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Biomedical subjects

C R Thomas

Publications and source records attributed to C R Thomas.

At least 73 records · Page 4Linked to original sources

Growth hormone increases IGF-I, collagen I and collagen III gene expression in dwarf rat skeletal muscle.

The effect of short-term treatment with biosynthetic growth hormone (GH) of male dwarf rats was studied in EDL and soleus muscles. In situ hybridisation revealed that in the untreated dwarf rat collagen I, collagen III and insulin-like growth factor-I (IGF-I) mRNA is mainly expressed by fibroblasts between the muscle fibre areas. Quantitative image analysis showed that, 8 h after a single GH injection, the level of mRNA for all three genes increased compared to the untreated dwarf animal. IGF-I mRNA levels were similar in normals and untreated dwarf rats but significantly increased 8 h after a single GH injection in EDL (P < 0.01) and soleus (P < 0.001). In untreated dwarf rats, collagen I and III gene expression was significantly less than in normal animals (P < 0.001). Collagen III gene expression also increased significantly 8 h after a single GH injection, in both muscles (P < 0.01). Collagen I gene expression showed significant increases 8 and 24 h after GH treatment in EDL (P < 0.01), although the increases seen in soleus did not reach significance. The effects of multiple GH injections (one, two or four) did not appear to be additive. The results of the time course studies are consistent with an intermediary role for IGF-I in the production of collagen in muscle.

Animals↗

Carcinoma of the male breast: update 1994.

In many ways, male and female breast cancers are similar, but do have some notable differences. Although the underlying etiology of male breast cancer may be partially due to hormonal or environmental changes, this disease is rare compared to female breast cancer. Most often, it presents as a painless lump, with estrogen receptor-positive infiltrating ductal carcinoma being the most common pathologic type. The main component of local therapy is either a radical or a modified radical mastectomy, with adjuvant chemotherapy proving useful. Estrogen receptor-positive tumors respond well to hormonal therapy. More research is needed in order to: (1) further characterize the molecular biological properties of male breast cancer tumors, (2) further investigate the role of adjuvant chemotherapy, and define successful regimens, and (3) determine optimal chemotherapy regimens in the treatment of metastatic disease. As this disease is a relatively rare condition, whenever possible, all patients should be allowed to participate in national cooperative group studies.

Breast Neoplasms, Male↗

Bidirectional placental transfer ('leak') of L-glucose in control and diabetic rats.

The placental transfer of D- and L-glucose was investigated in anaesthetised non-diabetic and streptozotocin-induced diabetic rats. Maternal to fetal transfer was determined by perfusing the fetal side of one placenta in situ whilst infusing a mixture of D-[3-3H]glucose and L-[1-14C]glucose into the maternal circulation. Back-transfer from the fetal to maternal circulation was assessed by determining the uptake of the radiolabelled glucoses from the perfusion fluid during a single passage through the placenta on the fetal side. Maternal diabetes resulted in a reduced utero-placental blood flow but an increased bidirectional transfer of D-glucose. Non-specific maternal to fetal placental transfer of L-glucose was greater in diabetic rats than in controls, and the loss of L-glucose during placental perfusion on the fetal side was, again, greater in diabetic than in control rats. This increased bidirectional 'leak' of glucose possibly reflects a functionally compromised placenta, caused by its formation in a diabetic milieu, and may explain the greater fetal-maternal glucose ratios found in diabetic rats relative to controls.

Animals↗

Radiation therapy for sarcoid of the thalamus/posterior third ventricle: case report.

There are a limited number of previously reported cases involving the use of radiation therapy for sarcoid of the brain. The case of a 22-year-old man with a thalamic/posterior third ventricle sarcoid mass that grew despite steroid medication is presented. The patient was treated with external beam radiation to a total dose of 20 Gy, with 2-Gy fractions over 14 elapsed days. A complete radiographic response was achieved 4 months after radiation was completed. Radiographic follow-up through 8 months postradiation shows no evidence of disease recurrence. Fractionated radiation therapy in low-to-moderate doses appears to be efficacious in steroid-refractory sarcoid of the brain.

Adult↗

Atrial natriuretic peptide-like (ANP-LIR) and ANP prohormone immunoreactive astrocytes and neurons of human cerebral cortex.

Atrial natriuretic peptide (ANP) represents a family of related peptides originally isolated from cardiac atria that have potent natriuretic, diuretic, and vasorelaxant properties. ANP has previously been localized in neurons of the rat brain in regions subserving cardiovascular functions and fluid/electrolyte balance and has been localized in astroglia of the canine brain. To determine whether ANP is present in astrocytes of the human brain and to validate the canine model for future studies, human brain tissue was obtained from autopsy cases with no brain damage or neurological or vascular disease. Human brains were obtained less than 3 h postmortem, and anterior cingulate and striate cortices were dissected following perfusion or immersion fixation. Immunohistochemical processing utilized antibodies against the processed form of ANP (ANP IV, ANP104-128) and against rat proANP (amino terminus) and the avidin-biotin-peroxidase technique. Isolated, strongly ANP-immunoreactive protoplasmic astrocytes were observed in all layers of the cingulate and striate cortex gray matter. ANP-positive fibrous astrocytes were observed in the white matter. Additionally, distinctive immunopositive astrocytes were found both within and immediately subjacent to the glia limitans. Antibody against the prohormone stained only protoplasmic astrocytes and sublimitans astrocytes and processes. In addition to the astroglia, ANP was detected in scattered multipolar neurons in the cerebral gray matter. These results provide additional evidence for diversity of peptide localization in astrocytes and suggest roles for ANP in the local regulation of cerebral blood flow, blood-brain barrier permeability, or cerebrospinal fluid volume.

Adult↗

Prediction of mechanical damage to animal cells in turbulence.

In previous work a model was proposed for estimation of disruption of animal cells in turbulent capillary flows using information about the hydrodynamics, and cell mechanical properties determined by micromanipulation. The model assumed that the capillary flow consists of a laminar sublayer and a homogeneous turbulent region, and within the latter eddies of sizes similar to or smaller than the cells interact with those cells, causing local surface deformations. The proposed mechanism of cell damage was that such deformations result in an increase in membrane tension and surface energy, and that a cell disrupts when its bursting membrane tension and bursting surface energy are exceeded. The surface energy of the cells was estimated from the kinetic energy of appropriate sized eddies. To test the model, cells were disrupted in turbulent flows in capillaries at mean energy dissipation rates ranging from 800 to 2 x 10(4) Wkg-1. The model assumed that the specific lysis rate is almost independent of the number of passes, which was verified by the experimental data. The implication was that despite the damage the cell mechanical properties did not change markedly during multiple recirculations through the capillaries. On average the model underestimated the cell disruption by about 15%. Although the model gave reasonably good predictions, it lacks proper explanation of the independence of the specific lysis rate on the number of passes. In this paper it is shown that this problem can be resolved in principle by consideration of the localisation of the energy dissipation in turbulent capillary flows. The necessity of further modelling of cell-turbulence interactions is demonstrated.

Animals↗

Measurement of hybridoma cell number, viability, and morphology using fully automated image analysis.

A novel automated image analysis method is described for characterizing the viability and morphology of animal cells from suspension cultures. With the aid of the exclusion dye Trypan Blue, the total and viable cell counts and the percentage of dead cells present are found. The area, perimeter, equivalent diameter, and circularity of the projected image of each cell are also measured, allowing the estimation of cell volume. The image analysis method is inherently sensitive, precise, consistent (non-operator dependent) and relatively fast, taking approximately 22 min to analyze one sample. The data it gives on individual cellular activity, as characterized by Trypan Blue uptake and cell morphology, are valuable in allowing early diagnosis of even subtle changes in the health of a culture. The method should permit better optimization of culture conditions, and will provide data for the modeling of cell population dynamics. As the conventional manual method is operator dependent, relatively limited in the amount of information it provides, and has a tendency to underestimate Trypan Blue takeup, it is suggested that image analysis be the preferred option for animal cell counting and viability determinations.

Animals↗

Utility of magnetization prepared GRE MRI for the detection of focal liver lesions.

We compared the efficacy of rapidly acquired magnetization prepared gradient-echo (MP-GRE) sequences with CT and standard MRI pulse sequences for the detection of focal liver lesions. Fourteen patients with 28 focal liver lesions were scanned. TI times of 300, 450, and 600 ms were used. MP-GRE lesion conspicuity was compared to corresponding CT, T1, T2, T2-post-superparamagnetic-iron-oxide (SPIO), and STIR images. It was found that the differences between MP-GRE and CT and MP-GRE and T1 MRI were not significant. However, overall anatomic detail was better with CT and T1 MRI than MP-GRE. Lesion conspicuity was significantly worse with the MP-GRE than with the T2, T2-post-SPIO, and STIR sequences (all p values = 0.00). Maximal liver signal nulling occurred at TI = 300 ms in 13 out of 14 patients. However, the T1 for optimal focal liver lesion conspicuity varied widely and could not be predicted before scanning. No new lesions were seen on the MP-GRE sequence that could not be seen on the CT or standard MRI sequences. As currently implemented, MP-GRE imaging offers no advantage in the detection of focal liver lesions over CT and standard MRI pulse sequences.

Adult↗

Pilot study for the evaluation of simultaneous cisplatin/5-fluorouracil infusion and limited radiation therapy in regionally recurrent head and neck cancer (EST P-C385).

From 1981 to 1989, 21 patients with heavily pretreated head and neck cancers were retreated with combined chemotherapy (CT) and irradiation (RT). All patients had previously received radiation therapy with doses of 50-70 Gy. Metastatic disease to lungs and/or osseous sites occurred in 4 patients. Treatment consisted of simultaneous cisplatin, 5-fluorouracil, and external beam radiation therapy, with planned doses of 20 to 70 Gy. The RT+CT was given over 5 consecutive days every 2 weeks. Four patients did not complete treatment due to toxicity (2 patients) or disease progression (2 patients). All patients developed grade 2-3 mucositis. Because of toxicity, 11 patients required treatment delays of 1 to 3 weeks. Clinically complete responses were noted in 10 patients (48%), with partial responses occurring in 5 patients (24%). Of the 21 patients, 18 have died: 13 had local and/or regional recurrence, 2 died of treatment toxicity and 3 died of intercurrent disease. Median time to progression was 5 months (range: 1-15 months). Three patients remain alive with no evidence of disease at 44, 86, and 88 months after retreatment.

Aged↗

Prevention by insulin treatment of endothelial dysfunction but not enhanced noradrenaline-induced contractility in mesenteric resistance arteries from streptozotocin-induced diabetic rats.

1. Streptozotocin-induced diabetic rats (Wistar) were implanted with sustained release insulin pellets (release rate = 4 u day-1) or with placebo pellets (palmitic acid) from the onset of glycosuria. 2. Noradrenaline sensitivity, endothelium-dependent relaxation to acetylcholine and endothelium-independent relaxation to sodium nitroprusside were assessed in mesenteric resistance arteries from the insulin-treated (IT) diabetic animals and compared to placebo-implanted (PI) diabetics and age-matched controls. 3. Arteries from PI-diabetic rats (8-10 weeks) demonstrated an enhanced maximal response to noradrenaline compared to controls, which was not prevented by insulin treatment (control 2.65 +/- 0.17 mN mm-1, n = 18 arteries versus PI-diabetic 3.73 +/- 0.40 mM mm-1, n = 5, P < 0.05; control versus IT-diabetic 4.02 +/- 0.19 mN mm-1, n = 22, P < 0.001). Sensitivity to noradrenaline was similar between the three groups. 4. In the presence of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), IT and PI arteries were more sensitive to noradrenaline than control arteries (pEC50: control 5.75 +/- 0.08, n = 17, versus PI-diabetic 6.14 +/- 0.09, n = 8, P < 0.05; control versus IT-diabetic 6.38 +/- 0.08, n = 20, P < 0.001). 5. The maximum contractile response to depolarizing 125 mM K+ was significantly enhanced in IT-diabetic arteries but not PI-diabetic when compared to control arteries (maximum response: control 3.74 +/- 0.15 mN mm-1, n = 18, versus PI-diabetic 3.61 +/- 0.19 mN mm-1, n = 11, NS; control versus IT-diabetic 4.66 +/- 0.18 mN mm-1, n = 22, P < 0.001). 6. Endothelium-dependent relaxation to acetylcholine was profoundly impaired in the PI-diabetic arteries, but in the IT-diabetic arteries was not significantly different from controls (pEC50: control 7.64 +/- 0.19, n = 17, versus PI-diabetic 6.07 +/- 0.12, n = 8, P < 0.001; control versus IT-diabetic 7.36 +/- 0.09, n = 22, NS). 7. Endothelium-independent relaxation to sodium nitroprusside was slightly but significantly impaired in the PI-diabetic arteries, but was not significantly different in the IT-diabetic arteries compared to controls (pEC50: control 7.78 +/- 0.10, n = 13, versus PI-diabetic 7.31 +/- 0.13, n = 13, P <0.05; control,versus IT-diabetic 7.64 +/- 0.09, n = 16, NS).

Acetylcholine↗

A comparison of the metabolic profiles of fetal and maternal plasma and placenta in normal and diabetic rats by 1H magnetic resonance spectroscopy.

Spectral analysis of spin-echo 1H magnetic resonance spectroscopy (MRS) data has revealed differences in the metabolic profiles of maternal and fetal plasma and placental extracts. Resonances from low-molecular weight components of the normal maternal and fetal plasma were attributed to glucose, lactate, creatine, citrate, amino acids and ketone bodies. There were also signals from lipoprotein molecules associated with lipid-transporting moeties contained in the plasma. The placental extract showed a similar composition to the plasma samples however the spectra were dominated by a large signal attributed to betaine, there was also an absence of signals from citrate, acetoacetate, acetone and lipoproteins. Diabetes caused profound changes in all tissue types indicating high levels of glucose and ketogenic activity. In both the maternal and fetal plasma there were increases in glucose, ketone bodies and valine in the diabetic rats, increases in lactate and alanine were confined to the fetal plasma and placenta. This study indicates that diabetes causes major changes in the composition of fetal plasma which in turn could interfere with the development of the fetus.

Amino Acids↗

Common emergencies in cancer medicine: infectious and treatment-related syndromes, Part I.

This two-part article, the last in a series of articles on cancer emergencies, summarizes the common medical emergencies that can occur as a result of infectious processes (Part I) and antitumor treatment secondary to chemotherapy, biological response modifiers, or radiotherapy (Part II). The use of high-dose cytotoxic agents, coupled with the common instillation of indwelling central venous access devices, have altered the spectrum of infectious etiologies that are appreciated in clinical practice. In addition, a myriad of cytotoxic agents and radiotherapeutic treatment schemes are used widely in clinical oncologic practice. While most of their related side effects are not considered life-threatening emergencies, they can be fatal if not recognized early and treated promptly. Moreover, some of these infectious and treatment-related sequelae can be prevented.

Antineoplastic Agents↗

Common emergencies in cancer medicine: infectious and treatment-related syndromes, Part II.

This article completes a summary of the common medical emergencies that can occur as a result of infectious processes (Part I) and antitumor treatment secondary to chemotherapy, biological response modifiers, or radiotherapy (Part II). The use of high-dose cytotoxic agents, coupled with the common instillation of indwelling central venous access devices, have altered the spectrum of infectious etiologies that are appreciated in clinical practice. In addition, a myriad of cytotoxic agents and radiotherapeutic treatment schemes are used widely in clinical oncologic practice. While most of their related side effects are not considered life-threatening emergencies, they can be fatal if not recognized early and treated promptly. Moreover, some of these infectious and treatment-related sequelae can be prevented. This article highlights some of these clinical observations.

Antineoplastic Agents↗

Participation in clinical trials: is it state-of-the-art treatment for African Americans and other people of color?

We have attempted to initiate a much needed constructive dialogue regarding the participation of African-American patients in clinical cancer research trials. It was our intent to provide a greater understanding of the historical context and evolving nature of clinical research trials pertaining to cancer. Some of the same challenges hold true for acquired immunodeficiency syndrome (AIDS)-related clinical research. Physicians interested in becoming a member of SOCRATES should contact Dr Roach at the University of California San Francisco.

Black or African American↗

Insulin-like growth factor-I gene expression is increased in the right ventricular hypertrophy induced by chronic hypoxia in the rat.

Rats were maintained in chambers and breathed air (control, n = 8) or an atmosphere containing 10% oxygen (hypoxic, n = 10) for 35 days. On completion of the experiment the hypoxic animals weighed less than the controls (hypoxic, 290 +/- 11.7g; control, 339 +/- 19.2g; means +/- S.E.M., p < 0.05). No differences in the left ventricular weights were found between groups but the right ventricular weights were greater in the hypoxic rats (hypoxic, 0.39 +/- 0.02g; control, 0.27 +/- 0.08g; p < 0.01). The amount of mRNA for IGF-I in the ventricles was quantified by Northern blot analysis. There was no difference between groups in IGF-I mRNA levels in the left ventricles (hypoxic, 1.07 +/- 0.41 absorbance units (AU); control, 0.73 +/- 0.33 AU). In the right ventricles, IGF-I mRNA was greater in hypoxic than in control rats (hypoxic, 2.37 +/- 0.75 AU; control, 0.64 +/- 0.11 AU; p < 0.05). This study demonstrates that expression of IGF-I mRNA is increased in the hypertrophied right ventricle of hypoxic rats; IGF-I may play a central role in the initiation and maintenance of this process.

Animals↗

MR imaging with i.v. superparamagnetic iron oxide: efficacy in the detection of focal hepatic lesions.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of superparmagnetic iron oxide (SPIO) in the detection of focal hepatic lesions on MR images. SUBJECTS AND METHODS: The study included 21 patients with 115 focal hepatic lesions and eight patients without focal hepatic lesions. T1- and T2-weighted MR images were obtained at 1.5 T before and 60 min after the end of injection of an SPIO agent. Contrast-enhanced CT scans were obtained in all patients within 10 days after MR imaging. The effect of SPIO on the signal intensity of the liver and spleen was assessed by using quantitative analysis of the region of interest. Efficacy was evaluated by using multiple criteria and unenhanced and SPIO-enhanced images. Evaluations included subjective assessment of image quality, counting the number of lesions detected, and statistical analysis of quantitative changes in the signal intensity of lesions and of normal liver. RESULTS: By all criteria, SPIO-enhanced T2-weighted MR images were superior to unenhanced T2-weighted images and to contrast-enhanced CT scans. Conversely, by all criteria, SPIO-enhanced T1-weighted MR images were worse than unenhanced T1-weighted images and contrast-enhanced CT scans. The mean lesion-to-liver contrast on T2-weighted images was 317% on unenhanced images and 1745% on SPIO-enhanced images. For T1-weighted, the mean contrast was 26% on unenhanced images and 18% on SPIO-enhanced images. CONCLUSION: SPIO is an efficacious contrast agent for the detection of focal hepatic lesions when T2-weighted MR images are used.

Contrast Media↗

Nocturnal urinary excretion of 6-hydroxymelatonin sulfate in prepubertal major depressive disorder.

Levels of the melatonin metabolite, 6-hydroxymelatonin sulfate, were measured in overnight urine from 31 prepubertal children with major depressive disorder and 15 normal control children with very low family loading for affective disorder. The two groups did not differ with regard to their nocturnal excretion of this compound, nor was any depressive subgroup identified whose 6-hydroxymelatonin sulfate excretion differed from that of the control group. Previous studies of pineal function in depression are reviewed and discussed in the context of the present investigation.

Adolescent↗