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Biomedical subjects

T Maloney

Publications and source records attributed to T Maloney.

At least 19 recordsLinked to original sources

Role of the anterior cingulate and medial orbitofrontal cortex in processing drug cues in cocaine addiction.

Our goal in the current report was to design a new functional magnetic resonance imaging (fMRI) task to probe the role of the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC) in processing of salient symptom-related cues during the simultaneous performance of an unrelated task in drug-addicted persons. We used a novel fMRI color-word drug Stroop task in 14 individuals with cocaine use disorders; subjects had to press for color of drug vs. matched neutral words. Although there were no accuracy or speed differences between the drug and neutral conditions in the current sample of subjects, drug words were more negatively valenced than the matched neutral words. Further, consistent with prior reports in individuals with other psychopathologies using different Stroop fMRI paradigms, our more classical color-word Stroop design revealed bilateral activations in the caudal-dorsal anterior cingulate cortex (cdACC) and hypoactivations in the rostro-ventral anterior cingulate cortex/medial orbitofrontal cortex (rACC/mOFC). A trend for larger rACC/mOFC hypoactivations to the drug than neutral words did not survive whole-brain corrections. Nevertheless, correlation analyses indicated that (1) the more the cdACC drug-related activation, the more negative the valence attributed to the drug words (r=-0.86, P<0.0001) but not neutral words; and (2) the more the rACC/mOFC hypoactivation to drug minus neutral words, the more the errors committed specifically to the drug minus neutral words (r=0.85, P<0.0001). Taken together, results suggest that this newly developed drug Stroop fMRI task may be a sensitive biobehavioral assay of the functions recruited for the regulation of responses to salient symptom-related stimuli in drug-addicted individuals.

Adult↗

Microcrystalline cellulose-water interaction--a novel approach using thermoporosimetry.

PURPOSE: To study the physical state of water in microcrystalline cellulose (MCC) and in silicified microcrystalline cellulose wet masses and the effect of granulation on different water fractions. METHODS: Thermoporosimetry, together with the solute exclusion technique, was used to measure different water fractions and pore size distributions of wet granules. To understand the effect of granulation on the physical state of water, both ungranulated and granulated wet masses were studied. In addition, dynamic and isothermal step melting procedures were compared. RESULTS: Four distinct fractions of water (nonfreezing, freezing bound, free, and bulk water) could be detected in MCC wet masses. Granulation decreased the volume of bulk water and increased the volume of freezing bound and free water. Consequently, granulated wet masses were able to hold more water inside the particles compared to ungranulated wet masses. Thus, granulation had a similar effect on MCC as beating has on cellulose fibers in the papermaking proces CONCLUSIONS: Thermoporosimetry and solute exclusion increased the understanding of MCC-water interaction and showed how the physical state of water in MCC wet masses changes during granulation.

Algorithms↗

A comparison of period amplitude analysis and FFT power spectral analysis of all-night human sleep EEG.

Zero-cross and zero-derivative period amplitude analysis (PAA) data were compared with power spectral analysis (PSA) data obtained with the fast Fourier transform in all-night sleep EEG from 10 subjects. Although PAA zero-cross-integrated amplitude showed good agreement with PSA power in 0.3-2 Hz, zero-cross analysis appears relatively ineffective in measuring 2-4 Hz and above waves. However, PAA zero-derivative measures of peak-trough amplitude correlated well with PSA power in 2-4 Hz. Thus, while PAA appears able to measure the entire EEG spectrum, the analytic technique should be changed from zero cross to zero derivative at about 2 Hz in human sleep EEG. PAA and PSA both demonstrate robust and interrelated across-night oscillations in three frequency bands: delta (0.3-4 Hz); sigma (12-16 Hz); and fast beta (20-10 Hz). The frequencies between delta and sigma, and between sigma and fast beta, did not show clear across-night oscillations using either method, and the two methods showed lower epoch-to-epoch agreement in these intermediate bands. The causes of this reduced agreement are not immediately clear, nor is it obvious which method gives more valid results. We believe that the three strongly oscillating frequency bands represent fundamental properties of the human sleep EEG that provide important clues to underlying physiological mechanisms. These mechanisms are more likely to be understood if their dynamic properties are preserved and measured naturalistically rather than being forced into arbitrary sleep stages or procrustean models. Both PAA and PSA can be employed for such naturalistic studies. PSA has the advantages of applying the same analytic method across the EEG spectrum and rests on more fully developed theory. Combined zero-cross and zero-derivative PAA demonstrates EEG oscillations that closely parallel those observed with spectral power, and the PAA measures do not rely on assumptions about the spectral composition of the signal. In addition, both PAA techniques can measure the relative contributions of wave amplitude and incidence to total power: These waveform characteristics represent different biological processes and respond differentially to a wide range of experimental conditions.

Adult↗

Sigma (12-16 Hz) and beta (20-28 Hz) EEG discriminate NREM and REM sleep.

All night sleep EEG from ten normal students were subjected to FFT spectral analyses. Delta (0.3-3 Hz), sigma (12-16 Hz) and beta (20-28 Hz) EEG showed strongly oscillating patterns across the night. The scattergram of sigma versus beta revealed two separate clusters. One cluster demonstrated a positive linear correlation between sigma and beta. The second cluster showed a range of beta, but a stable, low level of sigma activity. Points in the former cluster consisted of those from NREM epochs, and in the latter, from REM epochs. The present results suggest that REM and NREM EEG are composed of two sets of EEG frequency components, perhaps reflecting different neuronal pools.

Adult↗

Dream report length is more dependent on arousal level than prior REM duration.

Twenty two young adult subjects (Ss) were monitored for 2 consecutive nights in the sleep laboratory. Each S was awakened three times per night: at sleep onset and during the second (REMP2) and fourth (REMP4) REM periods. Length of time in each REMP prior to awakening was either 5 or 10 min, counterbalanced on successive nights. Sleep mentation reports were obtained by standardized interview and scored for total word count (TWC). TWC after 5 min of prior REM sleep did not differ significantly from TWC after 10 min of prior REM sleep. However, mean TWC from REMP4 awakenings was almost twice that from REMP2 awakenings. These findings are consistent with the hypothesis that the amount of recall from experimental REM awakenings depends on central arousal level and its effects on mnemonic processes.

Adult↗

Beta (20-28 Hz) and delta (0.3-3 Hz) EEGs oscillate reciprocally across NREM and REM sleep.

Across-night oscillations of beta (20-28 Hz) and delta (0.3-3 Hz) electroencephalograms (EEGs) were examined with spectral analysis in 10 normal young adult subjects (Ss). In each S, power densities of beta were found to oscillate reciprocally with delta power density across both nonrapid eye movement (NREM) and rapid eye movement (REM) sleep. Linear correlation coefficients between log power density of delta vs. beta were significant (p less than 0.0001) for each S. An incidental observation was that beta power within REM was reliably lower in epochs with more eye movement activity. The reciprocal relationship between beta and delta holds implications for sleep physiology and supplements our earlier finding that sigma (12-15 Hz) oscillates reciprocally with delta within NREM sleep. These descriptions of the continuously varying EEG across sleep provide information not available when EEG measures are tabulated by discrete NREM periods and REM periods.

Adolescent↗

Precise conservation of NREM period 1 (NREMP1) delta across naps and nocturnal sleep: implications for REM latency and NREM/REM alternation.

The delta integrated amplitude (DIA) in nonrapid eye movement period 1 (NREMP1) of daytime naps was precisely subtracted from the NREMP1s of ensuing nocturnal sleep, indicating that the brain can retain a record of DIA expressed in sleep episodes initiated 12.5 and 8.5 hours before nocturnal sleep onset. The DIA subtraction was primarily accomplished by reduced NREMP1 duration [earlier rapid eye movement (REM) onset], suggesting that the timing of REM period 1 (REMP1) onset is controlled by delta need. This result is consistent with the hypothesis that REM sleep occurs when a stimulus for NREM has been partially depleted.

Adult↗

Auditory event-related potentials during stage 2 NREM sleep in humans.

Event-related potential (ERP) recordings were used to investigate the nature of auditory stimulus evaluation during stage 2 sleep. Frequent and rare stimuli, differing in intensity and frequency, were presented to six adult subjects while awake and asleep. The latency and voltage distribution of one of the long-latency components evoked during sleep resembled the P3 component evoked while awake. However, it was attenuated in voltage and superimposed on N3, a large late negative component, most probably the slow potential of the K complex. The identification of a P3-like potential during sleep suggests that the P3 potential is not solely a marker of active cognitive processes, but contains a small component which reflects automatic, pre-attentive evaluation of deviant stimuli.

Journal Article↗

Prognostic significance of proliferation associated nucleolar antigen P120 in human breast carcinoma.

Nucleolar antigen P120 is detected in rapidly proliferating cells but not in normal resting cells or in many benign and slowly growing malignant tumors. The objective of the study was to determine whether the expression of P120 in breast cancer correlated with histopathological or biological properties associated with prognosis. In this retrospective study, 120 primary breast tumors were analyzed for P120; 114 of these tumors were also stained for the erbB-2 protein. Immunopositive staining was correlated with patient survival, nodal status, estrogen receptor levels, and number of mitoses. Sixty-nine % (83 of 120) of the tumors were positive for P120; 25% (28 of 114) stained positively for erbB-2. Of the 28 erbB-2 positive tumors 26 were also positive for the P120 protein. Forty-six % (55 of 120) of the specimens were from patients who later died from recurrent breast cancer; P120 was detected in 89% (49 of 55) of these specimens. In 52% of the survivors the P120 protein was also expressed. P120 negative tumors were highly correlative with survival (P = 0.0001); 84% (32 of 37) of patients with P120 negative tumors survived more than 7 years without evidence of recurrent disease. Multivariate analysis showed that the worst prognosis was for patients who had tumor positive nodes and expressed P120 (P = 0.0001); death occurred in 73% (30 of 41) of these patients. For the node negative patients who did not express P120, 5-year survival was 90% (19 of 21 patients); 5-year survival for the node negative patients who expressed P120 was significantly less (67%; 28 of 42 patients). Patients with P120 negative tumors had a good prognosis, irrespective of their nodal status. In this group, survival of node negative patients was 86% (18 of 21) and for those with positive nodes survival was 82% (13 of 16). A poor prognosis was found for patients with intense erbB-2 stained tumors (5 of 7 patients died). Weak staining of erbB-2 tumors (21 specimens) was not correlated with patient survival. Compared to P120 negative tumors, P120 positive tumors had greater numbers of mitoses (9.06 versus 6.65) and an almost 2-fold increase in the occurrence of positive nodes (one of every 4.67 versus one of every 8.81). The number of P120 positive tumors was greater in estrogen receptor positive tumors (75%) than in estrogen negative tumors (54%).(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗

Transformation of human breast epithelial cells by c-Ha-ras oncogene.

To determine whether the c-Ha-ras oncogene plays a role in the initiation of mammary carcinogenesis, an immortalized human breast epithelial cell line, MCF-10A, was transfected with the plasmid vector pHo6T1 containing the T24 Ha-ras oncogene and the aminoglycoside phosphotransferase gene, which confers resistance to geneticin. Transfected cells exhibited an altered pattern of growth and tridimensional morphology in collagen gel. They also exhibited anchorage-independent growth and loss of requirement for hormones and epidermal growth factor; in addition, they expressed invasiveness and increased collagenolytic activity in an in vitro system and became tumorigenic in irradiated nude mice, all properties indicative of malignant transformation. Transformed cells contained the mutated c-Ha-ras oncogene and expressed the p21 mutated protein. These data indicate that the c-Ha-ras oncogene is capable of inducing malignant phenotypes in immortalized human breast epithelial cells.

Breast↗

Bilateral breast cancer: one disease or two?

Our purpose was to determine whether bilateral breast cancer depends upon genetic predisposition to multiple tumors or, alternatively, represents two independent sporadic events. Biological concordance of hormone receptors and histopathology in bilateral tumors, family history of breast cancer, age at diagnosis, and survival were evaluated in 88 patients. The immunoreactivity of paired tumors from 51 patients to six different immunocytochemical markers was compared. Neither histologic patterns nor immunocytochemical reactions showed concordance between bilateral tumors. Absence of concordance (other than for estrogen receptors) and lack of associations with positive family history and early age of onset support an interpretation of independent tumor origins and does not suggest a major role for genetic determinants in the majority of cases of bilateral breast cancer.

Adult↗

A retrospective analysis of breast cancer based on outcome differences.

We reviewed tumors from two groups of patients with breast cancer, distinguished by differences in outcome. One group (85 cases) survived more than 8.5 years without tumor recurrence; the other 85 cases had recurrent disease within 2 years. Histologic and immunocytochemical studies on all cases were performed without patient identifiers and prior to review of clinical prognostic factors. As expected, lymph node and estrogen receptor status differed substantially between the groups, but menopausal status and family history for breast cancer did not. We noted that 27% of node-negative patients died within 5 years, and nine patients with four or more tumor-containing nodes were symptom-free for over 8.5 years. Histologic grade (degree of tubule formation) and nuclear grade (including mitotic rate) differed significantly between the groups, as did vascular invasion, including both lymphatics and blood vessels. Prognostic value attached to tumor border only when fat was invaded without fibroblastic or inflammatory response (P = .012). Subgrouping cases of infiltrating ductal carcinoma (not otherwise specified) was prognostically informative in the B subgroup, 69% of whom were in the rapidly recurrent tumor group. Immunocytochemical staining for c-erbB-2 was positive in 19.3% of cases, but was equally distributed between the two outcome groups. We conclude that traditional histologic parameters are highly informative, and that c-erbB-2 studies do not increase the value of histologic diagnosis.

Breast Neoplasms↗

Sigma (12-15 Hz) and delta (0.3-3 Hz) EEG oscillate reciprocally within NREM sleep.

Sleep EEG in the sigma and delta frequency bands was subjected to spectral analysis in 8 normal young adults. In each subject, power density of sigma and delta oscillated reciprocally during NREM sleep, confirming an observation made initially with period/amplitude analysis. In REM sleep, power density for both frequency bands was at its lowest levels. Correlation coefficients between power density of delta vs. 1/sigma for all artifact-free 20-s epochs of NREM sleep/night were highly significant for each subject. These results show that cyclic oscillation of EEG within sleep is not limited to delta frequencies. The reciprocal relation of sigma to delta holds implications for the EEG mechanisms of NREM sleep. This dynamic pattern may also prove useful for sleep stage scoring and for a finer empirical analysis of sleep in psychiatric and neurological disorders.

Activity Cycles↗

Acute deprivation of the terminal four hours of sleep does not increase delta (0-3-Hz) electroencephalograms: a replication.

This experiment evaluated further our previous finding that substitution of waking for the terminal 3-4 hr of sleep produces little or no increase in either visually scored or computer measures of delta sleep. Eleven young adults (mean age 24.5 yr) were studied on a baseline night, a night with sleep limited to an average of 188 min, and a recovery night. Visually scored sleep stages, eye movement activity and computer measures of 0-3 Hz were analyzed by nonrapid eye movement periods (NREMPs) and for all recorded sleep in each condition. In addition, we measured the heights, durations and areas under the curve manifested by the cyclic waxing and waning of 0-3-Hz integrated amplitude across sleep. Acute loss of 3.9 hr of sleep did not increase either visual or computer measures of delta electroencephalograms (EEG) on the recovery night, essentially confirming our previous findings. We hypothesize that augmentation of delta EEG above baseline levels after acute (one night's) sleep loss requires that disruption or loss of sleep from the first two NREMPs (or delta cycles). Rapid eye movement (REM) sleep durations on the recovery night were unaffected by the marked loss of REM sleep caused by partial deprivation. Although eye movements as well as stage REM were lost in the deprivation condition, eye movement density was significantly reduced rather than increased on the recovery night. This reduction is consistent with the hypothesis that REM activity varies inversely with sleep depth (or directly with central arousal level). The observations here, taken in association with previous results, suggest that a threshold for eye movement suppression by sleep deprivation in young adults lies in the range of 3-4 hr of prior sleep loss.

Adult↗

Two-dimensional gel analysis of polypeptides from normal, preneoplastic and neoplastic mouse mammary tissues.

High-resolution two-dimensional polyacrylamide gel electrophoresis (PAGE) was employed to reveal tumor-associated polypeptide changes, using the BALB/c C4 line mouse mammary model system, for which phenotypic and immunogenic alterations accompanying tumor progression are well defined. In the first set of experiments, polypeptide patterns from 20 micrograms whole tissue lysates of normal mammary gland, C4 preneoplastic hyperplastic alveolar nodule outgrowth (HAN) and spontaneous tumor from C4 HAN were compared. In order to normalize for differential cellularity and extracellular protein content in the whole tissues, our analysis included polypeptide patterns from serum, increased concentration of protein from whole normal mammary gland, and primary cultures of epithelial cells from normal gland, HAN and tumor. Using a computer-based image-analysis system, 90 polypeptides were identified in C4 tumor that were absent in C4 HAN, normal mammary gland and serum. None of the 90 polypeptides could be shown to represent a definite qualitative change in the protein composition of tumor epithelium as they were found to be either present in a higher concentration of protein from whole normal gland, or present in the primary epithelial culture from HAN, or absent in the primary epithelial culture from tumor. Conversely in the second set of experiments, when epithelial cultures were used as the starting point for comparisons to locate tumor-associated polypeptides, none of the 15 polypeptides that were present in cultures from three different tumors, and absent in the culture from normal mammary gland was specific to C4 tumor, as they were present in whole tissues of normal gland. Thus our experimental approach detected significant quantitative but no qualitative polypeptide changes in whole tumor tissue, or in tumor-derived epithelial cell cultures. This finding may reflect the limitations of the two-dimensional PAGE method, and warrants caution in the use of such gel analysis alone to identify tumor-associated proteins.

Animals↗

Adjuvant CMFVP versus melphalan for operable breast cancer with positive axillary nodes: 10-year results of a Southwest Oncology Group Study.

Four hundred forty-one women with operable breast cancer with histologically positive axillary nodes were randomized to receive either combination cyclophosphamide (60 mg/m2 orally everyday for 1 year); fluorouracil (300 mg/m2 intravenously [IV] weekly for 1 year); methotrexate (15 mg/m2 IV weekly for 1 year); vincristine (0.625 mg/m2 IV for 10 weeks); prednisone (30 mg/m2 orally days 1 to 14, 20 mg/m2 days 15 to 28, 10 mg/m2 days 29 to 42) (CMFVP) or single-agent melphalan (L-PAM) (5 mg/m2 orally every day for 5 days every 6 weeks for 2 years) chemotherapy after a modified or radical mastectomy between January 1975 and February 1978. Patients were stratified according to menopausal status and number of positive nodes (one to three, more than three nodes) before randomization. Seventy-eight patients were ineligible, most (56) because they were registered more than 42 days from surgery. Maximum duration of follow-up is 12 years, with a median of 9.8 years. The treatment arms were balanced with respect to age, menopausal status, and number of positive nodes. Among eligible patients, disease-free survival and survival were superior with CMFVP (P = .002, .005, respectively). At 10 years, 48% of patients treated with CMFVP remain alive and disease-free and 56% remain alive, compared with 35% alive and disease-free and 43% alive on the L-PAM arm. Disease-free survival and survival were significantly better with CMFVP compared with L-PAM only in premenopausal patients and patients with four or more positive nodes. Both regimens were well tolerated, although toxicity was more severe and more frequent with CMFVP. We conclude that after 10 years of follow-up, adjuvant combination chemotherapy with CMFVP is superior to single-agent L-PAM in patients with axillary node-positive primary breast cancer. The major advantage is in premenopausal women and in patients with more than three positive axillary nodes.

Age Factors↗

Lack of benefit of adjunctive chemotherapy in stage I malignant melanoma: a Southwest Oncology Group Study.

In 1975, the Southwest Oncology Group initiated an adjuvant study in localized malignant melanoma testing the value of aggressive chemotherapy using carmustine, hydroxyurea, and dacarbazine versus a control arm. Median disease-free survival was 7.1 years for the control arm and 6 years for the treatment arm. Survival was identical for both arms with 65% of the patients alive at 6 years. We conclude that carmustine, hydroxyurea, and dacarbazine chemotherapy is of no value as adjuvant treatment for localized melanoma.

Adult↗