Search PubMed⌕ Search

Biomedical subjects

T Suda

Publications and source records attributed to T Suda.

At least 469 records · Page 26Linked to original sources

Colocalization of corticotropin-releasing factor and vasopressin in the paraventricular nucleus of the human hypothalamus.

The anatomical relationship between corticotropin-releasing factor (CRF)-containing cells and arginine vasopressin (AVP)-containing cells in the human hypothalamus was investigated by immunocytochemistry. In the paraventricular nucleus of the hypothalamus (PVH), CRF-like immunoreactivity (CRF-LI) was present exclusively in parvocellular cells, while AVP-like immunoreactivity (AVP-LI) was present in both parvocellular and magnocellular cells. No CRF-immunoreactive neurons were observed in the supraoptic nucleus. All CRF-immunoreactive parvocellular cells in the PVH were also AVP immunoreactive. We confirmed the presence of AVP in the CRF-immunoreactive cells by using two kinds of anti-AVP antisera, one of which recognized the side chain of AVP while the other recognized the ring structure of AVP. Colocalization of CRF-LI and AVP-LI was observed not only in the same perikarya but also in the same nerve fibers of parvocellular cells. The present results raise the possibility that AVP and CRF may be secreted together into the human portal circulation.

Adolescent↗

Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors.

The mechanism of action of macrophage colony-stimulating factor (M-CSF) in osteoclast development was examined in a co-culture system of mouse osteoblastic cells and spleen cells. In this co-culture, osteoclast-like multinucleated cells (MNCs) were formed within 6 d in response to 10 nM 1 alpha,25(OH)2D3 added only for the final 2 d of culture. Simultaneously adding hydroxyurea for the final 2 d completely inhibited proliferation of cultured cells without affecting 1 alpha,25(OH)2D3-stimulated MNC formation. Autoradiographic examination using [3H]-thymidine revealed that osteoclast progenitors primarily proliferated during the first 4 d, whereas their differentiation into MNCs occurred predominantly during the final 2 d of culture in response to 1 alpha,25(OH)2D3. When anti-M-CSF antibody or anti-M-CSF receptor antibody was added either for the first 4 d or for the final 2 d, the MNC formation was similarly inhibited. In co-cultures of normal spleen cells and osteoblastic cells obtained from op/op mice, which cannot produce functionally active M-CSF, the lack of M-CSF either for the first 4 d or for the final 2 d failed to form MNCs in response to 1 alpha,25(OH)2D3 added for the last 2 d. These results clearly indicate that M-CSF is indispensable for both proliferation of osteoclast progenitors and their differentiation into mature osteoclasts.

Animals↗

Corticotropin-releasing hormone, proopiomelanocortin, and glucocorticoid receptor gene expression in adrenocorticotropin-producing tumors in vitro.

To differentiate between ectopic ACTH syndrome and Cushing's disease, gene expression of corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC), and glucocorticoid receptor was examined in 10 pituitary adenomas (Cushing's disease) and in 10 ectopic ACTH-producing tumors. CRH increased plasma ACTH levels in all patients with Cushing's disease and in five patients with ectopic ACTH syndrome whose tumors contained CRH and CRH mRNA. In five CRH nonresponders, CRH was not detected in tumors that contained no CRH mRNA or that contained only long-size CRH mRNA. Dexamethasone (Dex) decreased plasma ACTH levels in all patients with Cushing's disease and in three patients with ectopic ACTH-producing bronchial carcinoid. These tumors contained glucocorticoid receptor mRNA. CRH increased and Dex decreased ACTH release and POMC mRNA levels in pituitary adenoma and bronchial carcinoid cells. PMA increased POMC mRNA levels only in carcinoid cells. These results reveal characteristics of ectopic ACTH-producing tumors: long-size CRH mRNA and PMA-induced POMC gene expression. In addition, there are two ectopic ACTH syndrome subtypes: tumors containing ACTH with CRH (CRH responder) and tumors without CRH. Dex decreases ACTH release and POMC mRNA levels in some bronchial carcinoids. Therefore, CRH and Dex tests have limited usefulness in differentiating between Cushing's disease and ectopic ACTH syndrome.

8-Bromo Cyclic Adenosine Monophosphate↗

The biological roles of the third component of complement in osteoclast formation.

We previously reported that 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] tissue-specifically stimulated the production of the third component of complement (C3) in bone in vitro and in vivo. In the present study, we examined the possible roles of C3 in bone using bone marrow cultures with antibodies against C3 and C3 receptors (Mac 1, 8C12, and 7G6) and the purified mouse C3 protein. The C3 protein produced preferentially by stromal cells in response to 1 alpha,25-(OH)2D3 was distributed in macrophage-like mononuclear cells and small cells with few nuclei. Adding anti-C3 antibody together with 1 alpha,25-(OH)2D3 to bone marrow cultures greatly inhibited not only the appearance of tartrate-resistant acid phosphatase (TRAP)-positive mononuclear and multinucleated cells, but also the growth of macrophage-like mononuclear cells and stromal cells. The inhibitory effect of anti-C3 antibody on osteoclast-like cell formation was most prominent when it was added between days 2-4 of the 6-day culture period, which corresponded to the late proliferative phase and the early differentiation phase of osteoclast development. Adding anti-C3 receptor antibodies also inhibited osteoclast-like cell formation induced by 1 alpha,25-(OH)2D3. When C3 receptors were detected by the binding of C3-coated sheep red blood cells or immunostaining, the localization of C3 receptor-positive cells coincided exactly with that of C3 protein-positive cells. C3 receptors were expressed mainly in macrophage-like mononuclear cells, TRAP-positive mononuclear cells, and TRAP-positive small cells with few nuclei. TRAP-positive large cells with many nuclei were totally negative for C3 receptors. When macrophage-colony-stimulating factor (M-CSF), the purified C3 protein, and 1 alpha,25-(OH)2D3 were added to bone marrow methylcellulose cultures, separately or in combination, M-CSF-dependent colony formation was strikingly inhibited by 1 alpha,25-(OH)2D3, but the inhibition was prevented by simultaneously adding C3. These results provide additional evidence that osteoclast progenitors are indeed cells of the monocyte-macrophage lineage. It is likely that the C3 produced by stromal cells in response to 1 alpha,25-(OH)2D3 is somehow involved in osteoclast development by potentiating M-CSF-dependent proliferation of bone marrow cells and induction of osteoclast differentiation.

Acid Phosphatase↗

Rat stem cell factor and IL-6 preferentially support the proliferation of c-kit-positive murine hemopoietic cells rather than their differentiation.

We have investigated the effect of stem cell factor (SCF) alone and in combination with interleukin-3 (IL-3) or interleukin-6 (IL-6) on the proliferation and maintenance of primitive hemopoietic progenitor cells. Results from liquid preculture of either unfractionated bone marrow cells or lineage (Lin)-c-kit+ cells indicates that the combination of SCF + IL-3 results in the greatest expansion of total nucleated cell numbers; however, the combination of SCF + IL-6 results in the greatest expansion of colony-forming cells in culture (CFU-C) and in spleen (CFU-S). Morphologic examination confirmed the increase in immature cells after culture with SCF + IL-6 and, therefore, this combination is deemed superior for the expansion of primitive cells in liquid culture. Reconstitution assays using congenic mice (Ly5) revealed that cultured cells in the presence of SCF + IL-6 contained stem cells that were capable of reconstituting the hemopoiesis in lethally irradiated mice. Although it remains unclear whether SCF + IL-6 directly supports the self-renewal of stem cells, SCF + IL-6 is a powerful tool for manipulating primitive hemopoietic cells in vitro.

Animals↗

Fucosylation index of alpha-fetoprotein, a possible aid in the early recognition of hepatocellular carcinoma in patients with cirrhosis.

We report here on three patients with cirrhosis for whom an early recognition of hepatocellular carcinoma was made possible by the measurement of the degree of fucosylation (fucosylation index) of alpha-fetoprotein. Increased levels of this index associated with a moderate increment of serum concentration of alpha-fetoprotein were observed in three patients with cirrhosis who showed no indication of hepatocellular carcinoma by several imaging modalities. Four years after the onset of an increase in the fucosylation index, small hepatocellular carcinoma with a tumor diameter less than 2 cm was revealed in case 1. In cases 2 and 3, small hepatocellular carcinomas were detected 24 mo and 9 mo, respectively, after the first sign of the increase in the index. However, the development to hepatocellular carcinoma was not detected in five patients with cirrhosis in whom continuous increments of serum concentration of alpha-fetoprotein with low levels of fucosylation index were observed during the prospective follow-up from 3 to 9 yr. These findings indicated that the fucosylation index of alpha-fetoprotein can be used as an aid in an early recognition of hepatocellular carcinoma, especially in patients with cirrhosis during the follow-up process in which the moderate increment of serum concentration of alpha-fetoprotein is noted.

Carcinoma, Hepatocellular↗

Expression of c-kit mRNA and protein during the differentiation of human hematopoietic progenitor cells.

To investigate how c-kit and c-kit ligand play a role in the function of hematopoietic stem cells, we determined the expression of c-kit in sorted human hematopoietic stem cells, CD34+CD33- cells and CD34+CD33+ cells. CD34+ cells constituted approximately 1% of the population of gated bone marrow cells and contained colony-forming cells. Two-color analysis by a fluorescence-activated cell sorter (FACS) revealed that about one-third to one-half of the total CD34+ cell population were positive for the CD33 antigen. To analyze the relative accumulation of c-kit mRNA in sorted cells, we used the reverse transcription-polymerase chain reaction (RT-PCR) method, followed by Southern blot analysis. There was a linear relationship between the amount of input RNA and products amplified in the range of 10(3) to 10(5) cells. Using this procedure, we carried out an analysis of c-kit mRNA expression in CD34+CD33-, CD34+CD33+, CD34-CD33+, and CD34-CD33- cells. Enhanced expression for c-kit mRNA was observed solely in CD34+CD33- cells. In contrast, flow cytometry shows that c-kit protein was expressed most abundantly in CD34+CD33+ cells. Colony-forming cells were generated on a human stromal cell layer for 5 weeks initiated with CD34+CD33- cells but not with CD34+CD33+ cells. During co-culture with stromal cells, CD34+CD33- cells differentiated into CD34+CD33+ cells. From these findings, it is concluded that CD34+CD33+ cells are direct progenies of CD34+CD33- cells. In this differentiation pathway, the expression of c-kit mRNA decreased and the c-kit protein increased.

Animals↗

[Acute exacerbation following bronchoalveolar lavage in idiopathic interstitial pneumonia].

We report two cases of idiopathic interstitial pneumonia (IIP) with acute deterioration after bronchoalveolar lavage (BAL). Case 1 was a 54-year-old woman, and case 2 was a 75-year-old man. Both were diagnosed as having IIP, and hospitalized with complaints of high fever and dyspnea. After BAL, the degree of dyspnea increased. White blood cell count and lactate dehydrogenase were elevated, and PaO2 was decreased. Chest X-ray revealed consolidation of the upper lung fields and reticulo-granular shadows spreading through both lungs. BAL fluid examination showed an elevated neutrophil fraction (case 1: 6.5%, case 2: 35.2%), suggesting respiratory tract infection although bacteria could not be detected. Case 1 died of respiratory failure despite corticosteroid therapy. Autopsy revealed diffuse alveolar damage with focal pneumonia in the right S6 corresponding to the upper lobe consolidation. Case 2 improved after antibiotic therapy. These findings suggest that aspiration of infected fluid during BAL can cause acute exacerbation of IIP. It is important to recognize that the BAL procedure can induce an acute exacerbation of IIP.

Acute Disease↗

Long-term cinemicrography of erythroblasts from a patient with congenital dyserythropoietic anemia type III: direct observation of dysplastic erythroblast formation.

Erythroblasts from a patient with congenital dyserythropoietic anemia type III (CDA III) were observed by time-lapse phase-contrast cinemicrography. The erythroblasts were compressed with a new mechanical device; this procedure enhanced the visualization of their structures. Soret band micrography was carried out simultaneously to assess cytoplasmic hemoglobinization. The proliferation and differentiation course of the majority of CDA III erythroblasts was similar to that of normal erythroblasts. The formation of dysplastic erythroblasts showed two patterns of progression: (1) Usually, the process began with the appearance of a well-demarcated clear area in the nucleus of immature erythroblasts. This clear area reappeared in the progeny of the immature erythroblasts, at an increased incidence and in increasing size and rigidity. It finally came to occupy most of the nucleus, compartmentalizing it. The maturing cells displayed vigorous movement and progression of hemoglobinization and the nuclei became lobular; they grew to the cell size at which most CDA III erythroblasts divide, but did not do so. (2) Less frequently seen were abnormalities in mitosis and cellular behavior (e.g., tri- or bi-polar mitosis and subsequent fusion of daughter cells) or rapid growth of one daughter cell with concomitant shrinkage of the other.

Anemia, Dyserythropoietic, Congenital↗

[Two cases of acute eosinophilic pneumonia with precipitating antibody against Trichosporon cutaneum and Trichoderma viride].

Two cases of acute eosinophilic pneumonia are described. The patients presented with an acute febrile illness, dry cough, severe hypoxemia and diffuse pulmonary infiltrates. Total cell count and the number of eosinophils were increased in bronchoalveolar lavage fluid. The TBLB specimen showed eosinophilic infiltration of alveolar walls and spaces. Precipitating antibodies against Trichosporon cutaneum and Trichoderma viride were noted in the patients' sera, and environmental provocation tests gave positive results. The clinical features of acute eosinophilic pneumonia resemble those of summer type hypersensitivity pneumonitis. From these results, we consider that there is a certain degree of overlap between the two diseases.

Adult↗

[Refractory bilateral pneumothoraces complicated with interstitial pneumonitis after bone marrow transplantation].

We report here a case of 33 year-old-man with refractory bilateral pneumothoraces during the treatment for interstitial pneumonitis 6 months after bone marrow transplantation (BMT). He was diagnosed as having acute myelogenous leukemia (AML) M1. He was treated with chemotherapy, and cerebral irradiation. BMT was performed in August 1989 from a sibling donor whose human leukocyte antigen was matched, ABO blood type mismatched. Preconditioning regimen was cyclophosphamide and total body irradiation (TBI). BMT was successful without major graft versus host disease. Thereafter he complained of respiratory symptom and was admitted on June 14 1990. Computed tomogram (CT) scan showed interstitial and alveolar shadows. We started the treatment against bacterial infection, Pneumocystis carinii, cytomegalovirus (CMV) and against interstitial pneumonitis with bolus dose of steroid. The transbronchial lung biopsy specimen revealed interstitial pneumonitis without typical CMV nor pneumocystis carinii pneumonia. Although a CT scan showed improvement of pneumonitis, bilateral pneumothoraces occurred. The adhesion therapy became successful after the reduction of steroid dosage. A pneumothorax rarely occurs after BMT. In this case it is speculated that TBI might be responsible for interstitial pneumonitis, and the steroid might have inhibited the adhesion therapy of pneumothorax.

Adult↗

[The efficacy of semiselective intraarterial infusion therapy in advanced or recurrent gastric cancer].

We use CDDP and have compared the semiselective intraarterial infusion (ia group) with intravenous infusion (i.v. group) by measuring levels of the administered drug in blood and the abdominal organ tissues. In portal blood, the ia group showed a significant increase compared with the i.v. group. The patient tissue level was compared between the two groups. Higher levels were obtained in the peritoneum in the ia group. These results suggest that semiselective intraarterial infusion therapy is effective in peritoneal dissemination.

Cisplatin↗

[Evaluation of surgical treatment for spontaneous pneumothorax].

To evaluate the effect of surgical treatment for spontaneous pneumothorax, we examined eighty patients who underwent the surgical treatment. Out of these, thirty five patients (53.0%) were the recurrent episode of the disease, since we vigorously chose surgical treatment for the second attack of the disease. Operative complications were observed in 6 cases (7.1%) including 2 cases of lasting air leakage and 1 case of bleeding, pneumonia, wound infection and atelectasis. Postoperative recurrence was not seen. From a viewpoint of prevention of the postoperative recurrence, the surgical treatment is effective and safe method.

Adolescent↗

[Vitamin D].

1 alpha,25-Dihydroxyvitamin D3 [1 alpha,25(OH)2D3], the active form of vitamin D3, stimulates intestinal calcium absorption and osteoclastic bone resorption, resulting in the elevation of plasma calcium. Recent studies have revealed that 1 alpha,25(OH)2D3 also promotes differentiation of various cells such as myeloid leukemia cells, lymphocytes, macrophages and skin keratinocytes. The target cells of 1 alpha,25(OH)2D3 possess 1 alpha,25(OH)2D3 receptors (VDR) which belong to the steroid thyroid retinoic acid receptor gene family. The complex of VDR and 1 alpha,25(OH)2D3 binds to vitamin D3-responsive elements (VDRE) present in the promoter region of target genes of 1 alpha,25(OH)2D3. In bone, osteoblasts possess VDR and synthesize several proteins, such as BGP, osteopontin and the third component of complement (C3), in response to 1 alpha, 25(OH)2D3. 1 alpha, 25(OH)2D3 is involved in the differentiation of osteoclast progenitors into mature osteoclasts directly and also by an indirect mechanism involving some proteins produced by osteoblasts. In this review article, we show the mode of action and the biological function of 1 alpha, 25(OH)2D3.

24,25-Dihydroxyvitamin D 3↗

In vivo and in vitro stem cell function of c-kit- and Sca-1-positive murine hematopoietic cells.

c-kit is expressed on hematopoietic stem cells and progenitor cells, but not on lymphohematopoietic differentiated cells. Lineage marker-negative, c-kit-positive (Lin-c-kit+) bone marrow cells were fractionated by means of Ly6A/E or Sca-1 expression. Lin-c-kit+Sca-1+ cells, which consisted of 0.08% of bone marrow nucleated cells, did not contain day-8 colony-forming units-spleen (CFU-S), but 80% were day-12 CFU-S. One hundred cells rescued the lethally irradiated mice and reconstituted hematopoiesis. On the other hand, 2 x 10(3) of Lin-c-kit+Sca-1- cells formed 20 day-8 and 11 day-12 spleen colonies, but they could not rescue the lethally irradiated mice. These data indicate that Lin-c-kit+Sca-1+ cells are primitive hematopoietic stem cells and that Sca-1-cells do not contain stem cells that reconstitute hematopoiesis. Lin-c-kit+Sca-1+ cells formed no colonies in the presence of stem cell factor (SCF) or interleukin-6 (IL-6), and only 10% of them formed colonies in the presence of IL-3. However, approximately 50% of them formed large colonies in the presence of IL-3, IL-6, and SCF. Moreover, when single cells were deposited into culture medium by fluorescence-activated cell sorter clone sorting system, 40% of them proliferated on a stromal cell line (PA-6) and proliferated for more than 2 weeks. In contrast, 15% of the Lin-c-kit+Sca-1-cells formed colonies in the presence of IL-3, but no synergistic effects were observed in combination with SCF plus IL-6 and/or IL-3. Approximately 10% proliferated on PA-6, but most of them degenerated within 2 weeks. The population ratio of c-kit+Sca-1+ to c-kit+Sca-1- increased 2 and 4 days after exposure to 5-fluorouracil (5-FU). These results are consistent with the relative enrichment of highly proliferative colony-forming cells by 5-FU. These data show that, although c-kit is found both on the primitive hematopoietic stem cells and progenitors, Sca-1+ cells are more primitive and respond better than Sca-1- cells to a combination of hematopoietic factors, including SCF and stromal cells.

Animals↗