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Biomedical subjects

J Yoshida

Publications and source records attributed to J Yoshida.

At least 253 records · Page 14Linked to original sources

Gene therapy against an experimental glioma using adeno-associated virus vectors.

The efficacy of gene therapy for glioma was examined using adeno-associated virus (AAV)-based vectors to deliver genes to experimental tumors in mice. Stereotactic injection of 2 x 10(5) U-251SP human glioma cells into the brains of nude mice produced tumors of 19.06 +/- 1.79 mm2 17 days after injection. Employing a high titer preparation of AAV vector containing the gene for beta-galactosidase (AAV-lacZ), dose-dependent transduction of U-251SP cells was seen in vitro. When 1.6 x 10(10) AAV-lacZ particles were directly injected into tumors in vivo, 30-40% of the cells along the needle track expressed beta-galactosidase. Transduction of U-251SP cells in vitro with an AAV vector containing a bicistronic gene encoding both herpes simplex thymidine kinase and human interleukin-2 (AAV-tk-IRES-IL2) rendered them sensitive to the cytocidal effects of ganciclovir (GCV) and IL-2 was produced in a dose-dependent manner. Cocultures of AAV-tk-IRES-IL2 transduced cells and nontransduced cells proved highly sensitive to GCV indicating the contribution of the bystander effect. Stereotactic delivery of 6 x 10(10) AAV-tk-IRES-IL2 particles into day 7 tumors in nude mice followed by administration of GCV for 6 days, resulted in a 35-fold reduction in the mean volume of tumors compared with controls. Normal brains did not suffer from any toxic effect of the administration of AAV-tk-IRES-IL2 and GCV. These results indicate that high titer AAV vector treatment may be safe and effective for in vivo gene therapy of human brain tumors.

Animals↗

Development of a target-directed magnetic resonance contrast agent using monoclonal antibody-conjugated magnetic particles.

We developed a novel magnetic resonance (MR) imaging contrast agent, MAb-magnetite, that was prepared by covalently linking polyethylene glycol-coated magnetite to a monoclonal antibody specific for a human glioma cell-surface antigen. When MAb-magnetite was injected intravenously into tumor-bearing nude mice at a dose of 100 mumol Fe/kg body weight, a 50% decrease in the T2 signal intensity of the tumor was observed, immediately following administration and continued for 48 h. Microscopic observation of the tumor tissue demonstrated localization of MAb-magnetite in cancer cells. These results suggest that MAb-magnetite is a promising agent for MR imaging of neoplasms.

Animals↗

[Teaching experience of laparoscopic cholecystectomy: a report from Beijing].

I arrived at Beijing on August 13, 1995, having been appointed to a tutor for laparoscopic cholecystectomy (LSC) in the Sino-Japanese Friendship Hospital therein by the Japan International Cooperation Agency. This hospital was inaugurated in 1984 and accommodates up to 1,300 in patients. In the history of surgery, nevertheless, the laparoscopic method is revolutionary in that many doctors share the operative field, make judgments, and perform procedures, all of which are open to observers. These features, however, attest the Chinese philosophy of the surgeons and the Asian idea to respect the elderly in the traditional Chinese clinic. We therefore attempted to create a team for endoscopic surgery by junior surgeons and sought cooperation to anesthesiologists and nurses in the operating room. On August 21, 1995. I attended the first operation as an endoscopist teaching the mini-laparotomy method at the placement of a trocar. Even in the introductory period of LSC, we had to treat patients immediately after gallstone attack. Thus I detailed the precautions at dissecting the triangle of Calot. We found the EndoflexTM retractor of great use in those patients with severe adhesion. While paying respect for their dignity, we told the necessity of teamwork where one has to give way sometimes for the establishment of this new type of operative style. A total of eight patients underwent LSC by the time I left China on September 10, 1995. We wish that this seed of laparoscopic surgery would proliferate in this young hospital located, however, in the capital of a country with eternal history.

Adult↗

Molecular neurosurgery using gene therapy to treat malignant glioma.

In the last decade, the prognosis of brain tumor patients has dramatically improved due to recent advances in microsurgical techniques and the development of functioning neuroimaging, computer-assisted neuronavigation, endoscopic surgery, intravascular surgery and radiosurgery. According to a report by the Committee of Brain Tumor Registry of Japan, the ten year survival rate of patients with benign brain tumors (meningioma, neurinoma and pituitary adenoma) is more than 95%. In contrast, patients with glioma (which constitute 33% of primary brain tumor cases) still have a poor prognosis, especially in the case of malignant (anaplastic astrocytoma and glioblastoma). This poor prognosis is related to the fact that malignant glioma cells aggressively infiltrate into normal brain tissues, making total removal of the tumor impossible. The median survival time of glioblastoma patients is less than 2 years, despite multimodality treatment with extensive surgical resection and adjuvant therapies using radiation and immunochemotherapy. In order to overcome this formidable neoplasm, the effectiveness of molecular neurosurgery using gene therapy has been investigated since 1992. In this paper, molecular genetic studies and the current state of gene therapy for malignant brain tumors are described, and the future direction of this fascinating approach is discussed.

Animals↗

Current management and long-term prognosis of hepatolithiasis.

OBJECTIVE: To assess the surgical and endoscopic treatment results and long-term prognosis of hepatolithiasis. DESIGN: Retrospective case series. SETTING: University hospital. PATIENTS: Eighty-five consecutive patients with hepatolithiasis treated between 1980 and 1993. MAIN OUTCOME MEASURES: Location of calculi, associated diseases, treatment procedures, and long-term prognosis were analyzed. RESULTS: Thirty-eight percent of the 85 patients had stones only in intrahepatic ducts, while others had intrahepatic and extrahepatic calculi. Seventy-two percent of the patients had repeated biliary surgery, and 14% were associated with liver cirrhosis. After surgery combined with cholangioscopy and electrohydraulic lithotripsy, the complete stone clearance rate was 71%. The treatment-related mortality rate was 3.8%; the stone recurrence rate after complete stone removal was 11%. However, it was notable that 17 patients (20%) died of related diseases during a mean follow-up of 6 years. The reasons for death were liver failure, bleeding from esophageal varices, hepatocellular carcinoma, and cholangiocarcinoma. CONCLUSION: Improvement of stone clearance rate is evident by a systematic approach. Complete relief from calculi, bile stasis, and cholangitis at an early stage of the disease is mandatory to prevent progressive liver damage, because repeated recurrence of intrahepatic calculi and cholangitis ultimately lead to irreversible liver damage and hepatobiliary carcinomas with a high mortality.

Adult↗

Growth inhibition of intracerebral rat glioma by transfection-induced human interferon-beta.

In our previous study on liposome-mediated transfection of the human interferon-beta (HuIFN-beta) gene into subcutaneously implanted human gliomas in nude mice, we found that HuIFN-beta was produced and secreted by the tumor cells and that the growth of solid tumors was completely inhibited. The present study investigated the growth-inhibitory effect of liposomes containing the HuIFN-beta gene inserted into a vector (pSV2IFN-beta) on T9 rat glioma implanted into the brains of rats. Tumor cells and liposomes containing pSV2IFN-beta or other additives were simultaneously injected into the brains of rats. HuIFN-beta was detected in solid gliomas growing in the brains of rats injected with liposomes and magnetic resonance imaging (MRI) showed that tumor growth was inhibited. In addition, the latent period until the appearance of neurological symptoms was significantly prolonged in rats treated with liposomes containing pSV2IFN-beta. However, the survival time of the treated rats was not significantly increased.

Animals↗

Malignant lymphoma of the thyroid with evidence of an Epstein-Barr viral infection concomitant with thalassemia minor: report of a case.

We report herein the unusual case of a 53-year-old Japanese man in whom malignant lymphoma of the thyroid was found to coexist with asymptomatic thalassemia minor and an elevated titer (1:80) of immunoglobulin G against the Epstein-Barr viral capsid antigen. A total thyroidectomy with lymphadenectomy was performed, and the thyroid was found to be almost replaced by the neoplasm, the microscopy of which revealed malignant lymphoma of the diffuse, large-cell type. The existence of this case led us to question whether malignant lymphoma of the thyroid and an elevated titer for the Epstein-Barr virus might have a possible mutual association.

Antigens, Viral↗

Nosocomial propagation of multiresistant Staphylococcus aureus: an analysis using biotyping and drug sensitivity.

We performed an epidemiologic study of multi-resistant Staphylococcus aureus in our hospital. We combined bacteriologic biotyping and sensitivity to 19 drugs to conduct an environmental investigation. We assumed that complete matching in two or more strains denoted nosocomial propagation. A total of 667 isolates were recovered from a total of 144 patients. In a general surgical ward, 19 (52.8%) out of 36 patients developed an infection. The number of strains for every biotype and the combined susceptibility tended to show negative correlation (r = -0.376) before and after 1990, when an isolation policy was initiated. A similar regression analysis disclosed that between the general surgical ward and other wards the number of strains tended to show a positive association (r = 0.349). Thus, the isolation system employed in the general surgical ward may have arrested the persistence of intraward strains but permitted the interward travel of strains. In conclusion, an analysis of the propagation of multiresistant S. aureus using biotyping and drug sensitivity was found to be an effective method for evaluating the most appropriate measures to counter the endemic spread of this microbe.

Anti-Bacterial Agents↗

Differential binding patterns of three antibodies (VOBM1, VOBM2, and VOM2) in the rat vomeronasal organ and accessory olfactory bulb.

Immunohistochemical properties of monoclonal antibodies raised against the rat vomeronasal epithelium were examined in adult rats. Three monoclonal antibodies, VOBM1, VOBM2, and VOM2, reacted specifically to the luminal surface of the sensory epithelium of the vomeronasal organ. In addition, the reactivities of VOBM1 and VOBM2 were detected in the vomeronasal nerve layer and the glomerular layer of the accessory olfactory bulb. Electron-microscopic study revealed differential patterns of the immunoreactivity of the three antibodies to the microvilli of vomeronasal sensory epithelium. VOBM1 immunoreactivity was found on the microvilli of the supporting cells, whereas VOBM2 immunoreactivity was found on those of the sensory cells. VOM2 immunoreactivity was observed on the microvilli of both the sensory and supporting cells. These results suggest that the three antibodies recognize different antigens on the vomeronasal sensory epithelium. In particular, VOBM2 antibody appears to react to an antigen specific to the microvilli of the vomeronasal sensory cells.

Animals↗

Staging, scoring and grading of medulloblastoma. A postoperative prognosis predicting system based on the cases of a single institute.

Although recently survival of some medulloblastoma patients increased remarkably, it remains a serious diagnosis in others. In order to predict the postoperative prognosis in patients treated for medulloblastoma, a new staging, scoring and grading system was developed. Sixty-six patients operated on microsurgically between 1975 and 1990 at a single neurosurgical center were fully followed-up. No patient was excluded due to a poor postoperative course. Completion of commonly used radiotherapy protocols was attempted in all patients. Survival of patients was evaluated by the Kaplan-Meier method. The following 5 parameters were selected to define subgroups: patients' age, tumour location and histology, degree of resection and presence or absence of metastases. Patients older than 10 years had a better prognosis than individuals aged 10 or less (p < 0.01), patients with lateral tumours had a better prognosis than patients with midline tumours with brain stem infiltration (p < 0.05), patients with complete tumour resection had a more favourable prognosis than individuals with subtotal (p < 0.01) or partial resection (p < 0.001), patients without metastases at the time of diagnosis had a better prognosis than individuals without such evidence (p < 0.001), patients with the desmoplastic tumour variant had a better prognosis than patients with classical tumour histology (p < 0.01). According to the prognosis of a distinct subgroup, scoring points were distributed which correlated with the degree of inter-subgroup significances. The sum of a single patient's scoring points was called the total score. Based on this score, three groups of prognosis were distinguished.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A super long-acting LH-RH analogue induces regression of hypothalamic hamartoma associated with precocious puberty.

We treated a 1-year-old female with a hypothalamic hamartoma and precocious puberty with leuprolide acetate depot, a super long-acting hormone-releasing hormone analogue (Tap-144-SR; [D-Leu6-[des-Gly10-NH2] LH-RH ethylamide acetate). The infant's major symptoms were genital bleeding and gynaecomastia. The LH-RH analogue (30 micrograms/kg) was injected subcutaneously once every 4 weeks. Clinical and laboratory manifestations of precocious puberty showed marked improvement. A follow-up after 16 months of treatment, the size of the tumour decreased significantly and remained unchanged for 2 years of further follow-up. To the best of our knowledge, this is the first hypothalamic hamartoma case in whom a decrease of tumour size under treatment with LH-RH analogue has been documented. But, because diagnosis of hamartoma is only based on neuroradiological and not on histological examinations, the possibility of a gangliocytoma cannot be excluded with certainty.

Delayed-Action Preparations↗

The order of ward rounds influences nosocomial infection. A 2-year study in gastroenterologic surgery patients.

We studied the effect of the order of ward rounds on nosocomial infection in gastroenterologic surgery patients. The subjects were patients with gastrointestinal diseases admitted between September 1992 and August 1994. During the 1st year, the round proceeded indiscriminately among recovery rooms and rooms with stable patients and isolated patients with methicillin-resistant Staphylococcus aureus (MRSA). In the subsequent year, the round started in the recovery rooms and moved into the general rooms with stable patients and finally into the isolation rooms. Against the time course, piecewise linear regression analyses were made with the number of culture-positive patients and the quantities of antibiotics and disinfectants used. Of a total of 1894 strains from 264 patients, isolates of MRSA (n = 200) decreased from 150 in the 1st year to 50 in the 2nd year. The number of MRSA-positive patients showed the point of inflexion in the analysis at the change of round order, with a later decrease. The trend was similar for Candida (n = 99) and Enterococcal (n = 225) species. The amount of antibiotics was unchanged while the amount of disinfectants used decreased in the 2nd year. Thus, the round re-ordering appeared to help prevent nosocomial infection. Ward rounds for patients who have had gastroenterologic surgery should proceed from compromised hosts to stable patients, and then isolated patients.

Anti-Infective Agents, Local↗

Comparison of gentamicin nephrotoxicity between rats and mice.

Toxic effects of gentamicin administration (10-80 mg/kg body weight, subcutaneously (s.c.), once daily for 7 days) on several enzyme activities of kidney and duodenal mucosa together with other parameters were compared between male rats and mice. In Wistar rat kidney, tubular brush border Mg(2+)-dependent, HCO3(-)-stimulated ATPase (Mg(2+)-HCO3(-)-ATPase) activity was inhibited by 40-80 mg/kg gentamicin in an almost dose-dependent manner with no changes in microsomal Mg(2+)-Na(+)-K(+)-ATPase activity. Cytosol carbonic anhydrase (CA) activity was inhibited only by 80 mg/kg gentamicin. In rat duodenal mucosa, Mg(2+)-HCO3(-)-ATPase and CA activities were unchanged by any dose of gentamicin. Rat serum urea nitrogen (UN), GOT and GPT concentrations and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity were significantly increased by 80 mg/kg gentamicin. In ddY mice, however, almost all parameters described above were unaffected by gentamicin except for the urinary NAG activity which was increased only by 80 mg/kg gentamicin. The concentration of gentamicin in cytosol of rat whole kidney was approximately 3.4-fold higher compared with that in mouse kidney after 80 mg/kg treatment. In light microscopic analysis, 80 mg/kg gentamicin produced necrosis in the greater part of rat kidney proximal tubuli with no pathological findings in mouse kidney. In conclusion, Mg(2+)-HCO3(-)-ATPase activity in brush border membrane of rat proximal tubuli was selectively damaged in gentamicin nephrotoxicity, indicating that the rats are the suitable model for studies of gentamicin nephrotoxicity in humans.

Animals↗

Reinforced cytotoxicity of lymphokine-activated killer cells toward glioma cells by transfection of the killer cells with the gamma-interferon gene.

Lymphokine-activated killer (LAK) cells generated from peripheral blood lymphocytes incubated with recombinant interleukin-2 were transfected with the human gamma-interferon (HuIFN-gamma) gene by means of liposomes having a positive charge on their surface. The cells secreted significant amounts of HuIFN-gamma (reaching more than 5 U/ml) into the culture medium. The HuIFN-gamma produced by the cells induced intercellular adhesion molecule-1 (ICAM-1) and enhanced the expression of Fas antigen on the surface of human glioma cells. Also, LAK cells transfected with HuIFN-gamma gene exhibited reinforcement of cytotoxicity toward human glioma cell lines (U251-MG and SK-MG-1). Furthermore, the reinforcement was significantly quenched by anti-ICAM-1 and/or anti-TNF-alpha monoclonal antibody.

Antibodies, Monoclonal↗

[Effect of an extract prepared from "dai-bofu-to" on morphine withdrawal responses].

A water-extract (TJ-97) prepared from "Dai-bofu-to", a "Kampo" medicine (Chinese traditional prescriptions composed of herbal drugs) was tested for its potency to modulate morphine withdrawal responses in animals. TJ-97 significantly attenuated naloxone-induced contraction of the segments of the ileum isolated from morphine-dependent guinea pigs in the absence and presence of atropine. TJ-97 also inhibited the contractile responses of the segments to electrical field stimulation at a low frequency and those to nicotine, but not those to exogenously applied ACh or substance P. The rats given i.p. TJ-97 and 30 min later challenged with naloxone showed significantly lowered frequency of excretion and diminished amount of feces, including soft stools (diarrhea), as compared with the saline-injected control rats. These findings suggest that TJ-97 inhibits the release of ACh and substance P or substance P-like peptide(s) from the nervous structures in the wall of the ileum.

Animals↗

Growth inhibition of human glioma cells by superinduced human interferon-beta.

Superinduction of human interferon-beta (HuIFN-beta) from human glioma cells has greater cytotoxicity than purified HuIFN-beta derived from fibroblasts. However, superinduction requires several reagents like polyI:polyC, cycloheximide, and actinomycin D, which may contaminate the conditioned medium and obscure the effect of superinduced HuIFN-beta. The present study used minimum doses of polyI:polyC and cycloheximide without actinomycin D to superinduce HuIFN-beta. The superinduced HuIFN-beta was purified by passing the medium through molecular sieve column chromatography. Fractionation of the eluate provided semipurified superinduced HuIFN-beta which demonstrated a growth inhibitory effect against both the U251-MG autologous human glioma cell line and the SK-MG-1 homologous glioma cell line. This effect was neutralized by addition of anti-HuIFN-beta monoclonal antibody (YSB-1). In a separate experiment, combinations of superinduction reagents were found not to have growth inhibitory effects because all inhibition in superinduced medium was completely neutralized by YSB-1. Superinduced HuIFN-beta has a pure growth inhibitory effect on both autologous and homologous glioma cells, so may affect autocrine secretion of cytokines.

Antibodies, Monoclonal↗

[A case report of epidermoid carcinoma in the cerebello-pontine angle].

A case of epidermoid carcinoma in the cerebello-pontine (CP) angle is presented. A 42-year-old male was admitted with a complaint of experiencing double vision for four months in January, 1992. During neurological examination, right abducens palsy, right facial dysesthesia, and atrophy of the right temporal muscle were noted. Magnetic resonance (MR) imaging revealed a mass of low intensity in the right CP angle, which was prominently enhanced with gadolinium. Malignancy was suspected because the tumor on MR enlarged rapidly in a month, so the first surgical resection was performed. Suboccipital exploration of the right CP angle was performed in February. At first, a fragile, pearly part of the mass typical of epidermoid was exposed behind the seventh and eighth cranial nerve complex. Then, a grayish, fibrous part was exposed, which involved the fifth cranial nerve and was attached to the tentorium and the brainstem. Histological diagnosis of the fragile part of the tumor revealed a typical epidermoid cyst and that of the fibrous part was squamous cell carcinoma. During postoperative examinations on other parts of the body, such as endoscopic studies of the trachea and the esophagus, no abnormality was shown. Therefore the tumor was diagnosed as a primary intracranial epidermoid carcinoma. Post-operatively, conventional fractionated external-beam focal irradiation was carried out, which caused regression of the residual tumor for eleven months. Subsequently, palsy of the right side of the tongue and paresis of the contralateral side of the extremities and face developed with increase of the right abducens palsy. MR imaging indicated regrowth of the tumor. The second operation via the subtemporal approach was unsuccessful, because the tumor was fibrous and firmly attached to the brainstem.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗