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Biomedical subjects

Y Tsukada

Publications and source records attributed to Y Tsukada.

At least 181 records · Page 10Linked to original sources
PubMed1988

The role of myelination in learning performance observed in two strains of myelin-deficient mutant mice (shiverer and mld).

In order to study whether myelination is involved in learning performance, the behavior of myelin-deficient mutant mice (shiverer and mld) was examined. Shiverer is a deletion mutant of the myelin basic protein (MBP) gene causing severe myelin deficits due to the complete absence of MBP, while mld, allelic mutant to shiverer, shows lowered MBP expression, resulting in less severe effects. Shiverer clearly showed deficits in successive reversal learning, while mld showed less deficits in the learning performance. Both mutant mice showed no deficits in the radial maze performance, which is though to show the natural foraging behavior of rodents. These results suggest that myelin formation is related to learning but not to natural behavior.

Animals↗
PubMed1988

The effects of co-administration of selenium and cis-platin (CDDP) on CDDP-induced toxicity and antitumour activity.

The therapeutic antitumour activity and host toxicity of cis-platin (CDDP), which was administered with selenium (sodium selenite) was studied on the growth of a human yolk sac tumour grown in nude mice. Treatment consisted of CDDP single agent chemotherapy (3 weeks) or preliminary PVB combination chemotherapy (CDDP + vinblastine + bleomycin, 2 weeks). Selenium was co-administered from day 1 to 5 with each therapeutic regimen. The administration of CDDP alone caused significant reduction in tumour burden but at higher doses there was significant host toxicity. The co-administration of selenium together with CDDP (CDDP: selenium, molar ratio = 3.5:1) did not affect the anti-tumour activity of CDDP but it did cause a decrease of parameters of host toxicity including lethality, increasing the 50% lethal dose (LD50) from 9.3 mg kg-1 to 17.5 mg kg-1. The parameters of host toxicity which were altered by selenium co-administration were nephrotoxicity, myeloid suppression and weight loss. Our study suggested that selenium co-administration allows higher doses of CDDP with reduction of apparent toxicity, resulting in a higher therapeutic index and possibly indicating a potential increase in the utilization of CDDP in clinical cancer chemotherapy.

Animals↗
PubMed1988

Expression of a high molecular weight mucin-type glycoprotein in human colon cancer as defined by monoclonal antibody 1D3.

Murine monoclonal antibody 1D3 recognizes a high molecular weight acidic mucin restricted to the epithelium of normal colonic mucosa and goblet cells. Of 72 colonic carcinoma specimens examined, 29 were found to have detectable level of 1D3 antigen by an indirect immunoperoxidase staining assay on fixed, paraffin-embedded tissue sections. In some specimens a focal staining pattern was observed, while in others 50-90% of tumor cells were stained. Of 28 cases having adjacent normal mucosa, all 28 showed intense staining reaction in the normal mucosa and goblet cells despite the fact that 18 of the tumors were unstained. One of 1 colonic diverticulosis, 2 of 2 ulcerative colitis, 3 of 3 villo-glandular polyps, 19 of 20 adenomatous polyps and 17 of 19 hyperplastic polyps were also stained heavily for the 1D3 antigen. Colonic carcinomas displayed a range of staining patterns and a great degree of antigenic heterogeneity. Well-differentiated tumors characterized by typical goblet cells were almost always positive (10 of 12). As cellular structure became disorganized, as in moderately-differentiated tumors, about 33% of the tumors (17 of 51) stained for 1D3 antigen. As the tumor became more invasive with further disorientation of cellular features, as in poorly differentiated tumors, very few specimens (2 of 9) were positive. It was apparent that with the progression of de-differentiation there was a gradual loss of 1D3 antigen in human colonic tumors.

Antibodies, Monoclonal↗
PubMed1988

The impact of aggressive debulking surgery and cisplatin-based chemotherapy on progression-free survival in stage III and IV ovarian carcinoma.

Forty consecutive patients with stage III and IV invasive ovarian carcinoma were treated on a phase II protocol consisting of optimal debulking surgery, induction cisplatin, cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy, 6-month interval laparoscopy, reinduction cisplatin, PAC chemotherapy, and second-look procedure. All 40 patients have either disease progression or have completed the 12-month protocol. Eighty-seven percent of the patients (35) underwent optimal (less than or equal to 2 cm residual) debulking surgery before chemotherapy, in spite of the fact that 50% (20) were referred to Roswell Park Memorial Institute (RPMI) as inoperable after initial surgery elsewhere. There were no postoperative deaths and chemotherapy was started in less than or equal to 14 days in 97% of the patients. Of the 40 patients, 30% (12) achieved a pathologic complete remission (11) or a clinical complete remission (one patient refused second-look surgery). The estimated 3-year survival rate was 62%, but the 3-year progression-free survival rate was only 29%. The median survival time was 48 months. The estimated 3-year progression-free survival rate was 31% for residual disease less than or equal to 2 cm. For the five patients with residual disease greater than 2 cm, four died within 3 years. The median survival time of patients with less than or equal to 2 cm residual disease was 48 months, as compared with 21 months for those with greater than 2 cm residual disease. Although the estimated 3-year survival rate of 62% is noteworthy, the 3-year progression-free survival rate of only 29% is probably indicative that in spite of extensive debulking surgery and cisplatin-based chemotherapy as used in this protocol, the long range proportion of patients "cured" will remain small.

Adenocarcinoma↗
PubMed1988

Molecular approaches to learning and memory.

We are now at the stage of neurophysiology where learning and memory can be subjects of studies at a strictly molecular level, on the basis of the well-established finding that these higher nervous activities are sustained by, and formed in, the physicochemical events of specified neural mechanisms in the brain. As for the neurophysiological process of memory, much evidence has shown that short-term memory and long-term memory probably result from different molecular events in the brain, i.e., the former from reversible chemical modification of the synapses concerned, and the latter from reorganization of the synapses following synthesis of protein and its axonal transport, which causes the enduring consolidation of memories. How does the experience of individual organisms trigger the protein synthesis in the brain required for long-term memory? What is the role of protein molecules thus formed? What is the mechanism for the regulation of gene expression in the reorganization of neuronal circuits? Many such difficult problems need to be solved. Recently, cholinergic and glutamatergic neuron networks have attracted much attention because there is a strong possibility that they play a critical role in memory. The clinical implication of these findings in human memory deficit, as exemplified in senile dementia, further emphasizes the importance of neurobiological elucidation of the molecular mechanism for learning and memory.

Animals↗
PubMed1988

[Experimental study on immune serum therapy of cancer].

The effect of specific antisera to alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) are described as one of the immune serum therapy of cancer. This fundamental approach especially in case of specific antisera to AFP was developed to confirm the effect of purified antibodies to AFP and its mechanism in experimental systems. Bi-specific monoclonal antibody to hepatoma membrane antigen is also added as one of the models for application of the immune serum therapy of cancer in rats.

Animals↗
PubMed1988

[Effect of a conjugate of adriamycin and an antibody to human alpha-fetoprotein (AFP) on AFP-producing hepatic tumors].

We have studied the effect of an anti-FP antibody coupled via a dextran bridge to adriamycin on six AFP-producing liver tumors (3 cases with hepatoma and 3 cases with liver metastases from an AFP-producing gastric cancer). Results have revealed that MR was observed in 2 out the 5 of surviving evaluated cases. The toxicity of this conjugate was not evident in all cases, except for a low-grade fever. Further, an autopsy revealed no remarkable change in the histology of the case that had ended in death. These results indicate that this conjugate can be considered one of the treatment therapies available for a nonresectable AFP-producing tumor.

Aged↗
PubMed1987

Immunohistochemical studies on synapse formation by embryonic cerebellar tissue transplanted into the cerebellum of the weaver mutant mouse.

Normal cerebellar tissue, obtained from 15-day-old CBA/JNCij mouse embryos, was transplanted into the cerebellum of 4-week-old weaver mice. At the 6th week after the transplantation, the grafted tissue was distinguishable from the host cerebellum, developing a trilaminar organization. The formation of synapses by the implanted granule cells was analyzed immunohistochemically with antiserum against synaptic vesicle protein, Synapsin I. Some areas in the host cerebellum as well as in the grafted tissue were intensely stained by anti-Synapsin I serum, suggesting that the implanted granule cells make synaptic contacts with the neuronal cells.

Animals↗
PubMed1987

Therapeutic effect of treatment with polyclonal or monoclonal antibodies to alpha-fetoprotein that have been conjugated to daunomycin via a dextran bridge: studies with an alpha-fetoprotein-producing rat hepatoma tumor model.

Purified monoclonal mouse or polyclonal horse antibodies (Ab) to rat alpha-fetoprotein (AFP) were conjugated with daunomycin via a dextran bridge. The therapeutic effect of these Ab-daunomycin conjugates on an AFP-producing rat hepatoma which was inoculated s.c. in Donryu rats was studied. Tumors (s.c.) and distant metastases were present by 14 days after tumor inoculation and the serum AFP level was 35 micrograms/ml. The injection of the Ab-daunomycin conjugate, started on day 14, significantly prolonged host survival with inoculated controls having a median survival of 25 days compared to 57 and 60 days for the treated groups. In a second study the Ab-daunomycin conjugates were injected i.v. every other day for five times after the surgical resection of the s.c. tumor. There was a slight therapeutic effect with either antibody or daunomycin alone but treatment with the AFP Ab-daunomycin conjugates significantly prolonged survival and 60% of these treated animals were "tumor free" when sacrificed on day 100. Serial quantitation of the concentration of AFP in the serum of the treated tumor-bearing or in the tumor-resected rats correlated with the therapeutic effectiveness of the Ab-daunomycin conjugates. These experiments show that the optimal treatment with specific antibody-drug conjugates will be in hosts where there is a small residual tumor burden such as may exist following resection of a primary tumor mass. They further show that the serial quantitation of serum AFP can be utilized to determine if residual tumor is present following treatment with Ab-daunomycin conjugates.

Animals↗
PubMed1987

A long way from the wilderness: thirty memorable years of the Japanese Neurochemical Society.

The history and antecedents of the Japanese Neurochemical Society (JSN) are described. Particulars of the founding in 1958, and of the formal establishment in 1962, are given, together with an outline and description of the JSN's recent activities, including its contributions to the 4th International Meeting of the International Society for Neurochemistry (ISN) in Tokyo in 1973. Suggestions are made for the development of a perspective, and for the promotion, of the ultimate, fundamental purposes of neuroscience, and for the proper internalization of the JSN.

History, 20th Century↗
PubMed1987

Immunohistochemical, biochemical and electron microscopic analysis of myelin formation in the central nervous system of myelin deficient (mld) mutant mice.

Myelin deficiency (mld) is an autosomal recessive mutation in mice and is considered to be allelic to the shiverer (shi) mutation. Mld mice are characterized by hypomyelination of the central nervous system (CNS). They show typical symptoms such as tremor, tonic convulsion and ataxic movement. Subcellular fractionation of the CNS revealed that the MBP bands were greatly decreased in the P2A (myelin) fraction and the total content of myelin basic protein (MBP) was much lower than that in the control in all parts of the CNS. Sections from mld mice were examined by immunohistochemical tests with MBP antiserum, and a mosaic expression of MBP was found in the myelin of the mld mice. Since the major dense line is considered to be composed mainly of MBP, we investigated the myelin of mld mice by electron microscopy and found that there were 3 types of myelin: (1) a normal type compact myelin with a major dense line, (2) a shiverer-type myelin with no major dense line, and (3) a mixed-type myelin, in which within a myelin lamella the major dense line abruptly changes to cytoplasm of oligodendrocytes.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1987

Inefficient transcription of the myelin basic protein gene possibly causes hypomyelination in myelin-deficient mutant mice.

A hereditary dysmyelination mutation, named myelin deficient (mld), is considered to be allelic to shiverer, a deletion mutation of the myelin basic protein (MBP) gene. The present study showed that MBP expression is greatly reduced in mld, but that it is still detectable. Northern blot analysis revealed that the pronounced decrease in the MBP level in mld resulted from a reduced mRNA level and was not caused by deletion of a large portion of the MBP gene as in shiverer. Southern blot studies with BamHI-digested chromosomal DNA suggested some part of the MBP gene, at least the 5'-portion, was duplicated in mld. These results indicated that the mld and shiverer mutations were different from each other, even though genetic allelism between the two was reconfirmed. We also examined the developmental pattern of the gene expression of MBP and that of another protein, myelin proteolipid protein (PLP), specifically expressed in the oligodendrocyte, in mld by RNA dot blot study. The mRNA level of MBP in mld was greatly reduced during the active myelination stages, gradually increasing and remaining constant in the later stages. The PLP-mRNA content in mld was almost normal (60-80% that of control) at any stage of development. All these findings imply that the primary defect in mld is due to reduced transcriptional activity of the MBP gene.

Alleles↗
PubMed1987

Conjugates of mitomycin with anti-alpha-fetoprotein antibody: antitumor effect against alpha-fetoprotein-producing human gastric carcinoma implanted in nude mice.

Conjugates of mitomycin (MMC) with an affinity-purified horse anti-human alpha-fetoprotein (AFP) antibody were prepared by direct conjugation or by indirect conjugation mediated by human serum albumin; 1a-[4-(N-succinimidoxycarbonyl)butyryl]-MMC was used in the preparation. In therapeutic experiments with athymic nude mice inoculated with the human AFP-producing gastric carcinoma OSS, the conjugates caused a greater inhibition of the tumor growth than did an unconjugated mixture of anti-AFP antibody and MMC or similar conjugates with normal horse immunoglobulin. The AFP serum level and its ratio to tumor volume were low in the group of mice treated with anti-AFP conjugate. The enhanced drug activity of the anti-AFP conjugates was not observed against human gastric carcinoma YSS (no AFP production) in nude mice; this suggests the involvement of the specific antibody-antigen interaction in the activity of the anti-AFP conjugates.

Animals↗
PubMed1987

Multiple endocrine neoplasia IIA found at autopsy.

A case is presented of a 32-year-old black female who died from adult respiratory distress syndrome with disseminated intravascular coagulopathy. At autopsy she was found to have typical multiple endocrine neoplasia IIA, a combination of medullary carcinoma of the thyroid, bilateral adrenal pheochromocytoma and nodular hyperplasia of the parathyroid.

Adrenal Gland Neoplasms↗
PubMed1987

[Traumatic spinal subarachnoid hematoma presenting with Brown-Séquard syndrome].

We report a rare case of traumatic spinal subarachnoid hematoma with Brown-Séquard syndrome following hyperextension injury. A 43-year-old man was admitted to our hospital four days after hyperextension cervical injury complaining of nuchal pain, left hemiparesis and dysesthesia of the left arm. On the third hospital day, neurological examination revealed left C2,3 level Brown-Séquard syndrome. High cervical plain CT scan showed a high density area in the left spinal canal from C1 vertebral body level to C2-3 intervertebral level. Emergency operation was performed and a left-sided subarachnoid hematoma was removed. The left C2 and C3 nerve roots were markedly stretched and the cord was shifted to the right. Neither vascular abnormality nor tumor was found and no traumatic change was seen on the cord. The Brown-Séquard syndrome disappeared soon after surgery, but the weakness of the left arm and anesthesia at the level of left C2 dermatome remained until six months after operation. Review of the literature revealed no such a case as the one in which the patient developed a spinal subarachnoid hematoma following hyperextension injury without any preexisting disease or injury of the spine. Brown-Séquard syndrome caused by spinal subarachnoid hematoma was not found on the literature either. So we believe that this is the first report of case of such lesion. The mechanism of subarachnoid clot formation on hyperextension injury may be due to transient dislocation of the spine with tearing of the anterior longitudinal ligament or to crushing of the cord between the ligamentum flavum, which bulged forward on hyperextension, and the posterior aspect of the vertebral body.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Subcultured astrocytes suppress the proliferation of neuroblasts in vitro.

The effects of subcultured astrocytes on the proliferation of neuronal precursor cells (neuroblasts) from rat embryonic cerebral hemispheres were examined. The survivability of neurons and the neurite outgrowth were significantly enhanced by the subcultured astrocytes compared to those of neurons plated on poly-L-lysine-coated coverslips. The incorporation of [3H]thymidine into neuroblasts was remarkably suppressed by the subcultured astrocytes indicating that the astrocytes inhibit the proliferation of neuroblasts. These results suggest that astrocytes enhance the maturation of neuroblasts possibly via either cell-cell contact or trophic substances.

Animals↗
PubMed1986

Possible association of platelet-derived growth factor (PDGF) with the appearance of reactive astrocytes following brain injury in situ.

The association of platelet-derived growth factor (PDGF) with the appearance of reactive astrocytes following injury was investigated by using a specific antagonist of PDGF, Trapidil. The cerebral cortex of 4-week-old male rats was unilaterally injured with a 22-gauge needle. Immunohistochemical staining with antiserum to glial fibrillary acidic protein revealed that reactive astrocytes had increased in number around the wound by 2 days following the injury and had spread to the ipsilateral areas distant from the wound by 3 days. The appearance of reactive astrocytes in areas distant from the wound was dramatically suppressed by the administration of Trapidil. This finding indicates that PDGF might play a role in gliosis following injury.

Animals↗