Henry H. Mantsch

IR spectroscopy and IR microscopy of human breast tumors, xenografted breast tumors, and breast tumor cell lines

IR spectra of breast tumor cell lines and breast tumor tissues have been measured. IR measurements of tumor cells revealed that approximately 15 cells are necessary to obtain spectra of good signal-to-noise ratio using an IR microspectrometer equipped with a conventional IR thermal source. Comparative studies of human breast tumor cell line suspensions demonstrated that MCF-7 cells and drug-resistant NCI/ADR cells can be differentiated based on their IR spectra. The most striking differences between MCF-7 and NCI/ADR were found in features assigned to CH2 and CH3 stretching vibrations of lipid acyl chains and PO2 stretching vibrations of nucleic acids. To assess the potential of IR spectroscopy for the diagnosis of breast tumor tissues, thin sections of tissue were mapped by FTIR microspectroscopy. The spectra of these maps were analyzed using functional group mapping techniques and cluster analysis, and the output values of the different approaches were then reassembled into IR images of the tissue. A comparison of the IR images with the standard light microscopic images of the corresponding areas suggested that: (i) chemical mapping based on single band intensities is an easy way to detect microscopic fat droplets within tissue; (ii) the comparison of IR images based on band intensities at 1054 and 1339 cm-1 provides information on tissue areas containing tumor cells; (iii) cluster analysis of the spectra is superior to the single band approach and more appropriate for differentiation between tissue types.

Near-infrared Spectroscopy, In Vivo Tissue Analysis by

In vivo near-infrared (NIR) spectroscopy has the potential of becoming an important tool in a number of areas in clinical medicine. Technological developments in photonics that have been spurred on by the communication revolution have set the stage for rapid advancement of optical and NIR spectroscopy based on noninvasive or minimally invasive medical diagnostic techniques. The goal of this article is to review the current capabilities and limitations of in vivo NIR spectroscopy and highlight the impact of these capabilities and limitations in selected areas where NIR spectroscopy is being used to address clinical problems. The optical properties of tissues are briefly reviewed, as are the instrumental methods available to the experimentalist. These properties and methods largely dictate the feasibility of an in vivo spectroscopic diagnostic approach and constrain the scope of problems that can be tackled using optical–NIR spectroscopy. Some of the more successful applications are described, including studies of tissue oxygenation, ischemia, and viability. A number of factors that can confound interpretation of in vivo NIR results are discussed. The number and magnitude of confounding influences that arise in in vivo spectroscopy can be daunting to the experimentalist and may represent the largest barrier in transforming in vivo spectroscopic measurements into clinically meaningful and reliable information. In vivo NIR spectroscopy abounds with opportunity and challenge.

Sequential unfolding events in proteins monitored by 2D correlation analysis of FTIR spectra

The Cro-V55C (cysteine cross-linked) dimer of the λ Cro repressor protein undergoes thermal unfolding in two discrete steps. The secondary structure of the stable equilibrium intermediate exhibits partial unfolding and reorganization at the N-terminal ends while other parts of the structure (some of the β-sheets) remain intact. To test whether the transition from the native to the intermediate state involves sequential events, we used a 2D-IR approach capable of detecting small differences of individual spectral features in response to external factors. The 2D-IR analysis shows that the intermediate state is formed in closely related sequential steps. To interpret the experimental 2D-IR data, 2D correlation plots for single and multiple sequential events were simulated. These plots were compared with the experimental data and translated into structural changes occurring within Cro-V55C. They reveal that the formation of the stable intermediate starts with the unfolding of the short N-terminal β-strand, fo...

Modification of the Extracellular Matrix in the Infarcted Rat Heart Probed by FTIR Spectroscopy

Heart disease remains the leading cause of death in the industrialised world, accounting for 50% of all deaths in North America. Overwhelmingly the most important form of heart disease is ischaemic heart disease (IHD), which usually (90% of cases) takes the form of a myocardial infarction (MI) as a result of artherosclerosis (AS). Fissuring of an AS plaque results in thrombosis, which can cause blockage of the coronary arteries leading to ischaemia. Prolonged ischaemia (20 minutes) leads to irreversible damage to the heart. If the initial ischaemic event is survived, significant modifications of the extracellular matrix (ECM) of the heart become apparent after about 7 days, leading to pronounced scar formation after 6–8 weeks. As the ECM plays an important role in maintaining the mechanical and electrical properties of the heart, modifications of the ECM have pronounced pathological effects, resulting in reduced compliance of the left ventricle and potentially fatal arrhythmias (due to modification of conduction properties of the tissues).

Non-Subjective Diagnosis of Arthritic Disorders by Multivariate Analysis of IR Spectra of Synovial Fluid

Arthritis is the commonest disabling disease in the developed world, the 100 diseases classified as arthritis affecting over 4 million people in Canada alone. Despite the widespread occurrence and associated social and economic costs, arthritis remains difficult to diagnose and stage, in part due to the non-specific nature of many of the symptoms. Current diagnostic methods rely upon X-ray investigations and the experience of a rheumatologist. In addition, clinical laboratory tests are often required. Diagnosis by these methods involves subjectivity, is usually only possible when considerable damage to the joint has already occurred and is costly and time consuming. A non-subjective method for the rapid diagnosis of arthritis would be of great benefit.