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S Eto

Publications and source records attributed to S Eto.

At least 109 records · Page 6Linked to original sources
PubMed1994

Interleukin-4 inhibits spontaneous and parathyroid hormone-related protein-stimulated osteoclast formation in mice.

We examined the in vivo effects of recombinant murine IL-4 (rmIL-4) on spontaneous and stimulated mouse osteoclast formation. EC-GI cells, which produce PThrP and IL-1 alpha, were explanted in nude mice. These EC-GI cell-bearing nude mice developed hypercalcemia (4.90 +/- 0.68 mM), and the calcium levels were decreased to near normal (3.48 +/- 0.73 mM, p < 0.05) at day 3 by continuous infusion of rmIL-4 at a dose of 7 micrograms/day. When infused with 0.6 nmol/day of PTHrP(1-34) in ICR mice, rmIL-4 at a dose of 1 or 5 micrograms/day for 3 days caused a marked inhibitory effect on hypercalcemia induced by PTHrP(1-34) (3.73 +/- 0.56-2.54 +/- 0.14 mM, p < 0.01). However, rmIL-4 alone did not change the serum calcium in mice. Histomorphometric analysis revealed that rmIL-4 inhibits both spontaneous and PTHrP(1-34)-stimulated osteoclast formation in mice, with a decrease in osteoclastic surface and in the number of osteoclasts per mm bone surface, respectively. We conclude that IL-4 inhibits spontaneous and stimulated bone resorption resulting from inhibition of osteoclast formation and modulates the development of humoral hypercalcemia of malignancy.

Animals↗
PubMed1994

Androgen receptors, 5 alpha-reductase activity and androgen-dependent proliferation of vascular smooth muscle cells.

To assess the direct effect of androgen on the development of atherosclerosis, we investigated the effect of androgen and its receptor expression in rat vascular smooth muscle cells (VSMC) isolated from rat aorta. We detected the androgen receptor mRNA in VSMC by reverse transcription of the total RNA coupled with amplification of the resulting cDNA by polymerase chain reaction. Binding studies revealed the presence of a single class of binding sites for testosterone (Kd 7.37 nM, Bmax 10.59 fmol/mg protein) and dihydrotestosterone (DHT; Kd 4.89 nM, Bmax 11.37 fmol/mg protein) in VSMC. Measurement of 5 alpha-reductase activity suggested that testosterone is converted to DHT in VSMC (Km 0.36 microM, Vmax 623 fmol/mg protein/h). Moreover, in the present study, DHT significantly stimulated DNA synthesis of VSMC (120-160% of control). The mitogenic activity of testosterone is much less potent than that of DHT. Considering these results, we concluded that androgen may directly accelerate atherosclerosis by stimulating the proliferation of VSMC.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1994

The receptor, metabolism and effects of androgen in osteoblastic MC3T3-E1 cells.

We investigated the androgen receptor (AR), metabolism and effects of androgens in osteoblastic MC3T3-E1 cells. AR was proved as a transcript of a 10-kb mRNA and as a 110-kDa protein. An immunocytochemical study showed that AR was located mainly in the nuclei. Specific binding of [3H]DHT was observed in both the nuclear and cytosol fractions. MC3T3-E1 cells possessed approximately 1190 binding sites per cell and most of the sites (1150 sites) situated in the nucleus. The apparent Kd value in the nuclear fraction was 1.35 nM for [3H]DHT binding, and it was similar to that for [3H]testosterone. In the competition analysis, there was not much difference in the displacement of the [3H]DHT binding from AR between the addition of radioinert DHT and testosterone. In studies of 5 alpha-reductase activity and aromatase activity of the cells, both activities were lower than the respective values in classical androgen target tissues. Androgens stimulated the incorporation of [3H]thymidine into the cell, and DHT and testosterone had a similar potency on the cell proliferation. Thus, these results suggest testosterone itself acts mainly on the osteoblasts without conversion to DHT.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1994

Interleukin-1 alpha as an autocrine growth factor for acute lymphoblastic leukaemia cells.

We describe a case of B-lineage acute lymphoblastic leukaemia (ALL) with proliferation of leukaemic cells through an interleukin-1 alpha (IL-1 alpha) autocrine mechanism. Flow cytometric analysis using the IL-1 receptor type II (IL-1Rt II) monoclonal antibody (mAb) demonstrated the expression of the IL-1Rt II on leukaemic cells: this is the first report in IL-1RtII-positive freshly isolated ALL cells from a patient. In accordance with the expression of IL-1RtII, the leukaemic cells proliferated in response to exogenous IL-1 alpha. In addition, anti-IL-1 alpha mAb markedly inhibited the spontaneous cell proliferation. Furthermore, Northern blot analysis detected IL-1 alpha mRNA without any stimulation. These observations suggest that IL-1 alpha may play an important role as an autocrine growth factor in some cases of ALL.

Adult↗
PubMed1994

Treatment of malignancy-associated hypercalcemia with YM175, a new bisphosphonate: elevated threshold for parathyroid hormone secretion in hypercalcemic patients.

The effect of a new third generation bisphosphonate, YM175 (cycloheptylamino-methylene bisphosphonate), on serum calcium (Ca) and intact PTH levels was examined in 79 malignancy-associated hypercalcemia patients with serum Ca levels higher than 2.75 mmol/L. A single infusion of 2.5, 5, and 10 mg YM175 reduced serum Ca levels in a dose-dependent manner. YM175 was about 6 times more potent than 3-amino-hydroxypropylidene-1,1-bisphosphonate. Among 23 patients treated with 10 mg YM175, serum Ca decreased by more than 0.5 mmol/L in 20 patients and was normalized in 11 patients. Serum intact PTH was subnormal in all of these patients before treatment and remained subnormal in 12 patients (suppressed PTH group), but was elevated to normal or high levels after treatment in the remaining 11 patients (responsive PTH group). Serum Ca was significantly higher throughout the study period in the suppressed PTH group, and mean serum Ca at the nadir did not decrease below 2.90 mmol/L in this group. However, the rate or magnitude of reduction in serum Ca was not different in the two groups. Polynomial regression analysis revealed that the threshold of serum Ca for PTH secretion was elevated to 2.75 mmol/L in the responsive PTH group, whereas it was about the upper limit of normal when both groups were combined (2.59 mmol/L). Furthermore, in the responsive PTH group, the threshold for PTH secretion during the decreasing serum Ca phase (days 4 and 6) was higher than that during the increasing serum Ca phase (days 10 and 14). The changes in the threshold for PTH secretion were also observed in patients treated with lower doses of YM175. These results demonstrate that YM175 is one of the most potent currently available bisphosphonates, and that the threshold for PTH secretion is elevated in at least some malignancy-associated hypercalcemia patients. In addition, there appears to be a difference in the threshold for PTH secretion between the decreasing and increasing serum Ca phases similar to the previously reported hysteresis phenomenon.

Adult↗
PubMed1994

Detection of 1-acetamino-3-(1-naphthyloxy)-2-propanol as a new metabolite of propranolol.

1-Acetamino-3-(1-naphthyloxy)-2-propanol which is an acetyl conjugate of N-desisopropylpropranolol (AcNDP) was detected as a new metabolite of propranolol (PL) from the incubation medium of isolated rat hepatocyte system and from the urinary extracts of a patient under PL therapy as well as a healthy volunteer given PL. In the case of the hepatocyte systems, the optical selectivity of PL elimination and the metabolite formation were discussed by HPLC determination, and the effect of pretreatment by phenobarbital (PB) or 3-metylcholanthrene (3-MC) on the metabolism was also clarified.

Acetamides↗
PubMed1994

Adrenal insufficiency in a patient with acquired immunodeficiency syndrome.

A 46-year-old man was admitted because of hypotension and consciousness disturbance. He was a patient with hemophilia B, and diagnosed as having an AIDS-related complex 2 years prior to admission. On admission he had severe hyponatremia. Hormonal studies revealed that he had Addison's disease. Serum cytomegalovirus (CMV) antibody titers were high, and a CMV antigen was detected in his urine, which suggested CMV adrenalitis caused by an active CMV infection. After the administration of hydrocortisone and ganciclovir, his general clinical condition and biochemical test results were back to normal. However, the adrenal dysfunction was irreversible, despite the treatment with ganciclovir. With an increase in the number of AIDS patients, we have to consider adrenal insufficiency due to a CMV infection in patients with AIDS.

AIDS-Related Complex↗
PubMed1994

Familial primary hyperparathyroidism complicated with Wilms' tumor.

We describe a familial occurrence of primary hyperparathyroidism. The proband is a 60-year-old woman who had a parathyroid adenoma. Her older sister had a parathyroid adenoma with cementifying jaw fibroma and her younger sister died of parathyroid adenocarcinoma with pulmonary metastasis at the age of 38. We have not yet obtained evidence for other endocrine disorders suggesting multiple endocrine neoplasia (MEN) in this pedigree. The proband is complicated with Wilms' tumor. It is now widely accepted that respective predisposed genes of MEN type 1 and Wilms' tumor, and PTH gene are located on chromosome 11. The manifestation observed in this case may be related to mutational abnormalities on chromosome 11.

Adenocarcinoma↗
PubMed1994

[Hypercalcemia in malignancy].

Malignant tumors are often complicated by hypercalcemia (malignancy associated hypercalcemia: MAHC) which causes various clinical symptoms. Hypercalcemia may occasionally lead to death. Unfortunately, many physicians caring for patients with malignant diseases are not aware of this danger. Hypercalcemia is seen in about 15% of patients with solid tumors. This condition is more frequent in some malignant proliferative hematological diseases. In patients with multiple myeloma, the incidence of hypercalcemia is about 20%. The rate of complication by hypercalcemia is as high as 80% in patients with adult T cell leukemia. The symptoms of hypercalcemia include anorexia, easy fatigability, nausea, and vomiting. These symptoms are often mistaken for adverse effects of anticancer drugs or as signs of aggravation of malignant disease. If abnormal thirst and polydipsia are noted in patients with malignant disease, a diagnosis of MAHC should always be considered because these two symptoms are highly characteristic of hypercalcemia. Caution should be exercised when CNS symptoms such as unstable emotions or somnolence are noted. These symptoms in patients with MAHC may lead to death, if untreated. The corrected serum calcium level should always be monitored in patients with malignant disease, so that a possible diagnosis of MAHC may not be overlooked when these symptoms appear. MAHC is caused by the bone resorption stimulating factor (BRSF), which is produced and secreted by the tumor cells. BRSF may act systemically to cause increased bone resorption, resulting in hypercalcemia. MAHC occurring in this manner is called the 'humoral hypercalcemia of malignancy (HHM)'. BRSF produced by multiple myeloma or bone metastasis enhances bone resorption through local osteolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitonin↗
PubMed1993

Inhibitory effect of interleukin 4 on production of interleukin 6 by adult T-cell leukemia cells.

Freshly isolated leukemic cells from patients with adult T-cell leukemia (ATL) produce high levels of interleukin 6 (IL-6), which is suggested to play an important role in thrombocytosis, elevation of C-reactive protein, and hypercalcemia in ATL. In this study, we investigated the effects of T-cell growth factors such as interleukin 2 (IL-2) and interleukin 4 (IL-4) on IL-6 production by ATL cells in vitro. Although IL-2 and/or IL-4 enhanced the cell proliferation of freshly isolated ATL cells from seven of nine patients, IL-2 did not affect the IL-6 release in most cases. In contrast, another T-cell tropic factor, IL-4 markedly inhibited the release of IL-6 in the conditioned medium in all cases. This IL-4-mediated inhibition of IL-6 release was completely abrogated by the addition of anti-IL-4 monoclonal antibody. Time course experiments demonstrated that IL-4 reduced the secretion of IL-6 for a prolonged period of time (more than 72 h). By Northern analysis, IL-4 reduced the transcription level of IL-6 mRNA. Furthermore, by flow cytofluorometry with the use of anti-human IL-4 receptor monoclonal antibody, ATL cells showed the significant level of IL-4 receptor on their cell surfaces without any stimulation. These data suggest that IL-4 may play an important regulatory role in the production of IL-6 in ATL.

Aged↗
PubMed1993

Enhancing effect of interleukin-2 on production of parathyroid hormone-related protein by adult T-cell leukemia cells.

Leukemic cells from patients with adult T-cell leukemia (ATL) can produce a calcium-regulating protein, parathyroid hormone-related protein (PTHrP). Moreover, it has been reported that ATL cells produce some cytokines besides PTHrP and that these cells respond to the T-cell growth factors, interleukin-2 (IL-2) and interleukin-4 (IL-4). To elucidate whether PTHrP produced by ATL cells is regulated by IL-2 or IL-4, we investigated the in vitro effects of IL-2 and IL-4 on the release of PTHrP. IL-2 increased the release of PTHrP into the conditioned medium from leukemic cells in some, but not all, ATL patients; however, IL-4 did not affect the PTHrP release. PTHrP messenger RNA (mRNA) levels were increased in ATL cells cultured in the presence of IL-2. These data suggest that IL-2 plays a role in the regulation of hypercalcemia by enhancing the production of PTHrP in ATL patients.

Aged↗
PubMed1993

An HTLV-I carrier who developed CD4+ T-CLL expressed the IL-2 receptor beta chain alone without expressing the alpha chain.

We describe a case of T-chronic lymphocytic leukaemia (T-CLL) with monoclonal proliferation of CD3+4+8- T cell expressing the interleukin 2 receptor (IL-2R) beta chain without expressing the alpha chain. Southern blot analysis of T-cell receptor beta chain gene revealed rearranged bands. The serum antibody was positive against human T-cell lymphotropic virus type I (HTLV-1)-associated antigens, but monoclonal integration of proviral DNA was not detected in the leukaemic cells. In accordance with the expression of IL-2R beta chain, the leukaemic cells proliferated in response to exogenous IL-2 without prior stimulation. However, culture supernatants of these cells did not show IL-2 activity. Since the role of the IL-2R beta chain in freshly isolated cells from T-CLL patients is not well understood, detailed analysis of this case would give us valuable information on the role of IL-2/IL-2R system in the proliferation of the leukaemic T cells.

Aged↗
PubMed1993

The actions of endothelin on single cells in the anteroventral third ventricular region and supraoptic nucleus in rat hypothalamic slices.

Endothelin (ET), a peptide consisting of 21 amino-acid residues was recently isolated from the culture supernatant of porcine aortic endothelial cells. ET has been reported to be a more potent vasoconstrictor than angiotensin II. Other studies suggest that ET is involved in central control of the autonomic nervous system and body water regulation. Extracellular recordings were made from neurons in the anteroventral third ventricle (AV3V) and supraoptic nucleus (SON) in rat hypothalamic slice preparations. ET-3 was applied at concentrations of 10(-10) M to 3 x 10(-7) M. Of 226 AV3V neurons tested, 48 (21%) were excited, 8 (4%) were inhibited, and 170 (75%) were unaffected by ET-3 at 10(-7) M. The threshold concentration to evoke the responses was approximately 10(-9) M. Of 144 SON neurons tested, 64 had a phasic firing pattern and 80 had a non-phasic firing pattern. Of 64 phasic neurons tested, 39 (61%) were inhibited by ET-3 at 10(-7) M, 25 (39%) were non-responsive and none was excited. Of 80 non-phasic neurons tested, 14 (17.5%) were inhibited by ET-3 at 10(-7) M, 66 (82.5%) were non-responsive and none was excited. The effects of ET-1 were compared with those of ET-3. The number of neurons responding to ET-1 and their responsiveness were almost the same as for ET-3. To investigate whether the ET responses are dependent on Ca2+ influx, a Ca2+ free medium and the Ca2+ antagonist, nicardipine, were used. The excitatory responses of AV3V neurons to ET were maintained in the Ca2+ free medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Interleukin-4 induces proliferation of adult T-cell leukemia cells.

To evaluate the effect of IL-4 on the growth of leukemic cells from adult T-cell leukemia (ATL) patients (ATL cells) and determine whether the IL-4 autocrine mechanism is involved in the growth of ATL cells, we studied the proliferative response of ATL cells, from 11 patients, cultured in the presence or absence of IL-4 in vitro. Leukemic cells from 10 of the 11 patients examined proliferated in response to both IL-2 and IL-4 in a dose-dependent manner. The proliferative response to IL-4 was higher than that obtained with IL-2 in 8 patients. The expression of the IL-2 receptor (IL-2R) alpha alpha-chain in leukemic cells from some patients was also enhanced by IL-4. The IL-4 receptor was demonstrated by flow cytometry on the surface of ATL cells. Neither IL-4-induced proliferation of ATL cells nor IL-4-induced IL-2R expression on ATL cells was inhibited by anti-Tac or anti-IL-2 antibody and, therefore, these effects of IL-4 are considered independent of endogenous IL-2 activity. However, IL-2 and IL-4 were undetectable in the culture supernatants of ATL cells from any patient by enzyme-linked immunosorbent assay. Interferon-gamma (IFN-gamma) partially inhibited IL-2 or IL-4-induced proliferation of ATL cells. These results suggest that leukemic cells from ATL patients proliferate by an IL-2 or IL-4 paracrine mechanism in lymphoid tissue in vivo and that IFN-gamma inhibits IL-2- or IL-4-induced proliferation of ATL cells.

Aged↗
PubMed1993

Autocrine stimulation of interleukin-1 in the growth of human thyroid carcinoma cell line NIM 1.

We reported first in this study that human thyroid cell line NIM 1 established from a patient with papillary adenocarcinoma of the thyroid associated with hypercalcemia and peripheral neutrocytosis produced interleukin (IL)-1 alpha and IL-1 beta in the culture supernatant and cell lysate as detected by murine thymocyte proliferative response and enzyme-linked immunosorbent assay. Production of IL-1 alpha and IL-1 beta was further confirmed by the demonstration of IL-1 alpha and IL-1 beta messenger ribonucleic acid expression with Northern blot hybridization analysis. The in vitro growth of NIM 1 cells was inhibited by the addition of anti-IL-1 alpha and IL-1 beta antibody. The growth of NIM 1 cells was further enhanced by the addition of recombinant human IL-1 alpha and IL-1 beta, whereas this enhancement was also inhibited by the addition of anti-IL-1 antibody. IL-1 receptors were expressed on NIM 1 cells. These results suggest that IL-1 plays a regulatory role in the growth of NIM 1 cells by an autocrine mechanism.

Adenocarcinoma↗
PubMed1993

Angiotropic lymphoma of paranasal sinuses with initial symptoms of oculomotor nerve palsy.

A 78-year-old female was found to have angiotropic lymphoma, a rare fatal disease, with initial symptoms of oculomotor nerve palsy. A biopsy of the paranasal sinus mucosa showed that the small vessels were occupied by large mononuclear cells which upon immunohistochemical examination tested positive for pre B-cell markers. She felt a gradually increasing pain in her left thigh. Magnetic resonance imaging suggested the involvement of neoplastic cells in the left femoral bone marrow. Following chemotherapy treatment remission was achieved. Early diagnosis of angiotropic lymphoma appears very significant, as this disorder could be well controlled by systemic chemotherapy.

Aged↗