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PubMed2004

[Fundamental study of magnetization transfer contrast (MTC) effect: optimization of MT pulse condition using experimental phantom].

Magnetization transfer contrast (MTC) was evaluated by changing the off-set frequency and pulse intensity of MTC with the spoiled gradient echo (SPGR) sequence (T2*-weighted image) using an experimental phantom that included olive oil, protein, fiber, collagen, and pure water. The intensity of pure water reached a constant level just above the off-set frequency (1200 Hz) regardless of MT pulse power. The contrast-to-noise ratio (CNR) in each of the phantom materials was maximal at the MT pulse power of 2500 degrees (equivalent flip angle). The CNR and image noise obtained by body coil were inferior to those obtained with an extremity coil. In clinical application, the MTC effect on chondrosarcoma was higher (MT ratio, ROI-1:0.448, ROI-2:0.382) than those of other cases in this study. Since the image contrast was improved between the malignant fibrous histiocytoma (MFH, MT ratio, ROI-1:0.282, ROI-2:0.289) and peripheral tissues, extraskeletal extension could be observed more easily than without MTC imaging. In conclusion, the effects of MTC might be in providing useful information, in presuming composed tissues, differential diagnoses, and extent to the surrounding structures because of changing the image contrast to surrounding tissues corresponding to the rate of included bound water.

Bone Neoplasms↗
PubMed2000

Medullary thyroid carcinoma (MTC)--clinical and molecular aspects on the basis of own experience.

In our clinic 19615 patients were operated over 25 years on for goiter. Malignant thyroid neoplasms were found in 1049 (5.3%) patients including 875 (83.4%) women and 174 (16.6%) men. Sixty two adult patients (42 women and 20 men were operated on for medullary thyroid carcinoma (MTC). Thyroid cancer was diagnosed in this group pre or intraoperatively in 44 (71%) patients and postoperatively, on histologic examination, in 18 (29%) patients. These patients were reoperated. Radical operations (total thyroidectomy with regional lymph node removal) were conducted in 43 (69.3%) patients and palliative ones in 19 (30.7%) patients. After MTC surgery, MEN 2A (MTC and an adrenal tumor) were diagnosed by means of imaging techniques (USG, CT) in 6 (9.7%) patients. All adrenal tumors were unilateral. Five of these patients were operated, and pheochromocytoma was confirmed by histopathologic examination. Two years after the MTC operation, 1 women was lost to follow-up. After a year, she was admitted to hospital for severe hypertension and died of cerebral hemorrhagia. Pheochromocytoma was revealed by autopsy. All patients were treated complementarily after the MTC operation. Different combinations of teleradiotherapy, chemotherapy and substitutive doses of levothyroxine were used. Ten (23.2%) of 43 patients operated radically were reoperated 1-3 years after the first operation due to loco-regional tumor recurrence. Radical reoperations were performed in 4 patients, and palliative ones in 6. Over a 0.5-23-year follow-up period, 26 (41.9%) patients died, including 20 of cancer, and 6 of other reasons. Four out of 36 living patients have clinical or biochemical symptoms of neoplastic disease. The follow-up period of MEN 2 patients operated on ranged from 1 to 6 years. Up to now, no tumor in the second adrenal gland has been diagnosed in any of these patients. Genetic (molecular) tests performed in 31 out of 36 living patients revealed mutations of RET gene in 4 (12.9%).

Adrenal Gland Neoplasms↗
PubMed1996

Distinction between sporadic and hereditary medullary thyroid carcinoma (MTC) by mutation analysis of the RET proto-oncogene. "Study Group Multiple Endocrine Neoplasia Austria (SMENA)".

Germline and somatic mutations of the RET proto-oncogene are important pathogenetic factors in hereditary and sporadic forms of medullary thyroid carcinoma (MTC). We have therefore analysed exons 10, 11, 13, 14 and 16 of this gene in 85 individuals from 16 Austrian families who, according to clinical criteria, were at risk of suffering from hereditary forms of MTC. We found mutations (codons 620,634 and 804) in the germline of 3 families with familial medullary thyroid carcinoma (FMTC), of 5 with multiple endocrine neoplasia type 2A (MEN 2A; codon 634) and of 2 with multiple endocrine neoplasia type 2B (MEN 2B; codon 918). The codon 804 mutation in one FMTC family led to the substitution of Val (GTG) for Met (ATG) and has not been reported previously. Within these 10 families, 32 carriers and 32 non-carriers were identified. Somatic mutations in the tumors of 3 other families suggested a sporadic origin of the neoplasms. In the remaining 3 families, no mutations were identified. Fifty-nine individuals with an apparently sporadic MTC lacked germline mutations in the RET gene, whereas 7 of 24 available tumors (29%) contained a somatic mutation in codon 918. Our findings provide further evidence that molecular genetic evaluation of hereditary and sporadic forms of MTC is a necessary prerequisite for counselling and management of patients and their families.

Adult↗
PubMed1997

Apparent diffusion coefficient (ADC) and magnetization transfer contrast (MTC) mapping of experimental brain tumor.

Brain tumor tissue contains different pathological areas, such as tumor cell rich parts, necrotic tissues, and cyst. Furthermore, both neovascularization and edema formation progress along with the tumor progression. In this study we employed diffusion weighted (DW) and magnetization transfer contrast (MTC) imaging to chronologically investigate the biological characteristics of a rat glioma. RG-2 glioma cells were implanted stereotactically into the right hemisphere of male Wistar rats. MR images were taken 1, 2 and 3 weeks after inoculation. Apparent diffusion coefficient (ADC) and MTC values were calculated as follows; ADC = -ln (SI-DW/SI-T2)/1096, MTC = 1-SI-MTon/SI-MToff. Each mapping image was made based on the calculated average values of four pixels. The spatial signal changes and the real values were compared to the histological findings. The apparent increase of ADC was noted in the parenchyma adjacent to tumor suggesting the progression of edema. The tumor itself had similar or slightly increased ADC. Cystic and necrotic components appeared 2 weeks after implantation and they showed significantly higher ADC than those calculated in the contralateral putamen. On the other hand, MTC was slightly decreased in the parenchyma adjacent to the tumor, markedly within the tumor, and maximally in the cystic and necrotic area suggesting accumulation of macromolecules such as growth factors, cytokines, and serum albumin.

Animals↗
PubMed1994

Somatic and MEN 2A de novo mutations identified in the RET proto-oncogene by screening of sporadic MTC:s.

Since germline mutations in the RET proto-oncogene (RET) predisposing to tumor development in Familial Medullary Thyroid Carcinoma (FMTC), Multiple endocrine neoplasia type 2A (MEN 2A), and Multiple endocrine neoplasia type 2B (MEN 2B) were reported, it has become possible to identify gene carriers with a very high degree of accuracy. Mutations in FMTC and MEN 2A exclusively affect cysteine residues in exon 10 and 11 of RET, whereas in MEN 2B codon 918 in exon 16 is involved. This latter mutation has also been described in a subset of apparently sporadic medullary thyroid carcinomas (MTC). Mutations in MEN 2B often occur as de novo germline mutations, whereas de novo mutations have not yet been described in FMTC or MEN 2A. We analyzed ten MTC:s and ten pheochromocytomas, all clinically judged to be sporadically occurring, by direct DNA sequencing of exons 10, 11, and 16 of RET. This analysis revealed a de novo germline mutation of codon 634 in exon 11 in a patient with MTC. In addition, somatic mutations of codon 918 in exon 16 in six of the remaining MTC:s were found. Interestingly, the presence of this somatic mutation was associated with a significantly less favorable clinical outcome.

Adult↗
PubMed1990

The mutation for medullary thyroid carcinoma with parathyroid tumors (MTC with PTs) is closely linked to the centromeric region of chromosome 10.

Two new morphs (F and G) detected by the centromeric alpha satellite probe p alpha 10RP8 and D10Z1 in HinfI digests are linked to the PstI polymorphisms of D10Z1, confirming their chromosome 10 location. The F and G morphs were in strong linkage disequilibrium with each other but were in weak linkage disequilibrium with the A and B morphs defined in PstI digests. Data for haplotypes formed by using the A and F morphs improved the lod score for linkage between the disease locus for multiple endocrine neoplasia type 2A (MEN2A) and D10Z1 (Z = 14.06 at theta = 0) in the six large families studied by Wu et al. Furthermore, the locus that codes for a distinct phenotype, medullary thyroid carcinoma (MTC) with parathyroid tumors (PTs) and no pheochromocytomas (PHEOs) (referred to as MTC with PTs), in one of the families was closely linked to two markers, D10Z1 and RBP3, with lodscores of 2.86 and 3.54, respectively, at theta = 0. A possible allelic association was noted between disease phenotypes and centromeric haplotypes. The phenotype MTC and PHEOs with and without PTs was associated with the same relatively common centromeric haplotype (A + B-F-G-) in the four families in which all four morphs could be determined, while the phenotype MTC with PTs was associated with the rare centromeric haplotype (A-B-F-G+) in one family.

Adrenal Gland Neoplasms↗
PubMed1995

[Long-term survival in two cases of multiple liver metastasis successfully treated with intraoperative ultrasound-guided microwave tumor coagulation (MTC)].

Since April 1990, multiple metastatic liver tumors have been treated with intraoperative ultrasound-guided microwave tumor coagulation (MTC) in combination with postoperative intraarterial chemotherapy. Twenty-four patients have been enrolled in this therapeutic modality and two of five patients treated in 1990 achieved long-term survival. In case 1, a 67-year-old woman was diagnosed as bearing gastric leiomyosarcoma with multiple liver metastasis. Total gastrectomy was performed, and six hepatic lesions were treated by MTC along with implantation of an intraarterial reservoir. Postoperative intraarterial chemotherapy was administered in a selective or subselective manner. Her survival time was 4 years and 6 months. In case 2, a 47-year-old man was diagnosed as having liver metastasis from descending colon cancer 1 year and 5 months after left hemicolectomy. When he was laparotomized for the treatment of adhesive ileus, three metastatic liver tumors were treated with MTC. Afterward, he underwent hepatic resection, intraarterial and intraportal chemotherapy. He survived for 5 years and 5 months after being diagnosed with liver metastasis. MTC is one of the useful modalities for the treatment of multiple liver metastasis.

Aged↗
PubMed1994

[A comparable study of microwave tissue coagulation (MTC) and CO2 laser in treatment of cervical erosion].

In a randomized study, 300 patients with cervical erosion were allocated to either MTC(154) or CO2 Laser(146). The patients were treated on an outpatient basis without anesthesia. In the case of initial treatment failure the same method was to be used for retreatment. All the patients were followed-up for an average of 11 weeks (8-12). 142 of 154 microwave-coagulated patients (92.20%) and 116 of 146 Laser-evaporated patients (79.45%) were cured after one treatment, and there was significant difference between MTC and Laser group (P < 0.005). Bleeding during operation occurred in 5 of 154 MTC group (3.25%) and 32 of 146 Laser group (21.92) (P < 0.005). The result suggested that MTC had higher cure rate and less complications. It is easy to handle, safe and economic.

Adult↗
PubMed1997

[Unruptured intracranial aneurysms: evaluation with high-resolution MR angiography with magnetization transfer contrast (MTC) and tilted optimized nonsaturating excitation (TONE)].

Forty-one patients with suspected intracranial aneurysms were evaluated by conventional three-dimensional (3D) time-of-flight (TOF) MR angiography (MRA) or high-resolution 3D TOF MRA with magnetization transfer contrast (MTC) and tilted optimized nonsaturating excitation (TONE). Correlative study was done with conventional angiography in all patients. 3D TOF MRA detected 30 of 36 aneurysms depicted at conventional angiography. The overall rate of sensitivity for the detection of aneurysms was 83%. Unruptured aneurysms were unlikely to occur in the anterior communicating artery (3%), but were frequently found at the bifurcation of the middle cerebral artery (33%). Conventional MRA showed 7 of 9 aneurysms demonstrated at catheter angiography. The rate of sensitivity of conventional MRA for aneurysms smaller than 5 mm and greater than or equal to 5 mm were 0% and 100%, respectively. High resolution MRA with MTC and TONE demonstrated 23 of 27 aneurysms detected by catheter angiography. Sensitivities of high resolution MRA with MTC and TONE for aneurysms smaller than 5 mm and greater than or equal to 5 mm were 71% and 100%, respectively. Our results indicate that high-resolution 3D TOF MRA with MTC and TONE can provide precise, accurate depiction of intracranial aneurysms larger than or equal to 5 mm.

Adult↗
PubMed1991

Investigation of cerebral ischemia using magnetization transfer contrast (MTC) MR imaging.

The effects of cerebral ischemia in rat brain were monitored as a function of time using proton MR imaging. Spin-spin relaxation time (T2), proton density, and magnetization transfer contrast (MTC) were measured by MR imaging at various time intervals during a 1-week period following the induction of ischemic damage. Ischemic injury was characterized by a maximization of both T2 value and MTC appearance at 24 hr postischemic injury. These changes were accompanied by a gradual increase in MR observable water density over the first few days of ischemia. A reduction in the magnetization exchange rate between "free" and "bound" water protons as measured by MTC imaging is at least partially responsible for the elevation in T2 values observed during ischemia, and may accompany breakdown of cellular structure.

Animals↗
PubMed2003

Degradation of (+)-catechin by Acinetobacter calcoaceticus MTC 127.

Acinetobacter calcoaceticus MTC 127 was able to grow on catechin and protocatechuic acid (PCA) as sole carbon source. Cells induced with catechin oxidized catechin and PCA at rates higher than cells of uninduced cultures. Two aromatic compounds, PCA and phloroglucinol carboxylic acid (PGCA) were isolated from culture filtrate of cells grown in catechin and characterized by infrared spectrometry and high performance thin-layer chromatography. Moreover, A. calcoaceticus MTC 127 produced high levels of PCA compared to PGCA in the degradation of catechin. Based upon these results, a pathway for the degradation of (+)-catechin in A. calcoaceticus MTC 127 is proposed. Enzymes extracted from catechin-induced culture showed catechin oxygenase (cox) and protocatechuate 3,4-dioxygenase (pcd) activities. Catechin oxygenase was purified by column chromatography and SDS-PAGE analysis showed a single band with an apparent molecular weight of 47 kDa.

Acinetobacter calcoaceticus↗
PubMed1999

[The quantification of the magnetization transfer contrast (MTC) effect by calculating MT quotients: does it yield additional information for the differentiation of benign and malignant diseases of the locomotor apparatus?].

PURPOSE: To investigate the potential information of the amount of magnetization-transfer effect in musculoskeletal lesions and to compare MT ratios from benign and malignant musculoskeletal lesions. MATERIAL AND METHOD: 49 patients with malignant tumors (3 osteosarcoma, 3 malignant fibrous histiocytoma, 4 chondrosarcoma, 2 Ewing sarcomas) and benign lesions (8 chondroma, 2 fibrous dysplasia, 3 osteoid-osteoma, 6 ganglion cyst, 3 cyst, 3 osteomyelitis, 4 tendinitis, 3 rotator cuff tear, 5 scar tissue) were scanned using routine MRI protocols including T1- and T2-weighted spin echo as well as T2*-weighted gradient echo (FFE) sequences at 1.5 Tesla (ACS II, Philips Medical). Additionally MTC images were generated by combining the FFE sequence and the off-resonance MT technique (-1500 Hz off-resonance frequency, 1770 degrees flip angle and 50 ms pulse duration). MT ratios were calculated as Slo-Slm/Slo. RESULTS: The MT ratio of benign lesions was 26 +/- 15%, that of malignant lesions was 22 +/- 6%. The difference was statistically not significant. As expected muscle showed a high MT ratio of 50 +/- 8%. Scar tissue demonstrated an MT ratio of 39 +/- 16% which was significantly higher than the tumor MT ratios. CONCLUSION: MTC (MT ratios) failed to show significant differences between benign and malignant lesions as was expected due to basic differences in cellularity, rate of mitosis and chromatin content. MTC might however gain more importance in separating scar tissue from recurrent tumor in the future.

Adolescent↗
PubMed2001

A large family with hereditary MTC: role of RET genetic analysis in differential diagnosis between MEN 2A and FMTC.

Germline mutations of the RET proto-oncogene cause three different cancer syndromes: multiple endocrine neoplasia type 2A (MEN 2A), multiple endocrine neoplasia type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). In the absence of biochemical and/or clinical evidence of pheochromocytoma and hyperparathyroidism, patients with MEN 2A disease display the same phenotype of FMTC disease, although prognosis and clinical management in both affected and unaffected familial members are quite different. We studied a family with hereditary MTC, whose proband was referred to us because of enlarged cervical nodes and increased calcitonin serum levels 28 years after the total thyroidectomy for MTC. Cervical node dissection was carried out and subsequently the presence of MTC metastasis was histologically confirmed. A RET genomic mutation at codon 634 (TGC-->TTC) was identified in the proband and in seven out of 19 familial members studied. Accordingly, a hereditary disease was suggested. However, the strong association of RET mutation at codon 634 with the presence of pheochromocytoma in MEN 2 disease suggested a more rigorous management in all gene carriers. Indeed, during the follow-up pheochromocytoma was subsequently identified in the proband. This finding suggests that all families with a pedigree suggestive of FMTC should be regarded at risk from MEN 2A disease, at least when a critical mutation in the RET cysteine domain is detected.

Adolescent↗
PubMed2004

Comparison of (99)mTc-methoxyisobutylisonitrile myocardial single-photon emission computed tomography and electron beam computed tomography for detecting coronary artery disease in patients with no myocardial infarction.

BACKGROUND: Previous studies have compared single-photon emission computed tomography (SPECT) and electron beam computed tomography (EBCT) in detection of coronary artery disease (CAD) in patients with myocardial infarction (MI). The purpose of this study was to compare SPECT with EBCT in detection of CAD in patients with no MI. METHODS: One hundred and forty-seven patients with suspected CAD underwent stress-rest (99)mTc-methoxyisobutylisonitrile ((99)mTc-MIBI) myocardial SPECT, cardiac EBCT and coronary angiography (CAG) within one month. Of them, 73 patients (aged 52.6 +/- 10.6 years old) with no history of MI were included in this study. Coronary artery calcium (CAC) was defined as a CT value >or= 130 HU within the boundary of coronary artery on EBCT. RESULTS: There were 35 and 38 patients with or without CAD according to CAG. Ninety-six percent of the patients with abnormal SPECT and CAC had a coronary arteries stenosis >or= 50%, and 90.9% patients with normal SPECT and EBCT showed no CAD. The sensitivity of SPECT and EBCT in detection of CAD was comparable, and the specificity of SPECT (92.1%) was significantly higher than that of EBCT (55.3%) (P < 0.005). For the detection of individual coronary artery stenosis, both sensitivity and specificity of SPECT (75.0% and 93.7%) were significantly higher than those of EBCT (53.3% and 76.7%) (P < 0.025 and P < 0.005, respectively). In patients without chest pain, the sensitivity and specificity of SPECT (76.9% and 91.4%) were significantly higher than those of EBCT (23.1% and 69.0%) in detection of a coronary artery stenosis of >or= 50% (P < 0.01 and P < 0.005, respectively). However, in patients with chest pain, both sensitivity and specificity of SPECT were comparable to those of EBCT. In patients or= 50% (P < 0.005), and the specificity of SPECT was comparable to that of EBCT. In patients > 45 years old, the specificity of SPECT (94.3%) was significantly higher than that of EBCT (70.5%) (P < 0.005), and the sensitivity of SPECT was comparable to that of EBCT. CONCLUSION: (99)mTc-MIBI myocardial perfusion SPECT has higher accuracy than that of EBCT in detection of CAD in patients without MI.

Adult↗
PubMed2005

RET mutation status in medullary thyroid cancer(MTC) patients and the significance of genetic screening for mutations in their immediate relatives--a preliminary report.

Multiple Endocrine Neoplasia (MEN) 2A is an inherited disease characterized by the development of medullary thyroid carcinoma (MTC), pheochromocytoma(PHCH) and hyperparathyroidism(HPT). It has recently been shown to be associated with germline mutations in the RET proto-oncogene. Genetic testing for RET mutations will, therefore allow the identification of people with asymptomatic MEN 2 who can be offered prophylactic thyroidectomy and biochemical screening as preventive measures. No genetic study based on RET mutation detection has been available in India so far. The aim of the present study is to detect the proportion of MTC cases having inherited germline or somatic RET mutations and to identify family members at risk for MEN and, thereby the feasibility of screening for MEN. DNA extracted from the peripheral blood and somatic (tumor) tissues were subjected to PCR using primers for exons 10,11 and 16. A few samples were subjected to direct sequencing. Germline mutations were identified in 3 of 4 MEN 2A patients, 18 of 24 sporadic MTC(SMTC), 2 of 4 children of MEN2A and 8 relatives of SMTC. Common mutation was in exon 10 and 11 (c634). It is recommended that RET mutation analysis and counseling of patients and their immediate relatives be introduced on a regular basis to identify gene carriers.

Carcinoma, Medullary↗
PubMed1994

[Possibility of local control of breast cancer by microwave tissue coagulator (MTC)].

The tissue injury caused by microwave tissue coagulator (MTC) was assessed clinically and pathologically in a case of advanced breast cancer with skin invasion. On condition that the output was 10 watts and radiation lasted for 90 seconds at one time, temperature on breast skin was measured after each radiation. The maximum temperature was over 60 degrees C at the needle electrode and over 42 degrees C at 10 mm from the electrode after 21 radiations. From assessment of the resected specimen after operation, the following results were obtained. The mechanism of tissue injury by MTC consists of direct heat injury and infarct by circulatory disturbance. The extent of injury from the needle electrode is approximately 10 mm in the former mechanism and 15 mm in the latter. In conclusion, MTC is useful for the therapy of local recurrence of the breast cancer because of effectiveness in control of tumor-oozing and occurrence of tumor necrosis.

Breast Neoplasms↗
PubMedDate not supplied

Quantification of intracellular calcitonin gene transcripts in human medullary thyroid carcinoma (MTC) by in situ hybridization.

The human calcitonin gene generates 2 distinct mature mRNAs by alternative RNA processing, encoding calcitonin (CT) in thyroid C-cells or a neuropeptide (CGRP) in the brain. We evaluated quantitatively by in situ hybridization the expression of the CT gene in tissue section of 5 MTCs (2 sporadic and 3 familial forms). The primary tumor of one MTC was compared to a brain metastasis. In situ hybridization was carried out with tritiated cDNA probes coding for CT and CGRP mRNA. After autoradiography the number of silver grains was counted in 400 cells by computerized analysis of digitized images and expressed as the labelling level (L.L. = grain area/cell area per day of autoradiographic exposure). This was used to calculate the relative abundance per cell of the specific messengers studied, which depends on the autoradiographic efficiency and the specific activity of the probe used. The CT mRNA content was 3.25-6.55 10(-10) micrograms equivalents in the 3 familial forms of MTC and 4.95-9.25 10(-10) micrograms equivalents for the 2 sporadic forms. The levels of CT mRNA in the brain metastasis and in the primary tumor were identical (4.10 10(-10) micrograms equivalents). CGRP mRNA expression was weaker in the sporadic and in the familial thyroid tumors (0.60-1.65 10(-10) micrograms equivalents). The content of mRNA CGRP in the brain metastasis (0.60 10(-10) micrograms equivalents) was lower than that in the primary tumor (1.05 10(-10) micrograms equivalents).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed2001

Adsorption and desorption of chemotherapeutic drugs from a magnetically targeted carrier (MTC).

Magnetically targeted carriers (MTCs) are composite microparticles made from metallic iron and activated carbon. Particles, loaded with doxorubicin in the pharmacy (MTC-DOX), are infused intra-arterially through the artery feeding the tumor. With the aid of an externally positioned permanent dipole magnet, they can be localized and retained within a tumor mass. MTC-DOX is currently in use in a Phase I/II clinical study as a delivery vehicle for doxorubicin in primary hepatocellular carcinoma. The adsorption and desorption of doxorubicin, mitomycin C, camptothecin, methotrexate, verapamil and 9AC onto MTCs have been analyzed. Each of these chemotherapeutic agents has a different mechanism of action, suggesting that some benefit may be derived from combined delivery to a tumor using MTCs and magnetic targeting. Each drug displays different behavior with respect to adsorption and desorption. However, this behavior can be described for each drug with a non-linear thermodynamic model. The thermodynamic model predicts a controlled release rate by adjusting a number of parameters, including initial drug loading concentrations. This is confirmed with in vitro extraction experiments using human plasma as the extraction medium.

Adsorption↗