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Retinoblastoma occurs with increased frequency in children born with a deletion of the long arm of chromosome 13. Recent reviews have noted that the region 13q14 is consistently deleted in documented cases. Prometaphase and late prophase banding allowed Yunis and Ramsay to determine that a deletion in one patient included the sub-bands q14 . 12, q14 . 13, and q14 . 2, and a portion of q14 . 11 and q14 . 3. We report the results of similar cytogenetic techniques applied in the case of a 26 month old Caucasian female with unilateral retinoblastoma, moderate developmental delay, and subtle dysmorphology. Prometaphase banding of cultured skin fibroblasts revealed the karyotype: mos46,XX/46,XX,del(13)(q13 . 1q14 . 11). Only the sub-band q14 . 11 is deleted in both our patient and that of Yunis and Ramsay. The results are consistent with the localisation of the retinoblastoma susceptibility gene(s) in the sub-band 13q14 . 11. Electrophoretic analysis and activity assays of red blood cell esterase D are consistent with hemizygous expression of that marker in our proband. Comparison with published esterase D analyses in families with retinoblastoma permits the assignment of the esterase D locus to that same sub-band, 13q14 . 11. [ABSTRACT FROM PUBLISHER]

Five pedigrees (including an expanded version of a previously reported pedigree) exhibited typical autosomal dominant retinitis pigmentosa were analysed for linkage of RP to 29 genetic markers. No significant lod scores resulted. The largest lod score is +1.51 and suggests linkage between RP and Rh blood group at an estimated recombination fraction of 20% in males and 40% in females. Further studies are needed to confirm or refute this suggested linkage. [ABSTRACT FROM PUBLISHER]

Seventeen independently derived primary mouse-human hybrid clones were scored for the expression of human phosphoglycolate phosphatase (PGP) by electrophoresis and for the presence of human chromosomes with the aid of Q banding. The correlation of biochemical and cytogenetic analyses shows that the segregation of human PGP in these hybrids is concordant only with human chromosome 16, thus enabling the assignment of the genetic locus for PGP to human chromosome 16. [ABSTRACT FROM AUTHOR]

The unaddressed palliative care needs of patients with advanced, nonmalignant, lung disease highlight the urgent requirement for new models of care. This study describes a new integrated respiratory and palliative care service and examines outcomes from this service. The Advanced Lung Disease Service (ALDS) is a long-term, multidisciplinary, integrated service. In this single-group cohort study, demographic and prospective outcome data were collected over 4 years, with retrospective evaluation of unscheduled healthcare usage. Of 171 patients included, 97 (56.7%) were male with mean age 75.9 years and 142 (83.0%) had chronic obstructive pulmonary disease. ALDS patients had severely reduced pulmonary function (median (interquartile range (IQR)) forced expiratory volume in 1 s 0.8 (0.6-1.1) L and diffusing capacity of the lung for carbon monoxide 37.5 (29.0-48.0) % pred) and severe breathlessness. All patients received nonpharmacological breathlessness management education and 74 (43.3%) were prescribed morphine for breathlessness (median dose 9 mg·day -1 ). There was a 52.4% reduction in the mean number of emergency department respiratory presentations in the year after ALDS care commenced (p=0.007). 145 patients (84.8%) discussed and/or completed an advance care plan. 61 patients died, of whom only 15 (24.6%) died in an acute hospital bed. While this was a single-group cohort study, integrated respiratory and palliative care was associated with improved end-of-life care and reduced unscheduled healthcare usage., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at openres.ersjournals.com

Floating catalyst chemical vapor deposition uniquely generates aligned carbon nanotube (CNT) textiles with individual CNT lengths magnitudes longer than competing processes, though hindered by impurities and intrinsic/extrinsic defects. We present a photonic-based post-process, particularly suited for these textiles, that selectively removes defective CNTs and other carbons not forming a threshold thermal pathway. In this method, a large diameter laser beam rasters across the surface of a partly aligned CNT textile in air, suspended from its ends. This results in brilliant, localized oxidation, where remaining material is an optically transparent film comprised of few-walled CNTs with profound and unique improvement in microstructure alignment and crystallinity. Raman spectroscopy shows substantial D peak suppression while preserving radial breathing modes. This increases the undoped, specific electrical conductivity at least an order of magnitude to beyond that of single-crystal graphite. Cryogenic conductivity measurements indicate intrinsic transport enhancement, opposed to simply removing nonconductive carbons/residual catalyst.

An electromagnetic transmitter typically consists of individual components such as a waveguide, antenna, power supply, and an oscillator. In this communication we circumvent complications associated with connecting these individual components and instead combine them into a non-traditional, photonic enabled, compact transmitter device for tunable, ultrawide band (UWB) radiation. This device is a centimeter scale, continuous, thin film superconducting ring supporting a persistent super-current. An ultrafast laser pulse (required) illuminates the ring (either at a point or uniformly around the ring) and perturbs the super-current by the de-pairing and recombination of Cooper pairs. This generates a microwave pulse where both ring and laser pulse geometry dictates the radiated spectrum's shape. The transmitting device is self contained and completely isolated from conductive components that are observed to interfere with the generated signal. A rich spectrum is observed that extends beyond 30 GHz (equipment limited) and illustrates the complex super-current dynamics bridging optical, THz, and microwave wavelengths.

A phase hologram was machined on an optical fiber tip using a focused ion beam (FIB) system so that a ring-shaped beam emerges from the fiber tip. The fiber used for this work was a commercial single-mode optical fiber patch cable for a design wavelength of 633 nm with a germanosilicate core. The ring-shaped beam was chosen to ensure a simple geometry in the required phase hologram, though the Gerchberg-Saxton algorithm can be used to calculate a hologram for an arbitrary beam shape. The FIB machining took approximately 45 min at 30 kV and 200 pA. The radius of the resulting ring beam was 0.083 m at 1 m standoff, as compared to 0.1 m as was initially desired. Results suggest that this imaging technique may provide a basis for a beam-shaping method with several advantages over the current commercial solutions, having permanent alignment, compactness, and mechanical robustness. However, it would appear that minimizing the speckle pattern will remain a critical challenge for this technique to become widely implemented.

RbAp46 and RbAp48 (pRB-associated proteins p46 and p48, also known as RBBP7 and RBBP4, respectively) are highly homologous histone chaperones that play key roles in establishing and maintaining chromatin structure. We report here the crystal structure of human RbAp46 bound to histone H4. RbAp46 folds into a seven-bladed beta propeller structure and binds histone H4 in a groove formed between an N-terminal alpha helix and an extended loop inserted into blade six. Surprisingly, histone H4 adopts a different conformation when interacting with RbAp46 than it does in either the nucleosome or in the complex with ASF1, another histone chaperone. Our structural and biochemical results suggest that when a histone H3/H4 dimer (or tetramer) binds to RbAp46 or RbAp48, helix 1 of histone H4 unfolds to interact with the histone chaperone. We discuss the implications of our findings for the assembly and function of RbAp46 and RbAp48 complexes.

As part of our studies of the organization of the cat sacrocaudal spinal cord (S3-Ca7), the portion of the neuraxis that innervates the tail, we have begun to evaluate the behavioral effects of hemisection or complete transection at the level of Ca1. Clinical observations that the tail strongly deviated to the side of a hemisection indicated the presence of an ipsilateral hypertonia. After complete transection of the spinal cord, the tail became ventroflexed in a midline position and exhibited spasticity, i.e., hypertonia, hyperreflexia, and clonus. Bowel and bladder functions and hindlimb gait and reflexes remained intact following either lesion. Quantitative behavioral measures corroborated our clinical observations. With the tail tethered to a force transducer, tail muscle tone was measured after the tail was passively positioned. Following a transection, resistance to dorsiflexion of the tail was greater than resistance to ventroflexion. In addition, tonic deviation of the tail was documented with videotape analysis while cats walked on a plank. Normal cats walked with the tail sharply dorsiflexed and centered. In contrast, the tail deviated ipsilaterally in cats with a hemisection, and the tail was ventroflexed in cats with a transection. These observations indicate that the sacrocaudal spinal cord provides a model with special advantages for investigation of changes in segmental motor functions following spinal cord injury. The effects of lesions on the tail are quantifiable and can resemble that spasticity observed after spinal cord injury in humans. Importantly, minimal effects on locomotive and autonomic functions were observed following hemisection or transection of the sacrocaudal spinal cord.

3-Phosphonoalanine has been made by the Strecker synthesis from phosphonoacetaldehyde, which is easily prepared from vinyl acetate. It gives phosphonopyruvate by transamination when treated with glyoxylate. Phosphonolactate, an analogue of phosphoglycerate, is prepared by reducing phosphonopyruvate. Diazotization of phosphonoalanine was investigated as a route for making phosphonolactate: addition of NaNO2 to the isoelectric form of phosphonoalanine gave much scission of the C-P bond with release of phosphate; addition of HBr prevented this release and gave largely the bromo acid. The supplement reports the synthesis of arsonolactate, a similar analogue, by treating chlorolactate with alkaline arsenite.

Three separate somatic cell fusions were made between Chinese hamster lines and human lymphocytes containing (1) a 3/4 translocation, (2) an X/9 translocation, and (3) a 17/9 translocation. Eleven independently derived hybrids showed that only human chromosome 22 was consistently present when human ACONM was expressed and absent when human ACONM was not expressed. These studies assign a gene for human ACONM to chromosome 22, and are consistent with prior gene-mapping results.

Evaluation of a family in which electrophoretic variants of the eznyme galactose-1-phosphate uridyl transferase (GALT) and 9qh variants occur demonstrates close linkage between these two traits: lod score of 3.67 at theta = 0. Taken with information indicating GALT is on the short arm of chromosome 9, these linkage data suggest that this locus is close to the centromere on the short arm of chromosome 9.

Lymphocytes from a patient with classic galactosemia (GALT deficiency) were hybridized with a Chinese hamster cell line. Electrophoretic valuation of GALT in 31 independently derived interspecific hybrid clones failed to demonstrate expression of the human GALT gene even when human chromosome 9 was present. Possible mechanisms for this lack of expression are presented.

Gene marker analyses have been carried out in a patient with 10q(q23 leads to qter) duplication. The observed elevation of red cell glutamic oxaloacetic transaminase activity is compatible with earlier somatic cell hybridization studies that mapped the locus to this region. Hexokinase-1 activity in the red cells was normal,which is consistent with its prior assignment to the unaffected part of chromosome 10(10pter leads to q23).

A newly developed electrophoretic technique for human galactose-1-phosphate uridyl transferase confirms the multiple band patterns for the Duarte and Los Angeles variants. This represents the first confirmation for the Los Angeles variant. The observed frequencies of N, D, and LA types are similar to earlier reports for these variants.

Rabbit antibodies to purified human placental galactose-1-phosphate uridyltransferase (EC 2.7.7.12) were used to establish immunologic cross-reactivity patterns for the enzyme in hemolysates, prepared from red cells of a normal individual, a homozygous Duarte variant, and a heterozygous Los Angeles variant. The antibody immunoprecipitated all three forms of the enzyme. The amount of antibody absorbed by each hemolysate was related to the different levels of activity, and examination of hemolysate/antibody reaction mixtures by starch gel electrophoresis revealed that the antibody quantitatively precipitated all of the isoenzyme forms that characterize these three genetic variants.

A patient with aniridia and an interstitial deletion of the bands p13-p14 of the short arm of chromosome 11 was studied to determine the relative locations of the gene(s) encoding for the aniridia-Wilms' tumor association with other genes on the same chromosome. Quantitative analysis was performed on the red blood cell enzymes lactic acid dehydrogenase-A (LDH-A) and catalase, the genes for which are located on the short arm of chromosome 11. The activity of LDH-A was normal; the activity of catalase was reduced to approximately half normal. This evidence supports loci for the genes encoding for both catalase and the aniridia-Wilms' tumor association within the bands p13-p14 of the short arm of chromosome 11; the normal activity of LDH-A supports a locus outside this region.

The expression of human esterase D was evaluated quantitatively and qualitatively in five persons with partial deletions or duplications of chromosome 13. The results showed that the locus of this enzyme is at band 13q14. Deletion of this same band in other subjects has been found previously to indicate a predisposition to the development of retinoblastoma, which was present in the four individuals in this study who had partial deletions of chromosome 13. Because of this close synteny, esterase D evaluation should aid in the diagnosis and genetic counseling of retinoblastoma.

Evaluation of three families with hereditary retinoblastoma demonstrates close linkage of the gene for this tumor with the genetic locus for esterase D. These results assign the gene for the hereditary form of retinoblastoma to band q14 on chromosome 13, the same region which is affected in the chromosome deletion form of this eye tumor, and therefore suggest a common underlying mechanism in the pathogenesis of these two forms of retinoblastoma.

A GLO-I "null" allele in a family was indicated by an abnormal segregation pattern and by half normal red cell enzyme activity in carriers. This is the third reported instance of this uncommon allele, and the first with confirmation by quantitation of enzyme activity.

Based upon aberrant segregation of glutamate pyruvate-transaminase (GPT) and reduced enzyme activity on electrophoresis, seven new families with a GPT null allele were identified during genetic linkage analysis for a number of different traits.

Serum cholinesterase (butyrylcholinesterase, EC 3.1.1.8, BChE) is controlled by two genetic loci, CHE1 and CHE2. The CHE1 locus has been mapped to 3q, but the map location of CHE2 is uncertain. In an effort to clarify the location of CHE2, we combined all the published linkage analysis data for CHE2 (as summarized in the Keats Linkage Database) with the data from the UCLA Linkage Database. Exclusions with substantial portions of the genome could be made (notably with portions of chromosomes 1, 2, 3, 4, 6, 7, 8, 9, 14, 16, 18, 19, 20, 22, and LG1). Although not quite statistically significant (zeta = 2.51), loose linkage (theta = 0.32) of CHE2 with the haptoglobin locus on 16q22 was the most likely conclusion from the family data. In addition, calculating the lod score between CHE2 and the available linkage map of chromosome 16 (markers HBA, PGP, FRA16A, and HP) resulted in an overall lod score of 3.2. This result is particularly intriguing given the hybridization of a BChE cDNA (designated CHEL3) to the same region. Resolution of the issue will require more detailed linkage studies of CHE2 on chromosome 16 and a better understanding of the relationship between the CHE1 and CHE2 loci with respect to production of serum cholinesterases.

Twelve information bone marrow transplants, with at least one difference in ABO and/or Lewis types between donor and recipient, were retrospectively studied. ABH and Lewis antigens were determined in plasma, erythrocytes, and lymphocytes. Donor lymphocytes acquired the ABH and Lewis antigens from the recipient's plasma in the same way that donor erythrocytes acquired the Lewis antigens from it. Lymphocytotoxicity detected type 1 ABH and Lewis antigens only, providing evidence for the existence of combined ABH and Lewis antigens on lymphocytes. This was in contrast with the ABH antigens on type 2 chains of red cells, which are devoid of Lewis specificities. The differences in genetic control, probable chemical structure, and cellular origin of these two types of ABH antigens are presented in a theoretical model that accounts for most of the known data.

Although a constitutional chromosomal deletion including 13q14 has been found to date in all retinoblastoma patients whose esterase D activity is 50 percent of normal, one female patient has been found who has 50 percent esterase D activity in all normal cells examined but no deletion of 13q14 at the 550-band level. Therefore, she has the smallest constitutional chromosomal deletion within 13q14 that is associated with susceptibility to retinoblastoma. Two stem lines were identified in a retinoblastoma from this patient, and each one had a missing 13 chromosome. No detectable esterase D activity was found in the tumor, indicating that the normal nondeleted 13 chromosome was lost in both stem lines. Thus the data from this patient not only show that there is a total loss of genetic information at the location of the retinoblastoma gene within the tumor, but also imply that recessive genes may play an important role in the development of certain human tumors including retinoblastoma.

A chromosome 13 deletion in a patient with sporadic retinoblastoma appears to have separated the loci for retinoblastoma and esterase D. This study indicates that: (1) the retinoblastoma locus is distinct from the esterase D locus; and (2) the linear order of these genes is centromere-esterase D-retinoblastoma.

A gene dosage effect was observed for esterase D in a patient with trisomy 13. Isoelectric focusing of hemoglobin from the same patient showed three unidentified bands. A gene dosage effect for several other enzymes was not observed in two other patients with trisomy 13.

A linkage analysis is reported for three branches of a single family segregating for autosomal dominant retinitis pigmentosa. A statistically significant lod score of 3.9 is obtained for the RP locus and AMY2 at a recombination frequency of 1%. This linkage indicates that the RP locus is on the no. 1 chromosome since the AMY2 locus has been placed on the short arm of 1. Lod scores are reported for four other loci on chromosome 1; none of these achieve statistical significance. Analyses are reported for 23 additional autosomal markers and close linkage with RP can be excluded for a number of these.

Electorphoretic and quantitative assays of esterase D in a Caucasian family demonstrate the inheritance of a null allele, which was observed in the heterozygous state in six individuals.

Analogues of dihydroxyacetone phosphate and of 3-phosphoglycerate were made in which the phosphate group, -O-PO(3)H(2), is replaced by the phosphonomethyl group, -CH(2)-PO(3)H(2). The analogue of dihydroxyacetone phosphate is a substrate for aldolase and glycerol 1-phosphate dehydrogenase (Stribling, 1974), but not for triose phosphate isomerase. The analogue of 3-phosphoglycerate oxidizes NADH under the combined action of 3-phosphoglycerate kinase and glyceraldehyde 3-phosphate dehydrogenase if ATP is added. Thus four out of the five glycolytic enzymes tested handle the phosphonomethyl compounds like the natural phosphates.