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Biomedical subjects

T Koh

Publications and source records attributed to T Koh.

At least 37 records · Page 2Linked to original sources
PubMed1999

Efficacy of blood purification therapy for heat stroke presenting rapid progress of multiple organ dysfunction syndrome: a comparison of five cases.

Five patients were admitted to our hospital because of classical heat stroke during the heat waves which attacked our country in the summers 1994 and 1995. The clinical and laboratory findings of all patients suggested the rapid progress of multiple organ dysfunction syndrome (MODS). Blood purification (BP) therapy, in addition to conventional treatment, was performed in three of the patients. Despite their disastrous general condition, all completely recovered or recovered sufficiently to be transferred to a rehabilitation hospital. Two additional patients were treated with conventional treatment only and both died in 1-3 days after admission. Clinical characteristics and laboratory findings on admission showed no differences between the cases receiving BP therapy and those not receiving BP therapy. These findings suggest that, in heat stroke patients, additional BP therapy may provide a better prognosis than conventional therapy only. These beneficial effects of BP may have been due mainly to the removal of proinflammatory cytokines related to heat stroke.

APACHE↗
PubMed1999

Lymphocytic hypophysitis presenting with diabetes insipidus: MR findings.

It has been thought that neurohypophysial involvement manifesting as central diabetes insipidus in lymphocytic hypophysitis is rare. The radiological and clinicopathological features of two cases represent a variant of lymphocytic adenohypophysitis and/or lymphocytic infundibulo-neurohypophysitis are discussed.

Diabetes Insipidus↗
PubMed1999

Priming, second-hit priming, and apoptosis in leukocytes from trauma patients.

BACKGROUND: Polymorphonuclear leukocytes (PMNL) play important roles in both host defenses and systemic inflammatory responses after insults. The objectives of this study are to examine the serial changes in PMNL priming and apoptosis in severely injured patients and to evaluate the impact of second hits on primed PMNL function and systemic vascular endothelial damage. METHODS: Twenty-four severely injured patients (mean Injury Severity Score, 31.1 +/- 9.7) were included. Infections were seen as second hits after trauma in seven patients. Oxidative activity, phagocytosis, and apoptosis of PMNL from serial blood samples were measured by flow cytometry. Oxidative activity with no stimulus and with formylmethionyl-leucyl-phenylalanine (FMLP) were analyzed as the priming index and FMLP response, respectively. Interleukin (IL)-6, IL-10, PMNL elastase, and thrombomodulin concentrations in blood were also measured before and after the second hit. RESULTS: The PMNL priming index was elevated from days 2 to 13, especially days 2 to 5 after injury. FMLP response was enhanced from days 2 to 21 after injury. Apoptosis of PMNL was inhibited for as long as 3 weeks after injury. Infections as second hits after trauma enhanced both the priming index and the FMLP response within 24 hours after diagnosis of infection and increased serum IL-6 concentrations. However, serum thrombomodulin levels were not affected by second hits. All patients with second hits survived. CONCLUSION: Severe trauma stimulated acute-phase priming in PMNL and inhibited apoptosis. Infections after trauma induced second-hit priming in PMNL, but the unchanged serum levels of thrombomodulin suggest that priming per se may not cause systemic vascular endothelial damage.

Adult↗
PubMed1999

Errors in the spleen-blood partition coefficient for water in C15O2 steady-state PET.

The aim of this study was to clarify if the value of 0.93, determined for patients with normal livers, is useful as a pathological spleen-blood partition coefficient for water when the splenic blood flow is quantified by the C15O2 steady-state method. A steady-state PET scan with continuous inhalation of C15O2 and a dynamic PET scan with a H(2)15O bolus injection were performed. From 157 patients, 392 slices were chosen as having planes that encompassed the spleen and provided regions of interest with full signal imaging. A comparison of the results of the steady-state and dynamic methods was performed. When 0.93 was adopted as the spleen-blood partition coefficient for water, an error of about 25% was seen in the splenic blood flow of patients with cirrhosis. When measuring splenic blood flow, the H(2)15O dynamic method is necessary. However, a rough estimate of splenic blood flow is possible by the C15O2 PET steady-state method, if this error is known.

Adult↗
PubMed1999

[Clinical evaluation of weekly hepatic arterial infusion chemotherapy in patients with unresectable metastatic liver cancer].

Twenty-five cases with unresectable metastatic liver cancers were experienced in our hospital over the past five years who underwent weekly 24-hour continuous hepatic arterial infusion chemotherapy using 5-FU and CBDCA. The response rate was 20%, the median survival was 23 months, and the one/two year overall survival rates averaged 81.3/45.5%. In 77% of patients, this therapy prevented death from hepatic metastases. Moreover, since adverse effects were limited compared with bolus infusion, weekly 24-hour continuous hepatic arterial infusion chemotherapy was thought to be a favorable method.

Adult↗
PubMed1999

[Five cases of cerebral and/or cerebellar embolism after insertion of a heparin-coated catheter from the left thoracoacromial artery].

We reported five cases of cerebral and/or cerebellar embolism after insertion of a heparin-coated catheter from the left thoracoacromial artery for multiple liver metastases. They were one patient with multiple liver metastases from the angiosarcoma of the scalp, and 4 others with gastrointestinal cancer liver metastases. The first case suffered a cerebeller embolism just after removal of a catheter that had been obstructed. In this case, it is possible that the thrombus quickly migrated into a cranial vessel from around the catheter. In the others with patent catheters, the cerebral embolisms occurred more than a month after insertion of the catheters. In the latter cases, it is thought that embolisms did not occur because of catheter insertion maneuver. However, a thrombus that grew around the catheter migrated into the left common carotid artery or the left vertebral artery. The anti-coagulation therapy should be considered for prophylactic treatment.

Aged↗
PubMed1998

The gene responsible for pseudohypoparathyroidism type Ib is paternally imprinted and maps in four unrelated kindreds to chromosome 20q13.3.

Hypocalcemia and hyperphosphatemia caused by parathyroid hormone (PTH)-resistance are the only discernible abnormalities in pseudohypoparathyroidism type Ib (PHP-Ib). Because mutations in the PTH/PTH-related peptide receptor, a plausible candidate gene, had been excluded previously, we conducted a genome-wide search with four PHP-Ib kindreds and established linkage to a small telomeric region on chromosome 20q, which contains the stimulatory G protein gene. We, furthermore, showed that the genetic defect is imprinted paternally and thus is inherited in the same mode as the PTH-resistant hypocalcemia in kindreds with PHP-Ia and/or pseudo-pseudohypoparathyroidism, two related disorders caused by different stimulatory G protein mutations.

Chromosome Mapping↗
PubMed1998

The multiple untranslated first exons and promoters system of the oestrogen receptor gene in the brain and peripheral tissues of the rat and monkey and the developing rat cerebral cortex.

Recent studies on the human oestrogen receptor (ER) gene have revealed the complex system with the multiple untranslated first exons and promoters in the ER gene expression. Little information is however available on the system in the ER gene of the rat or nonhuman primate. The rat genomic library was first screened by the rat ER cDNA (0-1) probe. One of the four positive clones (lambda rEgE1) was subcloned and sequenced. The nucleotide sequence was found to contain the exon 0, the intron 0, and the exon 1 with its 3'-ends. The novel untranslated first exons, the exon ON and the exon OS, were further identified. These results indicated the presence of at least four subtypes of the rat ER mRNAs; the messages transcribed from promoter P-0 (ER mRNA (0-1)), putative promoter P-1 (ER mRNA (1-1)), promoter P-ON (ER mRNA (ON-1)) and promoter P-OS (ER mRNA (OS-1)). The P-O- or P-1 driven message (0-1) or (1-1) appeared to be expressed most strongly in major oestrogen central- (anterior pituitary, AP, hypothalamus-preoptic area, HPOA, and amygdala, AMG) and peripheral targets (uterus and ovary). The message (ON-1) was strongly expressed in the liver and kidney, but not in the HPOA, AMG, cerebral cortex, CC, and cerebellum, Ce. The OS-1 message was expressed variably but generally in the tissues examined except for the CC and Ce. Thus, the region- and tissue specific expression of the rat ER gene is likely to be regulated by the multiple untranslated exons and promoters system. Furthermore, when the ER mRNA subtypes were examined in the rat neonatal CC where the ER protein level rose transiently, considered as a model for the development of the ER or progestin receptor A and B isoforms, the expression of the ER mRNAs seemed to be differential postnatally, implicating some stage dependent usage of the promoters in the development. In the monkey, we identified the untranslated first exon OS, the homologue of the rat exon OS. Interestingly, the exon C was found to consist of two different exons, the exon OK and the exon OG. By the alternative usage of the promoters and the alternative splicing, at least six ER mRNA subtypes, that is, ER mRNAs (0-1), (1-1), (OS-1), (OS-OG-1), (OK-1) and (OK-OG-1) were identified in the monkey tissues. These messages were also differentially distributed in the monkey brain and other tissues. It was noteworthy that the P-OK driven messages were expressed almost exclusively in the monkey liver. These results have suggested that the systems of the multiple untranslated first exons and promoters and the alternative splicing are involved in the regulation of the region- and tissue specific expression of the ER gene in the brain and peripheral tissues of the rat and monkey. Stage-related usage of the promoters was also suggested in the ER gene expression in the CC of the postnatal rat in development.

Amino Acid Sequence↗
PubMed1997

Expression of nm23 protein in pulmonary adenocarcinomas: inverse 1orrelation to tumor progression.

Immunohistochemical assessment was made of nm23 protein expression in pulmonary adenocarcinoma. Of the 147 adenocarcinomas 67% (99/147) were weakly and 33% (48/147) strongly positive for nm23 protein. nm23 protein expression in primary tumors was shown to correlate inversely with advancing pathologic stage and the degree of metastasis in regional lymph nodes (P < 0.05). The staining of tumors without nodal metastasis was more intense than with nodal metastasis (P < 0.02). Nodal metastasis was seen in 37% (55/147) cases examined. The immunoreactivity to nm23 protein in tumor cells of nodal metastasis was essentially the same as in those of primary tumors (P < 0.01). Significant correlation between patient prognosis and immunoreactivity for nm23 in primary tumors (P < 0.05) was demonstrated. But none could be found between immunoreactivity and other parameters such as histologic grading, distant metastasis, tumor size or disease-free survival. Neither was there any significant correlation between pathologic parameters examined and the expression of nm23 in any histologic subtype. Multivariate analysis using Cox's proportional hazards regression model with five variables indicated nm23 and lymph node metastasis to contribute to overall patient survival. Based on risk ratio disadvantageous state/advantageous states, the gravity of prognostic factors was assessed for lymph node metastasis as 9.25, nm23 expression as 2.06, distant metastasis as 1.23, pathologic stage as 0.78 and tumor size as 0.77. The results suggested that in pulmonary adenocarcinoma a reduced expression of nm23 protein was associated with lymph node metastasis and poor patient survival.

Adenocarcinoma↗
PubMed1997

CD16 antigen density on neutrophils in chronic myeloproliferative disorders.

Using flow cytometry, we quantitatively examined the density of the CD16 (IgG Fc receptor III) antigen on neutrophils in healthy control subjects, in patients with neutrophilia due to bacterial infection, and in patients with chronic myeloproliferative disorders (chronic myeloid leukemia [CML], polycythemia vera, or essential thrombocythemia). The density was expressed as the mean fluorescence intensity of neutrophils stained with fluorescein isothiocyanate-labeled anti-CD16 monoclonal antibody. We also determined leukocyte alkaline phosphatase activity semiquantitatively in the same population. The mean (+/- SD) density of the CD16 antigen on neutrophils in patients with CML (n = 13; 240.4 +/- 134.8) was lower (P<.001 ) than in healthy control subjects (n = 25; 656.6 +/- 238.0), and the density was also lower than in patients with bacterial infection (n = 15; 671.5 +/- 288.1), polycythemia vera (n = 7; 552.6 +/- 99.9), or essential thrombocythemia (n = 11; 671.5 +/- 411.5). The density of the CD16 antigen was 300 or more in all healthy control subjects and in all patients examined, except for those with CML. The CD16 antigen density was less than 300 in 10 of the 13 patients with CML. Leukocyte alkaline phosphatase activity was also low in 10 of the 13 patients with CML. These findings indicate that flow cytometric analysis of the density of neutrophil CD16 antigen is useful for the differential diagnosis of CML from other chronic myeloproliferative disorders.

Adult↗
PubMed1997

Lack of mutations of preproparathyroid hormone gene in three kindreds with familial isolated hypoparathyroidism.

The mutations of the preproparathyroid hormone (preproPTH) gene have been reported to cause some cases of familial isolated hypoparathyroidism (FIH). We investigated the preproPTH gene of five affected subjects of three Japanese kindreds with FIH. The mode of inheritance in FIH of two families was thought to be autosomal dominant, and the FIH of the other was probably inherited in an autosomal recessive manner. Exons 1, 2 and 3 of the preproPTH gene and its exon-intron boundaries were analyzed with either polymerase chain reaction and single strand conformational polymorphism, or direct sequencing of the amplified DNA. We did not detect any mutations in the amplified regions of the preproPTH gene, but an A to G transition in intron 1 was identified in all of the affected subjects. Among them, four were heterozygote, and the other was homozygote. This transition was considered to be a polymorphism, which was the same as reported previously. These results indicate that the preproPTH gene abnormalities are not responsible for FIH in these families. Further studies are required to elucidate whether genes coding for other molecules, such as calcium-sensing receptor, are involved in FIH.

Base Sequence↗
PubMed1997

Loss of heterozygosity at the N-ras locus in 7,12-dimethylbenz[a] anthracene-induced rat leukemia.

The 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat leukemia model enables scientists to analyze cells altered by carcinogens at various stages of leukemogenesis. We have reported that a consistent type of point mutation. A-->T transversion at the second base in codon 61 of the N-ras gene, was present in this leukemia and that this mutation appeared in bone marrow cells as early as 48 h after a single dose of DMBA. In addition, two leukemia cell lines with the N-ras mutation had no wild-type N-ras allele. Therefore, we examined whether these alterations were essential to the DMBA-induced leukemias. In the study reported here, we confirmed the occurrence of this N-ras mutation in 18 (86%) of 21 primary leukemias and loss of the N-ras wild-type allele in 12 (67%) of 18 leukemias with the mutated N-ras. By using microsatellite markers on chromosome 2, loss of heterozygosity (LOH) at the N-ras locus was observed in eight leukemias, all of which were shown to have lost the wild-type N-ras allele by mutant-allele-specific amplification. These results suggest that LOH related to loss of the wild-type N-ras allele reproducibly occurs in leukemias with the N-ras mutation. Considering the timing of the N-ras mutation and LOH, it is likely that the N-ras mutation is induced early, and cells that have lost the wild-type N-ras allele seem to develop into leukemia. We believe that this system provides a suitable model for studying a series of genetic alterations from the earliest stage of carcinogenesis that cannot be approached in human malignancies.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

[A case of red blood cell(RBC) agglutination on peripheral blood smear and effect of cefpirom sulfate].

We observed red blood cell (RBC) agglutination on peripheral blood smear and an abnormal RBC distribution histogram that suggested the influence of cefpirom sulfate. The patient was receiving cefpirom sulfate when RBC agglutination and the abnormal pattern were recognized, but these abnormalities disappeared as soon as the drug was withdrawn. When the peripheral blood sample was re-examined after warming for an hour at 37 degrees C, the abnormal pattern almost disappeared and RBC agglutination became minimal. We also observed cold agglutination reaction by using O type washed RBCs from a healthy individual that were reacted with cefpirom sulfate, but found only minimal agglutination at RT. As the drug concentration and plasma concentration were increased, we observed more agglutination at 4 degrees C, but this agglutination disappeared after incubation for an hour at 37 degrees C. The cold agglutinin titer was normal. We thus believe that the cause of RBC agglutination in this case was caused by cefpirom sulfate.

Cells, Cultured↗
PubMed1997

The specific N-ras mutation in rat 7,12-dimethylbenz[a]anthracene (DMBA)-induced leukemia.

Intravenous injections of 7,12-dimethylbenz[a]anthracene (DMBA) induce erythroblastic leukemia (erythroleukemia) with #2 trisomy and Long #2 in Long-Evans rats. Recently, a consistent type of mutation, A to T transversion in codon 61 of N-ras gene, was found in all of 6 cultured leukemia cell lines and 13 primary leukemias induced by DMBA using polymerase chain reaction (PCR) and direct sequencing. On the contrary, no mutation was observed in Ha- and Ki-ras genes in these leukemias. The consistent occurrence of the above N-ras mutation in DMBA-induced leukemias indicates that N-ras gene plays an important role in DMBA-leukemogenesis. Mutations in ras genes generally takes place during the initiation stage of carcinogenesis because they often appear in the premalignant stage of tumors. In order to detect the N-ras mutation in an early stage of leukemogenesis, we designed the mutant-allele-specific amplification (MASA) method to detect the mutation in bone marrow (BM) cells of DMBA-treated rats. The MASA method was sensitive enough to detect one mutant cell mixed in 10(6) normal cells. Using this method, the N-ras mutation was found in BM cells 2 days after single DMBA injection and thereafter throughout the preleukemic stage. These results suggest that the N-ras mutation is an earliest event in DMBA-induced leukemogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1997

Establishment and characterization of 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat erythroleukemia cell lines.

To investigate molecular mechanisms and biological behaviors of 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat erythroleukemia, we established 8 new culture cell lines from 7 primary erythroleukemias. We designated them KYD-10, 12, 17, 32, 38, 44A, 44B, and 49. Representative clones isolated from each cell line in early passage were analyzed cytogenetically and genetically. All cell lines except KYD-12 possessed the specific N-ras mutation at the 2nd base of codon 61. Four of them showed #2 trisomy (KYD-10, 32, 38, 44B), and the rest normal diploid karyotype (2n). KYD-32 cells showed Robertson type II #2 trisomy which had never been clonally isolated in vitro although it was reported in some DMBA leukemias in vivo. We further studied the genomic imbalance related to the N-ras allele using mutant-allele-specific amplification (MASA) method. Deletion of normal N-ras allele was found in 5 of 8 cell lines. KYD-32 and 38 retained the normal N-ras allele. The specific N-ras mutation and allelic loss of wild type N-ras were correlated with advanced cell proliferation in culture probably independent of #2 trisomy.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

The untranslated first exon 'exon 0S' of the rat estrogen receptor (ER) gene.

Recently, we have isolated the untranslated first exon 'exon ON' of the rat estrogen receptor (ER) gene from the liver by the use of the 5'-rapid amplification of cDNA ends (5'-RACE) method. To investigate the existence of other untranslated first exon(s), we further analyzed the 5'-untranslated region (UTR) of ER mRNA in the rat liver in this study. Total RNA from the livers of 8-week-old male Wistar rats was subjected to 5'-RACE with the antisense primers located in exon 1 of the rat ER gene. The inserts of four clones (clones 3, 4, 7 and 8) were sequenced. The nucleotide sequences of the clones revealed the existence of a previously unidentified untranslated first exon (we termed it 'exon OS') which was spliced onto exon I of the rat ER mRNA. The distribution of ER mRNA containing 'exon OS' (ER mRNA (OS-1)) in several brain regions and various peripheral tissues of 8-week-old male and female Wistar rats was further analyzed by the use of the reverse transcription-polymerase chain reaction. ER mRNA (OS-1) was found to be widely distributed in the rat brain and peripheral tissues. The distribution of the message was different from that of ER mRNA containing exon 0 (the first reported 5'-UTR form of rat ER mRNA) or of ER mRNA with exon ON which was reported in our recent report. These results indicate that (1) 'exon OS' is a novel untranslated first exon of the rat ER gene, (2) rat ER mRNAs possess at least three forms of 5'-UTRs which are exon 0, exon ON, and exon OS, (3) the tissue specific expression of ER is regulated, at least in part, by the usage of differential promoters in the rat.

Alternative Splicing↗