Biomedical subjects

M Fukase

Publications and source records attributed to M Fukase.

At least 37 records · Page 2Linked to original sources

PubMed1994

Persistent expression of proto-oncogene c-fos stimulates osteoclast differentiation.

We analyzed c-fos mRNA expression by northern blotting analysis in chicken osteoclast precursors which spontaneously differentiate to multinucleated osteoclasts in 5-6 days. Osteoclast precursors as well as mature multinucleated osteoclasts showed constitutive expression of c-fos mRNA which is not found in osteoblasts. The c-fos expression was enhanced transiently by serum, dibutyryl cAMP (10(-4) M) and phorbol 12-myristate 13-acetate (TPA) (5 x 10(-7) M). To clarify the role of c-fos in osteoclast differentiation, c-fos DNA was transfected into osteoclast precursors. Greater than 2 fold increases in tartrate resistant acid phosphatase (TRAP) and bone resorptive activity were observed in the transfected cells compared to controls 3 days after transfection, suggesting that prolonged expression of c-fos caused enhanced osteoclast differentiation.

Acid Phosphatase↗

PubMed1994

Protein kinase C is crucial for the stimulation of sodium-dependent phosphate transport by parathyroid hormone-related peptide in osteoblast-like cells.

In the present study, we investigated the role of parathyroid hormone-related peptide (PTHrP)-responsive dual signal transduction systems in the regulation of sodium-dependent phosphate (Pi) transport by PTHrP in UMR-106 cells. Exposure of the cells to 10(-7) M human (h) PTHrP-(1-34) induced a significant increase in Pi uptake within 15 min of incubation. The peptide stimulated Pi uptake dose-dependently at the range of 10(-11)-10(-7) M. Activation of protein kinase C (PKC) by 12-O-Tetradecanoyl phorbol-13-acetate (TPA) also increased Pi uptake in time- and dose-dependent manners similar to PTHrP. In contrast, neither activation of adenylate cyclase by 10(-5) M forskolin nor calcium ionophore treatment with 10(-7) M A23187 affect Pi uptake. These agents failed to influence on Pi uptake even in combined treatment with TPA. The PTHrP-induced increase in Pi uptake was strongly inhibited by pretreating cells with PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) (50 microM), and by down-regulating PKC with a prolonged TPA pretreatment. These results indicate that the messenger system mediated by PKC, rather than adenylate cyclase or cytosolic calcium, plays a crucial role in the regulation of sodium-dependent Pi transport by PTHrP in the osteoblast-like cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1994

Calcitonin directly acts on mouse osteoblastic MC3T3-E1 cells to stimulate mRNA expression of c-fos, insulin-like growth factor-1 and osteoblastic phenotypes (type 1 collagen and osteocalcin).

The present study was performed to examine whether calcitonin directly acted on mouse osteoblastic MC3T3-E1 cells to stimulate the mRNA expression of insulin-like growth factor-1 (IGF-1) and c-fos, followed by an increase in their proliferation and differentiation. Eel calcitonin increased [3H]thymidine incorporation and alkaline phosphatase activity as well as the mRNA expression of type 1 collagen and osteocalcin which were characteristic of osteoblasts. Eel calcitonin (10(-8)M) induced c-fos mRNA transiently after its addition, followed by gene expression of IGF-1, an important autocrine/paracrine growth factor in the regulation of osteoblastic proliferation. We first demonstrated that calcitonin directly acted on osteoblasts to stimulate transcription of c-fos and IGF-1 genes as well as functional phenotypes including type 1 collagen and osteocalcin.

Animals↗

PubMed1994

Direct involvement of cAMP-dependent protein kinase in the regulation of alkaline phosphatase activity by parathyroid hormone (PTH) and PTH-related peptide in osteoblastic UMR-106 cells.

The present study was performed to characterize the participation of parathyroid hormone (PTH)- and PTH-related peptide (PTHrP)-responsive dual signal transduction systems [cAMP-dependent protein kinase (PKA) and Calcium/protein kinase C (Ca/PKC)] in the regulation of alkaline phosphatase (ALP) activity in osteoblastic osteosarcoma cells (UMR-106). Both human (h) PTH-(1-34) and hPTHrP-(1-34) at 10(-8) M stimulated ALP activity to the similar degree. Dibutyryl, cAMP (dbcAMP) (10(-5), 10(-4) M) and Sp-diastereoisomer of adenosine cyclic 3',5'-phosphorothioate (Sp-cAMPS), a direct stimulator of PKA (10(-4) M) also stimulated its activity. Phorbol 12-myristate 13-acetate (PMA), an activator of PKC, (10(-7), 10(-6) M) did not affect its activity, while calcium ionophores, A23187 and ionomycin (10(-7), 10(-6) M) inhibited it. Although Rp-diastereoisomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS), a direct inhibitor of PKA, (10(-4) M) did not affect ALP activity by itself, it significantly antagonized not only Sp-cAMPS-induced increase in ALP activity, but also PTH- and PTHrP-induced one. The present study first indicated that the activation of PKA was directly involved and acted as a main pathway in the regulation of ALP activity by PTH and PTHrP in osteoblasts.

Alkaline Phosphatase↗

PubMed1994

Cross-talk of parathyroid hormone-responsive dual signal transduction systems in osteoblastic osteosarcoma cells: its role in PTH-induced homologous desensitization of intracellular calcium response.

The present study was designed to characterize the cross-talk of parathyroid hormone (PTH)-responsive dual signal transduction systems (cAMP-dependent protein kinase (PKA) and calcium/protein kinase C [PKC]) and its participation in PTH-induced homologous desensitization of intracellular calcium ([Ca2+]i) in osteoblastic UMR-106 cells. Although our recent study revealed that prolonged (more than 2 h) pretreatment with PKC-activating phorbol ester, phorbol 12-myristate 13-acetate (PMA) significantly decreased the PTH-stimulated cAMP production, pretreatment with PMA (10(-7) and 10(-6) M) but not 10(-6) M 4 alpha-phorbol 12,13-didecanoate (PDD), incapable of activating PKC for 30 min significantly augmented 10(-7) M hPTH-(1-34)-stimulated cAMP production. H-7 (50 microM), a PKC inhibitor, significantly antagonized this PMA-induced effect. Pretreatment with 10(-6) M PMA for 30 min did not affect PTH receptor binding but significantly augmented a cAMP responsiveness to 10(-5) M forskolin and 1 microgram/ml cholera toxin. Pertussis toxin (0.5 microgram/ml) did not affect the PMA-induced augmentation of the PTH-stimulated cAMP production. PTH caused a complete homologous desensitization of [Ca2+]i response within 30 min. Pretreatment with 10(-4) M dibutyryl cAMP for 30 min and 6 h significantly reduced and completely blocked the PTH-induced increase in [Ca2+]i, respectively. Pretreatment with 10(-4) M Sp-cAMPs, a direct PKA activator, for 30 min completely blocked the PTH-induced increase in [Ca2+]i. Rp-cAMPS (10(-4) M), an antagonist of PKA, slightly but significantly antagonized the PTH-induced homologous desensitization of [Ca2+]i response. The present study indicates that the time of exposure to PKC activation is a critical determinant in modulating the cAMP system, while PKA activation counterregulatorily acts on the [Ca2+]i system, and that PKA activation is linked to the PTH-induced homologous desensitization of [Ca2+]i response.

Adenylyl Cyclases↗

PubMed1994

Second messenger signaling of c-fos gene induction by parathyroid hormone (PTH) and PTH-related peptide in osteoblastic osteosarcoma cells: its role in osteoblast proliferation and osteoclast-like cell formation.

The present study was performed to clarify second messenger signaling in parathyroid hormone (PTH)-induced c-fos gene expression, to characterize the participation of the c-fos gene in the regulation of osteoblast proliferation and function as well as osteoclast-like cell formation by PTH and to compare these effects of PTH with those of PTH-related peptide (PTHrP). Both human (h) PTH-(1-34) and hPTHrP-(1-34) at 10(-8) M induced a transient c-fos gene expression to a similar degree in osteoblastic osteosarcoma cells, UMR-106. N6,O2'-dibutyryl adenosine 3',5'-cyclic monophosphate (dbcAMP) as well as Sp-diastereoisomer of adenosine cyclic 3',5'-phosphorothioate (Sp-cAMPS), an activator of cAMP-dependent protein kinase (PKA), induced a weak c-fos gene expression. Although Rp-diastereoisomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS), an inhibitor of PKA, almost completely antagonized dbCAMP- and Sp-cAMPS-induced expression of c-fos gene, it did not cause an obvious inhibition of PTH- or PTHrP-induced expression. Phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), induced an intense expression of the c-fos gene, while 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD), incapable of activating PKC, and calcium ionophores (A23187 and ionomycin) did not. Protein kinase C inhibitor (H-7, 50 microM) completely blocked the expression of the c-fos gene by PTH as well as by PTHrP). Antisense oligodeoxynucleotides (as-ODN) complementary to c-fos mRNA, which have been shown to inhibit its mRNA translation, at 1 microM significantly antagonized PTH- and PTHrP-induced inhibition of [3H] thymidine incorporation and stimulation of osteoclast-like cell formation in the presence of osteoblasts, but not an increase in alkaline phosphatase activity, compared to control oligodeoxynucleotides with same nucleotides as as-ODN but with a random sequence. The present study indicates the involvement of PKC system in c-fos gene expression by PTH as well as PTHrP and also indicates the involvement of the c-fos gene in the regulation of bone cell physiology by PTH and PTHrP.

Cell Division↗

PubMed1994

Femoral and spinal bone mineral density in Japanese osteoporotics with hip fracture.

In the present study, bone mineral density (BMD) of femoral neck and lumbar spine was compared between 38 Japanese female patients with hip fracture (age 63-89 years, mean +/- SD 76 +/- 7 years) and 162 age-matched female controls (age 62-90 years, mean +/- SD 75 +/- 7 years). BMD was measured in the femoral neck and lumbar spine (L2-4) using dual-photon absorptiometry (Norland model 2600). BMD values of femoral neck as well as lumbar spine were significantly lower in patients with hip fracture than in controls (0.504 +/- 0.097 v 0.597 +/- 0.101, p < 0.01, for femoral neck; 0.661 +/- 0.146 v 0.720 +/- 0.128, p < 0.05, for lumbar spine). Patients with hip fracture and controls were stratified according to their BMD levels at two measuring sites, and the ratio of the number of patients and controls at each BMD level was calculated as an indicator of fracture rate. This ratio showed an exponential increase as the femoral neck BMD declined, but only a gradual increase as the lumbar spine BMD declined. Specificity-sensitivity analysis revealed that BMD values of 0.59 and 0.54 g/cm2 at the femoral neck provided a specificity of 52% and 68% with a sensitivity of 90% and 75%, respectively. These findings suggest that Japanese patients with hip fracture are more osteoporotic than age-matched controls and that the selective measurement of femoral neck would be useful for predicting the risk of hip fracture.

Aged↗

PubMed1994

The expression of parathyroid hormone-related protein in human breast cancer with skeletal metastases.

The relationship between the expression of parathyroid hormone-related protein (PTHrP) by breast cancer and skeletal metastases, was investigated using a monoclonal antibody against human PTHrP (4B3). The immunohistochemical localization of PTHrP was studied in sections of formalin-fixed, paraffin-embedded tissues from 28 breast cancers obtained surgically between 1980 and 1985. Of the 28 patients, 12 developed skeletal metastases, 8 developed lung metastases, and the other 8 were alive and disease-free at the time of this study. Sixteen of the 28 (57%) tumors showed positive immunoreactivity to 4B3, the PTHrP positive ratio being 83% in the patients who developed skeletal metastases, 38% in those who developed lung metastases, and 38% in those without recurrence, respectively. Thus, a significantly higher proportion of the patients who developed skeletal metastases were positive for PTHrP than the other two groups (P < 0.05). Furthermore, the level of positive staining was strongly related to positivity for estrogen and progesterone receptors (P < 0.01). These results are consistent with the hypothesis that PTHrP might be necessary for metastases to erode bone and grow in skeletal sites, and its expression could be related to certain hormones.

Antibodies, Monoclonal↗

PubMed1994

Meprin is predominantly involved in parathyroid hormone degradation by the microvillar membranes of rat kidney.

Hydrolysis of fragments of the C-terminal and mid-portions of parathyroid hormone (PTH) by a phosphoramidon-insensitive metallo-endopeptidase, previously purified by us from the microvillar membranes of rat kidney, and by the microvillar membranes of rat kidney themselves were investigated using a reverse-phase HPLC, and the amino acid sequences of each produced PTH metabolite were compared after their determination with an automated gas-phase protein sequencer. The results showed that both the purified microvillar endopeptidase and the microvillar membranes of rat kidney limited hydrolyzed human (h) PTH-(39-84) and hPTH-(39-68) mainly at peptide bonds flanked by a hydrophilic amino acid residue, where are characteristic for the purified microvillar endopeptidase but not for other known endopeptidase including endopeptidase 24.11. In addition, most of PTH metabolites generated by the microvillar membranes were insensitive to phosphoramidon and had amino acid sequences identical to those generated by the purified microvillar endopeptidase, indicating that these metabolites were produced by the enzyme integrated in the membranes. Since analysis of the N-terminal amino acid sequence of the purified microvillar endopeptidase revealed that it was structurally identical to rat meprin (EC 3.4.24.18), these results indicate that the purified microvillar endopeptidase or meprin is predominantly involved in PTH degradation by the microvillar membranes of rat kidney as an integral membrane protein.

Amino Acid Sequence↗

PubMed1994

Radial bone mineral content of normal Japanese infants and prepubertal children: influence of age, sex and body size.

The present study was performed to measure appendicular bone mass of Japanese infants and children, and to assess the influence of age, sex and body size on bone mass during the period of bone growth. The bone mineral content (BMC) and bone width (BW) at the distal third of the radius were measured by single photon absorptiometry (SPA) in 229 healthy Japanese infants and children aged 0-12 years, and the BMC/BW ratio was calculated to give the bone mineral density (BMD). BMC and BW increased with age until 2 years, while BMD did not obviously change until 2 years. After 2 years of age, the overall effect of aging appeared more prominent in BMC and BMD than in BW. There were no significant differences in BMC, BW and BMD between males and females aged 0-12 years. Age, body height, and body weight were strongly correlated with three parameters of bone mass (BMC, BW, and BMD). Among the three parameters of bone mass, BMC showed the highest Pearson coefficient of correlation with age (r = 0.955), body height (r = 0.957) and body weight (r = 0.966), as compared with BW and BMD. The present cross-sectional study provides normative data of the appendicular bone mass in healthy Japanese children, which may serve as a standard for assessment of bone mineralization in Japanese infants and children with medical problems.

Absorptiometry, Photon↗

PubMed1994

TGF-beta-induced macrophage colony-stimulating factor gene expression in various mesenchymal cell lines.

We report here that transforming growth factor-beta (TGF-beta) can increase the expression level of macrophage colony-stimulating factor (M-CSF) mRNA in a variety of mesenchymal cell lines derived from osteoblasts, bone marrow stromal cells, fibroblasts, and myoblasts. The M-CSF activity in the conditioned medium of mouse osteoblast-like MC3T3-E1 cells was increased by TGF-beta as well as interleukin-1 (IL-1) treatment. The increase of M-CSF mRNA expression was observed as early as 2 h after TGF-beta or IL-1 addition and was superinduced by cycloheximide treatment. Nuclear run-off assays revealed that the increase in M-CSF mRNA by TGF-beta as well as IL-1 occurred, at least in part, at the transcriptional level. Platelet-derived growth factor (PDGF) also enhanced the M-CSF production in MC3T3-E1 cells. Furthermore, TGF-beta and IL-1 distinctly induced both PDGF-A and PDGF-B chain mRNA in MC3T3-E1 with different time courses. Our present studies suggest that PDGF autocrine loop-dependent and loop-independent pathways could modulate the M-CSF production stimulated by TGF-beta or IL-1 and account for the complexity of the cytokine network involving M-CSF in vivo under various physiological and pathological conditions.

Animals↗

PubMed1994

IGF-I mediates the stimulatory effect of high calcium concentration on osteoblastic cell proliferation.

Since our recent study revealed that an increase in extracellular calcium ([Ca2+]e) but not magnesium enormously stimulated DNA synthesis in osteoblastic MC3T3-E1 cells at the minimal and maximal effective concentration of 3 and 5 mM, respectively, the present study was performed to clarify how an increase in [Ca2+]e caused a stimulation of DNA synthesis of these cells. Neither calcium channel blockers (verapamil, diltiazem, and nifedipine) and dantrolene, an inhibitor of Ca release from intracellular Ca pool, nor indomethacin, an inhibitor of prostaglandin synthesis, affected the high [Ca2+]e-induced increase in DNA synthesis. DNA synthesis first increased after a 12-h exposure to 5 mM [Ca2+]e, and cycloheximide eliminated the stimulatory effect of high [Ca2+]e on DNA synthesis, suggesting that this stimulatory effect of high [Ca2+]e was dependent on new protein synthesis. There is recent evidence that MC3T3-E1 cells constitutively produce and secrete insulin-like growth factor I (IGF-I) and possess IGF-I receptors. IGF-I antiserum (1:10,000 to 1:100) blocked the high [Ca2+]e-induced increase in DNA synthesis in a concentration-dependent manner. A neutralizing abolished DNA synthesis stimulated by high [Ca2+]e, indicating that IGF-I mediated the high [Ca2+]e-induced effect. Furthermore, high [Ca2+]e significantly increased the secretion of immunoreactive IGF-I into the medium as well as the expression of IGF-I mRNA. Present findings indicate that an increase in [Ca2+]e stimulated DNA synthesis of osteoblasts through the mechanism of an increase in the production and secretion of IGF-I.

3T3 Cells↗

PubMed1994

Role of interleukin-6 and prostaglandins in the effect of monocyte-conditioned medium on osteoclast formation.

There is evidence suggesting some role of mononuclear cells at the resorptive site in bone remodeling. The possibility was therefore postulated that these cells might provide some signal for osteoclast formation. We examined the effects of human monocyte-conditioned medium (CM) on the formation of osteoclast-like cells from hemopoietic blast cells in the absence of stromal cells and unfractionated bone cells in the presence of stromal cells. In both culture systems, the osteoclast-like cell formation induced by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or human parathyroid hormone (PTH)-(1-34) was significantly inhibited by adding 20% CM. The effects of monocyte-derived local regulators of bone turnover on osteoclast-like cell formation induced by 1,25(OH)2D3 or PTH were determined. Interleukin-6 (IL-6) inhibited osteoclast-like cell formation in both culture systems, whereas prostaglandin (PG) E2 significantly inhibited the formation only in the hemopoietic blast cell culture. The inhibitory effect of CM on osteoclast-like cell formation from hemopoietic blast cells was not observed when CM was prepared from monocytes pretreated with indomethacin. The inhibitory effect of CM and IL-6 on osteoclast-like cell formation in both culture systems was blocked by adding neutralizing IL-6 antibody. The present study demonstrated that CM inhibited osteoclast-like cell formation induced by 1,25(OH)2D3 and PTH presumably through the action of local regulators of bone turnover, such as IL-6 and PG. Our findings thus provide additional evidence that mononuclear cells play an important role at the resorptive site in bone remodeling.

Acid Phosphatase↗

PubMed1994

Carboxyl-terminal parathyroid hormone fragments stimulate osteoclast-like cell formation and osteoclastic activity.

The controversy still exists about the biological activity of carboxyl (C)-terminal PTH fragments. The present study was performed to examine the effect of C-terminal PTH fragments on osteoclast-like cell formation and bone-resorbing activity. In contrast to human (h) PTH-(1-34) or hPTH-(1-84), any C-terminal fragments examined [hPTH-(35-84), hPTH-(53-84), and hPTH-(69-84)] did not affect cellular cAMP production and intracellular calcium in osteoblastic UMR-106 cells. Although hPTH-(1-84) caused an increase in cAMP production and intracellular calcium less effectively than hPTH-(1-34) in UMR-106 cells, the former caused a stimulation of osteoclast-like cell formation in osteoblast-containing mouse bone cell cultures more effectively than the latter. All of the C-terminal fragments significantly stimulated osteoclast-like cell formation, and their effectiveness seemed to depend on the amino acid length of the fragments. The conditioned medium from UMR-106 cells pretreated with C-terminal PTH as well as amino-terminal PTH significantly stimulated osteoclast-like cell formation from mouse hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor. Moreover, all of the C-terminal fragments stimulated osteoclast-like cell formation from hemopoietic blast cells even in the absence of osteoblasts, and their effectiveness seemed to depend on the length of fragments. As for bone-resorbing activity by mature osteoclasts, all of the C-terminal fragments stimulated bone resorption in osteoblast-containing mouse bone cell cultures, whereas these fragments did not affect the bone-resorbing activity of isolated rabbit osteoclasts. The present study first indicates that C-terminal PTH fragments stimulate osteoclast-like cell formation as well as bone-resorbing activity by mature osteoclasts in the presence of osteoblasts and accelerate osteoclast-like cell formation from hemopoietic blast cells in the absence of osteoblasts.

Animals↗

PubMed1994

Calcitonin inhibits osteopontin mRNA expression in isolated rabbit osteoclasts.

Recent evidence indicates that osteopontin (Opn), one of the bone matrix proteins, plays an important role in the attachment of osteoclasts to bone matrix. Besides being elaborated by osteoblasts, this protein is also produced by osteoclasts. The present study was performed to examine the effect of calcitonin (CT) on Opn mRNA expression of isolated rabbit osteoclasts and to clarify the second messenger signaling of this effect. Eel CT inhibited Opn mRNA expression as well as bone-resorbing activity of isolated rabbit osteoclasts. Eel CT caused a transient increase in intracellular calcium followed by a sustained increase as well as an increase in cAMP production in these cells. Dibutyryl-cAMP (10(-4) M) and Sp-cAMPS (10(-4) M), an activator of cAMP-dependent protein kinase (PKA), as well as A23187 (10(-7) M), a calcium ionophore, and phorbol myristate acetate (10(-7) M), an activator of protein kinase C (PKC), caused a significant inhibition of Opn mRNA expression, and suppressed bone-resorbing activity of isolated osteoclasts. The present study is the first to demonstrate that CT inhibits Opn mRNA expression in isolated rabbit osteoclasts, presumably through the activation of PKA and calcium/PKC pathways, by which the bone-resorbing activity might be attenuated subsequently.

Animals↗

PubMed1994

Involvement of protein kinase C in the stimulation of sodium-dependent phosphate transport by parathyroid hormone in osteoblast-like cells.

The rat osteosarcoma cell line UMR-106 has an osteoblast-like phenotype and possesses parathyroid hormone (PTH)-responsive dual signal transduction systems [adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) and calcium-protein kinase C (Ca-PKC)]. These cells transport inorganic phosphate (Pi) by a Na(+)-dependent carrier under stimulation by PTH. The present study aimed to clarify PTH-responsive signal transduction mechanisms in the regulation of Na(+)-dependent Pi transport by PTH in UMR-106 cells. Exposure of these cells to 10(-7) mol/l PTH induced a significant increase in Pi uptake within 30 min of incubation and it became maximal after 2 h. Parathyroid hormone (10(-9)-10(-7) mol/l) stimulated Pi uptake dose dependently. Activation of PKC by 12-O-tetradecanoyl phorbol-13-acetate (TPA) also increased Pi uptake in time- and dose-dependent manners similar to PTH. In contrast, neither PKA activation by 10(-4) mol/l forskolin or by 10(-4) mol/l dibutyryladenosine 3',5'-cyclic monophosphate nor calcium ionophore treatment with 10(-7) mol/l A23187 or with 10(-7) mol/l ionomycin during 3-h incubations affect Pi uptake, except its increase by 10(-4) mol/l forskolin at a 3-h incubation. These agents had no influence on Pi uptake even in combined treatments with TPA. The PTH-induced increase in Pi uptake was abolished almost completely by pretreating cells with PKC inhibitors, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine dihydrochloride (H-7) (50 mumol/l) or staurosporin (10 and 50 nmol/l), and by down-regulating PKC with a prolonged TPA treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Lymphocytic hypophysitis, pustulosis palmaris et plantaris and eosinophilia.

We describe here a unique case of lymphocytic hypophysitis accompanied by pustulosis palmaris et plantaris and eosinophilia. The patient also suffered from panhypopituitarism with hyperprolactinemia and pituitary diabetes insipidus caused by lymphocytic hypophysitis. Complications of pustulosis palmaris et plantaris and eosinophilia with lymphocytic hypophysitis have not been reported previously. In the present case, the activities of the three diseases correlated well throughout the patient's course, suggesting that a common mechanism might possibly participate in their pathogenesis.

Adult↗

PubMed1994

Purification of meprin from human kidney and its role in parathyroid hormone degradation.

Meprin (EC 3.4.24.18) is known to occur in the kidneys of mice and rats, but has not previously been found in human kidneys. Here we report the isolation of meprin from human kidney and show that it has a role in the degradation of parathyroid hormone (PTH) in that organ. The purified human meprin had properties almost identical to those of rat meprin including molecular size, substrate specificity and inhibitor sensitivity, and it also cross-reacted well with an antibody raised against rat meprin. Both the purified human meprin and the microvillar membranes of human kidney readily hydrolyzed human parathyroid hormone [hPTH-(1-84)] into several fragments, whose amino acid sequences corresponded well to each other. Thus, meprin appears to play a major role in the PTH-degrading activity in the microvillar membranes of human kidney. Our results indicate that meprin, which so far has mainly been investigated in mice and rats, is found not only in these rodents, but also in the human kidney, and suggest that its physiological role in humans is to degrade PTH in the kidney.

Amino Acid Sequence↗