Biomedical subjects

K Sawai

Publications and source records attributed to K Sawai.

At least 19 recordsLinked to original sources

PubMed2006

Transgenic overexpression of brain natriuretic peptide prevents the progression of diabetic nephropathy in mice.

AIMS/HYPOTHESIS: Brain natriuretic peptide (BNP) is a potent vasorelaxing and natriuretic peptide that is secreted from the heart and has cardioprotective properties. We have previously generated hypotensive transgenic mice (BNP-Tg mice) that overproduce BNP in the liver, which is released into the circulation. Using this animal model, we successfully demonstrated the amelioration of renal injury after renal ablation and in proliferative glomerulonephritis. Glomerular hyperfiltration is an early haemodynamic derangement, representing one of the key mechanisms of the pathogenesis of diabetic nephropathy. Based on the suggested involvement of increased endogenous natriuretic peptides, the aim of this study was to investigate their role in the development and progression of diabetic nephropathy. MATERIALS AND METHODS: We evaluated the progression of renal injury and fibrogenesis in BNP-Tg mice with diabetes induced by streptozotocin. We also investigated the effect of BNP on high glucose-induced signalling abnormalities in mesangial cells. RESULTS: After induction of diabetes, control mice exhibited progressively increased urinary albumin excretion with impaired renal function, whereas these changes were significantly ameliorated in BNP-Tg mice. Notably, diabetic BNP-Tg mice revealed minimal mesangial fibrogenesis with virtually no glomerular hypertrophy. Glomerular upregulation of extracellular signal-regulated kinase, TGF-beta and extracellular matrix proteins was also significantly inhibited in diabetic BNP-Tg mice. In cultured mesangial cells, activation of the above cascade under high glucose was abrogated by the addition of BNP. CONCLUSIONS/INTERPRETATION: Chronic excess of BNP prevents glomerular injury in the setting of diabetes, suggesting that renoprotective effects of natriuretic peptides may be therapeutically applicable in preventing the progression of diabetic nephropathy.

Animals↗

PubMed2004

CT-based evaluation of axillary sentinel lymph node status in breast cancer: value of added contrast-enhanced study.

PURPOSE: To evaluate the diagnostic reliability of CT-based sentinel lymph node (SLN) size criteria for selecting the candidates for direct axillary dissection without SLN biopsy and to determine the value of added contrast-enhanced study. MATERIAL AND METHODS: Breast cancer patients (n = 107) underwent triple phasic (1-min, 3-min, 8-min) contrast-enhanced 5 mm-computed tomography (CT) of the breasts and axillae. In the CT image, the most inferior lymph node in the axilla was designated the SLN. Axillary status was judged based on SLN size criteria. CT density, enhancement rate, and peak enhancement time of each SLN were correlated with histopathological results. RESULTS: SLN size criteria demonstrated a sensitivity of 76% and a positive predictive value of 95% in predicting SLN metastasis. The density values at each scanning time-point were significantly different for metastatic and non-metastatic SLN. However, their enhancement rates differed significantly only at 1 min. Their peak enhancement occurred primarily at 1 min. The use of contrast-enhancement criteria improved the predictive sensitivity, but failed to decrease the false-positive rate of the SLN size criteria. CONCLUSION: The enhancement rate at 1 min proved to be the most useful parameter in contrast-enhanced CT studies; however, it failed in improving the accuracy of the SLN size criteria.

Adult↗

PubMed2004

Genetic polymorphisms and antiviral activity in the bovine MX1 gene.

Bovine MX1 cDNAs consisting of 2280 bp from 11 animals of five breeds and from a cultured cell line were sequenced and compared with previously reported data. Ten nucleotide substitutions were synonymous mutations, and a single nucleotide substitution at 458 resulted in an amino acid exchange of Ile (ATT) and Met (ATG). A 13-bp deletion-insertion mutation was also found in the 3'-UTR. Based on the nucleotide substitutions found in this study, bovine MX1 cDNA was classified into 11 genotypes. A phylogenetic tree of the 11 genotypes suggested that the genotypes observed in Brahman were a great genetic distance from other genotypes. An 18-bp deletion-insertion variation at position 171 was found to be the result of alternative splicing. The 18-bp deletion-insertion is located at the boundary between exon 3 and intron 3. Permanently transfected 3T3 cell lines expressing bovine MX1 mRNA were established to analyse the antiviral potential against VSVDeltaG*-G infection. Transfected cell clones expressing bovine MX1 mRNA showed a significantly smaller number of cells infected with VSVDeltaG*-G compared with the control cells. These results indicate that the bovine MX1 protein has potent antiviral activity.

3T3 Cells↗

PubMed2003

Use of loop-mediated isothermal amplification of the IS900 sequence for rapid detection of cultured Mycobacterium avium subsp. paratuberculosis.

We evaluated the usefulness of loop-mediated isothermal amplification (LAMP) in detecting specific gene sequences of Mycobacterium avium subsp. paratuberculosis (MAP). A total of 102 primer sets for LAMP was designed to amplify the IS900, HspX, and F57 gene sequences of MAP. Using each of two primer sets (P-1 and P-2) derived from the IS900 fragment, it was possible to detect MAP in a manner similar to that used with nested PCR. The sensitivity of LAMP with P-1 was 0.5 pg/tube, which was more sensitive than nested PCR. When P-2 was used, 5 pg/tube could be detected, which was the same level of sensitivity as that for nested PCR. LAMP with P-1 was specific. Although only 2 Mycobacterium scrofulaceum strains out of 43 non-MAP mycobacterial strains were amplified, the amplification reaction for these strains was less efficient than for MAP strains, and their products could be distinguished from MAP products by restriction digestion. LAMP with P-2 resulted in very specific amplification only from MAP, the same result obtained with nested PCR. Our LAMP method was highly specific, and the white turbidity of magnesium pyrophosphate, a by-product of the LAMP reaction, allowed simple visual detection. Our method is rapid, taking only 2 h, compared with 4 h for nested PCR. In addition, the LAMP method is performed under isothermal conditions and no special apparatus is needed, which makes it more economical and practical than nested PCR or real-time PCR. These results indicate that LAMP can provide a rapid yet simple test for the detection of MAP.

DNA Transposable Elements↗

PubMed2002

Video-assisted total glandectomy and immediate reconstruction for breast cancer.

This paper describes a new surgical technique and our clinical experience with video-assisted endoscopic total glandectomy via a middle axillary incision followed by immediate reconstruction with latissimus dorsi muscle flap (LDMF) performed in 17 patients with bigger, multiple tumors or extensive ductal spread of breast cancer. The novel techniques in this procedure are as follows: (1) By securing patients in a semi-lateral position and suspending the upper extremity, either supine or semi-lateral position can be easily achieved by simply rotating the operating table, resulting in a wider working space from the axillary to hip area. (2) By applying a retractor for skin flap traction, endoscopic glandectomy and reconstruction become safe and reliable. As a result, the mean number and size of tumors were 1.2 and 4.12 cm, respectively. Surgical margins of all the cases were pathologically negative and there were no recurrences observed during 14 months follow-up to date. Esthetic results have been satisfactory and the surgical wounds were not visible from the front in any case. Compared to mastectomy, this procedure shows the same therapeutic results, but offers a greater esthetic and psychological advantage to all the patients.

Breast Neoplasms↗

PubMed2002

Evaluation of axillary status in breast cancer. CT-based determination of sentinel lymph node size.

PURPOSE: To determine whether the location and size of sentinel lymph nodes (SLN) on CT are predictive of the axillary lymph node status in patients with breast cancer. MATERIAL AND METHODS: Forty patients with confirmed breast cancer underwent 5-mm CT of both breasts and axillae and the most inferior lymph node in the affected axilla was designated the SLN. Based on CT assessment of the axillary lymph node status, 22 (55%) patients then underwent dye- and gamma probe (DGP)-guided SLN biopsy followed by axillary dissection; 18 (45%) underwent dissection without prior SLN biopsy. The localization and status of the SLN determined on CT and by DGP-guided biopsy were compared. Biopsied and excised nodes were subjected to histopathologic examinations. RESULTS: All SLN identified on CT were close to the lateral thoracic artery and their localization corresponded well with SLN identified by the DGP-guided method. The positive predictive value of CT diagnosis was 100%. Histopathologic examination of excised nodes confirmed that none of the SLN biopsies was false-negative. CONCLUSION: Our CT criteria were highly accurate for identification and diagnostic assessment of SLN and useful for evaluating the axillary status in patients with breast cancer.

Adult↗

PubMed2001

C4d and C4bp deposition along the glomerular capillary walls in a patient with preeclampsia.

Complement (C) 4d and cofactor C4b binding protein (C4bp) are detected in the glomerular capillary walls of a patient with preeclampsia. A 32-year-old nullipara had proteinuria of 1.2 g/d and edema at the 33rd week of pregnancy. Gradually the urinary protein excretion increased, reaching 5.1 g/d at the 37th week. The patient also showed hypertension at this stage. After normal mature delivery, the level of the urinary protein excretion remained at 3 to 4 g/d. Renal biopsy performed by means of light and electron microscopy, 15 days after delivery, showed almost normal glomeruli and modest subendothelial widening. Immunohistochemistry indicated that immunoglobulin (Ig) A, IgG, C1q, C3c, and C4c were not deposited in the glomeruli, whereas weakly positive IgM and fibrin-related antigen (FRA) were observed. Conversely, C4d, C3d, and C4bp were strongly deposited. Protein S (PS) also was observed, with a similar distribution pattern to that of C4bp. Immunoelectron microscopy showed the deposition of C4d along the capillary walls and of C4bp in the subendothelium. These findings suggest that the C4 activation process as well as the regulation process of C system and of the inflammatory coagulation axis by C4bp and PS may play an important role in the pathophysiology of preeclampsia, so-called glomerular capillary endotheliosis (GCE).

Adult↗

PubMed2001

Intraglomerular metastasis from pancreatic cancer.

Few case reports have shown the presence of metastatic tumor cells in renal glomeruli. We report one case with intraglomerular metastasis proved at renal biopsy. A 60-year-old man suffered from weight loss and fever of unknown origin. Urinalysis revealed proteinuria with cellular and granular casts. Because vasculitis was suspected, renal biopsy was performed. Presence of tumor cells occupying the glomerular capillary lumina was shown by means of light microscopy and electron microscopy. Laboratory findings revealed elevated leukocyte count (28.9 x 10(3)/mm(3)), serum granulocyte colony-stimulating factor (G-CSF) (77 pg/mL), and serum CA 19-9 (21,885 U/mL). The patient soon developed disseminated intravascular coagulation and died. Autopsy findings revealed pancreatic cancer showing positive staining for G-CSF and CA 19-9. Tumor cells in the glomerular capillary lumina showed positive staining for CA 19-9 and proliferating cell nuclear antigen (PCNA). These results suggest that the pancreatic tumor cells producing G-CSF were entrapped in the glomerular capillary lumina where they proliferated. This may have been the first step in renal metastasis.

CA-19-9 Antigen↗

PubMed2001

[Concurrent chemoradiation therapy with nedaplatin for high-risk cervical cancer--clinical investigation of adverse events].

A clinical investigation of adverse events was conducted to confirm the safety of concurrent chemotherapy using nedaplatin (cisplatin derivative) and radiotherapy in the high-risk carcinoma of the uterine cervix. Seven patients who were treated with radical radiotherapy and 5 patients who were treated with adjunctive radiotherapy after radical hysterectomy and pelvic lymphadenectomy were eligible for the study. Nedaplatin was given intravenously at 70 mg/m2 on day 1 and day 29, and a total of 24 courses of nedaplatin administration were observed. None of the planned radiotherapy was postponed or discontinued due to side effects. Major adverse effects observed were gastrointestinal effects such as anorexia (66.7%), nausea and vomiting (33.3%) and diarrhea (66.7%). Grade 3 (in the 2nd course) and Grade 4 (in the 1st course) diarrhea was observed in one patient, which was easily relieved by antidiarrheal. Hematologic side effects were also major, including leukopenia (62.5%), neutropenia (75.0%), anemia (75.0%), and thrombocytopenia (33.3%). Hematologic effects were generally moderate; no Grade 4 (severe) effects were observed. Although these hematologic effects were lasting longer compared with radiation therapy alone, there were no significant differences in the seriousness of these side effects. Concurrent chemoradiation therapy with nedaplatin 70 mg/m2 every 4 weeks was safe and adverse effects were self-limited or resolved with medical management. Dose escalation in the phase III clinical study may be considered.

Adenocarcinoma↗

PubMed2001

[Minimally invasive surgery for breast cancer].

Breast conservation surgery has become a standard operation as a minimally invasive surgery for breast cancer in Japan. Now sentinel lymph node biopsy (SLNB), day surgery, and endoscopy assisted surgery are being introduced as more minimally invasive surgeries for breast cancer. When blue dye and/or isotope are injected into the peri-tumoral breast gland, the sentinel lymph nodes (SLN) can be detected easily, and node negative patients can be selected with certainty. When no metastasis is found in SLN by frozen section, T1N0 breast cancer patients can be treated without lymph node dissection. Using this technique, day surgery for patients who have clinically node-negative small breast cancer (less than 1.5 cm in diameter) is performed under local anesthesia. We have developed an endoscopy assisted conservation surgery for breast cancer. Using endoscopy, partial or total glandectomy with radical axillary lymph node dissection is performed via a 5 cm skin incision on the middle axillary line. When the amount of glandectomy is over one third, we perform immediate reconstruction using the latissimus dorsi. These minimally invasive surgeries for breast cancer will result in a better quality of life for breast cancer patients.

Adult↗

PubMed2001

[Current spread of HPN and HEN: issue for making choice in home care].

Recently a number of patients have received home enteral nutrition (HEN) as well as home parenteral nutrition (HPN) in Terumo's home healthcare network 'Home-Joint'. This study was undertaken to compare the patients who received HEN with those who received HPN. 1. HPN patients in 2000. Number: 1,789 (45% females), age: 0-101 (mean: 66 years old, 48% over 70 years old), diagnosis: cancer 54%, therapeutic periods: 0-916 days (mean: 80 days). 2. HEN patients in 2000. Number: 736 (40% females), age: 1-101 (mean: 50 years old, 33% over 70 years old), diagnosis: Crohn's disease 44%, therapeutic periods 0-1,618 days (mean: 183 days). 3. Adoption of HPN and HEN in home care agents. HPN only 66%, HEN only 24%, both HPN and HEN 10%. It suggested that following two issue take place against making choice of HPN or HEN in home nutrition care. 1) Adoption of both HPN and HEN in more clinics. 2) Establishment of the guidelines for systematic HPN/HEN choice.

Aged↗

PubMed2000

Caspase-dependent apoptosis by ectopic expression of E2F-4.

E2F is a family of transcription factors which regulates cell cycle and apoptosis of mammalian cells. E2F-1-3 localize in the nucleus, and preferentially bind pRb, while E2F-4 and 5 have no nuclear localization signal and preferentially bind p107/p130. E2F-6 suppresses the transcriptional activity of other E2F proteins. DP-1 and 2 are heterodimeric partners of each E2F protein. Using tetracycline-responsive promoters, here we compared the effects of ectopic expression of E2F-1, DP-1 and E2F-4 on cell cycle progression and apoptosis in Chinese hamster cell lines. We found that E2F-4, as well as DP-1 and E2F-1, induced growth arrest and caspase-dependent apoptosis. E2F-4 did not have a marked effect on cell cycle progression, while E2F-1 induced DNA synthesis of resting cells and DP-1 arrested cells in G1. Ectopic expression of E2F-4 did not activate E2F-dependent transcription. Our results suggest that expression of E2F-4 at elevated levels induces growth arrest and apoptosis of mammalian cells through a mechanism distinct from E2F-1 and DP-1.

Animals↗

PubMed2000

Cytokine production in chorioamnionitis.

Lymphohematopoietic cytokines play a significant role in many biological mechanisms including a number of reproductive processes such as ovulation, implantation, placentation, cervical dilation and parturition. Recent experiments have suggested that cytokines play a crucial role in the mechanisms of preterm labor and delivery, which are the leading causes of perinatal morbidity and mortality. Growing evidence suggests that infection is deeply concerned in the pathogenesis of preterm labor and delivery. Chorioamnionitis, a subset of intrauterine infection, has been identified in 20-33% of women with preterm delivery, and the inflammatory and related cytokines, interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8), showed substantial increases in the amniotic fluid at women with intrauterine infection. Although the precise mechanism for chorioamnionitis-driven preterm labor mediated via cytokines is still unknown, both IL-1 and TNF-alpha along with IL-6 enhance prostaglandin production by human amnion cells, chorionic cells and decidual cells. Analysis of the regulatory sequences in the 5' upstream regions of receptor gene for human oxytocin, a potent uterotonic agent, suggests a close relationship between preterm labor and inflammatory cytokines through induction at the oxytocin receptor. Prompt identification of the patients with intra-amniotic infection may be useful in clinical practice. At present, the measurement of IL-8 in maternal serum or the measurement of IL-6 in cervical secretion may be helpful as a non-invasive screening for chorioamnionitis.

Cervix Uteri↗

PubMed2000

Transduction of a murine dominant negative activation transcription factor 1 increases cell surface expression of the class I MHC on a human epidermoid tumor cell line.

The transcription of the MHC class I genes is regulated by interaction of cis-elements, located in the 5' genomic flanking regions, with sequence-specific trans-factors. We have identified a cis-regulatory element, 5'-TGACGCG-3', of the H-2D(d) gene. This cyclic adenosine-3',5'-monophosphate regulatory element (CRE)-like sequence, named H-2 binding factor 1 (H-2 BF1) binding motif, is highly conserved among species. In addition, we found that homo- and heterodimers of activation transcription factor 1 (ATF-1) and CRE binding protein (CREB) associate with the H-2 BF1 binding motif and activate transcription of the H-2D(d) gene. Here we demonstrate that a homologue of ATF-1, originally isolated and designated ATF-1DN, acts as a dominant repressor, blocking the ability of wild-type ATF-1 and CREB to bind to the H-2 BF1 probe in electrophoretic mobility shift assays (EMSA). We have utilized this molecule to analyze the participation of the H-2 BF1 complexes, consisting of the H-2 BF1 binding motif and ATF-1/CREB trans-factors, in the physiological regulation of MHC class I expression in tissue culture cells. A human epidermoid carcinoma cell line, A431, was transfected with ATF-1DN and clones expressing the gene transcripts were selected. When analyzed in the EMSA, nuclear proteins prepared from these clones exhibited a decreased shift of the H-2 BF1 probe corresponding to the levels of the ATF-1DN gene expression. Additionally, MHC class I expression of cells with reduced H-2 BF1 activity was significantly higher than in control cells lacking ATF-1DN. These findings indicate that in these carcinoma cells, the H-2 BF1 complexes negatively regulate the constitutive expression of MHC class I.

Activating Transcription Factor 1↗

PubMed2000

[A late phase II study of raltitrexed (ZD 1694) in chemotherapy-naive patients with advanced colorectal cancer].

A multicenter co-operative late phase II study of raltitrexed (ZD1694), a specific thymidylate synthase (TS) inhibitor, was conducted in chemotherapy-naive patients with advanced colorectal cancer. Raltitrexed was infused intravenously over 15 minutes once every three weeks. Between April 1996 and September 1998, 61 patients were enrolled and 58 were eligible. Fourteen patients experienced a partial response (PR), 22 no change (NC), 20 progressive disease (PD) and 2 no evaluable (NE). The overall response rate was 24.1% (95% CI: 13.9-37.2%). Responses were seen in lung (22.7%), liver (22.9%) and deep lymph nodes (10.0%). Median survival was 11.6 months. Grade 3 or 4 toxicities were: leukopenia (13.8%), neutropenia (24.1%), hemoglobin decrease (15.5%), FBC decrease (6.9%), hematocrit decrease (6.9%), thrombocytopenia (6.9%), transient SGPT increase (6.9%), nausea/vomiting (20.7%), anorexia (15.5%), and asthenia (6.9%). These adverse reactions were considered to be manageable. Only one death was associated with drug treatment. These results suggest that raltitrexed provides an effective and convenient treatment for patients with advanced and previously untreated colorectal cancer.

Adult↗

PubMed2000

Lymph-node staining with activated carbon CH40: a new method for axillary lymph-node dissection in breast cancer.

OBJECTIVE: To demonstrate the usefulness of activated carbon particles (CH40) as a vital staining dye for visualizing lymphatic vessels and lymph nodes in breast cancer. DESIGN: A retrospective evaluation. SETTING: Department of Surgery in Sendai National Hospital, Japan, a 716-bed teaching hospital. METHODS: To identify as many lymph nodes as possible in the axillary fat, by which we might decrease the possibility of the presence of undetected metastatic nodes, an emulsion of activated carbon particles (CH40) was injected into the centre of the mammary gland, close to the tumour site, 3 days before radical surgery. MAIN OUTCOME MEASURE: The number of lymph nodes found by the traditional method and by the CH40-injection method were recorded. RESULTS: After injection, the CH40 was readily adsorbed into regional lymphatics and streamed along with the lymph flow to blacken regional lymph nodes. The CH40-guided method increased the mean number of nodes per case found in the axilla from 8.4, by the traditional method, to 14.0 nodes per case. CONCLUSIONS: The use of the CH40 technique has two technical advantages; one is that it allows surgeons to locate the blackened lymph nodes at the time of surgery and the other is that it allows pathologists to look for the nodes in fatty tissue. Lymph-node dissection with the aid of activated carbon particles is inexpensive, easy to perform and enables the smallest lymph nodes to be easily recognized. CH40 is the technique of choice for the detection of axillary lymph nodes in cases where the number of lymph nodes detected by the traditional method is too small for accurate surgery. In conclusion, the present study demonstrates that CH40 could be an appropriate tool for more accurate staging of breast cancer axillary specimens.

Adult↗

PubMed2000

[Homocystinuria with generalized chorea and other movement disorders: a case report].

We report a 50-year-old right-handed woman who, at age 20, was diagnosed to have homocystinuria presumably due to cystathionine beta-synthase deficiency. At age 40 years, involuntary movements developed insidiously, affecting her face, neck and upper limbs. During the next 10 years, involuntary movements progressed and she could no longer walk. Examination disclosed bilateral lens dislocation and marfanoid skeletal deformity. Muscle strength was mildly decreased in the right arm and bilateral legs. There was hyperreflexia in the right upper and bilateral lower extremities without Babinski sign. Muscle tone was mildly increased in the neck and bilateral upper extremities. She had persistent generalized choreic movements, dystonia affecting the face and neck, and resting and postural tremor in the upper limbs and tongue. A cranial CT scan showed an old low density lesion in the left frontal area. Involuntary movements in homocystinuria is rare and, to our knowledge, only 9 cases have been reported. This case was unique in that involuntary movements developed in the adulthood.

Chorea↗

PubMed2000

[Current spread of HPN and its forecast--especially in the dual therapy of HPN and HOT].

In 1999, Terumo's home healthcare network 'Home-Joint' managed more than 1,000 patients who underwent home parenteral nutrition (HPN). This spread of HPN led some patients to undergo another home medical treatment during the same period. This report evaluates the patients who underwent dual home therapy (HPN and HOT: home oxygen therapy) in comparison with patients who underwent HPN only. 1. Single HPN patients in 1999. Number: 1,034 (male 57%), age: 1-99 (mean 65, 43% over 70), diagnosis: cancer 52%, therapeutic periods: 1-437 days (mean 81). 2. Dual HPN-HOT patients in 1999. Number: 27 (male 70%), age: 44-94 (mean 75, 70% over 70), diagnosis: cancer 59%, therapeutic periods: HPN 1-388 days (mean 91), HOT 1-827 days (mean 99). 3. Adoption of dual HPN-HOT therapy. It is suggested that the dual HPN-HOT therapy may be adopted for at least the following two types of patients. 1) Pulmonary failure with HPN, 2) Malnutrition on HOT.

Adolescent↗