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Biomedical subjects

H Okada

Publications and source records attributed to H Okada.

At least 217 records · Page 12Linked to original sources

Elevation of anti-cytokeratin 19 antibody in sera of the patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with collagen vascular disorders.

It has been suggested that cytokeratin 19 is expressed in regenerated bronchoepithelial cells in patients with pulmonary fibrosis, and serum cytokeratin 19 fragment is elevated in patients with pulmonary fibrosis. We hypothesized that serum antibodies to cytokeratin 19 may be formed in patients with pulmonary fibrosis. To prove the existence of anti-cytokeratin 19 antibodies in patients' sera, human recombinant cytokeratin 19 was stained with patients' sera by a Western immunoblot. Then, we tried to establish an enzyme-linked immunosorbent assay to quantitate anti-cytokeratin 19 antibody in the sera of patients with idiopathic pulmonary fibrosis (IPF) and pulmonary fibrosis associated with collagen vascular disorders (PF-CVD). We demonstrated the anti-cytokeratin 19 antibody in patient' sera by a Western immunoblot. In patients with IPF and PF-CVD, significantly high anti-cytokeratin 19 antibody was demonstrated compared with normal volunteers, patients with chronic bronchitis, and patients with pneumonia. These results suggest that anti-cytokeratin 19 antibody may have played a role in the process of lung injury in pulmonary fibrosis.

Adult↗

Decrease in apoptosis of germ cells in the testes of infertile men with varicocele.

To determine whether the regulation of apoptosis in the testes of patients with varicocele testes was abnormal, affecting germ-cell differentiation and sperm production, we studied apoptosis in the testes of normal men and infertile men with varicocele. In all, 56 testicular biopsy specimens were collected from 28 varicocele patients. The specimens from the testes of five normal volunteers with informed consent were used as controls. In situ end-labeled cells were counted with a CAS 200 image analyzer, and an apoptotic index (AI) was calculated by division of the number of labeled cells by the total number of spermatocytes and spermatogonia in over 20 seminiferous tubules. The apoptosis was also examined by electron microscope. The mean AI was 9.67 +/- 0.93% in normal testes (n = 5). In contrast, the mean AIs determined in the right and left testes of varicocele patients (n = 28) were 3.90 +/- 2.28% and 3.78 +/- 2.87%, respectively. The AIs recorded for the testes of varicocele patients were significantly lower than those noted for normal men (P < 0.05). In varicocele patients the AI obtained in the right testis was not statistically significantly different from that found in the left testis. The numbers of apoptotic cells per Sertoli cell also decreased in the testes of varicocele patients as compared with normal men (P < 0.01). Evaluation of all specimens, including the normal controls, revealed no significant correlation either between the AI and the sperm concentration on the seminogram or between the AI and Johnsen's mean score. There was also no relationship between the AI and the serum level of follicle-stimulating hormone, lutenizing hormone, testosterone, or estradiol. In conclusion, apoptosis is decreased in germ cells in the testes of infertile men with varicocele as compared with normal men.

Adult↗

Glycosylation of microtubule-associated protein tau in Alzheimer's disease brain.

In the neurofibrillary pathology of Alzheimer's disease (AD), neurofibrillary tangles (NFTs) contain paired helical filaments (PHFs) as their major fibrous component. Abnormally hyperphosphorylated, microtubule-associated protein tau is the major protein subunit of PHFs. A recent in vitro study showed that PHF tangles from AD brains are highly glycosylated, whereas no glycan is detected in normal tau. Deglycosylation of PHF tangles converts them into bundles of straight filaments and restores their accessibility to microtubules. We showed that PHF tangles from AD brain tissue were associated with specific glycan molecules by double immunostaining with peroxidase and alkaline phosphatase labeling. Intracellular tangles and dystrophic neurites in a neuritic plaque with abnormally hyperphosphorylated tau, detected with the monoclonal antibodies AT-8 and anti-tau-2, were also positive with lectin Galanthus nivalis agglutinin (GNA) which recognizes both the N- and O-glycosidically linked saccharides. Colocalization was not seen in the extracellular tangles and amyloid deposition, suggesting that the glycosylation of tau might be associated with the early phase of insoluble NFT formation. Thus, although abnormal phosphorylation might promote aggregation of tau and inhibition of the assembly of microtubules, glycosylation mediated by a GNA-positive glycan appears to be responsible for the formation of the PHF structures in vivo.

Alzheimer Disease↗

Gastric ulcers in SCID mice induced by Helicobacter pylori infection after transplanting lymphocytes from patients with gastric lymphoma.

BACKGROUND & AIMS: Several studies have indicated that host factors are important in Helicobacter pylori-induced gastroduodenal diseases. We examined the pathological role of host immune responses in H. pylori infection by reconstituting components of the human immune system into severe combined immunodeficient (SCID) mice by transplantation of peripheral blood mononuclear cells (PBMCs) from H. pylori-infected patients. METHODS: PBMCs obtained from patients with mucosa-associated lymphoid tissue (MALT) lymphoma were injected intraperitoneally into SCID mice, designated MALToma-hu-SCID mice. One month after transplantation, H. pylori was administered orally to the mice. The mice were killed and examined for pathological changes and immunologic features. RESULTS: Human lymphocytes were detected in hu-SCID mice, and T- and B-cell functions were preserved for 1 month. Administration of H. pylori led to gastric ulcers with bleeding in the MALToma-hu-SCID mice. The gastric mucosa of control mice injected with Escherichia coli or transplanted with PBMCs from patients with peptic ulcers or gastritis or from healthy volunteers showed no pathological changes. CONCLUSIONS: Host immune responses against H. pylori appear to be involved in the development of gastric ulcers in patients who have MALT lymphoma.

Animals↗

Conservative therapy for stage T1b, grade 3 transitional cell carcinoma of the bladder.

OBJECTIVES: To retrospectively evaluate the usefulness of transurethral resection of bladder tumor (TURBT) and intravesical instillation for pT1bG3 transitional cell carcinoma of the urinary bladder. METHODS: Between May 1984 and May 1997, 45 patients with pT1bG3 transitional cell carcinoma of the urinary bladder underwent TURBT and intravesical instillation with bacillus Calmette-Guerin (BCG) or other anticancer agents. Random biopsy was carried out in 37 patients. The recurrence-free survival rate was determined by tumor size, number of tumors, lymphovascular invasion, and drugs used for intravesical instillation. The median follow-up period was 63 months (range 4 to 145) after the initial TURBT. RESULTS: Of 37 patients who underwent random biopsy, concomitant carcinoma in situ was detected in 18 patients (48.6%). The incidence of concomitant CIS was significantly higher in patients with multiple tumors (P = 0.029). Vesical recurrence was noted in 16 patients (35.6%). The overall 1-, 3-, and 5-year recurrence-free survival rates were 88.5%, 66.7%, and 66.7%, respectively. Progression (muscular invasion) occurred in only 2 patients (4.4%). Total cystectomy was performed in 4 patients, including the 2 patients with progressive disease, and 2 patients with recurrent CIS that resisted BCG therapy. None of the patients died of bladder cancer. CONCLUSIONS: Our results suggest that aggressive attempts at initial or subsequent TURBT combined with BCG therapy achieved good control of pT1bG3 transitional cell carcinoma of the urinary bladder.

Adult↗

Estrogen effects on platelet-activating factor and platelet-activating factor acetylhydrolase activity in rat uterus during the late stages of pregnancy.

The platelet-activating factor (PAF) concentration of the uterus spontaneously increased during pregnancy. When 17alpha-ethynylestradiol (0.25 mg/kg) was administered subcutaneously to pregnant rats for 3 days starting on Day 17 of pregnancy, some rats delivered prematurely on Day 20. However, none of the vehicle-treated (80% dimethylsulfoxide and 20% ethanol) pregnant rats delivered prematurely. The PAF concentration of the uterus in pregnant rats treated with 17alpha-ethynylestradiol was significantly higher than in those treated with vehicle on Days 19 and 20. On the other hand, the specific activity of uterine PAF-acetylhydrolase (PAF-AH) in pregnant rats treated with 17alpha-ethynylestradiol was significantly lower than in those treated with vehicle on Days 19 and 20, and the plasma PAF-AH activity in pregnant rats treated with estrogen was also significantly lower than in treated with vehicle on Days 18, 19, and 20. These findings indicate that estrogen increases PAF concentrations in the rat uterus, and this was correlated with a decrease in PAF-AH in the uterus and plasma. The increase in PAF concentrations in the uterus may be related to premature delivery and labor caused by PAF's known effect on myometrial contraction.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

Cavitary lung cancer with an aspergilloma-like shadow.

A 66-year-old man who complained of cough and haemoptysis had a cavitary lesion with the meniscus sign in the right lower lung field on his chest X-ray and CT scan. He had smoked 40 cigarettes daily, for about 46 years. Initially, he was diagnosed with aspergilloma and given an antifungal agent. After 2 months, the cavitary lesion showed a slight irregularity of the inner border. The walls were irregularly thickened and were surrounded by infiltrative densities compared with the previous chest radiograph. Enlargement of right hilar and mediastinal lymph nodes was also observed. The fungus ball-like shadow was fixed on the anterior wall of the cavity and its position was not altered with the patient's movements. These radiographic findings led to suspicion that the lesion might be malignant. Transbronchial lung biopsy of the cavity wall and CT guided needle aspiration biopsy of the fungus ball-like lesion were performed. Microscopic examination revealed a squamous-cell carcinoma in both the cavity wall and the fungus ball-like lesion. There was no evidence of fungal elements. In conclusion, the meniscus sign is most often associated with benign diseases such as aspergilloma, however, one should remember that carcinoma may be a cause.

Aged↗

Thoracoscopic surgery and pleurodesis for pleuroperitoneal communication in patients on continuous ambulatory peritoneal dialysis.

Two patients on continuous ambulatory peritoneal dialysis (CAPD) developed right massive hydrothorax and were diagnosed as having pleuroperitoneal communication. Thoracoscopic surgery and pleurodesis were performed. It showed that one was caused by multiple flaws in the diaphragm and that the other was attributable to multiple blebs in the diaphragmatic dome. After the procedure, both of them had no recurrence of hydrothorax and underwent CAPD safely. We recommend thoracoscopic surgery and pleurodesis as the first choice of therapeutic methods for pleuroperitoneal communication.

Endoscopy↗

Prostatitis--the Japanese viewpoint.

Japanese inclusion criteria in acute and chronic bacterial prostatitis are explained. Objective criteria of acute prostatitis are a bacterial count of 10(4) cfu/ml or more and 10 or more WBCs/hpf in VB1 or VB2. Criteria for chronic prostatitis are a bacterial count of 10(3) cfu/ml or more (if only Gram-positive cocci are isolated from EPS, a bacterial count of 10(4) cfu/ml or more is required) and 10 or more WBCs/hpf (including macrophages) in EPS or VB3. Secondly, we describe recent topics such as bacterial biofilm formation in prostatic tissues by electron microscopy in three out of 12 patients with intractable chronic prostatitis.

Acute Disease↗

Expression of two Trichoderma reesei xylanases in the fission yeast Schizosaccharomyces pombe.

Two xylanase genes (xyn1 and xyn2) were amplified by the polymerase chain reaction (PCR) technique from first-strand cDNA prepared from mRNA of Trichoderma reesei QM9414. The genes were located under the human cytomegalovirus gene promoter (CMVp) on copy-number-controlled plasmids (pTLxyn1 and pTLxyn2). When both plasmids were introduced into Schizosaccharomyces pombe, functional xylanases (XYN I and XYN II) were secreted by the recombinant yeasts. The secreted XYN I protein had a molecular mass of 21 kDa whereas XYN II was produced as two molecular forms with sizes of 21 and 28 kDa, the former being not glycosylated and the latter N-glycosylated. XYN I was secreted in the culture medium at a level of about 25 microg/ml and XYN II at about 170 microg/ml. The recombinant xylanases had the same characteristics with respect to the effects of temperature and pH on the enzyme activity as the native ones.

Journal Article↗

Effective cytokine gene therapy against an intracranial glioma using a retrovirally transduced IL-4 plus HSVtk tumor vaccine.

To explore the potential for molecular immunotherapies in the treatment of malignant gliomas, we evaluated the efficacy of subcutaneous tumor cell vaccines in the treatment of intracranial 9L tumors, using 9L gliosarcoma cell lines stably transduced with the murine interleukin-4 cDNA (9L-IL4), the herpes simplex virus-thymidine kinase cDNA (9L-Tk) or both (9L-IL4-Tk). The expression of multiple genes from a single transcript was achieved by incorporating internal ribosomal entry site (IRES) cassettes in the retroviral constructs. Subcutaneous immunization of rats with nonirradiated 9L-IL4 cells or 9L-IL4-Tk cells followed by treatment with ganciclovir (GCV) completely protected the animals from a subsequent intracranial challenge with wild-type 9L cells. In contrast, only 50% of animals immunized with 9L-Tk cells and 0% of 9L-neo immunized animals rejected the same challenge with wild-type 9L. More importantly, treatment of established (day 3) intracranial 9L tumors with genetically engineered tumor cells resulted in long-term survival (> 100 days) for 25-43% of 9L-IL4-Tk immunized animals and for 27% of nonirradiated 9L-IL4 immunized animals. In striking contrast, no 9L-Tk, 9L-neo or irradiated 9L-IL4 immunized animals survived for more than 33 days. As a marker of a cellular immune response, splenocytes from nonirradiated 9L-IL4, 9L-Tk or 9L-IL4-Tk immunized animals produced interferon-gamma (IFN-gamma) in greater amounts than those from 9L-neo immunized or Hank's balanced salts solution (HBSS) treated animals when stimulated with wild-type 9L in vitro. Our findings support the use of tumor cell vaccines expressing the IL-4 and HSVtk genes for the treatment of malignant gliomas.

Animals↗

Diffuse submucosal cysts of the stomach: report of two cases in association with development of multiple gastric cancers during endoscopic follow up.

BACKGROUND: Diffuse submucosal cysts of the stomach have been suggested as a predisposing condition for the development of gastric cancer, especially multiple cancers. We report here two cases of diffuse submucosal cysts of the stomach associated with multiple gastric cancers which were detected during endoscopic follow-up. METHODS AND RESULTS: The first patient was a 75-year-old man and the second patient was a 72-year-old man. In the first case, we performed an endoscopic examination every year and detected an advanced cancer and two early cancers on the fifth year of the follow up. Because one of these cancers was advanced, we examined the second patient endoscopically every six months. In this patient, we detected two early cancers after 1.5 years follow up. CONCLUSIONS: We suggest that patients with this disorder should be examined regularly by endoscopy for the detection of gastric cancer, preferably every six months.

Adenocarcinoma↗

Outcome of precise vesicourethral anastomosis following retropubic radical prostatectomy using a Foley catheter.

PURPOSE: In order to evaluate precise anastomosis using a Foley catheter, complications following radical retropubic prostatectomy were examined. METHODS: Twenty-one patients underwent radical retropubic prostatectomy. Precise vesicourethral anastomosis was performed, visualizing the urethral stump by raising up the urogenital diaphragm using a Foley catheter. Complications, such as prolonged urinary extravasation and temporary urinary retention, were checked when the catheter was removed. Incontinence was evaluated both within 6 weeks and more than 6 weeks after operation. Anastomotic and urethral strictures were also checked during follow up. RESULTS: The follow-up period ranged from 4 to 47 months (mean (+/- SD) 22.0 +/- 12.1 months). Eighteen of 21 patients (85.7%) achieved continence after the operation. However, two patients still had stress incontinence and one patient had mild incontinence. Neither prolonged urinary extravasation nor temporally urinary retention were observed. Anastomotic and urethral stricture were not experienced during follow up. CONCLUSIONS: Precise anastomosis using a Foley catheter is technically easy and useful, even for relatively inexperienced urologists, to perform. Patients can often achieve continence following this procedure.

Adult↗

Clinical outcome of microsurgery for obstructive azoospermia.

BACKGROUND: Recent technical advances in microscopy have greatly improved the reconstruction of the seminal tract in cases of obstructive azoospermia. METHODS: We evaluated the clinical outcome of 28 patients with obstructive azoospermia who underwent microsurgical reconstruction (i.e. vasovasostomy or unilateral epididymovasostomy). Diagnoses included postvasectomy (n = 9), childhood inguinal herniorrhaphy (n = 10) and cases of unknown cause (n = 9). Six of the unknown cases proved to be inoperable. We analyzed the outcome of the surgical reconstructions of operable cases according to the causes of obstruction, duration of obstruction, quality of the fluid obtained from the distal seminal tract (concentration, morphology and motility of sperm) and the histologic findings of the testis. RESULTS: The surgical outcome was analyzed with regard to the incidence of patency and pregnancy. The incidence of patency achieved in nine vasectomy cases was 89%, while the incidence of pregnancy was 44%. In contrast, the incidence of patency in the nine operable cases with herniorrhaphy was 44%, while the pregnancy rate was 0%. Of four cases of unknown cause who underwent epididymovasostomy, the incidence of patency was 100% and the incidence of pregnancy was 75%. The outcomes were worse in post-vasectomy cases with long-term obstruction of more than 10 years; however, this was not statistically significant. The outcome was significantly worse in cases with low sperm concentrations. There was no significant relationship between histologic findings and surgical outcome. CONCLUSIONS: The surgical outcome of vasovasostomy of postherniorrhaphy cases was significantly worse than that of post-vasectomy cases. With regard to epididymovasostomy, a unilateral repair was clinically evaluated.

Adult↗

Pharmacokinetics of natural human IFN-alpha in hemodialysis patients.

A pharmacokinetic study of natural human interferon-alpha (IFN-alpha) was conducted in hemodialysis patients. Natural human IFN-alpha was intramuscularly (i.m.) administered to 8 hemodialysis patients at a single dose of 5 million IU and to 7 patients undergoing hemodialysis at the same dose once daily for 5 successive days. The serum antiviral activity was determined by a cytopathic effect bioassay. In the single dose study, the serum antiviral activity reached a maximum (Cmax) of 56.4 +/- 33.3 IU/ml at 8.3 +/- 2.7 h after dosing, and the area under the serum concentration-time curve (AUC0-24h) was 957.2 +/- 601.8 IU h/ml. The Cmax and AUC0-24h values at day 5 following the repeated dosing were both 2.6-fold higher than those of day 1, and the serum antiviral activity reached a steady state within 3 days after initiation of repeated administration. The serum antiviral activity in hemodialysis patients showed a tendency to increase compared with that in the subjects with normal renal function, but the magnitude of the differences was not great. In one nonhemodialysis patient with poor renal function (creatinine clearance < 30 ml/min), no increases in serum antiviral activity owing to repeated dosing were observed. The main adverse events seen were fever (4 of 13, 30.8%), leukopenia (3 of 13, 23.1%), and fatigue (2 of 13, 15.4%). These results suggest that dosage modifications of natural human IFN-alpha are unnecessary for patients with low renal function, even those undergoing hemodialysis.

Aged↗

Brain activation during maintenance of standing postures in humans.

The regulatory mechanism of bipedal standing in humans remains to be elucidated. We investigated neural substrates for maintaining standing postures in humans using PET with our mobile gantry PET system. Normal volunteers were instructed to adopt several postures: supine with eyes open toward a target; standing with feet together and eyes open or eyes closed; and standing on one foot or with two feet in a tandem relationship with eyes open toward the target. Compared with the supine posture, standing with feet together activated the cerebellar anterior lobe and the right visual cortex (Brodmann area 18/19), and standing on one foot increased cerebral blood flow in the cerebellar anterior vermis and the posterior lobe lateral cortex ipsilateral to the weight-bearing side. Standing in tandem was accompanied by activation within the visual association cortex, the anterior and posterior vermis as well as within the midbrain. Standing with eyes closed activated the prefrontal cortex (Brodmann area 8/9). Our findings confirmed that the cerebellar vermis efferent system plays an important role in maintenance of standing posture and suggested that the visual association cortex may subserve regulating postural equilibrium while standing.

Adult↗