Initial experience with the transanal approach for lateral pelvic lymph node dissection in rectal cancer.

BACKGROUND: The efficacy and safety of transanal lateral pelvic lymph node dissection (TaLPLND) in rectal cancer has not yet been clarified. The aim of the present study was to evaluate the short-term results as an initial experience of TaLPLND. METHODS: This retrospective study included patients with middle to lower rectal cancer who underwent TaLPLND from July 2018 to July 2021. Our institutions targeted lymph nodes in the internal iliac area and the obturator area for lateral pelvic lymph node dissection (LPLND). RESULTS: A total of 30 consecutive patients with rectal cancer were included in this analysis. The median age was 60 years (range, 36-83 years), and the male-female ratio was 2:1. The median operative time was 362 min (IQR, 283-661 min), and the median intraoperative blood loss was 74 ml (IQR, 5-500 ml). Intraoperative blood transfusion was required in one case. No cases required conversion to laparotomy. TaLPLND was performed bilaterally in 13 patients (43.3%). Five patients (16.7%) underwent LPLND with combined resection of the internal iliac vessels. The median distance of the distal margin from the anal verge was 20 mm. The pathological radial margin (pRM) was positive in one case, and the negative pRM rate was 96.7%. Short-term postoperative complications (Clavien-Dindo classification grade ≥ II) were observed in nine cases (30.0%). There were no cases of reoperation or mortality. The median number of harvested lateral pelvic lymph nodes was 11 (range, 3-28). On pathological examination, lateral pelvic lymph nodes were positive for metastasis in seven cases (23.3%). CONCLUSIONS: TaLPLND appeared to be beneficial from an oncological point of view because it was close to the upstream lymphatic drainage from the tumor. The short-term outcomes of this initial experience indicate that this novel approach is feasible.

Respiratory mechanics and peripheral airway inflammation and dysfunction in asthma.

BACKGROUND: Clinical application of the forced oscillation technique (FOT) has progressed with the spread of commercially available FOT devices. The correlation between respiratory impedance and spirometry has been reported; however, the association with airway inflammation and pulmonary function, in the lung periphery in particular, is unclear. OBJECTIVE: To assess whether respiratory impedance is associated with peripheral airway inflammation and dysfunction in asthma. METHODS: Subjects included 78 patients with overall controlled asthma. We measured whole-breath or within-breath respiratory system resistance (Rrs) and reactance (Xrs) using a commercially available multi-frequency FOT device (MostGraph-01), and assessed the correlation with the fraction of exhaled nitric oxide (FeNO), alveolar nitric oxide concentration (CANO), maximal NO flux in the conductive airways (J'awNO), and the N2 phase III slope of single breath N2 washout (delta N2 ). RESULTS: The differences between inspiratory and expiratory phases of Xrs at 5 Hz (X5), resonant frequency (Fres), and a low-frequency reactance area (ALX) were significantly correlated with CANO; however, there was no correlation between respiratory impedance and FeNO or J'awNO. The delta N2 values were significantly correlated with whole-breath, inspiratory, and expiratory Rrs and Xrs, except for R20. CONCLUSIONS AND CLINICAL RELEVANCE: We conclude that respiratory impedance reflects peripheral airway inflammation and ventilation inhomogeneity.

Pulmonary dendritic cell accumulation in usual interstitial pneumonia and nonspecific interstitial pneumonia.

BACKGROUND: Pulmonary dendritic cells (DCs) are key regulators of immune responses. An increased accumulation of DCs was reported in the lungs of patients with idiopathic interstitial pneumonia (IIP). OBJECTIVE: This study aimed to investigate the number of pulmonary DCs in patients with collagen vascular disease associated interstitial lung diseases (CVD-ILDs). DESIGN: Lung tissue samples obtained from 27 patients with IIP and 39 patients with CVD-ILD were detected using monoclonal antibodies against CD1a, CD1c, CD83, Langerin and DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN). RESULTS: No significant differences in the number or distribution of DCs were observed between patients with IIP and CVD-ILDs. When DC marker expression was analyzed according to pathological subgroup, patients with idiopathic usual interstitial pneumonia (UIP) showed increased DC-SIGN staining when compared with CVD-UIP (p < 0.05). CONCLUSION: Both mature and immature DCs accumulate in CVD-ILDs. The number of DCs expressing DC-SIGN in CVD-UIP was decreased compared with that in idiopathic UIP. The variation in accumulated DC-SIGN-positive cells might help to explain the differences in the development and maintenance of lung inflammation between idiopathic UIP and CVD-UIP.

Assessment of Heating on Titanium Alloy Cerebral Aneurysm Clips during 7T MRI.

BACKGROUND AND PURPOSE: Patients with cerebral aneurysms often undergo MR imaging after microsurgical clipping. Ultra-high-field MR imaging at 7T may provide high diagnostic capability in such clinical situations. However, titanium alloy clips have safety issues such as adverse interactions with static magnetic fields and radiofrequency-induced heating during 7T MR imaging. The purpose of this study was to quantitatively assess temperature increases on various types of titanium alloy aneurysm clips during 7T MR imaging. MATERIALS AND METHODS: Five types of titanium alloy aneurysm clips were tested, including combinations of short, long, straight, angled, and fenestrated types. Each clip was set in a phantom filled with gelled saline mixed with polyacrylic acid and underwent 7T MR imaging with 3D T1WI with a spoiled gradient recalled acquisition in the steady-state technique. Temperature was chronologically measured at the tips of the clip blade and head, angled part of the clip, and 5 mm from the tip of the clip head using MR imaging-compatible fiber-optic thermometers. RESULTS: Temperature increases at all locations for right-angled and short straight clips were <1°C. Temperature increases at the angled part for the 45° angled clip and the tip of the clip head for the straight fenestrated clip were >1°C. Temperature increases at all locations for the long straight clip were >2°C. CONCLUSIONS: Temperature increases on the right-angled and short straight clips remained below the regulatory limit during 7T MR imaging, but temperature increases on the 45° angled, straight fenestrated, and long straight clips exceeded this limit.

Usefulness of serum procalcitonin levels in pulmonary tuberculosis.

There are very few data on serum procalcitonin (PCT) levels in pulmonary tuberculosis (PTB) patients who are negative for HIV. We assessed serum PCT in consecutive patients diagnosed with pulmonary tuberculosis or community-acquired pneumonia (CAP) on admission to discriminate between PTB and CAP, and examined the value of prognostic factors in PTB. 102 PTB patients, 62 CAP patients, and 34 healthy volunteers were enrolled. Serum PCT in PTB patients was significantly lower than in CAP patients (mean ± sd 0.21 ± 0.49 versus 4.10 ± 8.68 ng·mL⁻¹; p < 0.0001). By receiver-operating characteristic curve analysis, serum PCT was an appropriate discrimination marker for PTB and CAP (area under the curve 0.866). PTB patients with ≥ 0.5 ng·mL⁻¹ (normal cut-off) had significantly shorter survival than those with < 0.5 ng·mL⁻¹ (p < 0.0001). Serum PCT is not habitually elevated in HIV-negative PTB patients and is a useful biomarker for discriminating between PTB and CAP; however, when serum PCT is outside the normal range, it is a poor prognostic marker.

[Patient skin injury in cardiac intervention procedures].

PURPOSE: To discuss the circumstances of patient skin injury in cardiac interventional radiology (IVR). To demonstrate the importance of evaluating the patient radiation dose in IVR. To show the need for the appropriate patient follow-up after IVR to identify radiation effects. To highlight the incidence of skin injuries during IVRs. CONTENT ORGANIZATION: Evaluation of 400 consecutive percutaneous coronary interventions (PCIs). The radiation dose, number of cine runs, and fluoroscopic time were recorded for all patients. The skin on the patients' backs was reviewed periodically after PCI to identify radiation injury. The relationships between patient skin effects and factors such as the radiation dose were investigated. Reviewing previous reports of patient radiation injury occurrence rate, fluoroscopic time, radiation dose (if available), etc. SUMMARY: Although increasing numbers of case reports of patient radiation injury resulting from IVR are being published, these reports likely represent a small fraction of actual cases. Radiation skin injury in IVR is overlooked clinically in many patients. Patients who receive a high radiation dose while undergoing IVR should be followed to identify radiation skin effects, and physicians should seek to establish whether a patient has had previous IVR, together with the entrance site and radiation dose.

The cell cycle-dependent nuclear import of v-Jun is regulated by phosphorylation of a serine adjacent to the nuclear localization signal.

Cell cycle-dependent phosphorylation and nuclear import of the tumorigenic transcription factor viral Jun (v-Jun) were investigated in chicken embryo fibroblasts. Nuclear accumulation of v-Jun but not of cellular Jun (c-Jun) is cell cycle dependent, decreasing in G1 and increasing in G2. The cell cycle-dependent regulation of v-Jun was mapped to a single serine residue at position 248 (Ser248), adjacent to the nuclear localization signal (NLS). Ser248 of v-Jun represents an amino acid substitution, replacing cysteine of c-Jun. It was shown by peptidase digestion and immunoprecipitation with antibody to the NLS that v-Jun is phosphorylated at Ser248 in the cytoplasm but not in the nucleus. This phosphorylation is high in G1 and low in G2. Nuclear accumulation of v-Jun is correlated with underphosphorylation at Ser248. The regulation of nuclear import by phosphorylation was also examined using NLS peptides with Ser248 of v-Jun. Phosphorylation of the serine inhibited nuclear import mediated by the NLS peptide in vivo and in vitro. The protein kinase inhibitors staurosporine and H7 stimulated but the phosphatase inhibitor okadaic acid inhibited nuclear import mediated by the NLS peptide. The cytosolic activity of protein kinases phosphorylating Ser248 increased in G0 and decreased during cell cycle progression, reaching a minimum in G2, whereas phosphatase activity dephosphorylating Ser248 was not changed. These results show that nuclear import of v-Jun is negatively regulated by phosphorylation at Ser248 in the cytoplasm in a cell cycle-dependent manner.

Evaluation of patient radiation dose during cardiac interventional procedures: what is the most effective method?

Cardiac interventional radiology has lower risks than surgical procedures. This is despite the fact that radiation doses from cardiac intervention procedures are the highest of any commonly performed general X-ray examination. Maximum radiation skin doses (MSDs) should be determined to avoid radiation-associated skin injuries in patients undergoing cardiac intervention procedures. However, real-time evaluation of MSD is unavailable for many cardiac intervention procedures. This review describes methods of determining MSD during cardiac intervention procedures. Currently, in most cardiac intervention procedures, real-time measuring of MSD is not feasible. Thus, we recommend that physicians record the patient's total entrance skin dose, such as the dose at the interventional reference point when it can be monitored, in order to estimate MSD in intervention procedures.

Effect of radiation monitoring method and formula differences on estimated physician dose during percutaneous coronary intervention.

BACKGROUND: Currently, one or two dosimeters are used to monitor radiation exposure in most cardiac laboratories. In addition, several different formulas are used to convert exposure data into an effective dose (ED). PURPOSE: To clarify the effect of monitoring methods and formula selection on the estimated ED for physicians during percutaneous coronary interventions (PCIs). MATERIAL AND METHODS: The ED of physicians during cardiac catheterization was determined using an optically stimulated luminescence dosimeter (Luxel badge). Two Luxel badges were worn: one beneath a personal lead apron (0.35-mm lead equivalent) at the chest and one outside of the apron at the neck. RESULTS: The difference in the average ED of seven physicians was approximately fivefold (range 1.13-5.43 mSv/year) using the six different formulas in the clinical evaluation. The estimated physician ED differed markedly according to both the monitoring method and formula selected. CONCLUSION: ED estimation is dependent on both the monitoring method and the formula used. Therefore, it is important that comparisons among laboratories are based on the same monitoring method and same formula for calculating the ED.

A PHANTOM STUDY TO DETERMINE THE OPTIMAL PLACEMENT OF EYE DOSEMETERS ON INTERVENTIONAL CARDIOLOGY STAFF.

The International Commission on Radiological Protection has substantially reduced the recommended maximum annual eye lens dose for workers. Use of a dedicated eye dosemeter is one method for accurate dose monitoring. The main aim of this study was to yield recommendations for optimal placement of eye dosemeters to estimate the eye dose to interventional cardiology physicians and nurses. A phantom measurement was conducted to simulate typical interventional cardiology procedures. Considering eight X-ray tube angulations, the left side of the head position provide good estimates for physician, and the forehead position provide good estimates for nurse.

Mycobacterium avium complex disease: prognostic implication of high-resolution computed tomography findings.

To evaluate the prognostic implications of computed tomography (CT) findings in assessing responses to treatment in Mycobacterium avium complex (MAC) pulmonary disease without underlying lung disease, high-resolution (HR)CT findings were correlated based on the results of sputum conversion after anti-MAC therapy. A total of 59 patients underwent HRCT before treatment and the therapeutic efficacy was evaluated by the results of sputum conversion. Atelectasis, cavities and pleural thickening on HRCT were significantly more frequent and extensive among patients in the sputum nonconverted group than among those in the converted group. Furthermore, bronchiectasis was also significantly more extensive among patients in the nonconverted group, even though there was no significant difference in frequency between these two groups. These results suggest that high-resolution computed tomography findings are good predictors of response to treatment in Mycobacterium avium complex pulmonary disease.

Eosinophilia in bronchoalveolar lavage fluid and architectural destruction are features of desquamative interstitial pneumonia.

AIMS: Desquamative interstitial pneumonia (DIP) is a rare pattern of diffuse parenchymal lung disease known to overlap with respiratory bronchiolitis-interstitial lung disease (RB-ILD). The aim was to review biopsy-proven cases of DIP to investigate further the clinical, imaging and histological features of this disease. METHODS AND RESULTS: Twenty patients fulfilled the pathological criteria: 19 men and one woman with a mean age of 54 years. Clinical features, bronchoalveolar lavage (BAL) data, radiological findings, pathological findings other than criteria, effect of therapy and outcome were examined. The BAL data for 17 cases revealed marked eosinophilia (mean 18%) and moderate neutrophilia (mean 11%). Computed tomography in 17 patients showed peripheral involvement in all cases with a clear margin in 64% and thin-walled cysts in 35% of cases. Additional pathological features were a distinct lobular distribution (70%) and architectural destruction (70%) with cyst formation (55%). Eighteen of the 19 patients (95%) improved under steroid pulse and/or oral therapy. Sixteen subjects (80%) are alive, three died of other diseases and one died of DIP 74 months after the diagnosis. Percent vital capacity increased significantly and new thin-walled cysts appeared in one case. CONCLUSIONS: BAL eosinophilia, lobular distribution and architectural destruction with cyst formation are characteristic features of DIP.

The eta isoform of protein kinase C is localized on rough endoplasmic reticulum.

The eta isoform of protein kinase C, isolated from a cDNA library of mouse skin, has unique tissue and cellular distributions. It is predominantly expressed in epithelia of the skin, digestive tract, and respiratory tract in close association with epithelial differentiation. We report here that this isoform is localized on the rough endoplasmic reticulum in transiently expressing COS1 cells and constitutively expressing keratinocytes. By the use of polyclonal antibodies raised against peptides of the diverse D1 and D2/D3 regions, we found that immunofluorescent signals were strongest in the cytoplasm around the nucleus and became weaker toward the peripheral cytoplasm. Under immunoelectron microscopic examination, electron-dense signals were located on the rough endoplasmic reticulum and on the outer nuclear membrane which is continuous with the endoplasmic reticulum membrane. However, no signals were detected in the nucleus, inner nuclear membrane, smooth endoplasmic reticulum, Golgi apparatus, mitochondria, or plasma membrane. Treatment of the cells in situ with detergents suggested association of the isoform of protein kinase C with intracellular structures. By immunoblotting, a distinct single band with an M(r) of 80,000 was detected in whole-cell lysate and in rough microsomal and crude nuclear fractions, all of which contain outer nuclear membrane and/or rough endoplasmic reticulum. We further demonstrated the absence of a nuclear localization signal in the pseudosubstrate sequence. The present observation is not consistent with the report of Greif et al. (H. Greif, J. Ben-Chaim, T. Shimon, E. Bechor, H. Eldar, and E. Livneh, Mol. Cell. Biol. 12:1304-1311, 1992).

Induction of differentiation in normal human keratinocytes by adenovirus-mediated introduction of the eta and delta isoforms of protein kinase C.

Protein kinase C (PKC) plays a crucial role(s) in regulation of growth and differentiation of cells. In the present study, we examined possible roles of the alpha, delta, eta, and zeta isoforms of PKC in squamous differentiation by overexpressing these genes in normal human keratinocytes. Because of the difficulty of introducing foreign genes into keratinocytes, we used an adenovirus vector system, Ax, which allows expression of these genes at a high level in almost all the cells infected for at least 72 h. Increased kinase activity was demonstrated in the cells overexpressing the alpha, delta, and eta isoforms. Overexpression of the eta isoform inhibited the growth of keratinocytes of humans and mice in a dose (multiplicity of infection [MOI])-dependent manner, leading to G1 arrest. The eta-overexpressing cells became enlarged and flattened, showing squamous cell phenotypes. Expression and activity of transglutaminase 1, a key enzyme of squamous cell differentiation, were induced in the eta-overexpressing cells in dose (MOI)- and time-dependent manners. The inhibition of growth and the induction of transglutaminase 1 activity were found only in the cells that express the eta isoform endogenously, i.e., in human and mouse keratinocytes but not in human and mouse fibroblasts or COS1 cells. A dominant-negative eta isoform counteracted the induction of transglutaminase 1 by differentiation inducers such as a phorbol ester, 1alpha,25-dihydroxyvitamin D3, and a high concentration of Ca2+. Among the isoforms examined, the delta isoform also inhibited the growth of keratinocytes and induced transglutaminase 1, but the alpha and zeta isoforms did not. These findings indicate that the eta and delta isoforms of PKC are involved crucially in squamous cell differentiation.

The recessive phenotype displayed by a dominant negative microphthalmia-associated transcription factor mutant is a result of impaired nucleation potential.

In the DNA binding domain of microphthalmia-associated transcription factor (MITF), four mutations are reported: mi, Mi wh, mi ew, and mi or. MITFs encoded by the mi, Mi wh, mi ew, and Mi or mutant alleles (mi-MITF, Mi wh-MITF, Mi ew-MITF, and Mi or-MITF, respectively) interfered with the DNA binding of wild-type MITF, TFE3, and another basic helix-loop-helix leucine zipper protein in vitro. Polyclonal antibody against MITF was produced and used for investigating the subcellular localization of mutant MITFs. Immunocytochemistry and immunoblotting revealed that more than 99% of wild-type MITF and Mi wh-MITF located in nuclei of transfected NIH 3T3 and 293T cells. In contrast, mi-MITF predominantly located in the cytoplasm of cells transfected with the corresponding plasmid. When the immunoglobulin G (IgG)-conjugated peptides representing a part of the DNA binding domain containing mi and Mi wh mutations were microinjected into the cytoplasm of NRK49F cells, wild-type peptide and Mi wh-type peptide-IgG conjugate localized in nuclei but mi-type peptide-IgG conjugate was detectable only in the cytoplasm. It was also demonstrated that the nuclear translocation potential of Mi or-MITF was normal but that Mi ew-MITF was impaired as well as mi-MITF. In cotransfection assay, a strong dominant negative effect of Mi wh-MITF against wild-type MITF-dependent transactivation system on tyrosinase promoter was observed, but mi-MITF had a small effect. However, by the conjugation of simian virus 40 large-T-antigen-derived nuclear localization signal to mi-MITF, the dominant negative effect was enhanced. Furthermore, we demonstrated that the interaction between wild-type MITF and mi-MITF occurred in the cytoplasm and that mi-MITF had an inhibitory effect on nuclear localization potential of wild-type MITF.

Influence of the target vessel on the location and area of maximum skin dose during percutaneous coronary intervention.

BACKGROUND: A number of cases involving radiation-associated patient skin injury attributable to percutaneous coronary intervention (PCI) have been reported. Knowledge of the location and area of the patient's maximum skin dose (MSD) in PCI is necessary to reduce the risk of skin injury. PURPOSE: To determine the location and area of the MSD in PCI, and separately analyze the effects of different target vessels. MATERIAL AND METHODS: 197 consecutive PCI procedures were studied, and the location and area of the MSD were calculated by a skin-dose mapping software program: Caregraph. The target vessels of the PCI procedures were divided into four groups based on the American Heart Association (AHA) classification. RESULTS: The sites of the MSD for AHA #1-3, AHA #4, and AHA #11-15 were located mainly on the right back skin, the lower right or center back skin, and the upper back skin areas, respectively, whereas the MSD sites for the AHA #5-10 PCI were widely spread. The MSD area for the AHA #4 PCI was larger than that for the AHA #11-15 PCI (P<0.0001). CONCLUSION: Although the radiation associated with PCI can be widely spread and variable, we observed a tendency regarding the location and area of the MSD when we separately analyzed the data for different target vessels. We recommend the use of a smaller radiation field size and the elimination of overlapping fields during PCI.

Dietary fat and meat intake and idiopathic pulmonary fibrosis: a case-control study in Japan.

SETTING: There is sparse epidemiologic information regarding the role of dietary factors in the development of idiopathic pulmonary fibrosis (IPF). OBJECTIVE: To examine the relationship between specific types of fatty acids and selected foods high in fat and IPF in Japan. DESIGN: Included were 104 cases aged > or = 40 years who had been diagnosed in the last 2 years in accordance with the most recent criteria. Controls aged > or = 40 years consisted of 56 hospitalised patients diagnosed as having acute bacterial pneumonia and four out-patients with common cold. RESULTS: Intake of saturated fatty acids, mono-unsaturated fatty acids, n-6 polyunsaturated fatty acids and meat was independently associated with an increased risk of IPF. Specifically, the multivariate OR for comparison of the highest with the lowest quartile of intake of saturated fatty acids was 6.26 (95%CI 1.79-24.96, P for trend = 0.01) and for meat it was 7.19 (95%CI 2.15-27.07, P for trend = 0.02). Intake of cholesterol, n-3 polyunsaturated fatty acids, fish, eggs and dairy products was not related to the risk. CONCLUSION: These findings suggest that consumption of saturated fatty acids and meat may increase the risk of IPF.

Inhibition of DNA synthesis and sugar uptake and lack of induction of ornithine decarboxylase in human epidermal cells treated with mouse skin tumor promoters.

The present study was undertaken to investigate the possibility that 12-O-tetradecanoylphorbol-13-acetate (TPA) is active as a tumor promoter in human skin. Human epidermal and dermal cells were isolated from the skin of normal subjects by trypsinization and separation of the epidermis from the dermis. Cells in primary culture were exposed to a wide range of TPA concentrations (0.001 to 1000 ng/ml) for various time intervals, and its effect on DNA synthesis, sugar uptake, and polyamine synthesis was measured. Results obtained using human cells were compared with those for the corresponding cells isolated from Sencar mice. In human epidermal cells, TPA did not stimulate but instead inhibited DNA synthesis and uptake of 2-deoxy-D-glucose (DG), a glucose analogue. Inhibition of DNA synthesis could be detected at a dose of TPA as low as 0.1 ng/ml, while at 10 ng/ml DNA synthesis was 50 to 70% of the control. Inhibition of DG uptake depended on concentration of and length of exposure to TPA. Exposure to TPA (10 ng/ml) for 3 hr resulted in a 35% inhibition of DG uptake. Furthermore, exposure of human epidermal cells to TPA under various conditions, including the use of uncultured, freshly isolated cells and of a low-calcium medium, did not result in induction of ornithine decarboxylase, a key enzyme in the synthesis of polyamine. Teleocidin B, a tumor promoter, structurally unrelated to TPA but with an ornithine decarboxylase inducibility in mouse skin similar to that of TPA, also failed to induce ornithine decarboxylase activity in human epidermal cells. Mouse epidermal cells reacted differently from human epidermal cells on addition of TPA. DNA synthesis, sugar uptake, and polyamine synthesis were all stimulated. DG uptake alone was stimulated in human and mouse dermal cells treated with TPA.

Presence of specific binding sites for phorbol ester tumor promoters in human epidermal and dermal cells in culture but lack of down regulation in epidermal cells.

The presence of specific binding sites for phorbol esters was demonstrated in human epidermal and dermal cells in culture by assay of binding of [3H]phorbol-12,13-dibutyrate (PDBU) to intact cells. The specificity of the binding was shown by displacement of the binding with biologically active tumor promoters, such as 12-O-tetradecanoylphorbol-13-acetate, teleocidin B, and mezerein, but not with inactive derivatives. The equilibrium binding data were analyzed by the Scatchard method and fitted by a straight line to the model of a single class of binding sites. Human epidermal cells bound PDBU with a Kd of 28 nm at 3.7 X 10(6) molecules per cell, while human dermal cells bound PDBU with a Kd of 27 nm at 2.1 X 10(6) molecules per cell. These values were compared with those of epidermal and dermal cells of mice. Although mouse cells showed the same affinity as did human cells, mouse epidermal cells bound one-third as much as human epidermal cells, and mouse dermal cells bound one-fifth as much as human dermal cells. When precultured with unlabeled PDBU for 24 hr, [3H]PDBU binding decreased time dependently in all cells except human epidermal cells. Thus, the binding of phorbol esters to human epidermal cells is unique in that there are a large number of binding sites compared with mouse epidermal cells, and there is no down regulation.

Systemic inhibition of tumor promoter-induced ornithine decarboxylase in 1 alpha-hydroxyvitamin D3-treated animals.

Topical application of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], an active form of vitamin D3, was previously shown to inhibit the induction of ornithine decarboxylase (ODC) and tumor promotion by tumor promoters in mouse skin. In the present study, this observation in skin was extended to other tissues, such as the stomach, colon, and liver, using 1 alpha-hydroxyvitamin D3 [1 alpha (OH)D3], which is converted to 1 alpha,25(OH)2D3 in the liver without hormonal control and thus evokes the systemic effects, if any, of 1 alpha,25(OH)2D3. When mice were given 1 alpha (OH)D3 at a dose of 5 micrograms by gastric tube, their plasma level of 1 alpha,25(OH)2D3 increased to a peak of about 18-fold the normal level after 12 h, followed by hypercalcemia (about 14 mg/dl), which reached a peak on Days 2 to 3. In 1 alpha (OH)D3-treated mice, induction of epidermal ODC by 12-O-tetradecanoylphorbol-13-acetate was markedly inhibited, the inhibition being maximal 2 to 4 days after 1 alpha (OH)D3 administration. ODC induction in the glandular stomach mucosa of rats by NaCl, a tumor promoter in stomach carcinogenesis, was also inhibited dose and time dependently by 1 alpha (OH)D3. Similarly, 1 alpha (OH)D3 treatment of rats markedly inhibited the induction of ODC in the colon mucosa by deoxycholate, a tumor promoter of colon carcinogenesis, and of ODC in the liver by phenobarbital, a promoter of liver carcinogenesis. These results suggest that an active form of vitamin D3 has a systemic inhibitory effect on induction of ODC activity by tumor promoters.