Asymmetric orbital-lattice interactions in ultrathin correlated oxide films.

Using resonant x-ray spectroscopies combined with density functional calculations, we find an asymmetric biaxial strain-induced d-orbital response in ultrathin films of the correlated metal LaNiO3 which are not accessible in the bulk. The sign of the misfit strain governs the stability of an octahedral "breathing" distortion, which, in turn, produces an emergent charge-ordered ground state with an altered ligand-hole density and bond covalency. Control of this new mechanism opens a pathway to rational orbital engineering, providing a platform for artificially designed Mott materials.

Light and heavy chain components of gamma globulins in urines of normal persons and patients with agammaglobulinemia.

A heavy chain component of gammaG-globulins in normal urines has the characteristics of the proteolytic digestion product, Fc-fragment. This fragment is estimated to compose up to 15% of the gamma globulins present in urines. In contrast to urinary light chains, the urinary Fc-like fragment probably represents a catabolic component in normal gammaG-globulin metabolism. The light chains of the urine constitute more than half the total gamma globulin present. The calculated kappa/lambda ratio of light chains averaged 1.9 in ten urines, but the ratio in individual urines varied widely to either side of this figure. In two adult patients with agammaglobulinemia whose sera contained less than one-hundredth the normal gamma globulin levels, the urinary Fc-like fragment was absent, whereas the light chain levels were only one-tenth the average normal level. Treatment with exogenous gamma globulins resulted in normal or near normal Fc-like fragment excretion, whereas light chain excretion was only modestly affected.

Superconductor to Mott insulator transition in YBa2Cu3O7/LaCaMnO3 heterostructures.

The superconductor-to-insulator transition (SIT) induced by means such as external magnetic fields, disorder or spatial confinement is a vivid illustration of a quantum phase transition dramatically affecting the superconducting order parameter. In pursuit of a new realization of the SIT by interfacial charge transfer, we developed extremely thin superlattices composed of high Tc superconductor YBa2Cu3O7 (YBCO) and colossal magnetoresistance ferromagnet La0.67Ca0.33MnO3 (LCMO). By using linearly polarized resonant X-ray absorption spectroscopy and magnetic circular dichroism, combined with hard X-ray photoelectron spectroscopy, we derived a complete picture of the interfacial carrier doping in cuprate and manganite atomic layers, leading to the transition from superconducting to an unusual Mott insulating state emerging with the increase of LCMO layer thickness. In addition, contrary to the common perception that only transition metal ions may respond to the charge transfer process, we found that charge is also actively compensated by rare-earth and alkaline-earth metal ions of the interface. Such deterministic control of Tc by pure electronic doping without any hindering effects of chemical substitution is another promising route to disentangle the role of disorder on the pseudo-gap and charge density wave phases of underdoped cuprates.

Manic-depressive illness among poor urban Hispanics.

Manic-depressive illness is reported to occur infrequently among some racial or ethnic groups and among lower socioeconomic groups. The authors investigated the incidence of manic-depressive illness among a random sample of 90 lower socioeconomic Hispanic patients admitted to the psychiatric inpatient unit of an urban hospital. They made a retrospective diagnosis based on DSM-III criteria and independent of the hospital diagnosis. Ten patients (11%) were diagnosed as manic-depressive--a rate three times the national admission rate. The authors discuss the significance of this finding and its relationship to sociocultural aspects of the Hispanic patient.

Manic-depressive illness among poor urban blacks.

In psychiatric epidemiology it has generally been accepted that manic-depressive illness rarely occurs among blacks and lower socioeconomic groups. The authors conducted a retrospective study to examine the frequency of manic-depressive illness among lower income urban blacks admitted to an acute psychiatric inpatient unit of an urban hospital. The medical records of a random sample of 117 black psychiatric patients were reviewed for determination of manic-depressive illness as well as socioeconomic characteristics. Eighteen subjects (15%) were diagnosed as manic-depressive. The authors present possible explanations for this finding and the ramifications for future investigations.

Rapid cell culture procedure for tissue samples.

Cell culture is an integral part of genetic studies, including cytogenetic, metabolic, and DNA analyses. Standard culture procedures used today involve plating minced tissue explants in dishes and waiting 3 to 4 weeks for adequate growth. We describe a method that utilizes collagenase digestion of tissue biopsies, enabling cell harvest as soon as 3 days after culture initiation; this has been used successfully in our laboratory for cytogenetic and metabolic studies. Culture duration can be controlled by the cell plating density. Although collagenase digestion of tissues is commonly used in cytogenetics laboratories for tumor or chorionic villous dissociation, we have found that few labs have considered using this rapid and efficient procedure for routine tissue samples.

Smith-Lemli-Opitz syndrome in a female with a de novo, balanced translocation involving 7q32: probable disruption of an SLOS gene.

A 3-month-old infant girl had manifestations of the Smith-Lemli-Opitz syndrome (SLOS) including typical positional anomalies of the limbs, apparent Hirschsprung disease, cataracts, ptosis, anteverted nares, cleft of the posterior palate, small tongue, broad maxillary alveolar ridges, and abnormally low serum cholesterol levels. Chromosomal analysis showed a de novo balanced translocation interpreted as 46,XX,t(7;20)(q32.1;q13.2). We hypothesize that the translocation breakpoint in this case interrupts one SLOS allele and that the other allele at the same locus has a more subtle mutation that was inherited from the other parent. This case, as well as cytogenetic observations in other SLOS cases, suggests that SLOS could be due to autosomal recessive mutation at a gene in 7q32.

Incidence of 15q deletions in the Angelman syndrome: a survey of twelve affected persons.

Prometaphase chromosome study of 12 persons with an established diagnosis of the Angelman syndrome demonstrated that 5 had a 15q12 deletion appearing similar to that commonly observed in the Prader-Willi syndrome. Phenotype-karyotype correlation did not show any obvious clinical differences between those with and those without the deletion and no clinical overlap between Angelman and Prader-Willi syndrome was apparent. Our survey suggests that 15q12 deletions are frequent in Angelman syndrome but presence of the deletion does not appear to distinguish different clinical phenotypes. Experience with the cytogenetic study of Prader-Willi syndrome predicts that considerable complexity will emerge between the presence of 15 chromosome abnormalities and clinical expression of Angelman syndrome.

Clinical, cytogenetic, and molecular evidence for an infant with Smith-Magenis syndrome born from a mother having a mosaic 17p11.2p12 deletion.

We describe an infant with del(17) (p11.2p12) whose deleted chromosome was inherited from a mosaic mother. The child had manifestations consistent with Smith-Magenis syndrome. The mother appeared to be of normal intelligence and she had minimal findings of Smith-Magenis syndrome. Separation of chromosome 17 homologues in somatic cell hybrids and molecular studies confirmed the cytogenetic diagnoses and the fact that the mother was mosaic. Furthermore, molecular analysis demonstrated novel breakpoints in this family, with the deletion extending into and completely encompassing the markers duplicated in Charcot-Marie-Tooth (CMT) disease. Although this Smith-Magenis syndrome patient is completely deleted for the CMT region, her electrophysiological findings are different from those found in CMT. This is the only reported case of Smith-Magenis syndrome with transmission from a partially affected mosaic mother. Transmission of interstitial deletions from mosaic parents may be more common than thought; therefore, parental chromosomes should be examined when interstitial deletions are identified.

Preaxial acrofacial dysostosis (Nager syndrome) associated with an inherited and apparently balanced X;9 translocation: prenatal and postnatal late replication studies.

We report on an infant with preaxial acrofacial dysostosis (Nager syndrome) who was diagnosed prenatally as having an apparently balanced X/autosome translocation [46,X,t(X;9)(p22.1;q32)mat] inherited from a previously diagnosed mosaic translocation carrier mother [46,XX/46,X,t(X;9)(p22.1;q32)]. Replication studies on amniocytes showed the normal X chromosome to be late replicating while the same studies repeated on the infant's lymphocytes showed the translocated X chromosome to be late replicating in most cells. Late replication studies of the mother's lymphocytes demonstrated that the normal X chromosome was late replicating in most cells. The presence of Nager syndrome in this infant may be the result of critical breakpoints and/or position effects on chromosome 9, inducing expression of a gene responsible for the syndrome.

Juvenile rheumatoid arthritis in velo-cardio-facial syndrome: coincidence or unusual complication?

We report on two patients with velo-cardio-facial syndrome (VCFS) and juvenile rheumatoid arthritis (JRA). The first, a 9-year-old girl, presented with microcephaly, characteristic face, congenital heart disease, and velopharyngeal insufficiency. Fluorescence in situ hybridization (FISH) study showed deletion of D22S75 (N25), confirming the diagnosis of VCFS. At age 7, she developed joint pain, and polyarticular JRA was diagnosed. Awareness of this case led to the subsequent diagnosis of VCFS (also confirmed by FISH) in another, unrelated 12-year-old girl with characteristic face, hypernasal speech, and obesity. JRA was first diagnosed in this case at age 5 years, and she subsequently developed severe polyarticular disease. Neither patient had clinical or laboratory evidence of immunodeficiency. This observation represents the first report of the association of JRA with VCFS and raises the question of whether this is a coincidental association or a rare complication of this condition.

Maternal origin of 15q11-13 deletions in Angelman syndrome suggests a role for genomic imprinting.

Six persons with the classical Angelman syndrome (AS) phenotype and de novo deletions of chromosome 15q11-q13 were studied to determine the parental origin of the chromosome deletion. Four of the 6 patients had informative cytogenetic studies and all demonstrated maternal inheritance of the deletion. These findings, together with other reported cases of the origin of the chromosome 15 deletion in AS, suggest that deletion of the maternally contributed chromosome leads to the AS phenotype. This contrasts with the Prader-Willi syndrome (PWS) in which a similar deletion of the paternally contributed chromosome 15 is observed. In deletion cases, a parental gamete effect such as genomic imprinting may be the best model to explain why apparently identical 15q11-q13 deletions may develop the different phenotypes of AS or PWS.

Cytogenetic and molecular analysis in Angelman syndrome.

We report on cytogenetic and molecular analyses of 29 Angelman syndrome (AS) individuals ascertained in 1990 through the first National Angelman Syndrome Conference. High resolution GTG- and GBG-banded chromosomes were studied. Standard molecular analysis with six 15q11q13 DNA sequences was used to analyze copy number and parental origin of 15q11q13. Concordance between molecular and cytogenetic data was excellent. The combined data showed that 23 of the 27 probands (85%) on whom we had definitive results have deletions of the chromosome 15q11q13 region. Two classes of deletion were detected molecularly: most patients were deleted for the 5 more proximal probes, but in 2 cases the deletion extended distally to include in sixth probe. In the 13 cases where the parental origin of the deleted chromosome 15 could be established, it was maternal. There were no cases of uniparental disomy. Cytological observations of the relative sizes of the heterochromatic regions of the short arm of chromosome 15 suggested that chromosomes with large heterochromatic blocks may be more prone to de novo deletion.

Prevalence of 22q11 region deletions in patients with velopharyngeal insufficiency.

Velo-cardio-facial syndrome, DiGeorge syndrome, conotruncal anomaly face syndrome, tetralogy of Fallot, and pulmonary atresia with ventricular septal defect are all associated with hemizygosity of 22q11. While the prevalence of the deletions in these phenotypes has been studied, the frequency of deletions in patients presenting with velopharyngeal insufficiency (VPI) is unknown. We performed fluorescence in situ hybridization for locus D22S75 within the 22q11 region on 23 patients with VPI (age range 5-42 years) followed in the Craniofacial Clinic at the University of Florida. The VPI occurred either as a condition of unknown cause (n=16) or as a condition remaining following primary cleft palate surgery (n=7). Six of sixteen patients with VPI of unknown cause and one of seven with VPI following surgery had a deletion in the region. This study documents a high frequency of 22q11 deletions in those presenting with VPI unrelated to overt cleft palate surgery and suggests that deletion testing should be considered in patients with VPI.

Relationship between CO and transit times for dye and thermal indicators in central circulation.

We investigated two factors that may influence the estimation of lung water by the thermal-dye double-indicator-dilution method: 1) changes in cardiac output (CO), and 2) thermal equilibration with cardiac tissue. In theory, the difference between mean transit times of thermal and dye indicators (delta MTT) is proportional to the extravascular volume of distribution of the thermal indicator (VODev) and inversely related to CO. The delta MTT also includes a time element DT due to the difference in response times of the measuring instruments such that delta MTT = VODev/CO + DT. In nine anesthetized dogs we recorded 286 aortic thermal and dye curves following left atrial (LA) and right atrial (RA) injections as CO was increased from 2.35 to 6.65 ml X s-1 X kg-1 by isoproterenol infusion, and a regression of delta MTT on CO-1 was performed. DT was measured in vitro for comparison with the y-intercept. In six of nine dogs the slope of the regression for LA injections was not different from zero, indicating that there is no measurable volume of distribution for thermal indicator in cardiac tissue. For RA injections the relationship between delta MTT and CO-1 was linear in all experiments, with an average correlation coefficient of 0.97 +/- 0.01 (SE), indicating that the VODev was constant over a threefold increase in CO. Although the in vitro measurement of DT agreed closely with the average of the y-intercepts of the regressions, small between-subject differences in DT can lead to apparent flow-related changes in extravascular thermal volume computed in the conventional fashion using the in vitro estimate of DT.

Effect of PEEP and type of injury on thermal-dye estimation of pulmonary edema.

We investigated the effect of positive end-expiratory pressure (PEEP) on the extravascular thermal volume of the lung (ETV) determined by the thermal-dye technique in three canine models of pulmonary edema created by injection of alpha-naphthylthiourea (ANTU) or oleic acid (OA) into the pulmonary circulation or intrabronchial instillation of hydrochloric acid (HCl). ETV was determined before, during, and after ventilation with 14 cmH2O PEEP, and final ETV was compared with the extravascular lung mass (ELM) determined postmortem. Final ETV correctly estimated ELM in 12 animals with ANTU injury, ETV/ELM = 1.04 +/- 0.13, but underestimated after HCl injury (n = 5), ETV/ELM = 0.61 +/- 0.23, and OA injury (n = 6), ETV/ELM = 0.73 +/- 0.19. Whereas PEEP had no consistent effect on extravascular thermal volume in ANTU edema, there was a reversible increase in ETV during PEEP in animals with HCl or OA injury and underestimation of ELM. The increase in ETV during PEEP averaged 9.3 +/- 3.8 ml/kg (62 +/- 42%) over the mean of the pre- and post-PEEP values after HCl injury (P less than 0.01) and 6.7 +/- 4.4 ml/kg (47 +/- 35%) after OA injury (P less than 0.02). There was an inverse correlation between the change in ETV during PEEP and the ETV/ELM ratio for animals with HCl and OA injury (r = -0.94). We conclude that PEEP produces a reversible increase in ETV in some models of lung injury by allowing for distribution of thermal indicator through a larger fraction of the lung water and that this response may be useful to detect underestimation when gravimetric measurements are not available.

Perfusion distribution and lung thermal volume in canine hydrochloric acid aspiration.

We investigated the effects of a brief period of positive end-expiratory pressure (PEEP) ventilation or nitroglycerin (NTG) infusion on the distribution of pulmonary blood flow and extravascular thermal volume (ETV) in anesthetized dogs with unilateral HCl lung injury. ETV was determined by the thermal dye technique by use of a monoexponential extrapolation to exclude recirculating indicator, and regional blood flow was determined by a particle distribution technique (radiolabeled plastic microspheres). The lungs were weighted after the animals were killed, and extravascular lung mass (ELM) was determined with the use of hemoglobin to correct for trapped lung blood. Measurements were obtained before instillation of HCl into the right lung and repeated 3 h later before, during, and after PEEP ventilation or NTG infusion. Fractional perfusion of the severely injured portion of the right lung (Qinj/QT) fell from 44.3 +/- 11.1% at base line to 27.8 +/- 15.4% after the onset of lung injury. PEEP produced an acute reversible increase in ETV (63 +/- 37% over average of pre- and post-PEEP values), and the changes in ETV were closely correlated with changes in Qinj/QT (r = 0.91). NTG infusion produced insignificant increases in ETV (14 +/- 10% over average of pre- and postinfusion values) and Qinj/QT (59 +/- 35%), but the changes in ETV and Qinj/QT were strongly correlated (r = 0.92). The fraction of extravascular lung mass detected by the thermodilution measurement averaged 0.44 (range 0.24-0.77).(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous expression of fra(11)(q23) in a patient with Ewing's sarcoma and t(11;22)(q23;q11).

Cytogenetic analysis of a Ewing's sarcoma revealed a 46,XX,t(8;18)(q11;q21.3), t(11;22)(q23-24;q11-12) chromosome pattern. Observation of t(11;22) is consistent with other reported cases of Ewing's sarcoma. One breakpoint in this translocation, 11q23, coincides with the location of a folate-sensitive fragile site. Examination of peripheral blood leukocyte chromosomes from the patient revealed a 46,XX chromosome pattern with spontaneous, fluorodeoxyuridine-, and Bactrim-induced expression of fra(11)(q23). This may be the first demonstration of constitutional fra(11)(q23) expression in a patient with a neoplasm that exhibits a chromosome rearrangement involving this breakpoint and the first observation of spontaneous expression of this fragile site. These results provide a basis for discussion of the relationship between fragile sites and chromosome rearrangements.

Fluorescence in situ hybridization assessment of the telomeric regions of jumping translocations in a case of aggressive B-cell non-Hodgkin lymphoma.

We report a jumping translocation involving a donor chromosome 1 long arm in a case of aggressive B-cell non-Hodgkin lymphoma (NHL). Conventional cytogenetic banding studies demonstrated a breakpoint distal to the heterochromatic region of the donor 1q chromosome. Characterization by fluorescence in situ hybridization (FISH) of the jumping translocation demonstrated an apparent telomeric sequence loss of the recipient chromosomes. Additional cytogenetic aberrations, including the t(18;22) translocation associated with non-Hodgkin lymphoma, were also observed in this case. Cytogenetically similar cases of jumping translocations reported in the literature have implicated a preferential involvement of the donor chromosomes' heterochromatic regions and the telomeric regions of the recipient chromosomes. Jumping translocations are still considered rare and their appearance is associated with a poor prognosis. The presence of these specific findings for this case are discussed and compared with those previously reported in other hematologic disorders.

Thermodilution measurement of lung water.

The detection and measurement of pulmonary edema by the thermal-dye method appears to be accurate and reproducible under specified laboratory conditions. The ETV, which represents the difference in distribution volumes of the diffusible (thermal) indicator and the intravascular (green dye) indicator, should closely estimate the ELM (ETV = 0.984 ELM). Experimental measurements of ETV have shown a very good correlation with ELM, with a tendency for overestimation in normal lungs and underestimation in severely edematous lungs. In contrast to previous measurements using isotopic water methods, thermal-dye measurements have revealed that the estimation of ELM by ETV in severe edema (alveolar flooding) does not plateau. The limitations of the thermal-dye technique reflect the evenness of lung perfusion. Depending on their size and number, emboli produce perfusion defects and reduce ETV. Airway injury also reduces ETV, apparently by redistribution of blood flow. Alterations of ETV by hemodynamic factors suggest that reduction in perfusion pressure may be more significant than changes in flow, although more data are needed. Atelectasis without a reduction in blood flow does not decrease ETV. PEEP may increase ETV when lung injury is not uniform, perhaps by redistributing blood flow, and this maneuver may be useful in detecting underestimation of ELM. Position of the thermistor produces the greatest degree of variability by distorting the thermodilution curve and prolonging the MTT. This results in an increased ETV and an overestimation of ELM. In laboratory studies, the measurements of ETV can be validated by gravimetric analyses of lung water. Since this method of validation is not possible in clinical studies, measurements of ETV in patients must be interpreted in light of limitations demonstrated in the laboratory. Suggestions for avoiding the most common errors in measuring ETV are listed in Table 3.