Biomedical subjects

M Inaba

Publications and source records attributed to M Inaba.

At least 235 records · Page 13Linked to original sources

PubMed1995

[Experimental evaluation of a new gelatin-impregnated woven Dacron vascular prosthesis (CL301)].

We investigated the biological response and biodegradation of CL301, a presealed woven Dacron prosthesis (UBE woven) with glutaraldehyde stabilized gelatin. The sealant does not affect its handling characteristics because of the glycerin treatment. The total content of endotoxin in the CL301 was 5.3 +/- 0.5 pg/mg of sealant material (1.7 +/- 0.2 pg/cm2), which was 1/5 and 1/6 of that found in Hemashield and Gelseal, respectively. The pyrogen test was negative and the content was estimated below the minimum pyrogenic doses for thoracic aortic surgery. Five cm-long grafts with a diameter of 10 mm were implanted into the descending thoracic aorta of dogs weighing 10-16 kg. These grafts were retrieved 2 hours, 7, 10 days, 5, 8 and 10 weeks after implantation. Thrombus-free surfaces were 28%, 77%, at 5 and 10 weeks and there was no excessive inflammatory response to the sealant. The total, and the effective sealant remaining were 80.6%, 56.5% at 5 weeks, 60.8%, 38.3% at 10 weeks, respectively. The sealant was removed more rapidly from the inner surface than from the outer. In half of the graft area, the sealant was removed or detached from the Dacron surface 5 weeks after implantation, indicating that delayed resorption of the sealant substantially did not affect the healing process. We conclude that because of the harmless amount of endotoxin and effective sealing for 5 weeks, followed by an acceptable healing process experimentally, CL301 is the presealed Dacron graft of choice for thoracic aortic surgery.

Animals↗

PubMed1994

Characterization of Na(+)-dependent L-glutamate transport in canine erythrocytes.

Characteristics of the high-affinity Na(+)-dependent L-glutamate transport system in canine erythrocytes were studied by using intact cells and resealed ghosts. The L-glutamate transport showed a precise dependence on extracellular Na+ and intracellular K+. Kinetical analysis revealed that two Na+ ions and one K+ ion were involved in each L-glutamate transport cycle. The L-glutamate transport was inhibited most potently by threo-3-hydroxyaspartate and L-cysteinesulfinate (at 25 microM, 83% and 79% inhibition, respectively) and weakly by dihydrokainate and DL-alpha-aminoadipate (at 25 microM, 21% and 17% inhibition, respectively). From these stoichiometrical and pharmacological properties we concluded that the L-glutamate transport system in canine erythrocytes is a product of the L-glutamate transporter gene family and resembles a neuronal transporter rather than a glial one. L-Glutamate uptake was increased by internal, but not external, HCO3- when the internal and external anions of the erythrocytes were replaced by several other anions. Moreover, this enhancement was blocked by inhibition of carbonic anhydrase, which indicated that L-glutamate transport was at least partly dependent on HCO3- generated inside the cells. These observations indicate that anion countertransport is coupled to the high-affinity Na(+)- and K(+)-dependent L-glutamate transport in canine erythrocytes.

Animals↗

PubMed1994

The tissue distribution of the B7-2 costimulator in mice: abundant expression on dendritic cells in situ and during maturation in vitro.

B7-2 is a recently discovered, second ligand for the CTLA-4/CD28, T cell signaling system. Using the GL-1 rat monoclonal antibody (mAb), we monitored expression of B7-2 on mouse leukocytes with an emphasis on dendritic cells. By cytofluorography, little or no B7-2 was detected on most cell types isolated from spleen, thymus, peritoneal cavity, skin, marrow, and blood. However, expression of B7-2 could be upregulated in culture. In the case of epidermal and spleen dendritic cells, which become highly immunostimulatory for T cells during a short period of culture, the upregulation of B7-2 was dramatic and did not require added stimuli. Lipopolysaccharide did not upregulate B7-2 levels on dendritic cells, in contrast to macrophages and B cells. By indirect immunolabeling, the level of staining with GL-1 mAb exceeded that seen with rat mAbs to several other surface molecules including intercellular adhesion molecule 1, B7-1, CD44, and CD45, as well as new hamster mAbs to CD40, CD48, and B7-1/CD80. Of these accessory molecules, B7-2 was a major species that increased in culture, implying a key role for B7-2 in the functional maturation of dendritic cells. B7-2 was the main (> 90%) CTLA-4 ligand on mouse dendritic cells. When we applied GL-1 to tissue sections of a dozen different organs, clear-cut staining with B7-2 antigen was found in many. B7-2 staining was noted on liver Kupffer cells, interstitial cells of heart and lung, and profiles in the submucosa of the esophagus. B7-2 staining was minimal in the kidney and in the nonlymphoid regions of the gut, and was not observed at all in the brain. In the tongue, only rare dendritic cells in the oral epithelium were B7-2+, but reactive cells were scattered about the interstitial spaces of the muscle. In all lymphoid tissues, Gl-1 strongly stained certain distinct regions that are occupied by dendritic cells and by macrophages. For dendritic cells, these include the thymic medulla, splenic periarterial sheaths, and lymph node deep cortex; for macrophages, the B7-2-rich regions included the splenic marginal zone and lymph node subcapsular cortex. Splenic B7-2+ cells were accessible to labeling with GL-1 mAb given intravenously. Dendritic cell stimulation of T cells (DNA synthesis) during the mixed leukocyte reaction was significantly (35-65%) blocked by GL-1.(ABSTRACT TRUNCATED AT 400 WORDS)

Abatacept↗

PubMed1994

Application of pharmacokinetically guided dose escalation with respect to cell cycle phase specificity.

BACKGROUND: In 1986, the concept of pharmacokinetically guided dose escalation (PGDE) was proposed to predict the maximum tolerated dose (MTD) of an antitumor drug in humans from animal data. We have previously shown that antitumor drugs can be classified into two types, depending on their cytotoxic mechanisms: type 1 drugs, which are cell cycle phase-nonspecific agents, i.e., area under the curve for drug concentration in the plasma versus time (AUC)-dependent drugs; and type 2 drugs, which are cell cycle phase-specific agents, i.e., those that are time dependent. PURPOSE: The validity of the assumption that the AUC at the dose lethal for 10% of mice administered drug (LD10) is equal to the AUC at MTD for humans, the premise on which PGDE is based, was examined for type 1 and 2 drugs. METHODS: Findings in the literature, including those of Collins and co-workers, were retrospectively analyzed. The human/mouse ratios for the AUC were compared with each other and with the human/mouse dose ratios, based on milligram per meter square of body surface area, the measurement currently used in clinical trials of antitumor drugs. For six of the type 1 drugs, the human/mouse ratio for the AUC of total drug (AUC) and that of unbound drug (AUCu), which has been considered a determinant of pharmacologic and toxicologic effects, were also compared. RESULTS: There was an excellent correlation between log AUC at LD10 for mice and log AUC at MTD for humans for type 1 drugs (r = .898), but not for type 2 drugs (r = .677). For type 1 drugs, the correlation between mouse AUC at LD10 and human AUC at MTD was better for unbound drug (r = .961) than for total drug (r = .892). CONCLUSIONS: PGDE is useful for type 1 drugs; differences in protein binding between species should, however, be considered when using this method.

Animals↗

PubMed1994

Translation initiation from non-AUG codons in COS1 cells is mRNA species dependent.

Sendai virus P/C mRNA, human erythrocyte membrane protein 4.1 mRNA and PDGF-B chain mRNA were used to test whether translation initiation from non-AUG codons in COS1 cells was mRNA species dependent. Site-directed mutants of the authentic translation start sites of these mRNAs to alternate start codons showed that while P/C mRNA is capable of initiating translation from non-AUG start sites the other two mRNAs are not. Our study shows that translation initiation from non-AUG codons is mRNA species dependent and suggests that higher order structure of an mRNA determines the non-AUG translation start site.

Animals↗

PubMed1994

Requirement of donor-derived stromal cells in the bone marrow for successful allogeneic bone marrow transplantation. Complete prevention of recurrence of autoimmune diseases in MRL/MP-Ipr/Ipr mice by transplantation of bone marrow plus bones (stromal cells) from the same donor.

MRL/MP-Ipr/Ipr (MRL/Ipr) mice possess radioresistant (9.5 Gy) abnormal stem cells and show a recurrence of autoimmune diseases within 5 mo of conventional allogeneic bone marrow transplantation. We recently have found that the MHC preference exists between hemopoietic stem cells and stromal cells; when bones are engrafted, donor-derived stromal cells present in the engrafted bones can migrate into the recipient bone marrows, which are replaced with both donor-derived stromal cells and hematopoietic cells. Based on these findings, we attempted to prevent the recurrence of autoimmune diseases in MRL/Ipr mice by the transplantation of both bone marrow cells and bone (as a source of stromal cells). MRL/Ipr mice were irradiated (8.5 Gy) and then reconstituted with C57BL/6 bone marrow cells plus bone grafts. The mice survived more than 48 wk after this treatment. Immunohistologic studies revealed that the mice were completely free from both lymphadenopathy and autoimmune diseases such as lupus nephritis and rheumatoid arthritis. Sera from these mice showed normal levels of circulating immune complexes and rheumatoid factors. Normal functions of both T cells and B cells were noted. Abnormal T cells such as Thy-1+B220+ cells present in nontreated MRL/Ipr mice could not be seen in the thus-treated mice. In addition, to our surprise, spleen cells from treated mice showed completely normal in vitro primary anti-SRBC responses. These results indicate that stromal cells in allogeneic bone marrow transplantation play a crucial role not only in the prevention of graft failure but also in the successful cooperation among APCs, T cells, and B cells. Although MRL/Ipr mice are radiosensitive and usually die of interstitial pneumonia or fatty liver due to the side effects of radiation, it should be noted that this strategy allows a reduction in the radiation dose (9.5 Gy-->8.5 Gy), and that these mice can survive more than 48 wk without showing any symptoms of autoimmune diseases.

Animals↗

PubMed1994

The involvement of polyamines in the activation of vitamin D receptor from porcine intestinal mucosa.

In the intracellular process of the action of calcitriol, vitamin D receptor is thought to undergo some kind of physiochemical change, called activation, before the receptor binds to the vitamin D response element of the gene. In this paper, the effects of polyamines and their analogues on the sedimentation properties of vitamin D receptor prepared from porcine intestinal mucosa, and on DNA binding activity of the receptor, were studied. In sucrose density gradient analysis, polyamines decreased the sedimentation coefficient of vitamin D receptor in a dose-dependent fashion. Polyamines increased DNA binding activity of vitamin D receptor dose-dependently. These findings show that polyamines can activate vitamin D receptor in vitro. Among naturally existing polyamines, spermidine and spermine, but not putrescine, were effective within their physiological intracellular concentrations, suggesting that both spermidine and spermine can activate vitamin D receptor in vivo as well. Sucrose density gradient analysis using various kinds of polyamine analogues having various numbers of cations showed that the number of cation of polyamines is important for the efficiency to change the sedimentation coefficient of vitamin D receptor, and that the distance between two cationic charges does not play an important role.

Animals↗

PubMed1994

Presence of gene expression of vitamin D receptor and 24-hydroxylase in OK cells.

We investigated the gene expression of 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) receptors (VDR) and 25-hydroxy-vitamin D3-24-hydroxylase (24-hydroxylase) in opossum kidney (OK) cells. Reverse transcription-polymerase chain reaction demonstrated the presence of VDR gene expression in OK cells. Northern hybridization, using rat VDR cDNA, also demonstrated a 4.4 kbp VDR mRNA expression which was affected by serum but not by 1,25(OH)2D3 and/or parathyroid hormone stimulation. Stimulation with 1,25(OH)2D3 induced 24-hydroxylase mRNA expression which peaked at 6 h. This study clearly demonstrates for the first time the presence of VDR and 24-hydroxylase gene expression in OK cells, suggesting that OK cells are a useful model for investigating the genetic action mechanisms of 1,25(OH)2D3.

Animals↗

PubMed1994

Protein kinase C is involved in 24-hydroxylase gene expression induced by 1,25(OH)2D3 in rat intestinal epithelial cells.

Effects of protein kinase C (PKC) inhibitor and activator on 1,25(OH)2D3-induced gene expression were examined in rat intestinal epithelial cells, IEC-6 cells. A potent PKC inhibitor, H-7 (20 microM), completely abated 1,25(OH)2D3-induced 24-hydroxylase gene expression at 3 and 6 h. The effect of H-7 was dose dependent with IC50 around 5 microM. Other protein kinase inhibitors, HA-1004 and H-89 (20 microM), had no effects. Furthermore, the activation of PKC by 12-O-tetradecanoylphorbol-13-acetate (TPA) potentiated the effect of 1,25(OH)2D3 by 1 h. TPA appeared to exert its effect at a transcriptional step, since mRNA stability was not affected by TPA treatment. At 3 h after the treatment of the cells with H-7 and TPA, vitamin D receptor (VDR) contents estimated by 3H-1,25(OH)2D3 binding capacity were 72.4 and 63.2% of vehicle-treated cells without significant changes of binding affinities, suggesting that the effect of H-7 and TPA was not the result of changes in VDR content or its binding affinity. In conclusion, PKC is involved in 1,25(OH)2D3-induced 24-hydroxylase gene expression in IEC-6 cells between 1,25(OH)2D3-VDR binding and VDR-induced gene transactivation.

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

PubMed1994

Plantar or dorsalis pedis artery bypass in Buerger's disease.

The peripheral type of Buerger's disease is unresponsive to conservative therapy when accompanied by multisegmental occlusion at the level of the ankle. Between November 1983 and April 1993, we performed 15 bypasses below the ankle for this type of thromboangiitis obliterans in 13 patients (mean age 45.7 years), including four females. Ten patients had intractable toe ulcers with severe pain, and five had foot-threatening ischemia or disabling foot claudication. Eleven patients were heavy smokers, two were passive smokers, and six had a history of sympathectomy. All patients had occlusion of the three main crural arteries or both of the tibial arteries at the ankle. Of the 15 bypasses, 10 were to the medial or lateral plantar arteries, two were to the common plantar artery, and three were to the dorsalis pedis artery. There were three early and three late graft failures. The causes of early graft failure were thrombosis at the site of cross-clamping, anastomosis to a diseased segment, and arterial spasm. The three late failures (> 3 months) were due to disease progression in patients who continued to smoke, whereas all grafts remained patent and functioned well in patients who stopped smoking. Because patients with thromboangiitis obliterans are relatively young and active, early healing of ulcers and restoration of normal limb function are important objectives in their treatment. Bypass to the foot arteries can provide an excellent outcome, although special techniques and postoperative cessation of smoking are essential for success.

Adult↗

PubMed1994

Antroduodenal motility and transpyloric fluid movement in patients with diabetes studied using duplex sonography.

BACKGROUND/AIMS: To elucidate the relationship between diabetic autonomic neuropathy and gastrointestinal motility, antroduodenal motility was studied in patients with diabetes using duplex sonography. METHODS: Antroduodenal motility, transpyloric fluid movement, and velocity curves of fluid flow were studied using duplex sonography in 32 patients with diabetes and 10 healthy subjects after their ingestion of a meat soup. RESULTS: The frequency of antroduodenal coordination was significantly reduced in patients with diabetes with both early and definite autonomic neuropathy compared with healthy subjects (P < 0.05 and P < 0.01, respectively). The frequency and duration of end-cycle reflux episodes were also significantly reduced in patients with early and definite autonomic neuropathy compared with healthy subjects (P < 0.05 and P < 0.01, respectively). The frequency of end-cycle reflux episodes was closely correlated with the frequency of antroduodenal coordination in both healthy subjects (r = 0.859; P = 0.002) and patients with diabetes (r = 0.929; P = 0.0001). There was a significant correlation between fasting plasma glucose concentrations and the frequency of antroduodenal coordination in patients with diabetes (r = -0.361; P = 0.039). CONCLUSIONS: These findings suggest that reduced frequency and duration of end-cycle reflux episodes may be an early indicator of diabetic gastroparesis that may be related mainly to autonomic neuropathy but also in part to acute hyperglycemia.

Adult↗

PubMed1994

Functional analysis of thymic B cells.

The expression of low- and high-affinity interleukin-5 receptors (IL-5Rs) on thymic B cells and reactivity of thymic B cells to IL-5 was investigated. Thymic B cells consist of two populations (CD5+ and CD5- B cells), as previously described. Three-color FACS analyses using anti-CD5, anti-IgK, and anti-IL-5R mAbs reveal that approximately 60% of both populations (CD5+ and CD5-) in the thymus possess IL-5R, detected by mAb H-7. In Scatchard plot analyses, IL-5Rs on thymic B cells are observed as low affinity receptors; the high-affinity IL-5R, which is known to be expressed on some IL-5-activated splenic B blasts or some IL-5-dependent cell line cells, is not clearly detected on thymic B cells. The reactivity of thymic B cells to IL-5 is found to be significantly lower than that of splenic B cells both in proliferative responses and LPS-induced IgM and IgA antibody responses. These findings are compatible with the expression of the low-affinity IL-5R on thymic B cells. The responsiveness of thymic B cells to either IL-6 or the combination of IL-4, IL-5 and IL-6 is also lower than that of splenic B cells. Furthermore, the thymic B cells are found to induce neonatal tolerance. Therefore, thymic B cells act as antigen-presenting cells in the negative selection of thymocytes, rather than as antibody-producing cells under the influence of foreign antigens and/or regulatory cytokines.

Animals↗

PubMed1994

Evaluation of antitumor activity of navelbine (vinorelbine ditartrate) against human breast carcinoma xenografts based on its pharmacokinetics in nude mice.

The in vitro antitumor activity of navelbine (NVB, KW-2307), a newly synthesized vinca alkaloid, was compared with that of adriamycin (ADM) against human breast carcinomas inoculated into nude mice at the maximum tolerated dose (MTD) and clinically equivalent dose (CED). The plasma levels of NVB after intravenous injection into nude mice at doses of 1.2 and 4.8 mg/kg diminished rapidly during the early phase (0-1 h), followed by a very long shallow one. NVB was still detected 96 h after administration at a dose of 4.8 mg/kg. The pharmacokinetic parameters of NVB in plasma indicated that NVB extensively distributes to tissues. The CED of NVB was provisionally decided to be 4.8 mg/kg based on the comparison of AUC values at 24-infinity h between human patients and nude mice. When compared by a single injection of MTD (NVB, 16 mg/kg; ADM 12 mg/kg), NVB was effective against all four tumor lines, MC-2, MC-8, MMKY and H-31, while ADM was effective only against H-31. On the other hand, the body weight loss by NVB was mild as compared with that by ADM, indicating that the antitumor activity of NVB is superior to that of ADM at their MTDs. A single injection of NVB at its CED (4.8 mg/kg) produced a poor antitumor effect and no or little toxicity in terms of body weight loss, as compared with those at MTD. However, when NVB was administered intermittently at CED, it exhibited significant antitumor activity against three tumor lines. The body weight loss was still mild even on this intermittent schedule.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma, Papillary↗

PubMed1994

Different modes of cell-killing action between DNA topoisomerase I and II inhibitors revealed by kinetic analysis.

We compared the modes of cell-killing by DNA topoisomerase I and II inhibitors. The effects of camptothecin (CPT), KT-6528 and UCE6 upon colony formation by inhibiting DNA topoisomerase I, and of etoposide (VP-16), teniposide, amsacrine and UCT4-A as inhibitors of DNA topoisomerase II were analyzed based upon a kinetic method that distinguishes between cell cycle phase-specific and -nonspecific agents. Human colorectal cancer WiDr cells were exposed to several concentrations of each agent for various periods and 90%-inhibitory concentrations (IC90) at each time were determined by means of a clonogenic assay. When exposure times and corresponding IC90s were plotted on a log-log scale, all inhibitors of DNA topoisomerase II gave curves including a linear portion with a slope of -1, which is characteristic of cell cycle phase-nonspecific agents. In contrast, the curves for all inhibitors of DNA topoisomerase I had a much steeper slope than -1, which is typical of cell cycle phase-specific agents. In agreement with this finding, the cells were remarkably accumulated in the G2-M phase when exposed to VP-16, but in late S-phase when exposed to CPT as determined by a flow cytometric assay. These results indicated that the two classes of agents kill cells in a quite different manner although they are inhibitors of similar enzymes.

Amsacrine↗

PubMed1994

Impaired homologous upregulation of vitamin D receptor in rats with chronic renal failure.

We studied the homologous regulation of the vitamin D receptor (VDR) in the duodenum of rats with chronic renal failure. Mean basal nuclear 3H-labeled 1 alpha,25-dihydroxyvitamin D3 ([3H]1,25(OH)2D3) binding capacity was 48 and 43 fmol/mg protein for sham-operated and uremic rats with similar dissociation constants (Kd), respectively. These results coincided with those of immunoblot analysis, which found that VDR protein level of uremic rats was 87.6% that of sham-operated rats. In uremic rats, 1,25(OH)2D3, 2.0 micrograms/kg, failed to upregulate VDR protein levels until 24 h, in contrast to the significant increases produced in sham-operated rats at both 12 (1.55-fold) and 24 h (1.75-fold). Baseline level of VDR mRNA in uremic rats, determined by Northern blot analysis, was comparable to that in sham-operated rats. Treatment with 1,25(OH)2D3 slightly decreased VDR mRNA at 6-24 h in the sham-operated rats, in contrast to the increase seen at 6 h in uremic rats. These results suggest that the homologous upregulation of VDR was attenuated in rats with chronic renal failure because of an impairment at a translational and/or posttranslational step.

Analysis of Variance↗

PubMed1994

Potentiated 1,25(OH)2D3-induced 24-hydroxylase gene expression in uremic rat intestine.

24-Hydroxylase has been considered a major enzyme regulating metabolism of circulating 1 alpha, 25-dihydroxyvitamin D3 [1,25(OH)2D3]. To understand the metabolism of 1,25(OH)2D3 in chronic renal failure, we examined 1,25(OH)2D3-induced 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase) gene expression in the intestine of uremic rats. Northern blot and dot blot analyses showed that the induction of duodenal 24-hydroxylase gene expression was 2.0- to 3.8-fold greater in uremic rats than in sham-operated rats (P < 0.05, Student's t-test) at 6 h after 1,25(OH)2D3 administration. Gene induction of calbindin D9k by 1,25(OH)2D3 was not augmented in uremic group. In situ hybridization analysis revealed that the induction of 24-hydroxylase mRNA by 1,25(OH)2D3 was observed exclusively in the columnar epithelium of the crypt and the lower part of the villi, suggesting that the stage of epithelial cell differentiation is a major determinant of 1,25(OH)2D3-induced 24-hydroxylase gene expression. In uremia, 1,25(OH)2D3-induced 24-hydroxylase gene expression was accelerated selectively, possibly because of poorly differentiated epithelial cells.

Animals↗

PubMed1994

Autoimmune diseases as stem cell disorders.

Using an animal model for insulin-dependent diabetes mellitus (IDDM), the NOD mouse, we have demonstrated that allogeneic bone marrow transplantation (BMT) has a preventative effect on IDDM, and that a combined transplantation of pancreas and bone marrow can be used to treat IDDM. We have also shown that BMT has a curative effect on systemic autoimmune disease in (NZB x NZW) F1, BXSB, and (NZW x BXSB) F1 mice but not in MRL/lpr mice. Since MRL/lpr mice possess abnormal radioresistant hemopoietic stem cells (HSCs), they suffer a relapse 5 months after BMT. Recently, we have found that major histocompatibility complex (MHC)-matched stromal cells in the bone marrow are essential to the support of HSCs in the Go phase. We therefore attempted to treat autoimmune diseases in MRL/lpr mice by the transplantation of stromal cells with HSCs. Transplantation of HSCs with bone to recruit stromal cells was indeed found to have a curative effect on autoimmune diseases in the mice. These results indicate that BMT with bone graft will become a valuable strategy for the treatment of patients with both systemic and organ-specific autoimmune diseases. To prove that autoimmune diseases originate from defects in HSCs, we transferred the HSCs of autoimmune-prone mice to normal mice. BMT or transplantation of stem-cell concentrates induced organ-specific and/or systemic autoimmune diseases in [NOD-->C3H/HeN] and [(NZW x BXSB)F1-->C3H/HeN or C57BL/6J] chimeric mice. These results provide direct evidence that the etiopathogenesis of autoimmune diseases, including both organ-specific and systemic autoimmune diseases, is attributable to defects in the HSCs themselves. We further provide that various intractable diseases such as non-insulin-dependent diabetes mellitus and chronic nephritis (focal glomerulosclerosis) are also organ-specific autoimmune diseases, and that BMT can be used to treat them.

Animals↗

PubMed1994

[A case of temporary severe disequilibrium hypercalcemia].

The patient, a 69-year-old woman, was admitted to Osaka City University Hospital on July 25, 1992, for severe hypercalcemia. Laboratory data on admission revealed severe hypercalcemia of 14.9 mg/dl and renal dysfunction with serum creatinine of 2.9 mg/dl. As reflected by increased urinary excretions of pyridinoline and deoxypyridinoline and suppressed serum levels of parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D, increased bone resorption seemed to be a main factor for the development of hypercalcemia. The development of hypercalcemia seemed to be acute because of (i) her severe symptoms caused by hypercalcemia and (ii) impaired renal function which improved after normalization of serum calcium. Following combination therapy of saline infusion and furosemide, there was a gradual decrease and later normalization of serum calcium together with serum creatinine. Even 8 months after discontinuation of the therapy for hypercalcemia, the serum calcium level has remained within the normal range. Measurement of serum factors which have hypercalcemia effects such as PTH, parathyroid hormone-related peptide and cytokines (interleukin-1 alpha, interleukin-1 beta, interleukin-2, interleukin-6 and tumor necrosis factor-alpha) were all within the normal range. In summary, hypercalcemia in this patient was regarded as a kind of disequilibrium hypercalcemia due to a combination of increased bone resorption and decreased renal capacity to excrete calcium. Furthermore, since it was temporary and has not recurred despite no treatment, her hypercalcemia developed due to imbalance in calcium regulation but not due to any organic disease.

Acute Disease↗