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Biomedical subjects

N J Baldwin

Publications and source records attributed to N J Baldwin.

13 recordsLinked to original sources
PubMed1997

31P magnetic resonance spectroscopy detection of response-predictive adenosine triphosphate decrease in irradiated radiation-induced fibrosarcoma-1 tumors.

RATIONALE AND OBJECTIVES: In previous phosphorus-31 (31P) magnetic resonance (MR) spectroscopy studies of radiation-induced fibrosarcoma (RIF-1), tumor model single-dose x-ray irradiation was applied at subcurative doses. A more effective x-ray does was used in this study, allowing correlation of treatment efficacy with the early changes observed in the 31P MR spectra of RIF-1 tumors. METHODS: Subcutaneous RIF-1 tumors of 60 mice were examined by 31P MR spectroscopy shortly before a single localized x-ray dose of 40 Gy and at eight times (2, 12, 24, 48, 72, 120, 168, and 216 hours) thereafter. RESULTS: Early increases in the relative concentration of inorganic phosphate and decreases in adenosine triphosphate (ATP), most notably at 2 and 12 hours (each P < 0.00001), were observed that lasted up to 48 hours after irradiation. Phosphomonoester and tumor pH showed decreases that reversed even earlier. Reduction of ATP measured at 48 hours after irradiation was, however, correlated with percent tumor shrinkage observed during the subsequent weeks (r = -0.59; P < 0.00001). CONCLUSIONS: Sustained loss of RIF-1 tumor ATP is predictive of treatment efficacy. Temporary depression of high-energy phosphate in favor of inorganic phosphate does not necessarily lead to cell death.

Adenosine Triphosphate↗
PubMed1997

Reducing alcohol consumption. Comparing three brief methods in family practice.

OBJECTIVE: To compare the effects of three brief methods of reducing alcohol consumption among family practice patients. DESIGN: Patients randomly assigned to one of three interventions were assessed initially and at 3-, 6-, and 12-month follow-up appointments. SETTING: Family practice clinic composed of 12 primary care physicians seeing approximately 6000 adults monthly in a small urban community, population 40,000. PARTICIPANTS: Through a screening questionnaire, 134 men and 131 women were identified as hazardous drinkers (five or more drinks at least once monthly) during an 11-month screening of 1420 patients. Of 265 patients approached, 180 agreed to participate and 159 (83 men and 76 women) actually participated in the study. INTERVENTIONS: Three interventions were studied: brief physician advice (5 minutes), two 30-minute sessions with a physician using cognitive behavioural strategies or two 30-minute sessions with a nurse practitioner using identical strategies. MAIN OUTCOME MEASURES: Quantity and frequency (QF) of drinking were used to assess reduction in hazardous drinking and problems related to drinking over 12 months of follow up. RESULTS: No statistical difference between groups was found. The QF of monthly drinking was reduced overall by 66% (among men) and 74% (among women) for those reporting at least one hazardous drinking day weekly at assessment (N = 96). Men reported drinking significantly more than women. CONCLUSIONS: These results indicated that offering brief, specific advice can motivate patients to reduce their alcohol intake. There was no difference in effect between brief advice from their own physician or brief intervention by a physician or a nurse.

Adult↗
PubMed1996

Immunomagnetic isolation of magnetoferritin-labeled cells in a modified ferrograph.

Pan T, helper, and cytotoxic lymphocytes were isolated from the human peripheral blood mononuclear cell fraction by antibody staining, ferritin labeling, and deposition on glass slides. Two distinct forms of ferritin were used: one was native horse spleen ferritin, and the other was magnetoferritin. Magnetoferritin was obtained by reconstituting the horse spleen ferritin iron core with superparamagnetic magnetite instead of the usual paramagnetic ferrihydrite crystal. The cell deposition on microscopic glass slides in the magnetic field was obtained by an instrument that was adapted from an industrial magnetic deposition analyzer, the ferrograph. The identity of cells in the magnetic deposits was confirmed by comparing the cell fractions in the feed and in the eluate with the use of flow cytometry. The immunostaining protocol amplified the number of ferritin molecules per cell surface antigen 20-70 times. Magnetoferritin, but not native ferritin, imparted a sufficient magnetic moment to cells to deplete the labeled cell population between 67 and 88% of its initial concentration in a magnetic field of 1.67 Tesla (T), a field gradient of 2.57 T/mm, and a flow rate of 0.01 ml/min. This study showed that the magnetic moment of magnetoferritin was sufficient for immunomagnetic isolation of lymphocytes from mononuclear cell preparations in the modified ferrograph.

Animals↗
PubMed1996

In situ 19F MRS measurement of RIF-1 tumor blood volume: corroboration by radioisotope-labeled [125I]-albumin and correlation to tumor size.

Tumor blood volume (TBV) is an important factor in the metabolism of a tumor and in its response to therapy. Until recently, the only methods to determine TBV were highly invasive and many involved radioisotopes. In this study, a perfluorocarbon (PFC) emulsion, Oxypherol, was monitored by 19F magnetic resonance spectroscopy (MRS). TBVs as determined by 19F MRS of in situ and excised radiation-induced fibrosarcoma (RIF-1) tumors (n = 9), were strongly correlated with the TBV measured by a radioisotope labeled albumin method (slopes of 1.1 and 0.8 with R = 0.86 and 0.91, respectively, by linear regression). In general, the TBV as calculated from the in situ MRS measurements (n = 24) decreased from 28 to 5 ml/100 g tumor mass for tumors ranging in mass from 0.15 to 2 g. However, there was an indication of an initial increase of TBV in tumors smaller than 0.5 g.

Albumins↗
PubMed1996

Oxygenation and metabolic status of KHT tumors as measured simultaneously by 19F magnetic resonance imaging and 31P magnetic resonance spectroscopy.

To evaluate the relationship between the partial pressure of oxygen (pO2) and the energy-related phosphorous metabolites in individual KHT murine sarcomas more clearly, the spatial distributions of pO2 were obtained simultaneously with 31P magnetic resonance spectra, and repeatedly as a function of growth. The pO2 maps, derived from serial images of the spin-lattice relaxation times of sequestered perfluorocarbon emulsions, were heterogeneous spatially, which is characteristic of solid tumors. Collectively, the median pO2 of the seven KHT tumors of mass varying from 0.2 to 1.8 g decreased from 60 to 0 mmHg, but it increased in one of five tumors which were followed in the growth study. The pHMRS and the high-energy ratio of phosphocreatine + nucleoside triphosphates to total observed phosphorous (TP) dropped on average as a function of tumor growth, while the low energy ratio of P(i) to TP increased. Also, for the tumors as a whole, the pH and high-energy ratio increased with increasing median pO2 while the low energy ratio decreased, but the 31P values of some tumors did not follow this general trend. These individual variations suggest the need for simultaneous and repeated measurements of phosphorous metabolites and oxygen tension for complete information regarding the tumor status in experimental studies and therapeutic procedures in humans.

Animals↗
PubMed1994

Screening for hazardous drinking. Using the CAGE and measures of alcohol consumption in family practice.

OBJECTIVE: To determine the drinking practices of a family practice population, to examine the CAGE and questions about drinking as a method of screening for hazardous alcohol use, and to examine the relationship between alcohol consumption and CAGE items, particularly in a subgroup of hazardous drinkers. DESIGN: Random survey of patients representative of a clinic population. SETTING: Family practice clinic. PATIENTS: Of 1420 patients approached while waiting to see a family physician for medical reasons, 1376 agreed to participate; 1334 turned in usable questionnaires. MAIN OUTCOME MEASURES: Drinking measures and CAGE items; CAGE questions and levels of alcohol use were used to determine current drinking practices. A subgroup of hazardous drinkers was examined in greater detail. RESULTS: Forty percent of male patients and 11% of female patients reported at least one "hazardous" drinking (four or more drinks) day in the past month. Answering yes to CAGE items was more specific to drinking for male subjects, who also reported a greater number of maximum drinks with a CAGE score of 2 or more. CONCLUSIONS: This brief questionnaire was a feasible tool for identifying family practice patients who could be at risk for developing alcohol problems. All patients could be invited to complete the questionnaire while waiting for their appointments.

Adolescent↗
PubMed1991

19F magnetic resonance spectroscopy studies of the metabolism of 5-fluorouracil in murine RIF-1 tumors and liver.

The metabolism of 5-fluorouracil (5FU) in tumors and livers of RIF-1 tumor-bearing C3H mice given i.p. injections of 5FU was serially monitored by 19F magnetic resonance spectroscopy. The levels of 5FU and fluoronucleotide detected in the tumors after a dose of 130 mg/kg (n = 13) were less than one-third of those after 260-mg/kg 5FU (n = 14). During the days after these doses, tumor size decreased by 24 +/- 3 and 52 +/- 6 SEM%, respectively. A second 130-mg/kg dose, given at day 7 after the first 130-mg/kg dose, resulted in still lower tumor fluorine levels and little change in tumor size. There was a significant correlation between the magnetic resonance spectroscopy-detected fluoronucleotide levels and the shrinkage of tumors after the 260-mg/kg dose (r = 0.44; P = 0.024). In mouse liver, the degradation of 5FU to alpha-fluoro-beta-ureidoprobionic acid and alpha-fluoro-beta-alanine after the 260-mg dose (n = 13) was slower than after a dose of 130 mg/kg (n = 14). For the respective doses, the half-life of 5FU was 59 +/- 7 versus 28 +/- 2 SEM min (P less than 0.0001). There was a negative correlation between the levels of 5FU catabolite (alpha-fluoro-beta-ureidoprobionic acid and alpha-fluoro-beta-alanine) in liver and fluoronucleotide in tumor (r = -0.80; P = 0.0020), which indicates that the degradation in liver and the activation of 5FU in tumor are competing processes.

Animals↗
PubMed1991

Multinuclear MR investigation of the metabolic response of the murine RIF-1 tumor to 5-fluorouracil chemotherapy.

The metabolic response of the RIF-1 tumor to 5-fluorouracil (a single dose of 260 mg 5FU/kg, ip) was monitored in 10 mice using 19F and 31P MR spectroscopy. 19F MRS revealed a continuous drop in tumor 5FU level and an increase in the fluoronucleotide (Fnuc) signal to a plateau value of 50% of the initial 5FU level, during the first 2 h after chemotherapy. Although the 31P MR spectra of the tumors showed no significant initial changes, the total level of MR visible tumor phosphate decreased and tumor pH increased during the subsequent days. The changes in phosphate metabolism and tumor pH did not correlate with the detected fluorine levels or tumor response. However, the pretreatment Pi level, the plateau Fnuc level, and the 5FU induced decrease in tumor volume showed significant correlation. This indicates that both 19F and 31P MR spectroscopy have potential for predicting response to 5FU chemotherapy.

Animals↗
PubMed1989

Therapeutic response of breast carcinoma monitored by 31P MRS in situ.

In situ phosphorous MRS was employed to study the metabolites of normal and cancerous breasts, and the alterations of tumor response to therapy. In a group of 7 normal volunteers and 12 patients, the total mobile phosphate content of breast carcinomas was found to be at least two to three times higher than that of the normal breast measured off menstruation. The metabolite profiles of normal and tumorous breasts are coarsely similar. In both cases the intracellular pH (pHi) was either neutral or slightly alkaline (pH greater than 7.0). Prior to treatments, the metabolite levels of phosphoryl monoester-to-ATP ratio of breast neoplasms were higher than those of the controls and decreased after the patients received a few treatments while the pHi fluctuated at a value greater than 7.0. The phosphoryl diester-to-ATP ratio also demonstrated to a lesser extent a decreasing trend in response to therapy.

Breast↗
PubMed1989

Human neoplasm pH and response to radiation therapy: P-31 MR spectroscopy studies in situ.

Thirty-five human neoplasms from various sites and of various histologic types and stages were examined with phosphorus-31 magnetic resonance spectroscopy in situ. The tumors included 13 squamous cell carcinomas of the head and neck (lymph nodes), eight Hodgkin lymphomas, six non-Hodgkin lymphomas, four carcinomas of the breast, one melanoma, one sarcoma, one neuroblastoma, and one mucoepidermoid sarcoma of the salivary glands. Thirty-four of the neoplasms had normal to slightly alkaline pH before irradiation. During fractionated radiation therapy, the pH stayed in a range of from near neutral to alkaline and rose to 7.6-8.0 at several time points of radiation therapy for some tumors. These results suggest that most tumor cells in human neoplasms are well oxygenated and that only a negligible fraction are chronic hypoxic cells. The fluctuating alkaline pH during radiation therapy occurred regardless of the responsiveness of the treated tumors.

Carcinoma, Squamous Cell↗
PubMed1987

Response of a non-Hodgkin lymphoma to 60Co therapy monitored by 31P MRS in situ.

High quality 31P MR spectra (signal to noise ratio (S/N) approximately 18, 15 min acquisition for each spectrum) were consistently obtained with surface coils over a period of 6-week RT. Both transient and steady state alterations in metabolites in response to RT were found in this case. The transient changes occurred during the first 3 hr immediately after the 3rd fractionated RT, these changes include the transient elevation of the PCr resonance, a decrease in PDE and an increase in intracellular pH. The monitoring showed that the metabolites approached steady state approximately 2 hr after the fractionated radiation intervention, suggesting that in vivo MRS can be useful for studying the dynamics of tumor response to RT such as repair of potential lethal damage, growth delay, and reoxygenation etc. The steady-state MR spectra showed the net response to each intervention and can clinically be useful for predicting and measuring the result of the fractionated RT. In this case study, the PDE peak which contains the phospholipid metabolites GPC and GPE, is the most sensitive resonance in response to RT. After the 3rd RT, prior to tumor size reduction, the PDE to ATP ratio decreased 33% and intracellular pH increased to 7.34 +/- 0.05 from 7.27 +/- 0.05. In the subsequent RT interventions, both the tumor size and PDE/ATP ratio continually decreased whereas the pH values remained alkaline and fluctuated around 7.34 to 7.65. The data suggest that the phospholipid metabolite PDE may signal important alterations in membrane metabolism that eventually lead to cell death.

Cobalt Radioisotopes↗
PubMed1978

Characterization and construction of molecular cloning vehicles within Staphylococcus aureus.

Four chloramphenicol resistance (Cm) and four tetracycline resistance (Tc) plasmids from Staphylococcus aureus were characterized by restriction endonuclease mapping. All four Tc plasmids had molecular masses of 2.9 megadaltons (Mdaltons) and indistinguishable responses to seven different restriction endonucleases. The four Cm plasmids (pCW6, pCW7, pCW8, and pC221) had molecular masses of 2.6, 2.8, 1.9, and 2.9 Mdaltons, respectively. The four Cm plasmids also differed both in the level of resistance to Cm and in susceptibility to retriction endonucleases. Single restriction endonuclease sites contained within each plasmid included the following: in pCW6 for HindIII, XbaI, HpaII, and BstEII; in pCW7 for HindIII, BstEII, BglII, HaeIII, and HpaII; in pCW8 for HindIII, HaeIII, and HpaII; in pC221 for HindIII, BstEII, and EcoRI. The molecular cloning capabilities of pCW8 and pC221 were determined. Cm and erythromycin resistance (Em) recombinant plasmids pCW12, PCW13, and pCW14 were constructed and used to transform S. aureus 8325-4. A 2.8-Mdalton HindIII fragment from plasmid pI258 was found to encode Em resistance and contain single sites for the retriction endonucleases BglII, PstI, HaeIII, and HpaII. The largest EcoRI fragment (8 Mdaltons) from pI258 contained the HindIII fragment encoding Em resistance intact. Cloning of DNA into the BglII site of pCW14 did not alter Em resistance. Cloning of DNA into the HindIII site of pCW8 and the HindIII and EcoRI sites of pC221 did not disrupt either plasmid replication of Cm resistance.

Anti-Bacterial Agents↗