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Biomedical subjects

K Nishihara

Publications and source records attributed to K Nishihara.

At least 19 recordsLinked to original sources

Effect of itraconazole on the pharmacokinetics of digoxin in guinea pigs.

The effect of itraconazole (ITZ) on the pharmacokinetics of digoxin (DGX) was investigated in guinea pigs. The plasma concentrations of DGX in guinea pigs following treatment with ITZ (20 mg/kg intraperitoneally (i.p.)) after intravenous (i.v.) administration of DGX (0.125 mg/kg) were significantly higher than in the controls. The percentage cumulative excretion (6.9%) of DGX in bile of the ITZ-treated group up to 6 h after administration of DGX was significantly reduced (p < 0.05) compared with 10.5% in the control. The percentage cumulative excretion (3.1%) of DGX in urine of the ITZ-treated group up to 6 h after administration was also one third that in the controls. The total, biliary, renal and metabolic clearances for DGX in the ITZ-treated group were significantly reduced, while the V(dss) was unaffected. The plasma unbound fraction of DGX (ranged 47-58%) in the ITZ-treated group was generally similar to that in the controls (50-57%). The blood-to-plasma concentration ratio of DGX (range 1.28-1.42) in the absence of ITZ did not change in the presence of ITZ. Based on these results, the pharmacokinetic interaction between DGX and ITZ may be due not only to a reduction in the renal clearance but also to a reduction in the metabolic clearance of DGX by ITZ.

Animals

Surgical approach to ossification of the thoracic yellow ligament.

BACKGROUND: Symptomatic ossification of the yellow ligament (OYL) at the lower thoracic level is uncommon. Although wide laminectomy has, until now, been the primary treatment for this disease, we propose a less invasive technique based on a new method of three-dimensional computed tomography (CT). METHODS: The clinical features and radiologic imaging findings of 37 patients with OYL (mean age, 54 years) were analyzed. The surgical approach was selected based on the position of the depicted OYL on 3D CT scan in each patient. RESULTS: The male-to-female ratio was 3:1. Involvement of the upper thoracic region was seen 11 times; of the middle region 8 times, and of the lower region 40 times (several patients had involvement in more than one region). About half of the patients complained of gait disturbance on admission caused by the markedly enlarged OYL. No postoperative complications were found. Neurologic deterioration was observed in only one patient. CONCLUSIONS: OYL should be treated as early as possible, using the least invasive technique available. By using 3D CT, we were able to perform limited surgery consisting of foraminotomy or extended partial laminectomy at the affected level after confirming the anatomic location of the OYL. In laterally extended OYL, it is necessary to decompress the radicular artery in order to prevent ischemic damage to the spinal cord.

Aged

Composite glandular-neuroendocrine carcinoma of the hilar bile duct: report of a case.

We report herein an unusual case of a composite glandular-neuroendocrine carcinoma of the hilar bile duct. A 71-year-old Japanese woman was admitted to our hospital suffering from general fatigue, progressive jaundice, and a high fever. Computed tomography and angiography findings revealed a solid hypervascular mass in the hepatic hilus. Thus, a subsegmentectomy of the liver (S4, S5) and bile duct resection with lymph node dissection were performed. A tumor measuring 6.0 x 3.0 cm was found to be located in the bile duct of the hepatic hilus. Histologically, the tumor was composed of well-differentiated adenocarcinoma and small cell neuroendocrine carcinoma cells, with a histological transition between the two components. Grimelius' method revealed the presence of diffuse positive tumor cells in neuroendocrine carcinoma. The neuroendocrine tumor cells were also diffusely immunoreactive to chromogranin A. To the best of our knowledge, only 22 previous cases of composite glandular-neuroendocrine carcinoma in the biliary tract have been reported; however, this is the first case report of a clearly composite tumor of the hilar bile duct.

Adenocarcinoma

Benzodiazepine effects on human sleep EEG spectra: a comparison of triazolam and flunitrazepam.

The effects of 0.5 mg triazolam (TRI) and 4 mg flunitrazepam (FNZ) on the sleep electroencephalogram (EEG) were studied in eleven (six for TRI, and five for FNZ) healthy young male subjects. C3 EEG channel data of one baseline night, three drug nights and two withdrawal nights were recorded and their analyzed using a fast Fourier transformation (FFT) method. Changes in the 0.5 Hz to 40 Hz power spectrum showed that: 1) both TRI and FNZ increased higher frequency activity and reduced lower frequency activity on the drug nights; 2) on drug nights, NREM sigma frequency power was more strongly enhanced by TRI than FNZ, while the beta power of both NREM and REM was more strongly enhanced by FNZ than TRI; 3) NREM alpha power increased on the second night of withdrawal from both TRI and FNZ; 4) the power spectra for both NREM and REM sleep returned to baseline levels by the fourth night of withdrawal from either TRI or FNZ. These findings suggest that 0.5 mg TRI and 4 mg FNZ have both common and differing pharmacological effects on the central nervous system. Such differences could be caused by differences in the dose, half-life or systemic distribution of these two drugs.

Adult

Chaperone coexpression plasmids: differential and synergistic roles of DnaK-DnaJ-GrpE and GroEL-GroES in assisting folding of an allergen of Japanese cedar pollen, Cryj2, in Escherichia coli.

Plasmids that can be used for controlled expression of the DnaK-DnaJ-GrpE and/or GroEL-GroES chaperone team were constructed in order to facilitate assessment of the effects of these chaperone teams on folding or assembly or recombinant proteins in Escherichia coli. A typical pACYC184-based plasmid which was obtained could express the major DnaK-DnaJ-GrpE and GroEL-GroES chaperone teams from separate promoters when L-arabinose and tetracycline, respectively, were added in a dose-dependent fashion. The model protein used to determine whether this system was useful was an allergen of Japanese cedar pollen, Cryj2, which was unstable when it was produced in E. coli K-12. The effects of chaperone coexpression on the folding, aggregation, and stability of Cryj2 were examined in the wild type and in several mutant bacteria. Coexpression of the DnaK-DnaJ-GrpE and/or GroEL-GroES chaperone team at appropriate levels resulted in marked stabilization and accumulation of Cryj2 without extensive aggregation. Experiments performed with mutants that lack each of the chaperone proteins (DnaK, DnaJ, GrpE, GroEL, and GroES) or heat shock transcription factor sigma 32 revealed that both chaperone teams are critically involved in Cryj2 folding but that they are involved in distinct ways. In addition, it was observed that the two chaperone teams have synergistic roles in preventing aggregation of Cryj2 in the absence of sigma 32 at certain temperatures.

Allergens

Changes in sleep patterns of young women from late pregnancy to postpartum: relationships to their infants' movements.

We studied changes in the sleep patterns of ten young women from late pregnancy (36 weeks) to the sixth postpartum week, focusing on the relationship between the women's sleep patterns and their infants' movements. The mothers' polysomnograms and their infants' ankle actigrams were simultaneously recorded using a Medilog 9000 at home in three sessions, during the first, third, and sixth postpartum weeks. The mother-infant pairs slept in close proximity. Two subjects had difficulty with their infants and were dealt with as a separate group. Analysis for the eight subjects who adapted well to the postpartum period showed that wake time after sleep onset increased significantly during the postpartum period compared with late pregnancy given responsibility for feeding. Stage 3 + 4 and Stage REM did not change across the four sessions (pregnancy, first, third, and sixth postpartum weeks), but Stage 2 decreased significantly from pregnancy to postpartum. There was a high synchronization between infants' movements and mothers' wakefulness. Eight mothers did not complain of sleep disturbance, while the two mothers who had difficulty with their infants did. We suggest that mothers who tolerate well sleep interruption arising from feeding and maintain their Stages 3 + 4 and REM should not be considered as suffering from sleep disturbance. Mothers who have difficulty with their infants and complain of sleep disturbance should be considered as suffering from sleep disturbance.

Adult

[Metastasis of small cell lung cancer to the parotid gland as the initial clinical manifestation, followed by metastases to the pituitary gland and lumber spinal cord].

The patient was a 48-year-old woman. In January 1995, she noted swelling in the left parotid gland, and saw an otorhinolaryngologist. Needle biopsy showed small cell carcinoma, and she was subsequently admitted to our hospital. Chest radiography revealed a tumor shadow in the hilus of the right lung. Bronchial biopsy revealed small cell carcinoma of the lung (T 4 N 3 M 1, stage IV). Chemotherapy, with a CDDP-VP-16 regimen, achieved no response. She later developed bitemporal hemianopsia and abducens nerve palsy. Brain MRI revealed metastasis in the pituitary gland. Chemotherapy and radiotherapy were efficacious for only a few months. She also developed pain and numbness in the left leg, attributable to intramedullary metastasis (L 1/2, L 4/5) shown on MRI. It is extremely rare for a metastasis to the parotid gland to be the initial clinical manifestation of a small cell lung cancer which later develops widespread metastases to the pituitary gland and lumbar spinal cord.

Carcinoma, Small Cell

Synergistic roles of HslVU and other ATP-dependent proteases in controlling in vivo turnover of sigma32 and abnormal proteins in Escherichia coli.

Production of abnormal proteins during steady-state growth induces the heat shock response by stabilizing normally unstable sigma32 (encoded by the rpoH gene) specifically required for transcription of heat shock genes. We report here that a multicopy plasmid carrying the hslVU operon encoding a novel ATP-dependent protease inhibits the heat shock response induced by production of human prourokinase (proUK) in Escherichia coli. The overproduction of HslVU (ClpQY) protease markedly reduced the stability and accumulation of proUK and thus reduced the induction of heat shock proteins. In agreement with this finding, deletion of the chromosomal hslVU genes significantly enhanced levels of proUK and sigma32 without appreciably affecting cell growth. When the deltahslVU deletion was combined with another protease mutation (lon, clpP, or ftsH/hflB), the resulting multiple mutations caused higher stabilization of proUK and sigma32, enhanced synthesis of heat shock proteins, and temperature-sensitive growth. Furthermore, overproduction of HslVU protease reduced sigma32 levels in strains that were otherwise expected to produce enhanced levels of sigma32 due either to the absence of Lon-ClpXP proteases or to the limiting levels of FtsH protease. Thus, a set of ATP-dependent proteases appear to play synergistic roles in the negative control of the heat shock response by modulating in vivo turnover of sigma32 as well as through degradation of abnormal proteins.

ATP-Dependent Proteases

Retrospective analysis of 70 operations for gallbladder carcinoma.

BACKGROUND: The clinical course of patients with carcinoma of the gallbladder depends on the depth of tumour invasion. This study was conducted to clarify the prognostic factors affecting survival and appropriate surgical strategy based on depth of invasion of gallbladder carcinoma according to the pathological tumour node metastasis (pTNM) classification. METHODS: A total of 70 patients who underwent surgical resection were reviewed retrospectively with regard to the type of operation, histopathological findings of the resected gallbladder carcinoma and clinical follow-up after operation. RESULTS: Twelve patients with pT1 gallbladder carcinoma fared favourably following cholecystectomy or extended cholecystectomy. In 13 of 26 patients with pT2 gallbladder carcinoma, lymph node metastasis was evident: pN1 in eight and pN2 in five. The 3-year survival rate of patients with pT2 gallbladder carcinoma was 28 per cent after cholecystectomy, 91 per cent after extended cholecystectomy and 67 per cent after hepatectomy. In 21 of 28 patients with pT3 or pT4 gallbladder carcinoma, surgical margins were affected by malignant cells. The 1-year survival rate of patients with pT3 or pT4 gallbladder carcinoma was 24 per cent, even after hepatectomy. Significant prognostic factors were age, macroscopic type, histological grade, depth of invasion, lymph node metastasis, pathological stage, lymphatic invasion, venous invasion, perineural invasion and involved surgical margins. CONCLUSION: Cholecystectomy was adequate for pT1 gallbladder carcinoma. Extended cholecystectomy or hepatectomy with extrahepatic bile duct resection and lymph node dissection (pN1 and pN2) were justified for pT2 gallbladder carcinoma. The survival of patients with more advanced gallbladder carcinoma remains dismal.

Adult

[Intraoperative and follow-up color Doppler echocardiography for evaluating the surgical results of aortic valvuloplasty in a patient with bicuspid aortic valve].

A 21-year-old man underwent aortic valvuloplasty for aortic regurgitation due to bicuspid aortic valve. After the initial procedure for valvuloplasty of the anterior cusp, transesophageal color Doppler flow imaging revealed a significant regurgitant jet directed posteriorly as observed preoperatively. After an additional valvuloplastic procedure for the anterior cusp, the size of the regurgitant signal was reduced and directed to the center of left ventricular outflow tract. The surgery was then completed. On the 5th postoperative day, an aortic regurgitant murmur reappeared and color Doppler echocardiography showed a mild but significant regurgitant jet directed toward the interventricular septum, which may have been due to contraction of the anterior cusp treated by valvuloplasty. Aggravation of the aortic regurgitation in the early stage after plastic surgery is important and requires consideration in the intraoperative assessment.

Adult

Anaplastic carcinoma showing rhabdoid features combined with mucinous cystadenocarcinoma of the pancreas.

A 52-year-old Japanese woman presented with complaints of back pain, loss of appetite, and weight loss; her diagnosis was a mass in the pancreatic tail. A distal pancreatectomy combined with lymph node dissection was performed. The tumor measured 10.0 x 9.5 x 8.0 cm and consisted of a cystic mass and a solid area. Histologically, the cystic mass represented a typical mucinous cystadenocarcinoma, whereas the solid portion was composed of anaplastic tumor cells with round eosinophilic intracytoplasmic inclusions, as seen in malignant rhabdoid tumor of the kidney. The hyaline-like intracytoplasmic inclusions were weakly positive for periodic acid-Schiff and were resistant to diastase. There was a gradual transition between the mucinous cystadenocarcinoma and the anaplastic carcinoma showing rhabdoid features. Additionally, the tumor cells of the anaplastic carcinoma were immunoreactive to both epithelial membrane antigen and vimentin. These findings suggest that the anaplastic carcinoma with rhabdoid features developed from the mucinous cystadenocarcinoma of the pancreas.

Carcinoma

Granular cell tumors of the breast: a report of two cases.

Granular cell tumors (GCT) are rare neoplasms, and only 173 cases of benign GCT of the breast have been documented. We report herein the cases of two patients with this tumor and discuss the methods of diagnosis and treatment. The first patient was a 60-year-old woman who presented with a firm ill-defined mass in her left breast. Mammography showed a dense shadow with spicula and skin thickness, and ultrasonography revealed a hypoechoic mass with an irregular border. Radical mastectomy was performed under the wrong preoperative diagnosis of breast cancer. The second patient was a 31-year-old woman who presented with an elastic-hard mass in her left breast. Mammography showed a well-demarcated dense mass, and ultrasonography revealed a well-defined hypoechoic mass with a large depth-width ratio. Fine-needle aspiration cytology (FNAC) showed a large number of histiocytic cells with abundant granular cytoplasm. An excisional biopsy was performed, and histological examination confirmed a diagnosis of GCT. GCT is benign, but often misdiagnosed as breast cancer both clinically and radiologically. Therefore, histological examination is essential for making a correct diagnosis, while FNAC is also useful. Local resection is still the treatment of choice, and surgeons should do their utmost to avoid performing needless radical mastectomy.

Adult

Cutaneous metastases from pancreatic cancer.

Cutaneous metastases originating from pancreatic cancer are relatively rare. Five cases of metastatic pancreatic cancer to the skin are presented and discussed with a review of 17 previous case reports. In 20 cases, the cutaneous metastases were present prior to the diagnosis of pancreatic cancer. The most common site of cutaneous metastases originating from pancreatic cancer was the umbilicus. Although such cases are rare, it is important to note that metastatic lesions in the skin may be the first sign and one type of distant metastases originating from pancreatic cancer.

Adenocarcinoma

Flunitrazepam effects on human sleep EEG spectra: Differences in NREM, REM and individual responses.

Flunitrazepam (FNZ) (4mg), an intermediate type benzodiazepine (BDZ) hypnotic, was administered orally to five healthy male subjects (Ss) for seven consecutive nights. Sleep EEG from the baseline night (BLN), the initial drug night (IDN), the fourth and the seventh drug nights (4DN, 7DN) was subjected to fast Fourier transform (FFT) analysis. During NREM sleep of 4DN and 7DN the sigma band (11.0-12.5 Hz) activity was similarly enhanced in every S. In REM of 4DN and 7DN beta band (23.0-29.0 Hz) was enhanced, but with larger variations among Ss. High intra-individual consistency of the relative EEG power patterns on 4DN and 7DN was observed. These results suggest that 1) EEG responses to FNZ are different in sleep states; explorations of these differences may provide better understandings of sleep mechanisms, and 2) individual variations in EEG responses may reflect individual variations of the BDZ receptor system. These methods may be useful for exploring receptor changes in neuropsychiatric disorders.

Adult

Flunitrazepam effects on human sleep EEG spectra. II: Sigma and beta alterations during NREM sleep.

Flunitrazepam (FNZ) is known to enhance the higher EEG frequencies, including sigma (10-15 Hz) and beta (20-28 Hz). Both sigma and beta frequency bands show an inverse relationship with delta (0.3-3 Hz) during NREM periods, as we have previously reported. It is not known whether generation of these two EEG frequencies is mediated by the same or different neuronal mechanisms. In this report, we compare alterations of delta, sigma and beta EEG induced by FNZ (4 mg) orally administered to five healthy male subjects for seven consecutive nights. Sleep EEG on the baseline night (BLN), and the fourth and seventh drug nights (4DN, 7DN) was subjected to fast Fourier transform (FFT) analysis. On drug nights, sigma was enhanced without regard to delta amount, but beta was enhanced only during epochs containing low delta. Thus, sigma and beta EEG were altered differently by the same pharmacological agent. These results suggest that sigma and beta EEG are mediated by different neuronal mechanisms.

Adult