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Biomedical subjects

K Kojima

Publications and source records attributed to K Kojima.

At least 271 records · Page 15Linked to original sources

Localization of parathyroid glands using technetium-99m-tetrofosmin imaging.

UNLABELLED: Preoperative localization of hyperactive parathyroid glands is useful to minimize operative time and reduce patient morbidity. This investigation compared the sensitivity of radionuclide imaging with 99mTc tetrofosmin with that of ultrasonography and magnetic resonance (MR) imaging in patients with hyperparathyroidism. METHODS: Twenty-six patients with primary (n = 7) or secondary (n = 19) hyperparathyroidism were imaged with 99mTc tetrofosmin, ultrasound and MR imaging of the neck and thorax to localize the lesions. The presence of hyperparathyroidism was identified by an intact parathyroid hormone in vitro assay. The parathyroid/normal thyroid tissue activity ratio was calculated for all patients with evidence of an abnormality on tetrofosmin images. Pathological findings were compared with the results of imaging in 18 of the 26 patients who underwent parathyroidectomy. RESULTS: Technetium-99m tetrofosmin scans demonstrated focal uptake in 46 glands of 26 patients. The uptake was categorized as slight in 78.3% (36/46) and intense (parathyroid/normal thyroid tissue activity ratio, > 1.4) in 21.7% (10/46). Ultrasonography and MR imaging identified 44 and 47 glands, respectively, in these patients. Eleven of the 18 patients who underwent parathyroidectomy within 1 mo after tetrofosmin imaging had hyperplastic glands, while 7 had parathyroid adenomas. Tetrofosmin imaging successfully localized 7 of 7 (100%) adenomas and 27 of 37 (73.0%) hyperplastic glands. The sensitivities of each technique for localizing abnormal parathyroid glands were 77.3% (34/44) for tetrofosmin imaging: 68.2% (20/44) for ultrasonography: and 68.2% (30/44) for MR imaging. Technetium-99m tetrofosmin uptake ratio in the 18 patients with surgical exploration was not proportional to several oxyphil cells. CONCLUSION: Technetium-99m tetrofosmin parathyroid imaging may be useful for localizing abnormal glands in patients with primary and secondary hyperparathyroidism. The sensitivity of 99mTc tetrofosmin parathyroid imaging was high as compared to ultrasonography or MR imaging. The prolonged retention of tetrofosmin may not depend on the number of mitochondria-rich oxyphil cells.

Adenoma↗

[A case of anti-basement membrane (BM) mediated disease presenting renal and pulmonary symptoms by divergent timing].

A case of 49-year-old man with anti-GBM antibody and who manifested pulmonary and renal symptoms at divergent times. Thirty-six years previously, renal disease with unneglectable degree of proteinuria was noticed. One month before admission, he was found by chance to have elevated serum creatine (Scr); 3.4 mg/dl. At admission, his Scr was 13.7 mg/dl and Hb 12.7 g/dl, TP 5.2 g/dl with 3+ proteinuria and no glucosuria. He was a heavy smoker and remained so while admitted. Renal biopsy presented fibrocellular crescents in 100% of glomeruli with striking tubulointerstitial involvement. Immunofluorescence showed linear IgG deposition along the glomerular capillary wall. Hemodialysis was instituted, and after 13 hospital days, anti-GBM antibody at admission was high at 128 U, with negative PANCA. Plasmapheresis was also performed, but on the next day pulmonary hemorrhage occurred with a concomitant rise of anti-GBM to 250 U. Thus, steroid pulse therapy was conducted in combination with plasmapheresis. Pulmonary hemorrhage subsided along with lowering of anti-GBM (48 U), but renal failure persisted. The patient died of septicemia. Based on the clinical course of the case, the term "anti-BM mediated disease" may more properly delineate the entity of the disease rather than the classical eponym "Goodpasture's disease" which requires coexistence of pulmo- and renal manifestations for definition.

Anti-Glomerular Basement Membrane Disease↗

[Liver metastases from breast cancer 14 years after radical mastectomy; successful treatment with hepatic arterial infusion chemotherapy and systemic endocrine therapy--a case report].

The patient was a 73-year-old woman who was admitted to our hospital for epigastric discomfort and body weight loss. She had undergone radical right mastectomy in March 1982. Ultrasonography and computed tomography revealed multiple tumors in the liver. Three of the tumor markers (CA-125, CA 19-9, and CA 15-3) were positive. US-guided fine needle aspiration biopsy of the liver tumor showed small atypical cells with solid cell nests. Immunohistochemical tests revealed estrogen receptor was positive. We diagnosed the patient as recurrent breast cancer metastatic to liver, 14 years postoperatively. The liver tumors were successfully controlled with the combination of intra-arterial infusion chemotherapy (5-fluorouracil, epirubicin, and mitomycin C) along with systemic endocrine therapy (medroxyprogesterone acetate and fadrozole hydrochloride hydrate).

Aged↗

Sequence analysis of normal and rearranged NSP5 genes from human rotavirus strains isolated in nature: implications for the occurrence of the rearrangement at the step of plus strand synthesis.

We determined the nucleotide sequences of normal and rearranged NSP5 genes from the human rotavirus strains (Mc323 and Mc345, respectively) which had previously been isolated from Thai infants with diarrhea in the same epidemic season. While the two strains shared G serotype 9 specificity and subgroup I specificity and they showed a high level of overall genomic relatedness to each other, they exhibited different RNA profiles; a long pattern for Mc323 and a super-short pattern for Mc345. Their NSP5 sequences were more closely related to those of porcine rotaviruses than to those of human rotaviruses. Mc345 NSP5 gene was shown to have concatemerization. In a head-to-tail orientation resulting in its length being 1182 bp, as compared with the Mc323 NSP5 sequence which was 664 bp in length. Sequence analysis suggested that the rearrangement found in the strain Mc345 occurred at the step of plus strand synthesis.

Base Sequence↗

The proliferation index of MIB-1 as a prognostic factor for patients with transitional cell carcinoma of the upper urinary tract.

BACKGROUND: Recently, several reports have shown that immunohistochemical analysis using MIB-1 antibody, which recognizes Ki-67 (a human nuclear antigen expressed of proliferating cells), is a useful method for determining the proliferative activity of various cancers. In this study, the authors evaluated the prognostic usefulness of the proliferation index using MIB-1 antibody in transitional cell carcinoma of the upper urinary tract. METHODS: Proliferation activity was investigated immunohistochemically using monoclonal antibody MIB-1 in formalin fixed, paraffin embedded tissues obtained from 67 specimens of renal pelvic and ureteral cancer. The MIB-1 proliferation index values were calculated from each sample as the percentage of positive nuclei expressed in tumor cells and the clinicopathologic correlation evaluated. RESULTS: The MIB-1 proliferation index values were correlated with prognostic parameters such as pathologic stage ( < or = pT1 vs. > or = pT2, P < 0.0005), histologic grade (G1 vs. G2, P < 0.01; G1 vs. G3, P < 0.0001; G2 vs. G3, P < 0.001), and prognosis (P < 0.0001). When patients were subgrouped using index values, patients with higher indices ( > or = 24%) had significantly poorer survival (P < 0.0001). This was especially observed in the G2 group, in which 9 of 10 patients in the higher indices subgroup had a high incidence of recurrence and died. In contrast, only 2 of 29 patients in the lower indices subgroup died. The higher indices subgroup had significantly worse cause specific survival (P < 0.0001). Furthermore, with regard to the muscle invasive tumors ( > or = pT2), the higher indices subgroup also had significantly worse cause specific survival (P < 0.0001). CONCLUSIONS: The results of the evaluation of prognostic parameters indicate that the MIB-1 proliferation index is a useful prognostic factor and may enhance the accuracy of conventional morphologic grading and pathologic staging systems.

Adult↗

Selective removal of human serum amyloid P component from rat blood by use of an immunoaffinity membrane in an extracorporeal circulation system.

We examined the suitability of an immunoaffinity membrane (IAM) bearing specific antibody as a ligand for removing human serum amyloid P component (hSAP) from blood passed through a simple extracorporeal circulation system established in rats. The specific antibody was the most effective of the various ligands tested for removing hSAP from human blood. To determine the value of the hSAP in human or rat plasma, we also developed a simple ELISA. In the rat extracorporeal circulation system, the hSAP level in the inlet blood to the IAM module decreased to 49% of the initial concentration within 60 min. In contrast, the hSAP remained at the initial concentration throughout the study in the module without the IAM. The use of this extracorporeal circulation system in this case allows preclinical evaluation of the ex vivo removal of a human plasma component in an animal model. Biocompatibility of the IAM was also examined. No change in blood cell counts or activation of the coagulation system occurred after contact with the IAM. Non-specific adsorption was not observed, since there was no statistically significant difference in IgG, complement C3, or albumin level between the pre- and post-treatment with this module. The immunological effects of the IAM were also examined using this system. Four weeks after the termination of the extracorporeal circulation, the rats examined showed no detectable antibody titer to the ligand.

Adsorption↗

Characterization of carbohydrate-binding protein p33/41: relation with annexin IV, molecular basis of the doublet forms (p33 and p41), and modulation of the carbohydrate binding activity by phospholipids.

A protein, p33/41, expressed in bovine kidney and many other tissues was identified as a lectin which binds to sialoglycoproteins and glycosaminoglycans in a calcium-dependent manner. Partial amino acid sequences of p33/41 are highly homologous to those of calcium/phospholipid-binding annexin protein, annexin IV (endonexin), p33/41 exhibited similar calcium/phospholipid-binding activity (Kojima, K., Ogawa, H., Seno, N., Yamamoto, K., Irimura, T., Osawa, T., and Matsumoto, I. (1993) J. Biol. Chem. 267, 20536-20539). To further characterize p33/41, we cloned the p33/41 cDNA and characterized the recombinant protein encoded by this cDNA. Oligonucleotide probes were synthesized based on partial amino acid sequences of p33/41 and used for screening. A p33/41 cDNA clone was isolated encoding a protein of 319 amino acids with a calculated molecular mass of 35,769 Da. The deduced amino acid sequence was identical to that of bovine annexin IV except for one amino acid substitution. The recombinant protein gave two 33-kDa (p33) and 41-kDa (p41) bands on SDS-polyacrylamide gel electrophoresis under non-reducing conditions, and only one 33-kDa band under reducing conditions, as did the native protein. Mass spectrometric analysis combined with site-directed mutagenesis of each of the four cysteine residues of the recombinant protein revealed that p41 is a dimer of p33 cross-linked at Cys-198 via a disulfide bond. The recombinant protein bound to columns of heparin and fetuin glycopeptides in a calcium dependent manner and to phospholipid vesicles composed of phosphatidylserine (PS)/phosphatidylcholine (PC), phosphatidylethanolamine (PE)/PC or phosphatidylinositol (PI)/PC. Furthermore, concurrent binding assays showed that the binding of the recombinant protein to phospholipid vesicles was not affected by heparin, whereas that to heparin was influenced by the phospholipid composition of the vesicles; the highest binding was observed with vesicles composed of PE/PC. These results suggest that p33/41 binds two types of ligands via different sites and that phospholipids modulate the carbohydrate binding activity of p33/41.

Amino Acid Sequence↗

Molecular cloning and characterization of murine IL-12 genes.

IL-12 is a heterodimeric cytokine composed of two covalently linked chains, p40 and p35. p40 expression appears to be restricted to monocytes/macrophages and B cells and is highly regulated, while p35 is more ubiquitously and constitutively expressed. To investigate the mechanism involved in the regulation of IL-12 expression, we molecularly cloned and characterized the murine p40 and p35 genes. The p40 gene spans over 14 kb, consists of eight exons and seven introns, and was shown to be localized on chromosome 11A5-B2 by fluorescence in situ hybridization. A single major transcription initiation site was detected by primer extension analysis, and a TATA box was found at approximately 30 bp upstream from the transcription initiation site. The 5' flanking region preceding the transcription initiation site induced the enhanced expression of a promoterless reporter gene after LPS stimulation when transfected into a macrophage-like cell line. In contrast, the p35 gene spans over 8 kb and consists of seven exons and six introns on chromosome 6C, and multiple transcription initiation sites were detected. The 5' flanking region lacks canonical TATA and CAAT boxes at the appropriate position, but, instead, contains GC-rich sequences and constitutively mediated promoter activity when placed upstream of a promoterless reporter gene and transfected into a B cell lymphoma cell line. Thus, the characteristics of promoter regions of p40 and p35 genes are quite different, and this would account for the different regulations of p40 and p35 expression.

Amino Acid Sequence↗

Rapid killing of murine lymph node T blasts by intestinal intraepithelial lymphocytes in vitro.

We examined the effect of murine intestinal intraepithelial lymphocytes (IEL) on the proliferation of murine lymph node T cells (LN-T) in vitro. An IEL fraction prevented the proliferation of LN-T stimulated with antigen and X-irradiated spleen cells, or with anti-CD3 monoclonal antibodies (mAb). Concanavalin A-activated LN-T were less sensitive. Such an inhibitory activity was recovered from a CD8-depleted population by panning of bulk IEL using anti-CD8 alpha mAb. This population of BALB/c IEL showed less granzyme A activity, and its surface markers were positive for CD8 (4%), CD3 (80-90%), CD4 (2-6%), alpha-beta TcR (45-70%), and gamma-delta TcR (4-9%). Asialo-GM1 and Thy1.2 were variably expressed, but interleukin-2 (IL-2) receptor-alpha and Fc gamma receptor were not. By contrast, no cytotoxicity against YAC-1 was detected in a CD8-depleted IEL population by a 6-h 51Cr-release assay. Although IEL from severe-combined immunodeficient mice lacking CD4, CD8 and TcR, but expressing IL-2 receptor, showed cytotoxicity against YAC-1, their inhibitory activity against LN-T was almost the same as that by IEL from BALB/c mice. When LN-T blasts (greater than 75% CD4+) activated with anti-CD3 were treated with CD8-depleted IEL, intact cellular DNA of the T blasts disappeared within 1 h with increased amounts of small-sized DNA. These results suggest that CD8- IEL directly and nonspecifically kill lymph node CD4+ T blasts and possibly down-regulate TcR-mediated proliferation of peripheral T cells in the gut epithelium.

Animals↗

Structure and function of rotavirus NSP1.

Studies on the structure and function of the nonstructural proteins (NSP1-NSP5) of rotaviruses are important for dissection of the morphogenesis and replication processes of rotavirus. Above all, NSP1, the product of gene 5, has several interesting features, such as extreme sequence diversity, a highly conserved cysteine-rich region, RNA-binding activity, accumulation on the cytoskeleton, and non-random segregation in reassortment. Recently, comparable NSP1 sequence analysis has been performed on a number of rotavirus strains from various species. Furthermore, characterization of mutants with rearranged NSP1 genes has helped to elucidate the structure-function interaction of NSP1. We isolated and characterized two interesting mutants which have a large deletion including the cysteine-rich region or a nonsense codon at the early portion in the open reading frame (ORF) of the NSP1 gene. In this report, we summarize the structure and function of NSP1.

Amino Acid Sequence↗

Chronological changes in bone mineral content following gastrectomy.

Recent advances in the modalities of quantitatively assessing bone mineral content have resulted in an increasing awareness of metabolic bone disease as a late complication following gastrectomy. In this study, 98 postgastrectomy patients were examined by quantitative computed tomography (QCT). The bone mineral density index (BMDI), defined as 100 x (measured bone mineral density divided by that of age- and sex-matched controls), was used to evaluate the actual effect of gastrectomy on bone disorders. The BMDI values following gastrectomy were 80.4 +/- 27.3, with no significant difference between men and women, or between total and distal gastrectomy. Moreover, no significant differences were observed between the BMDI values within 6 months, being 92.6 +/- 37.3, and those 6 months to 1 year post gastrectomy, being 79.6 +/- 31.2; however, a significant and sharp decrease to 70.5 +/- 36.0 was evident after 1-2 years. The regression coefficient of the BMDI measured within 2 years postoperatively was lower than that measured after 2 years. These findings suggest that the influence of gastrectomy on bone metabolism is induced within 2 years, after which the bone mineral content decreases in accordance with physiological nature. Thus, we conclude that the treatment for bone disease resulting from gastrectomy would only be effective if initiated within a short period after surgery.

Adult↗