculation of the rat.

In an attempt to establish or supplement the three dimensional features of splenic microvasculature vascular corrosion casts and freeze-cracked tissue blocks of the rat spleen were studied by electron microscopy (SEM & TEM) with special reference on the filtration mechanism of blood cells (RBCs) in the spleen. Both open and closed circulation were observed. TEM investigation showed that macrophages were often found to be located outside the abluminal surface and between two venous sinus branches. Some of them occasionally extend their filopodia and emerge through intercellular slits (IES) out to the luminal surface of the venous sinus. In many cases discontinuity of the junctional complex of the endothelial cells is occasionally identified; this may behave as a detour to prolong RBC passage through the reticular space, thus facilitating their contact with phagocytic cells. SEM observation on vascular corrosion casts have provided clear evidence of direct arteriovenous connection in the rat spleen. Observation on the freeze-cracked tissue block showed a consistent evidence that the macrophages occasionally extend their filopodia and emerge through IES out to the luminal surface of the venous sinus. It indicated that a great majority of the RBCs passing through meshwork of the reticular space of the red pulp, i.e., open circulation would be detected by the macrophages dwelling in the reticular space. The RBCs passing through the fast component. i.e., closed circulation were also subjected to detection and phagocytosis either by macrophages dwelling in the reticular space while their passage through the discontinuity of the junctional complex to the reticular space or by macrophages emerging through IES while their passage along the venous sinus wall. Ultrastructural studies provide an evidence that the spleen performs it filtration function by a multifiltration mechanism.

Animals↗

Effect of lipopolysaccharide on the production of colony-stimulating factors by the stromal cells in long-term bone marrow culture.

The production of colony-stimulating factors (CSFs) by murine bone marrow stromal cells was studied with Dexter long-term bone marrow culture (LTBMC). For induction of CSF release, various concentrations (0.5-40.0 microgram/ml) of bacterial lipopolysaccharide (LPS) were added to nonrecharged 3-week-old LTBMCs consisting of an intact or macrophage-depleted adherent cell layer. The depletion of monocytes/macrophages from freshly prepared bone marrow cell suspension was performed by carbonyl-iron incorporation before establishment of LTBMC. The supernatants (Sup) of normal LTBMCs contained a low level of macrophage colony-stimulating factor (M-CSF) that was produced by the adherent cells but not by the nonadherent cell elements. No colony inhibitor was found in the Sup of LTBMCs, whereas a colony-promoting activity (CPA) was detected in medium conditioned by the adherent marrow cells (AC-CM). CPA could enhance the colony formation of myeloid progenitor cells when used in combination with recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF). The production of CSFs peaked at about 24 h after refeeding, but it then declined to only half the optimal activity at the end of the week. Addition of LPS to the intact LTBMC invariably increased the production of a GM-CSF-like cytokine. The release of this cytokine was dose dependent and peaked at a dosage of 20 micrograms/ml of LPS at 24 h after treatment. In contrast, macrophage-depleted marrow-adherent cells failed to respond to LPS for CSF secretion. These results suggest that LPS can stimulate marrow macrophages to directly release CSF or to potentiate the production of CSF by other stromal cells.

Animals↗

[Treatment of adult acute lymphoblastic leukemia with Ad-VP-L regimen].

From 1985 to 1989, we treated a total of 24 adult patients with acute lymphoblastic leukemia, 17 males and 7 females, median age 26 (range 16-70 yr), with a protocol consisting of remission induction with Adriamycin (ADR), vincristine (VCR), prednisolone (PDN) and 1-asparaginase (ASP), followed by two consolidation courses with ADR, VCR, cyclophosphamide, methotrexate and PDN (Ad-VEMP), combined with CNS-prophylaxis (intrathecal MTX and PDN). Cyclic chemotherapy with VMM (vindesine, 6-MP and MTX) and Ad-VEMP regimen or therapy with VMM regimen only was used to maintain remission. Twenty patients (83.3%) achieved complete remission. The median durations of overall survival and complete remission were 20 and 18 months respectively. The significant unfavorable prognostic factors associated with survival were old age (more than 50 yr), high WBC counts on admission (more than 20,000/microliters) and low nadir of WBC counts (less than 500/microliters). The responders who received ASP for a period of 10 days had longer survival durations than did other responders. Remission did not continue long enough with our protocol, although a high CR rate was achieved. We conclude that the design of consolidation and maintenance therapy must be improved in order to obtain a longer duration with our protocol.

Adolescent↗

[Pharmacokinetics and distribution of isotetrandrine in rats].

A reversed-phase HPLC method for determination of isotetrandrine (ITD) in biological specimens was developed. The mobile phase composed of 0.2% (w/v) SDS, 47% acetonitrile and 53% distilled water (pH 2), at a flow rate of 1.5 ml/min with determination wavelength of 230 nm. The drug concentration-time curves of ITD in rats after iv of 12.5, 25 and 50 mg/kg were shown to fit a two-compartment open model with half-lives of 67.1 +/- 6.22 68.0 +/- 2.57 and 97.6 +/- 14.6 min, respectively. At doses of 12.5 and 25 mg/kg, the elimination of the drug from plasma was found to be in accord with linear kinetics, but when the dosage was 50 mg/kg, a non-linear kinetics was observed. Following ig ITD 100 and 250 mg/kg, the plasma concentration-time curves exhibited two marked peaks. Half-lives of elimination after ig doses was much longer than after iv administration, with mean values of 9.35 +/- 3.24 h (100 mg/kg) and 9.01 +/- 3.02 h (250 mg/kg). Distribution of the drug in rats was extensive, highest level of the drug was found in the lung and lowest in plasma after iv administration. Following ig administration, highest level of the drug was found in the liver and lowest in plasma.

Alkaloids↗

A coin as a tracheal foreign body for 30 years.

A rare case of long-standing tracheal foreign body, a coin retained in the trachea for over 30 years, is presented. A 35-year-old female patient came to the hospital complaining of recurring cough and sensation of a lump in the throat since childhood. A round radiopaque shadow between the clavicles was found in routine chest X-ray film. She recalled swallowing a coin at about the age of five. Reviewing an old film taken for her cough problem at another hospital 11 years previously, we noted the same shadow at the same level. A rusty coin was removed through a ventilating bronchoscope from the trachea, where a narrow sulcus and some granulation tissue were found. Her complaints disappeared thereafter.

Adult↗

Insulinlike growth factor II expression and oval cell proliferation associated with hepatocarcinogenesis in woodchuck hepatitis virus carriers.

Insulinlike growth factor II (IGF-II) is a highly mitogenic fetal growth factor suspected of regulating the growth of a wide spectrum of tissues via an autocrine or paracrine mode of action or both. High steady-state levels of IGF-II RNA were detected in 45% of hepatocellular carcinomas (HCCs) arising from woodchuck livers with persistent woodchuck hepatitis virus (WHV) infection. Analysis of WHV RNA in the same HCCs revealed that HCCs with high levels of IGF-II RNA contained low or undetectable levels of WHV RNA and HCCs with low levels of IGF-II RNA contained high levels of WHV RNA. Integrated WHV DNA was present in HCCs from both groups, but viral DNA replicating forms were present, predominantly in HCCs with low levels of IGF-II. Several IGF-II RNAs, the most prominent of which were poly(A) species of approximately 3.75 and 1.1 to 1.3 kilobases, were detected only in precancerous nodules and HCCs. Levels of IGF-II were elevated two- to three-fold in the serum of woodchucks with chronic active hepatitis preceding the occurrence of HCC. Proliferation of a population of oval cells, which arise from portal tract regions in the liver, preceded the development of HCC and was a prominent feature of livers from which tumors with high levels of IGF-II occurred. The HCCs tended to have distinct histological features according to their growth factor status. Tumors with low levels of IGF-II were generally highly differentiated acinar-trabecular HCCs, whereas tumors with high levels of IGF-II were more anaplastic, with regions of fibrosis and fatty accumulation. A model to relate the pathology of WHV infection to oval cell proliferation and IGF-II expression in the development of these heterogeneous HCCs is presented.

Animals↗

Simultaneous determination of gastrodin and its metabolite by HPLC.

A rapid and specific HPLC method for the simultaneous determination of gastrodin and its metabolite gastrodigenin (p-hydroxybenzyl alcohol) in rat plasma, bile, liver, urine and faeces is described. The separation was achieved by using a reversed phase column (YWG-C18) eluted with methanol-water (2.5:97.5 v/v). Phloroglucinolum was used as internal standard and the peaks were detected at UV 221 nm. The protein precipitation with ethanol was a very simple and rapid method for sample preparation. The gastrodin and gastrodigenin were quantitated by measuring the peak-height ratios. There was a linear concentration range of 10-320 micrograms/mL in the assay for both compounds. The coefficients of variation (within-day) for samples spiked with gastrodin and gastrodigenin were 2.94% and 3.08%, respectively. The method demonstrated a high specificity and was suitable for use in pharmacokinetic studies.

Animals↗

Transcription of genomic bovine and Xenopus laevis DNA species by RNA polymerase III in HeLa-cell cytosol extracts.

RNA transcribed from genomic Xenopus laevis DNA by RNA polymerase III in HeLa-cell extract was found in discrete size classes and was transcribed from at least two different Xenopus repeat DNA species. Very little 5S ribosomal RNA was transcribed, contrasting with results obtained on transcription of genomic Xenopus DNA by Xenopus extract [Bogenhagen et al. (1982) Cell 28, 413-421]. The low transcription was not due to an inability to use 5S rDNA templates, since the cloned Xenopus 5S ribosomal gene and pseudogene were effective templates for RNA polymerase III in HeLa extract. RNA transcribed from genomic bovine DNA by RNA polymerase III in HeLa-cell cytosol extract consisted of 120-nucleotide RNA and a larger amount of heterogeneously sized RNA (180-650 nucleotides). Only a small portion of the 120-nucleotide RNA was 5S rRNA. Most of the 120-nucleotide RNA and the larger RNA species were transcribed from one bovine repeat DNA. Genes for 5S rRNA and bovine repeat DNA were transcribed roughly in proportion to their frequency in Bos, contrasting with results in a homologous system in which transcription of repeat genes is repressed [Furth (1985) Biochem. Biophys. Res. Commun. 131, 551-556]. Bovine 5S rRNA genes appear to be concentrated on one DNA fragment obtained by restriction-enzyme-HindIII digestion of genomic bovine DNA.

Animals↗

Deletion in chromosome 11p associated with a hepatitis B integration site in hepatocellular carcinoma.

Hepatitis B virus (HBV), a virus with known carcinogenic potential, integrates into cellular DNA during long-term persistent infection in man. Hepatocellular carcinomas isolated from viral carriers often contain clonally propagated viral DNA integrations. As small chromosomal deletions are associated with several types of carcinomas, the occurrence of chromosomal deletions in association with HBV integration in hepatocellular carcinoma was studied. HBV integration was accompanied by a deletion of at least 13.5 kilobases of cellular sequences in a human hepatocellular carcinoma. The viral DNA integration and deletion of cellular sequences occurred on the short arm of chromosome 11 at location 11p13-11p14. The cellular sequences that were deleted at the site of HBV integration were lost from the tumor cells, leaving only a single copy of the remaining cellular allele.

Animals↗

Transcription of 5S RNA by RNA polymerase III from genomic bovine DNA templates.

RNA polymerase III in an extract of HeLa cells transcribes RNA 5S in size from genomic bovine DNA template. This RNA represents a major fraction of the RNA synthesized. 5S RNA is not transcribed from bovine chromatin at equivalent concentrations and RNA the size of tRNA or tRNA precursor is not detected. At low UTP concentrations RNA slightly smaller in size than 5S is synthesized in addition to 5S RNA.

Animals↗

Transcription of bovine satellite DNA by purified RNA polymerase III.

Purified calf thymus RNA polymerase III synthesizes, from calf thymus DNA template, RNA which hybridizes to the major repeated sequence of Eco R1-digested calf thymus DNA. Similar results are obtained with RNA transcribed from calf thymus chromatin. It is suggested that this DNA sequence, which is derived from bovine satellite DNA, may be genetically active.

Animals↗