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Biomedical subjects

T Tsukada

Publications and source records attributed to T Tsukada.

At least 235 records · Page 13Linked to original sources

Induction of spermidine/spermine N1-acetyltransferase in needle-punctured rat lens as a model of traumatic cataract.

Isolated rat lens was punctured with a needle at a single point in the equatorial region and was incubated at 37 degrees C. Spermidine/spermine N1-acetyltransferase activity was increased about 5-fold at 8 h after the puncture. Concomitantly, putrescine content in the lens increased markedly at 8-16 h after the puncture, while spermidine levels were slightly depressed. Pretreatment of the lens with actinomycin D or cycloheximide blocked the increases of spermidine/spermine N1-acetyltransferase activity and putrescine content. Ornithine decarboxylase, on the other hand, was not induced to a detectable degree by this stimulus and 5 mM difluoromethylornithine could not block the increase of putrescine content. Polyamine oxidase showed a relatively constant activity that was sufficient for the metabolism of newly formed N1-acetylspermidine. These results suggested that, in the punctured lens, the polyamine levels were regulated predominantly by the activity of spermidine/spermine N1-acetyltransferase, but not by the induction of ornithine decarboxylase.

Acetyltransferases↗

Antitumor effect of methylglyoxal bis(butylamidinohydrazone), a new inhibitor of S-adenosylmethionine decarboxylase, against human erythroid leukemia K 562 cells.

Methylglyoxal bis(butylamidinohydrazone) (MGBB) inhibited S-adenosylmethionine decarboxylase (SAMDC) activity competitively with S-adenosylmethionine (SAM) showing the Ki value of 1.8 X 10(-5) M. MGBB showed less SAMDC-stabilizing effect in rat liver in vivo than did methylglyoxal bis-(guanylhydrazone) (MGBG). MGBB inhibited the growth of human erythroid leukemia K 562 cells. Putrescine, spermidine and spermine concentrations in MGBB-treated cells were depressed to 56%, 58% and 88% of the values of control cells, respectively. [35S]Methionine incorporation into trichloroacetic acid-insoluble fraction was decreased in the inhibitor-treated cells.

Adenosylmethionine Decarboxylase↗

Changing pattern of age-specific prevalence of hepatitis B surface antigen and corresponding antibody in Japan.

During the period 1978-1984 in Japan, the prevalence of hepatitis B surface antigen (HBsAg) in age groups below age 15 years was 18/2,550 (0.7%), and it was particularly low in the group below age 5 years (2/706 (0.3%)). The low prevalence of HBsAg in children under 15 years of age contrasted sharply with the much higher prevalence in persons age 15 years and older (36/2,050 (1.8%)). In accord with this, the prevalence of antibody to hepatitis B surface antigen (anti-HBs) was much lower in children below age 15 years than that in persons 15 years of age and older (29/2,550 (1.1%) vs. 242/2,050 (11.8%)). Furthermore, the prevalence of hepatitis B viral markers in 1978-1984 was lower than that during the period from 1972-1977 in every age group. A total of 13 (81%) of 16 mothers of carrier children, identified in 1978-1984, were positive both for HBsAg and hepatitis B e antigen in their sera. Now that mother-to-baby transmission appears to be the main route for establishing the persistent carrier state, its interruption should reduce the reservoir of hepatitis B virus, toward its eventual eradication, in Japan.

Adolescent↗

Inhibition of erythropoiesis by human parvovirus-containing serum from a patient with hereditary spherocytosis in aplastic crisis.

Aplastic phase serum from a patient with aplastic crisis of hereditary spherocytosis, which was demonstrated to contain human parvovirus, inhibited in vitro erythroid colony formation almost completely. Human parvovirus was resistant to heating for 30 min at 56 degrees C. The suppressive effect of the serum was completely abrogated by adding convalescent phase serum from another patient with aplastic crisis of hereditary spherocytosis. Some normal sera had similar neutralizing ability. The results suggested that aplastic crisis of a patient with hereditary spherocytosis is caused by human parvovirus and that the neutralizing test could offer a tool for predicting the future occurrence of aplastic crisis in the patients with chronic hemolytic anemia.

Adolescent↗

Changes in components of fast axonally transported proteins in the optic nerves of diabetic rabbits.

Proteins synthesized in retinal ganglion cells were labeled with 35S-methionine or 3H-leucine to the vitreous cavity, and the components of fast axonally transported proteins were studied in 20 nerves of 10 normal rabbits and 34 nerves of 17 alloxan-induced diabetic rabbits. Proteins in the optic nerves were separated by SDS-polyacrylamide gel electrophoresis, and axonally transferred proteins were studied by fluorography. In diabetic animals, the axonally transported radioactivity was one-fifth that of the controls. In the fluorographic spectrum of 35S-methionine-labeled proteins, relative proportion of 120kDalton(D)-proteins were increased by 43%, and 29kD proteins were decreased by 65% in diabetic rabbits. Relative proportion of other proteins, such as 24k, 36k, 68k, 150k and 180kD, were the same in control and diabetic rabbits. The quantitative reduction and change in spectrum of fast axonally transported proteins are compatible with the vulnerability and dysfunctions of nerve fibers in diabetic patients.

Animals↗

Immunoglobulin class switch from IgG to IgA in a patient with smoldering multiple myeloma.

Serum of a 67-year-old male patient with smoldering multiple myeloma was shown to contain two monoclonal immunoglobulins, IgG and IgA. For the initial seven months, monoclonal IgG was predominantly elevated. During the next one year and eight months, however, serum concentration of the monoclonal IgA increased, with a concomitant decrease of IgG. N-terminal amino acid sequences of heavy and light chains separated from monoclonal IgG and IgA were analyzed. Both light chains were lambda-type and showed identical amino acid sequences of variable regions. The heavy chains also had the same N-terminal amino acid sequence between IgG and IgA. These results strongly suggest that two monoclonal proteins, IgG and IgA, in this patient were produced by B lymphocytes within a clone and that class switch from IgG to IgA in immunoglobulin production during B cell differentiation has taken place in the clinical course of this case.

Aged↗

A new method to measure the pattern reversal visual evoked response in infants and young children.

A modification was made of the conventional method of recording the pattern reversal visual evoked response (VER) to study the VER in infants and young children. Application of this modified method to 36 patients, the majority of them with retinopathy of prematurity, showed that this method is useful in the evaluation of the visual function in infants and young children, and also in a 12-year-old mentally retarded girl.

Child↗

Human atherosclerosis. II. Immunocytochemical analysis of the cellular composition of human atherosclerotic lesions.

The authors have performed immunocytochemical investigations of the distribution of various cell types in human atherosclerotic plaques using monoclonal antibodies specific to smooth muscle cells (CGA7 [Gown et al, J Cell Biol 1985, 100:807-813] and HHF35 [Tsukada et al, Am J Pathol (In press)] ); lymphocytes (T200 antigen); endothelial cells (Factor VIII and the Ulex europeus agglutinin); and macrophages, the latter with a new macrophage-specific antibody HAM56. All studies were performed on methanol-Carnoy's-fixed, paraffin-embedded tissues. In areas of grossly normal aorta, significant numbers of macrophages were noted within areas of diffuse intimal thickening. The cellular composition of the following three types of raised lesions were analyzed: fibro-fatty lesions, which, despite their gross appearance, consistent with fibrous plaques, were composed almost exclusively of macrophages and lymphocytes and almost devoid of smooth muscle cells; fibrous plaques, which were predominantly composed of smooth muscle cells displaying considerable morphologic heterogeneity and an admixture of blood-borne cells; advanced plaques, which were characterized by complex layers of smooth muscle cells and macrophages with considerable variation from region to region. Also noted were foci of medial and even intimal vascularization subjacent to the more advanced plaques. These studies demonstrate the application of monoclonal antibody technology to the study of the cellular composition of human atherosclerotic lesions.

Adult↗

[Clinical effects of TA-077 in non-Hodgkin's lymphomas].

Ten patients with non-Hodgkin's lymphomas (NHL), six untreated and four with previous chemotherapy, were treated with TA-077, a new derivative of nitrosourea. Partial remission was observed in three untreated cases (30%) of NHL [Case 1: 71-year-old female with B cell lymphoma/diffuse small cell type, Case 2: 79-year-old male with T cell lymphoma/diffuse large cell type, and Case 3: 64-year-old female with adult T cell leukemia lymphoma (ATLL)]. Remission durations were as follows: Case 1; 33 days, Case 2; 38 days and Case 3; 14 days. Side effects were transient anorexia (40%), nausea & vomiting (30%), liver dysfunction (10%) and delayed hematological toxicities (80%). Hematological toxicities consisted of leukocytopenia (80%), thrombocytopenia (60%) and anemia (20%). Our study suggests that TA-077 is a useful agent as one of the drugs used in combination chemotherapy against NHL, since it was effective for refractory T cell malignancies such as ATLL.

Adult↗

Effect of chronic denervation on pharmacological responsiveness of coronary vessels.

We have hypothesized that the well-established regional heterogeneity of the properties of the vascular smooth muscle results from peculiarities of the microenvironment in every region. In particular, the coronary vasculature has well-established differences between large and small coronary arteries in their responsiveness to alpha and beta agonists, nitroglycerin and adenosine. To test our hypothesis, we altered the micro-environment of coronary vessels by chronic surgical sympathectomy in dogs. Our in vitro studies on vessels from normally innervated hearts confirmed previous studies and showed that in large vessels, alpha and beta epinephrine or norepinephrine responses can be demonstrated; the alpha effect is dominant and epinephrine is a more potent alpha agonist than is norepinephrine. In small vessels only a beta catecholamine effect can be demonstrated. Chronically sympathectomized blood vessels show an alpha norepinephrine effect in small vessels. Denervation caused a reduction in the sensitivity to K+-induced contraction in both large and small vessels. In large vessels the responses to nitroglycerin were not affected by denervation, whereas in small vessels the sensitivity to adenosine was reduced. These results indicate that chronic denervation alters the pharmacological responsiveness of the vasculature to various agonists indicating that vascular smooth muscle possesses the ability to respond to long-term modulatory influences arising in the immediate environment.

Adenosine↗

Structure of the human vasoactive intestinal polypeptide gene.

Vasoactive intestinal polypeptide (VIP) is a 28-amino-acid hormone produced primarily by neural tissues. The amino acid sequence of VIP is similar to that of a number of gastrointestinal hormones, including glucagon and secretin. VIP is synthesized as part of a polyprotein, pre-proVIP, which generates, in addition to VIP, an additional bioactive peptide known as PHM. As a first step toward understanding the molecular basis of pre-proVIP gene expression, we have isolated the pre-proVIP gene and have determined its structure. The gene is approximately 9 kb long and is interrupted by six introns which appear to divide the gene into functional domains. One of the introns occurs within the 3'-untranslated region of the gene.

Amino Acid Sequence↗

Modulation of luteinizing hormone(LH) release by clonidine and opioid peptides in castrated male rats.

The effect of clonidine, a central alpha-adrenergic agonist, on the suppression of LH release induced by beta-endorphin or FK33-824, an endogenous opioid peptide or its synthetic analog, was investigated in castrated male rats, with or without pretreatment with reserpine. Pulsatile LH secretion was inhibited by intravenous injection of FK33-824 (400 micrograms/kg), or intraventricular injection of beta-endorphin (5 micrograms). Without pretreatment with reserpine, intraperitoneal administration of clonidine (1 mg/kg) failed to reverse the inhibition of LH release induced by these peptides. However, with pretreatment with reserpine (10 mg/kg), clonidine abolished the inhibitory effect on LH secretion induced by these peptides in castrated male rats. These data indicate that, unlike the results in ovariectomized, steroid-primed rats, pretreatment with reserpine allows the alpha-adrenergic system to act more peripherally than the opioid neuronal system in a neuronal network-regulating LH release in castrated male rats.

Animals↗