Tumourigenic non-small-cell lung cancer mesenchymal circulating tumour cells: a clinical case study.

BACKGROUND: Over the past decade, numerous reports describe the generation and increasing utility of non-small-cell lung cancer (NSCLC) patient-derived xenografts (PDX) from tissue biopsies. While PDX have proven useful for genetic profiling and preclinical drug testing, the requirement of a tissue biopsy limits the available patient population, particularly those with advanced oligometastatic disease. Conversely, 'liquid biopsies' such as circulating tumour cells (CTCs) are minimally invasive and easier to obtain. Here, we present a clinical case study of a NSCLC patient with advanced metastatic disease, a never smoker whose primary tumour was EGFR and ALK wild-type. We demonstrate for the first time, tumorigenicity of their CTCs to generate a patient CTC-derived eXplant (CDX). PATIENTS AND METHODS: CTCs were enriched at diagnosis and again 2 months later during disease progression from 10 ml blood from a 48-year-old NSCLC patient and implanted into immunocompromised mice. Resultant tumours were morphologically, immunohistochemically, and genetically compared with the donor patient's diagnostic specimen. Mice were treated with cisplatin and pemetrexed to assess preclinical efficacy of the chemotherapy regimen given to the donor patient. RESULTS: The NSCLC CDX expressed lung lineage markers TTF1 and CK7 and was unresponsive to cisplatin and pemetrexed. Examination of blood samples matched to that used for CDX generation revealed absence of CTCs using the CellSearch EpCAM-dependent platform, whereas size-based CTC enrichment revealed abundant heterogeneous CTCs of which ∼80% were mesenchymal marker vimentin positive. Molecular analysis of the CDX, mesenchymal and epithelial CTCs revealed a common somatic mutation confirming tumour origin and showed CDX RNA and protein profiles consistent with the predominantly mesenchymal phenotype. CONCLUSIONS: This study shows that the absence of NSCLC CTCs detected by CellSearch (EpCAM(+)) does not preclude CDX generation, highlighting epithelial to mesenchymal transition and the functional importance of mesenchymal CTCs in dissemination of this disease.

A rare case report showing direct association between hepatitis B and bulbar palsy.

Bulbar Palsy is B/L impairment of function of cranial N. 9, 10, 11, 12 at lower motor neuron level either at nuclear or fascicular level in medulla or B/L lesion of lower cranial N. outside brainstem. We present case of viral hepatitis who initially presented with classical signs and symptoms of hepatitis B followed by characteristic features of bulbar palsy in form of difficulty in swallowing and slurring of speech reduced gag reflex, weak palatal movement. Other causes for bulbar palsy were excluded and indirect laryngoscopy confirmed presence of bulbar palsy. Patient had no previous neurological abnormality, there are many studies in the past for association of hepatitis B and bulbar palsy but no one confirmed about a direct association between hepatitis B and bulbar palsy. To best of knowledge this is the first case report which shows direct association between hepatitis B and bulbar palsy.

Spontaneous transdiaphragmatic intercostal hernia: a rare clinical entity.

The herniation of abdominal contents through a diaphragmatic and chest wall rent has been uncommonly reported in literature. Also known as a transdiaphragmatic intercostal hernia (TDIH) or intercostal pleuroperitoneal hernia, it occurs when the disruption of diaphragmatic or intercostal muscles leads to an acquired herniation of abdominal contents. It is usually seen to occur following a traumatic incident. We report the case of an elderly male who presented with a reducible lump in the left chest and breathlessness on exertion, in the absence of any trivial or occult trauma, and how this was managed adequately via surgery alone.

Manifestations of cerebral tuberculosis.

Intracranial tuberculosis continues to be a serious problem in both the developing and developed world, with significant morbidity and mortality. It has protean manifestations and at times, poses significant diagnostic challenges to both the radiologist and the treating physician. This pictorial essay aims to acquaint the radiologist with the varied imaging spectrum of intracranial tuberculosis, both the common and uncommon appearances.

High frequency of heterozygosity in GJB2 mutations among patients with non-syndromic hearing loss.

OBJECTIVE: To determine the prevalence of GJB2 mutations among subjects with congenital, non-syndromic, sensorineural hearing loss, within a north Indian population. MATERIALS AND METHODS: This was a case-control study in which the frequencies of the three most prevalent GJB2 mutations (35delG, W24X and 167delT) were studied. Polymerase chain reaction restriction fragment length polymorphism assays were performed to detect these mutations. The entire coding region of the GJB2 gene was sequenced in all patients, and also in any of their family members who showed GJB2 mutations. RESULTS: The 35delG mutation was found to be the most prevalent mutation (21 per cent), followed by the W24X mutation (7 per cent). This is the first report of the 35delG mutation in an Indian population. One patient was a compound heterozygote for 35delG/W24X. The 167delT mutation was not observed in any patient. CONCLUSIONS: These findings challenge the classical view that the W24X variant of the GJB2 gene represents a single 'founder' mutation.

Microscopic optical model calculations of 4He, 12C-nucleus absorption cross sections.

Calculations of absorption cross sections using a microscopic first-order optical potential for heavy-ion scattering are compared with experiments. In-medium nucleon-nucleon (NN) cross sections were used to calculate the two-body scattering amplitude. A medium-modified first-order optical potential was obtained for heavy-ion scattering using the in-medium two-body scattering amplitude. A partial wave expansion of the Lippmann-Schwinger equation in momentum space was used to calculate the absorption cross sections for various systems. The results are presented for the absorption cross sections for 4He-nucleus and 12C-nucleus scattering systems and are compared with the experimental values in the energy range 18-83A MeV. The use of the in-medium NN cross sections is found to result in significant reduction of the free space absorption cross sections in agreement with experiment.

A Green's function method for high charge and energy ion transport.

A heavy-ion transport code using Green's function methods is developed. The low-order perturbation terms exhibiting the greatest energy variation are used as dominant energy-dependent terms, and the higher order collision terms are evaluated using nonperturbative methods. The recently revised NUCFRG database is used to evaluate the solution for comparison with experimental data for 625A MeV 20Ne and 517A MeV 40Ar ion beams. Improved agreements with the attenuation characteristics for neon ions are found, and reasonable agreement is obtained for the transport of argon ions in water.

Space proton transport in one dimension.

An approximate evaluation procedure is derived for a second-order theory of coupled nucleon transport in one dimension. An analytical solution with a simplified interaction model is used to determine quadrature parameters to minimize truncation error. Effects of the improved method on transport solutions with the BRYNTRN data base are evaluated. Comparisons with Monte Carlo benchmarks are given. Using different shield materials, the computational procedure is used to study the physics of space protons. A transition effect occurs in tissue near the shield interface and is most important in shields of high atomic number.

Reaction of sorbic acid in wheat flour doughs: reaction with thiols.

The general characteristics of the reaction between sorbic acid and thiols are reviewed. Cysteine adds to the conjugated diene in position 5 to form the substituted 3-hexenoic acid. This is labile in acid solution, yielding a quantitative amount of sorbic acid. When wheat flour doughs are treated with sorbic acid and heated, a significant amount of the sorbic acid is not recovered on extraction with methanol. The use of acidified methanol leads to a quantitative recovery of the preservation and evidence is presented to suggest that sorbic acid-thiol adducts are formed. This is the first report of 'reversibly bound' sorbic acid in a food.

Momentum transfer in relativistic heavy ion charge-exchange reactions.

Relativistic heavy ion charge-exchange reactions yield fragments (delta Z = +1) whose longitudinal momentum distributions are downshifted by larger values than those associated with the remaining fragments (delta Z = -1, -2, ...). Kinematics alone cannot account for the observed downshifts; therefore, an additional contribution from collision dynamics must be included. In this work, an optical model description of collision momentum transfer is used to estimate the additional dynamical momentum downshift. Good agreement between theoretical estimates and experimental data is obtained.

Optical model description of momentum transfer in relativistic heavy ion collisions.

An optical model description of momentum transfer in relativistic heavy ion collisions, based upon composite particle multiple-scattering theory, is presented. The imaginary component of the complex momentum transfer, which comes from the absorptive part of the optical potential, is shown to be the main contributor to the momentum loss of the projectile. Within the context of the Goldhaber formalism, predictions of fragment momentum distribution observables are made and compared with experimental data. Use of the model as a tool for estimating collision impact parameters is also discussed.

Asymptotic expansions of the hydrogenic radial dipole integral.

A method is presented for an asymptotic expansion of the hydrogenic radial dipole integral for discrete-discrete transitions from initial state n'l' to final state nl. The advantage of this simple method is that it allows all the necessary algebraic manipulations to be done by the computer programming package REDUCE-2. Expansion coefficients up to the coefficient of the l/n17 term are obtained for all initial states with n' < or = 10. However, only the coefficients which are not calculated by Klarsfeld are tabulated in this paper.

Nucleophilic reactions of sorbic acid.

The conjugated dienoic acid structure of sorbic acid renders it susceptible to nucleophilic attack. Nucleophiles known to react with sorbic acid include sulphite ion and amines. These attack the molecule in position 5 and, in the cse of amines, cyclization to form substituted dihydropyridones may follow. Recent investigations show that thiols in general can also add to sorbic acid. Cysteine, for example, reacts slowly with sorbic acid at 80 degrees C and pH 5.5, leading to 5-substituted 3-hexenoic acid. In general, reaction products are difficult to isolate from aqueous reaction mixtures as they are susceptible to acid- and base-catalysed hydrolysis. A synthesis of model compounds may be carried out by reaction of sorbate esters with the appropriate thiol (or its ester if it is an acid) in the presence of the corresponding sodium alkoxide. It is interesting that alkyl thiols give di-adducts with sorbate ester whilst low molecular weight thiols containing an oxygen atom give a monoadduct. The mechanism of this reaction and its implications to the preparation of samples for toxicological evaluation are discussed. The reaction of sorbic acid with nitrite ion is unusual and its mechanism is considered.

Moments of dipole oscillator-strength distribution for the helium sequence.

The moments S(mu) for -6 < or = mu < or = 2 and L(mu) for mu = 0, 1 and 2 are calculated for the helium sequence for atomic numbers Z up to 30 under a screened hydrogenic model. In this model, one describes the atom by single-particle hydrogenic wavefunctions and treats the initial and the final state as characterised by two different effective charge parameters Zi and Zf, respectively. An asymptotic expansion is made of the differential oscillator strength of the screened hydrogenic model. Assuming the value 287.6 for the coefficient of the term epsilon -7/2 for helium atom as given by Salpeter and Zaidi, the parameter Zf is determined for the helium sequence. This approach has resulted in values which are in reasonable agreement with the various moment values of other authors.

Correlations in alpha-alpha scattering and semi-classical optical models.

We show the equivalence of semi-classical solutions to optical model coupled-channel equations derived from Watson's form of the nucleus-nucleus multiple-scattering series to the Glauber multiple-scattering series. A second-order solution to the semi-classical coupled-channel elastic amplitude is shown to be nearly equivalent to a second-order optical-phase-shift approximation to the Glauber amplitude if the densities of all nuclear excited states are approximated by the ground-state density. Using the Jastrow method to model the two-body density we find an average excited-state density to be of negligible importance in the double-scattering region of alpha-alpha scattering.

Screened hydrogenic radial integrals.

The screened hydrogenic radial integral both for discrete-discrete and discrete-continuum transitions is expressed in forms suitable for obtaining closed-form expressions for specific transitions. Two effective charge parameters Zi and Zf, respectively, for the initial state and for the final state are retained in these formulas. As examples, explicit expressions for a few transitions are derived and a method for obtaining a series for a discrete-discrete radial integral, suitable for large final-state principal quantum numbers, is indicated.

Asymptotic screened hydrogenic radial integrals.

The screened hydrogenic radial dipole integral for discrete-discrete transitions from initial state n'l' to final state nl is asymptotically expanded to the lowest order such that the final quantum number n --> infinity. The analytical expression obtained is in terms of confluent hypergeometric functions, and explicit expressions for a few of the specific transitions are derived from them as examples.

Differential oscillator strengths and dipole polarizabilities for transitions of the helium sequence.

The dipole radial integral for an initial discrete 1s state and a final continuum state has been calculated under the screened hydrogenic model. In this model, single-electron hydrogenic wave functions are employed and the initial and the final states are treated by two different effective-charge parameters. Numerical values of differential oscillator strengths for transitions from 1s 21S to the continuum for the helium sequence ions are obtained. Also calculated are the dipole polarizabilities, which are found to be in excellent agreement with the results of other authors.

1s2 1S-1s np 1P transitions of the helium isoelectronic sequence members up to Z = 30.

Radial integrals have been calculated under the one-electron hydrogenic model. Two different values of the effective charge parameter, one for the initial state and the other for the final state, are retained in these formulae. The model is able to reasonably reproduce the existing dipole oscillator strength values with little effort. The dipole oscillator strength values are given for many ions for the first time.

Static multipole polarisabilities and second-order Stark shift in francium.

The multipole polarisability of the ground state of francium is calculated by utilising both the variational technique of Davison and the quantum defect theory underlying the Bates-Damgaard method. This approach is also shown to yield reasonable results for other alkali atoms. Second-order Stark shift for the ground state of francium is presented as a function of field strength for possible future experimental comparison.