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Biomedical subjects

A Kawai

Publications and source records attributed to A Kawai.

At least 91 records · Page 5Linked to original sources
PubMed1998

High complication rate of reconstruction using Ilizarov bone transport method in patients with bone sarcomas.

We performed five reconstructions by bone transport in patients with bone sarcoma: three osteosarcomas, one Ewing's sarcoma and one chondrosarcoma. Four sarcomas were in the distal femur and one in the shaft of the tibia. Four patients received multidrug chemotherapy. The average length of the skeletal defect after tumour resection was 17 (range 10-25) cm. All patients underwent double elongation from both proximal and distal sites of the bone defect. The average follow-up period was 48 (range 40-66) months, and the average duration of external fixation was 32 months (range 579-1340 days). In one case, bone formation was satisfactory, but in the other cases, it was poor and slow. The average treatment index was 95 (range 53-191) days per 1 cm of elongation. In one case, the bone fragment disappeared during the bone transport. In one case, the end of the bone protruded from the skin, and osteomyelitis set in. This patient underwent above-knee amputation due to failure of infection control. Three patients suffered talipes equinus. One patient died of pulmonary metastasis. Two patients had fair and three had poor function. This method is not recommended for patients with bone sarcoma who may have a poor prognosis, as it has an unacceptably high complication rate.

Adolescent↗
PubMed1998

Value of thallium-201 scintigraphy in bone and soft tissue tumors.

The potential role of thallium-201 (201Tl) scintigraphy in the imaging of various musculoskeletal tumors was investigated in 80 patients. Uptake of 201Tl was observed in 17 (100%) malignant bone tumors, 6 (100%) giant cell tumors, and 2 of 8 (25%) benign bone tumors. Nineteen of 30 malignant soft tissue tumors (63%) were positive for 201Tl scintigraphy, while 2 of 14 benign soft tissue tumors (14%) yielded positive results. None of 6 liposarcomas were visualized by 201Tl scintigraphy. There was no 201Tl uptake in the tissues of 5 non-tumorous conditions. Ten patients with osteosarcoma were evaluated by 201Tl scintigraphy both pre- and post-chemotherapy. There was a significant correlation between changes in tumor-to-normal count ratio and percent necrosis of the resected tumor. The mean decrease in tumor-to-normal count ratio was 71% for patients with >/=90% tumor necrosis and 26% for those with <90% tumor necrosis. Serial 201Tl scintigraphy, with quantitative analysis of alterations in 201Tl uptake, may provide a quantitative and objective measure of the effect of preoperative chemotherapy in patients with malignant bone tumors.

Adolescent↗
PubMed1998

Cloning and chromosomal mapping of a novel ABC transporter gene (hABC7), a candidate for X-linked sideroblastic anemia with spinocerebellar ataxia.

We isolated a novel human ATP-binding cassette (ABC) transporter cDNA, determined its nucleotide sequence, and designated it human ABC7 (hABC7). The nucleotide sequence was highly homologous to the ATM1 gene in yeast, which encodes an ABC transporter (yAtm1p) located in the mitochondrial inner membrane. The deduced human product, a putative half-type transporter, consists of 752 amino acids that are 48.9% identical to those of yAtm1p. A computer-assisted protein structural and localization analysis revealed that the mitochondrial targeting signal of yAtm1p is conserved in the N-terminal region of the primary sequence of the hABC7 protein, and therefore this product is also likely to be located in the mitochondrial inner membrane. The evidence strongly suggests that the hABC7 gene is a counterpart of ATM1 and that its product is probably involved in heme transport. We mapped the hABC7 gene to chromosome Xq13.1-q13.3 by fluorescence in-situ hybridization. As band Xq13 has been implicated in X-linked sideroblastic anemia with spinocerebellar ataxia, hABC7 becomes a candidate gene for this heritable disorder.

5-Aminolevulinate Synthetase↗
PubMed1998

Role of the pons in hypoxic respiratory depression in the neonatal rat.

The main purpose of this study was to evaluate the role of the pons in hypoxic respiratory depression (HRD) of the neonatal rat. Experiments were conducted using the isolated brainstem-spinal cord preparation of the neonatal rat (1-3 days old). The brainstem was transected at various levels. We found that ablation of the diencephalon decreased respiratory frequency (fR), and conversely, that ablation of the midbrain or pons increased fR. In the preparation with the pons intact (without the midbrain), hypoxia (superfusate PO2 = 56 mmHg) caused strong depression of respiratory activity, which was characterized by a steady decrease in fR and in integrated inspiratory burst amplitude (integral of Phr). In the preparation with the intact ventral pons (without midbrain and dorsal pons) we observed similar, though weaker, HRD. When the entire pons was ablated, integral of Phr was little depressed by hypoxia and thus, HRD was further attenuated. We conclude that the pons contributes importantly to the induction of hypoxic respiratory depression in the neonatal rat. Both the ventral and dorsal portions of the pons are involved in the control of hypoxic respiratory depression. In addition, we show that the respiratory modulatory functions of the diencephalon (facilitating) and midbrain (inhibitory) are already expressed at the time of birth.

Animals↗
PubMed1998

Minimally invasive cardiac surgery in the adult: surgical instruments, equipment, and techniques.

To clarify the special instruments and equipment used for minimally invasive cardiac surgery (MICS), we examined the initial experiences with MICS operations with ministernotomy or minithoracotomy at our institution. Fifty adult patients with congenital, valvular, and/or ischemic heart diseases underwent MICS operations, and all surgical procedures were completed without conversion to full sternotomy. The length of the skin incision was about 10 cm or less in all patients. Postoperative recovery was favorable, and the majority of the patients were discharged from the hospital around the end of the second postoperative week. In this series of patients, an oscillating bone saw, lifting type retractor, 2 blade spreader, cannula with a balloon, and right-angled aortic clamp among other items, were very useful for successfully performing various operations with MICS approaches and techniques. The associated results suggest that MICS with ministernotomy or minithoracotomy was feasible using special instruments and equipment and could be encouraged for adult patients with various cardiovascular diseases.

Adult↗
PubMed1998

The 21-kDa polypeptide (VAP21) in the rabies virion is a CD99-related host cell protein.

In our monoclonal antibody (MAb) stocks prepared against the BHK-21 cell antigens, two (#11875 and 28276) recognized a 21-kDa polypeptide (referred to as VAP21) which is efficiently incorporated into the rabies virion. By using these MAbs, we isolated the cDNA clones that encoded a polypeptide of 144 amino acids from our BHK-21 cell cDNA library. Based on the following evidence, the cDNA was assumed to encode a full-length sequence of VAP21 antigen: i) expression of the cDNA in animal cells resulted in the production of a polypeptide recognized by the two MAbs, and its electrophoretic mobility was the same as that of authentic VAP21 antigen; and ii) immunization with the products from the cDNA-transformed E. coli cells raised specific antibodies in rabbits that recognized a 21-kDa polypeptide in the virion. From the deduced amino acid sequence, it is suggested that the VAP21 antigen has a molecular structure of type-I transmembrane protein containing characteristic proline-rich and glycine-rich regions in its ectodomain. Homology searches resulted in finding homologous sequences (totally about 40% homology) in the human MIC2 gene product (CD99; 32-kDa) of T lymphocytes. These results suggest that the VAP21 antigen in the rabies virion is a cellular CD99-related transmembrane protein.

12E7 Antigen↗
PubMed1998

Studies on rabies virus RNA polymerase: 1. cDNA cloning of the catalytic subunit (L protein) of avirulent HEP-flury strain and its expression in animal cells.

To investigate the RNA polymerase of rabies virus, we cloned a cDNA of the catalytic subunit (called L protein because of its large molecular size) of the HEP-Flury strain, an avirulent strain obtained by high frequencies of serial embryonated hen egg passages. Nucleotide sequencing showed that the cDNA encodes a long polypeptide of 2,127 amino acids (Mr. 242,938). A comparison of the deduced amino acid sequence with that of other strains (PV and SAD B19) indicated that the sequence was highly conserved, except for several amino acid substitutions which were accumulated in some limited regions. A fragment of the cDNA was used for expression in Escherichia coli (E. coli) to prepare the L antigen for raising the antibodies in rabbits. Immunoprecipitation studies with the rabbit antiserum showed that the polypeptides produced in the L cDNA-transfected COS-7 cells displayed almost the same electrophoretic mobility as that of authentic L protein. Immunofluorescence studies indicated that both L and P (another subunit of RNA polymerase) proteins displayed colocalized distribution with the nucleocapsid antigen (N) in the cytoplasmic inclusion bodies, where envelope proteins (G and M) were absent. On the other hand, expression of the L protein alone did not cause inclusion body-like granular distribution, suggesting that the inclusion body-like accumulation depends on certain interaction(s) with other viral gene products, probably with the ribonucleoproteins comprising the inclusion bodies.

Amino Acid Sequence↗
PubMed1998

Studies on the rabies virus RNA polymerase: 2. Possible relationships between the two forms of the non-catalytic subunit (P protein).

We investigated the relationship between the two forms of rabies virus P protein, a non-catalytic subunit of rabies virus RNA polymerase. The two displayed different electrophoretic mobilities as 37- and 40-kDa polypeptides, hence termed as p37 and p40, respectively. Double labeling experiments with [3H]leucine and [32P]orthophosphate demonstrated that p40 was much more phosphorylated than p37. Treatment of the virion proteins with alkaline phosphatase eliminated only p40, and not 37-kDa polypeptide. The p37 was a major product of the P gene, and was accumulated in the infected cell and incorporated into the virion. On the other hand, p40 was apparently detected only in the virion, and little detected in the cells. Treatment of infected cells with okadaic acid, however, resulted in significant accumulation of p40 in the cell, suggesting that p40 was continuously produced in the cell but dephosphorylated quickly. We detected both 37- and 40-kDa products in P cDNA-transfected animal cells, while only a 37-kDa product was produced in Escherichia coli. Incubation of 37-kDa products from E. coli with the lysates of animal cells in vitro resulted in the production of a 40-kDa product, which was also shown to be suppressed by the heparin. From these results, it is suggested that p40 is produced by the hyperphosphorylation of a 37-kDa polypeptide, which depends on certain heparin-sensitive cellular enzyme(s) and occurs even in the absence of the other viral gene products, and that p40 is reverted quickly to p37 in the infected cells, probably being dependent on some virus-induced factor(s).

Amino Acid Sequence↗
PubMed1998

PEX12, the pathogenic gene of group III Zellweger syndrome: cDNA cloning by functional complementation on a CHO cell mutant, patient analysis, and characterization of PEX12p.

Rat PEX12 cDNA was isolated by functional complementation of peroxisome deficiency of a mutant CHO cell line, ZP109 (K. Okumoto, A. Bogaki, K. Tateishi, T. Tsukamoto, T. Osumi, N. Shimozawa, Y. Suzuki, T. Orii, and Y. Fujiki, Exp. Cell Res. 233:11-20, 1997), using a transient transfection assay and an ectopic, readily visible marker, green fluorescent protein. This cDNA encodes a 359-amino-acid membrane protein of peroxisomes with two transmembrane segments and a cysteine-rich zinc finger, the RING motif. A stable transformant of ZP109 with the PEX12 was morphologically and biochemically restored for peroxisome biogenesis. Pex12p was shown by expression of bona fide as well as epitope-tagged Pex12p to expose both N- and C-terminal regions to the cytosol. Fibroblasts derived from patients with the peroxisome deficiency Zellweger syndrome of complementation group III (CG-III) were also complemented for peroxisome biogenesis with PEX12. Two unrelated patients of this group manifesting peroxisome deficiency disorders possessed homozygous, inactivating PEX12 mutations: in one, Arg180Thr by one point mutation, and in the other, deletion of two nucleotides in codons for 291Asn and 292Ser, creating an apparently unchanged codon for Asn and a codon 292 for termination. These results indicate that the gene encoding peroxisome assembly factor Pex12p is a pathogenic gene of CG-III peroxisome deficiency. Moreover, truncation and site mutation studies, including patient PEX12 analysis, demonstrated that the cytoplasmically oriented N- and C-terminal parts of Pex12p are essential for biological function.

Amino Acid Sequence↗
PubMed1998

Peripheral primitive neuroectodermal tumors in adults: documentation by molecular analysis.

PURPOSE: The Ewing tumor (ET) family of peripheral primitive neuroectodermal tumors (pPNETs) are primitive small round-cell tumors (SRCTs) of the bone and soft tissue that occur predominantly in children and adolescents. However, pPNETs only rarely enter the differential diagnosis of bone and soft tissue SRCTs in adults. Recently, gene fusions between the EWS gene and different members of the ETS transcription factor family have been shown to occur in virtually all pPNETs and thus constitute a pathognomonic marker for this tumor subclass. The aim of the present study was to document EWS/ETS fusion gene expression in suspected pPNETs of adults as objective evidence for the existence of this tumor family in older patients. PATIENTS AND METHODS: The three contributing molecular diagnostic laboratories retrospectively compiled a cohort of all SRCT cases in which EWS/ETS gene fusions had been shown by molecular analysis. This cohort was surveyed for cases that occurred in patients aged 40 years or older, which were then analyzed for their clinical and pathologic features. RESULTS: Nine patients between 40 and 65 years of age were found to have tumors positive for EWS/ETS gene fusions. Standard histopathologic and clinical features of these cases, other than age, were similar to those of childhood pPNETs. Patients were initiated on appropriate therapy after molecular analysis confirmed the diagnosis of pPNET. CONCLUSION: Identification of an EWS/ETS gene fusion is useful in providing objective evidence of the diagnosis of pPNET in patients over the age of 40 years. This diagnosis should be considered in adults who present with bone and soft tissue SRCTs and appropriate biopsy specimens should be collected for molecular analysis at the time of diagnosis.

Adult↗
PubMed1998

EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma.

PURPOSE: More than 90% of Ewing's sarcomas (ES) contain a fusion of the EWS and FLI1 genes, due to the t(11;22)(q24;q12) translocation. At the molecular level, the EWS-FLI1 rearrangements show great diversity. Specifically, many different combinations of exons from EWS and FLI1 encode in-frame fusion transcripts and result in differences in the length and composition of the chimeric protein, which functions as an oncogenic aberrant transcription factor. In the most common fusion type (type 1), EWS exon 7 is linked in frame with exon 6 of FLI1. As the fundamental pathogenetic lesion in ES, the molecular heterogeneity of these fusion transcripts may have functional and clinical significance. PATIENTS AND METHODS: We performed a clinical and pathologic analysis of 112 patients with ES in which EWS-FLI1 fusion transcripts were identified by reverse-transcriptase polymerase chain reaction (RT-PCR). Adequate treatment and follow-up data were available in 99 patients treated with curative intent. Median follow-up in these 99 patients was 26 months (range, 1 to 140 months). Univariate and multivariate survival analyses were performed that included other prognostic factors, such as age, tumor location, size, and stage. RESULTS: Among the 99 patients suitable for survival analysis, the tumors in 64 patients contained the type 1 fusion and in 35 patients contained less common fusion types. Stage at presentation was localized in 74 patients and metastatic in 25. Metastases (relative risk [RR] = 2.6; P = .008), and type 1 EWS-FLI1 fusion (RR = 0.37; P = .014) were, respectively, independent negative and positive prognostic factors for overall survival by multivariate analysis. Among 74 patients with localized tumors, the type 1 EWS-FLI1 fusion was also a significant positive predictor of overall survival (RR = 0.32; P = .034) by multivariate analysis. CONCLUSION: EWS-FLI1 fusion type appears to be prognostically relevant in ES, independent of tumor site, stage, and size. Further studies are needed to clarify the biologic basis of this phenomenon.

Adolescent↗
PubMed1998

Studies on the antiviral mechanisms of protein kinase inhibitors K-252a and KT5926 against the replication of vesicular stomatitis virus.

We investigated the antiviral mechanisms of K-252a, a broad non-specific protein kinase inhibitor which was isolated from Nocardiopsis sp. and its derivative (KT5926), against vesicular stomatitis virus (VSV) replication in BHK-21 cells. Although K-252a (5 microM) and KT5926 (15 microM) similarly suppressed the viral primary and secondary transcriptions and genomic RNA synthesis in vivo, the inhibitory mechanisms did not seem to be the same; phosphorylation of the viral NS protein was suppressed by K-252a, which might account for the decreased viral RNA synthesis caused by K-252a. On the other hand, KT5926, being known to preferentially inhibit myosin light chain kinase (MLCK), had little effect on NS protein phosphorylation. Cellular casein kinase II, which is believed to be involved in the phosphorylation of the N-terminal side (domain I) of NS protein, was not inhibited at all by KT5926 even at 15 microM under in vitro assay conditions, and was only weakly inhibited by K-252a at 1 to 10 microM. Neither inhibitor seemed to directly affect viral protein synthesis, but affected it indirectly as a secondary effect of reduced viral RNA synthesis. These results suggest that both the KT5926-sensitive and the KT5926-resistant but K-252a-sensitive functions are involved in the essential processes of viral RNA synthesis. The KT5926-sensitive function(s) might not be involved in the NS protein phosphorylation, but may participate in some other way in the process of virus replication. On the other hand, the KT5926-resistant, K-252a-sensitive function(s) are probably involved in NS protein phosphorylation. The possible nature of those functions is discussed.

Alkaloids↗
PubMed1998

Reconstruction of bone defect using the bone transport technique for a case of osteosarcoma of the femur.

There are few reports on skeletal reconstruction using the bone transport technique to repair bone defects caused by resections of tumors associated with osteosarcoma. We attempted to reconstruct a 23 cm bone defect after resection of an osteosarcoma of the left femur, and succeeded in gaining 17 cm by bone transport. Five years after surgery, this patient remains alive without metastasis or local recurrence.

Bone Regeneration↗
PubMed1998

Prosthetic knee replacement after resection of a malignant tumor of the distal part of the femur. Medium to long-term results.

We evaluated the medium to long-term results of treatment with a custom prosthetic knee replacement after wide resection of a primary malignant tumor of the distal part of the femur in forty consecutive patients. The duration of follow-up ranged from five to seventeen years (median, eight years). At the time of the latest follow-up, thirty-five (88 per cent) of the forty patients were free of disease and five (13 per cent) were alive with metastatic disease. No local recurrence was observed. Twenty early complications occurred in eighteen patients (45 per cent). Aseptic loosening of the femoral component, which necessitated a revision in eleven patients at an average of fifty-one months, was the most frequent mode of failure. The rate of prosthetic survival, as estimated with use of the Kaplan-Meier method, was 85, 67, and 48 per cent at three, five, and ten years. Univariate analysis demonstrated that the rate of prosthetic survival was significantly worse for male patients, for those in whom at least 40 per cent of the femur had been resected, for those who had had total resection of the quadriceps muscles or subtotal resection (preservation of only the rectus femoris muscle), and for those in whom a straight femoral stem had been used (p < 0.05 for all comparisons). Multivariate analysis showed that the independent adverse prognostic factors for prosthetic survival were male gender, resection of at least 40 per cent of the femur, and fixation of the femoral stem with cement. The rate of limb salvage was calculated, with use of the Kaplan-Meier method, to be 93 per cent at three years and 90 per cent at five and ten years. At the latest follow-up examination, the functional scores according to the classification system of the Musculoskeletal Tumor Society ranged from 14 to 29 points; the mean was 24 points, which represents function that is 80 per cent that of normal. The mean scores in the categories of walking supports and gait were better for the patients in whom the quadriceps muscles had been preserved than for those who had had total or subtotal resection of those muscles. Although advances in imaging and local therapy narrow the indications for an extra-articular resection of a tumor, the implant that was used in the present study continues to be used in approximately 15 per cent of patients who have a fracture or an intra-articular extension of the tumor that necessitates extensive extra-articular resection.

Adolescent↗
PubMed1998

Interrelationships of clinical outcome, length of resection, and energy cost of walking after prosthetic knee replacement following resection of a malignant tumor of the distal aspect of the femur.

The relationships between the functional score according to the system of the International Society of Limb Salvage, the extent of resection, energy cost of walking, and gait characteristics were studied in thirty-six patients who had had segmental knee replacement after resection of a malignant tumor of the distal aspect of the femur. The mean free-walking velocity was 62.3 meters per minute (79 per cent of normal), which was a result of decreases in both cadence and stride length. The mean net energy cost during walking was 35 per cent greater than that of normal controls and correlated with the percentage of the femur that had been resected. All patients had decreased single-limb support time on the affected side compared with the unaffected side. There was a weak correlation between the asymmetry of the single-limb support time and the percentage of the femur that had been resected. The mean extensor torque of the affected knee was 30 per cent that of the unaffected knee when one head of the quadriceps muscle had been excised, 19 per cent when two heads had been excised, 4 per cent when three heads had been excised, and 1 per cent when four heads had been excised. The patients who had had an extra-articular resection had lower mean extensor and flexor torques at the knee compared with those who had had an intra-articular resection. The asymmetry of the single-limb support time was inversely related to the residual extensor and flexor torques. The overall score according to the system of the International Society of Limb Salvage ranged from 17 to 29 points (mean, 24.6 points; 82 per cent of normal). The net energy cost, percentage of maximum aerobic capacity, and asymmetry of the single-limb support time had significant negative correlations with the overall functional score. Multivariate analysis showed that the overall functional score and the percentage of the femur that had been resected were the two most important factors that predicted the net energy cost. To our knowledge, this is the first objective validation of the functional score according to the system of the International Society of Limb Salvage. As the net energy cost can be predicted from universally available, inexpensive measures, investigators can easily use it as a clinical and research tool to evaluate prosthetic performance and to assess operative outcome.

Adolescent↗
PubMed1998

Evaluation of the effect of preoperative chemotherapy in bone sarcomas. 99mTc-HMDP scintigraphy in 34 cases.

We quantitatively analyzed images of 99mTc-HMDP bone scintigraphy in 34 bone sarcomas before and after preoperative chemotherapy. The isotopic uptake was calculated as tumor-to-background ratio (TBR), and the changes in TBR before and after chemotherapy were calculated as the alteration ratio. The histological effect of preoperative chemotherapy was classified in 4 grades, according to Huvos. We defined good scintigraphic responders as cases having decreased uptake after chemotherapy, with an alteration ratio > or = 60%. There was a positive correlation (Rho = 0.76, p < 0.001) between the histological effect and the alteration ratio. Of the 17 good histological responders, 13 showed a good scintigraphic response. The average alteration ratio in 17 cases with good response (68%) was higher than that in 17 cases showing poor response (-9.9%) (p < 0.001). 3 patients with pathologic fractures and 1 with primarily normal uptake showed false negative findings. The sensitivity of this method was 100% and the specificity was 81%.

Adolescent↗
PubMed1998

Osteosarcoma of the pelvis. Oncologic results of 40 patients.

The cases of 40 patients with osteosarcoma of the pelvis treated between 1977 and 1994 were reviewed. The location of the tumor was ilium in 30 patients, ischium in four, pubis in one, and sacrum in five. Most (58%) of the tumors were of the chondroblastic subtype. Thirty patients had surgical excision of the tumors: 10 with hemipelvectomies and 20 with limb sparing procedures. A wide margin was achieved in 16 of 30 (53%) patients, including 12 of 14 who had no sacral tumor involvement. Positive margins occurred at the sacrum in 11 patients, lumbar vertebra in one, perirectal space in one, and contralateral pubic body in one. Macroscopic tumor emboli within the regional large vessels were found in seven patients. The incidence of local recurrence was 32%: 13% in wide excisions, 38% in marginal excisions, and 80% in intralesional excisions. The 1- and 5-year overall patient survivals were 73% and 34%, respectively. Patients who had a surgical excision of the primary tumor had a significantly better survival than did those treated without surgery (5-year survival; 41% and 10%, respectively). Tumor size, surgical excision of the primary tumor, surgical margin, and type of surgical procedure were the prognostic factors for patients with Stage IIB tumors.

Adolescent↗