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Biomedical subjects

K Yamada

Publications and source records attributed to K Yamada.

At least 505 records · Page 28Linked to original sources

Pineal region metastasis appearing as hypointensity on T2-weighted magnetic resonance imaging--case report.

A 48-year-old female presented with headache and limitation of upward gaze. She had a history of total gastrectomy for gastric adenocarcinoma 2 years previously. Computed tomography with contrast medium and T1-weighted magnetic resonance (MR) imaging with gadolinium showed ring-like enhancement of a solitary mass in the pineal region with obstructive hydrocephalus. T2-weighted MR imaging showed the tumor as hypointense. This MR imaging finding complicated the preoperative diagnosis, but malignancy was suspected from the medical history. The tumor was subtotally resected via the occipital transtentorial approach with a rigid endoscope. Histological examination of the surgical specimen revealed adenocarcinoma cells with extensive coagulation necrosis, which might have contributed to the hypointensity on T2-weighted MR imaging. Correct diagnosis of metastatic adenocarcinoma based only on MR imaging may be difficult in such cases, but metastatic adenocarcinoma of the pineal region must be considered in the differential diagnosis of pineal tumors.

Adenocarcinoma↗

Effects of ovariectomy on parafollicular cells in the rat.

Changes in the parafollicular cells in the thyroid gland of ovariectomized rats were investigated to clarify the relationship between the secretory function of sex hormones and that of parafollicular cells. Compared with control rats, the ovariectomized rats exhibited decreases in 1) the number of parafollicular cells in the thyroid glands, 2) the number of secretory granules in the parafollicular cells, and 3) the area occupied by the Golgi complex. These results suggest that the lack of estrogen caused by ovariectomy reduces the synthesis and release of calcitonin in parafollicular cells, which may be one of the causes of osteoporosis.

Animals↗

Bombesin-like peptides: studies on food intake and social behaviour with receptor knock-out mice.

Bombesin (BN)-like peptides and receptors for these peptides are widely distributed in mammalian peripheral tissues and the central nervous system. The physiological and behavioural functions of these peptides have been clarified by both in vivo and in vitro studies. In spite of intensive investigations, the functions of endogenous BN-like peptides remain unclear. In order to specify these functions, our group and another laboratory generated by gene targeting mutant mice that lack one of the three BN-like peptide receptors found in mammals, ie neuromedin B receptor (NMB-R; BB1), gastrin-releasing peptide receptor (GRP-R; BB2), or bombesin receptor subtype-3 (BRS-3; BB3). Using these mutant mouse, we have found unexpected phenotypes, such as hyperphagia and obesity in the BRS-3-deficient mouse, and abnormal social behaviour in the GRP-R-deficient mouse. In the present study, we present our most recent findings in addition to previous studies and discuss the functions of BN-like peptides related to feeding and social behaviour from the point of view of knock-out mice studies.

Animals↗

Bone regeneration at rabbit skull defects treated with transforming growth factor-beta1 incorporated into hydrogels with different levels of biodegradability.

OBJECT: Skull bone regeneration induced by transforming growth factor-beta1 (TGFbeta1)-containing gelatin hydrogels (TGFbeta1-hydrogels) was investigated using a rabbit skull defect model. Different strengths of TGFbeta1 were examined and compared: different TGFbeta1 doses in gelatin hydrogels with a fixed water content, different water contents in gelatin hydrogels with a fixed TGFbeta1 dose, and TGFbeta1 in solution form. In addition, regenerated skull bone was observed over long time periods after treatment. METHODS: Soft x-ray, dual energy x-ray absorptometry, and histological studies were performed to assess the time course of bone regeneration at a 6-mm-diameter skull defect in rabbits after treatment with TGFbeta1-hydrogels or other agents. The influence of TGFbeta1 dose and hydrogel water content on skull bone regeneration by TGFbeta1-hydrogels was evaluated. Gelatin hydrogels with a water content of 95 wt% that incorporated at least 0.1 microg of TGFbeta1 induced significant bone regeneration at the rabbit skull defect site 6 weeks after treatment, whereas TGFbeta1 in solution form was ineffective, regardless of dose. The in vivo degradability of the hydrogels, which varied according to water content, played an important role in skull bone regeneration induced by TGFbeta1 -hydrogels. In our hydrogel system, TGFbeta1 is released from hydrogels as a result of hydrogel degradation. When the hydrogel degrades too quickly, it does not retain TGFbeta1 or prevent ingrowth of soft tissues at the skull defect site and does not induce bone regeneration at the skull defect. It is likely that hydrogel that degrades too slowly physically impedes formation of new bone at the skull defect. Following treatment with 0.1-microg TGFbeta1-hydrogel (95 wt%), newly formed bone remained at the defect site without being resorbed 6 and 12 months later. The histological structure of the newly formed bone was similar to that of normal skull bone. Overgrowth of regenerated bone and tissue reaction were not observed after treatment with TGFbeta1 -hydrogels. CONCLUSIONS: A TGFbeta1-hydrogel with appropriate biodegradability will function not only as a release matrix for the TGFbeta1, but also as a space provider for bone regeneration. The TGFbeta1-hydrogel is a promising surgical tool for skull defect repair and skull base reconstruction.

Absorptiometry, Photon↗

Biosynthesis of pyridoxine: origin of the nitrogen atom of pyridoxine in microorganisms.

The amide nitrogen atom of glutamine was incorporated into pyridoxine in four eukaryotes, Emericella nidulans, Mucor racemosus, Neurospora crassa and Saccharomyces cerevisiae, and two prokaryotes, Staphylococcus aureus and Bacillus subtilis, but not in the following prokaryotes, Pseudomonas putida, Enterobacter aerogenes and Escherichia coli. On the other hand, the nitrogen atom of glutamate was incorporated into pyridoxine in P. putida, E. aerogenes and E. coli, but not in S. aureus and B. subtilis. These results suggest that there are at least two different biosynthetic routes for pyridoxine and the difference does not depend on prokaryotes and eukaryotes.

Eukaryotic Cells↗

Pharmacokinetic consideration on administration regimen of lamivudine in japanese patients infected with HIV-1.

OBJECTIVE: The typical regimen for lamivudine is 150 mg bis in die (bid). However, pharmacokinetic values of lamivudine will differ among individual patients. In addition, few studies regarding the pharmacokinetics of lamivudine in the Japanese people have so far been reported. Therefore, we have aimed to examine the variation in the pharmacokinetic values of lamiduvine present in six Japanese patients with HIV-1 infection. PATIENTS AND METHODS: Lamivudine concentrations were measured in three hemophiliacs (HIV-1-asymptomatic carrier, AC) and three non-hemophiliacs (2 of these patients were AC and one had AIDS-related complex, ARC). In order to simulate the lamivudine plasma concentrations found in chronic oral administration, we added an absorption compartment to the two-compartment model. RESULTS: The mean +/- SD of Tmax, Cmax, AUC(0 - infinity) and t1/2beta were 1.2 +/- 0.5 (hours), 1,280 +/- 267 (ng/ml), 6,778 +/- 2,763 (ng x h/ml), and 10.3 +/- 4.7 (hours), respectively. Although these values were comparable on average to those previously reported, there were noticeable differences with respect to the various time courses of drug plasma concentration among each patient. CONCLUSION: Computations speculated that the trough and peak plasma concentrations as well as the AUC at steady-state change significantly depending on each patient. It suggests that individual pharmacokinetic values of lamivudine should be determined before deciding the optimal administration dose for specific patients.

Adult↗

[Cardiovascular effects of the thiazolidinedione troglitazone].

Troglitazone, a newly introduced insulin sensitizer, has been implicated in prevention and treatment of atherosclerotic cardiovascular disease especially associated with type 2 diabetes mellitus and insulin resistance. Beneficial effects of troglitazone on multiple risk factor syndrome have been reported in terms of blood pressure lowering effect and ameliorations of dyslipidemia and hyperinsulinemia. Moreover, in vitro and in vivo studies have shown vasodilating and antiatherogenic effects as well as cardioprotective action of this compound. Thus, troglitazone may have potential to prevent and delay diabetic heart disease and large vessel complications.

Animals↗

Constitutively active STAT5A and STAT5B in vitro and in vivo: mutation of STAT5 is not a frequent cause of leukemogenesis.

We recently identified several constitutively active forms of signal transducers and activators of transcription 5 (STAT5) using polymerase chain reaction-driven random mutagenesis followed by retrovirus-mediated expression screening. All constitutively active STAT5 showed constitutive phosphorylation on their tyrosine residues and induced factor-independent growth in a mouse interleukin-3-dependent cell line, Ba/F3. Sequence analysis of these active STAT5 revealed two important mutations: S710F and N642H. The N642H mutation localized in the SH2 domain was able to induce autonomous growth of Ba/F3 cells by itself, whereas S710F in the effector domain was able to induce autonomous growth of Ba/F3 cells in concert with a second mutation including H298R and E150G. Recently, constitutive activation of STAT5 has been reported in patients' leukemic cells and is implicated in leukemogenesis. We attempted to clarify whether leukemic cells harbored activating mutations primarily in STAT5 proteins, and analyzed the sequence of STAT5 derived from 49 leukemic patients. No mutations were found, however, in the regions surrounding S710 and N642 of STAT5A and corresponding residues of STAT5B. We also cloned full-length cDNAs for STAT5s from three patients whose leukemic cells exhibited constitutive tyrosine phosphorylation of the STAT5 protein and expressed the derived STAT5 proteins in Ba/F3 cells. However, none of these clones exhibited constitutive tyrosine phosphorylation or gave rise to FI proliferation of Ba/F3 cells. These results indicate that constitutive activation of STAT5 is a secondary event in most leukemias.

Animals↗

Repair of leaking postinfarction ventricular septal defect under circulatory arrest via left thoracotomy.

We treated a 60-year-old woman for postinfarction ventricular septal defect (VSD) and closed it by the infarction exclusion method. Postoperatively she was complicated by Candida sternal mediastinitis and residual shunt of VSD. After her sternal infection came under control we repaired the leaking VSD via left thoracotomy under hypothermic circulatory arrest. She recovered well and repair of the leaking VSD under circulatory arrest via left thoracotomy seemed to be a safe and promising alternative for VSD repair.

Blood Vessel Prosthesis Implantation↗

[An successful case of combined daily oral administration of UFT and low-dose etoposide for multiple metastases of lung cancer].

The authors treated a 49-year old female patient, who had multiple metastases of lung cancer, by combined daily oral administration of UFT and low-dose ETP. She was admitted to our hospital due to complaints of cough and dyspnea, and multiple nodular shadows were seen in both lungs on chest X-rays. The pulmonary lesion was diagnosed as pulmonary metastasis of lung cancer (squamous cell car) by lung biopsy under CT-guide. She also had bone metastasis of the ribs and cerebellar metastasis from the lung cancer. Combination chemotherapy of UFT 300 mg/body daily and etoposide 25 mg/body daily was performed for 13 months. The pulmonary metastatic tumors were reduced significantly. No side effects of the carcinostatic agents were noted. She is now doing well. Combined daily oral administration of UFT and low-dose etoposide is considered to be safe and effective, and the treatment useful for recovering QOL in advanced lung cancer patients.

Administration, Oral↗

[A case of effective bisphosphonate therapy of sequential pamidronate and incadronate for bone metastases from breast cancer].

A 55-year-old woman complained of neck pain ten years after undergoing surgery. She was diagnosed as having bone metastases and treated using pamidronate therapy with doxifluridine, tamoxifen and fadrozole, which was assessed as effective. She complained of neck pain 32 months after pamidronate infusion. CT revealed that the sclerosis had continued but new lytic lesions were detected in the cervical vertebra. Thus, we attempted incadronate and medroxyprogesterone acetate (MPA) administration. After 2 months, incadronate therapy with MPA relieved her neck pain. CT revealed lytic lesions of cervical vertebra showing sclerosis 3 months after this treatment and the sclerosis has continued. Bisphosphonate therapy of sequential pamidronate and incadronate with MPA administration is a useful treatment for bone metastasis from breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

The effect of abrupt cessation of total parenteral nutrition on serum glucose: a randomized trial.

The common clinical practice of gradually tapering total parenteral nutrition (TPN) to prevent hypoglycemia may be unnecessary. This randomized prospective study assessed the blood glucose profiles of patients whose TPN was abruptly discontinued in comparison with those whose TPN was gradually tapered to determine whether abrupt cessation can be performed safely. Patients were randomized into the abrupt cessation or the tapered protocol. A symptomatic hypoglycemic questionnaire was administered at regular intervals. Fingerstick glucose sampling was performed at 30-minute intervals and compared prospectively. From October 1996 through July 1997, 21 patients receiving TPN consented to participate in this study. Inclusion criteria included 1) duration of TPN infusion >24 hours, 2) age >18 years, and 3) establishment of enteral feeding at the time of TPN discontinuation. Patients had a baseline blood glucose level followed by repeat glucose measurements at 30-minute intervals until 90 minutes after TPN was completely discontinued in the tapered group and 120 minutes after cessation in the abrupt group. The rate of TPN tapering was in 25 per cent increments over 90-minute intervals. Ten patients were randomized into the tapered group and 11 patients in the abrupt group. None of the patients developed symptomatic hypoglycemia. There was no difference between the lowest blood glucose in the abrupt group in comparison with that of the tapered group (108.6+/-11.5 vs 108.2+/-9.8 respectively; P = 0.98). No patient had a significant change in hypoglycemia questionnaire score. There was no significant difference in age, duration of TPN, steroid use, or enteral caloric intake between the two groups. We conclude that there was no symptomatic hypoglycemia, and glucose profiles returned to a similar baseline level in those whose TPN was abruptly stopped when compared with those in the tapered group. These data demonstrate that patients receiving TPN can have parenteral nutrition abruptly stopped without the development of significant hypoglycemia.

Adult↗

[A case of effective chemotherapy using CAF followed by docetaxel for advanced breast cancer].

A huge mass measuring 13 x 12 cm and wide cutaneous edema were detected in the right breast of a 51-year-old woman. Under a diagnosis of locally advanced breast cancer (T4bN2M1, stage IV) with liver metastases, we attempted sequential neoadjuvant chemotherapy. After three courses of CAF therapy (cyclophosphamide, doxorubicin (DXR), 5-FU), the primary tumor was decreased by 56% and the liver metastases had disappeared. A minor pathologic response was observed. Subsequently, three courses of docetaxel (TXT) administration were carried out. The primary tumor was then decreased by 75% and the axillary metastases had disappeared. Histopathological examination showed gross viable tumor cells in the residual tumor and positive axillary lymph nodes. The only toxic effect was nausea (grade 1) and no major adverse effects were observed. Neoadjuvant chemotherapy with sequential DXR followed by TXT is a useful treatment for locally advanced breast cancer.

Antineoplastic Agents, Phytogenic↗

Complementation of an hMSH2 defect in human colorectal carcinoma cells by human chromosome 2 transfer.

The human colorectal tumor cell line LoVo has a homozygous deletion in the hMSH2 gene from exon 3 to exon 8, is deficient in mismatch repair (MMR) activity, and exhibits microsatellite instability. To determine whether the introduction of a wild type hMSH2 into LoVo restores MMR activity and stabilizes microsatellite loci, we transferred a chromosome 2 fragment containing hMSH2 into a homologous recombination-proficient chicken DT40/human hybrid (DT40 2C) and a human chromosome 2 in a mouse A9 hybrid to LoVo. Transfers of these chromosomes into LoVo resulted in LoVo both with and without a wild-type hMSH2. Complete correlation was found between the presence of the wild-type hMSH2 and hMSH2 expression, an increased stability in microsatellite loci, and competency in MMR. The hMSH2-positive LoVo hybrids also showed an increased sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine. This enhanced toxicity is associated with G(2) cell-cycle arrest followed by premature mitosis and cell death. These results suggest that hMSH2 may be responsible for complementing mutator and drug-resistant phenotypes in chromosome 2-transferred LoVo cells. To test whether the hMSH2 in DT40 2C cells can be modified by homologous recombination, we transfected DT40 2C with a targeting vector containing an hMSH2 exon 4 disrupted by the zeocin-resistant gene. The results showed that the hMSH2 locus in DT40 2C was efficiently targeted by an exogeneously transfected homologous sequence, suggesting that transfer of a modified hMSH2 from DT40 2C to LoVo via chromosome transfer could be used to determine the function of hMSH2.

Animals↗

[CD8-positive diffuse large B-cell lymphoma].

In May, 1998, a 63-year-old woman was admitted for treatment of relapsed malignant lymphoma. In March 1997, a diagnosis of diffuse large B-cell lymphoma(DLBL), clinical stage IIISE A, was made from a biopsy specimen of the tumor in the left buccal mucosa. Six cycles of CHOP regimen were given, and complete remission was achieved. However, relapse of the lymphoma was suspected, and the patient was transferred to our hospital. On admission, a right tosillar mass, 8 mm in diameter, was found, and a biopsy showed DLBL. The immunophenotype of the lymphoma cells was CD3- CD4- CD5- CD8+ CD10- CD19+ CD20+ CD23- CD25+ IgL (lambda)+, and dual staining confirmed that the cells were CD8+ and CD19+. The patient was an HTLV-1 carrier, but monoclonal integration of HTLV-1 proviral DNA into the lymphoma cells was not detected. She was diagnosed as having CD8+ DLBL, clinical stage IA. Because she responded to salvage chemotherapy, autologous peripheral blood stem cell transplantation was performed and complete remission was obtained. To our knowledge, this is the first report of CD8+ DLBL.

CD8 Antigens↗

[Anesthesia for a cervical myelopathy patient with tracheal stenosis].

A 71-year-old male with cervical myelopathy was scheduled for C 3-7 laminectomy. Once he had been rejected of general anesthesia in other hospital because of his tracheal stenosis. The diameter of the narrowest part of his trachea was 5 mm probably resulting from tracheostomy at 2 years of age. His cervical myelopathy seemed to be no problem for anesthesia induction because he had no problems in his neck movement and opening mouth. We evaluated his tracheal stenosis carefully using bronchofiberscopy, chest X-ray, computed tomography and pulmonary function tests. After intravenous fentanyl 100 micrograms and midazolam 2.5 mg, it was impossible to ventilate the patient. Therefore, tracheal intubation was performed immediately after lidocaine administration into the trachea. During surgery, tracheal tube dilated the narrowed portion. After surgery, the tracheal tube was removed under bronchofiberscopic observation without any problems. Tracheal stenosis was observed by chest X-ray after surgery, but he had no complaints.

Aged↗