Subjective, neuropsychological, and neural markers of memory in older adults.

OBJECTIVES: To investigate the relationship between the P300 event-related potential, neuropsychological measures of memory, subjective memory complaints (SMCs), and indicators of psychosocial functioning. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study of 79 community-based older adults, aged 60-75 years, participants completed online surveys and in-person neuropsychological and electroencephalogram (EEG) assessments. MEASUREMENTS: Measures included: the Change subscale of the Metamemory in Adulthood Questionnaire, NIH Toolbox Emotions battery (Perceived Stress and Psychological Well-Being), Geriatric Depression Scale, Geriatric Anxiety Scale, electrocortical measures (EEG), California Verbal Learning Test, 3rd Edition, and diagnostic ratings for mild and major neurocognitive disorders based on full neuropsychological battery, clinical interview, and two-clinician consensus. RESULTS: P300 amplitude was associated with long-delay verbal memory recall and diagnostic rating. SMCs were not associated with objective memory or diagnostic rating. SMCs were associated with higher perceived stress, anxiety, and depression symptoms and lower psychological well-being. CONCLUSIONS: Neural indicators such as the P300 may be useful for early detection of cognitive impairment. SMCs were not a reliable indicator of early memory impairment in relation to neuropsychological or neural indicators, but may be a useful indicator of unreported stress and mood symptoms in clinical settings.

Paraneoplastic syndrome - a rare but treatable cause of non-thyroid-related extraocular muscle enlargement.

Paraneoplastic syndrome is a rare but reversible cause of non-thyroid-related extraocular muscle enlargement. We present a 71-year-old lady with diplopia, restricted eye movements, suppressed thyroid-stimulating hormone and enlargement of all extraocular muscles while on thyroxine replacement for hypothyroidism. She had distant history of metastatic breast cancer treated with chemotherapy, surgical resection and tamoxifen. She had negative anti-thyroid autoantibodies and thyroid ultrasound was not consistent with autoimmune thyroid disease. Carcinoembryonic antigen and cancer antigens 15-3, 125 and 72-4 were elevated, and whole-body positron emission tomography-computed tomography showed avid liver, left adrenal and skeletal lesions, with liver biopsy confirming breast cancer recurrence. She received prednisone and chemotherapy (letrozole, palbociclib) and achieved normalisation of eye movements and reduction in her EOME at 9-month follow-up. Our case highlights the importance of exploring paraneoplastic syndrome as a treatable cause of EOME in a patient lacking features of thyroid orbitopathy and autoimmune thyroid disease.

First-Principles and Thermodynamics Study of Compositionally Tuned Complex Metal Oxides: Cation Release from the (001) Surface of Mn-Rich Lithium Nickel Manganese Cobalt Oxide.

Compositional tuning of nanoscale complex metal oxides (CMOs) can lead to enhanced performance and favorable properties for a variety of energy-related applications. However, investigations of the nanoscale CMOs used in energy storage technologies demonstrate that these nanomaterials may have an adverse biological impact, highlighting a fundamental knowledge gap between nanomaterial design and the structure and properties at the end of life. CMO nanomaterials can enter the environment due to improper disposal, where they undergo subsequent (as of yet poorly understood) nanoscale transformations that may affect biological response and, ultimately, environmental fate. This points to the need for studies at the nano-bio interface that can be used to shape rules for the redesign of CMOs: materials that are are potentially more benign by design and serve as examples of sustainable nanotechnology. The example given here is to enrich lithium nickel manganese cobalt oxide, Li x(Ni yMn zCo1- y- z)O2 (NMC), with Mn to create a family of materials that are less expensive and potentially less toxic to a wide range of organisms. In this paper, we investigate the structure and electronic states of Mn-rich NMC at the density functional theory (DFT) level to elucidate the interplay of redox properties, oxidation state, and coordination environment of a compositionally tuned CMO. We find that the oxidation states of Ni and Co remain mostly unaffected while Mn exists as both Mn2+ and Mn4+. Our models show that the ratio of Mn2+ and Mn4+ varies with changes in the coordination environment, such as the identity of neighboring atoms and surface OH group coverage. The surface metal release properties of Mn-rich NMC compositions are predicted using a DFT + solvent ion model and show that Mn-rich NMC compositions are inherently more prone to dissolution than NMC and that this is attributed to the changes in oxidation state of the transition metals in Mn-rich NMC.

Anomalous biliary and vascular anatomy-Potential pitfalls during cholecystectomy.

Laparoscopic cholecystectomy is usually a low-risk procedure associated with a short stay and a low rate of conversion to open surgery. Complications are sometimes associated with anomalous vascular or biliary anatomy. Outlined below are the variations in vascular and biliary anatomy which may result in complications either due to involvement in the inflammatory process or inadvertent division during dissection. Clin. Anat. 30:1103-1106, 2017. © 2017 Wiley Periodicals, Inc.

Effect of oral cholecalciferol 2,000 versus 5,000 IU on serum vitamin D, PTH, bone and muscle strength in patients with vitamin D deficiency.

UNLABELLED: Treatment of vitamin D deficiency for 3 months with oral cholecalciferol 5,000 IU daily was more effective than 2,000 IU daily in achieving optimal serum 25-hydroxyvitamin D (25OHD) concentrations. Optimal 25OHD serum level calculated to be 63.8 nmol/L. All parameters of muscle strength improved following administration of cholecalciferol for 3 months. INTRODUCTION: The aim of this study was to determine the optimal dose of cholecalciferol required to achieve target serum 25OHD level ≥ 75 nmol/L and its relationship to both bone turnover and muscle strength. METHODS: Thirty deficient patients (serum 25OHD ≤ 50 nmol/L) were randomly assigned into two groups-i.e. 2,000 and 5,000 IU/day. Data were collected at baseline, at 2 and 3 months post-therapy: (a) clinical demographics, (b) dietary calcium recall, (c) physical tests of muscle function and (d) biochemistry. Statistical analysis used paired student t test and analysis of variance. Regression analysis was used to determine relationship between serum 25OHD and parathyroid hormone (PTH). RESULTS: Twenty-six (87%) patients completed 3 months of therapy. The percent increase in serum 25OHD (compared to baseline) was 82.7% in 2,000-IU group and 219.5% in 5,000-IU group. All participants (100%) achieved a serum 25OHD concentration >50 nmol/L; only 5 subjects (45.4%) in 2,000-IU group compared to 14 subjects (93.3%) in 5,000-IU group achieved final 25OHD concentration ≥ 75 nmol/L (p < 0.01). In the regression analysis, the reflexion point at which the PTH level increased above the normal range was calculated to be 63.8 nmol/L 25OHD. All parameters of muscle strength showed trends in improvements following the administration of both the 2,000 and 5,000 IU doses. No patient reported untoward side effects and no patient developed hypercalcaemia. CONCLUSION: Treatment for 3 months with oral cholecalciferol 5,000 IU daily may be more effective than 2,000 IU daily in achieving optimal serum 25OHD concentrations in vitamin D-deficient patients.

Role of carcinoembryonic antigen as a marker for colorectal liver metastases.

Carcinoembryonic antigen (CEA), a marker for colorectal adenocarcinoma, can monitor disease progression and treatment response. This study aims to determine the accuracy of CEA in the detection and resectability of colorectal liver metastases. Patients with primary colorectal cancer were divided into three groups: resectable hepatic metastases (group 1), unresectable metastases (group 2), and disease-free cases (group 3). The CEA concentration was recorded pre- and post-hepatectomy in group 1 and on radiological confirmation of disease state in the other groups. It was expressed as median (95% confidence interval [CI]), with predictors of concentration determined. Group 1 (n=141) had pre-operative CEA of 8.9 (4.6-13.1), with 38.1% of patients being normal. Maximum tumour diameter correlated with CEA level (r=0.41, P<0.0001). Post-hepatectomy CEA was 2.3 (1.9-2.7; P<0.0001), with 81.1% of patients being normal. Group 2 (n=158) had CEA of 20.6 (9.4-31.9). Group 3 (n=361) had CEA of 2.0 (1.8-2.2). Sensitivity of CEA pre- and post-hepatectomy was 61.2% and 69.3%, respectively, while specificity was 79.8% for both groups. Concentration was elevated in hepatic colorectal metastases but is not a marker of resectability. A CEA reduction post-resection indicates that it may be used as an indicator of treatment response, while CEA is increased by tumour burden and lesion size.

Expression of osteopontin coregulators in primary colorectal cancer and associated liver metastases.

BACKGROUND: A transcription regulatory complex (TRC) that includes Ets1, Ets2, PEA3 and ß-catenin/T-cell factors regulates osteopontin (OPN) that is implicated in colorectal cancer (CRC) dissemination. The consistency of OPN transcriptional control between primary CRC and metastases is unclear. This study investigates expression and prognostic significance of the OPN-TRC in primary human CRC and associated colorectal liver metastases (CRLM). METHODS: Osteopontin-TRC factors were assayed by digital microscopy in 38 primary CRCs and matched CRLM specimens and assessed against clinical prognosis. RESULTS: In primary CRC, OPN expression intensity correlated with that of its co-activators, PEA3 (r=0.600; P<0.01), Ets1 (r=0.552; P<0.01), Ets2 (r=0.521; P<0.01) and had prognostic significance. Osteopontin intensity in primary CRC inversely correlated with the interval between diagnosis and resection of CRLM. Overall OPN intensity was lower in CRLM than primary CRC and correlations with co-activators were weaker, for example, Ets1 (P=0.047), PEA3 (P=0.022) or nonsignificant (Ets2). The ratio of OPN expression in CRLM vs primary CRC had prognostic significance. CONCLUSION: This study supports transcriptional control of OPN by known coregulators in both primary and secondary CRC. Weaker associations in CRLM suggest involvement of other unknown factors possibly from the liver microenvironment or resulting from additional genetic or epigenetic changes that drive tumour metastatic capability in OPN transcriptional control.

Lessons learnt from delayed diagnosis of FGF-23-producing tumour-induced osteomalacia and post-operative hungry bone syndrome.

Tumour-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by a fibroblast growth-factor-23 (FGF-23)-secreting phosphaturic mesenchymal tumour (PMT) and is characterised by hypophosphataemic osteomalacia. We present a 36-year-old man initially presenting with diffuse bone and joint pain who was inappropriately treated for presumed ankylosing spondylitis for 2 years. Whole-body bone scan suggested metabolic bone disease, prompting referral to our endocrine institution. He was subsequently diagnosed with persistent hypophosphataemia, inappropriately high renal tubular phosphate excretion, 1,25-dihydroxyvitamin D3 suppression, severe osteoporosis and severe osteomalacia. FGF-23 concentrations (140 ng/L) were raised 3-fold above the upper limit of normal. Initial Gallium-68 (68Ga) DOTATATE positron emission tomography (PET)/CT scan missed an active lesion in the left fibular head as the field only included the mid-brain to the proximal femora. Histopathology results from tumour resection confirmed a PMT over-expressing FGF-23. Serum phosphate and FGF-23 normalised immediately post-operatively. He developed severe hypocalcaemia 3-weeks post-operatively (1.77 mmol/L) which normalised after 1 month of high-dose caltrate and calcitriol therapy. Osteomalacia, osteoporosis and associated symptoms resolved during medium-term follow-up with >100% improvement in his bone mineral density. This case report and discussion highlights the pitfalls contributing to delayed diagnosis of TIO and alerts clinicians to the potential complication of hungry bone syndrome post-tumour resection.

Management of liver trauma.

BACKGROUND: Blunt and penetrating liver trauma is common and often presents major diagnostic and management problems. METHODS: A literature review was undertaken to determine the current consensus on investigation and management strategies. RESULTS: The liver is the most frequently injured organ following abdominal trauma. Immediate assessment with ultrasound has replaced diagnostic peritoneal lavage in the resuscitation room, but computerised tomography remains the gold standard investigation. Nonoperative management is preferred in stable patients but laparotomy is indicated in unstable patients. Damage control techniques such as perihepatic packing, hepatotomy plus direct suture, and resectional debridement are recommended. Major complex surgical procedures such as anatomical resection or atriocaval shunting are now thought to be redundant in the emergency setting. Packing is also recommended for the inexperienced surgeon to allow control and stabilisation prior to transfer to a tertiary centre. Interventional radiological techniques are becoming more widely used, particularly in patients who are being managed nonoperatively or have been stabilised by perihepatic packing. CONCLUSIONS: Management of liver injuries has evolved significantly throughout the last two decades. In the absence of other abdominal injuries, operative management can usually be avoided. Patients with more complex injuries or subsequent complications should be transferred to a specialist centre to optimise final outcome.

Tryptophan catabolites in mesenteric lymph may contribute to pancreatitis-associated organ failure.

BACKGROUND: Multiple organ failure (MOF) is the key determinant of mortality in acute pancreatitis (AP). Mesenteric lymph cytotoxicity contributes to organ failure in experimental models of systemic inflammation. The aim of this study was to evaluate the mesenteric lymph pathway and the lymph injury proteome in experimental AP-associated MOF, and to test the hypothesis that immunoregulatory tryptophan catabolites contribute to mesenteric lymph cytotoxicity. METHODS: Using an experimental model of AP in rats, the humoral component of mesenteric lymph in AP was compared with that from sham-operated control animals, using in vitro and in vivo cytotoxicity assays, high-throughput proteomics and high-performance liquid chromatography. The experimental findings were corroborated in a cohort of 34 patients with AP. RESULTS: Compared with biologically inactive lymph from sham-operated rats, mesenteric lymph in AP became cytotoxic 3 h after induction. Hierarchical clustering of lymph proteomic mass spectra predicted the biological behaviour of lymph. Levels of the immunoregulatory tryptophan catabolite, 3-hydroxykynurenine, were increased in cytotoxic lymph and re-created cytotoxicity in vitro. In humans with AP, plasma kynurenine concentrations correlated in real time with MOF scores and preceded a requirement for mechanical ventilation and haemodialysis. CONCLUSION: These results support the concept that mesenteric lymph-borne kynurenines may contribute to pancreatitis-associated MOF.

A sensitive stain for aluminum in undecalcified cancellous bone.

Aluminum is known to accumulate with age in bone and other tissues of humans, even in the absence of renal disease. Our study aimed to develop a histological staining method sufficiently sensitive to detect aluminum in plastic sections of undecalcified bone biopsies from healthy volunteers as well as from patients with renal and non-renal bone diseases. We used quantitative histomorphometry to measure the percentage of trabecular surface stained by aluminum and found that our new method was approximately 50% more sensitive for detecting aluminum than the Acid Solochrome Azurine (ASA) method which in turn was significantly more sensitive than the Aluminon method. Aluminon is widely used in pathology laboratories for diagnostic purposes despite concerns in the literature about Aluminon's limited sensitivity for aluminum. Our histomorphometric results showed that the newly developed method stained approximately 10% of the trabecular surface in bone sections from healthy controls, 38% from renal patients, 26% from patients with vitamin D deficiency, and 29% from patients with osteoporosis. Histomorphometric measurements of aluminum-stained trabecular surfaces in sections stained with ASA were consistent with those obtained in Walton-stained sections but proportionately lower. Moreover, the Walton and ASA methods stained aluminum at similar locations in adjacent bone sections. As the ASA and Walton methods are considerably more sensitive for bone aluminum than the Aluminon method, we recommend that either of them should be used in place of the Aluminon method for routine diagnostic purposes.

Parathyroid hypertension. A reversible disorder.

A retrospective study of 75 patients who were surgically cured of primary hyperparathyroidism from 1976 to 1984 was performed to evaluate the blood pressure and metabolic responses to parathyroid surgery. Published data on the population prevalence of hypertension (HT) in South Africa were used for comparison. The overall prevalence of HT before surgery was 47%, compared with 23% in the general population. Hypertension was most frequent in patients older than 60 years (62% vs 39% expected). Renal insufficiency was found in 13 of 35 hypertensive patients and in two of 40 normotensive patients. However, the prevalence of HT in patients with normal creatinine levels (37%) exceeded that expected. The frequency of urolithiasis and mean levels of serum and urine calcium and phosphate were similar in normotensive and hypertensive patients. Parathyroidectomy resulted in a substantial fall in both mean systolic and mean diastolic blood pressures in 54% of the hypertensive subjects, unrelated to improvement in renal function.

Comparative effects of glibenclamide and metformin on ambulatory blood pressure and cardiovascular reactivity in NIDDM.

OBJECTIVE: To compare the effects of chronic glibenclamide and metformin therapy on blood pressure (BP) and cardiovascular responsiveness in patients with NIDDM. RESEARCH DESIGN AND METHODS: Fourteen patients with NIDDM received metformin or glibenclamide for 1 month in a double-blind, randomized crossover study. At the end of each treatment period, patients were tested for forearm vascular responsiveness to intrabrachial arterial infusion of diazoxide (an ATP-sensitive potassium channel opener), acetylcholine, sodium nitroprusside, and norepinephrine, BP responses to intravenous infusions of NE and angiotensin II, BP responses to cold pressor testing and isometric exercise, and 24-h ambulatory BP monitoring. RESULTS: Metformin and glibenclamide produced similar glycemic control. Mean 24-h BPs did not differ between the two groups, but mean 24-h heart rates were significantly lower (75 +/- 6 bpm vs. 80 +/- 6 bpm) on glibenclamide therapy than on metformin. Plasma norepinephrine levels were significantly higher on glibenclamide (6.41 +/- 1.77 vs. 4.26 +/- 1.54 mmol/l, P < 0.01), and systolic BP responses to intravenous norepinephrine and angiotensin II were significantly higher on glibenclamide than on metformin (P < 0.02 and P < 0.05, respectively). Systolic BP responses to cold pressor testing appeared higher on glibenclamide than on metformin, but the difference did not quite achieve statistical significance (P = 0.052). Baseline forearm vascular resistance did not differ between the two drugs, nor did forearm vascular resistance responses to diazoxide, acetylcholine, sodium nitroprusside, and norepinephrine differ. CONCLUSIONS: Glibenclamide therapy is accompanied by greater systolic BP responses to norepinephrine and angiotensin II and higher plasma norepinephrine levels than those that occur on metformin therapy. Lower heart rates on glibenclamide therapy despite evidence of greater sympathetic activity suggests that glibenclamide may have negative chronotropic effects.

Effects of testosterone and venesection on spinal and peripheral bone mineral in six hypogonadal men with hemochromatosis.

To measure the effect of testosterone replacement and venesection on spinal and peripheral bone mineral we prospectively studied six hypogonadal men and six eugonadal men with idiopathic hemochromatosis for 24 months. Venesections were performed every week on all patients, and intramuscular injections of testosterone were administered every 3 weeks to the hypogonadal men only. Bone mineral was measured by quantitative computed tomography in the spine and by single-photon absorptiometry in the forearm. During the 24 month period of observation serum testosterone concentrations and serum ferritin levels became normal. In the hypogonadal men mean lumbar spine bone mineral increased by 13.1 +/- 4.9% (95% CI, 0.5-25.6) and mean forearm bone mineral increased by 4.7 +/- 3.8% (95% CI, -5.1 to 14.6). In contrast in the eugonadal men treated over the same period, mean lumbar spine bone mineral decreased by 3.5 +/- 2.8% (95% CI, -10.9 to 3.8, P less than 0.01) and mean forearm bone mineral remained virtually unchanged (0.07 +/- 0.9%; 95% CI, -1.7 to 3.1, P less than 0.05). These data suggest that bone mineral increases in the lumbar spine and in the forearm in hypogonadal men with hemochromatosis treated by testosterone replacement and venesection.

Camurati-Engelmann disease: two case reports describing metadiaphyseal dysplasia associated with cerebellar ataxia.

This clinical report describes two patients presenting with progressive diaphyseal dysplasia (Camurati-Engelmann Disease) and cerebellar ataxia. The clinical and magnetic resonance imaging findings of the bony and cerebellar lesions are presented.

A therapeutic dilemma: suppressive doses of thyroxine significantly reduce bone mineral measurements in both premenopausal and postmenopausal women with thyroid carcinoma.

We measured lumbar spine, femoral neck, and forearm bone mineral (BMD) in 24 women (14 premenopausal and 10 postmenopausal) who had been treated with total thyroidectomy and 131 Iodine ablation therapy for nonanaplastic thyroid carcinoma and 24 case controls. At the time of the study, all patients were free of cancer (negative 131 Iodine whole body scan and serum thyroglobulin levels less than 0.3 micrograms/L) and all were receiving doses of T4 sufficiently high to prevent a rise in a serum thyroid-stimulating hormone concentration after an iv bolus of TRH. Femoral neck BMD were significantly reduced in both the premenopausal women (89 +/- 3.8% of case controls, 95% CI, 81 to 98) and postmenopausal women (77 +/- 3.9% of case controls; 95% CI, 68 to 86) receiving T4. Lumbar spine BMD and forearm BMD were unaffected in the premenopausal women, but significantly reduced in the postmenopausal women receiving T4 (lumbar spine BMD = 84 +/- 6.2% of case controls; 95% CI, 70 to 98 and forearm BMD = 89 +/- 5.6% of case controls; 95% CI, 76 to 101). Serum bone Gla-protein, a marker of bone turnover, was significantly increased in both the premenopausal and the postmenopausal women receiving T4 compared to case controls (P less than 0.001 for the difference between patient groups and controls). Whereas the cumulative dose of T4 was highly correlated with the femoral neck BMD in the premenopausal patients (r = 0.528; P less than 0.05); the presence of hypogonadism was the main determinant of the lumbar spine and forearm BMD. This data confirms that premenopausal and postmenopausal women receiving suppressive doses of T4 for thyroid carcinoma have diminished bone mineral measurements and are at risk for osteoporosis.

Serum vitamin D metabolites are not responsible for low turnover osteoporosis in chronic liver disease.

We measured the concentrations of vitamin D-binding protein (DBP), total 25-hydroxyvitamin D, total 1,25-dihydroxyvitamin D [1,25-(OH)2D], and free 1,25-(OH)2D in sera of 107 patients with histologically proven chronic liver disease. Bone density measurements and dynamic skeletal histomorphometry were also performed. Osteoporosis, as defined by arbitrary criteria, was found in 42 patients (39%), while no patient had osteomalacia. Serum concentrations of vitamin D-binding protein, 25-hydroxyvitamin D, total 1,25-(OH)2D, and free 1,25-(OH)2D were reduced in patients with cirrhosis, but not in the noncirrhotic patients. Bone formation rates, which were low in 55 patients (51%), were correlated with liver functions, but not with the concentrations of either vitamin D metabolite. A subgroup of 44 patients with low serum 1,25-(OH)2D concentrations and low bone formation rates failed to show an appropriate increase in serum bone Gla protein after 1,25-(OH)2D3 administration even though serum concentrations of 1,25-(OH)2D rose normally. These data suggest that the bone disease in patients with hepatic disorders is not related to the serum concentrations of vitamin D metabolites or the effect of these metabolites on osteoblast function.

Acquired osteosclerosis associated with intravenous drug use and hepatitis C infection.

Hepatitis C has recently been recognized as a secondary cause of osteosclerosis; a further example, the first outside of North America, is described. A 37-year-old man with a history of intravenous drug use and known to be hepatitis C antibody positive presented with bone pain. Radiographs and magnetic resonance imaging demonstrated an increase in cortical and trabecular bone that on biopsy was of a normal lamellar pattern but markedly sclerotic. Biochemical markers of bone formation (serum osteocalcin) and resorption (urinary hydroxyproline excretion rate) were both markedly elevated. Pain lessened following administration of pamidronate. Biochemical markers of bone turnover fell towards their reference ranges 12 months after initiating pamidronate therapy but without significant change in bone mineral density. Osteosclerosis is a rare complication of hepatitis C infection, the symptoms of which are controllable with diphosphonate therapy.

Syndrome of myelofibrosis and osteosclerosis: a series of case reports and review of the literature.

Myelofibrosis (MF) is a chronic disorder characterized by bone marrow evidence of myeloid metaplasia associated with reactive fibrosis, angiogenesis, and osteosclerosis. We report serum biochemistry, noninvasive markers of bone turnover, tetracycline-labeled bone histomorphometry, and bone densitometry (DXA) data of four men presenting with newly diagnosed biopsy-proven MF and osteosclerosis. The mechanisms and putative growth factors responsible for this syndrome are examined.

Tumor expression studies indicate that HEM-1 is unlikely to be the active factor in oncogenic osteomalacia.

HEM-1 was isolated as a putative factor responsible for oncogenic osteomalacia by Kumar et al. (Proc Assoc Am Phys 107:296-305; 1995). The cDNA was identified on the basis of PTH-like immunoreactivity; however, no studies have been reported of the expression of HEM-1 mRNA in oncogenic osteomalacia tumors. In this study, expression of HEM-1 mRNA was investigated in two oncogenic osteomalacia tumors and in a series of normal tissues. An HEM-1 PCR product was amplified from a cDNA library from one of the tumors, with six base changes identified, as compared with the published sequence. No expression was detected, however, in the oncogenic osteomalacia tumors either by Northern blot analysis or by reverse transcriptase PCR. This indicates that, although a region of HEM-1 sequence is present in the tumor cell cDNA library, any HEM-1 expression must be at very low levels. It is unlikely, therefore, that the HEM-1 product is the active factor responsible for oncogenic osteomalacia. In the normal tissues examined, human placenta, fibroblasts, parathyroid gland, liver, fetal bone, and rat kidney cortex, HEM-1 mRNA was not detected, suggesting that it does not have a physiological role in these tissues.