Biomedical subjects

N Koike

Publications and source records attributed to N Koike.

At least 37 records · Page 2Linked to original sources

PubMed2000

Benefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinoma.

PURPOSE: The objective of this study was to determine the benefits of adjuvant radiotherapy after radical resection of locally advanced main hepatic duct carcinoma (Klatskin tumor). METHODS AND MATERIALS: We conducted a retrospective review of 63 patients who underwent surgical resection of Stage IVA Klatskin tumor. Of the 63 patients, 47 had microscopic tumor residue (RT1). Twenty-eight of the 47 patients with RT1 were treated by adjuvant radiotherapy and the remaining 19 patients were treated exclusively by surgical resection. Seventeen of the 28 patients with RT1 were treated by both intraoperative radiotherapy (IORT) and postoperative radiotherapy (PORT); of the remaining 11 patients with RT1, 6 underwent resection and IORT, and 5 underwent resection and PORT. RESULTS: The major complication and 30-day operative death rates were significantly lower in the radiation group (9.5% and 0.0%, respectively) than in the resection alone group (28.5% and 9.5%, respectively). Of the eight 5-year survivors with RT1, 6 had adjuvant radiotherapy and the remaining 2 had resection alone. Adjuvant radiotherapy for patients with RT1 yielded significantly (p = 0.0141) higher 5-year survival rates (33.9%) than in the resection alone group (13.5 %). The best 5-year survival rate (39.2 %) was found in patients who underwent a combination of IORT and PORT after resection. The local-regional control rate was significantly higher in the adjuvant radiation group than in the resection alone group (79.2% vs. 31.2%). CONCLUSION: Our data clearly suggest the improved prognosis of patients with locally advanced Klatskin tumor by integrated adjuvant radiotherapy with IORT and PORT to complete gross tumor resection with acceptable treatment mortality and morbidity.

Adult↗

PubMed2000

Radical resection of hilar bile duct carcinoma and predictors of survival.

BACKGROUND: Patients with carcinoma of the main hepatic duct have a poor prognosis. This study attempted to identify clinicopathological predictors of survival after resection. METHODS: A retrospective review was performed of 114 patients who presented with hepatic ductal carcinoma between 1976 and 1998. Of the 114 patients, 98 had a radical resection, three underwent palliative resection and 13 were not treated surgically. Forty-six patients with stage IVA disease had microscopic tumour residue after resection. Of these, 28 patients were treated with radiotherapy and the remaining 18 had resection alone. RESULTS: The overall operative morbidity and mortality rates were 14 and 4 per cent respectively. The overall 5-year survival rate after resection was 28 per cent. Nineteen patients survived for more than 5 years, including ten with stage IVA disease. The main prognostic factors were performance status; jaundice; tumour location; gross appearance; histological grade; T, N and M categories in tumour node metastasis (TNM) classification; TNM stage; and residual tumour. Adjuvant radiotherapy, tumour extension into the hepatic ducts, histological grade, N and residual tumour were independent predictive factors by multivariate Cox analysis. CONCLUSION: This study suggests that radical resection provides the best survival rate for patients with hilar bile duct carcinoma. For patients with stage IVA disease, following complete gross resection radiotherapy improved treatment outcome.

Adult↗

PubMed2000

Growth factor-expressing mast cells accumulate at the thyroid tissue-regenerative site of subacute thyroiditis.

The localization and biological roles of the multifunctional cell type mast cells remain unclear in subacute thyroiditis that is characterized by both epithelioid granuloma formation and thyroid tissue repair. We examined their immunolocalization with tryptase of a mast cell marker, using the biopsy specimens from 12 cases. In the epithelioid granuloma, no mast cells were detected in any of the cases, although a small number of them (4.6 +/- 2.4) were seen at the fibrous stroma around the granuloma in all cases. By contrast, in all cases, increased mast cells (28 +/- 7.2) localized at the thyroid tissue-regenerative site where both thyroid folliculogenesis and angiogenesis take place. To elucidate possible roles of mast cells in the disease, we also examined their immunoexpressions of vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF), transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF), which affect thyroid folliculogenesis and angiogenesis. In all 12 cases, mast cells displayed all of these growth factors in a manner not specific to the infiltrating site. The data suggest that growth factor-expressing mast cells may play crucial roles in the thyroid tissue repair of subacute thyroiditis, modulating thyroid folliculogenesis and angiogenesis; and that the multifunctionality of the cells may be partly dependent on their expressions of various growth factors.

Acute Disease↗

PubMed2000

Synthesis and pharmacokinetics of 1 alpha-hydroxyvitamin D3 tritiated at 22 and 23 positions showing high specific radioactivity.

A novel synthesis of a radioactive compound of 1 alpha-hydroxyvitamin D3 (1 alpha OHD3) (1) and its pharmacokinetics are described. Radioactive 1 alpha OHD3 tritiated at 22 and 23 positions ([22,23-(3)H4]1 alpha OHD3) (5) was prepared via key reactions of the reduction of acetylenic side chain in the ketone (12) with tritium gas in the presence of palladium-charcoal and the subsequent Wittig reaction with the A-ring synthon (16). [22,23-(3)H4]1 alpha OHD3 (5) showed high specific radioactivity (111.5 Ci/mmol) and was used successfully in pharmacokinetics studies with rats. In the pharmacokinetics studies, the plasma concentration level of the active form of vitamin D3, 1 alpha,25-dihydroxy-vitamin D3 [1 alpha,25(OH)2D3], after oral or intravenous administration of [22,23-(3)H4]1 alpha OHD3 (5), showed longer half-life, lower maximum concentration, and lower area under the curve than those after treatment of 1 alpha,25(OH)2D3 tritiated at 26 and 27 positions (4). These results might suggest a beneficial therapeutic utility of 1 alpha OHD3 (1) over the treatment of 1 alpha,25(OH)2D3 (2).

Administration, Oral↗

PubMed2000

Cyclooxygenase expression in the gallbladder.

The COX expressions were evaluated separately in the epithelium and in the stroma of gallbladder cancer, chronic cholecystitis, xanthogranulomatous cholecystitis (XGC) and the normal gallbladder. In normal gallbladder COX-2 expression rate was significantly higher in the epithelium than in the stroma. The COX-2 expression rate in the epithelium of non-cancerous adjacent epithelium to cancerous lesion was significantly lower than those not only of cancer, but also chronic cholecystitis, XGC and normal gallbladder. In stroma, the COX-2 expression rate in cancer, chronic cholecystitis and XGC were significantly higher than that of the normal gallbladder. The rate in non-cancerous adjacent stroma to cancer is significantly lower than that of cancer and XGC. However, the difference of rate between of normal and of chronic cholecystitis was not significant. The COX-2 expression rates were significantly higher in both the epithelium and the stroma in the well and moderately differentiated cancer group than in the poorly and undifferentiated cancer group. Our results suggest that COX-2 expression in the gallbladder may be regulated by various factors and not directly related to carcinogenesis. The significance of its repression in the non-cancerous adjacent tissue to cancer lesion should be re-evaluated.

Cholecystitis↗

PubMed1999

Immunohistochemical expression of growth factors in subacute thyroiditis and their effects on thyroid folliculogenesis and angiogenesis in collagen gel matrix culture.

The inflammatory-mechanistic basis of subacute thyroiditis remains unclear. To elucidate the roles of vascular endothelial cell growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-BB (PDGF), transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF) in the inflammatory process, their immunoexpression was examined in biopsy specimens of ten cases. At the granulomatous stage, all cases expressed VEGF, bFGF, PDGF, and TGF-beta1 in monocytes/macrophages infiltrating into follicle lumina, and in both epithelioid histiocytes and multinucleated giant cells of the granulomas. In fibroblasts and endothelial cells around the granulomas, all cases displayed VEGF, bFGF, and PDGF, but TGF-beta1 was detected only in fibroblasts in two cases. No cases expressed EGF in any of the above cell types. At the regenerative stage, all cases expressed VEGF, bFGF, and EGF in regenerating thyrocytes, whereas three and no cases displayed PDGF and TGF-beta1, respectively. Ten, seven and six cases expressed PDGF in fibroblasts, endothelial cells, and monocytes, respectively. In these cell types, all cases expressed VEGF and bFGF, whereas no cases displayed TGF-beta1 and EGF. To estimate the roles of these growth factors in thyroid tissue regeneration, their effects on thyroid folliculogenesis and angiogenesis were examined using collagen gel culture of thyrocytes and endothelial cells, respectively. Cell proliferation was also studied by bromodeoxyuridine (BrdU) uptake. EGF decreased follicle formation and TGF-beta1 drastically inhibited it, but the others had no effect. VEGF showed the greatest effect on vessel formation, although all of the others promoted it. EGF and VEGF or bFGF caused the highest BrdU uptake in thyrocytes and endothelial cells, respectively. The data suggest firstly, that at the granulomatous stage of subacute thyroiditis, growth factor-rich monocytes/macrophages infiltrating into follicle lumina trigger the granulomatous reaction, and VEGF, bFGF, PDGF, and TGF-beta1 produced by the stromal cell types tested mediate the reaction; secondly, that at the regenerative stage, EGF serves follicle regeneration through its mitogenic effect on thyrocytes, although some cofactors with EGF are involved in folliculogenesis and the decreased expression of TGF-beta1, a fibrogenic factor, contributes to thyroid tissue repair; and thirdly, that VEGF and bFGF are more responsible for the angiogenesis at both stages than the other factors studied.

Cell Culture Techniques↗

PubMed1999

Treatment of gallbladder cancer by radical resection.

BACKGROUND: The use of radical resection for gallbladder cancer is controversial. This study evaluated results of resection for gallbladder cancer and analysed prognostic factors. METHODS: A retrospective review of 135 patients who underwent surgical resection for gallbladder cancer between 1976 and 1998 was performed. Of these, 123 patients underwent radical resection and the remaining 12 had palliative resection. The resections included 32 hepatopancreatoduodenectomies and 57 with adjuvant radiotherapy. Twelve prognostic factors were analysed. A subset of 96 patients with stage IV disease was analysed separately with respect to residual tumour level and adjuvant radiotherapy. RESULTS: Surgical resection was associated with a 5-year survival rate of 36 per cent, with a mean follow-up time of 870 days. Twenty-two patients have survived more than 5 years including three with stage IV disease. Overall operative morbidity and mortality rates were 13 and 4 per cent respectively. The 5-year survival rate decreased with disease stage: 100, 78, 69 and 11 per cent for stages I (n = 13), II (n = 19), III (n = 7) and IV (n = 96) respectively. Performance status, jaundice, histopathological type and grade, primary tumour, lymph node, distant metastasis, stage grouping, residual tumour level and adjuvant radiotherapy were significant prognostic factors. CONCLUSION: With careful patient selection, radical resection for gallbladder cancer improves the prognosis with acceptable operative mortality and morbidity rates, even for stage IV disease, provided that complete gross tumour resection is combined with radiotherapy.

Adult↗

PubMed1999

Region-dependent difference in the sleep-promoting potency of an adenosine A2A receptor agonist.

The present study has demonstrated that the sleep-promoting potency of 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido adenosine (CGS21680), a selective agonist for the adenosine A2A receptor, varies depending on the location of the administration. CGS21680 was continuously administered to rats through a chronically implanted cannula for 6 h during their active phase. The tip of the cannula was located in the subarachnoid space or the brain ventricle neighbouring the established brain areas implicated in the regulation of sleep-wake phenomena, i.e. rostral basal forebrain, medial preoptic area, lateral preoptic area, posterior hypothalamus, and dorsal tegmentum of the pons and medulla. At an infusion rate of 2.0 pmol/min, the magnitude of increase in non-rapid eye movement sleep varied from 14 min (a 15% increase) to 96 min (a 103% increase), and those of rapid eye movement sleep varied from 6 min (a 40% increase) to 28 min (a 264% increase) from the respective baseline values. The largest increases in both types of sleep occurred when CGS21680 was administered to the subarachnoid space underlying the rostral basal forebrain. These findings were interpreted to mean that the major, if not the only, site responsible for the CGS21680-inducing sleep was located in or near the rostral basal forebrain. This interpretation was supported by the findings that the administration of CGS21680 to the rostral basal forebrain produced predominant expression of Fos within the shell of the nucleus accumbens and the medial portion of the olfactory tubercle, and that the microdialysis perfusion of CGS21680 into the shell of the nucleus accumbens also exhibited a sleep-promoting effect.

Adenosine↗

PubMed1999

22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis.

UNLABELLED: 22-Oxacalcitriol ameliorates high-turnover bone and marked osteitis fibrosa in rats with slowly progressive nephritis. BACKGROUND: 22-Oxacalcitriol (OCT) is a unique vitamin D analogue with less calcemic activity than calcitriol, and it effectively suppresses parathyroid hormone (PTH) secretion in uremic rats. This study was performed to examine the long-term effect of intravenously administered OCT on high-turnover bone disease in model rats of slowly progressive renal failure. METHODS: Slowly progressive renal failure rats were made by a single injection of glycopeptide isolated from rat renal cortical tissues. At 250 days, glycopeptide-induced nephritis (GN) rats were divided into three groups with the same levels of serum creatinine and PTH, and they received either OCT (0.03 or 0.15 microg/kg body wt) or vehicle given intravenously three times per week for 15 weeks. RESULTS: Renal function of GN rats deteriorated very slowly but progressively, as assessed by the increase of serum creatinine concentration. At sacrifice, serum PTH levels, bone formation markers, bone resorption markers, and fibrosis volume were significantly elevated in vehicle-treated GN rats compared with those of sham-operated rats, suggesting the development of high-turnover bone disease with osteitis fibrosa. In contrast, in the GN-OCT 0.15 microg/kg group, these high PTH levels and high-turnover bone and fibrosis were significantly decreased. Such amelioration of bone abnormalities by OCT was not accompanied by either hypercalcemia or further deterioration of renal function. CONCLUSIONS: These data indicate that OCT may be a useful and safe agent not only for the suppression of PTH, but also for the amelioration of osteitis fibrosa and high-turnover bone without causing hypercalcemia in chronic dialysis patients.

Animals↗

PubMed1999

Behçet's disease and antibody titers to various heat-shock protein 60s.

It has been suggested that the 65 kDa heat-shock protein (HSP) of Streptococcus in recurrent aphthae within the oral cavity may be involved in the uveoretinitis of Behçet's disease, possibly through sensitization of the immune system. To investigate this possibility, we examined serum antibody titers for various members of the 60 kDa family of HSPs and their implications with regard to a role for HSP60s in Behçet's disease. We isolated HSP60 of Streptococcus pyogenes from the margin of oral aphthae in one Behçet's disease patient with severe uveoretinitis and the HSP60s of Yersinia enterocolitica, retinoblastoma cell line clone Y79, and bovine retinal extract and investigated the reaction of each of these HSP60s with 100-fold diluted serum samples from 20 Behçet's disease patients using anti-HSP60 antibody titers determined by ELISA. The anti- Streptococcus HSP60 antibody and anti-retinal HSP60 antibody titers of the 100-fold diluted serum samples from the Behçet's disease patients were both significantly higher than those of similarly diluted serum samples from healthy donors. The results of the ELISA antibody titer assay showed that, although the various HSP60s share a common basic antigenicity, they differed in reactivity to the anti-HSP60 antibodies in the sera of the Behçet's disease patients. The results indicate that subtle but significant differences exist in the antigenicity of the various HSP60s tested, all of which share a common basic antigenicity and are of approximately the same molecular weight, and suggest that an immuno-cross-reaction between retinal and streptococcal HSPs and a related autoimmune response may be involved in the development of Behçet's disease.

Adult↗

PubMed1999

Color Doppler ultrasonography in patients with subacute thyroiditis.

We studied the utility of color Doppler ultrasonography in patients with subacute thyroiditis. Eighteen patients with subacute thyroiditis (SAT) with painful goiter and thyrotoxicosis underwent color Doppler ultrasonography during the acute and recovery stages of the disease. Thyroid vascularization in these patients was compared with that of 15 untreated patients with Graves' disease and 17 control subjects. During the acute stage of subacute thyroiditis, color Doppler ultrasonography showed low echogenicity without increased tissue vascularity in the affected swollen thyroid. In the recovery stage, color Doppler ultrasonography showed isoechogenicity with slightly increased vascularization. Vascularization became normal at 1 year follow-up time. In contrast, marked by increased vascularization was observed in patients with untreated Graves' disease. Color Doppler ultrasonography showed clear differences between SAT and Graves' disease patients. Vascularity was significantly correlated with serum free thyroxine (FT4) and thyrotropin (TSH) concentrations in the recovery stage (3 months after the initial ultrasonography). Color Doppler ultrasonography accurately visualized lesions without increased vascularity in the acute stage of SAT and lesions of slightly increased vascularity in the recovery stage. Color Doppler ultrasonography may be a useful, noninvasive, and rapid method for differentiating SAT from Graves' disease and for evaluating and monitoring the location and activity of lesions in SAT.

Adult↗

PubMed1999

Increased sensitivity of cholera toxin detection by enzyme-linked immunosorbent assay with chemical immobilization of antibody onto nylon surface providing hydrophobicity.

We developed an improved method to chemically immobilize antibodies on a nylon surface using a styrene maleic anhydride copolymer having an aryl group, which provides hydrophobicity to the nylon surface. We applied it to a modified enzyme-linked immunosorbent assay (slip-ELISA) for the detection of cholera toxin (CT). The sensitivity of slip-ELISA for CT detection was 1,000 times higher than that of conventional methods of physical adsorption using polystyrene plates, and 10 times higher than that of the method of chemical immobilization using maleic anhydride methylvinyl ether copolymer.

Antibodies, Monoclonal↗

PubMed1999

Anti-herpesvirus activities and cytotoxicities of 2-thiopyrimidine nucleoside analogues in vitro.

Twenty 2-thiopyrimidine nucleoside analogues were synthesized and examined for inhibitory activity against herpes simplex virus (HSV) type 1 and 2, varicella-zoster virus (VZV), human cytomegalovirus (HCMV) and thymidine kinase-deficient HSV (HSV-TK-) replication in vitro. 2-thiouracil (thymine) arabinoside, 2'-deoxy-2-thiouridine (or 2-thiothymidine) and their 5-halogenated derivatives showed anti-HSV activity in both RPM18226 (human B-lymphoblastoid cells) and MRC-5 (human embryo lung cells). 2'-deoxy-5-halogenated-2-thiocytidines were also inhibitory against HSV, whereas 2-thiocytosine arabinoside and its derivatives were not inhibitory against HSV replication, except 5-bromo and 5-iodo congeners (TN-31, TN-32). Substitution of the halogen atom at the 5-position of the pyrimidine rings to an atom with a higher molecular weight increased anti-HSV and VZV activities, except for the anti-HSV activity of 2-thiouracil arabinosides. 2'-deoxy-5-methyl-, and 2'-deoxy-5-iodo-2-thiouridines (TN-17, TN-44) showed the most potent anti-HSV activity, and 2'-deoxy-5-chloro- and 2'-deoxy-5-bromo-2-thiocytidines were potent inhibitors of VZV replication. However, none of the compounds inhibited HCMV and HSV-TK- replication. TN-31 and TN-32 were shown to inhibited HCMV and HSV-TK- as well as HSV and VZV replication. The cytotoxicity of the 2-thio-pyrimidine nucleoside analogues was less than that of the 2-oxy-congeners of the compounds (5-iodo-2'-deoxyuridine, 5-iodo-2'-deoxycytidine, thymine arabinoside and cytosine arabinoside). The selectivity index of 2'-deoxy-5-iodo-2-thiouridine (TN-44) was higher than that of 5-iodo-deoxyuridine. TN-17 and TN-44 were not cytotoxic to resting or stimulated human peripheral blood mononuclear cells at 400 microM, although TN-32 was cytotoxic at a concentration of 20 microM.

Antiviral Agents↗

PubMed1999

Immunohistochemical analysis of Bcl-2, Bax, and Bak expression in thyroid glands from patients with subacute thyroiditis.

Bcl-2 family proteins are important regulators of apoptosis. To clarify a role of apoptosis and the expression of Bcl-2 family proteins in the pathogenesis of subacute thyroiditis (SAT), we evaluated the expression of Bcl-2, Bax, and Bak by immunohistochemistry and apoptosis by in situ end labeling of fragmented DNA in thyroid tissues from 11 patients with SAT. Apoptotic nuclei were found in granulomas, especially in macrophages/histiocytes and lymphocytes, and in the regenerating follicular cells, but were rarely found in the area of fibrosis. The mean (+/-SD) percentage of apoptotic follicular cells was significantly greater in SAT than that in controls (1.4 +/- 0.8% vs. 0.4 +/- 0.6%). Bcl-2, Bak, and Bax were strongly expressed in the granulomas and regenerating thyroid follicular cells from patients with SAT. Bcl-2 and Bak, but not Bax, were expressed in follicular cells from normal controls. The percentage of apoptotic cells and the expression of Bax in follicular cells did not correlate with age or serum levels of thyroid hormones, C-reactive protein, or thyroglobulin. These data suggest that apoptosis may be involved in the development of SAT and that Bax expression in regenerating thyrocytes may be important for the recovery of SAT.

Adolescent↗

PubMed1999

[Chemoradiation therapy for advanced esophageal cancers--report of 3 cases].

Three cases of prominent-type advanced esophageal cancer were treated with chemoradiation therapy using a 5-FU analog and low dose CDDP. All cases showed a complete response after the treatment. Only mild bone marrow suppression was found in one case. This protocol will be applied for patients with prominent-type advanced esophageal cancers, especially high risk patients.

Aged↗

PubMed1998

Identification of the mammalian homologues of the Drosophila timeless gene, Timeless1.

We have identified novel mammalian homologues of a Drosophila clock gene, timeless, and designated them as human TIMELESS1 (hTIM1) and mouse Timeless1 (mTim1), respectively. These genes were mapped by FISH to chromosomal regions 12q12-13 in human and 10D3 in mouse. The deduced amino acid sequences of hTim1 and mTim1 proteins were 1208 and 1197 amino acids in length and shared 83% identity. Northern blot analysis identified a single transcript of 4.5 kb expressed widely in many tissues examined. Unlike the Drosophila counterpart, the levels of the mTim1 transcript exhibited no prominent circadian oscillation in the mouse brain.

Animals↗

PubMed1998

Sustained osteoblast nuclear receptor binding of converted 1alpha, 25-dihydroxyvitamin D3 after administration of 3H-1alpha-hydroxyvitamin D3: a combined receptor autoradiography and radioassay time course study with comparison to 3H-1alpha, 25-dihydroxyvitamin D3.

The present study was undertaken to clarify the receptor distribution and the pharmacokinetics of 3H-1alpha(OH)D3, and 3H-1alpha,25(OH)2D3 for comparison. Receptor autoradiography was used after intravenous injection to 3-day-old neonatal rats and radioassay-HPLC after oral application to young adult rats. Corresponding results were obtained from both receptor autoradiography and radioassay. After 3H-1alpha(OH)D3 administration, uptake was delayed but sustained over a long period of time and the concentration of silver grains (autoradiography) or recovered 3H-1alpha,25(OH)2D3 (radioassay) peaked at a lower level. After 3H-1alpha,25(OH)2D3 administration, osteoblast nuclear, whole bone uptake and retention of radiolabeled compound were relatively rapid and short in duration. Nuclear uptake in osteoblasts after administration of 3H-1alpha(OH)D3 was abolished in competition studies with 10-fold unlabeled 1alpha,25(OH)2D3. These results indicate that 1alpha(OH)D3 continuously supplies osteoblasts with converted 1alpha,25(OH)2D3 and would not spread to the cells because of the low binding affinity of the receptor. Accordingly, 1alpha(OH)D3 appears to have some therapeutic properties different from 1alpha,25(OH)2D3 because of a relatively slow and sustained accumulation of the receptor and less Cmax (pharmacokinetics) compared with 1alpha,25(OH)2D3.

Animals↗

PubMed1998

In vivo dose-related receptor binding of the vitamin D analogue [3H]-1,25-dihydroxy-22-oxavitamin D3 (OCT) in rat parathyroid, kidney distal and proximal tubules, duodenum, and skin, studied by quantitative receptor autoradiography.

1,25-Dihydroxy-22-oxavitamin D3 (OCT) is a new synthetic analogue of 1,25(OH)2D3 with a low calcemic effect. This study utilized quantitative receptor autoradiography to determine the dose-related receptor binding and saturation among the vitamin D target cells: parathyroid chief cells, kidney distal and proximal tubule epithelium, duodenal absorptive epithelium, and epidermal keratinocytes. Rats were injected with 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, or 16.0 microgram/kg bw of [26-3H]-OCT and sacrificed 1 hr afterwards. Then autoradiographs were prepared under identical conditions. In these target cells, nuclear uptake of radioactivity increased with dose and then achieved a plateau. However, their saturation doses showed differences: parathyroid chief cells 1-2 microgram duodenal absorptive epithelium, distal tubule epithelium, and epidermal keratinocytes 4-6 microgram proximal tubule epithelium 8 microgram (per kg bw). In contrast, in nontarget cells, such as liver and duodenal smooth muscle, radioactivity did not concentrate in the nuclei but increased in the cytoplasm with dose, without plateauing. These results provide the first information on the relative saturabilities of various target cell populations with a vitamin D ligand. Parathyroid chief cells required the relatively lowest receptor saturation dose. This suggests a high sensitivity and response to OCT treatment with related therapeutic potential for the regulation of parathyroid function.

Animals↗