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Biomedical subjects

K Ogata

Publications and source records attributed to K Ogata.

At least 145 records · Page 8Linked to original sources

Interleukin-8 participates in angiogenesis in non-small cell, but not small cell carcinoma of the lung.

We examined interleukin-8 (IL-8) production in 17 lung cancer cell lines, IL-8 expression in tumor specimens and IL-8's contribution to tumor-induced angiogenesis in vivo. Eight of 13 non-small cell lung cancer cell lines constitutively produced high levels of IL-8. Four small cell lung cancer cell lines produced little or no IL-8. Immunohistochemical analysis of transbronchial biopsy specimens revealed IL-8 staining within adenocarcinomas (22/32), squamous cell carcinomas (12/21) and large cell carcinomas (2/3), but not within most small cell carcinomas (1/22). Anti-IL-8 antisera blocked tumor angiogenesis by two IL-8 producing cell lines in a mouse model.

Adenocarcinoma↗

Investigation of the pyrimidine preference by the c-Myb DNA-binding domain at the initial base of the consensus sequence.

The principal determinant of the pyrimidine preference by the c-Myb DNA-binding domain at the initial base of the consensus sequence was investigated by mutation of both the protein and the DNA base pairs, with analysis by a filter binding assay. Amino acid residue 187 was revealed to interact with the pyrimidine base position, as estimated from our previous complex structure. Unexpectedly, since the pyrimidine preference is retained even in the Gly187 mutant, the principal origin of the base specificity should not occur via the direct-readout mechanism, but by an indirect-readout mechanism, namely in the intrinsic "bendability" of the pyrimidine-purine step of the DNA duplex. A significant but rather small positive base pair roll is detectable in the conformation of DNA in complex with the c-Myb DNA-binding domain. Following the conventional chemical rules of the direct-readout mechanism, amino acid mutagenesis at position 187 yielded several new base preferences for the protein.

Amino Acid Sequence↗

Natural killer cells in the late decades of human life.

We examined the lymphocyte subsets and indices of natural killer (NK) cell activity (lytic unit (LU), index of absolute NK cell activity in vivo (ALU), and NK cell activity on a per-cell basis (PCNK)) in 82 people (age, 30-99 years) who were immunologically normal. Although the number of NK cells was maintained throughout the examined age range, the ALU and PCNK values correlated negatively with age. We then examined whether any of the various immunologic parameters, including the function and cell counts of NK cells, T cells, and neutrophils, related to past infectious episodes and death in the follow-up period in 44 elderly subjects (age, 63-98 years). Only low ALU and PCNK values correlated with a past history of severe infection, while low LU, ALU, and PCNK values were the only parameters which correlated with death due to infection during the follow-up period. We propose that human NK cells do not escape the aging process and that a low NK cell function relates to the development of severe infections, which may be fatal, in elderly subjects.

Adult↗

Delayed manifestation of aortic stenosis after blunt abdominal trauma: report of a case.

Delayed manifestation of aortic stenosis caused by abdominal blunt trauma is rare. We report herein the case of a 67-year-old man who was taken to a nearby hospital after being crushed between a heavy truck and a wall. An emergency laparotomy was performed, revealing only a mesenteric tear which was repaired. He was discharged after an uneventful postoperative course; however, 1 month later he began to experience intermittent claudication, and presented to our hospital in December 1994, 1 year after the first operation. Angiography and enhanced computed tomography (CT) demonstrated infrarenal abdominal aortic dilatation with distal stenosis. Both the dilated and stenotic lesions were resected and bypass surgery ws performed. Pathologic examination demonstrated that the intima had been lacerated circumferentially and everted distally, causing the aortic stenosis. To our knowledge, this is the first case of the delayed manifestation of traumatic aortic stenosis to be documented in Japan. The etiology of this rare complication of blunt trauma is described in this report.

Abdominal Injuries↗

Self-compressive osteotomy of the greater trochanter.

We have designed a dihedral osteotomy of the greater trochanter which is V-shaped with the apex infero-medially. A single screw is used for fixation. The osteotomy was used in 24 hips (23 patients), as part of a transtrochanteric approach for acetabular reconstruction, carried out for dysplasia or in complicated acetabular fractures. There were no cases of nonunion or painful bursitis at an average follow up of 20 months. The method provides a stable reduction and bony union because of the self-compressive effect of the abductor muscles.

Acetabulum↗

The effect of wedged insoles on the thrust of osteoarthritic knees.

We describe a method of quantifying the lateral/medial thrust of the knee which occurs in the early phase of walking. We have used this method to evaluate the effects of wedged insoles on the lateral and medial thrust for normal knees and knees with unicompartment osteoarthritis (OA). A laterally elevated (valgus) insole decreased the lateral thrust of both normal and osteoarthritic knees. A medially elevated (varus) insole increased the lateral thrust. In 50 symptomatic knees with medial compartment OA, decreasing the lateral thrust with a valgus insole reduced pain on walking in 27. Patients whose pain was reduced by valgus insoles tended to have earlier OA and to have a significantly greater reduction in the lateral thrust than in the 23 remaining unaffected knees. A varus insole was effective in decreasing the medial thrust and reducing pain in all ten knees with lateral compartment OA. We recommend the use of valgus insoles for patients with painful early medial compartment OA and the use of varus insoles for lateral compartment OA.

Acceleration↗

Construction of a Fibrobacter succinogenes genomic map and demonstration of diversity at the genomic level.

The genomic cleavage map of the type strain Fibrobacter succinogenes S85 was constructed. The restriction enzymes AscI, AvrII, FseI, NotI, and SfiI generated DNA fragments of suitable size distribution that could be resolved by pulsed-field gel electrophoresis (PFGE). An average genome size of 3.6 Mb was obtained by summing the total fragment sizes. The linkages between the 15 AscI fragments of the genome were determined by combining two approaches: isolation of linking clones and cross-hybridization of restriction fragments. The genome of F. succinogenes was found to be represented by the single circular DNA molecule. Southern hybridization with specific probes allowed the eight genetic markers to be located on the restriction map. The genome of this bacterium contains at least three rRNA operons. PFGE of the other three strains of F. succinogenes gave estimated genome sizes close to that of the type strain. However, RFLP patterns of these strains generated by AscI digestion are completely different. Pairwise comparison of the genomic fragment distribution between the type strain and the three isolates showed a similarity level in the region of 14.3% to 31.3%. No fragment common to all of these F. succinogenes strains could be detected by PFGE. A marked degree of genomic heterogeneity among members of this species makes genomic RFLP a highly discriminatory and useful molecular typing tool for population studies.

Animals↗

Arthroscopic technique: two-piece excision of discoid meniscus.

This article describes a new arthroscopic technique of excision of complete discoid meniscus with a tear in which the discoid is divided into anterior and posterior pieces for removal. It is easy to perform because an excellent visualization of the posterior segment is obtained after removal of the anterior piece. The extent of intrasubstance pathology can be evaluated with a transverse cut to the mid portion of the discoid, and therefore, it is easy to determine the width of the rim to be retained. Because the meniscus is divided into two pieces, a large portal is not required for removal.

Adult↗

Evaluation of patellar retinacular tension during total knee arthroplasty. Special emphasis on lateral retinacular release.

Tension of a suture placed to the patella to close the medial capsule during 35 primary total knee arthroplasties was measured. The increase in tension with flexion after arthrotomy was significantly smaller in 10 knees with a subvastus incision (subvastus group) than in 25 knees with a standard medial parapatellar incision (standard group). With the prosthesis in place, the patella showed maltracking with the no-thumb technique in 1 knee (10%) of the subvastus group and in 9 knees (36%) of the standard group. A lateral retinacular release was performed in 5 of these 10 knees but not in the remaining 5 knees because the increase in tension was a minimum. There was no case of patellar maltracking at an average follow-up period of 2.1 years after surgery, suggesting that a lateral release is not always needed if retinacular tension shows no significant increase, even cases where the patella dislocates with the no-thumb technique.

Aged↗

Rationale and hematologic target points in response-oriented individualized induction chemotherapy for acute myeloid leukemia.

Response-oriented individualized induction chemotherapy (ROIIC) has been reported to achieve a high complete remission (CR) rate in acute myeloid leukemia (AML). In ROIIC, drug dose is modified for each patient to achieve hematologic target points, based on the concept that this achievement, not a preset drug dose, increases the likelihood of attaining CR. However, the existing target points lack objectivity, therefore prohibiting worldwide use of ROIIC. In addition, the achievement of these target points does not statistically relate to CR, which contradicts the concept of ROIIC. To solve these problems, we evaluated various parameters of 117 AML cases treated by ROIIC to identify the factors relating to CR. Of 117 AML subjects, 75 achieved CR with ROIIC and most cases achieving CR did so with one ROIIC course. Not the administered dose of drugs but several hematologic parameters at the end of ROIIC correlated significantly with CR. A total of four parameters, all related to the leukemic cell mass, were independent predictive factors of CR. A formula consisting of these parameters predicted CR cases with high sensitivity (98%) and non-CR cases with high specificity (96%). Based on this formula, an objective target point (a bone marrow blast mass ratio between before and after ROIIC of below 0.15), valid for dose modification during ROIIC, was established. These results validate the concept of ROIIC and enable objective dose modification in ROIIC and universal application of this therapy. Further, the formula predicting non-CR cases at the end of ROIIC is useful for deciding early therapeutic intervention for such cases.

Acute Disease↗

Identification of indispensable residues for specific DNA-binding in the imperfect tandem repeats of c-Myb R2R3.

The individual repeats, R2 and R3, of the minimum specific DNA-binding domain (R2R3) of c-Myb have very similar structures, with a helix-turn-helix variation motif, although their sequence identity in the tandem repeats is only 31%. From previous mutational and structural studies, the third helices in both repeats were shown to directly recognize the specific base sequence, PyAACG/TG. In order to elucidate the reason for the imperfection of the tandem repeats at amino acid positions other than the recognition helices, a series of R2R3 mutants was generated by swapping the helices and the N-terminus in R2 to those in R3. Consequently, the sequence composing the first helix of R2 was found to be essential for specific DNA-binding, in addition to the third recognition helix of R2. Further mutational studies revealed that the only indispensable residues in the first helix are Val103 and Val1O7, which are involved in the hydrophobic core of R2. These residues do not directly interact with the DNA, but they contribute to the correct formation of helix 1 and the characteristic packing of R2, which is slightly different from that of R3, and are required for specific base recognition through strong cooperativity with R3.

Binding Sites↗

Prediction of protein side-chain conformations by principal component analysis for fixed main-chain atoms.

A method of side-chain prediction without calculating the potential function is introduced. It is based on the assumption that similar side-chain conformations have a similar structural environment around the side chains. The environment information is represented by vectors that were obtained from principle component analysis and represented by the variance of positions of main-chain atoms around side chains. This information was added to the side-chain library (rotamer library) made from X-ray structures. Side-chain conformations were constructed using this side-chain library without using potential functions. An optimal solution was determined by comparing environmental information with the backbone conformation around the side chain to be predicted and native ones in the library. The method was performed for 15 proteins whose structures were known. The result for the root-mean-square deviation between the predicted and X-ray side-chain conformations was approximately 1.5 A (the value for core residues was approximately 1.1 A) and the percentage of predicted chi 1 angles correct within 40 degrees was approximately 65% (75% for the core). The computational time was short (approximately 60 s for the prediction of proteins with 200 amino acid residues). About 70% of the side-chain conformations were constructed by location of the main-chain atoms around the central C beta atom and the average of r.m.s.d. was approximately 1.4 A (for core residues the average was approximately 1.0 A).

Animals↗

[Bacteriological studies on sporadic diarrhea diseases in Oita District, 1985-1996].

Approaching the problem of how close the sporadic diarrhea diseases correlate with epidemics of infectious diarrheas, including food poisonings, bacteriological studies were made on the characteristics of sporadic diarrheas in the past 10 years and analyzed. In collaboration with physicians, mostly pediatricians, in Oita district during 1985 to 1986 and 1989 to 1996, a total of 1707 specimens was obtained from diarrhea patients, suspected of bacterial cause. We have isolated 717 strains from 670 specimens (ca 40% of the total). The majority were; Campylobacter, Salmonella and EPEC with the rate of about 40, 24 and 23% respectively. On the other hand, isolation of Vibrio spp. and Staphylococcus were very few. The yearly trend of detection rates of such major agents were as follows: Campylobacter had the highest rate in the early period, 1989, but thereafter tended to decrease. In contrast, Salmonella continued to increase in rate through the study period until the present when it exceeds that of Campylobacter. This alternation is due primarily to the rapid increase of S. Enteritidis since its recent appearance. VTEC stays at a low rate with a slow increase showing no prevalence so far. From the above results the following may meet with attention. Vibrios and Staphylococci, known as popular agents for food poisonings, seem unlikely to correlate with sporadic diarrheas. Instead, the evidence that recent food poisoning is often represented by Salmonella, especially S. Enteritidis, suggests that epidemics of infectious diarrhea may be attributed to the background of common sporadic diarrheas.

Adolescent↗

Plasma soluble interleukin-2 receptors in patients with myelodysplastic syndromes.

We examined the plasma soluble interleukin-2 receptor (sIL-2R) level in 80 subjects with myelodysplastic syndromes (MDS) and analyzed its correlation with hematologic/immunologic parameters and the subsequent clinical course. Compared with low-risk MDS (refractory anemia (RA) and RA with ringed sideroblasts) and normal individuals, the plasma sIL-2R level was significantly elevated in high-risk MDS (three other MDS subtypes and acute leukemia following MDS) patients. There was a significant negative correlation between the plasma sIL-2R level and the absolute counts of T and natural killer cells. Furthermore, the plasma sIL-2R level showed a significant positive correlation with the total cell mass and blast mass in particular, in the marrow, but not with the absolute count of IL-2Ralpha-chain-positive lymphocytes in the circulation. Fourteen of our 40 low-risk MDS subjects developed at least one of the following events during the follow-up period: erythrocyte transfusion dependence, infections requiring hospitalization, disease progression or MDS-related death. The plasma sIL-2R level was significantly higher in these patients than in event-free low-risk cases. By logistic regression analysis of various parameters in the 40 low-risk subjects, the plasma sIL-2R level was identified as a valuable independent parameter for predicting the development of events. Based on these findings, we hypothesize that the sIL-2R plays a role in the development of morbidity and mortality in MDS by inducing immunologic dysfunction.

Biomarkers, Tumor↗

Cell cycle modulation by hematopoietic growth factors in myelodysplastic syndromes: analysis by three-color flow cytometry.

Investigations of the effects of hematopoietic growth factors (HGFs) on the cell cycle of cells from myelodysplastic syndrome (MDS) have been hampered by technical difficulties. In this study, using a recently established flow cytometric method that enables detailed analysis of the cell cycle (Gzero-, G1-, S-, and G2/M-phases) of target cells in a heterogeneous cell population, we examined the effects of granulocyte colony-stimulating factor (G-CSF) and other HGFs on the cell cycle of CD13-positive cells (blasts and other malignant myelocytic and monocytic cells) in MDS. The cell cycle response to G-CSF (decrease in Gzero-phase cells and increase in S-phase cells) was heterogeneous among MDS cases. When the data for 13 MDS cases and 15 de novo AML cases were compared statistically, the magnitude of cell cycle activation by G-CSF was weaker for the cells from the MDS cases. Stem cell factor, interleukin-3, or a combination of these HGFs with G-CSF reduced the Gzero-phase cell percentage in all examined MDS cases whose cell cycle was unresponsive to G-CSF alone. When cytosine arabinoside was added to cells with or without stimulation by HGFs, the viable G0-phase cell count was reduced in HGF-stimulated cells compared with unstimulated cells in seven of eight cases. The present results suggest that G-CSF-induced cell cycle stimulation of malignant cells can be expected in a fraction of MDS patients and that even in MDS patients whose cells do not respond to G-CSF, employment of other HGFs and their combination with G-CSF is worth consideration. The results also suggest that a well-designed therapy using HGFs and chemotherapeutic drugs may reduce the quiescent (Gzero) cell count in MDS, which is assumed to be responsible for drug resistance derived from cell kinetics.

Cell Cycle↗