Impact of shield location on staff and caregiver dose rates for I-131 radiopharmaceutical therapy patients.

The goal of this study is to investigate the effect of the location and width of a single lead shield on the dose rate of staff and caregivers in a hospital room with an I-131 patient. The best orientation of the patient and caregiver relative to the shield was determined based on minimizing staff and caregiver radiation dose rates. Shielded and unshielded dose rates were simulated using a Monte Carlo computer simulation and validated using real-world ionisation chamber measurements. Based on a radiation transport analysis using an adult voxel phantom published by the International Commission on Radiological Protection, placing the shield near the caregiver yielded the lowest dose rates. However, this strategy reduced the dose rate in only a tiny area of the room. Furthermore, positioning the shield near the patient in the caudal direction provided a modest dose rate reduction while shielding a large room area. Finally, increased shield width was associated with decreasing dose rates, but only a four-fold dose-rate reduction was observed for standard width shields. The recommendations of this case study may be considered as potential candidate room configurations where radiation dose rates are minimized, however these findings must be weighed against additional clinical, safety, and comfort considerations.

OCCUPATIONAL EYE LENS DOSE OVER SIX YEARS IN THE STAFF OF A US HIGH-VOLUME CANCER CENTER.

This paper summarizes the dose to the eye lens of workers of Memorial Sloan Kettering Cancer Center, a high-volume US oncologic and associated diseases facility. The doses presented in this report were collected from personal dosemeter readings using optically stimulated luminescence badges to estimate Hp(3). Doses were collected for 5950 clinical and research workers between January 2012 and December 2017. The median eye lens dose for all monitored workers was 0.23 mSv y-1. Workers performing, or supporting, fluoroscopy procedures received the highest unprotected eye lens dose of all workers with a median eye dose of 10 mSv. The use of leaded glasses by this group reduced the actual doses to the lens. Nurses and technicians involved in positron emission tomography injections received median eye lens dose of 1.2 mSv.

A masquerading mass: an unusual presentation of IgG4-related systemic disease with tubulointerstitial nephritis.

IgG4 tubulointerstitial nephritis (IgG4-TIN) is the most common form of IgG4 renal disease. When IgG4-TIN is accompanied by other systemic manifestations the disease is known as IgG4-related systemic disease (IgG4-RSD). IgG4-RSD is well recognised in the form of tubulointerstitial nephritis (IgG4-related TIN) and may present with renal failure by mimicking neoplasms (tumefactive lesions) or with both features. We describe a case of IgG4-RSD initially presenting as a submandibular mass and subsequently presenting two years later with secondary infiltration of the kidney causing tubulointerstitial nephritis. This case highlights the importance of recognising IgG4-RSD as a non-malignant disease with presentations having commonly shared features including tumour-like swelling of involved organs and its ability to mimic many systemic diseases. In the majority of patients it can be treated successfully with corticosteroids.

Chemoprevention gene therapy (CGT) of pancreatic cancer using perillyl alcohol and a novel chimeric serotype cancer terminator virus.

Conditionally replication competent adenoviruses (Ads) that selectively replicate in cancer cells and simultaneously express a therapeutic cytokine, such as melanoma differentiation associated gene- 7/Interleukin-24 (mda-7/IL-24), a Cancer Terminator Virus (CTV-M7), hold potential for treating human cancers. To enhance the efficacy of the CTV-M7, we generated a chimeric Ad.5 and Ad.3 modified fiber bipartite CTV (Ad.5/3-CTV-M7) that can infect tumor cells in a Coxsackie Adenovirus receptor (CAR) independent manner, while retaining high infectivity in cancer cells containing high CAR. Although mda-7/IL-24 displays broad-spectrum anticancer properties, pancreatic ductal adenocarcinoma (PDAC) cells display an intrinsic resistance to mda-7/IL-24-mediated killing due to an mda-7/IL-24 mRNA translational block. However, using a chemoprevention gene therapy (CGT) approach with perillyl alcohol (POH) and a replication incompetent Ad to deliver mda-7/IL-24 (Ad.mda-7) there is enhanced conversion of mda-7/IL-24 mRNA into protein resulting in pancreatic cancer cell death in vitro and in vivo in nude mice containing human PDAC xenografts. This combination synergistically induces mda-7/IL-24-mediated cancer-specific apoptosis by inhibiting anti-apoptotic Bcl-xL and Bcl-2 protein expression and inducing an endoplasmic reticulum (ER) stress response through induction of BiP/GRP-78, which is most evident in chimeric-modified non-replicating Ad.5/3- mda-7- and CTV-M7-infected PDAC cells. Moreover, Ad.5/3-CTV-M7 in combination with POH sensitizes therapy-resistant MIA PaCa-2 cell lines over-expressing either Bcl-2 or Bcl-xL to mda-7/IL-24-mediated apoptosis. Ad.5/3-CTV-M7 plus POH also exerts a significant antitumor 'bystander' effect in vivo suppressing both primary and distant site tumor growth, confirming therapeutic utility of Ad.5/3-CTV-M7 plus POH in PDAC treatment, where all other current treatment strategies in clinical settings show minimal efficacy.

Efficacy of a supersaturated calcium phosphate oral rinse for the prevention and treatment of oral mucositis in patients receiving high-dose cancer therapy: a review of current data.

Oral mucositis (OM) is a painful and debilitating complication of cancer therapy that can adversely affect patients' treatment regimens and quality of life. It is also considered to be a substantial burden on the financial and human resources of health services. Despite progress in the understanding of the pathophysiology of OM and the number of new treatments that have been developed, there remains an unmet need for effective preventative measures in clinical practice. Literature on oral healthcare management in oncology patients suggests that a preventative approach consisting of a supersaturated Ca2+ / PO4(3-) oral rinse (Caphosol(®)) aimed at maintaining oral hygiene, moistening and lubricating the oral cavity, effectively reduces the incidence and severity of OM. This review looked at data from all known adult and paediatric studies investigating the use of Caphosol(®) in patients receiving high-dose cancer therapy in order to evaluate its efficacy for both the prevention and treatment of OM. Thirty studies were identified. The majority of these studies (n = 24) found Caphosol(®) to be efficacious at reducing the grade and/or duration, as well as pain associated with OM. Despite important limitations, these data warrant serious consideration for the inclusion of Caphosol(®) in regimens for preventing or reducing the debilitating effects of OM.

Effect of leaded glasses and thyroid shielding on cone beam CT radiation dose in an adult female phantom.

OBJECTIVES: This study aims to demonstrate the effectiveness of leaded glasses in reducing the lens of eye dose and of lead thyroid collars in reducing the dose to the thyroid gland of an adult female from dental cone beam CT (CBCT). The effect of collimation on the radiation dose in head organs is also examined. METHODS: Dose measurements were conducted by placing optically stimulated luminescent dosemeters in an anthropomorphic female phantom. Eye lens dose was measured by placing a dosemeter on the anterior surface of the phantom eye location. All exposures were performed on one commercially available dental CBCT machine, using selected collimation and exposure techniques. Each scan technique was performed without any lead shielding and then repeated with lead shielding in place. To calculate the percent reduction from lead shielding, the dose measured with lead shielding was divided by the dose measured without lead shielding. The percent reduction from collimation was calculated by comparing the dose measured with collimation to the dose measured without collimation. RESULTS: The dose to the internal eye for one of the scans without leaded glasses or thyroid shield was 0.450 cGy and with glasses and thyroid shield was 0.116 cGy (a 74% reduction). The reduction to the lens of the eye was from 0.396 cGy to 0.153 cGy (a 61% reduction). Without glasses or thyroid shield, the thyroid dose was 0.158 cGy; and when both glasses and shield were used, the thyroid dose was reduced to 0.091 cGy (a 42% reduction). CONCLUSIONS: Collimation alone reduced the dose to the brain by up to 91%, with a similar reduction in other organs. Based on these data, leaded glasses, thyroid collars and collimation minimize the dose to organs outside the field of view.

Chemoprevention gene therapy (CGT): novel combinatorial approach for preventing and treating pancreatic cancer.

Pancreatic cancer remains one of the deadliest of all cancers despite aggressive surgical treatment combined with adjuvant radiotherapy and chemotherapy. Chemoresistance and radioresistance are the principal causes of failure of pancreatic cancer patients to respond to therapy. Conditionally replication competent adenovirus (CRCA)-based cancer gene therapy is an innovative strategy for treating cancers displaying inherent resistance to treatment. Limitations of current adenovirus (Ad)-based gene therapies for malignant tumors include lack of cancer-specificity, and effective and targeted delivery. To remedy this situation, CRCAs have been designed that express E1A, necessary for Ad replication, under the control of a cancer-specific progression elevated gene-3 promoter (PEG-Prom) with concomitant expression of an immunomodulatory cytokine, such as mda-7/IL-24 or interferon-γ (IFN-γ), under the control of a ubiquitous and strong cytomegalovirus promoter (CMV-Prom) from the E3 region. These bipartite CRCAs, when armed with a transgene, are called cancer terminator viruses (CTVs), i.e., Ad.PEG-E1A-CMV-mda-7 (CTV-M7) and Ad.PEG-E1A-CMV-IFN-γ (CTV-γ), because of their universal effectiveness in cancer treatment irrespective of p53/pRb/p16 or other genetic alterations in tumor cells. In addition to their selective oncolytic effects in tumor cells, the potent 'bystander antitumor' properties of MDA-7/IL-24 and IFN-γ embody the CTVs with expanded treatment properties for both primary and distant cancers. Pancreatic cancer cells display a "translational block" of mda-7/IL-24 mRNA, limiting production of MDA-7/IL-24 protein and cancer-specific apoptosis. Specific chemopreventive agents abrogate this "translational block" resulting in pancreatic cancer-specific killing. This novel chemoprevention gene therapy (CGT) strategy holds promise for both prevention and treatment of pancreatic cancers where all other strategies have proven ineffective.

Guidelines on obtaining consent for systemic anti-cancer therapy in adults.

This guideline, initially drawn up for use in the UK, is essentially based on ethical principles and should be applicable across other jurisdictions. The document specifically addresses the issues which surround obtaining consent from adults for the administration of systemic anti-cancer therapy in the haemato-oncology setting. Consenting to a treatment or procedure is a complex medical, ethical, and legal issue. The process of obtaining consent and the general steps that should be taken by the healthcare professional involved in obtaining consent from a patient are discussed, and the potential legal and ethical pitfalls which can be encountered are outlined. Of fundamental importance are the requirements that agreement must be given voluntarily, based on adequate information, and the patient must have the ability to understand and retain the information given and be in a position to use it in order to reach a decision. The consenting process should include an explanation of the expected outcomes and possible side effects of treatment even if these are unlikely to occur, and the nature of the consenting process undertaken should be clearly documented. Obtaining consent in an emergency situation is also discussed, as is the process of consenting in individuals with impaired capacity or special needs. Withdrawal of consent and refusal of treatment are also considered.

Significant reduction in dental cone beam computed tomography (CBCT) eye dose through the use of leaded glasses.

OBJECTIVE: In light of the increased recognition of the potential for lens opacification after low-dose radiation exposures, we investigated the effect of leaded eyeglasses worn during dental cone-beam computerized tomography (CBCT) procedures on the radiation absorbed dose to the eye and suggest simple methods to reduce risk of radiation cataract development. STUDY DESIGN: Dose measurements were conducted with the use of 3 anthropomorphic phantoms: male (Alderson radiation therapy phantom), female (CIRS), and juvenile male (CIRS). All exposures were performed on the same dental CBCT machine (Imtec, Ardmore, OK) using 2 different scanning techniques but with identical machine parameters (120 kVp, 3.8 mA, 7.8 s). Scans were performed with and without leaded glasses and repeated 3 times. All measurements were recorded using calibrated thermoluminescent dosimeters and optical luminescent dosimetry. RESULTS: Leaded glasses worn by adult and pediatric patients during CBCT scans may reduce radiation dose to the lens of the eye by as much as 67% (from 0.135 ± 0.004 mGy to 0.044 ± 0.002 mGy in pediatric patients). CONCLUSIONS: Leaded glasses do not appear to have a deleterious effect on the image quality in the area of clinical significance for dental imaging.

First Report of Potato spindle tuber viroid in Cape Gooseberry (Physalis peruviana) in New Zealand.

In February 2009, 10 cape gooseberry plants (Physalis peruviana) grown from seed on a domestic property in Christchurch, New Zealand, showed severe leaf distortion, fasciation and etiolation of growing tips, and weak flowering. Symptoms were first observed in the emerging seedlings. No virus particles were observed in sap from infected plants with the electron microscope. Total RNA was isolated from leaves of the 10 plants with a Qiagen RNeasy Plant Mini Kit (Valencia, CA). All 10 plants tested positive for Potato spindle tuber viroid (PSTVd) by real-time reverse transcription (RT)-PCR (1) and by RT-PCR with PSTVd-specific primers (3) and generic pospiviroid primers (4). For both conventional PCRs, the expected 359-bp amplicons were sequenced directly and sequences were aligned together to create a consensus sequence (GenBank Accession No. FJ797614). BLASTn analysis showed 98% nucleotide identity to PSTVd (EU862231, DQ308556, X17268, and AY532801-AY532804). Sap from one of the infected plants was mechanically inoculated onto healthy P. peruviana, Solanum lycopersicum 'Rutgers', Chenopodium amaranticolor, C. quinoa, Cucumis sativum 'Crystal Apple', Gomphrena globosa, Nicotiana benthamiana, N. clevelandii, N. occidentalis '37B', N. tabacum 'WB', N. sylvestris, and Phaseolus vulgaris 'Prince'. After 4 weeks, the leaves of the 'Rutgers' tomato plants were showing severe distortion, purpling, and necrosis of mid-veins and P. peruviana plants were showing distortion of newly emerging apical leaves. Healthy control P. peruviana were asymptomatic. Symptoms appeared milder than that observed in the original P. peruviana plants, but this may be related to different environmental conditions or age or growth stage of the plants when inoculated. All other indicator plants were symptomless, but along with P. peruviana, tested positive for PSTVd by real-time RT-PCR (1). The presence of PSTVd was further confirmed in one original symptomatic and the mechanically inoculated P. peruviana plants and in the indicator plants by dot-blot hybridization with a digoxygenin-labeled synthetic ssRNA probe specific to the full-length PSTVd genome. PSTVd has been reported in New Zealand previously in commercial glasshouse crops of tomatoes and peppers (2), but was eradicated and so remains a regulated pest. The plants were grown from seeds imported from Germany and it is possible that the infection was seedborne. PSTVd was reported in young cape gooseberry seedlings in Germany and Turkey but the infection was asymptomatic (5). Symptoms were associated with the PSTVd-infected cape gooseberry in New Zealand. To our knowledge, this is the first report of the viroid in domestically grown plants in New Zealand, and only the second report of PSTVd in cape gooseberry worldwide. Our findings suggest that this species is an emerging host for PSTVd and that dissemination of seed may provide a pathway for international movement of the viroid. References: (1) N. Boonham et al. J. Virol. Methods 116:139, 2004. (2) B. S. M. Lebas et al. Australas. Plant Pathol. 34:129, 2005. (3) A. M. Shamoul et al. Can. J. Plant Pathol. 19:89, 1997. (4) J. T. H. Verhoeven et al. Eur. J. Plant Pathol. 110:823, 2004. (5) J. T. H. Verhoeven et al. Plant Dis. 93:316, 2009.

The Prospective Oral Mucositis Audit: relationship of severe oral mucositis with clinical and medical resource use outcomes in patients receiving high-dose melphalan or BEAM-conditioning chemotherapy and autologous SCT.

The Prospective Oral Mucositis Audit was an observational study in 197 patients with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL) undergoing, respectively, high-dose melphalan or BEAM chemotherapy and autologous SCT at 25 European centres. We evaluated the relationship between severe oral mucositis (SOM; WHO Oral Toxicity Scale grade 3-4) and local and systemic clinical sequelae and medical resource use. SOM occurred in 44% of patients. The duration of SOM (mean 5.3 days) correlated with time to neutrophil engraftment. The following parameters increased gradiently with maximum grade of oral mucositis: duration of pain score >or=4, opioid use, dysphagia score >or=4, total parenteral nutrition (TPN) use, incidence and/or duration of fever and infection, and duration of antibiotic use. SOM increased the duration of TPN use by 2.7 days (P<0.001), opioids by 4.6 days (P<0.001), and antibiotics by 2.4 days (P=0.045). SOM prolonged hospital stay by 2.3 days (P=0.013) in MM patients, but not in NHL patients (who tended to have a longer hospital stay). In conclusion, this analysis of prospectively collected observational data provides important insight into the scope and impact of SOM in the European transplant setting.

Occurrence of Hibiscus chlorotic ringspot virus in Hibiscus spp. in New Zealand.

Hibiscus spp. are popular ornamental plants in New Zealand. The genus is susceptible to Hibiscus chlorotic ringspot virus (HCRSV), a member of the genus Carmovirus, which has been reported in Australia, El Salvador, Singapore, the South Pacific Islands, Taiwan, Thailand, and the United States (1-4). In May of 2004, chlorotic spotting and ringspots were observed on the leaves of two H. rosa-sinensis plants in a home garden in Auckland, New Zealand. When inoculated with sap from symptomatic leaves, Chenopodium quinoa and C. amaranticolor developed faint chlorotic local lesions 12 to 15 days later. Phaseolus vulgaris exhibited small necrotic local spots 10 days postinoculation. No symptoms were observed on inoculated plants of Cucumis sativus, Gomphrena globosa, Nicotiana Clevelandii, N. tabacum, or N. sylvestris. Plants of H. rosa-sinensis and the three symptomatic indicator species tested positive for HCRSV using polyclonal antiserum (Agdia Inc., Elkhart, IN) in a double antibody sandwich (DAS)-ELISA. Forward (5'-GGAACCCGTCCTGTTACTTC-3') and reverse (5'-ATCACATCCACATCCCCTTC-3') primers were designed on the basis of a conserved region in the coat protein gene (nt 2722-3278) of HCRSV isolates in GenBank (Accession Nos. X86448 and DQ392986). A product of the expected size (557 bp) was amplified by reverse transcription (RT)-PCR with total RNA extracted from the four infected species. Comparison of the sequence of the amplicon from H. rosa-sinensis (GenBank Accession No. EU554660) with HCRSV isolates from Singapore and Taiwan (GenBank Accession Nos. X86448 and DQ392986) showed 99 and 94% nucleotide identity, respectively. From 2006 to 2008, samples from a further 25 symptomatic hibiscus plants were collected from different locations in the Auckland region. Nineteen, including plants of H. diversifolius, H. rosa-sinensis, and H. syriacus, tested positive for HCRSV by RT-PCR. To our knowledge, this is the first report of HCRSV in New Zealand and of the virus in H. diversifolius and H. syriacus. HCRSV is considered to be widespread in New Zealand. References: (1) A. A. Brunt et al. Plant Pathol. 49:798, 2000. (2) S. C. Li et al. Plant Pathol. 51:803, 2002. (3) H. Waterworth. No.227 in: Descriptions of Plant Viruses. CMI/AAB, Surrey, UK, 1980. (4) S. M. Wong et al. Acta Hortic. 432:76, 1996.

First Report of Passiflora latent virus in Banana Passionfruit (Passiflora tarminiana) in New Zealand.

Passiflora latent virus (PLV) naturally infects cultivated and wild Passiflora species in Australia, Germany, Israel and the United States (1-3). In March 2004, chlorotic lesions were observed on leaves of three vines of Passiflora tarminiana on one site in Auckland, New Zealand. Chenopodium amaranticolor and C. quinoa inoculated with sap from symptomatic leaves developed chlorotic local spots, followed by systemic leaf chlorosis and necrosis. Local symptoms appeared more quickly on C. quinoa (12 days) than on C. amaranticolor (20 days). No symptoms were observed on inoculated plants of Nicotiana benthamiana, N. clevelandii, N. occidentalis, N. tabacum, or Phaseolus vulgaris. Electron microscopy of crude sap preparations from infected C. quinoa, C. amaranticolor, N. occidentalis, and P. tarminiana showed flexuous, filamentous virus particles approximately 650 nm long. Plants of P. tarminiana and the three inoculated indicator species containing virus particles tested positive by PLV polyclonal antiserum in double-antibody sandwich (DAS)-ELISA (DSMZ, Braunschweig, Germany) and immunosorbent electron microscopy (Stephan Winter, DSMZ, personal communication). Nucleic acid was extracted from leaves of plants of each of the four viruliferous species with an RNeasy Plant Mini Kit (Qiagen, Doncaster, Australia) and then used in reverse transcription (RT)-PCR tests with novel forward (5'-CGAGACACACGCAAACGAA-3') and reverse (5'-CAGCAAAGCAAAGACACGA-3') primers specific to a 523-bp fragment of the PLV polyprotein. PCR products of the expected size were obtained, and an amplicon from P. tarminiana was directly sequenced (GenBank Accession No. EU257510). A BLAST search in GenBank showed 94% nucleotide sequence identity with a PLV isolate from Israel (GenBank Accession No. DQ455582). To our knowledge, this is the first finding of PLV in P. tarminiana and the first report of the virus in New Zealand. Chenopodium spp. have been reported previously as experimental hosts (2,3), and this study revealed that N. occidentalis also can be infected latently with PLV. P. tarminiana is a weed in New Zealand and subject to active control measures to manage the species. Economically important species such as P. edulis and P. ligularis are potentially susceptible to the virus. These species are not grown commercially in the surrounding area but are common in domestic Auckland gardens. Infected vines were removed from the site and destroyed, and symptomatic vines have not been observed at other sites. References: (1) R. D. Pares et al. Plant Dis. 81:348, 1997. (2) S. Spiegel et al. Arch. Virol. 152:181, 2007. (3) A. A. Stihll et al. Plant Dis. 76:843, 1992.

Differentiation of embryonic mesenchymal cells to odontoblast-like cells by overexpression of dentin matrix protein 1.

Cells of the craniofacial skeleton are derived from a common mesenchymal progenitor. The regulatory factors that control their differentiation into various cell lineages are unknown. To investigate the biological function of dentin matrix protein 1 (DMP1), an extracellular matrix gene involved in calcified tissue formation, stable transgenic cell lines and adenovirally infected cells overexpressing DMP1 were generated. The findings in this paper demonstrate that overexpression of DMP1 in pluripotent and mesenchyme-derived cells such as C3H10T1/2, MC3T3-E1, and RPC-C2A can induce these cells to differentiate and form functional odontoblast-like cells. Functional differentiation of odontoblasts requires unique sets of genes being turned on and off in a growth- and differentiation-specific manner. The genes studied include transcription factors like core binding factor 1 (Cbfa1), bone morphogenetic protein 2 (BMP2), and BMP4; early markers for extracellular matrix deposition like alkaline phosphatase (ALP), osteopontin, osteonectin, and osteocalcin; and late markers like DMP2 and dentin sialoprotein (DSP) that are expressed by terminally differentiated odontoblasts and are responsible for the formation of tissue-specific dentin matrix. However, this differentiation pathway was limited to mesenchyme-derived cells only. Other cell lines tested by the adenoviral expression system failed to express odontoblast-phenotypic specific genes. An in vitro mineralized nodule formation assay demonstrated that overexpressed cells could differentiate and form a mineralized matrix. Furthermore, we also demonstrate that phosphorylation of Cbfa1 (osteoblast-specific transcription factor) was not required for the expression of odontoblast-specific genes, indicating the involvement of other unidentified odontoblast-specific transcription factors or coactivators. Cell lines that differentiate into odontoblast-like cells are useful tools for studying the mechanism involved in the terminal differentiation process of these postmitotic cells.

Transient reexpression of an embryonic autonomous growth phenotype by adult carotid artery smooth muscle cells after vascular injury.

High rates of vascular smooth muscle cell (SMC) replication are observed, at least transiently, after injury to the arterial wall and contribute to the formation of a neointima. Neutralizing antibodies designed to inhibit growth of SMC have only been variably successful in inhibiting neointima formation, raising the possibility that neointimal cell proliferation involves unique growth mechanisms. This study examined the possibility that SMC isolated from injured rat carotid arteries would express an autonomous, mitogen-independent growth phenotype similar to that utilized by embryonic vascular SMC during periods of rapid growth. We found that primary cultures of SMC isolated 7 and 14 days after injury, times at which high in vivo replication rates were observed, demonstrated high intrinsic DNA synthetic rates compared to SMC isolated from uninjured arteries or at 2, 4, 21, and 28 days after injury where in vivo replication rates were far less. Subcultured SMC isolated from 7-day injured vessels (Neo7 SMC) exhibited a stable, autonomous growth phenotype, did not secrete detectable mitogenic activity, and had decreased alpha-actin and myosin expression compared to mitogen-dependent SMC. Heterokaryons constructed between autonomous Neo7 SMC and mitogen-dependent SMC exhibited a mitogen-dependent growth phenotype suggesting that nonautonomous SMC produce factors that actively inhibit autonomous growth. In contrast, heterokaryons constructed between Neo7 SMC and autonomous embryonic SMC retained an autonomous growth phenotype. We examined the expression of known tumor suppressors to determine if any of these factors played a role in inhibiting SMC autonomous growth. p27, p53, pRb, and PTEN were abundantly expressed by Neo7 SMC and e17 SMC under both basal and serum stimulated conditions. The data suggest that the mechanisms driving SMC replication during neointimal formation are self-driven and self-regulated, and that at specific times after injury, SMC escape normal growth suppressive mechanisms through the loss of intracellular growth suppressor activity.

Synaptophysin staining in normal brain: importance for diagnosis of ganglioglioma.

Neuronal and mixed glioneuronal tumors traditionally have comprised a very small percentage of intrinsic central nervous system neoplasms, although they are somewhat more common among juvenile brain tumors and in the temporal lobe. Neuronal differentiation increasingly is recognized in pleomorphic xanthoastrocytoma, intraventricular neurocytoma, and subependymal giant cell astrocytoma. However, the diagnostic distinctions between subtle ganglioglioma (with rare neurons) and infiltrating glioma with entrapped neurons and between infiltrating oligodendroglioma and parenchymal neurocytoma are problematic but may be clinically important. Recently, it was proposed that perisomatic synaptophysin immunostaining in the human central nervous system reliably and selectively discriminates neoplastic from nonneoplastic neurons. Using this criterion, the number of brain stem and spinal cord gangliogliomas could be increased substantially. We canvassed synaptophysin immunostaining patterns in the normal brain stem, cerebellum, and forebrain, and found that synaptophysin-positive neurons are distributed broadly in the normal human brain. In disturbed neocortical tissue, such as near vascular malformations, synaptophysin-positive neurons and irregular white-matter synaptophysin immunostaining are visualized. Although synaptophysin-positive neurons are found in gangliogliomas and archipelagos of synaptophysin reactivity are found in neurocytomas, these patterns clearly are not pathognomonic for glioneuronal tumors and must be interpreted with caution whenever other histologic or ultrastructural evidence of neuronal differentiation is lacking.