Volumetric response and pattern of failure of histone altered high grade glioma in adults following management with radiation therapy.

PURPOSE: H3K27M- and H3G34R-mutant gliomas are recently-classified subgroups of high-grade gliomas (HGGs) affecting younger adults. This study aimed to describe patterns of infiltration and failure, and the volumetric response of these tumours to radiotherapy. METHODS: Patients with histone-mutant gliomas aged 16-50 years, managed from 2009 to 2021 were identified and clinical, radiological and histopathological characteristics collected. Tumour volume was assessed on MRI at diagnosis, pre-radiotherapy, month + 1, + 3 and + 5 post-radiation and at relapse. RESULTS: Of 538 IDH1/2 wild-type HGGs, 18(15%) had a histone alteration. Eleven were H3K27M- and 7 H3G34R-mutant respectively. Median age at diagnosis was 20 years (range17-48 years). Median overall survival was 20 months (95%CI 14-29 months). Both H3K27M- and H3G34R-mutant tumours exhibited extensive T2F infiltration involving a median of 4 neuroanatomical subsites at diagnosis. Median volume of disease pre-radiotherapy on T1gd and T2F respectively was 0.5cm3 (IQR:0-1.7cm3) and 11.9 cm3 (IQR:7.5-29.6cm3) for H3K27M and 0.9cm3 (IQR:0-8.4cm3) and 43.8cm3 (IQR:25.2-86.6 cm3) for H3G34R tumours. T2F volume reduction > 50% was observed 3-months post-IMRT in 7(64%) patients with H3K27M and 1(14%) with H3G34R tumours. Fourteen patients had relapsed. Relapse was local-only, distant-only and both in 4(44%), 3(33%) and 2(22%) H3K27M-mutant and 1(20%), 2(40%), and 2(40%) H3G34R-mutant tumours. On last scan before death, leptomeningeal spread was present in 4/8(50%) and 1/5(20%) and subependymal spread in 4/8 (50%) and 0/5 H3K27M- and G34R-mutant cases respectively. CONCLUSION: H3K27M-mutant gliomas are highly responsive to radiotherapy but exhibit high propensity for subsequent leptomeningeal and subependymal spread. H3G34R-mutant tumours exhibit lesser early volumetric response to radiotherapy and propensity for distant in-brain failure.

Assessing children's exposure to manganese in drinking water using a PBPK model.

A previously published human PBPK model for manganese (Mn) in infants and children has been updated with Mn in drinking water as an additional exposure source. Built upon the ability to capture differences in Mn source-specific regulation of intestinal uptake in nursing infants who are breast-fed and formula-fed, the updated model now describes the bioavailability of Mn from drinking water in children of ages 0-18. The age-related features, including the recommended age-specific Mn dietary intake, age-specific water consumption rates, and age-specific homeostasis of Mn, are based on the available human data and knowledge of the biology of essential-metal homeostasis. Model simulations suggest that the impact of adding drinking-water exposure to daily Mn exposure via dietary intake and ambient air inhalation in children is not greater than the impacts in adults, even at a drinking-water concentration that is 2 times higher than the USEPA's lifetime health advisory value. This conclusion was also valid for formula-fed infants who are considered at the highest potential exposure to Mn from drinking water compared to all other age groups. Our multi-route, multi-source Mn PBPK model for infants and children provides insights about the potential for Mn-related health effects on growing children and will thereby improve the level of confidence in properly interpreting Mn exposure-health effects relationships in children in human epidemiological studies.

18F-NaF PET/CT for the evaluation of temporomandibular joint disorder.

AIM: To investigate the usefulness of a quantitative parameter (maximum standardised uptake value [SUVmax]) of 18F-sodium fluoride (NaF) positron-emission tomography (PET)/computed tomography (CT) for the evaluation of temporomandibular joint (TMJ) disorder (TMD). MATERIALS AND METHODS: Seventy-six TMD patients (male: female=14:62, age=40.3±17.1 years, bilateral: unilateral=40:36) with 152 TMJs were enrolled. The 18F-NaF PET/CT parameter (SUVmax) was compared with the presence of TMJ arthralgia (arthralgic=86, non-arthralgic=66) and clinical subtypes based on the Research Diagnostic Criteria for TMD Axis I (TMD osteoarthritis=49, non-TMD osteoarthritis=67, and asymptomatic TMJ=36). Splint therapy was applied to 48 patients for 6 months without considering 18F-NaF PET/CT findings. Post-splint therapy 18F-NaF PET/CT was performed in 32 patients and clinical responses to the therapy were classified into improvement (n=33), no change (n=10), or aggravation (n=7) for 50 TMJs excluding asymptomatic TMJs (n=14). RESULTS: SUVmax was significantly greater in arthralgic TMJs than in non-arthralgic TMJs (6.62±3.56 versus 4.32±1.53, p<0.0001). SUVmax was also significantly greater in TMD osteoarthritis (6.75±3.85) than in non-TMD osteoarthritis (5.21±2.70) and asymptomatic TMJs (4.86±1.99; p=0.0386). After splint therapy, SUVmax was significantly increased in aggravated TMJs (from 7.80±3.72 to 11.00±5.74, p=0.0156), whereas no significant change in SUVmax was observed in improved (from 6.16±2.68 to 6.09±2.60, p=0.4915) and unchanged (from 6.46±4.19 to 6.77±4.32, p=0.3223) TMJs. CONCLUSIONS: 18F-NaF PET/CT is a useful imaging tool for TMD evaluation because SUVmax showed a fair diagnostic performance for arthralgic TMJ and TMD osteoarthritis, and a correlation with the therapeutic response.

Improved physiologically based pharmacokinetic model for oral exposures to chromium in mice, rats, and humans to address temporal variation and sensitive populations.

A physiologically based pharmacokinetic (PBPK) model for hexavalent chromium [Cr(VI)] in mice, rats, and humans developed previously (Kirman et al., 2012, 2013), was updated to reflect an improved understanding of the toxicokinetics of the gastrointestinal tract following oral exposures. Improvements were made to: (1) the reduction model, which describes the pH-dependent reduction of Cr(VI) to Cr(III) in the gastrointestinal tract under both fasted and fed states; (2) drinking water pattern simulations, to better describe dosimetry in rodents under the conditions of the NTP cancer bioassay; and (3) parameterize the model to characterize potentially sensitive human populations. Important species differences, sources of non-linear toxicokinetics, and human variation are identified and discussed within the context of human health risk assessment.

Musculoskeletal and central pain at 1 year post-stroke: associated factors and impact on quality of life.

BACKGROUND AND PURPOSE: Pain is common in post-stroke patients and has been shown to be associated with depression, fatigue, and decreased quality of life (QOL). However, studies examining different types of post-stroke pain are scarce. We investigated differences in the related factors and their QOL impacts between musculoskeletal pain (MSP) and central post-stroke pain (CPSP). METHODS: We assessed 364 consecutive stroke patients who were admitted to Asan Medical Center and contacted 12 months after stroke onset. We categorized pain and paresthesia as MSP, CPSP, combined pain, or other pain. Post-stroke depression (Beck Depression Inventory), fatigue (Fatigue Severity Scale), sleep disturbance (Verran Snyder-Halpern scale), social support (ENRICHED Social Support Instrument), and QOL (Medical Outcome Study 36-Item Short Form) were assessed. RESULTS: Of the 364 patients analyzed, 135 (37.1%) had pain, 78 (21.4%) had MSP, 22 (6.0%) had CPSP, 16 (4.4%) had combined pain, and 19 (5.2%) had other pain. In multivariate analyses, CPSP was related to modified Rankin scale (P=.004), sensory dysfunction (P<.001), thalamus lesion (P=.001), medulla lesion (P=.007), and fatigue (P=.026). MSP was related to motor dysfunction (P<.001) and fatigue (P=.003). QOL varied among groups with different types of pain (P<.001) and was the poorest in patients with combined pain. CONCLUSIONS: Pain is common 12 months post-stroke. The factors associated with CPSP and MSP differ, but are both closely associated with fatigue rather than depression. QOL is the poorest in patients with combined pain. Management of pain and fatigue may be important for improving the QOL in stroke patients.

Effect of endoscopy screening on stage at gastric cancer diagnosis: results of the National Cancer Screening Programme in Korea.

BACKGROUND: Although gastric cancer screening is common among countries with a high prevalence of gastric cancer, there is little data to support the effectiveness of this screening. This study was designed to determine the differences in stage at diagnosis of gastric cancer according to the screening history and screening method (upper gastrointestinal series (UGIS) vs endoscopy). METHODS: The study population was derived from the National Cancer Screening Programme (NCSP), a nationwide organised screening programme in Korea. The study cohort consisted of 19 168 gastric cancer patients who had been diagnosed in 2007 and who were invited to undergo gastric cancer screening via the NCSP between 2002 and 2007. RESULTS: Compared with never-screened patients, the odds ratios for being diagnosed with localised gastric cancer in endoscopy-screened patients and UGIS-screened patients were 2.10 (95% CI=1.90-2.33) and 1.24 (95% CI=1.13-1.36), respectively. CONCLUSIONS: Screening by endoscopy was more strongly associated with a diagnosis of localised stage gastric cancer compared with screening by UGIS.

Rural vs. urban disparities in association with lower urinary tract symptoms and benign prostatic hyperplasia in ageing men, NHANES 2001-2008.

OBJECTIVE: The objective of this study was to investigate rural/urban and socio-demographic disparities in lower urinary tract symptoms and benign prostatic hyperplasia (LUTS/BPH) in a nationally representative population of men. METHODS: Data on men age ≥40 years (N = 4,492) in the 2001-2008 National Health and Nutrition Examination Surveys were analysed. Self-report of physician-diagnosed enlarged prostate and/or BPH medication use defined recognised LUTS/BPH. Urinary symptoms without BPH diagnosis/medications defined unrecognised LUTS/BPH. Rural-Urban Commuting Area Codes assessed urbanisation. Unadjusted and multivariable associations (odds ratios (OR)) between LUTS/BPH and covariates were calculated using logistic regression. RESULTS: Recognised and unrecognised LUTS/BPH weighted-prevalence estimates were 16.5% and 9.6%. There were no significant associations between LUTS/BPH and rural/urban status. Significant predisposing factors for increased adjusted odds of recognised and unrecognised LUTS/BPH included age, hypertension (OR=1.4;1.4), analgesic use (OR=1.4;1.4) and PSA level >4 ng/mL (OR=2.3;1.9) when adjusted for rural/urban status, race, education, income, alcohol, health insurance, health care and proton pump inhibitor (PPI) use (all p ≤ 0.1). Restricting to urban men only (N = 3,371), healthcare use (≥4visits/year) and PPI's increased adjusted odds of recognised LUTS/BPH (OR=2.0;1.6); no health insurance and

Association of Balance Impairment with Risk of Incident Dementia among Older Adults.

BACKGROUND: A growing body of data suggests that balance impairment may be linked to the onset of dementia. OBJECTIVES: However, a large-scale epidemiologic investigation is needed to clarify its association in older adults. DESIGN: A retrospective-prospective hybrid database. SETTING: Cox proportional hazards regression model was used to assess the relationship between balance impairment and the risk of incident dementia, and the results were provided as adjusted hazard ratios (aHR) with 95% confidence intervals (CI). All participants were tracked until the date of incident dementia, death, or 31 December 2019 whichever came first. PARTICIPANTS: We analyzed 143,788 older adults who had at least one health screening between 2009 and 2019 from the Korea National Health Insurance Service-Senior Cohort. MEASUREMENTS: A total of 3,774 cases of dementia were discovered throughout 850,425 person-years of follow-up investigation. Balance impairment was associated with a risk of dementia compared to those without balance impairment (adjusted hazard ratio [aHR] 1.83; 95% CI, 1.69-2.00; P value <0.001). RESULTS: Risks of the Alzheimer's disease (aHR, 1.80; 95% CI, 1.65-1.96; P for trend <0.001) and the vascular dementia (aHR, 2.94; 95% CI, 1.89-4.58; P for trend <0.001) showed comparable trends and findings. CONCLUSIONS: Balance impairment was found to be independently associated with an increased risk of dementia in older adults.

Factors associated with post-stroke anger proneness in ischaemic stroke patients.

BACKGROUND AND PURPOSE: Factors related to post- stroke anger proneness (PSAP) are poorly studied. The aim of the present study was to determine the frequency of, and the factors related to, PSAP in the acute stage of stroke. Serotonin transporter protein genes and monoamine oxidase A (MAO-A) gene polymorphisms were also examined. METHODS: A total of 508 patients with acute IS were screened for PSAP at admission after stroke, using the modified Spielberger Trait Anger Scale. Blood samples were collected from each participant for DNA extraction and genotyping. The promoter of serotonin transporter protein (5-HTTLPR), the variable number of tandem repeat polymorphisms within intron 2 (VNTR STin2), and the 30-bp functional VNTR polymorphism in the promoter region of the MAO-A gene (MAOA-uVNTR) were genotyped. RESULTS: Post- stroke anger proneness was present in 15.1% of patients at admission. The factors related to PSAP were diabetes mellitus (P < 0.05), previous stroke (P < 0.01), motor and sensory dysfunction (P < 0.01), National Institutes of Health Stroke Scale (NIHSS) at admission (P < 0.01), and MAO-A gene polymorphism (P < 0.05). Multiple logistic regression analyses showed that previous stroke (95% CI: 1.33-4.25, P < 0.01), NIHSS at admission (95% CI: 1.09-1.26, P < 0.01), and low MAO-A activity (95% CI: 1.19-3.47, P = 0.01) were the factors related to PSAP. CONCLUSIONS: Our results show that PSAP is relatively prevalent and that previous stroke, neurological dysfunction and the MAO-A gene are involved in the development of PSAP.

Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness. METHODS: We applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas. RESULTS: Compared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas. CONCLUSIONS: Our results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.

Multivisceral transplantation using a 2.9 kg neonatal donor.

Prematurity and very low birthweight have often been considered relative contraindications to neonatal organ donation. Organ procurement from neonatal donors is further complicated by unclear guidelines regarding neonatal brain death. We report a successful case of multivisceral transplantation using a graft from a 10-day-old, 2.9 kg, neonatal donor born at 36 6/7 wk in a 3.2 kg, three month old with intestinal and liver failure secondary to midgut volvulus. There was immediate liver graft function with correction of recipient coagulopathy, but delayed normalization of laboratory values and delayed return of bowel function. At six-yr post-transplant follow-up, the patient has normal intestine and liver function. Her last histologically confirmed rejection episode was 30 months prior to last follow-up. This case suggests that multivisceral grafts from very young or small neonatal donors may be transplanted successfully in selected cases. We propose a re-examination of the brain death guidelines for premature and young infants to potentially increase the availability of organs for infant recipients.

Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness. METHODS: We applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas. RESULTS: Compared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas. CONCLUSIONS: Our results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.

Secular trends in adult male smoking from 1992 to 2006 in South Korea: age-specific changes with evolving tobacco-control policies.

OBJECTIVES: For years, South Korea has had one of the highest levels of tobacco use among males in the world, but a steady decline has been observed recently. This study examined how the smoking behaviour of male adults changed with age after the implementation of national tobacco control policies in 1995. STUDY DESIGN: Repeated cross-sectional study using a national survey. METHODS: Data were obtained from the 1992, 1995, 1999, 2003 and 2006 results of a repeated cross-sectional survey, the Social Statistics Survey. The smoking status of adult men was compared before (1992 and 1995 surveys) and after (1999, 2003 and 2006 surveys) the implementation of government-directed tobacco control policies using graphical methods and logistic regression analysis. RESULTS: After the implementation of tobacco control policies, the percentage of current male smokers decreased while the percentage of former smokers increased markedly. Smoking prevalence among older men (aged 50 years or more) reduced initially, and this decline was more pronounced after the tobacco control policies were implemented. Smoking prevalence in younger men (aged 30-49 years) declined in 2003 when more comprehensive tobacco control policies were implemented. CONCLUSIONS: This study suggests that comprehensive tobacco control policies in South Korea reduced smoking prevalence among males, initially among older men and later among both older men and younger men.

A familial case of pleuropulmonary blastoma.

PURPOSE: Pleuropulmonary blastoma (PPB) is a rare intrathoracic neoplasm of early childhood arising in the lung or visceral pleura. Approximately 150 cases have been reported in the literature, with only one previously documented case of PPB in siblings. PATIENTS AND METHODS: We present the case of two brothers diagnosed with PPB. RESULTS: A two month-old boy with an abnormal breathing pattern was referred for evaluation of a cystic mass discovered on chest radiograph. Computed tomography (CT) of the chest was performed at our institution which revealed findings compatible with congenital cystic adenomatoid malformation (CCAM) of the right middle and lower lobes. The patient underwent urgent thoracic exploration one week later after developing severe respiratory distress. Histological examination revealed PPB type I (cystic). The patient's 15-month-old brother was presumed to have a CCAM noted radiographically months earlier during an asthma exacerbation. He underwent elective cyst resection and was also found to have type I PPB. The index patient was treated with adjuvant chemotherapy due to the large size of the PPB and intraoperative spillage of cystic fluid during the emergent surgery. In contrast, the brother is being followed without adjuvant chemotherapy, given the much smaller size of the PPB, wide margins of resection, and lack of spillage. Family history included an uncle diagnosed at age 11 with an unusual form of T cell acute lymphoblastic leukemia. CONCLUSION: Although PPB is known to have a familial association with other neoplasms, this case represents only the second report of PPB occurring in siblings. The importance of thoroughly investigating and resecting pulmonary cystic masses in the pediatric population is highlighted by these cases.

Auditory cortex hyperconnectivity before rTMS is correlated with tinnitus improvement / Correlación entre hiperconectividad de la corteza auditiva antes del tratamiento con estimulación magnética transcraneal repetitiva y mejoría de los acúfenos

Introduction: Repetitive transcranial magnetic stimulation (rTMS) has been used as a potential treatment for tinnitus; however, its effectiveness is variable and unpredictable. We hypothesized that resting-state functional connectivity before rTMS may be correlated with rTMS treatment effectiveness. Methods: We applied 1-Hz rTMS to the left primary auditory (A1) and dorsolateral prefrontal cortices (DLPFC) of 10 individuals with tinnitus and 10 age-matched controls. Resting-state functional magnetic resonance imaging (fMRI) studies were performed approximately one week before rTMS. Seed-based connectivity analyses were conducted for each individual, with seed regions as rTMS target areas. Results: Compared to controls, the left superior temporal areas showed significantly increased positive connectivity with the left A1 and negative connectivity with the left DLPFC in the tinnitus group. The left frontoparietal and right cerebellar areas showed significantly increased negative connectivity with the left A1 and positive connectivity with the left DLPFC. Seed-based hyperconnectivity was correlated with tinnitus improvement (pre-rTMS vs. 2-week post-rTMS Tinnitus Handicap Inventory scores). Tinnitus improvement was significantly correlated with left A1 hyperconnectivity; however, no correlation was observed with left DLPFC connectivity. Positive rTMS outcomes were associated with significantly increased positive connectivity in bilateral superior temporal areas and significantly increased negative connectivity in bilateral frontal areas. Conclusions: Our results suggest that oversynchronisation of left A1 connectivity before rTMS of the left A1 and DLPFC is associated with treatment effectiveness.(AU)

Introducción: La estimulación magnética transcraneal repetitiva (EMTr) se ha utilizado como posible tratamiento para los acúfenos, aunque su efectividad es variable e impredecible. Planteamos la hipótesis de que existe una correlación entre la conectividad funcional en estado de reposo antes de aplicar EMTr y la efectividad de dicho tratamiento. Métodos: Aplicamos EMTr a 1 Hz sobre la corteza auditiva primaria (A1) y la corteza prefrontal dorsolateral (CPFDL) izquierdas de 10 pacientes con acúfenos y 10 controles del mismo rango de edad. Se realizaron estudios de resonancia magnética funcional (RMF) en estado de reposo de todos los pacientes aproximadamente una semana antes de la EMTr. En cada caso, se construyó un mapa de conectividad basado en las ROIs, en el que las ROIs eran las áreas que se tratarían con la EMTr. Resultados: La región temporal superior izquierda mostró una conectividad positiva significativamente mayor con el área A1 izquierda y mayor conectividad negativa con la CPFDL izquierda en los pacientes con acúfenos que en los controles. Además, las áreas frontoparietal izquierda y cerebelar derecha mostraron una conectividad negativa significativamente superior con el área A1 izquierda y mayor conectividad positiva con la CPFDL izquierda. La hiperconectividad de las ROIs se correlacionó con mejoría de los acúfenos según las puntuaciones pre-EMTr y 2 semanas post-EMTr en la escala Tinnitus Handicap Inventory. La mejoría de los acúfenos se correlacionó de manera significativa con la hiperconectividad del área A1 izquierda; sin embargo, no se encontró correlación con la conectividad de la CPFDL izquierda. El resultado favorable del tratamiento con EMTr se asocia con una mayor conectividad positiva en áreas temporales superiores de ambos hemisferios y con mayor conectividad negativa en áreas frontales bilaterales...(AU)

Serum amyloid A protein-related mRNA expression in herpes simplex virus type 2-transformed hamster cells.

A nearly full-length cDNA very similar to murine serum amyloid A protein was cloned from herpes simplex virus type 2-transformed hamster cells. The expression of mRNA was constitutive in these cells and could be superinduced by conditioned medium. Higher rates of nuclear runoff transcription in transformed and induced cells indicated some regulation at the transcriptional level.

Cell surface adenosine 5'-triphosphatase as an in vitro marker of the lineage and cytodifferentiation of oncogenic epithelial cells from rat liver parenchyma.

The relationship between the oncogenicity and the surface properties of cultured liver epithelial cells has been studied with the newborn Wistar rat-derived euploid line, RL34, and its heteroploid variants. An oncogenic variant, RL34HT, appeared to be more functionally active than its nononcogenic counterparts with respect to cell surface adenosine 5'-triphosphatase (ecto-ATPase) as well as to cytoplasmic enzymes such as tyrosine aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase. The cell surface of RL34HT was distinguished from those of nononcogenic and marginally oncogenic cell populations by the presence of abundant microvilli and by the absence of large external transformation-sensitive protein (fibronectin). High-Km and high-Vmax Ca2+-Mg2+ -ecto-ATPase was found in RL34HT. All nononcogenic cell lines had a flat granular surface membrane with high levels of fibronectin and also exhibited ecto-ATPase activity with low Km and low Vmax. When RL34HT was grown in dibutyryl cyclic adenosine 3',5'-monophosphate and theophylline, the external cell surface was partially restored to the polypeptide compositions of RL34, and there was an increase in Vmax of ecto-ATPase without a change in Km. The high-Km ecto-ATPase may be a useful indicator reflecting the lineage and cytodifferentiation of oncogenic liver epithelial cells, since it is also known to be localized at the bile canalicular microvilli of normal adult hepatocytes.

Analysis of chromosomes, nucleic acids, and polypeptides in hamster cells transformed by herpes simplex virus type 2.

Syrian hamster embryo fibroblasts were oncogenically transformed by UV-inactivated Herpes simplex type 2. Eighteen clones were isolated shortly after transformation occurred. Two clones and their tumor derivatives were studied using several techniques. The karyotype analysis revealed different chromosome patterns in the two clones and a tendency toward hypodiploidy in the tumor derivatives. All of these cell lines were shown by molecular hybridization to contain 40% of the HSV-genome in several copies. The viral DNA sequence complexity was retained in the tumor derivatives, but a decrease in the copy number was observed. Viral RNA's were detected by in situ hybridization in all the lines that were tested. Viral antigens could be observed in these transformed cells by immunofluorescence. Finally, polypeptide analysis showed three differences between normal and transformed cells.

Increasing Levels of Dietary Hempseed Products Leads to Differential Responses in the Fatty Acid Profiles of Egg Yolk, Liver and Plasma of Laying Hens.

The limited efficiency with which dietary alpha-linolenic acid (ALA) is converted by hens into docosahexaenoic acid (DHA) for egg deposition is not clearly understood. In this study, dietary ALA levels were increased via the inclusion of hempseed (HS) and hempseed oil (HO) in hen diets, with the goal of assessing the effects on the fatty acid (FA) profiles of total lipids and lipid classes in yolk, liver and plasma. Forty-eight hens were individually caged and fed one of six diets containing either HS:10, 20 or 30, HO:4.5 or 9.0 (%, diet) or a control (containing corn oil), providing a range (0.1-1.28 %, diet) of ALA. Fatty acid methyl esters of total lipids and lipid classes, including phosphatidyl choline (PtdCho) and ethanolamine (PtdEtn) in yolk, plasma and liver were then determined. Levels of n-3 FAs in both total lipids and lipid classes increased in all tissues. ALA and eicosapentaenoic acid (EPA) increased linearly, while docosapentaenoic acid and DHA increased quadratically. The FA profiles of yolk closely reflected levels in both plasma and liver. While ALA was highly concentrated in the triacylglycerol, it was low but equally distributed between PtdCho and PtdEtn in all tissues; however, the net accumulation was lower (P < 0.0001) in liver compared to yolk and plasma. Levels of EPA and ALA in yolk-PtdEtn were linearly (P < 0.0001; R (2) = 0.93) associated, and reflected those in liver-PtdEtn (P < 0.0001; R (2) = 0.90). In the liver, a strong inverse correlation (P < 0.0001; r = -0.94) between PL-DHA and ALA-to-EPA ratio in PtdEtn supports theories of low substrate availability, possibly limiting the conversion of ALA into DHA for egg enrichment.