Temporal change in the diagnosis and treatment rates of osteoporosis: results from the Korea National Health and Nutrition Examination Survey.

To compare the diagnosis andtreatment rates of osteoporosis and diabetes in Korea, a nationwide database was used. The results showed that although osteoporosis management is improving, it is still lower compared with that of diabetes; thus, further efforts are needed in this regard. INTRODUCTION: This study aimed to re-evaluate the diagnosis and treatment of osteoporosis from the KNHANES 2016-2017 and compare the temporal change of the rate with those of diabetes as another prevalent chronic disease in South Korea. METHODS: The prevalence of osteoporosis in 2016 was estimated using the previous data classified by age groups (50-59,60-69, and ≥70years) and the 2016 Korean census data. The physician diagnosis and treatment rates of osteoporosis in adults aged ≥50years were estimated using the 2016-2017 KNHANES data. The physician diagnosis and treatment rates of diabetes were evaluated using the KNHANES 2008-2009 and 2016-2017 data. RESULTS: The estimated physician diagnosisrate of osteoporosis increased from 29.9% in females and 5.8% in males in 2008-2009 to 62.8% in females and 22.8% in males in 2016-2017. The treatment rate for the estimated total number of patients with osteoporosis increased from 14.4% in females and 3.8% in males in 2008-2009 to 32.2% in females and 9.0% in males in 2016-2017. An increasing trend in the estimated treatment rateof physician-diagnosed osteoporosis patients was not observed (48.3% [2008-2009] vs 51.5% [2016-2017] in females; 42.6% [2008-2009] vs 42.2% [2016-2017] in males). The physician diagnosis and treatment rates of diabetes were considerably better and more stable than those of osteoporosis. CONCLUSION: Osteoporosis management in South Korea is improving but is insufficient compared with diabetes management. More extensive efforts are needed to improve the diagnosis and treatment rates of osteoporosis.

Development of the Asia Pacific Consortium on Osteoporosis (APCO) Framework: clinical standards of care for the screening, diagnosis, and management of osteoporosis in the Asia-Pacific region.

Guidelines for doctors managing osteoporosis in the Asia-Pacific region vary widely. We compared 18 guidelines for similarities and differences in five key areas. We then used a structured consensus process to develop clinical standards of care for the diagnosis and management of osteoporosis and for improving the quality of care. PURPOSE: Minimum clinical standards for assessment and management of osteoporosis are needed in the Asia-Pacific (AP) region to inform clinical practice guidelines (CPGs) and to improve osteoporosis care. We present the framework of these clinical standards and describe its development. METHODS: We conducted a structured comparative analysis of existing CPGs in the AP region using a "5IQ" model (identification, investigation, information, intervention, integration, and quality). One-hundred data elements were extracted from each guideline. We then employed a four-round Delphi consensus process to structure the framework, identify key components of guidance, and develop clinical care standards. RESULTS: Eighteen guidelines were included. The 5IQ analysis demonstrated marked heterogeneity, notably in guidance on risk factors, the use of biochemical markers, self-care information for patients, indications for osteoporosis treatment, use of fracture risk assessment tools, and protocols for monitoring treatment. There was minimal guidance on long-term management plans or on strategies and systems for clinical quality improvement. Twenty-nine APCO members participated in the Delphi process, resulting in consensus on 16 clinical standards, with levels of attainment defined for those on identification and investigation of fragility fractures, vertebral fracture assessment, and inclusion of quality metrics in guidelines. CONCLUSION: The 5IQ analysis confirmed previous anecdotal observations of marked heterogeneity of osteoporosis clinical guidelines in the AP region. The Framework provides practical, clear, and feasible recommendations for osteoporosis care and can be adapted for use in other such vastly diverse regions. Implementation of the standards is expected to significantly lessen the global burden of osteoporosis.

Urinary Pentosidine levels negatively associates with trabecular bone scores in patients with type 2 diabetes mellitus.

Pentosidine levels were higher in diabetic patients with vertebral fractures. Trabecular bone scores were negatively associated with pentosidine levels in diabetic patients only. Our results provide further evidence that AGEs are associated with the pathogenesis of bone fragility in patients with T2DM. INTRODUCTION: Type 2 diabetes mellitus (T2DM) is associated with fracture risk. Pentosidine, an advanced glycation end product (AGE), is associated with prevalent vertebral fractures (VFs) in patients with T2DM. Trabecular bone score (TBS) has been proposed as an index of bone microarchitecture associated with bone quality. This study evaluated the associations of urine pentosidine and TBS in T2DM and non-T2DM groups. METHODS: A total of 112 T2DM patients and 62 non-T2DM subjects were enrolled. TBS was calculated using TBS insight® software (version 2.1). Pentosidine levels were measured using high-performance liquid chromatography method. We compared the BMD, TBS, and pentosidine levels between those with and without VFs with or without adjustment for age and sex. The association with TBS, lumbar spine BMD, and pentosidine levels were also evaluated in both T2DM and non-T2DM groups. RESULTS: Pentosidine levels were significantly higher in T2DM patients with VFs. TBSs were significantly lower in patients with T2DM and VFs. In non-diabetic patients, there were no significant differences in TBS and pentosidine levels for those with and without VFs after adjustment for age and sex. Pentosidine levels were negatively associated with TBS only in patients with T2DM. In multivariate stepwise regression analysis, pentosidine levels were significantly associated with TBS in patients with T2DM. CONCLUSIONS: TBS and pentosidine could be used as a method to assess bone quality to identify T2DM patients at risk of VFs. Our results also provide further evidence that AGEs are associated with the pathogenesis of bone fragility in patients with T2DM.

The Introduction of Human Heme Oxygenase-1 and Soluble Tumor Necrosis Factor-α Receptor Type I With Human IgG1 Fc in Porcine Islets Prolongs Islet Xenograft Survival in Humanized Mice.

Apoptosis during engraftment and inflammation induce poor islet xenograft survival. We aimed to determine whether overexpression of human heme oxygenase-1 (HO-1) or soluble tumor necrosis factor-α receptor type I with human IgG1 Fc (sTNF-αR-Fc) in porcine islets could improve islet xenograft survival. Adult porcine islets were transduced with adenovirus containing human HO-1, sTNF-αR-Fc, sTNF-αR-Fc/HO-1 or green fluorescent protein (control). Humanized mice were generated by injecting human cord blood-derived CD34(+) stem cells into NOD-scid-IL-2Rγ(null) mice. Both HO-1 and sTNF-αR-Fc reduced islet apoptosis under in vitro hypoxia or cytokine stimuli and suppressed RANTES induction without compromising insulin secretion. Introduction of either gene into islets prolonged islet xenograft survival in pig-to-humanized mice transplantation. The sTNF-αR-Fc/HO-1 group showed the best glucose tolerance. Target genes were successfully expressed in islet xenografts. Perigraft infiltration of macrophages and T cells was suppressed with decreased expression of RANTES, tumor necrosis factor-α and IL-6 in treatment groups; however, frequency of pig-specific interferon-γ-producing T cells was not decreased, and humoral response was not significant in any group. Early apoptosis of islet cells was suppressed in the treatment groups. In conclusion, overexpression of HO-1 or sTNF-αR-Fc in porcine islets improved islet xenograft survival by suppressing both apoptosis and inflammation. HO-1 or sTNF-αR-Fc transgenic pigs have potential for islet xenotransplantation.

Presentation of available CTL epitopes that induction of cell-mediated immune response against HIV-1 Koran clade B strain using computational technology.

OBJECTIVE: Theoretical predicting cytotoxic T lymphocyte (CTL) epitopes are an important tool in vaccine design and CTL therapy for enhancing our understanding of the cellular immune system. We would like to identify available CTL epitopes against HIV-1 Korean clade B. CTL activity was assessed in freshly isolated peripheral blood mononuclear cells from Korean HIV patients in order to assess whether these CTL epitopes induce a cell-mediated immune response (CMI). METHODS: NetCTLpan1.1 software, which is the most popular prediction computer software package, and full atom-based simulation (FABS), which is a 3D modelling system for binding activity between epitopes and human leucocyte antigen (HLA) molecules, were used to predict the peptide-spanning Env region binding to HLA-A*24:02, HLA-A*02:01 and HLA-B*15:01, which are frequently found in the Korean population. Granzyme B and interferon-γ ELISPOT assays were used to determine whether identified CTL epitopes induce CMI. RESULTS: Three HIV-1 Korean clade B-specific Env CTL epitopes were identified: Gp41-RYL and Gp41-RQG are localized within gp41, and Gp120-LLQ within gp120. In in vitro assays using granzyme B ELISPOT, Gp120-LLQ and Gp41-RQG induced epitope-specific CTL responses in HLA-restricted cells. In ex vivo assay using IFN-γ ELISPOT, cell-mediated immune responses to Gp41-RYL were present in 50% of HLA-matched patients, and responses to Gp120-LLQ and Gp41-RQG were found in 33% of HLA-matched patients. CONCLUSION: In this study, we found that a prediction pipeline for CTL epitopes might be based on the most popular computer prediction software and FABS methods. Our results suggest that these CTL epitopes may provide useful tools and information for the development of a therapeutic vaccine against HIV-1 Korean clade B.

Subjective apnoea symptoms are associated with daytime sleepiness in patients with moderate and severe obstructive sleep apnoea: a retrospective study.

OBJECTIVES: Most previous studies have failed to show a relation between daytime sleepiness and apnoea severity in patients with obstructive sleep apnoea (OSA). We determined the relation between daytime sleepiness and subjective and objective apnoea severity in newly diagnosed patients with moderate-to-severe OSA. DESIGN: Retrospective cross-sectional study. SETTING: Tertiary referral centre. PARTICIPANTS: A total of 559 adults with newly diagnosed moderate and severe OSA. MAIN OUTCOME MEASURES: Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). Subjective and objective apnoea severities were assessed using the Sleep Breathing Scale (SBS) and polysomnography respectively. Sleep quality and depressive symptoms were evaluated using Medical Outcomes Study-Sleep Scale and Beck Depression Inventory (BDI) respectively. RESULTS: The mean ESS score was 9.8 (SD 5.0). ESS score was correlated with SBS score (P < 0.001), apnoea-hypopnoea index (AHI) (P = 0.027), minimal oxygen saturation (MinSaO2 ) (P = 0.021), body mass index (BMI) (P = 0.007) and BDI score (P < 0.001). Linear regression analysis showed that higher SBS (P = 0.005) and BDI scores (P < 0.001) were associated with higher ESS score after controlling for gender, BMI and AHI. Apnoea-hypopnoea index, MinSaO2 and BMI were not independently related to ESS score. CONCLUSIONS: Daytime sleepiness was related to subjective OSA symptoms but not objective apnoea severity measured by polysomnography in patients with moderate-to-severe OSA. These findings suggest the usefulness of the subjective apnoea severity as an indicator of OSA disease severity.

Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex.

Carney complex (CNC) is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumours and psammomatous melanotic schwannomas. CNC is inherited as an autosomal dominant trait and the genes responsible have been mapped to 2p16 and 17q22-24 (refs 6, 7). Because of its similarities to the McCune-Albright syndrome and other features, such as paradoxical responses to endocrine signals, genes implicated in cyclic nucleotide-dependent signalling have been considered candidates for causing CNC (ref. 10). In CNC families mapping to 17q, we detected loss of heterozygosity (LOH) in the vicinity of the gene (PRKAR1A) encoding protein kinase A regulatory subunit 1-alpha (RIalpha), including a polymorphic site within its 5' region. We subsequently identified three unrelated kindreds with an identical mutation in the coding region of PRKAR1A. Analysis of additional cases revealed the same mutation in a sporadic case of CNC, and different mutations in three other families, including one with isolated inherited cardiac myxomas. Analysis of PKA activity in CNC tumours demonstrated a decreased basal activity, but an increase in cAMP-stimulated activity compared with non-CNC tumours. We conclude that germline mutations in PRKAR1A, an apparent tumour-suppressor gene, are responsible for the CNC phenotype in a subset of patients with this disease.

Development of Allison scanner to measure transverse emittance at low energy beam transport of rare-isotope accelerator complex for ON-line experiments.

The Rare-isotope Accelerator complex for ON-line experiments is a heavy-ion accelerator facility that accelerates a stable or rare isotope beam up to 400 kW with an energy of 200 MeV/u. Various heavy-ion beams are generated from the Electron Cyclotron Resonance Ion Source, with an energy of 10 keV/u and separated according to A/Q at the first dipole magnet (DM). To measure beam transverse emittance at the Low Energy Beam Transport section, two Allison scanners are installed behind the DM for the X and Y directions. It consist of a servo motor for driving, a Faraday cup for current measurement, deflection plates, and electronic device. The measurable range of beam angle in of the Allison scanner is determined by the structure of the deflection plate and designed based on mathematical calculations. Experimental Physics and Industrial Control System (EPICS) is adopted to integrate and control a variety of devices. To control the complex measurement sequence of the Allison scanner, an EPICS sequencer module was used. Normalized emittance is calculated by python code with Pyepics module using phase space distribution data. In this paper, we present the detailed design of the Allison scanner, the configuration of the control system, and the experimental results using an Ar9+ 30 µA beam.

The importance of morphometric radiographic vertebral assessment for the detection of patients who need pharmacological treatment of osteoporosis among postmenopausal diabetic Korean women.

UNLABELLED: Many diabetic patients with vertebral fractures remain undiagnosed and untreated. We found that more than two-thirds of osteoporotic diabetic women could not be identified for pharmacological treatment according to the NOF guidelines if without radiographic vertebral assessment. This study shows the importance of radiographic vertebral assessment for identifying patients who need treatment for osteoporosis in diabetic women. INTRODUCTION: Diagnosis of vertebral fracture (VF) is important for identifying patients who need pharmacologic therapy for osteoporosis. However, many patients with vertebral fractures remain undiagnosed and untreated. This study evaluated the number of patients with VFs who would be unrecognized as candidates for osteoporosis treatments according to the National Osteoporosis Foundation (NOF) Clinician's Guidelines to the Treatment of Osteoporosis, among postmenopausal diabetic Korean women without spinal imaging. METHODS: A total of 873 postmenopausal diabetic women were enrolled. Lateral plain radiographs of the thoracolumbar spine and total hip BMD were obtained. The Fracture Risk Assessment Tool (FRAX®) probability was computed using the algorithm available online at http://www.shef.ac.uk/FRAX (South Korea version). The subjects with and without VFs were classified into candidates for osteoporosis treatment [Tx+by NOF] and not candidates for osteoporosis treatment [Tx−by NOF] according to the NOF pharmacologic treatment guidelines, regardless of the presence of VFs. RESULTS: Forty-six percent of postmenopausal diabetic womenhad morphometric VFs. Among the subjects with morphometric VFs, only 2% of the patients had previously diagnosed VFs by medical doctors. In addition, 73.6% of the patients with VFs were not included in the [Tx+by NOF] group, given the assumption of no radiographic diagnosis of VFs. CONCLUSIONS: With regard to increased risk of VFs in postmenopausal Korean women with type 2 diabetes mellitus, radiographic vertebral assessment would be useful for the clinical identification of osteoporosis and fractures.

A weekly administered sustained-release growth hormone reduces visceral fat and waist circumference in abdominal obesity.

Administration of recombinant human growth hormone (rhGH) in obesity has been known to lead to a decrease in visceral adiposity and an increase in lean body mass. Most studies have used supraphysiological doses of rhGH, which were administered daily or every other day. We aimed to evaluate whether weekly administered low dose of sustained-release rhGH (SR-rhGH) could play a therapeutic role in the treatment of abdominal obesity. Prospective, single-arm, open-label, multicenter pilot study was carried out. Participants were 26 adults aged 40-65 years old with abdominal obesity (male: waist circumference >90 cm, female: waist circumference >85 cm). The subjects were given 3 mg of SR-rhGH, administered subcutaneously, weekly for 26 weeks. SR-rhGH treatment for 26 weeks increased the IGF-1 level by 56.53±76.09 µg/l (SDS 0.77±1.12) compared to the baseline (p=0.0022). After 26 weeks, SR-rhGH treatment reduced abdominal visceral adipose tissue (VAT) (140.35±75.97 to 128.43±73.85 cm2, p=0.0038). Average waist circumference decreased from 96.25±6.41 to 91.93±6.13 cm (p<0.0001) after treatment. However, body weight or lean body mass did not show any significant change. In conclusion, SR-rhGH treatment for 26 weeks reduced abdominal visceral fat and waist circumference without severe adverse events. Further studies may be considered on the role of weekly administered SR-rhGH as a treatment for abdominal obesity.

A single-injection protein kinase A-directed antisense treatment to inhibit tumour growth.

Expression of the RI alpha subunit of cAMP-dependent protein kinase type I is enhanced in human cancer cell lines, in primary tumours, in cells after transformation and in cells upon stimulation of growth. We have investigated the effect of sequence-specific inhibition of RI alpha gene expression on in vivo tumour growth. We report that single injection RI alpha antisense treatment results in a reduction in RI alpha expression and inhibition of tumour growth. Tumour cells behaved like untransformed cells by making less protein kinase type I. The RI alpha antisense, which produces a biochemical imprint for growth control, requires infrequent dosing to halt neoplastic growth in vivo.

The analysis of PM2.5 and associated elements and their indoor/outdoor pollution status in an urban area.

UNLABELLED: In this study, elemental composition of PM2.5 and the status of indoor/outdoor pollution were investigated in a commercial building near a roadside area in Daejeon, Korea. A total of 60 parallel PM2.5 samples were collected both on the roof (outdoor) and in an indoor office of a building near a highly congested road during the spring and fall of 2008. The concentrations of 23 elements were analysed from these PM2.5 samples using instrumental neutron activation analysis. PM2.5 levels in indoor environment (47.6 ± 16.5 µg/m(3)) were noticeably higher than the outdoor levels (37.7 ± 17.2 µg/m(3)) with the I/O concentration ratio of 1.37 ± 0.33 [correlation coefficient (r) = 0.89, P < 0.001]. Principal component analysis results coincidently showed the predominance of sources such as soil dust, traffic, oil/coal combustion and road dust for both indoor and outdoor microenvironments. An isolated source in the indoor environment was assigned to environmental tobacco smoke (ETS) with high factor loading of Ce, Cl, I, K, La and Zn. The overall results of our study indicate that the sources of indoor constituents were strongly dependent on outdoor processes except for the ones affected by independent sources such as ETS. PRACTICAL IMPLICATIONS: An improved understanding of the factors affecting the indoor PM2.5 concentration levels can lead to the development of an efficient management strategy to control health risks from exposure to indoor PM2.5 and related toxic components. A comparison of our comprehensive data sets indicated that most indoor PM2.5 and associated elemental species were strongly enriched by indoor source activities along with infiltration of ambient outdoor air for a naturally ventilated building.

Assessment of Coronavirus disease, the nose pollution filter, fermented spicy Kimchee, and peppery hot soup consumed in Korea.

Recent statistics of Coronavirus diseases in Korea are studied with respect to many other countries. It is found that as of 8 February 2021, Korea has recorded 15.8 patients per 10,000 people, and this is used to calculate ratio to compare with other countries. On average, the number of Coronavirus patients in the world is 136.2 that is 8.6 times more than in Korea. The number of Covid-19 patients recorded in Korea is relatively smaller than other countries. There was no clear evidence on the atmospheric transport of Coronaviruses over 1 km to cause infection to other people. The infection of Coronaviruses appeared to occur mainly by close contact with an infected person or by airborne droplets in confined indoor environments, as noted earlier (Lancet, Respir Med 8(12):1159, 2020). To reduce the transmission of Coronavirus and related infections, the wearing of a pollution filter (mask) covering the nose and mouth is mandatory for Coronavirus patients. For the general public, however, we have invented a filter which covers only the nose. When there is no need for conversation and deep breathing, the nose band would be sufficient to filter out Coronavirus and air pollutants. Meanwhile, air and sea port activities including ground transport continued and strict policy on people mingle was not tightly enforced, and control measures to reduce infection were not so effective. However, it is believed that consuming fermented Korean spicy Kimchee and hot peppery soup plus warm rice tea helps in washing Coronaviruses around the throat deep down to the stomach. We find that cleansing the mouth and throat deeply including pathway is better than doing shallow gargling. A possible mechanism for cleansing the mouth and throat of Coronaviruses is here explored. This could have contributed to the relatively small number of Coronavirus patients observed in Korea.

Assessment of the impacts and transmission of coronavirus observed in the Republic of Korea in 2020-2021.

The pandemic of Coronavirus diseases occurred in the Republic of Korea from 19 January 2020. By March 2020, Korea had reported the second largest number of Coronavirus patients in the world. On the anniversary date (2021), however, with a 51.3 M population, Korea has had 73.115 K patients with 1.283 K deaths, and this stands at 86th in the world. On average, Korea has 14.3 patients per 10,000 people. Air-parcel trajectory analysis and airflows show that in the general westerly region, air parcels and pollutants could flow out and in all directions. This suggests initially that Coronaviruses from source areas in China could transmit to many sink regions and sectors including 228 subdivided counties in Korea. However, there were only relatively small numbers of Coronavirus patients in western sea sides of the Korean Peninsula in comparison with large numbers of Coronavirus disease patients in cities and in eastern sides. In particular, three counties in Korea, including Ong-jin, Mooju and Chang-heung, have zero patients of Coronavirus diseases. This suggests that a long-distance transmission of Coronavirus from Wuhan and other infected cities in China to western Korea likely did not occur. Moreover, there was no evidence on the potential transmission of Coronavirus from neighboring large cities to the above-mentioned isolated counties in Korea which are only 10 ~ 50 km away. In the biosphere, during the transmission stage, the inactivation of Coronavirus by UV rays appeared to occur effectively in 30 ~ 120 min, in agreement with the result of satellite and modeling studies. In turn, the air transmission of Coronaviruses and pollution from China and neighboring cities in Korea apparently had no impact to cause Coronavirus diseases at the 228 counties in Korea. The infection and spreading of Coronavirus diseases to other people in Korea mainly appeared to occur in confined indoor air environments. With the absence and lack of UV rays in indoor environments, Coronaviruses would be active there for hours or days longer than in the outdoor environments.

Cyclic AMP receptor triggers nuclear protein phosphorylation in a hormone-dependent mammary tumor cell-free system.

Adenosine 3',5'-monophosphate (cyclic AMP) receptor protein of 56,000 daltons increases markedly in mammary tumors induced by 7,12-dimethylbenz[a]anthracene (DMBA) after incubation of tumor slices with cyclic AMP, benzamide, and arginine. Incubation of cytosol from these tumor slices with nuclei from unincubated tumors results in nuclear uptake of the 56,000-dalton cyclic AMP receptor and in phosphorylation of the 76,000-dalton nuclear protein. Binding of the 56,000-dalton receptor and phosphorylation of the 76,000-dalton protein also occur in DMBA tumor nuclei when protein kinase type II of bovine heart is used. The results suggest that cyclic AMP receptor is involved in the nuclear events of a hormone-dependent mammary tumor.

In vivo inhibition of growth of two hormone-dependent mammary tumors by dibutyryl cyclic AMP.

Growth of hormone-dependent rat mammary tumors was arrested in vivo by N(6),O(2)'-dibutyryl cyclic adenosine 3',5'-monophosphate. Estrogen concentration did not change, but acid ribonuclease activity and synthesis increased during treatment with the dibutyryl cyclic nucleotide, as was shown during tumor regression due to hormonal deprivation. Growth arrest, thus, appears to derive from enhanced tissue catabolism.

Dibutyryl cyclic AMP mimics ovariectomy: nuclear protein phosphorylation in mammary tumor regression.

Growth of mammary carcinoma induced by 7,12-dimethyl-benz(a) anthracene is arrested by either ovariectomy or treatment with N6,O2-dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cyclic AMP). When this occurs, a new nonhistone protein species becomes the predominant endogenous substrate of cyclic AMP-dependent protein kinase in the tumor nuclei. Phosphorylation of this regression-associated protein ceases when resumption of tumor growth is induced by either the injection of 17 beta-estradiol or cessation of dibutyryl cyclic AMP treatment. Thus phosphorylation of regression-associated protein may play a role in the regression of hormone-dependent mammary tumors.

Growth arrest and morphological change of human breast cancer cells by dibutyryl cyclic AMP and L-arginine.

The growth in vitro of human breast cancer cells, line MCF-7, was inhibited by a daily supplement of L-arginine (1 milligram per milliliter). Arginine acted synergistically with dibutyryl adenosine 3',5'-monophosphate (cyclic AMP) (10(-6) molar) to enhance the growth inhibitory effect: the cell replication ceased completely within 2 days after treatment. The growth arrest accompanied a change in cell morphology and was preceded by increases in the cellular concentration of cyclic AMP, adenylate cyclase, and type II cyclic AMP-dependent protein kinase activities as well as a decrease of estrogen binding activity. The results suggest that growth of human breast cancer cells is subject to cyclic AMP-mediated regulation and that arginine may play a specific role in this process.