A guide to successful mL to L scale vitrification and rewarming.

Cryopreservation by vitrification to achieve an "ice free" glassy state is an effective technique for preserving biomaterials including cells, tissues, and potentially even whole organs. The major challenges in cooling to and rewarming from a vitrified state remain ice crystallization and cracking/fracture. Ice crystallization can be inhibited by the use of cryoprotective agents (CPAs), though the inhibition further depends upon the rates achieved during cooling and rewarming. The minimal rate required to prevent any ice crystallization or recrystallization/devitrification in a given CPA is called the critical cooling rate (CCR) or critical warming rate (CWR), respectively. On the other hand, physical cracking is mainly related to thermomechanical stresses, which can be avoided by maintaining temperature differences below a critical threshold. In this simplified analysis, we calculate deltaT as the largest temperature difference occurring in a system during cooling or rewarming in the brittle/glassy phase. This deltaT is then used in a simple "thermal shock equation" to estimate thermal stress within the material to decide if the material is above the yield strength and to evaluate the potential for fracture failure. In this review we aimed to understand the limits of success and failure at different length scales for cryopreservation by vitrification, due to both ice crystallization and cracking. Here we use thermal modeling to help us understand the magnitude and trajectory of these challenges as we scale the biomaterial volume for a given CPA from the milliliter to liter scale. First, we solved the governing heat transfer equations in a cylindrical geometry for three common vitrification cocktails (i.e., VS55, DP6, and M22) to estimate the cooling and warming rates during convective cooling and warming and nanowarming (volumetric heating). Second, we estimated the temperature difference deltaT and compared it to a tolerable threshold (deltaTmax) based on a simplified "thermal shock" equation for the same cooling and rewarming conditions. We found, not surprisingly, that M22 achieves vitrification more easily during convective cooling and rewarming for all volumes compared to VS55 or DP6 due to its considerably lower CCR and CWR. Further, convective rewarming (boundary rewarming) leads to larger temperature differences and smaller rates compared to nanowarming (volumetric rewarming) for all CPAs with increasing failure at larger volumes. We conclude that as more and larger systems are vitrified and rewarmed with standard CPA cocktails, this work can serve as a practical guide to successful implementation based on the characteristic length (volume/surface area) of the system and the specific conditions of cooling and warming. doi.org/10.54680/fr22610110112.

Outcomes in juvenile onset lupus: single center cohort from a developing country.

Introduction About 10-20% of systemic lupus erythematosus (SLE) patients have onset in childhood and have more severe organ involvement. Survival of juvenile SLE patients is improving worldwide. Long-term data of childhood onset SLE from developing countries is scarce. Methods Clinical and laboratory data at initial presentation and follow-up visits were retrieved from clinic files, hospital information system and personal interviews. Treatment received, complications, flares, outcomes and death were recorded. Survival was calculated using Kaplan-Meier survival curves and regression analysis was done for predictors of mortality. Results Children with SLE ( n = 273, 250 girls) had a median age at onset of 14 years and duration of illness prior to diagnosis at our hospital of 1 year. Fever and arthritis were the most common presenting manifestations. Renal disease was seen in 60.5% and central nervous system (CNS) disease in 29%. The median follow-up period in 248 patients was 3.5 years. Fourteen children died, and 10 of these had active disease at the time of death. The mean actuarial survival was 24.5 years and survival rates at 1, 5 and 10 years were 97.9%, 95% and 89% respectively. Fever, CNS disease, anti-dsDNA levels and serious infections predicted death on univariate and multivariate analysis. Infections were seen in 72 children (26.3%), and 38 of these infections were serious. One-third of the patients had damage on the last follow-up. Flares were seen in 120 children, the majority being major flares. Conclusion Outcomes of pediatric SLE in North Indian children are similar to those seen in developed countries. Infections pose a major challenge in these patients.

Urinary B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL): potential biomarkers of active lupus nephritis.

B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) help in B cell activation, maintenance and plasma cell survival. B cell infiltration has been demonstrated in kidneys of patients with lupus nephritis (LN). Serum levels of BAFF and APRIL have shown inconsistent relationships with lupus disease activity. We evaluated urinary levels of BAFF and APRIL as biomarker for LN. Thirty-six patients with proliferative lupus nephritis (AN), 10 with active lupus without nephritis (AL) and 15 healthy controls (HC) were studied. APRIL and BAFF levels were measured in both serum and urine using enzyme-linked immunosorbent assay (ELISA). Urine levels were normalized for urinary creatinine excretion. Urine levels were correlated with conventional disease activity markers and histology. Levels were reassessed in 20 AN patients at 6 months after treatment with cyclophosphamide. Urinary APRIL (uAPRIL) and BAFF (uBAFF) levels were raised significantly in AN. uAPRIL, but not uBAFF, correlated moderately with renal Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in AN (r = 0·36, P < 0·05). On receiver operator curve (ROC) analysis, uBAFF and uAPRIL showed an area under the curve (AUC) of 0·825 and 0·781, respectively, in differentiating between nephritis and non-nephritis, which performed better than low C3, C4 and raised anti-dsDNA antibodies. There was no correlation of serum levels with uBAFF (r = 0·187, P = 0·261) and uAPRIL (r = 0·114, P = 0·494). uAPRIL levels reduced after treatment (mean 125 pg/mg to 36 pg/mg, P < 0·05). uBAFF levels reduced in 16 responders while two of four non-responders had increase in levels. Thus, uBAFF and uAPRIL are potential biomarkers of proliferative lupus nephritis.

Investigating the Role of Plasma Glucose Concentration as a Phenotypic Marker for CYP2C9 Genetic Variants, in the Diabetic Population of Gujarat.

The present study was aimed to investigate the role of plasma glucose concentration as a phenotypic marker and to study the frequency distribution of CYP2C9 genetic variants in Gujarat state diabetic population. One hundred and nine unrelated diabetes mellitus patients treated with sulfonylureas were genotyped for CYP2C9*2 and CYP2C9*3 alleles. Their pre- and posttreatment postprandial blood glucose levels were recorded and mean glucose drop per milligram of drug values were calculated and further used as an index for phenotypic correlation. The frequencies of CYP2C9*1, CYP2C9*2 and CYP2C9*3 alleles in the Gujarat state diabetic population were 0.84, 0.07 and 0.09, respectively. The distribution of CYP2C9*1/*1, CYP2C9*1/*2, CYP2C9*1/*3, CYP2C9*2/*2, CYP2C9*2/*3 and CYP2C9*3/*3 genotypes were 0.73, 0.08, 0.13, 0.0, 0.06 and 0.0, respectively. Patients with CYP2C9*1/*2 genotype did not show any significant difference in the mean glucose drop per milligram of drug values when compared with wild-type patients in glipizide-treatment group. Patients with CYP2C9*1/*3 genotype showed greater mean glucose drop per milligram of drug values than patients with CYP2C9*1/*1 wild-type genotype for both glipizide and glimepiride while patients with CYP2C9*2/*3 genotype showed greater drop than patients with CYP2C9*1/*1 genotype only in the glipizide-treatment group. The presence of CYP2C9*3 allele significantly affected plasma glucose drop per milligram of drug values in patients taking glipizide and glimepiride, while effects of CYP2C9*2 allele were insignificant. Further studies are needed to confirm the effects of CYP2C9*2 allele on plasma glucose drop per milligram of drug values. However, plasma glucose concentration is a complex physiological marker that cannot be used to establish perfect genotype-phenotype correlation. Hence studies exploring robust phenotypic markers must be initiated.

A clinical study to compare the efficacy and safety of pregabalin sustained release formulation with pregabalin immediate release formulation in patients of diabetic peripheral neuropathic pain.

OBJECTIVE: To compare the efficacy and safety of sustained release (SR) formulation of pregabalin with immediate release (IR) formulation in patient with diabetic peripheral neuropathic pain. MATERIALS AND METHODS: In this open label, randomized, comparative, multicentric study, the primary efficacy measure was reduction in visual analogue scale (VAS) of short form McGill pain questionnaire (SF-MPQ) score from baseline to last visit. The secondary evaluation measures included reduction in SF-MPQ descriptive score and present pain intensity score and change in clinical global impression - improvement of illness (CGI-I) and clinical global impression - severity of illness (CGI-S) from baseline to last visit. Total duration of the study was 12 weeks. Safety evaluation was done by recording treatment emergent adverse events and laboratory investigations at baseline and end of treatment. RESULTS: Of 265 randomized patients, 133 received pregabalin SR tablets and 132 pregabalin IR. Patients randomized to both treatments responded to respective treatments. The least square means of VAS score in both the groups were reduced significantly (P <0.01). Reduction in both groups was similar (P = ns). At the end of the trial in both the groups, there was a significant reduction in the SF-MPQ descriptive score (P <0.01), severity of illness as well as clinically significant improvement in the symptoms. Difference between the groups for CGI-I (P = 0.37) and CGI-S (P = 0.41) score was not statistically significant. Treatment in both the groups was found safe and well tolerated. CONCLUSION: The study shows that the pregabalin SR is safe and effective in patients of diabetic peripheral neuropathic pain. The results of the study demonstrated that pregabalin SR has comparable efficacy and safety as pregabalin IR.

Association of filamin A and vimentin with hepatitis C virus proteins in infected human hepatocytes.

Chronic hepatitis C (CHC) infection caused by hepatitis C virus (HCV) is a major cause of liver disease and remains a major therapeutic challenge. A variety of host proteins interact with HCV proteins. The definitive role of cytoskeletal (CS) proteins in HCV infection remains to be determined. In this study, our aim was to determine the expression profile of differentially regulated and expressed selected CS proteins and their association with HCV proteins in infected hepatocytes as possible therapeutic targets. Using proteomics, qRT-PCR, Western blot and immunofluorescence techniques, we revealed that filamin A (fila) and vimentin (vim) were prominently increased proteins in HCV-expressing human hepatoma cells compared with parental cells and in liver biopsies from patients with CHC vs controls. HCV nonstructural (NS) 3 and NS5A proteins were associated with fila, while core protein partially with fila and vim. Immunoprecipitation showed interactions among fila and NS3 and NS5A proteins. Cells treated with interferon-α showed a dose- and time-dependent decrease in CS and HCV proteins. NS proteins clustered at the perinuclear region following cytochalasin b treatment, whereas disperse cytoplasmic and perinuclear distribution was observed in the no-treatment group. This study demonstrates and signifies that changes occur in the expression of CS proteins in HCV-infected hepatocytes and, for the first time, shows the up-regulation and interaction of fila with HCV proteins. Association between CS and HCV proteins may have implications in future design of CS protein-targeted therapy for the treatment for HCV infection.

Nutritive value, fermentation characteristics, and in situ disappearance kinetics of ensiled warm-season legumes and bahiagrass.

This study determined the nutritive value, ensiling characteristics, and in situ disappearance kinetics of bahiagrass (Paspalum notatum Flügge 'Tifton 9'), perennial peanut (Arachis glabrata Benth. 'Florigraze'), annual peanut [Arachis hypogaea (L.) 'FL MDR 98'], cowpea [Vigna unguiculata (L.) Walp. 'Iron clay'], and pigeonpea [Cajanus cajan (L.) Millsp. 'GA-2']. All forages were harvested at maturity stages that optimized dry matter (DM) yield and nutritive value. After harvest, forages were wilted to 45% DM, and 4 replicate bales of each legume and 8 bales of bahiagrass were wrapped in polyethylene and ensiled for 180 d. After each bale was opened, the forage was thoroughly mixed, and representative subsamples were taken for laboratory analysis and in situ incubation. Wilting and ensiling decreased the rumen-undegradable protein, water-soluble carbohydrate, crude protein (CP), and in vitro true digestibility (IVTD) of bahiagrass, perennial peanut, and cowpea, and increased their neutral detergent fiber (NDF) concentrations. Among haylages, CP concentration was greatest for annual peanut, followed by perennial peanut and cowpea, and least for bahiagrass. In contrast, NDF concentration was greater in bahiagrass than in legumes. Pigeonpea had the greatest NDF concentration among legumes and lowest IVTD of all haylages. All haylages were aerobically stable for at least 84 h, but pH was lower in perennial peanut and cowpea than in pigeonpea. Ammonia-N concentrations tended to be greater in legume haylages than in bahiagrass haylage. Butyrate concentration was greater in annual and perennial peanut than in bahiagrass. Total VFA concentration was greater in annual and perennial peanut and cowpea haylages than in bahiagrass haylage. Undegradable DM fractions were greater and extent of DM degradation was lower in bahiagrass and pigeonpea than in other haylages but lag time and degradation rates did not differ. Annual and perennial peanut and cowpea haylages were as aerobically stable and had greater CP, IVTD, and extent of degradation than did bahiagrass haylage; therefore, they are promising forages for dairy cow diets in the southeastern United States.

Intake, digestibility, and nitrogen retention by sheep supplemented with warm-season legume haylages or soybean meal.

The high cost of commercial supplements necessitates evaluation of alternatives for ruminant livestock fed poor quality warm-season grasses. This study determined how supplementing bahiagrass haylage (Paspalum notatum Flügge cv. Tifton 9) with soybean [Glycine max (L.) Merr.] meal or warm-season legume haylages affected the performance of lambs. Forty-two Dorper x Katadhin lambs (27.5 +/- 5 kg) were fed for ad libitum intake of bahiagrass haylage (67.8% NDF, 9.6% CP) alone (control) or supplemented with soybean meal (18.8% NDF, 51.4% CP) or haylages of annual peanut [Arachis hypogaea (L.) cv. Florida MDR98; 39.6% NDF, 18.7% CP], cowpea [Vigna unguiculata (L.) Walp. cv. Iron clay; 44.1% NDF, 16.0% CP], perennial peanut (Arachis glabrata Benth. cv. Florigraze; 40.0% NDF, 15.8% CP), or pigeonpea [Cajanus cajan (L.) Millsp. cv. GA-2; 65.0% NDF, 13.7% CP]. Haylages were harvested at the optimal maturity for maximizing yield and nutritive value, wilted to 45% DM, baled, wrapped in polyethylene plastic, and ensiled for 180 d. Legumes were fed at 50% of the dietary DM, and soybean meal was fed at 8% of the dietary DM to match the average CP concentration (12.8%) of legume haylage-supplemented diets. Lambs were fed each diet for a 14-d adaptation period and a 7-d data collection period. Each diet was fed to 7 lambs in period 1 and 4 lambs in period 2. Pigeonpea haylage supplementation decreased (P < 0.01) DM and OM intake and digestibility vs. controls. Other legume haylages increased (P < 0.05) DM and OM intake vs. controls; however, only soybean meal supplementation increased (P = 0.01) DM digestibility. All supplements decreased (P = 0.05) NDF digestibility. Except for pigeonpea haylage, all supplements increased (P < 0.01) N intake, digestibility, and retention, and the responses were greatest (P = 0.04) with soybean meal supplementation. Microbial N synthesis was reduced (P = 0.02) by pigeonpea haylage supplementation, but unaffected (P = 0.05) by other supplements. Efficiency of microbial protein synthesis was unaffected (P = 0.05) by diet. Ruminal ammonia concentration was increased (P = 0.01) by all supplements, but only soybean meal and annual peanut haylage increased (P < 0.03) plasma urea-N concentrations. Perennial peanut, annual peanut, and cowpea haylages are promising protein supplements for growing lambs.

Intake, digestibility, and nitrogen retention by sheep supplemented with warm-season legume hays or soybean meal.

The increasing cost of feed supplements necessitates evaluation of alternatives for ruminant livestock grazing poor quality warm-season grasses. This study determined how supplementing bahiagrass hay (Paspalum notatum Flügge cv. Pensacola) with soybean [Glycine max (L.) Merr.] meal or warm-season legume hays affected intake, digestibility, and N utilization by lambs. Dorper x Katadhin crossbred lambs (30.6 +/- 5.5 kg; n = 42) were fed bahiagrass hay (73.8% NDF, 8.1% CP) for ad libitum intake and supplemented with nothing (control), soybean meal, or hays of annual peanut [Arachis hypogaea (L.) cv. Florida MDR98; 46.2% NDF, 14.7% CP], cowpea [Vigna unguiculata (L.) Walp. cv. Iron clay; 62.2% NDF, 11.7% CP], perennial peanut (Arachis glabrata Benth. cv. Florigraze; 43.3% NDF, 15.2% CP), pigeonpea [Cajanus cajan (L.) Millsp. cv. GA-2; 78.6% NDF, 12.2% CP], or soybean (cv. Pioneer 97B52; 59.0% NDF, 13.5% CP). Legume hays were supplemented at 50% of total diet DM, and soybean meal was supplemented at a level (4.25% of diet DM) that matched the average dietary CP content (10.8%) of the legume hay-supplemented diets. The cowpea, pigeonpea, and soybean were harvested at respective maturities that maximized DM yield and nutritive value, and the peanuts were first cuttings. Diets were fed to 6 lambs per treatment for 2 consecutive 21-d periods. Supplementation with hays of annual and perennial peanut, cowpea, and soybean increased (P < 0.01) DMI vs. control, but apparent DM digestibility was only increased (P = 0.03) by supplementation with annual or perennial peanut hay. Compared with the control, N intake, digestibility, and retention were increased (P < 0.01) by supplementation with legume hay or soybean meal. Responses were greatest when annual or perennial peanut hays were fed. Ruminal ammonia concentration was increased (P < 0.01) by all legume hay supplements vs. the control. Microbial N synthesis and ruminally degraded OM were increased (P = 0.03) by perennial and annual peanut hay supplementation, but efficiency of microbial synthesis was not different (P = 0.52) among diets. Unlike other supplements, annual and perennial peanut hays increased DM and N intake and digestibility and improved microbial N synthesis; therefore, they were the best supplements for the bahiagrass hay under the conditions of this study.

Effects of Reduced Tillage, Resistant Cultivars, and Reduced Fungicide Inputs on Progress of Early Leaf Spot of Peanut (Arachis hypogaea).

Field experiments were conducted in 2000 and 2001 on Georgia Green, Florida MDR-98, and C-99R peanut (Arachis hypogaea) cultivars in Tifton, GA, to determine the effects of tillage practices on early leaf spot (Cercospora arachidicola) epidemics under standard fungicide regimes and fungicide regimes with fewer applications. Leaf spot epidemics were suppressed in reduced tillage (strip-till) plots compared with conventional tillage plots and were suppressed in MDR-98 and C-99R cultivars compared with the standard runner-type cultivar, Georgia Green. Within tillage and cultivar combinations, leaf spot intensity typically was lower in plots treated with fungicides at standard intervals (seven total applications) than in those treated at extended intervals (four total applications). However, in most cases, leaf spot control in extended interval treatments in the strip-till system was comparable to that in the standard interval treatments in conventional tillage. Based on these results, the number of fungicide applications could be reduced without compromising control of leaf spot when reduced tillage is used, especially if combined with moderately resistant cultivars. Suppression of leaf spot epidemics in the strip-till plots did not coincide with higher yields in either year. In 2001, yields were lower in strip-till plots than in conventional tillage plots. Yields were typically higher in the cultivar C-99R than in Georgia Green, regardless of the tillage treatment.

First Report of Rhizoctonia solani AG-2-4 on Carrot in Georgia.

Anastomosis group-2-4 (AG-2-4) of Rhizoctonia solani Kühn was formally described in 2002 (1), but it was first collected in 1983 in Georgia from corn (Zea mays L.) exhibiting symptoms of crown and brace root rot. Although occasionally present on diseased corn roots, the role that isolates of AG-2-4 play in crown and brace root rot of corn is not specifically known (2). More recently, as part of a broad multi-year (1996 to 2000) survey of root diseases in field grown carrot (Daucus carota L.), isolates of R. solani AG-2-4 were recovered from diseased carrot plants in various stages of growth from fields of sandy loam soil at many locations in southern Georgia, including commercial fields in Coffee and Tift counties. During the 1996 to 2000 growing seasons, 123 isolates of Rhizoctonia sp. (including multinucleate and binucleate types) were collected from lesions on developing and mature carrot roots. Of these, 34% were AG-2-4, 10% were AG-2-2IV, 6% were AG-4, and 32% were binucleate Rhizoctonia sp. The remaining 18% were lost prior to AG typing. An additional 40 isolates were collected from carrot seedlings or soil and of these, 55% were AG-4, 18% were AG-2-2IV but none were AG-2-4. Virulence on carrot seedlings by two isolates of AG-2-4 (777R1P5-SL2 and 758C) was compared with virulence of isolates of AG-4, AG-2-2IV, AG-2-1, and binucleate Rhizoctonia sp. Carrot seeds soaked for 5 min in 0.5% NaOCl were planted in petri dishes containing moist autoclaved sandy loam soil. Each dish was inoculated in the center with a 10-mm-diameter disk cut from a 9-day-old potato dextrose agar (PDA) culture of the appropriate isolate. Petri dishes were placed in a 26°C incubator for 9 days, and then the seedlings were rated for disease. Virulence on mature carrot root tissue was also assessed on the same set of isolates. Cross sections of carrot roots (5 to 10 mm thick) were surface disinfested in 0.5% NaClO for 5 min. Three cross sections were placed on moist filter paper in sterile petri dishes and each was inoculated with a 5-mm-diameter disk of inoculum cut from 8- to 10-day-old cultures growing on PDA. All treatments were rated for damage following incubation on a lab bench at 21 to 24°C for 7 days. Isolate 777R1P5-SL2 caused moderate damage to seedlings but minimal rotting of mature carrot root tissue. Isolate 758C did no damage to either seedlings or root tissue. The AG-4 and AG-2-2IV isolates killed all seedlings and caused extensive rot on mature root tissue. The AG-2-1 isolate caused moderate damage to seedlings and mature root tissue, whereas isolates of binucleate Rhizoctonia sp. damaged neither seedling nor mature root tissue. These data suggest that some isolates of R. solani AG-2-4 may be capable of causing minor damage to carrot seedlings in the field in Georgia, but isolates of R. solani AG-4 and AG-2-2IV pose greater threat to seedlings and mature roots of carrot. Published data shows that isolates of AG-2-4 can kill seedlings of lettuce, cauliflower, and broccoli in the laboratory (1). R. solani AG-2-4 also may be capable of killing these crops in the field, all of which are grown commercially in Georgia. To our knowledge, this is the first report of R. solani AG-2-4 on carrot in Georgia. References: (1) D. E. Carling et al. Phytopathology 92:43, 2002. (2) D. R. Sumner and D. K. Bell. Phytopathology 72:86.

Embryonal rhabdomyosarcoma with intracranial extension.

A case of embryonal rhabdomyosarcoma of the middle ear presenting with facial paralysis and a polypoidal aural mass who subsequently had convulsions due to intracranial extension is presented for its rarity.

A rare foreign body in the maxillary antrum.

A case of metallic foreign body getting impacted into maxillary antrum and orbit due to a blast in a furnace, presenting primarily with 20% facial burn & ocular symptoms is presented for its rarity.

Congenital teratoid tumour of nasopharynx with cleft palate.

A case of congenital nasopharyngeal teratoid tumour presenting since birth projecting into oral cavity through the palatal cleft & gradually increasing in size thus causing breathing & feeding difficulty in a four months old female child is presented here for its rarity. A brief review of literature and management of such patients is also discussed here.

A total system approach to sustainable pest management.

A fundamental shift to a total system approach for crop protection is urgently needed to resolve escalating economic and environmental consequences of combating agricultural pests. Pest management strategies have long been dominated by quests for "silver bullet" products to control pest outbreaks. However, managing undesired variables in ecosystems is similar to that for other systems, including the human body and social orders. Experience in these fields substantiates the fact that therapeutic interventions into any system are effective only for short term relief because these externalities are soon "neutralized" by countermoves within the system. Long term resolutions can be achieved only by restructuring and managing these systems in ways that maximize the array of "built-in" preventive strengths, with therapeutic tactics serving strictly as backups to these natural regulators. To date, we have failed to incorporate this basic principle into the mainstream of pest management science and continue to regress into a foot race with nature. In this report, we establish why a total system approach is essential as the guiding premise of pest management and provide arguments as to how earlier attempts for change and current mainstream initiatives generally fail to follow this principle. We then draw on emerging knowledge about multitrophic level interactions and other specific findings about management of ecosystems to propose a pivotal redirection of pest management strategies that would honor this principle and, thus, be sustainable. Finally, we discuss the potential immense benefits of such a central shift in pest management philosophy.

Localization of the human Ror1 gene (NTRKR1) to chromosome 1p31-p32 by fluorescence in situ hybridization and somatic cell hybrid analysis.

Ror1 is an orphan cell surface receptor with strong homology to the tyrosine kinase domain of growth factor receptors, in particular the Trk family. Southern blot analysis of genomic DNA from somatic cell hybrids revealed that Ror1 is located on chromosome 1. We have mapped the Ror1 gene to chromosome 1p12-p32 using PCR on a somatic cell hybrid panel that subdivides chromosome 1p. We have further localized the gene to chromosome 1p31-p32 by fluorescence in situ hybridization using a PAC clone that contains the Ror1 gene.

Congenital teratoid tumour of nasopharynx with cleft palate.

A case of congenital nasopharyngeal teratoid tumour presenting since birth projecting into oral cavity through the palatal cleft and gradually increasing in size thus causing breathing and feeding difficulty in a four months old female child is presented here for its rarity. A brief review of literature and management of such patients is also discussed here.

Human neural tissues express a truncated Ror1 receptor tyrosine kinase, lacking both extracellular and transmembrane domains.

Human heart, lung and kidney express a 6 kb mRNA encoding Ror1, a member of the receptor tyrosine kinase (RTK) family with as yet unknown ligand specificity. We used a Ror1 cDNA probe to screen a cDNA library prepared from the human neuronogenic teratocarcinoma line, NTera2, and cloned a 2373 nucleotide transcript. This transcript contains an open reading frame that encodes a 388 amino acid protein identical with the cytosolic, C-terminal region of ror1 but lacking the ror1 transmembrane and entire extracellular domains. Northern blots demonstrate that mRNA encoding this truncated Ror1 ('t-Rorl') is abundantly expressed in fetal and adult human CNS, in human leukemia, lymphoma cell lines, and in a variety of human cancers derived from neuroectoderm. While previous studies have documented alternative splicing patterns within 5' and 3' regions of mRNAs encoding various RTKs altering their ligand binding specificity or their intracellular signaling, the present report is the first to demonstrate tissue-specific alternative mRNA splicing causing loss of the entire extracellular and transmembrane regions of an RTK.