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Biomedical subjects

S Mordechai

Publications and source records attributed to S Mordechai.

At least 19 recordsLinked to original sources

Use of FTIR spectroscopy to distinguish between capsular types and capsular quantities in Streptococcus pneumoniae.

Fourier transform infrared (FTIR) spectroscopy has shown remarkable ability in distinguishing between bacterial species and identifying bacterial colony structures, when used in tandem with methods such as cluster analysis, principal component analysis, or linear discriminant analysis. The present work was aimed to evaluate the potential of FTIR-microscopy (FTIR-MSP) to distinguish between different serotypes and capsular quantities of Streptococcus pneumoniae. In general, the results obtained have consistently proven that the spectral information at the region 900-1,185 cm(-1) was sufficient to distinguish between various pneumococcal serotypes. Moreover, the method was able to differentiate between S. pneumoniae phase variants on the basis of their relative carbohydrate content. The unsupervised cluster analysis of the samples showed differences, not only in the carbohydrate content, but also in the region 1,350-1,480 cm(-1), which is dominated by absorptions due to lipids and phospholipids. This approach proved to be useful for the distinction between S. pneumoniae serotypes and between phase variants, which were shown to acquire different pathogenic capacity.

Bacterial Capsules↗

Distinction of cervical cancer biopsies by use of infrared microspectroscopy and probabilistic neural networks.

Fourier-transform infrared spectroscopy has shown alterations of spectral characteristics of cells and tissues as a result of carcinogenesis. The research reported here focuses on the diagnosis of cancer in formalin-fixed biopsied tissue for which immunochemistry is not possible and when PAP-smear results are to be confirmed. The data from two groups of patients (a control group and a group of patients diagnosed with cervical cancer) were analyzed. It was found that the glucose/phosphate ratio decreases (by 23-49%) and the RNA/DNA ratio increases (by 38-150%) in carcinogenic compared with normal tissue. Fourier-transform microspectroscopy was used to examine these tissues. This type of study in larger populations may help to set standards or classes with which to use treated biopsied tissue to predict the possibility of cancer. Probabilistic neural networks and statistical tests as parts of these biopsies predict the possibility of cancer with a high degree of accuracy (> 95%).

Algorithms↗

Protective autoimmunity: interferon-gamma enables microglia to remove glutamate without evoking inflammatory mediators.

Glutamate in excessive amounts is a major contributor to neuronal degeneration, and its removal is attributed mainly to astrocytes. Traumatic injury to the central nervous system (CNS) is often accompanied by disappearance of astrocytes from the lesion site and failure of the remaining cells to withstand the ensuing toxicity. Microglia that repopulate the lesion site are the usual suspects for causing redox imbalance and inflammation and thus further exacerbating the neurotoxicity. However, our group recently demonstrated that early post-injury activation of microglia as antigen-presenting cells correlates with an ability to withstand injurious conditions. Moreover, we found that T cells reactive to CNS-specific self-antigens protected neurons against glutamate toxicity. Here, we show that antigen-specific autoimmune T cells, by tailoring the microglial phenotype, can increase the ability of microglia-enriched cultures to remove glutamate. This T-cell-mediated effect could not be achieved by the potent microglia-activating agent lipopolysaccharide (LPS), but was dose-dependently reproduced by the Th1 cytokine interferon (IFN)-gamma and significantly reduced by neutralizing anti-IFN-gamma antibodies. Under the same conditions, IFN-gamma had no effect on cultured astrocytes. Up-regulation of glutamate uptake induced by IFN-gamma activation was not accompanied by the acute inflammatory response seen in LPS-activated cultures. These findings suggest that T cells or their cytokines can cause microglia to adopt a phenotype that facilitates rather than impairs glutamate clearance, possibly contributing to restoration of homeostasis.

Animals↗

Fourier transform infrared spectroscopy in cancer detection.

The rapid developments in the field of infrared spectroscopy in the past decade have demonstrated a potential for disease diagnosis using noninvasive technologies. Several earlier studies have highlighted the advantage of using infrared spectroscopy both in the near- and mid-infrared regions for diagnostic purposes at clinical levels. The areas of focus have been the distinction of premalignant and malignant cells and tissues from their normal state using specific parameters obtained from Fourier transform infrared spectra, making it a rapid and reagent-free method. While it still requires pilot studies and designed clinical trials to ensure the applicability of such systems for cancer diagnosis, substantial progress has been made in incorporating advances in computational methods into the system to increase the sensitivity of the entire setup, making it an objective and sensitive technique suitable for automation to suit the demands of the medical community. The development of fiber-optics systems for infrared spectroscopy have further opened up new and modern avenues in medical diagnosis at various levels of cells, tissues and organs under laboratory and clinical conditions.

Fiber Optic Technology↗

Virulence of Streptococcus pneumoniae may be determined independently of capsular polysaccharide.

Mice were inoculated intranasally with Streptococcus pneumoniae isolates of serotype 14 with different genetic backgrounds (14R, 14DW) and a capsular switch of 14R, strain 9VR (serotype 9V). Inoculation of the mice with 14R and 9VR resulted in 60% mortality. All the mice survived 14DW inoculation. No differences in lungs' bacterial loads were found 3 h following inoculation. Bacterial clearance of 5 logs was observed 48 h after inoculation with 14DW versus within 1 log 48 h after inoculation with 14R and 9VR. No significant differences in bacterial size or the capsular amount could be found between 14R and 14DW. We conclude that factor(s) in addition to the capsule, contribute to disease outcome.

Animals↗

Detection of abnormal proliferation in histologically 'normal' colonic biopsies using FTIR-microspectroscopy.

BACKGROUND: Abnormal crypt proliferation and development in the colon has been associated with premalignant stages of colon cancer. Conventionally, molecular markers are used to detect abnormal crypt proliferation. METHODS: In the present work, feasibility studies of FTIR-MSP to distinguish between normal and abnormal crypts from colon biopsies that show normal histopathological features have been undertaken. RESULTS: The results indicate that abnormal crypts show deviations in the pattern of absorbance in the Mid IR region along the crypt height when compared with the normal crypts. The crypts could be empirically classified into three groups such as crypts having a normal absorbance pattern for all biochemical components, crypts with abnormal absorbance pattern for some biochemical components and crypts with completely abnormal absorbance pattern along the height for all or most biochemical components studied by FTIR. The utilization of FTIR-MSP is proposed for diagnosis of abnormal metabolism at the molecular level of histologically completely normal-looking crypts, especially from those biopsies that are taken from sites far away from cancer. CONCLUSIONS: This method could give rise to a reduction in false-negative results during examination of biopsies using the conventional histopathological methods. The present method may be complementary to existing methods for precise demarcation of the zone of colostomy prior to colon cancer surgery.

Cell Division↗

Possible common biomarkers from FTIR microspectroscopy of cervical cancer and melanoma.

Detection of malignancy at early stages is crucial in cancer prevention and management. Fourier transform infrared (FTIR) spectroscopy has shown promise as a non-invasive method with diagnostic potential in cancer detection. Studies were conducted with formalin-fixed biopsies of melanoma and cervical cancer by FTIR microspectroscopy (FTIR-MSP) to detect common biomarkers, which occurred in both types of cancer distinguishing them from the respective non-malignant tissues. Both types of cancer are diagnosed on skin surfaces. The spectra were analysed for changes in levels of biomolecules such as RNA, DNA, phosphates and carbohydrate (glycogen). Whereas carbohydrate levels showed a good diagnostic potential for detection of cervical cancer, this was not the case for melanoma. However, variation of the RNA/DNA ratio as measured at I(1121)/I(1020) showed similar trends between non-malignant and malignant tissues in both types of cancer. The ratio was higher for malignant tissues in both types of cancer.

Biomarkers, Tumor↗

Characteristic absorbance of nucleic acids in the Mid-IR region as possible common biomarkers for diagnosis of malignancy.

FTIR spectroscopy has been extensively used to understand the differences between normal and malignant cells and tissues. In the present study, FTIR microspectroscopy was performed on biopsies to evaluate parameters deduced from changes in nucleic acid absorbance monitored at various characteristic wavenumbers in the Mid-IR region. The data showed that there were differences in the spectra of normal and malignant tissues from several organs such as colon, cervix, skin and blood with respect to absorbance due to nucleic acids. Similar results were observed in the case of cell lines that were transformed to induce carcinogenesis. Of the several ratios examined for consistency in differentiating cancer and normal tissues, the I(996 cm(-1))/I(966 cm(-1)) showed promise as a distinguishing parameter and was comparable to the I(1121 cm(-1))/I(1020 cm(-1)) ratio reported in many earlier studies. The absorbance of nucleic acids is presented with an emphasis on the application of FTIR microspectroscopy for diagnosis of malignancy. Our results indicate that usage of nucleic acid absorbance yield statistically significant parameters, which could differentiate normal and cancerous tissues.

Animals↗

Novel methodology for the follow-up of acute lymphoblastic leukemia using FTIR microspectroscopy.

In this report, we present a novel spectroscopic method of follow-up during chemotherapy treatment for B- and T-cell childhood leukemia patients. We isolated peripheral lymphocytes from blood drawn from patients before and after the chemotherapy and collected Microscopic FTIR (FTIR-MC) spectra of the isolated lymphocytes. Our results showed that nucleic acids content decreased in both types of patients. Changes in phospholipids and proteins level could be observed. The overall effects of drugs administered to the patients can be understood at the molecular level using FTIR-MC and these results are expected to stimulate wider applications of spectroscopy in leukemia research.

Adolescent↗

Application of FTIR microscopy for the characterization of malignancy: H-ras transfected murine fibroblasts as an example.

Recently, microscopic FTIR is widely used in the field of biology and medicine. FTIR can detect biomolecular changes in the cells and tissues responsible for various disorders. In this report, we characterize the H-ras transfected fibroblasts and its normal control using microscopic FTIR. The intensity of the normal fibroblasts was higher than that of H-ras transfected fibroblasts. Our studies showed significant differences occur in the concentration of vital metabolites upon transformation. The DNA and carbohydrates level decreased in the transformed cells compared to the controls. A linear correlation could be found between the levels of carbohydrates and phosphate, while the RNA/DNA ratio varied inversely with glucose/phosphate levels.

3T3 Cells↗

Fluorescence spectroscopy for detection of malignancy: H-ras overexpressing fibroblasts as a model.

Autofluorescence from intracellular chromophores upon illumination of cells by monochromatic light has been studied towards the development of novel noninvasive and sensitive technology for the early detection of cancer. To investigate the relationship between biochemical and morphological changes underlying malignant disease and resulting fluorescence spectra, an in vitro model system of a paired normal and malignant murine fibroblasts cell lines, differing in cancer-associated H-ras expression was employed. A comparison of fluorescence excitation and emission spectra of proliferative cells revealed that fluorescence intensity of malignant cells was significantly less than that of normal cells upon excitation at 290 nm. Fluorescence of both cell lines decreased with decreasing cell concentration, but at each concentration, normal cells had higher fluorescence intensity than malignant cells. Similar differences between the cell lines were observed when brought to quiescence or at stationary phase. Results suggested that the chromophore contributing most significantly to these spectra is tryptophan and its moieties in proteins. This model system demonstrates the specific contribution of H-ras to subcellular chromophores, resulting in a significant difference in their autofluorescence intensity, and implies the potential use of the technique for cancer detection. This model system is potent for analysis of the contribution of other oncogenes and their combinations towards spectral detection of cancer.

3T3 Cells↗

FTIR microscopic studies on normal and H-ras oncogene transfected cultured mouse fibroblasts.

Infrared absorption spectra are well known for their sensitivity to composition and three-dimensional structure of biomolecules. The biochemical changes in the sub-cellular levels developing in abnormal cells, including a majority of cancer forms, manifest themselves in different optical signatures, which can be detected by IR spectroscopy. We measured the IR absorption spectra of monolayers of cultured normal and H-ras transfected mouse fibroblasts, using a microscopic Fourier transform IR (micro-FTIR) technique. The absorption of normal cells was found to be higher than the malignant ones in the spectral range 600-3200 cm(-1). The carbohydrate and phosphate contents were higher in normal cells relative to H-ras transfected cells. An increase in the RNA/DNA ratio was observed for H-ras transfected fibroblasts, which correlates with the increased transcriptional activity expected for the cancerous cells. In part, the variation in absorbance between normal and ras transfected fibroblasts may be due to changes in the cell dimensions.

3T3 Cells↗

FT-IR microscopic characterization of normal and malignant human colonic tissues.

Fourier-transform infrared spectroscopy (FT-IR) employs a unique approach to optical diagnosis of tissue pathology based on the characteristic molecular vibrational spectra of the tissue. In this study, we report infrared absorption spectra of formalin fixed, paraffin embedded normal and malignant human colonic tissues from ten different patients. Our method is based on microscopic infrared study (FT-IR-microscopy) of thin tissue specimens in parallel with normal histopathological analysis, which serves as a reference. Our results indicate that the normal colonic tissue has a stronger absorption than the cancerous type over a wide region in all ten cases. The detailed analysis showed that there is a significant decrease in carbohydrate levels, total phosphate and also possibly creatine contents for cancerous tissue in comparison to the controls. Also, RNA/DNA ratio increased in cancerous tissues relative to the normals in all the patients. The results of Linear Discriminant Analysis (LDA) showed that the normal and malignant cells could be identified with about 89% accuracy.

Colon↗

Diamond-shaped optical fiber delivery system.

OBJECTIVE: Physicians who use laser systems are looking for new fiberoptic delivery systems with better performance. We searched for a delivery system with high power and with a tip of high durability that may be reused many times. SUMMARY BACKGROUND DATA: The delivery systems currently found on the market can burn and break easily. The surgeon may either finish the surgery with a damaged delivery system, or have to switch to a new one during surgery, thus increasing the inconvenience and cost of the surgery. METHODS: Distal tips of fibers used with Nd:YAG and diode lasers have been shaped and polished according to their specific function, including excision, vaporization, and coagulation of tissue. RESULTS: We have developed several prototypes of optical fiber delivery systems, and in particular, we have developed a prototype of a delivery system, called the Diamond-Shaped Optical Fiber Delivery System, or Diamond. By making the tip of an optical fiber diamond shaped, we are able to obtain greater mechanical resistance than that of other delivery systems that were tested in our laboratory. In the Colorectal Unit, we applied it in surgical procedures such as perianal fistulectomy, hemorrhoidectomy, and excision of condilomata acuminata and pilonidal cyst and sinuses. During cutting and coagulating, the system performed well with no technical problems. CONCLUSIONS: A new delivery system (Diamond) gave satisfactory performance during surgical operations. Its main component, the diamond-shaped distal end, provided high durability and was reused many times, thus improving the quality of operations and reducing expenses greatly.

Biophysical Phenomena↗