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Biomedical subjects

K Park

Publications and source records attributed to K Park.

At least 415 records · Page 23Linked to original sources

[Cyclosporin therapy for idiopathic thrombocytopenic purpura].

Nine adult patients with chronic idiopathic thrombocytopenic purpura (ITP) were treated with cyclosporin. Their platelet counts were all below 5 x 10(4)/microliters. It was administered orally at 5 mg/kg/day for 8 weeks. In one patient, the platelet count increased over 10 x 10(4)/microliters in 4 patients it did over 5 x 10(4)/microliters. Gingival hyperplasia was observed in one patient. Renal dysfunction was not observed in any patients. The elevation of PAIgG declined during the period of treatment. These results suggest that this therapy may be useful in refractory idiopathic thrombocytopenic purpura.

Administration, Oral↗

Attenuation in the regulation of the pyrBI operon in Escherichia coli. In vivo studies of transcriptional termination.

The attenuation model for transcriptional regulation of the Escherichia coli pyrBI operon is based on the assumption that transcription terminates upstream of the structural genes at a rho-independent terminator when cells contain high levels of UTP. When, however, the cells are limited for pyrimidines, the presence of ribosomes translating the short leader peptide is presumed to cause an alteration in the secondary structure of the terminator in a way that allows RNA polymerase to transcribe the entire operon. These two premises of transcriptional regulation were tested by using exonuclease protection assays to map the 3' ends of transcripts extracted from cells containing either ample or depleted concentrations of pyrimidines. The results support the model since 99% of the pyrBI transcripts terminated at the (G + C)-rich region of dyad symmetry upstream of the structural genes when cells were grown in excess uracil. In addition, a significant portion (36%) of the pyrBI transcripts extracted from cells containing reduced pyrimidine concentrations extended past the dyad into the structural genes. This observation correlated with the amounts of aspartate transcarbamoylase synthesized in cells under the various conditions. The mapping technique was also used to determine the position of the 5' ends of the transcripts to measure contributions of two potential start sites (P1 and P2) to the pool of pyrBI transcripts. The results show that under all conditions no more than 3% of the total transcripts had 5' ends corresponding to the upstream promoter, P1. In cells lacking P1 virtually all transcripts from P2 terminated at the (G + C)-rich hairpin when the cellular level of pyrimidines was high. Conversely 57% of the transcripts extended past the terminator when cells were grown in UMP. The S1 nuclease technique also provided a measure of the steady state level of transcripts originating at P2. In cells depleted of pyrimidines there was a 5-10-fold increase in these transcripts depending on the number of copies of pyrBI. This increase, which is independent of attenuation, is caused by a different regulatory mechanism which as yet has not been identified.

Aspartate Carbamoyltransferase↗

Structural features of the acetyl-CoA carboxylase gene: mechanisms for the generation of mRNAs with 5' end heterogeneity.

Acetyl-CoA carboxylase [acetyl-CoA:carbondioxide ligase (ADP-forming), EC 6.4.1.2] is the rate-limiting enzyme in the biogenesis of long-chain fatty acids. We have previously characterized five acetyl-CoA carboxylase mRNA species that differ in their 5' untranslated regions but not in the coding region. We have now characterized the exon-intron structure of the genomic DNA that encodes the 5' untranslated region of the mRNA. Generation of different forms of the mRNA is the result of the selective use of two promoters and differential splicing of five different exons. These five exons contain a total of 645 nucleotides and they are scattered over a 50-kilobase-pair genomic DNA region that we have characterized.

Acetyl-CoA Carboxylase↗

Meal-induced peptide tyrosine tyrosine inhibition of pancreatic secretion in the rat.

In the present studies we examined the distribution, release, and biological actions of peptide tyrosine tyrosine (PYY) in the rat. The concentration and distribution of PYY was highest in the ileum and colon as determined by both radioimmunoassay of rat tissue extracts and immunocytochemistry. An ultrastructural comparison of rat and dog colonic PYY cells revealed a bipolar distribution of peptide-containing secretory granules in both species. Serum PYY and pancreatic exocrine secretory responses were monitored after presentation of a meal to meal-trained rats (n = 12). A significant increase in PYY concentrations was not observed until 120 min after meal presentation, a delayed response similar to that previously observed in the dog. PYY responses were also observed in rats after perfusion of the intestine at the level of the duodenum and ileum with an 80 mOsm micellar solution of sodium oleate. Duodenal instillations of the fatty acids resulted in a maximum PYY response after 120 min, whereas rats subject to ileal perfusion of fat exhibited maximum PYY release within the first hour. In other experiments, infusion of exogenous PYY at 100 pmol.kg-1.h-1, which reproduced plasma PYY levels observed after a meal and perfusion of the gut with fat, significantly inhibited CCK-stimulated bile pancreatic volume (P less than 0.02), protein (P less than 0.01), and amylase (P less than 0.01) output. These studies demonstrate a bipolar distribution of PYY-containing secretory granules in cells of the jejunal, ileal, and colonic mucosa, and show that PYY is released in response to a meal in amounts sufficient to inhibit cholecystokinin-stimulated pancreatic secretion. Evidence is presented that PYY may mediate the delayed inhibition of pancreatic secretion that is observed in the rat after ingestion of a meal.

Animals↗

Promotion of incompatible allograft acceptance in rhesus monkeys given posttransplant antithymocyte globulin and donor bone marrow. II. Effects of adjuvant immunosuppressive drugs.

Previous studies from this laboratory demonstrated prolonged acceptance of MHC-mismatched kidney allografts in rhesus monkeys treated with posttransplant rabbit antithymocyte globulin (RATG)* and donor-specific bone marrow (DBM). Here we have investigated the effect of adjunctive immunosuppressive drugs on induction of allogeneic unresponsiveness in this primate model. Parameters examined included median kidney allograft survival time (MST), development of specific antidonor T lymphocyte-mediated cytotoxicity (LMC) and antidonor antibody-dependent cellular cytotoxicity (ADCC). Posttransplant infusion of DBM in RATG-treated kidney allograft recipients resulted in 70 days MST and a dramatic reduction in the incidence of antidonor LMC. However, development of antidonor ADCC was similar to that of RATG controls, suggesting an immune deviation or split tolerance in these animals. Adjunctive azathioprine did not have a beneficial effect in recipients given RATG & DBM, resulting in decreased MST and increased antidonor LMC responses. In contrast, adjunctive cyclosporine (CsA) and low-dose prednisone (P) exerted an additive immunosuppressive effect resulting in a 50% increase in MST and no detectable antidonor LMC. However, CsA & P appeared to enhance the humoral alloimmune response, increasing the incidence of recipients with antidonor ADCC. Long-term graft survival in this group was limited by chronic rejection and especially by CsA-associated toxicity. These studies point out deterrents and also directions for optimizing adjunctive immunosuppression in primates treated with posttransplant RATG & DBM. The results with CsA are relatively encouraging. However, the prevalence of alloantibody and of chronic rejection in these animals suggests that more homogeneous success with tolerance induction in this model may require adjunctive immunosuppressive strategies that reduce humoral immunity.

Adjuvants, Immunologic↗

Surgical correction of astigmatism using paired T-incisions.

Transverse incision astigmatic keratotomy procedures were performed, combined with radial keratotomy, in 16 eyes for correction of astigmatism and coexisting myopia. We used a transverse incision technique in which T-incisions vertically intersected radial incisions of the steepest corneal meridian. After a mean follow-up period of 10 months with a range of six to 27 months, an average 1.92 diopters of the cylinder was corrected. In comparison with 2.11 diopters of the cylinder corrected at postoperative one day, there was a 22.8% decrease in the effect of astigmatism correction after a postoperative period averaging 10 months.

Adolescent↗

The clinical report on six cases of epikeratoplasty.

After the first description of epikeratoplasty for the correction of aphakia by Kaufman in 1980, the application of epikeratoplasty has been extended further to the treatment of keratoconus and high myopia. Six epikeratoplasty for five eyes of high myopia and one eye of keratoconus were performed and followed up for an average of 4.9 months. All cases improved their uncorrected visual acuity, and the preoperative best corrected visual acuity improved or had no change postoperatively except for one case. In the cases of high myopia, the mean preoperative spherical equivalent of -19.4 D was corrected to an average -0.23 D with a range of -1.0 D to +2.5 D postoperatively. In the case of keratoconus, there was a mean decrease in 12.0 D of myopia in terms of the spherical equivalent, and the cornea was flattened by over 8 D in keratometry readings.

Adolescent↗

Factors affecting efficiency of colloidal gold staining: pH-dependent stability of protein-gold conjugates.

The preparation of stable protein-gold conjugates is important in the quantitative colloidal gold staining. The protein adsorption onto colloidal gold particles and pH-dependent stability of protein-gold conjugates were examined using albumin and fibrinogen as model proteins. Albumin stabilized gold sols at pH values higher than 5.0. The amount of albumin necessary to stabilize gold sols was lowest at pH 5.6 and slightly increased as the pH of the adsorption medium was increased. Albumin was also able to stabilize gold particles even at acidic pH values ranging from 3.5 to 4.5, if a sufficient amount of albumin was added. Stable fibrinogen-gold conjugates were obtained at pH values above 6.5. Unlike albumin, the same amount of fibrinogen was able to stabilize gold sols as pH was increased from 7 to 10. The stability of the prepared protein-gold conjugates was very sensitive to the pH of the storing medium. The protein-gold conjugates were least stable at the isoelectric pH of the protein. The results suggest that protein-gold conjugates should be prepared at pH where conjugates are most stable, instead of pH close to the isoelectric point.

Colloids↗

[A colorimetric method for determination of delta-bilirubin in serum using bilirubin oxidase (Trachyderma tsunodae)].

We developed a colorimetric method to measure delta-Bilirubin in human serum using bilirubin oxidase from Trachyderma tsunodae and diazo reagent. In the first step, bilirubin fractions except for delta-Bilirubin, such as diconjugated, monoconjugated and unconjugated forms, are removed by enzymatic oxidation at pH 8.0 in the presence of sodium salicylate. In the second step, delta-Bilirubin remaining after enzymatic oxidation is determined by the conventional indirect diazo method. The results obtained by this method showed intra-day CV of 2.4%, satisfactory linearity and good correlation (r = 0.93, p less than 0.001) with those obtained by high performance liquid chromatography method. This simple and rapid method was clinical useful for determining the bilirubin fractions in sera of hepatic patients.

Basidiomycota↗

[Treatment of acute leukemia with "MB-triple V" therapy--a comparative study of "MB-triple V" therapy and B-triple V therapy].

Eleven patients with acute leukemia were treated with MB-triple V therapy consisting of mitoxantrone, behenoyl-arabinoside, etoposide, vincristine and vindesine. In this regimen, the target points were set for WBC count in the peripheral blood (less than 1,500/microliters) and TNC count in the bone marrow (less than 15,000/microliters). In this study, we compared the WBC count in nadir state and the duration until WBC count returned to above 1,000/microliters between 11 patients with MB-triple V therapy and 15 patients with B-triple V therapy in which target points were not set. In particular, the standard distribution of WBC count in nadir state of MB-triple V group was significantly smaller than that of B-triple V group. The number of early deaths in the course of MB-triple V (0/11, 0%) decreased compared with B-triple V group (3/15, 20%). Seven patients of the eleven patients with this regimen achieved CR state (63.6%). Hereafter, further cases are necessary before this combination chemotherapy as a part of the induction therapy is evaluated.

Acute Disease↗

[Adoptive immunotherapy in patients with medulloblastoma by LAK cells].

Medulloblastoma is one of the most popular malignant brain tumors in children. It accounts for about 15% of all pediatric brain tumors. Radiochemotherapy has prolonged the 5-year survival rate up to 60-85% for patients with medulloblastoma. But the conventional therapy is not so effective to recurrent cases, especially with meningeal dissemination, and generally fatal. There remains a big problem of the neurotoxicity to infants in a growth process under the whole-neuraxis irradiation and chemotherapy. Aiming to relieve the radiation and antitumor drugs, adoptive immunotherapy is greatly expectant. We have had clinical trials of adoptive immunotherapy for 8 patients with medulloblastoma by lymphokine-activated killer (LAK) cells. They were from 2-9 years in age and had cerebrospinal fluid (CSF) dissemination of the tumors. All patients underwent the whole-neuraxis irradiation and chemotherapy. After they had CSF dissemination, they were submitted to an adoptive transfer of allogeneic LAK cells. LAK cells were induced from peripheral blood lymphocytes (PBL) of their relatives with human recombinant interleukin-2. 3-15 x 10(9) LAK cells were transferred intrathecally in 2-3 months. In 3 of 8 patients, neurological signs were improved and malignant cells had never been detected on CSF cytology after the adoptive immunotherapy. One among these 3 patients showed complete response in 20 months. Thus, this is an attractive treatment for patients with medulloblastoma, especially with CSF dissemination, which cannot be cured by current therapeutic intervention.

Brain Neoplasms↗

Application of video-enhanced interference reflection microscopy to the study of platelet-surface interactions.

Video-enhanced interference reflection microscopy (VEIRM) was used to examine contact sites between the ventral membrane of intact platelets and underlying surfaces. It was observed that the ventral membrane in the central granulomere region of fully spread platelets was separated from the surface, while the membrane in other regions was mostly in close contact. The VEIRM image of intact platelets was compared with the video-intensified fluorescence microscopic (VIFM) image of cytoskeletal structures labeled with rhodamine-phalloidin. The VEIRM was also used to visualize the cytoskeletal structures of platelets spread on glass surfaces. Platelets were treated with Triton X-100, glutaraldehyde and acetic acid in sequence. This method was used to follow the sequence of cytoskeletal reorganization of platelets after surface-induced activation. In addition, the effects of albumin and fibrinogen on the cytoskeletal reorganization of spreading platelets were investigated. On fibrinogen-coated surfaces, platelets developed extensive inner filamentous zones which encircled the central granulomere region. In the presence of albumin, however, platelet inner filamentous zones were very poorly developed.

Actins↗