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Biomedical subjects

Y Tsukada

Publications and source records attributed to Y Tsukada.

At least 145 records · Page 8Linked to original sources

Alpha-fetoprotein (AFP)-producing gastric carcinoma. Is it hepatoid differentiation?

Biochemical and immunohistochemical analyses were done on five cases of gastric carcinoma with excessive production of alpha-fetoprotein (AFP). Histologic and ultrastructural examination of these cases showed conventional poorly differentiated adenocarcinoma of cuboidal or polygonal tumor cells in the medullary area with scattered AFP-positive cancer cells. Comparative studies on serum AFP between these cases and in hepatocellular carcinoma (HCC) or in testicular yolk sac tumor cases using concanavalin A (ConA)-affinity and lens culinalis agglutinin A (LCA)-affinity sepharose columns revealed that the AFP derived from four cases had a high ConA nonadsorping rate and high LCA-reactive fraction similar to that of yolk sac tumor. The AFP from one case had a small LCA-reactive fraction similar to that of HCC. Further immunohistochemical study using several markers for liver cells or germ cell tumor did not show additional evidence of these tumor cells to differentiate into liver cells or yolk sac tumor cells. Thus, this study indicates that AFP-producing gastric carcinomas are not always derived from hepatoid differentiation of the foregut. These gastric carcinomas might be categorized into medullary tumor with gastrointestinal tract-specific AFP.

Adenocarcinoma↗

Histochemical studies on hyaluronic acid in the developing human retina.

Changes in the distribution of hyaluronic acid in the developing human retina were investigated histochemically with alcian blue staining and the Streptomyces hyaluronidase digestion method using 56 human embryos and fetuses ranging from 5 to 41 weeks of gestational age. Hyaluronic acid was first detected in the inner layer of the retina at 12 weeks. The site of accumulation extended towards the outer layer by 20 weeks. At the neonatal stage, longitudinal fibers, possibly the processes of Müller cells, were proved to contain hyaluronic acid. These findings suggest that Müller cells produce hyaluronic acid transiently from 12 weeks' gestation to the neonatal stage.

Aged↗

Increased uptake sites for serotonin and dopamine with decreased S2 serotonin receptors in microencephalic rat brain.

Methylazoxymethanol (MAM)-induced cerebral hypoplasia resulted in a significant increase in densities of both serotonin uptake sites in frontal cortex and dopamine uptake sites in striatum, suggesting serotonergic and dopaminergic axons terminals were compressed in the smaller brain volumes. The density of S2 serotonin receptors in MAM-lesioned frontal cortex was decreased probably due to down-regulation, while densities of D1 and D2 dopamine receptors in striatum were identical between MAM-lesioned rats and control rats.

Abnormalities, Drug-Induced↗

Intraoperative frozen section diagnosis of depth of myometrial invasion in endometrial adenocarcinoma.

From January 1981 to December 1988, a prospective trial was conducted on 216 consecutive patients undergoing hysterectomy for FIGO stage I endometrial adenocarcinoma to determine the accuracy of intraoperative frozen section (IFS) diagnosis of depth of myometrial invasion. IFS and D&C diagnoses were compared to the permanent section diagnosis to determine their accuracy. Patients with an IFS or D&C diagnosis of grade 3 carcinoma, deep myometrial invasion, cervical invasion, or adnexal involvement were considered high risk for paraaortic nodal metastasis, and paraaortic lymphadenectomy was performed. IFS correctly diagnosed the depth of myometrial invasion in 194 of 204 cases (95%). The sensitivity of IFS diagnosis of deep invasion was 87%, the specificity was 99%, the positive predictive value was 98%, and the negative predictive value was 94%. Grade, subtype, cervical invasion, and adnexal involvement were also accurately diagnosed. Based on IFS and D&C diagnosis, paraaortic lymphadenectomy was performed in 32% of patients, while 68% were considered low risk and were spared paraaortic lymphadenectomy. Eight patients (5%) were incorrectly diagnosed as low risk and did not have paraaortic lymphadenectomy performed. Sixty-five of seventy-three (90%) patients considered high risk on permanent section had paraaortic lymphadenectomies performed on the basis of IFS and D&C diagnosis. Inaccurate IFS diagnosis of depth of myometrial invasion can occur when tumor involves the uterine isthmus or cornua and when tumor invades areas of adenomyosis.

Adenocarcinoma↗

FK506, a novel immunosuppressive agent, induces antigen-specific immunotolerance in active Heymann's nephritis and in the autologous phase of Masugi nephritis.

FK506 is a new drug which has potent immunosuppressive activity. We studied its immunosuppressive effects on active Heymann's nephritis and the autologous phase of Masugi nephritis. The induction of active Heymann's nephritis was completely suppressed by FK506 injected simultaneously with the antigen (day 1) and then daily for 14 days at a dose of 0.64 mg/kg per day or more. With a lower dosage of this agent, antibody production and immune deposits in the glomerular basement membrane occurred despite the suppression of proteinuria. Similar results were obtained in rats on other treatment schedules (1-7 days or day 8-14 days duration). Rats that were prevented from developing Heymann's nephritis or the autologous phase of nephrotoxic antiserum nephritis by FK506 treatment exhibited a suppressed immune response to a second immunization of the same antigen even 4 weeks after cessation of drug administration: however, they developed antibodies when inoculated with other antigens. Rat peripheral leucocyte counts and serum creatinin were not remarkably influenced by the administration of FK506. These results indicate that FK506 has potent immunosuppressive activity, and it is suggested that it is able to induce an antigen-specific immunotolerance.

Animals↗

Xenogeneic neural transplantation: role of vasculature and MHC antigen in immunological rejection.

The reconstruction of blood vessels in a graft is one of the important events inducing immunological rejection. First, we investigated the reconstruction of blood vessels in a graft by using a monoclonal antibody against mouse endothelial surface antigen 1. Secondly, the lymphocyte proliferative response to Ia antigen were examined in mixed lymphocyte cultures by using monoclonal antibodies against Ia antigen. The results show that the blood vessels originating in the host tissue inoculate with those originating in the donor graft tissue and that the expression of Ia antigen on the vascular endothelial cells plays an important role in the immunological rejection through sensitization of peripheral lymphocytes.

Animals↗

The classification of the low birth-weight infants from the viewpoint of mental development.

Periodical checkups on 206 infants were carried out in order to elucidate which of various factors would pose decisive influence upon the retardation of mental development after birth with the AIKEN method. Correlations between average DQ (development quotient) and figures of physical measurements at birth were sought after. Consequently, weeks of gestation, body weight, cephalic circumference and body length at birth revealed certain correlation with the retardation of mental development. Multiple regression analysis disclosed highly significant correlations of body length and cephalic circumference toward the birth weight. Therefore, both weeks of gestation and birth weight are the direct contributory factors to average development quotient. Based on this result, a prediction equation for the mental development after birth has been proposed. Low average DQ was found in high percentages among infants born with toxemia of pregnancy or premature rupture of membranes. However, it is suggested that they are not the direct causes of such retardation, but are rather provoking short weeks of gestation and low birth weight. In summary, the newborn with less than 37 weeks of gestation and below 2,000 grams of birth weight would be named and classified as a SFD (small for dates) with the problem for mental development (MD-SFD).

Birth Weight↗

[A determination of anti-insulin receptor antibody in serum--a radioreceptor assay excluded the influence of insulin and anti-insulin antibody].

We studied an anti-insulin receptor antibody (IRAb) assay that excludes the influence of serum insulin and anti-insulin antibody in patients with anti-insulin antibody and normal subjects. The placental membranes strongly bound with 125I-insulin at 4 degrees C. The insulin specificity of the radioreceptor assay was confirmed by adding excess non-labeled insulin and other human hormones to the assay system. The strong correlation between the receptor binding reactivity (%) and the anti-insulin antibody levels was noted in the conventional direct IRAb assay (r = -0.95), but not in the present IRAb assay (r = 0.46) in 10 clinical samples. The placental membranes were stable as the target insulin receptor for IRAb assay at -80 degrees C for at least 4 months. A significant difference in IRAb levels was found between 10 patients with positive anti-insulin antibody and 20 normal controls (p less than 0.01, student t test). The coexistence of insulin and anti-insulin antibody were removed by absorbance to silicagel and by utilizing the two-step (indirect) assay, respectively. IRAb assay without the influence of serum cofactors showed excellent reproducibilities (CV 4.4% (N = 5) and 12.5% (N = 5) in within and between assay variations, respectively).

Autoantibodies↗

[Clinical significance of measurement of plasma melatonin concentration in women with irregular menstrual cycles].

To study the effects of melatonin on the human hypophyseal ovarian axis, we measured the concentrations of melatonin in the plasma of women with a regular menstrual cycle and of women with an abnormal menstrual cycle, at days 5 through 10 after the onset of menstruation or withdrawal bleeding. In seven women with a regular menstrual cycle, there was a tendency for the plasma melatonin concentration to gradually decrease chronologically from 49.0 +/- 9.8pg/ml (M +/- S.E.) at 9:30 h to 19.0 +/- 4.0pg/ml at 12:00 h. On the other hand, the plasma melatonin concentration at 21:30 h was 50.3 +/- 7.4pg/ml which was almost the same as the level at 9:30 h, while the concentration during the night significantly increased chronologically to 106.3 +/- 28.6pg/ml at 24:00 h. By comparing the plasma melatonin concentration measured during the day with that measured during the night, a significant difference was discovered after 21:40 h (p less than 0.05). The plasma melatonin concentration at 10:00 h and 22:00 h in 20 women with a regular menstrual cycle was 28.1 +/- 3.4pg/ml and 72.2 +/- 9.9pg/ml, respectively, showing a diurnal rhythm with a significantly higher level during the night than during the day. On the other hand, the plasma melatonin concentration in most of the women with an anovulatory cycle or amenorrhea was within the range of the mean level of +/- 1.5 x the standard deviation obtained from the 20 women with a regular menstrual cycle. However, an increase in plasma melatonin during the night was not found in three of nine women with an anovulatory cycle and one of two women with second grade amenorrhea.(ABSTRACT TRUNCATED AT 250 WORDS)

Circadian Rhythm↗

Metastatic patterns in histologic variants of ovarian cancer. An autopsy study.

The autopsy findings of 428 patients with various histologic types of ovarian cancer were studied to determine if metastatic patterns were different. Epithelial tumors were the most frequent (89%), followed by sarcomas (7.2%). Germ cell and stromal tumors each occurred in 1.9% of cases. Sites of metastasis were nearly identical, with no statistical difference among histologic types. The peritoneum was most frequently involved (83% to 100% of cases), but lymph node metastasis was common (50% to 60% of cases). Metastasis was more common to the paraaortic lymph nodes than to the pelvic lymph nodes. In seven of eight stromal tumors, hepatic metastasis was present but did not cause the patient's death. For epithelial tumors, metastasis to distant sites was dependent on nodal and intraperitoneal disease. However, this was not true in the 31 ovarian sarcomas or the series of germ cell or stromal tumors. This finding supports a hematogenous route of metastasis for ovarian sarcomas. Understanding the metastatic potential of ovarian cancer is important in designing effective treatment regimens.

Adult↗

Overcoming effect of antibody against rat alpha-fetoprotein (AFP) on the growth of daunorubicin-resistant mutant rat ascites hepatoma cell line AH66.

A daunorubicin (DNR)-resistant variant (AH66DR) of alpha-fetoprotein (AFP)-producing rat ascites hepatoma AH66 was established. AH66DR was 169 times more resistant to DNR than AH66. A growth-inhibitory effect due to the decrease in sugar uptake following treatment of the cell lines with specific antibody against highly purified rat AFP was also observed. Pre-incubation of both lines with antibody prior to the measurement of 2-deoxy-D-glucose (2dG) uptake resulted in a 45-55% decrease in 2dG uptake compared to control cells with a 2-fold reduction of Vmax value while the Km remained unchanged. Upon pre-incubating AH66DR with antibody, an increased intracellular level of DNR concentration with reduction of efflux rate was observed. A significantly superior cytotoxic effect against AH66DR, which reached almost the same level as the cytotoxic effect of DNR against AH66, was found, as compared to various other controls when tumor cells were cultured with a mixture of antibody and DNR. Our in vitro results suggest that the DNR-resistance of the AFP-producing tumor cells may be overcome if the cells are treated with specific antibody.

Animals↗

Mosaic reconstruction of blood vessels in mouse neocortical tissue transplanted into the third ventricle of rat brain.

Newborn mouse neocortical tissue was transplanted into the third ventricle of rat brain and the reconstruction and the origin of the blood vessels were investigated by using a monoclonal antibody against mouse endothelial surface antigen-1 (MESA-1). It was clearly demonstrated that some of the blood vessels in the graft originated in the donor mouse neocortical tissue. An India ink perfusion experiment revealed that the blood was supplied to the MESA-1-positive blood vessels. Furthermore, electron microscopic immunohistochemical studies demonstrated the existence of a mosaic reconstruction of blood vessels which consisted of mouse- and rat-derived vascular endothelial cells. It was concluded that the blood vessels originating in the donor tissue and those originating in the host tissue inoculate with each other in the grafted tissue.

Animals↗

Loss of heterozygosity on the short arm of chromosome 3 in carcinoma of the uterine cervix.

Loss of genes at specific chromosomal loci is a common genetic alteration in human tumors and is thought to be critical for unmasking the recessive genetic changes for tumorigenesis. To learn whether such recessive mutations are involved in the development of carcinoma of the uterine cervix, 18 fresh tumors were analyzed by Southern blot hybridization using 34 polymorphic DNA markers covering 19 different chromosomes. We found loss of heterozygosity at the D3S2 locus on chromosome 3p in all nine patients who could be evaluated. Human papillomavirus type 16 and type 18 were present in seven and three of 18 tumors, respectively, while no amplification of 13 oncogenes, including c-myc and H-ras, was detected in these tumors. These results suggest that recessive genetic changes on chromosome 3p are one of the important genetic alterations for the development of carcinoma of the uterine cervix. Since this locus is also lost commonly in lung cancer and in renal cell carcinoma, it is possible that these three different types of adult tumors result from mutations of the same recessive gene on chromosome 3p.

Blotting, Southern↗

Expression of Ia antigen on vascular endothelial cells in mouse cerebral tissue grafted into the third ventricle of rat brain.

The mechanisms of the immunological rejection after xenogeneic neural transplantation were investigated with special reference to the expression of class II major histocompatibility complex (MHC) antigen (Ia antigen) on the grafted tissue. Tissue from a newborn mouse cerebral cortex was transplanted into the third ventricle of a 4-week-old rat brain. Infiltration of cytotoxic T-cells into the grafted tissue was investigated immunohistochemically by using a monoclonal antibody (OX-8). The infiltration began 8 days after transplantation and continued until about 4 weeks when the tissue was completely rejected. The expression of Ia antigen was also investigated immunohistochemically. The Ia antigen was first detected in the grafted tissue at 6 days after transplantation. The Ia antigen was considered to be expressed on the vascular endothelial cells judging from the staining patterns and the location of India ink which was perfused from the host's left cardiac ventricle. The perfusion experiments with India ink also revealed that blood was supplied to the grafted tissue from 5 days after transplantation. These results suggest that the expression of Ia antigen on the vascular endothelial cells renders the grafted tissues competent to initiate and participate in the immune reaction. The results also raise a possibility that the expression of Ia antigen is triggered by blood supplied from the host brain. In addition, the results indicate that the Ia-positive blood vessels do not originate in the host brain but are intrinsic to the grafted tissue.

Animals↗