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Biomedical subjects

T Imada

Publications and source records attributed to T Imada.

At least 145 records · Page 8Linked to original sources

Structure and physiological actions of rat atrial natriuretic factor.

Natriuretic substances were purified from rat atrium (atrial natriuretic factor, ANF) and were shown to be identical with the inhibitor of norepinephrine-induced contraction of smooth muscle. Four native forms were isolated and their amino acid sequences were determined. The presence of a high-molecular-weight prohormone was shown. Complementary DNA (cDNA) encoding for the precursor was cloned and used to deduce the amino acid sequence of the prohormone. Genomic DNA for ANF was cloned and two introns were found. Several ANF peptides were synthesized. Structure-function studies showed that the ring structure was essential for the activity. Antibodies produced against the synthetic 25-amino acid residue ANF were used to develop a radioimmunoassay. The presence of ANF in rat plasma demonstrated that ANF is a circulating hormone. ANF was also found in the hypothalamus of rats. The ANF in plasma was found to be a low-molecular form, whereas that in atria and hypothalamus consisted of both the high-molecular-weight precursor and low-molecular-weight active ANF. The presence of messenger RNA for ANF was determined using ANF cDNA as a probe and was considered as evidence for ANF synthesis in the brain, atrium, and ventricles. ANF was shown to be released from the brain. ANF administered intracerebroventricularly was shown to inhibit angiotensin II and thirst-induced dipsogenesis. In vitro and in vivo experiments showed ANF inhibits release of vasopressin from posterior pituitary and renin from the kidneys. The hypotensive effect of ANF was examined at various doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

[The effect of gastrectomy on serum 5-FU concentrations of patients administered UFT per os].

Ten post-total gastrectomy patients and five postsubtotal patients were administered with UFT 3 capsules per os. Then the concentrations of the serums FT-207, 5-FU and Uracil, and that of 5-FU in the lymph-nodes were measured chronologically. The concentration of serum FT-207 reached to its peak one hour after administration of the regimen for both the total and subtotal gastrectomy patients and gradually lowered. The 5-FU serum concentration, on the other hand, showed a rapid drop after reaching a peak one hour after administration of the UFT for both the post-total and subtotal gastrectomy patients. The concentration of 5-FU in the lymph nodes remained five times as high as the serum concentration after four hours for both the post-total and subtotal gastrectomy patients.

Adult↗

Platelet factor XIII. The collagen receptor?

We have studied the binding of collagen fibers with platelet proteins using affinity chromatography on collagen-Sepharose. Only a few proteins from a platelet lysate were trapped by this column. When denatured collagen (gelatin) was used as the affinity ligand, the major protein did not bind and was identified as platelet Factor XIII by polyacrylamide gel electrophoresis, immunoprecipitation, and enzymic activity. This is a zymogen form of transglutaminase, which corresponds to the "a" subunit of the coagulation factor in plasma. Immunoglobulins specific for platelet Factor XIII obtained from antiserum raised against plasma Factor XIII were able to initiate platelet aggregation by themselves, in strong contrast to nonspecific antibodies. This specific immunoglobulin-mediated platelet aggregation required the presence of Ca2+. It was inhibited by aspirin and prostacyclin, but not by specific inhibitors for other agonists. These data suggest the possibility that the zymogen form of Factor XIII is located on the surface of platelets and may play a key role as the receptor for collagen-induced platelet aggregation.

Animals↗

Specific desensitization in the cytoskeletal assembly of platelet by receptor-dependent activations.

Cytoskeletal assembly induced by receptor-dependent or independent activation of bovine platelets was investigated. When platelets were preactivated with receptor-dependent stimulus, ADP or thrombin, cytoskeletal assembly was not induced repeatedly by the same agonist. However, in the case of receptor-independent stimulus, cryo-activation, the assembly was induced not only by receptor-dependent but also by independent stimulus. The desensitization, therefore, lies in the transmission of stimuli from receptors to cytoskeletal proteins.

Actins↗

Atrial pressure and secretion of atrial natriuretic factor into the human central circulation.

Atrial natriuretic factor, a peptide found in mammalian cardiac atria, has natriuretic and vasodilatory properties that may be important in the regulation of intravascular volume. To study factors related to its release in human subjects, intracardiac pressures and plasma atrial natriuretic factor concentrations in the central circulation were measured in 34 patients with a variety of cardiovascular disorders. Plasma atrial natriuretic factor concentration increased from the inferior vena cava to the right atrium (76 +/- 24 to 162 +/- 37 pg/ml, p less than 0.001) and from the vena cava to the aorta (76 +/- 24 to 177 +/- 46 pg/ml, p less than 0.001). Mean right atrial pressure was positively correlated with atrial natriuretic factor concentration in the pulmonary artery (r = 0.58, p less than 0.001), and mean pulmonary capillary wedge pressure was positively correlated with concentration in the aorta (r = 0.64, p less than 0.001). In six patients whose atrial natriuretic factor concentrations were measured at two different levels of atrial pressure, increased atrial pressure was accompanied by increased atrial natriuretic factor concentration in the pulmonary artery (p less than 0.01) and aorta (p less than 0.01). Atrial natriuretic factor levels measured in fresh myocardium from a patient undergoing cardiac transplantation showed tissue concentrations in the atria 500-fold higher than tissue concentrations in the ventricles. These data document that atrial natriuretic factor is found in human atrial myocardium and suggest that it may be released in response to increased atrial pressure. Such a secretory release mechanism is consistent with the hypothesis that atrial natriuretic factor plays a role in the regulation of circulatory volume.

Adult↗

Sodium loading and posture modulate human atrial natriuretic factor plasma levels.

Atrial natriuretic factor is postulated to act through atrial stretch receptors as a volume regulatory hormone that stimulates diuresis and natriuresis in response to increased atrial pressure. To characterize the stimuli associated with the release of atrial natriuretic factor in humans, we studied 14 normal subjects, both in the supine position and after 10 minutes in an upright posture, while they were on a regular diet (Day 0) and during 3 days of supplemental sodium chloride intake (8 g/day). Radioimmunoassay of plasma atrial natriuretic factor was performed with rabbit antibody to the human hormone amino acids (102-126). Urinary sodium excretion increased from 111 +/- 13 mEq/day (mean +/- SEM) on Day 0 to 275 +/- 15 mEq/day by the third day (Day 3) of high sodium intake. The level of atrial natriuretic factor in the supine position rose from 17 +/- 4 pg/ml (Day 0) to 76 +/- 13 pg/ml on Day 3 (p less than 0.001) and after 10 minutes in an upright posture on Day 3, the level fell to 32 +/- 10 (p less than 0.005). Plasma concentrations of atrial natriuretic factor correlated positively with spot and 24-hour urinary sodium excretion and weight gain, and correlated negatively with plasma aldosterone and renin activity. We conclude that the response of atrial natriuretic factor to sodium loading and posture change in humans is appropriate for a volume regulatory hormone.

Adult↗

Atrial natriuretic factor in spontaneously hypertensive rats: concentration changes with the progression of hypertension and elevated formation of cyclic GMP.

As hypertension developed in spontaneously hypertensive rats (SHR), the plasma concentration of atrial natriuretic factor (ANF) increased whereas its tissue concentration in the atria decreased. These observations suggest that ANF is secreted from the atria in response to hypertension. Atrial natriuretic factor contents in the hypothalamus and pons decreased with ageing in Wistar-Kyoto rats (WKY) but not in SHR. The responses of various SHR tissues to the hypotensive, vasorelaxant and cyclic GMP generating effects of ANF were more pronounced than in corresponding WKY tissues. The number of ANF receptors was reduced without change in the affinity in aortic smooth muscle and adrenals of SHR with established hypertension. These findings suggest that the elevated sensitivity to ANF of blood pressure of SHR can be in part explained by the increased sensitivity to ANF of guanylate cyclase in the vascular wall of SHR.

Animals↗

[A case of malignant lymphoma of the remnant stomach].

A 46-year-old woman was transferred to our facility with the complaint of epigastric discomfort of more than four months duration. She had undergone partial gastrectomy with Billroth I anastomosis 19 years prior to the admission. An upper GI series revealed multiple, variously sized elevated lesions scattered over the remnant stomach. Fiberscopic examination showed the gastric mucosa replaced by several elevated lesions and giant fold embellished by erosion, injection, and necrotic debris. Pathological examination revealed malignant lymphoma of the large cell type whose main growth was in the mucosa and submucosa. This case was significant in that malignant lymphoma occurred in the remnant stomach and that the tumor converted M-protein in the serum, which was confirmed as IgM-k in the cytoplasma immunohistochemically.

Blood Proteins↗

[Mechanism by which peritoneal disseminated metastasis develops in gastric cancer].

To clarify the peritoneal dissemination of gastric cancer 270 resected specimens were analyzed by methylene blue formalin fixation staining method. As a result, not only metastasis to lymph nodes but also very small disseminated metastatic lesions which had been overlooked before were observed in the greater omentum and lesser omentum. The relationship among this disseminated lesion, macroscopic peritoneal disseminated metastatic lesion, degree of serosal infiltration, area of infiltration and tissue type of the tumor was studied. The very small disseminated metastatic lesion was judged to be Po, accounting for 15.3 percent and 28.1 percent of 270 resected cases were positive for disseminated metastasis. Disseminated metastasis developed relatively early. The incidence of disseminated metastasis was higher in the poorly differentiated type than in the well-differentiated one. The case which showed break of the capsule of lymph node and infiltration into the area around lymph node accounted for 45.0 percent of the positive cases of lymphatic metastasis. Since very small disseminated lesions are present in the greater omentum, lesser omentum and the area around lymph node as described above, radical operation should been bloc resection of these lesions in gastric cancer.

Humans↗

Changes in the content of atrial natriuretic factor with the progression of hypertension in spontaneously hypertensive rats.

In order to assess possible roles of atrial natriuretic factor (ANF) in spontaneously hypertensive rats (SHR), we examined the content of immunoreactive-ANF in plasma, the atria, hypothalamus and pons of SHR and Wister Kyoto (WKY) rats by radioimmunoassay at different stages of age. With the progression of hypertension, plasma concentration of ANF increased whereas it decreased in the atria in SHR. This suggests ANF is secreted in response to hypertension. On the other hand, at hypothalamus and pons, ANF content was significantly higher in SHR than in WKY rats. This finding suggests possible involvement of ANF in the central regulation of blood pressure.

Aging↗

Lysis of platelets and erythrocytes by the incorporation of a unique oxygenated sterol: 22R-hydroxycholesterol.

We have found that an oxygenated sterol, 22R-hydroxycholesterol [(22R)-5-cholestene-3 beta, 22-diol], lyses not only platelets but also erythrocytes in a dose-dependent manner. The lysis of platelets and erythrocytes were evidenced by the release of intracellular proteins, lactate dehydrogenase and hemoglobin, respectively. Their morphological change was shown by scanning electron microscopy. Elevated temperature was required for the lysis, probably to redistribute the sterol in the lipid bilayers in the plasma membranes. When the sterol was incorporated at low temperature, the temperature had to be raised to readily lyse cells. This lytic effect was, surprisingly enough, restricted to the R-isomer; the S-isomer was only marginally effective. Furthermore, sitosterol and other oxygenated sterols, with a hydroxyl group at different positions in the side chain of cholesterol, were much less lytic, regardless of the configuration of the hydroxyl group introduced. A possible mechanism for this interesting phenomenon will be discussed in relation with a structural alteration in lipid bilayers in plasma membranes brought about by the incorporation of this unique oxygenated sterol.

Animals↗

Pathology of spontaneous colibacillosis in a broiler flock.

Forty-eight of 134 chickens collected from a flock on a broiler farm were diagnosed pathologically and microbiologically to have colibacillosis. Both acute septicemia (seven birds, 1 to 36 days old) and subacute serositis (41 birds, 5 to 57 days old) were found. The former consisted of necrosis with fibrinous exudates in the ellipsoids and lymphoid follicles of the spleen, and fibrinous thrombi in sinusoids of the liver with occasional necrosis of hepatic cells. The latter had fibrinopurulent inflammation with granulomatous changes in the serosal tissues--including the epicardium, pericardium, and hepatic peritoneal sac--accompanied by septicemic lesions in the spleen and liver. Respiratory lesions (airsacculitis, pneumonia, and tracheitis) were noted in most chickens affected with acute septicemia and subacute serositis. Degenerative changes also were observed in the bursa of Fabricius.

Acute Disease↗

Pathologic changes caused by transplacental infection with an adenovirus-like agent in pigs.

Five hysterectomy-derived colostrum-deprived pigs housed in individual cages with positive ventilation developed severe skin cyanosis and edema of the subcutaneous tissues in the submandibular, thoracic, and abdominal regions. The 5 pigs were killed 7 to 10 days after birth. Eosinophilic intranuclear inclusion bodies were found in endothelial cells of capillary and small blood vessels throughout the body. Ultrastructurally, nuclei of these affected endothelial cells contained small crystalline arrays of virus particles, which were considered to belong to the adenovirus-like group from their size and structure. The present results indicated that the porcine adenovirus-like agent might also have the ability to produce transplacental infection.

Adenoviridae↗

Agonist-specific desensitization of shape change of platelets.

Using scanning electron microscopy and light scattering we have investigated the shape change of bovine platelets. The extents of shape change obtained by ADP and 5-hydroxytryptamine(5HT) increased in dose-dependent manner, and the maximum obtained by these agonists were additive. The agonist-specific desensitization in shape change was observed with ADP, 5HT and thrombin. The extent of desensitization by pre-exposure to ADP was dependent upon the concentration of ADP. It was strongly indicated that receptors or their subsequent stimuli-transmission apparatus became unable to respond to further stimulation after the exposure to the initial stimulation.

Adenosine Diphosphate↗