Biomedical subjects

T H Chen

Publications and source records attributed to T H Chen.

At least 109 records · Page 6Linked to original sources

PubMed1995

Silicone injection granulomas of the breast: treatment by subcutaneous mastectomy and immediate subpectoral breast implant.

Silicone leakage from silicone breast prostheses with or without rupture of the prostheses is of great concern. Silicone injection for breast augmentation is still common in Asia, even though silicone injection induced granulomas and associated malignancy have been reported. A series of 24 women who had bilateral silicone injection granulomas in their breasts, requiring subcutaneous mastectomies and immediate breast reconstruction, is presented. Most of the patients had had one silicone injection into each breast. The patients' average age was 37.5 years and removal of the granulomas was done 3-20 years (mean 8.4 years) after the silicone injections. All patients had breast lumps and some had mastitis (21%) and dermatitis (16%) but none had palpable axillary lymph nodes. Mammograms showed diffuse, multiple granulomas of various sizes. Subcutaneous mastectomies were done via inframammary incisions. Immediate breast reconstruction was carried out with double-lumen silicone/saline implants or textured saline-filled implants inserted subpectorally via a separate axillary incision. The implants were entirely covered by the pectoralis major muscle and partially dissected serratus anterior fascia. Two cases had wound infections (8%) as early complications, and two cases developed hypertrophic scars (8%). At 6-41 months follow-up (mean 21.4 months), 69% of the patients had Baker II and 31% of the patients had Baker III breast capsular contractures.

Adult↗

PubMed1995

U-73122 inhibits carbachol-induced increases in [Ca2+]i, IP3, and insulin release in beta-TC3 cells.

We studied the effects of the aminosteroid U-73122, a putative phospholipase C (PLC) inhibitor, on carbachol-induced increases in insulin release, [Ca2+]i, and IP3 in beta-TC3 cells. Carbachol (0.1-100 microM) increased [Ca2+]i and carbachol (0.1-1000 microM) increased insulin release dose-dependently. Carbachol (100 microM) also increased inositol 1,4,5-trisphosphate (IP3) production. U-73122 (2-12 microM) inhibited the effects of carbachol on [Ca2+]i and insulin release in a dose-dependent manner, and at the highest dose studied (12 microM) it abolished or greatly attenuated all three effects of carbachol. In contrast, U-73343 (12 microM), the analog of U-73122 that does not inhibit PLC, only inhibited the effect of carbachol on [Ca2+]i by 20%, and did not inhibit the effect of carbachol on insulin release. Since carbachol increases IP3, [Ca2+]i, and insulin release by activating PLC, these results suggested that U-73122 inhibits phospholipase C-dependent processes in beta-TC3 cells.

Animals↗

PubMed1995

Bilateral gluteus maximus V-Y advancement musculocutaneous flaps for the coverage of large sacral pressure sores: revisit and refinement.

Surgical management of the sacral defect using the gluteal muscle or musculocutaneous flap has been well accepted over the years. In this study, refinements in the bilateral gluteus maximus V-Y advancement musculocutaneous flaps were made. These refinements include having sharper angle (60 degrees or less) at the donor sites of the flap, cutting the edges of the gluteal muscle of 3 cm beyond the skin flap, and cutting most parts of the gluteal muscle at a depth of only 2.5 cm (at the level of upper third portion). These improvements result in less tension closure of the donor site, easier closure of the advanced flaps in two planes without tension, and better preservation of most parts of the gluteal muscular insertions to the femur and their functions. The design of V-Y advancement has successfully maintained the superior and inferior gluteal vessels and inferior gluteal nerve. In this study, the average sacral defect was more than 12 cm in diameter, and each advanced flap was 15 x 12 x 3 cm in size. Of the 63 consecutive patients undergoing bilateral gluteus maximus V-Y advancement musculocutaneous flaps with refinements for coverage of large sacral pressure sores, 59 (93%) achieved complete healing after an average follow-up period of 28 months. Only 4 patients had recurrences of sacral sore. In this study, the duration of hospital stay for flap coverage averaged 38.5 days. Four patients (6%) had superficial dehiscences of the donor site requiring skin grafting. Ten patients (16%) developed stitch abscesses and 9 patients (14%) had wound infections, but no flap was lost. No significant functional impairment related to the flap procedure was noted. The operative technique described in this paper is not only simple and noninvasive, but with our refinements of flap design, the bilateral gluteus maximus V-Y advancement musculocutaneous flaps also provide reliable and durable coverage for large sacral pressure sores.

Adult↗

PubMed1995

Activation of two osmotin-like protein genes by abiotic stimuli and fungal pathogen in transgenic potato plants.

Osmotin-like proteins are encoded by at least six members of a multigene family in Solanum commersonii. A genomic clone (lambda pGEM2a-7) that contains two osmotin-like protein genes (OSML13 and OSML81) arranged in the same transcriptional orientation has been isolated. Restriction mapping and sequence analysis indicated that the two intronless genes correspond to the previously characterized pA13 and pA81 cDNAs. To study the transcriptional activation of OSML13 and OSML81 promoters, the 5' flanking DNA sequence (-1078 to +35 of OSML13 and -1054 to +41 of OSML81) was fused to the beta-glucoronidase (GUS) coding region, and the chimeric gene fusions were introduced into wild potato (S. commersonii) plants via Agrobacterium-mediated transformation. Analysis of the chimeric gene expression in transgenic potato plants showed that both 5' flanking DNA sequences are sufficient to impart GUS inducibility by abscisic acid, NaCl, salicylic acid, wounding, and fungal infection. Low temperature activated both chimeric genes only slightly. Infection with Phytophthora infestans resulted in strong GUS expression from both chimeric genes primarily in the sites of pathogen invasion, suggesting a limited diffusion of fungal infection-mediated signals. The expression patterns of both osmotin-like protein genes implicate their dual functions in osmotic stress and plant pathogen defense.

Abscisic Acid↗

PubMed1995

Regulation of Ca(2+)-conducting currents in parathyroid cells by extracellular Ca(2+) and channel blockers.

High extracellular Ca2+ concentrations ([Ca2+]o) produce sustained intracellular Ca2+ responses in parathyroid cells that correlate with suppression of parathyroid hormone release. Using whole cell patch clamping, we identified two types of Ca(2+)-conducting currents in these cells. Type 1 currents were enhanced by raising [Ca2+]o and blocked by Cd2+ and nifedipine, whereas type 2 currents were resistant to blockade by these agents. Both types of membrane currents were cation nonselective, voltage independent over a broad range of membrane potentials, and blocked by the trivalent ions La3+ and Gd3+ (> 98%). Cd2+, La3+, and Gd3+ had biphasic effects on membrane conductance (Gm). At submicromolar concentrations, these ions increased Gm, whereas at higher concentrations they reduced Gm. In contrast to ionic channel blockers, nifedipine had only an inhibitory effect on the Ca(2+)-conducting currents that were sensitive to changes in [Ca2+]o (dose inhibiting 50% of maximal response = approximately 3-10 x 10(-8) M). Microfluorimetric ratio-imaging analysis of single parathyroid cells loaded with fura 2 showed that Gd3+ inhibited sustained intracellular Ca2+ responses to high [Ca2+]o. These findings suggest that the Ca(2+)-conducting currents identified in these studies may play a role in regulating intracellular Ca2+ responses in this system.

Animals↗

PubMed1995

Effect of AVP and oxytocin on insulin release: involvement of V1b receptors.

We used a number of receptor antagonists to determine which receptors mediate the effect of arginine vasopressin (AVP) and oxytocin (OT) on insulin release. We found that OT (10(-7) M) and AVP (10(-8) M) increased insulin release from the perfused rat pancreas with similar magnitude. The antagonist with potent V1b receptor-blocking activity, dP[Tyr(Me)2]AVP (10(-7) M), abolished the effect of OT and AVP, whereas the highly selective OT receptor antagonist L-366,948 (10(-6) M) did not change the effect of OT, nor did a V1a receptor antagonist, d(CH2)5[Tyr(Me)2]AVP (10(-7) M), change the effect of AVP. The insulin-releasing potency of OT was estimated as 9-fold less than that of AVP in RINm5F cells. Selected AVP and OT antagonists were used to study their antagonism on AVP- and OT-induced insulin release from RINm5F cells, and the order of potencies of antagonists was estimated as dP[Tyr(Me)2]AVP > d(CH2)5[D-Phe2,Ile4]AVP > SR-49059 > d(CH2)5[Tyr(Me)2]AVP > desGly9d(CH2)5[Tyr(Et)2]VAVP (WK-3-6) approximately L-366,948. These results were consistent with the V1b receptor antagonistic activities of the antagonists. d[D-3-Pal]VP, a V1b receptor agonist, increased insulin release dose dependently (10(-9) to 10(-6) M), and this effect was antagonized by dP[Tyr(Me)2]AVP but not by WK-3-6 (10(-6) M). These results suggested that the stimulatory effect of both OT and AVP on insulin release from beta-cells may be mediated by V1b, but not by V1a or OT receptors.

Animals↗

PubMed1995

Mutational analysis of the cytoplasmic tail of the G protein-coupled receptor for parathyroid hormone (PTH) and PTH-related protein: effects on receptor expression and signaling.

The present studies were undertaken to examine the role of the cytoplasmic tail of the G protein-coupled receptor for PTH and PTH-related protein (PTHrP) on receptor signaling and expression. The wild type (WT) receptor (585 amino acids) and five truncated receptors whose cytoplasmic tails terminated at residues 507, 494, 474, 466, and 458 were expressed in COS-7 cells. Based on [125I]PTHrP binding, mutants T507, T494, and T466 displayed progressively decreased levels of expression, compared with WT. The tailless mutant T458 was not expressed in a functional form, whereas T474 was expressed at a level similar to WT. Comparable results were obtained when expression levels of WT and mutated PTH/PTHrP receptors were evaluated by Western blotting. Binding affinities were similar for all mutated receptors (IC50 = 1-2 nM). Immunocytochemistry showed that WT and mutated receptors were diffusely distributed, presumably at the cell surface, except for the tailless mutant T458, which displayed striking perinuclear localization. T458 did not display an adenylyl cyclase response to PTH, while the other mutants were similar to WT both with respect to their maximal adenylyl cyclase responses to PTH and to their EC50 values. Cai2+ signaling properties of these mutants were assessed as PTH-stimulated 45Ca efflux from Xenopus oocytes that had been injected with in vitro transcribed PTH/PTHrP receptor cRNAs. The WT and mutated receptors (except for T458) responded to PTH with significant (6- to 27-fold) increases in 45Ca efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

PubMed1995

Total hip arthroplasty in patients with ankylosing spondylitis: longterm followup.

OBJECTIVE: To evaluate the longterm functional effects of total hip arthroplasty (THA) on 46 patients. METHODS: Clinical and radiographic examinations were performed on 46 patients (74 THA) with ankylosing spondylitis (AS). The mean followup period was 100 months (range 37-174 months); 32 hips were followed for more than 10 years. RESULTS: Significant benefit was obtained in pain control (all but 2) and function (mean improvement in range of motion 128 degrees) in the early stage so that patients could be gainfully employed. An average 100 months after THA, the overall functional results were rated excellent in 21 hips, good in 28, fair in 7, and poor in 18. Only 6 hips (8%) in our series developed clinically significant (Class III or IV) heterotopic ossification. Seventeen hips needed a 2nd operation because of loosening (11 hips), deep infection (3), malposition of acetabular component (2), and prosthetic failure (1). Another 6 hips showed definite loosening on radiographs and needed to be revised. The total incidence of failure was 31% (23 hips). The average time from the index operation to loosening was 9.5 years (range 4-13 years). Factors contributing to component loosening were young age, short stature, and decreased postoperative range of motion. CONCLUSION: Total hip arthroplasty can be very important and beneficial to patients with AS, but the patients, being young and active, and with their rigid spines, do not treat their prostheses gently and are very dependent upon their mobility. They must be kept under supervision long after THA, probably for the rest of their lives, to identify possible longterm complications.

Adult↗

PubMed1995

Nonvascularized proximal fibular autograft to treat giant-cell tumor of the distal radius.

BACKGROUND: The Distal end of the radius is the third most common site where giant-cell tumors occur. High recurrent rate was reported after curettage. To manage such aggressive tumors, wide resection is the best treatment and nonvascularized proximal fibular autograft has been widely used for reconstruction. METHODS: Eight patients were treated here with this method from April, 1988 to April, 1992. Patients' average age was 40 years, and all had grade III. Of the four males and females, six tumors were over the dominant hands and the other two, over the nondominant ones. They were treated primarily with wide resection and reconstruction with osteochondral proximal fibular autograft, from either the ipsilateral or contralateral side. Bone anastomotic site was fixed with dynamic compression plate. The soft tissue was directly repaired in six patients and reinforced with extensor carpi radialis longus tendon in two. RESULTS: Patients were regularly followed from 14-60 months, for an average of 25 months. The average grip strength of the affected hands was 77% that of the unaffected sides. There were four distal radioulnar joint diastasis, one ulnar deviation of the wrist, one volar tilt of the carpal bones and one transient peroneal palsy over the donor site. No recurrence or metastasis was found up to the last follow-up. The average total range of motion of the affected wrist (supination, pronation, dorsiflexion and palmar flexion) was 185 degrees. All Patients were satisfied with the results. CONCLUSIONS: Using proximal fibular autograft to reconstruct the bony defect and joint after wide excision for distal radial giant-cell tumor gives satisfactory results. It is a widely accepted good method, though there are many problems still unresolved.

Adult↗

PubMed1994

Injection of bovine parathyroid poly(A)+ RNA into Xenopus oocytes confers sensitivity to high extracellular calcium.

Parathyroid cells detect increments in the extracellular [Ca2+], which lead to substantial increases in intracellular free Ca2+ ([Ca2+]i) and, ultimately, to suppression of parathyroid hormone (PTH) secretion. To determine whether mRNA from parathyroid tissue could confer sensitivity to high extracellular Ca2+, we isolated and injected total bovine parathyroid poly(A)+ RNA into Xenopus laevis oocytes. To assess translational activity of the RNA, PTH released into the media was measured. Intact PTH was detected in the medium for < or = 48 h, and injection of increasing amounts of RNA (approximately 0.5-50 ng/oocyte) led to the release of greater quantities of PTH. We screened for the expression of a putative Ca2+ sensor molecule by measuring 45Ca efflux from preloaded oocytes, in response to raising extracellular [Ca2+] from 0.7 to 5.7 mM. This increment in [Ca2+] stimulated 45Ca efflux by 249 +/- 52 cpm over 20 min from eggs injected with parathyroid poly(A)+ RNA (n = 22). This response was significantly greater than 45Ca efflux from any group of controls exposed to the same change in extracellular Ca2+ (p < 0.02), including oocytes injected with either water, cRNA for the platelet-derived growth factor (PDGF) BB receptor, or T cell poly(A)+ RNA. Size-fractionation of poly(A)+ RNA over sucrose gradients demonstrated that mRNA, which induced responsiveness to high extracellular Ca2+, was present in fractions with transcripts of approximately 5-9 kB. Injection of these fractions also conferred sensitivity to the presence of Ba2+ or Sr2+ (both at 5 mM) in the media.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Refinement of McIndoe's vaginal reconstruction with ORFIT "S" vaginal stent.

Using McIndoe's vaginal reconstruction with the ORFIT "S" vaginal stent, we achieved good results in 5 patients with congenital vaginal absence over the past 3 years. The ORFIT "S" vaginal stent is a semirigid, porous, and inexpensive stent. The application is easy intraoperatively, and minimal daily care is required for long-term postoperative dilatation. The stent keeps the neovagina in full acceptance of the speculum after long-term follow-up.

Equipment Design↗

PubMed1994

Examining the interaction of age x race pertaining to black-white differences at ages 15 to 93 on six Horn abilities assessed by K-FAST, K-SNAP, and KAIT subtests.

This study examined differences between black and white subjects on 6 abilities from Horn's Gf-Gc theory for 5 age groups between 15-19 and 55-93 years (total ns = 956 white and 128 black subjects). White respondents scored significantly higher on all 6 abilities, but differences on fluid reasoning and short-term apprehension and retrieval were less than .5 SD. Interactions of age x race were nonsignificant, indicating that the discrepancies between scores of black and white subjects did not vary as a function of age.

Adolescent↗

PubMed1994

Inhibition of insulin release by a formamidine pesticide amitraz and its metabolites in a rat beta-cell line: an action mediated by alpha-2 adrenoceptors, a GTP-binding protein and a decrease in cyclic AMP.

We tested the hypothesis that the formamidine pesticide amitraz and its metabolites inhibit insulin release from a rat beta-cell line (RINm5F) by decreasing intracellular cyclic AMP levels and examined whether GTP-binding proteins were involved in the process. Amitraz and its active metabolite BTS27271 (0.1-10 microM) inhibited insulin release that was induced by 100 microM of IBMX in a dose-dependent manner. Other metabolites of amitraz tested failed to inhibit insulin release. A potent and specific alpha-2 adrenoceptor agonist, medetomidine (0.1 microM), abolished the IBMX-induced insulin release. Amitraz, BTS27271 and medetomidine also decreased intracellular cyclic AMP concentrations that were elevated by IBMX administration. Moreover, all three drugs inhibited the insulin release stimulated by forskolin (1 microM), an adenylyl cyclase activator. Yohimbine (0.01, 0.1 and 1 microM), an alpha-2 adrenoceptor antagonist, prevented the inhibitory effect of amitraz and BTS27271 on insulin release, whereas prazosin (1 microM), an alpha-1 adrenoceptor antagonist, did not. Yohimbine, but not prazosin, also prevented the effect of amitraz, BTS27271 and medetomidine on IBMX-stimulated accumulation of cyclic AMP. Pretreatment of cells with PTX (0.1 micrograms/ml) for 16 h, antagonized the effects of amitraz and BTS27271 on IBMX-induced increase in insulin release. Thus, one mechanism by which amitraz and its metabolite BTS27271 decrease insulin release is by inhibiting adenylyl cyclase, an action mediated through a PTX-sensitive G-protein.

1-Methyl-3-isobutylxanthine↗

PubMed1994

Arginine vasopressin-stimulated insulin secretion and elevation of intracellular Ca++ concentration in rat insulinoma cells: influences of a phospholipase C inhibitor 1-[6-[[17 beta-methoxyestra-1,3,5(10)-trien- 17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122) and a phospholipase A2 inhibitor N-(p-amylcinnamoyl)anthranilic acid.

The present study investigated the mechanism by which arginine vasopressin (AVP) increases insulin secretion in rat insulinoma (RINm5F) cells by using a specific phospholipase C (PLC) inhibitor, 1-[6-[[17 beta-3-methoxyestra-1,3,5(10)-trien-17- yl]amino]hexyl]-1H-pyrrole-2,5-dione (U-73122), and a phospholipase A2 (PLA2) inhibitor, N-(p-amylcinnamoyl)anthranilic acid (ACA). AVP (0.1-100 nM) increased insulin secretion and cytosolic free Ca++ concentration ([Ca++]i) dose-dependently. AVP-induced increases in the intracellular concentration of inositol 1,4,5-trisphosphate (IP3) and [Ca++]i were dose-dependently inhibited by U-73122 (2-8 microM). At 8 microM, U-73122 abolished AVP's effect on IP3 and [Ca++]i, but AVP-induced increases in insulin secretion were only reduced by 35%. In contrast, 8 microM U-73122 did not reduce the ionomycin (a Ca++ ionophore, 100 nM)-induced increase in [Ca++]i. The discrepancy between the results of [Ca++]i and insulin secretion in U-73122 experiments is indicative of the multiple signal transduction pathways associated with the activation of AVP receptors, specifically the Ca(++)-independent pathway. The phospholipase A2 inhibitor ACA (100 microM) did not antagonize AVP (10 nM)-induced increases in insulin secretion. These results suggested: 1) U-73122 blocks PLC activities but fails to block other signal transduction pathways that trigger insulin secretion in these cells and 2) AVP increases insulin release from RINm5F cells through both the PLC-mediated Ca(++)-dependent and Ca(++)-independent pathways.

Animals↗

PubMed1994

Delayed treatment of ankle fracture.

BACKGROUND: Cases of old ankle fractures with different delayed treatments in different conditions were collected and evaluated to determine which treatments were optimal for individual type of fractures. METHODS: Sixteen cases of old ankle fractures were managed by open reduction and internal fixation, osteotomy, or removal of loose fragment according to the condition of the fractures between 1977 and 1987. The follow-up period was from 5 to 15 years with mean 7.9 years. The final result was evaluated by a modified performance index. RESULTS: All the 12 patients treated with open reduction and internal fixation for malposition got improved with the mean performance score rising from 37 before operation to 76 after operation. Improvement was also noted in all the 3 patients treated with osteotomy for malunion without significant arthritis, rising from 44 to 88. One patient had painful non-united fragment of medial malleolus, and removal of the loose fragment was done to improve the score from 58 to 96. CONCLUSIONS: Management of old ankle fractures can be effective and beneficial when appropriate treatments are given according to the different conditions of the fracture and joint.

Adult↗

PubMed1994

Bateman bipolar hemiarthroplasty for displaced intracapsular femoral neck fractures. Uncemented versus cemented.

Four hundred forty-seven patients with 451 displaced fractures of the femoral neck were treated with Bateman bipolar hemiarthroplasty (190 cemented and 261 uncemented) between 1985 and 1990 in the authors' institution. During a follow-up period of at least two years, the authors found less thigh pain (13% versus 46.2%) and higher Harris hip scores (86 versus 79) in the cemented group in comparison with the uncemented group. Radiographic examination showed less radiolucent zones and subsidence in the cemented group. Heterotopic ossification was more common in the cemented group. Despite the fact that the cemented group had longer operative times (average, 20 minutes) and more blood loss (average, 160 ml) during the operation, there was no significant difference in the early mortality rate observed between these two groups. The cemented prostheses provided better functional and radiographic results and fewer failures in the early stage. In addition, the cemented prostheses did not lead to more complications and higher mortality rates. Thus, for elderly patients who need early ambulation and functional recovery, the cemented Bateman bipolar prosthesis appears to be a better choice than the uncemented Bateman prosthesis.

Aged↗

PubMed1993

A novel M(r) 32,000 nuclear phosphoprotein is selectively expressed in cells competent for self-renewal.

We investigated the association between expression of a novel M(r) 32,000 nuclear phosphoprotein (pp32) and cell proliferation in vivo using the well-characterized physiological model of androgen-dependent regeneration of prostate in orchiectomized rats, pp32 is expressed at high levels in neoplastic cell lines and in certain anatomically defined stem cell compartments of normal human tissues such as intestinal crypt epithelial cells. Immunohistochemistry and in situ hybridization were used to monitor pp32 expression in rat ventral prostatic epithelium following castration and androgen restoration. Castrated rats retained only 6% of prostate wet weight compared to intact controls but were capable of complete gland restoration upon androgen replacement. In intact controls, pp32 expression localized to small acini at the periphery of the gland and to rare basal cells in the central regions. Ten days following castration, there was a 3,5-fold enrichment in the frequency of pp32-positive cells with greater than 56% of remaining epithelial cells expressing pp32 protein. In situ hybridization showed that all remaining epithelial cells contained pp32 mRNA. Upon testosterone replacement, pp32 expression and localization returned to that of intact controls. In order to determine the association between pp32 expression and cell division, DNA synthesis was monitored by bromodeoxyuridine incorporation during prostate involution and regeneration. Bromodeoxyuridine incorporation peaked 3 days after androgen replacement and occurred diffusely throughout the gland. Thus, pp32-positive cells are anatomically distinguishable from the population of terminally differentiating cells undergoing rapid expansion. Preliminary immunohistochemical studies of human prostatic neoplasia demonstrated increased expression of pp32 in human prostatic adenocarcinoma and prostatic intraepithelial neoplasia compared to benign prostatic hypertrophy and normal human prostate. The highest degree of expression occurred in the higher Gleason grades and prostatic intraepithelial neoplasia. This work suggests that pp32 is a nuclear protein which has a selective but presently undefined role in cells competent for self-renewal.

Adenocarcinoma↗

PubMed1993

Effects of high extracellular calcium and strontium on inositol polyphosphates in bovine parathyroid cells.

The addition of Ca2+ or a variety of divalent cations increases intracellular Ca2+ in parathyroid cells and suppresses secretion. Since 1,4,5-inositol trisphosphate (IP3) and 1,3,4,5-inositol tetrakisphosphate (IP4) mediate Ca2+ mobilization in other systems, we examined high Ca(2+)- and Sr(2+)-induced accumulation of IP3 and IP4 isomers by anion-exchange HPLC and measured 1,4,5-IP3 mass in parathyroid cells. Raising extracellular [Ca2+] from 0.5 to 3.0 mM increased 3H-1,4,5-IP3 within 5 s, which was confirmed by mass measurements. 3H-1,3,4-IP3 rose gradually by 10 s and increased for 60 s after the addition of Ca2+. Although we detected no change in 3H-1,3,4,5-IP4, the increase in 3H-1,3,4-IP3 suggests that 3H-1,3,4,5-IP4 was being formed. The addition of 4 mM SrCl2 produced similar changes in 1,4,5-IP3, which were confirmed by mass assay. 3H-1,3,4,5-IP4 did not change. However, Sr2+ induced a gradual increase in 3H-1,3,4-IP3, which remained above control levels for 5 minutes. Isotopic labeling studies in this system may underestimate changes in 1,4,5-IP3 mass, but both mass and radioisotopic analyses indicate that high extracellular Ca2+ and Sr2+ stimulate substantial increases in 1,4,5-IP3 without significant accumulation of 1,3,4,5-IP4. These studies suggest a role for 1,4,5-IP3 in intracellular Ca2+ mobilization by divalent cations in parathyroid cells.

Animals↗