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Biomedical subjects

Y Hirose

Publications and source records attributed to Y Hirose.

404 records · Page 23Linked to original sources

Structure and expression of variant BRCA2a lacking the transactivation domain.

BRCA1 and BRCA2 are tumor suppressor genes shown to be involved in 90% of familial breast cancers and also known to be involved in ovarian and prostate cancers. Both BRCA1 and BRCA2 gene products are regulated in a cell cycle-dependent manner and have potential transactivation function. Here, we show that BRCA2 undergoes differential splicing giving rise to a novel variant protein BRCA2a, lacking putative transcriptional activation domain. Both BRCA2a and BRCA2 are expressed at high levels in thymus and testis but moderate levels in mammary gland and prostate suggesting that BRCA2a and BRCA2 may have a role in the development and differentiation of these tissues.

Alternative Splicing↗

Nonspecific cross-reacting antigen-50/90 (NCA-50/90) as a new tumor marker.

BACKGROUND: The nonspecific cross-reacting antigen-50/90 (NCA-50/90) is a glycoprotein antigen which shares some antigenic determinants with carcinoembryonic antigen (CEA). No definite clinical value has been established for the measurement of NCA-50/90 in cancer patients. METHODS: We established and evaluated a chemiluminescent enzyme immunoassay (CLEIA) specific for NCA-50/90 using two monoclonal antibodies. RESULTS: No significant reactivity with 4 purified related antigens including CEA was found in the NCA-50/90 CLEIA. Serum samples (n = 572) from patients with malignant (n = 326) as well as from healthy individuals (n = 246) were analyzed by the NCA-50/90 CLEIA and by the established ACCESS CEA assay. The average sensitivity of NCA-50/90 for malignant disease was 40.8%, compared to 45.4% of CEA. Relatively high positive rates of NCA-50/90 were observed in sera from patients with lung cancer (72.0%), hepatoma (62.5%), pancreatic cancer (47.6%), breast cancer (35.6%), and colorectal cancer (34.5%). About 15% of patients with malignant disease were positive only for NCA-50/90. The levels of NCA-50/90 and CEA in sera from patients with malignant disease correlated only poorly. CONCLUSIONS: The present study suggests that increases in blood levels of NCA-50/90 occur in a population of cancer patients which is different from those with elevated levels of CEA and that NCA-50/90 might be useful for NCA-50/90-positive, but CEA-negative patients.

Animals↗

Carcinoma-associated antigens MK-1 and CEA in urological cancers.

BACKGROUND: The MK-1 antigen, recognized by monoclonal antibody FU-MK-1, is widely associated with human carcinomas. However, the expression and distribution of MK-1 in urological cancers is not well known. MATERIALS AND METHODS: We examined the expression of MK-1 in 10 urological tumor cell lines using flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR) and in 15 cancer tissue specimens by immunohistochemical staining, and then compared it with that of carcinoembryonic antigen (CEA). RESULTS: When analyzed by flow cytometry, MK-1 was positive in 2 out of 3 bladder, 3 out of 3 prostate and one out of 4 renal tumor cell lines, whereas CEA was negative in all the 10 tumor cell lines. RT-PCR confirmed the presence of MK-1 mRNA in all the six MK-1-positive tumor cell lines. An immunohistochemical study demonstrated that MK-1 was positive in 2 out of 5 bladder, 2 out of 5 prostate and one out of 5 renal cancer tissues. Again, however, CEA was negative in all the 15 urological cancer tissues tested. CONCLUSION: These findings suggest that MK-1 seems to be a useful biological marker for malignant urological tumors, especially in cases of bladder and prostate cancer.

Antibodies, Monoclonal↗

Targeting of LAK activity to CEA-expressing tumor cells with an anti-CEA scFv/IL-2 fusion protein.

BACKGROUND: Fusion of tumor-specific monoclonal antibody (MAb) and cytokines has proved to be an efficient way to target cytokines to tumor cells and hence focuses the killing activity of effector cells to the target cells. We previously produced a high affinity MAb, F11-39, against carcinoembryonic antigen (CEA), which is often overexpressed on the surface of various tumor cells. MATERIALS AND METHODS: To target the cytotoxicity of effector cells to CEA-expressing tumor cells, we employed recombinant DNA techniques to fuse recombinant human interleukin-2 (rhIL-2) to a single chain variable fragment (scFv) antibody derived from F11-39. The resulting fusion protein, designated F39scFv/IL-2, was expressed in the Sp2/0-Ag14 mouse hybridoma cells, purified by CEA-affinity chromatography and characterized for the CEA-binding specificity and the IL-2 biological activity. RESULTS: F39scFv/IL-2 protein effectively targeted rhIL-2 onto the surface of CEA-expressing tumor cells and consequently introduced a specific cytotoxicity of lymphokine-activated killer cells to the tumor cells. CONCLUSIONS: This approach may be used for in vivo administration to localize IL-2 to tumor tissues, maximizing the immune response to CEA-expressing tumors while keeping systemic side effects to a minimum.

Animals↗

[A case of Guillain-Barré syndrome with bulbar palsy showing the elevations of the anti-GD1a and GT1b antibodies].

We reported a 44-year-old woman with Guillain-Barré syndrome (GBS) showing elevations of serum anti-GD1a and anti-GT1b antibody levels. A few days after an upper respiratory infection, she felt numbness in her hands and feet, dysphagia and dysarthria, and weakness in her limbs. On admission, examination showed the paralysis of pharynx and neck, moderate weakness of face and upper limbs, and mild weakness of lower limbs. Sensory deficits were minimal on the distal side of extremities. Deep reflexes were decreased or absent. Laboratory examinations revealed the albumino-cytological dissociation in cerebrospinal fluid and the increase of anti-GD1a and anti-GT1b antibodies in serum. Nerve conduction studies demonstrated axonal damage to the motor nerves. With immunoadsorption therapy, she gradually recovered and the anti-GD1a and anti-GT1b antibodies were normalized. It was reported that the anti-GT1a antibody may be associated with a pharyngeal-cervical-brachial (PCB) variant of GBS (Ropper) and the similar cases including the present case. However, in the present case, the serum anti-GT1a antibody level was not increased, whereas those of anti-GD1a and anti-GT1b antibodies did. Therefore, these antibodies may also play a role in the development of PCB signs in GBS.

Adult↗

Enhancing osseointegration by capacitively coupled electric field: a pilot study on early occlusal loading in the dog mandible.

Expeditious postoperative appositional growth of bone to dental implants is desired for clinically successful fixation of oral implants. The present study was performed to evaluate the effect of applying a capacitively coupled electric field (CCEF) followed by functional loading on peri-implant osteogenesis in the dog mandible. Nine adult beagles were used in this study. All premolars on both sides of the mandible were removed from each dog. A physio-odontlam implant (POI, Ti-6AI-4v) with 2 stages (3.7 mm in diameter and 8.0 mm in length), whose surface had been treated with anodic oxidation and sandblasted, was placed into each test site by self-tapping. Daily application of CCEF (8 hours per day) was initiated on the day following surgery and continued for 14 days or 21 days. After CCEF treatment was finished for each period, a prosthetic abutment and a straight post were placed on each implant. Four days after placement of the post, implants were placed under functional loading for 30 days. The dogs were then sacrificed, and histologic and radiographic studies of the mandible were performed. Relatively well calcified, mature bone with a lamellar-like structure was observed by contact microradiography and histologic study (double staining with basic fuchsin-methylene blue) of the peri-implant region on the CCEF-treated samples. In contrast, poorly calcified, immature bone without a lamellar structure was observed in control sites not treated with CCEF. The bone area ratios of the CCEF-treated sides were larger than those of control sides. These results suggest that the application of CCEF after implant placement may enhance peri-implant osteogenesis, even with functional loading.

Animals↗

Flumazenil antagonizes the suppressive effect of midazolam on the somatosensory evoked potentials in the rat.

The effect of flumazenil, a specific benzodiazepine antagonist, on the midazolam-induced suppression of somatosensory evoked potentials (SEPs) following strong electrical stimulation of the upper lip was investigated in Wistar albino rats. The averaged SEPs were recorded from the contralateral surface of the skull in the temporal area. Each rat received midazolam in a dose of 10 mg/kg intraperitoneally. Five min after midazolam injection, the relative amplitude of the P1N1 wave of the SEPs was reduced significantly. A 0.5 mg dose of flumazenil or physiological saline was injected intraperitoneally 7.5 min after midazolam injection. The P1N1 amplitude recovered rapidly to the control value in the flumazenil group but not in the physiological saline group. No significant differences were found in the latencies of the P1 and N1 peaks before or after midazolam or flumazenil injection. It is suggested that flumazenil strongly antagonizes the midazolam-induced suppression of SEPs in the rat.

Anesthesia, Dental↗