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K Okada

Publications and source records attributed to K Okada.

At least 289 records · Page 16Linked to original sources
PubMed1999

Alpha2-antiplasmin gene deficiency in mice is associated with enhanced fibrinolytic potential without overt bleeding.

alpha2-antiplasmin (alpha2-AP) is the main physiologic plasmin inhibitor in mammalian plasma. Inactivation of the murine alpha2-AP gene was achieved by replacing, through homologous recombination in embryonic stem cells, a 7-kb genomic sequence encoding the entire murine protein (exon 2 through part of exon 10, including the stop codon) with the neomycin resistance expression cassette. Germline transmission of the mutated allele was confirmed by Southern blot analysis. Mendelian inheritance of the inactivated alpha2-AP allele was observed, and homozygous deficient (alpha2-AP-/-) mice displayed normal fertility, viability, and development. Reverse transcription-polymerase chain reaction confirmed the absence of alpha2-AP mRNA in kidney and liver from alpha2-AP-/- mice, in contrast to wild-type (alpha2-AP+/+) mice. Immunologic and functional alpha2-AP levels were undetectable in plasma of alpha2-AP-/- mice, and were about half of wild-type in heterozygous littermates (alpha2-AP+/-). Other hemostasis parameters, including plasminogen activator inhibitor-1, plasminogen, fibrinogen, hemoglobin, hematocrit, and blood cell counts were comparable for alpha2-AP+/+, alpha2-AP+/-, and alpha2-AP-/- mice. After amputation of tail or toe tips, bleeding stopped spontaneously in alpha2-AP+/+, as well as in alpha2-AP+/- and alpha2-AP-/- mice. Spontaneous lysis after 4 hours of intravenously injected 125I-fibrin-labeled plasma clots was significantly higher in alpha2-AP-/- than in alpha2-AP+/+ mice when injecting clots prepared from alpha2-AP+/+ plasma (78% +/- 5% v 46% +/- 9%; mean +/- SEM, n = 6 to 7; P =.02) or from alpha2-AP-/- plasma (81% +/- 5% v 46% +/- 5%; mean +/- SEM, n = 5; P =.008). Four to 8 hours after endotoxin injection, fibrin deposition in the kidneys was significantly reduced in alpha2-AP-/- mice, as compared with alpha2-AP+/+ mice (P </=.005). Thus, alpha2-AP-/- mice develop and reproduce normally; they have an enhanced endogenous fibrinolytic capacity without overt bleeding.

Alleles↗
PubMed1999

Expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor on B-1a cell from persistent lymphocytosis (PL) cows and lymphoma cell induced by bovine leukemia virus.

The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on B lymphocytes from persistent lymphocytosis (PL) cattle and lymphoma cells induced by bovine leukemia virus (BLV) was studied in vitro. Flow cytometric analysis showed that high levels of receptors to GM-CSF were expressed on these cell types. Proliferation of these B cells was induced in response to bovine GM-CSF. In tumor cell lines, the rate of cell proliferation was correlated with expression of GM-CSF receptors. A monoclonal antibody to GM-CSF inhibited lymphocyte proliferation and blocked the GM-CSF binding of lymphocytes. Cells expressing GM-CSF receptor were Ig positive and both CD5 and CD11 positive (B-1a cell). These results suggest that an abnormal expression of GM-CSF receptors on B lymphocytes from PL and lymphoma cells induced by BLV plays important roles in the PL and proliferation of lymphoma.

Animals↗
PubMed1999

High grade surface osteosarcoma: a clinicopathologic study of 46 cases.

BACKGROUND: High grade surface osteosarcoma is a rare subtype of osteosarcoma arising on the surface of bone, accounting for only 8.9% of surface osteosarcomas at the study institution. METHODS: This study reviews 46 cases of high grade surface osteosarcoma, comprised of 13 cases from the Mayo Clinic files and 33 from the authors' files. Histologic features were reviewed in all cases, and radiographs were reviewed in 29 cases. RESULTS: There was a definite male predominance, and 70% of the patients were in the second and third decades of life. Forty-four of the 46 patients had lesions involving the long bones, the most common site being the midportion of the femur. Radiographically, the majority of lesions showed dense to moderate mineralization with a fluffy, immature appearance. Radiating spicules of bone perpendicular to the long axis of the bone, characteristic of periosteal osteosarcoma, were sparse. Histologic findings were identical to those of conventional osteosarcoma. Overall, survival at 5 years was 46.1%. Statistical analysis revealed that marginal excision was associated with an increased risk of local recurrence and that the patients with Broders Grade 3 tumors had a better prognosis than those with Grade 4 tumors. A good response to chemotherapy was associated with better clinical outcome. CONCLUSIONS: High grade surface osteosarcoma is a rare subtype of surface osteoscarcoma that has a prognosis similar to that of conventional osteosarcoma, in contrast to the more common type of osteosarcoma arising on the surface of bone. Wide excision and effective systemic chemotherapy are associated with better clinical results.

Adolescent↗
PubMed1999

Structure of Thermus thermophilus HB8 aspartate aminotransferase and its complex with maleate.

The three-dimensional structures of pyridoxal 5'-phosphate-type aspartate aminotransferase (AspAT) from Thermus thermophilus HB8 and pyridoxamine 5'-phosphate type one in complex with maleate have been determined by X-ray crystallography at 1.8 and 2.6 A resolution, respectively. The enzyme is a homodimer, and the polypeptide chain of the subunit is folded into one arm, one small domain, and one large domain. AspATs from many species were classified into aminotransferase subgroups Ia and Ib. The enzyme belongs to subgroup Ib, its sequence being less than 16% identical to the primary sequences of Escherichia coli, pig cytosolic, and chicken mitochondrial AspATs, which belong to subgroup Ia whose sequences are more than 40% identical and whose three-dimensional structures are quite similar with the active site residues almost completely conserved. The first X-ray analysis of AspAT subgroup Ib indicated that the overall and the active site structures are essentially conserved between the AspATs of subgroup Ia and the enzyme of subgroup Ib, but there are two distinct differences between them. (1) In AspAT subgroup Ia, substrate (or inhibitor) binding induces a large movement of the small domain as a whole to close the active site. However, in the enzyme of subgroup Ib, only the N-terminal region (Lys13-Val30) of the small domain approaches the active site to interact with the maleate. (2) In AspAT subgroup Ia, Arg292 recognizes the side chain carboxylate of the substrate; however, residue 292 of the enzyme in subgroup Ib is not Arg, and in place of Arg292, Lys109 forms a salt bridge with the side chain carboxylate. The thermostability of the enzyme is attained at least in part by the high content of Pro residues in the beta-turns and the marked increase in the number of salt bridges on the molecular surface compared with the mesophilic AspAT.

Amino Acid Sequence↗
PubMed1999

Ovine MHC class II DRB1 alleles associated with resistance or susceptibility to development of bovine leukemia virus-induced ovine lymphoma.

For the further characterization of bovine leukemia virus (BLV)-induced leukemogenesis, we investigated the association between polymorphism of ovine leukocyte antigen (OLA)-DRB1 gene and tumor development after infection of sheep with BLV. We infected 28 sheep with BLV and cloned exon 2 of the OLA-DRB1 gene from asymptomatic animals and from animals with lymphoma Sequence analysis revealed that, among 12 healthy sheep without any evidence of tumor, ten (83.3%) carried DRB1 alleles encoding Arg-Lys (RK) at positions beta70/71 as compared with only 6 (37.5%) of the 16 sheep with lymphoma, which suggested that alleles encoding the RK motif might protect against development of tumors after infection by BLV. By contrast, alleles encoding Ser-Arg (SR) at positions beta70/71 were present at a significantly elevated frequency in sheep with lymphoma as compared with the healthy carriers, which indicated that OLA-DRB1 alleles encoding the SR motif might be positively related to susceptibility to tumor development. The two amino acids in these motifs line a pocket that accommodates the side chain of a bound peptide according to a model of the crystal structure of human leukocyte antigen (HLA)-DR1. To analyze immunoreactions of sheep with alleles that encoded RK or SR at beta70/71, we selected sheep with either the RK/SR genotypes or the SR/SR genotypes and immunized them with a mixture of multiple synthetic antigenic peptides that corresponded to T-helper, T-cytotoxic, and B-cell epitopes of the BLV envelope glycoprotein gp51. Two weeks after the last immunization, all of the sheep were challenged with BLV. Sheep with the RK/SR genotype produced neutralizing antibodies against BLV; they eliminated BLV completely within 28 weeks of the BLV challenge, and they gave strong lymphocyte-proliferative responses to the peptides used for immunization. Moreover, such animals did not develop lymphoma. By contrast, sheep with the SR/SR genotype continued to produce BLV throughout the experimental period and developed terminal disease. Our results indicate that the differences in immunoresponse were due to differences in major histocompatibility complex class II alleles and reflected the risk of BLV-induced leukemogenesis. In addition, it appears that susceptibility to tumor development may be determined to some extent by polymorphic residues binding to antigenic peptides directly within the binding cleft of the OLA-DR molecule.

Alleles↗
PubMed1999

Low susceptibility of specific inbred colonies of rats to nickel tumorigenesis in soft tissue.

Nickel sarcomatogenesis induced by a single intramuscular injection of 10 mg of nickel subsulfide (NiSS) into the soft tissue of two different colonies of Wistar rats was studied. In spontaneously hypertensive rats (SHR), a specific inbred colony of rats derived from a certain Wistar strain, the sarcoma induction rate was lower than that in common closed colony rats of the same strain (CWR). Sarcomas were induced in only 7 of the 30 rats (23.3%) in the SHR group (15 female and 15 male) but in 21 of the 31 rats (67.7%) in the CWR group (15 female and 16 male) (P < 0.005). The incidence of sarcoma induction was lower in female rats than in male rats in both the SHR (female 13.3% < male 33.3%) and CWR (female 53.3% < male 81.4%) groups. Primary tumors in the SHR group exhibited a lower grade of metastasis to lymph nodes (P < 0.001) and lungs (P < 0.05) than in the CWR group. Our study demonstrated that rats in a certain specific inbred colony are less susceptible to nickel tumorigenesis in soft tissue than rats in a common closed colony.

Animals↗
PubMed1999

Functional B-cell response in intrahepatic lymphoid follicles in chronic hepatitis C.

Intrahepatic lymphoid follicle (ILF) formation is one of the most characteristic and commonly observed histological features in patients with chronic hepatitis C. However, little is known regarding whether follicles in the liver belong to functional lymphoid tissues, where B cells are activated, differentiated, and proliferated, or if the lymphocytes are merely infiltrated after recruitment from the secondary lymphoid organs. To ascertain this possibility, we examined the expression of markers for B-cell activation, differentiation, and proliferation in ILFs in patients with chronic hepatitis C using surgically resected specimens, and compared them with specimens of perihepatic lymph nodes by an immunohistochemical technique. Germinal center (GC) formation in the ILFs was frequently found in HCV-positive cases. The distribution of immunoglobulin M (IgM)-, IgD-, and IgG-positive cells and the expression patterns of Ki-67, CD23, or bcl-2 and bcl-6 gene products in the follicles with GC formation in the liver of patients with chronic hepatitis C were similar to those of lymph nodes, indicating that B cells are activated, proliferated, and differentiated in the ILFs with GC formation in patients with chronic hepatitis C. Oligoclonal expansion of B cells in the livers with ILFs was confirmed by an analysis of immunoglobulin heavy chain (IgH) gene rearrangement determined by polymerase chain reaction (PCR). These data strongly suggest that ILFs with GC formation, which are frequently found in patients with chronic hepatitis C, may functionally be the same as those found in lymph nodes with respect to B-cell expansion and maturation.

Adult↗
PubMed1999

Selective visual and auditory attention toward utterances-a PET study.

The purpose of this study was to reveal functional areas of the brain modulating processing of selective auditory or visual attention toward utterances. Regional cerebral blood flow was measured in six normal volunteers using positron emission tomography during two selective attention tasks and a control condition. The auditory task activated the auditory, inferior parietal, prefrontal, and anterior cingulate cortices. The visual task activated the visual association, inferior parietal, and prefrontal cortices. Both conditions activated the same area in the superior temporal sulcus. During the visual task, deactivation was observed in the auditory cortex. These results indicate that there exists a modality-dependent selective attention mechanism which activates or deactivates cortical areas in different ways.

Adolescent↗
PubMed1999

Signalling in cell type specification.

Positional information is an important determinant in the establishment of cellular identity in plants. It is established during pattern formation and is maintained in growing organs. Cells maintain the ability to respond to changes in positional information during development indicating that the mechanism for perceiving such information must remain intact until relatively late in development. Once positional cues are perceived they set in motion a number of cascades resulting in the differentiation of particular cell types in defined locations. The circuitry underpinning these later events is being teased out using genetics. Evidence is emerging for the existence of an array of both positive and negative genetic regulators from studies in a number of diverse plant model systems

Arabidopsis↗
PubMed1999

Mucosa-associated lymphoid tissue lymphoma of the duodenum forming multiple polypoid lesions: report of a case.

We report herein the case of a patient found to have mucosa-associated lymphoid tissue (MALT) lymphoma of the duodenum forming multiple polypoid lesions. Endoscopic examination revealed multiple small nodules with a yellow-white, rough surface in the duodenal bulb. Histopathological and immunological findings subsequently suggested low-grade B-cell MALT lymphoma. Cytologically, MALT lymphoma is similar to multiple lymphomatous polyposis (MLP); however, this case, which involved multiple polypoid lesions, was confirmed not to be MLP.

Aged↗
PubMed1999

Immunohistochemical expression of p53 and bcl-2 proteins is not associated with sarcomatoid change in renal cell carcinoma.

An immunohistochemical study was conducted to examine the expression of p53 and bcl-2 proteins in RCC (renal cell carcinoma) with sarcomatoid change in order to determine whether abnormalities in those proteins are associated with an enhanced malignant potential of RCC. Paraffin-embedded tissues from 11 patients with RCC, in which sarcomatoid change was prominent, were stained using anti-p53, bcl-2 and Ki-67 antibodies. Immunoreactivities for these antibodies were compared between the sarcomatoid components and corresponding basic histologic (clear or papillary) components in individual cases. Measurement of the mean nuclear areas of each component was also performed using an image analyzer system. There was no substantial increase in immunoreactivity for p53 or bcl-2 proteins in sarcomatoid components as compared with basic components. In contrast, the percentage of Ki-67-positive cells and the mean nuclear area were significantly larger in sarcomatous components than in basic components. The expression of p53 and bcl-2 proteins was not likely to play a major role in the sarcomatoid change of RCC.

Adult↗
PubMed1999

Peritumoral edema in osteoid osteoma on magnetic resonance imaging.

OBJECTIVE: To determine whether there is a relationship between the peritumoral edema caused by osteoid osteoma seen on magnetic resonance (MR) imaging and the patient's age, duration of symptoms, or location of the lesion. DESIGN AND PATIENTS: All histologically proven osteoid osteomas seen in our institutions during a 5-year period in patients with known age, gender, duration of symptoms, and available radiological and MR imaging examinations were included in this study. The extent of the edema in the bone marrow and extraosseous soft tissue around the nidus of osteoid osteoma on T2-weighted MR imaging were graded from 1 (nonexistent) to 4 (extensive) by two masked observers. The relationships between the patient's age, duration of symptoms, and location of lesions were evaluated by Pearson's correlation coefficient and analysis of variance. RESULTS: Twenty-seven cases met the inclusion criteria. The observer agreement on grading was good. Patients of 15 years of age or younger had significantly higher grades than patients older than 15 years. There was a moderate negative linear correlation between the patient's age and peritumoral edema. No significant relationship was identified between edema and the duration of symptoms or the location of lesions. CONCLUSION: Osteoid osteomas in younger patients tend to be associated with more extensive peritumoral edema.

Adolescent↗
PubMed1999

Medication-induced hallucination and cerebral blood flow in Parkinson's disease.

Although hallucinations in Parkinson's disease (PD) are not unusual in the long-term treatment with anti-parkinsonian agents, their mechanism is not fully understood. We compared both the neuropsychiatric state and the results of 99mTc-labeled hexamethyl propyleneamine oxime single-photon emission computed tomography in 12 PD patients with medication-induced hallucinations and 21 PD patients without hallucinations. Hallucinatory patients showed significantly lower cerebral blood flow in left temporal regions than nonhallucinatory patients. The cerebral blood flow reduction in these regions may be related to the mechanism of medication-induced hallucinations in PD.

Aged↗
PubMed1999

Effects of diadenosine tetraphosphate on systemic and regional hemodynamics in dogs.

PURPOSE: Diadenosine tetraphosphate (AP(4)A) produces vasodilation and hypotension. If AP(4)A is to be employed clinically, its influence on systemic and regional hemodynamics needs to be investigated. In this study, we observed systemic and regional hemodynamics during reduction of mean arterial pressure (MAP) induced by AP(4)A in dogs. METHODS: Nineteen mongrel dogs were allocated to three groups: those given physiological saline (vehicle group) and dogs in which MAP was decreased either by 8% (8% group) or by 30% (30% group) by infusion of AP(4)A. Systemic hemodynamics and microsphere-determined regional blood flow to vital organs were assessed before and during AP(4)A infusion. RESULTS: In the 8% group, cardiac output (CO) increased, and systemic vascular resistance (SVR) decreased during AP(4)A infusion. Although regional blood flow to myocardium and portal organs increased, hepatic blood flow decreased. In the 30% group, heart rate and SVR decreased, and stroke volume index increased without change in CO. Regional blood flow to myocardium, kidneys, and portal organs increased. In both groups, cerebral blood flow remained unchanged. CONCLUSION: During the decrease in MAP induced by AP(4)A, there were increases in regional blood flow distributed to the myocardium, kidneys, and portal organs, without change in the blood supply to the brain. This finding suggests that AP(4)A may be clinically useful for reducing blood pressure without compromising blood flow to vital organs.

Journal Article↗
PubMed1999

Nitric oxide increases the amount of murine cytomegalovirus-DNA in mice latently infected with the virus.

At 5 wk after the intraperitoneal infection of murine cytomegalovirus (MCMV) in adult (C3H/He x BALB/c) F1 (CBF1) mice, MCMV-DNA was noted mainly in the salivary glands (SG). Since graft-versus-host reaction (GVHR) is well known as a major risk factor for CMV reactivation, parental BALB/c spleen cells were then intravenously transferred to these mice to induce GVHR. A high copy number of full-length MCMV-DNA was thus observed in the lungs as well as the hearts and livers at 4 to 6 wk after the cell transfer, whereas the copy numbers in SG after the cell transfer were comparable to those before the transfer. It was therefore suggested that the amount of MCMV-DNA noted in these organs had been increased by GVHR. However, no transcripts of MCMV-DNA could be detected. Since a marked expression of mRNA of inducible nitric oxide synthetase (iNOS) was noted in the lungs and the hearts during the course of GVHR, the role of NO in the increase of MCMV-DNA after the cell transfer was next examined. The administration of L-arginine, a substrate for NO, increased the amount of MCMV-DNA in the lungs and the hearts after the induction of GVHR. In contrast, the material which suppressed iNOS induction inhibited the emergence of MCMV-DNA. Therefore, the NO generated during the course of GVHR increased the amount of the viral DNA in the lungs and the hearts of the mice latently infected with MCMV. If the increase in the amount of viral genome is the initial step of viral reactivation from the latent state, then NO would thus trigger the initial step of the reactivation of the DNA virus. As the lungs are the major organ to produce NO after systemic stimulation, the observations of this study may explain why the lungs are the major site of CMV latency and why GVHR triggers CMV reactivation. These findings are thus considered to demonstrate that NO plays a novel role in viral infection.

Animals↗
PubMed1999

Superior protection in orthotopic rat lung transplantation with cyclic adenosine monophosphate and nitroglycerin-containing preservation solution.

BACKGROUND: Primary lung graft failure is common, and current lung preservation strategies are suboptimal. Because the decline in lung levels of cyclic adenosine monophosphate and cyclic guanosine monophosphate during preservation could enhance adhesiveness of endothelial cells for leukocytes as well as increase vascular permeability and vasoconstriction, we hypothesized that buttressing these levels by means of a preservation solution would significantly improve lung preservation. METHODS: An orthotopic rat left lung transplantation model was used. Lungs were harvested from male Lewis rats and preserved for 6 hours at 4 degrees C with (1) Euro-Collins solution (n = 8); (2) University of Wisconsin solution (n = 8); (3) low-potassium dextran glucose solution (n = 8); (4) Columbia University solution (n = 8), which contains a cyclic adenosine monophosphate analog (dibutyryl cyclic adenosine monophosphate) and a nitric oxide donor (nitroglycerin) to buttress cyclic guanosine monophosphate levels; or (5) Columbia University solution without cyclic adenosine monophosphate or nitroglycerin (n = 8). PaO2, pulmonary vascular resistance, and recipient survival were evaluated 30 minutes after left lung transplantation and removal of the nontransplanted right lung from the pulmonary circulation. RESULTS: Among all groups studied, grafts stored with Columbia University solution demonstrated the highest Pa O2 (355 +/- 25 mm Hg for Columbia University solution versus 95 +/- 22 mm Hg for Euro-Collins solution, P <.01, 172 +/- 55 mm Hg for University of Wisconsin solution, P <.05, 76 +/- 15 mm Hg for low-potassium dextran glucose solution, P <.01, and 82 +/- 25 mm Hg for Columbia University solution without cyclic adenosine monophosphate or nitroglycerin, P <.01) and the lowest pulmonary vascular resistances (1 +/- 0.2 mm Hg * mL-1 * min-1 for Columbia University solution versus 12 +/- 4 mm Hg * mL-1 * min-1 for Euro-Collins solution, P <.01, 9 +/- 2 mm Hg * mL-1 * min-1 for University of Wisconsin solution, 14 +/- 6 mm Hg * mL-1 * min-1 for low-potassium dextran glucose solution, P <.01, and 8 +/- 2 mm Hg * mL-1 * min-1 for Columbia University solution without cyclic adenosine monophosphate and nitroglycerin). These functional and hemodynamic improvements provided by Columbia University solution were accompanied by decreased graft leukostasis and decreased recipient tumor necrosis factor alpha and interleukin 1alpha levels compared with the other groups. In toto, these improvements translated into superior survival among recipients of Columbia University solution-preserved grafts (100% for Columbia University solution, 37% for Euro-Collins solution, P <.01, 50% for University of Wisconsin solution, P <.05, 50% for low-potassium dextran glucose solution, P <.05, and 13% for Columbia University solution without cyclic adenosine monophosphate and nitroglycerin, P <.01). CONCLUSION: Nitroglycerin and cyclic adenosine monophosphate confer beneficial vascular effects that make Columbia University solution a superior lung preservation solution in a stringent rat lung transplantation model.

Adenosine↗
PubMed1999

Long-term results of a randomized trial for the treatment of Stages B2 and C prostate cancer: radical prostatectomy versus external beam radiation therapy with a common endocrine therapy in both modalities.

OBJECTIVES: To improve the treatment of locally advanced prostate cancer (Stages B2 and C), a prospective randomized trial was conducted to compare radical prostatectomy versus external beam radiotherapy with the combination of endocrine therapy in both modalities. METHODS: One hundred patients were enrolled and 95 were evaluated. Forty-six patients underwent radical prostatectomy with pelvic lymph node dissection, and 49 were treated with radiation by linear accelerator with 40 to 50 Gy to the whole pelvis and a 20-Gy boost to the prostatic area. For all patients, endocrine therapy was initiated 8 weeks before surgery or radiation, and continued thereafter. The living patients were asked to respond to a quality-of-life questionnaire. RESULTS: The follow-up period ranged from 6.0 to 94.4 months (median 58.5). The progression-free and cause-specific survival rates at 5 years were 90.5% and 96.6% in the surgery group and 81.2% and 84.6% in the radiation group, respectively. The surgery group had better progression-free and cause-specific survival rates (P = 0.044 and 0.024, respectively). More patients in the surgery group complained of urinary incontinence. The questionnaire revealed that quality of life was less disturbed in the radiation group. CONCLUSIONS: Radical prostatectomy combined with endocrine therapy may contribute to the survival benefit of patients with locally advanced prostate cancer. External beam radiotherapy in combination with endocrine therapy can be used in selected patients because of its low morbidity.

Adenocarcinoma↗