Biomedical subjects
Publications and source records attributed to K Nishimura.
Testicular tumors in closely related family members are rare. We report a case of familial testicular cancer occurring in father-son pairs. The father had teratocarcinoma and his son developed pure seminoma. The association of a genetic factor in the etiology of testicular malignancy is discussed.
To clarify the absorption mechanism of 1,3-bis(2-ethoxycarbonylchromon-5-yloxy)-2-((S)-lysyloxy+ ++)propane dihydrochloride (N-556), a prodrug for the oral delivery of disodium cromoglycate (DSCG), a study was made using rats. N-556 gave the highest plasma level of DSCG following its injection into the loop at the upper part of the small intestine. N-556 was stable in acidic washings of gastric contents, but rapidly hydrolyzed to M1 with twin ethyl residues on DSCG in the washings of the small intestinal contents. N-556 and M1 were hydrolyzed to DSCG via M2 having a mono ethyl residue in the homogenate of the small intestinal mucosa. The oral absorption of M1 following its administration in 50% (v/v) propylene glycol solution was essentially the same as that of N-556. That of M1 administered in aqueous suspension was low. After the oral administration of N-556, a small amount of M2 and a trace of M3 having L-lysyl residue were detected in the portal plasma, but no hydrolytic intermediate except DSCG could be found in the general plasma. The major absorption mechanism of N-556 may thus be concluded as follows: N-556 given orally is transferred to the small intestine in essentially intact form. N-556 is then rapidly diffused to an aqueous layer on the surface of the mucosal membrane and hydrolyzed to M1. The resultant M1 is transported to the mucosal membrane and hydrolyzed to DSCG via M2. DSCG generated in the mucosal membrane is used for general circulation through the portal blood and liver.(ABSTRACT TRUNCATED AT 250 WORDS)
The population pharmacokinetics of theophylline were studied in 55 patients with stable chronic airway obstruction. Two hundred and seventy six theophylline serum concentrations after intravenous short infusion were analyzed using a nonlinear mixed-effect model. The influence of hepatic dysfunction, smoking habit, age and the measurement of arterial blood gases (oxygen tension: PaO2, carbon dioxide tension: PaCO2, blood pH) and clinical laboratory tests (serum albumin concentration, haematocrit) on the pharmacokinetic parameters of theophylline was examined by the likelihood ratio test. Assessment of each factor was made by a forward selection method. In the final regression model, the total body clearance (CL, l/h/kg) was related to the value of PaCO2 as well as to the presence of hepatic dysfunction, and the volume of distribution (Vd, l/kg) was related with the PaCO2 value as expressed in the following equations: CL = exp(-3.78 - 0.525.HF + 0.0233.PaCO2) and Vd = exp(-1.12 + 0.00934.PaCO2), where HF is a categorical variable with a value of unity if a patient has hepatic dysfunction otherwise zero. The interactions among blood gas measurements were observed and the CL and Vd of theophylline would be inversely correlated with PaO2 or pH, if we selected PaO2 or blood pH to be a more important factor than PaCO2. The inter-individual variabilities in CL and Vd were 38.5% and 12.5%, respectively, and the residual variability in theophylline serum concentrations was 10.6% as a coefficient of variation. This final model and the population parameters of theophylline will be useful for individualization of a drug dosage regimen by means of the Bayesian method.(ABSTRACT TRUNCATED AT 250 WORDS)
To investigate the additive effect of oral theophylline on combined inhaled anticholinergic agent and beta 2-agonist therapy, 12 patients with stable COPD (64.6 +/- 5.9 years) completed a randomized, double-blind placebo-controlled crossover trial of oral theophylline for a 4-week period (400 mg for 2 weeks, followed by 600 mg for 2 weeks). All of the patients continued to inhale both salbutamol, 200 micrograms, and ipratropium bromide, 40 micrograms, using a metered-dose inhaler four times a day. Spirometry was assessed before, and 15 and 60 min after the inhalation of bronchodilators at 2-week intervals. Even after the inhalation of salbutamol and ipratropium, theophylline significantly improved FEV1 and daily peak expiratory flow rate compared with the placebo. No significant improvement in the daily symptom scores for cough, sputum, wheezing, or shortness of breath was observed throughout the different phases of treatment. This study shows that the additive bronchodilating effect of theophylline, when used in combination with salbutamol, 200 micrograms, and ipratropium, 40 micrograms, is significant but small in stable COPD. The addition of theophylline did not significantly improve the patient's symptoms. Oral theophylline, when used in combination with an inhaled anticholinergic agent and an inhaled beta 2-agonist, may be of limited value in the treatment of stable COPD.
The purpose of this study was to evaluate the role of high-resolution computed tomography (HRCT) in the clinical diagnosis of diffuse infiltrative lung disease (DILD). Diagnostic accuracy was compared using both chest radiography and HRCT. One hundred thirty-four cases of DILD, representing 21 different diseases, were selected for study, and the disease state was confirmed either histologically or microbiologically. The HRCT images and chest radiographs, available in all cases, were reviewed separately and in random order by 20 physicians who were provided only with information on each patient's age and sex. Overall, a correct first-choice diagnosis was made in 38 percent using radiographs and in 46 percent using HRCT images (p < 0.01). The correct diagnosis was among the top three choices in 49 percent when chest radiographs were used, and in 59 percent when HRCT images were viewed (p < 0.01). The correct first-choice diagnosis increased remarkably when the HRCT was used in usual interstitial pneumonia, sarcoidosis, alveolar proteinosis, bronchiolitis obliterans organizing pneumonia, hypersensitivity pneumonitis, and pulmonary lymphangiomyomatosis. High-resolution computed tomography was confirmed to be superior to conventional radiography in the accurate diagnosis of DILD in clinical practice.
Oxitropium bromide is a novel anticholinergic bronchodilator agent. The purpose of this study was to compare the bronchodilating and cardiovascular effects of oxitropium (0.2 mg), fenoterol (0.4 mg), combined oxitropium and fenoterol (0.2 mg and 0.4 mg, respectively) over a 10-h test period. Fourteen patients with chronic obstructive pulmonary disease (COPD) (FEV1, 0.95 +/- 0.38L) were studied in a randomized, double-blind, placebo-controlled trial. Combined oxitropium and fenoterol produced significantly greater improvements in FEV1 over a time span of 15 min to 10 h and in the area under the time-FEV1 curve (AUC) than either oxitropium or fenoterol alone. The effects of oxitropium on both FEV1 and AUC values were similar to those of fenoterol. Oxitropium resulted in a greater increase in FEV1 than the placebo even after 10 h. In contrast; fenoterol produced a significant improvement in the FEV1 for only 15 min to 4 h. Oxitropium showed no adverse cardiovascular effects, whereas fenoterol was associated with an increased heart rate at 15 min and 1 h after the administration. We conclude that oxitropium bromide is an effective and safe bronchodilator for even elderly patients with COPD.
To investigate the effects of different routes of alimentation on lipid metabolism, lipid-free nutrients with the same amount of energy and composition were continuously administered via the oral cavity (oral group), directly to the stomach (enteral group), or into the superior caval vein (parenteral group) of unrestrained rats. The body weight gain 1 week after continuous nutrition was greater in enteral and parenteral groups than in the orally-fed group. In comparison with the orally-fed group, the enterally-fed group had significantly greater liver and retroperitoneal adipose tissue weights and hepatic lipid content, whereas the parenterally-fed group produced similar changes to those in the enteral group without significant accumulation of hepatic lipid. The rate of fatty acid synthesis after 1 week of alimentation was 3-fold higher in the liver in enterally-fed group, and approximately 10-fold higher in white adipose tissue in both enterally- and parenterally-fed groups than in orally-fed group. Plasma concentrations of catecholamines after 6 h were significantly higher in the orally-fed group than in either the enteral or parenteral group. However, plasma insulin concentrations were not significantly different among the three groups. The results indicate that lipid synthesis and its deposition in the liver and adipose tissue are greatly influenced by the route of alimentation, possibly owing to difference in the early neuro-hormonal responses to different routes of alimentation.
The submucosally embedded in situ appendix guarantees an ideal continence mechanism in patients with ileocecal urinary reservoirs. To date this modification of the Mainz pouch technique was performed successfully in 10 patients between September 1990 and October 1992. Pouch capacity ranged from 350 ml to 900 ml (mean: 565 ml), frequency of intermittent self-catheterization ranged from 3 to 7 times per day (mean: 4.4-5.4 times) and complete urinary continence without difficulty of self-catheterization was obtained in eight patients. Two patients with stomal stenosis needed to indwell a catheter. The follow up periods ranged from 3 to 24 months (mean: 14.7 months). The main advantages of appendix stoma technique are shorter operation time, a short ileal segment, no risk of nipple gliding or prolapse, no need for staples, thereby decreasing significantly the risk of stone formation, and facilitating easy catheterization. This method seemed to be valuable for continent urinary reservoir assuring patients of high quality of life.
The tissues consisted of adenocarcinoma of the prostate were examined by immunohistochemical study with monoclonal antibody (43-21-1-1) against gamma-seminoprotein (gamma Sm)2). The degree of staining regarding any correlation with the histological grade was evaluated. The prostatic tissues were obtained by transurethral resection or by fine needle biopsy from untreated 38 patients. The avidin-biotin peroxidase complex technique was used to stain on 3 microns-sections of 10% formalin fixed, paraffin embedded tissue. In addition, immunohistochemical staining with the commercialized antibodies to prostate-specific antigen (PSA; polyclonal, DAKO) and to prostatic acid phosphatase (PAP; polyclonal, DAKO) was done simultaneously for a comparative study. The degree of immunoperoxidase stain was classified into two categories, namely location and pattern, and was graded from 0 to 3, respectively. The product of the degree of location and the degree of pattern was noted as the total score. The mean of score was calculated in each histological grade. Then the means of total scores were compared and evaluated as having any statistical difference by Student's t test among 3 histological grades as well as among 3 primary antibodies used in this study. When the monoclonal antibody to gamma-Sm was used for immunoperoxidase staining, the means of total scores and the rates of negative reactions (% Negative) in 3 histological grades were 6.8 +/- 1.8 (M +/- SD) and 0% in well (N = 9), 4.4 +/- 2.4 and 14% in moderately (N = 22), and 1.8 +/- 2.3 and 54% in poorly differentiated lesions (N = 11), respectively. There were statistically significant differences (P < 0.05) among 3 histological grades.(ABSTRACT TRUNCATED AT 250 WORDS)
PURPOSE: To determine whether there is alpha 1-adrenergic receptor heterogeneity associated with the regulation of intraocular pressure (IOP) and mydriasis in rabbits, the authors tested the hypothesis by characterizing the ability of the selective alpha 1-adrenergic antagonist, bunazosin, to block the ocular hypertensive and mydriatic responses to alpha 1-adrenoceptor stimulation by either norepinephrine (NE) or phenylephrine (PE). METHODS: The effects of topical application of bunazosin on IOP and pupillary diameter were measured in unilateral superior cervical ganglionectomized (SCGX) rabbits after exposure to either NE or PE. RESULTS: Bunazosin (0.1%) alone only lowered the IOP in the normal eye and did not elicit a pupillary response on either side. NE (0.01-1.0%) by itself caused a concentration-dependent rise in IOP on both sides, but mydriasis did not occur on the normal side. In SCGX eyes, the sensitivity of the IOP response to NE increased tenfold over that measured on the normal side. Unlike on the normal side, concentration-dependent mydriatic responses occurred with 0.1 and 1% NE. After pretreatment with bunazosin (0.1%), neither NE (0.1%) nor PE (0.1%) evoked a rise in IOP. However, the mydriatic response to either one of these agonists in the SCGX eyes was less affected. By contrast, pretreatment with the alpha 2-adrenergic antagonist, 0.5% yohimbine, did not change the IOP increase elicited by 0.1% NE. CONCLUSIONS: These results suggest that the alpha 1-adrenergic receptors that regulate IOP and pupillary diameter are different from one another in the rabbit.
We studied cell kinetics of colo-rectal neoplasms using PCNA (the auxiliary protein of DNA polymerase-delta) immunohistochemistry. We analyzed the distribution pattern of PCNA positive cells on normal colon mucosa, adenoma (6 cases) and cancer (early: 33 cases, advanced: 6 cases). PCNA positive index (PI) was calculated as the percentage of PCNA positive tumor cells in relation to the total number (about 1000) of the tumor cells. PCNA positive indices were 30% in normal colon mucosa, 49% in adenoma and 72% in cancer, respectively. There were statistically significant differences between three mean values (p < 0.01). In normal colon mucosa PCNA positive cells are localized at the lower part of mucosa, but, in adenoma, they are found at the more upper part of mucosa too. In cancer, PCNA positive cells were localized diffusely and their immunoreactivity is higher than those of the normal mucosa and adenoma. In conclusion, our results suggests that the ratio of PCNA positive cells almost equivalents to growth fraction, and is correlated with the histological grading of colo-rectal tumor, but not correlated with depth of carcinoma. It is presumed that carcinoma has a higher ratio of PCNA positive cells than adenoma, and therefore carcinoma has higher proliferating cell density than adenoma.
The purpose of this study was two-fold; first to investigate the chemotactic response of periodontal cells to root surface components during wound healing following flap surgery; second, to investigate the chemoattractive effect of the root components on cell migration. Cells were obtained by culturing cells from monkey periodontal tissues and rat calvarial cells. Root surface components were obtained from teeth extracted at 4, 7, 10 and 14 days after flap surgery. The chemotactic response of the isolated cells to root surface components was quantitated by an in vitro assay using a 48 well microchemotaxis chamber. The effect of root components or other growth factors on the cell migration was evaluated using a three-dimensional gel system. Cemental components produced a strong chemotactic response for gingival fibroblasts, alveolar bone cells and rat calvarial cells. Kinetics of the chemotactic potential of cementum was characterized by an initial increase (up to 7 days after surgery), a transient decline (at 10 days after surgery) and a second increase (at 14 days after surgery). Cemental components obtained 7 days after surgery most profoundly facilitated invasion of gingival fibroblasts with comparable effects induced by PDGF and TGF-beta. These results suggest that cemental components influence the chemotactic migration of gingival fibroblasts at the initial stage of wound healing, and therefore, cementum plays an important role in periodontal regeneration.
We examined whether prophylactic antibiotics are necessary or not during the ESWL treatment for patients with urolithiasis. Twenty-eight patients with unilateral renal or ureteral stones composed of calcium oxalate, calcium phosphate or the mixed stones were treated with MPL 9000 between May 12 and September 30, 1992. Although 17 patients (60.7%) had complications of pyuria before treatment, none of the 28 patients had taken any prophylactic antibiotics during the treatment. To evaluate the clinical signs of infection, we examined the white blood cell count, in blood and urine sediment and serum C-reactive protein (CRP) value at the time of 1, 3 and 7 days after ESWL treatment, and body temperature and urine culture at the time immediately after the treatment in addition to the above-mentioned days, compared with the pre-treatment data. White blood cell count at one day after ESWL treatment was significantly elevated both in the patients with and without pyuria, while body temperature at the time immediately after the treatment was significantly elevated only in the patients with pyuria. Six of the 23 patients (26.1%) with preoperative sterile urine and who had urine culture immediately after ESWL, had bacteriuria. However, none of the 28 patients had any clinically significant infectious complications during ESWL treatment without any antibiotics therapy. We concluded that it is important to examine urine culture immediately after ESWL treatment for early protection from complication of urinary tract infection and that administration of prophylactic antibiotics is not necessary during ESWL treatment for patients with non-infection stones even concomitantly with pyuria.
We have isolated a potent inhibitor of enkephalin-degrading enzymes from the bovine spinal cord, and determined its amino-acid sequence and inhibitory activity against enkephalin-degrading enzymes. This new substance, isolated and identified from the bovine spinal cord, is composed of a heptapeptide (Leu-Val-Val-Tyr-Pro-Trp-Thr). The inhibitory activity (IC50) of this new substance against enkephalin-degrading enzymes, purified from monkey brain, are 3.3 micrograms.ml-1 against aminopeptidase, 1.4 microgram.ml-1 against dipeptidyl aminopeptidase, 2.4 micrograms.ml-1 against angiotensin converting enzyme, and 10 micrograms.ml-1 against enkephalinase. This new substance showed no inhibitory activity against enkephalin-degrading enzymes purified from kidney, blood, etc. According to the above results, this substance is thought to be a new neuromodulator derived from the spinal cord. Because it was derived from the spinal cord, we have named it "Spinorphin". The discovery in the bovine spinal cord of endogenous heptapeptide, Spinorphin, with inhibitory activity on enkephalin-degrading enzymes raises a number of pertinent questions which cannot be adequately dealt with in this study. It will now be possible, however, to test the very hypothesis that this new peptide act as neurotransmitters or neuromodulators at synaptic junctions.
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A case of renal cell carcinoma effectively treated by interferon-alpha and the embolization of the left renal artery is reported. A 69-year-old man was referred to us because of a left renal mass. We made a diagnosis of a left renal tumor with tumor thrombus in the renal vein and inferior vena cava, and multiple lung metastases by imaging examinations. At first the embolization of the left renal artery was selected and interferon-alpha treatment was performed for 3 months. At 3 months after the embolization, the metastatic lung tumors had completely disappeared and the left renal tumor and the tumor thrombus were reduced in size, so that left radical nephrectomy was performed. Pathological examination revealed that a small part of the tumor was viable renal cell carcinoma. After the operation, interferon-alpha treatment has been continued for 15 months and recurrence and metastasis have not been detected.
Spinorphin, a potent inhibitor of enkephalin degrading enzyme isolated from the bovine spinal cord, produces a dose-related inhibition of electrically evoked contractions of both MVD (mouse vas deferens) and GPI (guinea-pig ileum). Analgesic activity of Spinorphin was evaluated by the tail pinch method. The intraventricularly injected Spinorphin produced antinociceptive effect in a dose-dependent manner, in dose of 50-200 micrograms.mouse-1. Most Spinorphin was degraded when incubated in the spinal cord for 24 hs. However, approximately 86% of the Spinorphin was intact on HPLC when incubated with probestin, which is an inhibitor of aminopeptidase-M. Spinorphin has a high inhibitory activity against enkephalin degrading enzymes when compared to the various hydrolysis products. In conclusion, the most important structure for enkephalin inhibitory activity in Spinorphin. It is suggested that Spinorphin acts as a neuromodulator of enkephalin metabolism in the spinal cord.
Fenestrated Fontan operation was performed in a 19-year-old male with a diagnosis of right isomerism syndrome. Postoperatively, fungal endocarditis due to Candida Albicans and mediastinitis by Methicilin resistant Staphylococcus Aureus (MRSA) occurred. For Candida endocarditis, combined surgery and medical treatment with amphotericin B was effective. MRSA mediastinitis was successfully treated by continuous closed irrigation with 0.5% povidone-iodine solution. This is the 17th reported case of fungal endocarditis after open heart surgery in Japanese literature.