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Biomedical subjects

Y Hirao

Publications and source records attributed to Y Hirao.

At least 91 records · Page 5Linked to original sources

[Evaluation of urinary NMP22 (nuclear matrix protein 22) as a diagnostic marker for urothelial cancer--screening for urothelial cancer in patients with microscopic hematuria. NMP Study Group].

This study was undertaken to determine the clinical usefulness of NMP22 (Nuclear Matrix Protein 22) as a urinary marker for the screening of urothelial cancer in patients with microscopic hematuria, especially in comparison with that of voided urine cytology. Urinary NMP22 values were determined for 183 patients with microscopic hematuria by use of a UNMP22 Test kit, which is based on an enzyme-linked immunosorbent assay. All patients were entered in this study before cystoscopy was performed, and were evaluated for NMP22 values and voided urine cytology simultaneously from the same urine samples. Of the 183 patients with microscopic hematuria, 14 cases of urothelial cancer were detected. For the other cases, 65 were of benign diseases and 104 were designated NED (No Evidence of Disease). The median NMP22 values for urothelial cancer, benign diseases, and NED were 26.5 U/ml (95% CI: 18.5-228.2; 4.9 U/ml (95% CI: 3.6-8.3), and 5.9 U/ml (95% CI: 4.8-6.5), respectively. The urinary NMP22 value for urothelial cancer was significantly higher than for benign diseases and NED. When the cut-off value of urinary NMP22 was set at 12 U/ml, the positive rate of NMP22 for urothelial cancer was 85.7%, significantly higher than the 50% positive rate by voided urine cytology. This study indicates that urinary NMP22 is a useful tool for the screening of urothelial cancer in patients with microscopic hematuria.

Adult↗

[An elderly patient with purpura nephritis that appeared after extracorporeal shock wave lithotripsy].

We report a 63-year-old male patient with purpura nephritis, which appeared 7 days after extracorporeal shock wave lithotripsy (ESWL). He was referred to our clinic because of a petechial rash on both lower extremities, pretibial edema and massive proteinuria. Urinalysis showed proteinuria and hematuria and some hyaline casts. A 24-hour urine sample contained 5.0 g of protein. Renal function on admission was decreased: serum creatinine was 1.5 mg/dl and creatinine clearance, 21 ml/min. Immunoserological tests demonstrated an increase in serum IgA (424.3 mg/dl). A skin biopsy revealed leukocytoclastic vasculitis. A renal biopsy showed endocapillary proliferation in a diffuse, but segmental fashion. However, no crescent formation was seen. Immunofluorescence microscopy disclosed mesangial staining for IgA and C3. Electron microscopy demonstrated severe injury to endothelial and epithelial cells: detachment of endothelial and epithelial cells, foot process effacement and macrophage infiltration. Electron-dense deposits were observed in the subendothelial and paramesangial areas. Because renal function was deteriorating rapidly, methylprednisolone pulse therapy and immunosuppressive treatment were implemented. Treatment was effective and the patient's renal function and proteinuria improved remarkably. The electron microscopic findings in this case of purpura nephritis seemed to be more severe than usual, suggesting that ESWL may aggravate glomerular damage.

Drug Administration Schedule↗

Oocyte control of granulosa cell development: how and why.

Interaction between oocytes and granulosa cells is complex and involves both gap junctions and paracrine signalling factors. Oocyte development in antral follicles is highly dependent on communication with cumulus cells, a subset of granulosa cells that is intimately associated with oocytes. Cumulus cells express characteristics distinct from the mural granulosa cells of preovulatory follicles. The thesis of this paper is that, without the influence of oocytes, the pathway of granulosa cell differentiation in antral follicles leads to the establishment of the mural granulosa cell phenotype. Oocytes in antral follicles abrogate that pathway of granulosa cell differentiation and promote the development of the cumulus cell phenotype. Oocytes may do this in order to control their own microenvironment by regulating differentiation of the supporting cells that are in direct communication with them. Possibly, some aspects of the mural granulosa cell phenotype are antagonistic to, or insufficient for, supporting the final stages of oocyte development. We present evidence that oocytes control their environment by suppressing differentiation of the mural granulosa cell phenotype and promoting differentiation of the cumulus cell phenotype. They achieve this suppression via the secretion of labile paracrine signalling factors. Errors in this regulatory mechanism, whether instigated by defects in the production of oocyte-derived ligands or granulosa cell responses to them, may result in the production of oocytes unable to undergo embryo development or that undergo abnormal follicular development.

Cell Differentiation↗

[Clinical findings of neurogenic bladder in patients with Parkinson's disease, multiple sclerosis and spinocerebellar degeneration].

Clinical symptoms, urodynamic findings, and urological treatment of 35 patients with neurogenic bladder dysfunction caused by Parkinson's disease (11 patients), multiple sclerosis (10 patients), and spinocerebellar degeneration (14 patients) were reviewed retrospectively. Most of the patients had a relatively low stage of disease, when they were first seen by their urologists. Chief urological complaints were of irritation in 63.6% of Parkinson's disease and 64.3% of spinocerebellar degeneration cases, compared with obstruction in 80.0% of multiple sclerosis cases. Cystometry revealed underactive detrusor function in 69.2% of the patients with spinocerebellar degeneration but no abnormalities in the patients with Parkinson's disease or multiple sclerosis. Of 34 patients, excluding one patient lost to follow-up, the period of urological management ranged from one to 44 weeks with a mean of 11.0. The final methods of urinary drainage in 34 patients consisted of voluntary voiding in 20, clean intermittent catheterization in 11 including eight by self catheterization, incontinence into diaper in two, and indwelling catheter in one. Five patients were compelled to change urinary drainage method from voluntary voiding to clean intermittent catheterization because of increasing residual volume in four and progressing bladder deformity in one. However, none of them showed the clinical signs of primary disease progression. These findings indicate that in patients with Parkinson's disease, multiple sclerosis, and spinocerebellar degeneration, the urological symptoms can appear even in the early stage of disease. In addition, close follow-up is important in the urological management of neurogenic bladder patients with these diseases, because the disorders of the lower urinary tract may progress regardless of the status of the primary disease.

Activities of Daily Living↗

[Difference between the clinical significance of Credé voiding and Valsalva voiding in the urological management of spina bifida patients].

Retrospective analyses were performed to elucidate the clinical significance between Credé voiding (n = 56) and Valsalva voiding (n = 22) in the urological management of spina bifida patients who do not match the indication of clean intermittent catheterization. The age at initiating the urological management ranged from 0 to 31 years old (mean 2.1) in the Credé voiding and from 0 to 20 years old (mean 4.5) in the Valsalva voiding group. Seventeen patients in the Credé voiding group and 13 in the Valsalva voiding group were followed up for more than 10 years with a mean follow-up period of 14.6 and 13.7 years, respectively. Three patients in the Credé voiding group and one in the Valsalva voiding group showed progression of bladder deformity. In one patient in the latter group, vesicoureteral reflux newly appeared. In the Valsalva voiding group, disappearance or improvement of hydronephrosis was seen in three patients and that of hydroureter in three, bladder deformity in one, and vesicoureteral reflux in one. On the contrary, no patients in the Credé voiding group showed favorable changes in these pathological conditions except for disappearance of vesicoureteral reflux in one patient. Although these findings suggest possible superiority of Valsalva voiding over Credé voiding in the preservation of urinary tract, the differences between the two groups were not statistically significant. The clinical significance of Valsalva voiding remains to be elucidated through further study in neurogenic bladder patients.

Abdomen↗

Immunosuppressive drugs inhibit the production of interleukin-6 and interleukin-8 in cultured cardiac myxoma cells.

Cardiac myxoma cells produce large amounts of interleukin (IL)-6 and IL-8. To determine whether immunosuppressive agents could be used to treat cardiac myxoma, we tested the effects of dexamethasone and three of the newer second-generation immunosuppressive drugs, cyclosporin A, tacrolimus, and deoxyspergualin, on the production of IL-6 and IL-8 in these cells. Cultured cardiac myxoma cells were used as in vitro model of cardiac myxoma. Cells were tested for 24 hours with 10(-7) M dexamethasone, 10(-6) M cyclosporin A, 10(-8) M tacrolimus, and 10(-6) M 15-deoxyspergualin, with aliquots of conditioned medium being assayed for cytokine levels at 0, 6, 12, and 24 hours. Cardiac myxoma cells isolated from 4 patients all produced quantities of IL-6 and IL-8. The concentrations of IL-6 in the medium after 7 days in culture ranged from 79,000 to 2,740,000 pg/ml, and the concentrations of IL-8 ranged from 40,000 to 1,000,000 pg/ml. Exposure of cyclosporin A and dexamethasone almost completely inhibited the production of IL-6 and IL-8 after 24 hours of treatment. Tacrolimus inhibited the production of both cytokines by 55%, while 15-deoxyspergualin reduced IL-6 levels by 24% and IL-8 levels by 48% after separate 24 hour treatments. These results suggest that these newer immunosuppressive agents may be useful in reducing the production of IL-6 and IL-8 in patients with cardiac myxoma.

Aged↗

Infrequent somatic alteration of p16/MTS1 in human primary superficial bladder cancers.

Although superficial bladder cancer, usually presenting as low grade transitional cell carcinomas, are easily resected by transurethral intervention, their frequent recurrence and progression of satage or grade of the recurrent tumors in some cases is a major problem in urology. Deletion of chromosome 9, bands 9p21-22 in bladder cancers including the lowest grade and stage, suggest potential location of candidate tumor suppressor genes. Recently, p16/MTS1 was isolated from 9p21-22 as a multiple tumor suppressor gene, which regulates the cyclin dependent kinase 4 in the G1/S phase of the cell cycle. In the present study, somatic alterations of p16/MTS1 were examined concentrating on histologically defined superficial bladder carcinomas by polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) technique using paraffin embedded materials. Infrequent alterations of p16/MTS1 in superficial bladder cancers, one deletion and one silent mutation in 15 cases, were detected. The results suggest that p16/MTS1 mutation is not involved in the development of superficial urinary bladder carcinomas.

Base Sequence↗

Urethral opening pressure in patients with myelodysplasia.

We evaluated 60 patients with myelodysplasia using the urethral opening pressure (UOP) which is defined as the total intravesical pressure at the moment when urine passes through the external sphincter by the Credé or the Valsalva maneuver. Twenty nine of the patients showed UOP value greater than 35 cmH2O and 31 below 35 cmH2O. In the high pressure group, patients showed a tendency to preserve sphincter activity and had mild paralysis of the lower extremities. In contrast, most of patients in the low pressure group showed an underactive sphincter and severe paralysis of the lower extremities. The incidence of deterioration of the upper urinary tract, vesicoureteral reflux (VUR) and bladder deformity were significantly high in the high pressure group than those in the low pressure group (75.9% vs 16.1%, 72.4% vs 22.6%, 82.8% vs 29.0%, respectively, P < 0.05). During the follow-up period (42 months on average), the voiding methods were changed in 15 patients from the Credé maneuver to clean intermittent catheterization, and total of 12 operations were performed (10 antiVUR operation and two with an ileocystoplasty). Finally, approximately 90% of the patients in both the high and the low pressure groups were evaluated as improved or stable in the upper urinary tract, VUR and bladder deformity after conservative or surgical managements. UOP is considered to be one of the useful parameters to select the high risk patient in the urological management of myelodysplastic patients.

Adolescent↗

[Treatment for hormone-refractory or relapsing prostatic cancer].

Androgen ablative treatments for advanced prostatic cancer have achieved great progress with new concepts of therapy in the last decade such as chemical castration with LH-RH analogue and total androgen ablation. However, in treatment for hormone-refractory or relapsing prostatic cancer it remains controversial whether cytotoxic chemotherapy is acceptable or palliative, and whether there is an alternative treatment for this incurable disease. The current status of cytotoxic chemotherapy for advanced prostatic cancer patients in Nara Medical University since 1980 is reported in this paper with the some review of recent advances in hormone-independent prostatic cancer treatment. The overall objective response rate of CDDP-based multi-drug regimens including CDDP monotherapy was 49.6% (CR 0% + PR 49.6%). Response rate of primary chemotherapy group constituted with untreated patient was 67.2%, against 23.9% in the hormone refractory or relapse group. Five-year survival rate was 61.1% in the primary chemotherapy group, 35.5% in the hormone refractory group and 40.6% in the relapse group. Basically, there was no significant difference in response rates and survival rates among the groups of CDDP monotherapy, CDDP+bleomycin+vinblastine, CDDP+cyclophosphamide+adriamycin or CDDP+etoposide. The different response rates among the regimens seemed mainly to depend on the population of refractory or relapsing cases in each group. The important problems remaining unsolved in the research of chemotherapy for prostatic cancer are that there is no effective breakthrough agent and the lack of the harmonization in response criteria. The new agents are under development based on the cellular biology of hormone-refractory prostatic cancer, and there is a bright future in the treatment of this intractable disease.

Aged↗

[Plasma allantoin in patients undergoing maintenance hemodialysis].

Recently, it has been noted that radical molecules participate in the pathogenesis of some of the complications associated with long-term dialysis therapy, such as amyloidosis. Since allantoin is produced from uric acid almost exclusively by the hydroxy radical, we investigated the plasma concentrations of allantoin in 71 patients with chronic renal failure who were on maintenance hemodialysis. Our specific objective was to investigate the relation of allantoin to the plasma concentrations of beta2-microglobulin and methylguanidine to evaluate the potential of allantoin as a significant parameter of the radical reaction. Although plasma allantoin was not detected in 15 healthy controls, plasma concentrations of allantoin increased markedly in all of the hemodialysis patients (42.6 +/- 37.7 nmol/mL) and wide variation was observed from 4.3 to 185.2 nmol/mL. In addition, we confirmed significant correlations between plasma concentrations of allantoin and beta2-microglobulin as well as serum concentrations of methylguanidine/creatinine and hyaluronic acid (r - 0.456, p < 0.0005, r = 0.313, p < 0.005, r = 0.368, p < 0.01, respectively). Although evidence for a direct link between plasma allantoin levels and amyloidosis was not obtained, the increase in the plasma concentrations of allantoin suggested its clinical significance as a parameter of the radical reaction that is thought to participate closely in the pathogenesis of dialysis-related amyloidosis. From a practical point of view, the measurement of plasma allantoin can be expected to become a significant method of measuring radical members which may be useful in the prophylaxis of some of the complications induced by free radicals.

Adolescent↗

[Serum and urinary pyridinium cross-links in patients with predialysis chronic renal failure].

The concentrations of pyridinoline (Pyr), a novel marker of bone resorption, were simultaneously measured in both serum and urine samples by ion-paired high-performance liquid chromatography in 27 patients with predialysis chronic renal failure. The patients consisted of 19 males and 8 females, whose creatinine clearance (Ccr) ranged from 2.5 to 47.6 ml/min. The influence of residual renal function on serum Pyr and the clinical significance of serum and urinary Pyr were analyzed in patients with predialysis chronic renal failure. There were significant correlations between serum Pyr and serum Cr (r = 0.76) and between Pyr clearance and Ccr (r = 0.70). In addition, significant correlations were observed serum and urinary Pyr (r = 0.64) and between both serum and urinary Pyr and HS-PTH (r = 0.96 and r = 0.61, respectively) and osteocalcin (r = 0.80 and r = 0.73, respectively). However, serum bone alkaline phosphatase isoenzyme (ALP3) was correlated with neither serum nor urinary Pyr. There was no correlation between the ratio of serum Pyr/serum Cr and the metabolic bone markers (HS-PTH, osteocalcin and ALP3). There was a correlation between Ccr and urinary Pyr, although it was statistically significant (p < 0.1). These date led to the following conclusions: (1) serum Pyr in patients with oredialysis chronic renal failure is influenced by reduced renal function and (2) urinary pyr shows a state of bone resorption when an adegvafe level of renal function is maintained. This suggests that patients with an advanced stage of renal osteodystrophy are included among cases of predialysis chronic renal failure.

Adult↗

Local gastric and serum concentrations of rebamipide following oral administration to patients with chronic gastritis.

The potential anti-ulcer action of rebamipide (CAS 11911-87-6, OPC-12759) on experimental and clinical injury to the gastric mucosa depends on its presence in sufficient concentration in the gastric mucosa. To investigate its local penetration, rebamipide levels in the gastric mucosa and serum were measured. A dose of 100 mg of rebamipide was given orally (tablet) to patients with chronic gastritis (n = 32). Gastroscopy was performed between 22 and 353 min after drug ingestion. Venous blood was sampled for determination of serum concentrations. Samples were analyzed by high-performance liquid chromatography (HPLC). The maximal concentration in the gastric mucosa was reached after 30-60 min, and the concentration remained elevated for about 120 min thereafter. The mean mucosal concentration of rebamipide between 30 and 120 min after ingestion was 60.0 +/- 109.8 micrograms/g of tissue, which was higher than 0.1 mmol/l (37 micrograms/g of tissue). The serum concentration of rebamipide peaked about 30-60 min after drug ingestion and remained elevated for about 5 h thereafter. The mean serum concentration of rebamipide between 30 and 120 min after ingestion was 0.25 +/- 0.23 microgram/ml, being below the level of 1.0 mumol/l (0.37 microgram/ml). Data indicate that the concentration of rebamipide in the gastric mucosa resulted from local penetration, and suggest that the blood level and systemic distribution of rebamipide have little effect on its antioxidative and anti-neutrophilic activities.

Adult↗

[Serum prostate specific antigen for the early detection of prostate cancer in outpatients of internal medicine].

Screening was performed on 102 patients aged 60 years or older who visited the Outpatient Department of Internal Medicine in Tane General Hospital between June 1994 and May 1995. Of those screened, 36 patients (35.3%) had elevated prostate specific antigen (PSA) values, and 20 of them visited the Urological Department, and underwent digital rectal examination (DRE) and transrectal ultrasonography (TRUS) for further screening. Of the 16 patients who underwent ultrasound guided biopsies of the prostate, 7 patients were found to have prostate cancer. Therefore, the cancer detection rate was 6.9%, which was about 4 times higher than that of mass-screening examinations previously reported in the Japanese literature. These findings suggested that the screening using PSA in outpatients of Internal Medicine may be useful for the early detection of prostate cancer.

Aged↗

[The role of prostate specific antigen in diagnosis of localized adenocarcinoma of the prostate. Nara Uro-Oncology Research Group].

The number of cases of prostate carcinoma (PCA) is steadily inceasing in Japan. The clinical application of a reliable tumor marker, prostate specific antigen (PSA) for the diagnosis, as well as the increasing elderly population in Japan may account for this increase. The subjects were patients at the Nara Medical University and its affiliated hospitals; 1) 687 cases without PCA were evaluated for age-specific PSA and the incidence of abnormal PSA following urological manipulations, 2) 135 cases with histological proven BPH by transurethral resection of prostate (TUR-P) were examined for PSA density (PSAD) and positive PSA rate in BPH, 3) 135 cases receiving a needle biopsy with suspicion of PCA were examined for the efficacy of PSA and PSAD and other parameters, and 4) 459 PCA cases treated between 1988 and 1994, were examined for specific PSA and PSAD values by stage and degree of cell differentiation. The PSA assay used in this study was MARKIT-M PA (normal range < or = 3.6 ng/ml). The PSA was decreased gradually with age in non-PCA patients, and abnormal PSA was found in 5.5% of these patients following manipulations. The average PSA was 2.95 +/- 2.03 ng/ml in 130 BPH patients (mean age: 71.1 +/- 7.0 years old. and average prostate volume: 32.9 +/- 16.1 ml). And abnormal PSA level (more than 3.61 ng/ml) was found in 22.3%. The mean PSAD was 0.1.0 +/- 0.06, and PSAD was below 0.15 in 86.1% of these BPH cases. Among the 135 cases receiving a needle biopsy, 33 cases had PSA values between 3.61 and 10.0 ng/ml. Of these cases, PCA was found in 18.5% of the 27 cases with a PSAD below 1.5, and in 33.3% of the 6 cases with a PSAD over 1.5. PSA and PSAD were proportionally increased with stage, and a significant difference in the PSA value was observed between stage B1 and B2, and stage C and D (P < 0.05). However, PSA and PSAD values were not significantly correlated with the cell differentiation in PCA stage A2-C. In total, PSA was 18.1 ng/ml in well, 23.9 ng/ml in moderately and 35.9 ng/ml in poorly differentiated type PCA. The positive rate of PSA was 22.3, 65.4 and 83.5%, that of prostate acid phosphatase (PAP) was 10.0, 17.8 and 45.8%, and that of GSM was 25.0, 14.7 and 68.4%, in BPH, stage A PCA and stage BPCA, respectively. In conclusion, PSA is the most reliable tool in the diagnosis of localized PCA. However, the differential diagnosis of BPH and localized PCA is difficult when the PSA value is between 3.61 and 10.0 ng/ml, and accurate staging of localized PCA is difficult with PSA or PSAD alone. At present, it is necessary to use all possible tools for the early detection of localized PCA, and to perform the needle biopsy in all PCA-suspicious cases.

Acid Phosphatase↗

[Clinical study of testicular cancer].

Since April 1986, a prospective clinical trial for testicular cancer has been underway by our Nara Uro-Oncology Research Group. One hundred and forty-eight cases of germ cell tumor were entered into this study between April, 1986 and August, 1995. They included 99 cases (66.9%) of seminoma and 49 cases (33.1%) of non-seminomatous germ cell tumor (NSGCT). The mean age of seminoma cases (39.7 yrs) was higher than that (30.2 yrs) of NSGCT cases. One hundred and twenty-three cases were treated according to our protocol. In the treatment group, one patient with stage I seminoma died of other diseases and one patient each with stage II and stage III seminoma died of cancer. Three patients with stage III NSGCT died of cancer. The 5-year survival rate was 100% for stage I seminoma, and stage I and stage II NSGCT, 75.0% for stage II seminoma, 0% for stage III seminoma and 66.7% for stage III NSGCT. These findings suggest that new treatment modalities should be introduced into our protocol in the future.

Adolescent↗