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Biomedical subjects

K Putnam

Publications and source records attributed to K Putnam.

13 recordsLinked to original sources
PubMed2002

Working memory and apolipoprotein E: what's the connection?

Two robust findings in the Alzheimer's literature are that patients with Alzheimer's disease (AD) show executive function and primacy deficits. The present study examined whether we would find similar deficits when comparing two groups of middle-aged individuals who differed with respect to genetic risk for AD, based on their apolipoprotein E (APOE) genotype. All individuals were screened as normal on a battery of standardized cognitive measures. They were tested on the "Operation span task", which engages the central executive component of working memory [J. Exp. Psychol.: Gen. 128 (1999) 309, J. Exp. Psychol.: Gen. 126 (1997) 211, J. Mem. Language 39 (1998) 418] by dividing attention between processing math operations and remembering words. Individuals were grouped according to APOE genotype ( epsilon 4 carrier versus epsilon 4 non-carrier), matched on age and education, and their Total span and Primacy scores were compared. Despite having no overt symptoms of dementia or deficits on a series of standardized psychometric tests, the epsilon 4 carriers showed divided-attention and primacy deficits on the Operation span task, when compared to the epsilon 4 non-carriers. As a point of comparison, Primacy scores were extracted from the first trial of the "Buschke selective reminding task" [J. Verbal Learn. Verbal Behav. 12 (1973) 543] for these same individuals, and no group differences were found. The Buschke task is a list-learning task that does not require divided attention. These findings suggested that the epsilon 4 carriers were less able to divide their attention, when compared to the epsilon 4 non-carriers. The findings provide the first direct evidence for a relationship between APOE genotype and cognitive performance on measures of divided attention and primacy with non-demented individuals who showed no cognitive impairments on standardized measures.

Aged↗
PubMed2001

Hippocampal complex and retrieval of recent and very remote autobiographical memories: evidence from functional magnetic resonance imaging in neurologically intact people.

It has been argued that the role of the hippocampus in memory is time-limited: during a period of memory consolidation, other brain regions such as the neocortex are said to acquire the ability to support memory retention and retrieval on their own. An alternative view is that retention and retrieval of memory for autobiographical episodes depend on the hippocampal complex, regardless of the age of the memory. We examined the participation of the hippocampal complex in a functional magnetic resonance imaging (fMRI) study in which participants were asked to recollect autobiographical events that occurred either within the last 4 years or more than 20 years ago. We found equivalent levels of hippocampal activation in both conditions in all participants (N = 10). In addition, activation in neocortical regions did not differ as a function of the age of the memory, even though most of the recent memories recalled were less than 2 years old and the remote memories more than 35 years old. The results support the notion that the hippocampal complex participates in retention and recovery of even very old autobiographical memories, and place boundary conditions on theories of memory consolidation.

Autobiographies as Topic↗
PubMed1999

Regional brain function, emotion and disorders of emotion.

Significant progress has been made in our understanding of the neural substrates of emotion and its disorders. Neuroimaging methods have been used to characterize the circuitry underlying disorders of emotion. Particular emphasis has been placed on the prefrontal cortex, anterior cingulate, parietal cortex, and the amygdala as critical components of the circuitry that may be dysfunctional in both depression and anxiety.

Affective Symptoms↗
PubMed1998

Chemical and biological studies of a new cigarette that primarily heats tobacco. Part 3. In vitro toxicity of whole smoke.

Mainstream smoke from Kentucky reference low "tar" (1R4F) and ultra-low "tar" (1R5F) cigarettes and a test cigarette (TOB-HT), that primarily heats tobacco, was compared for cytotoxic and genotoxic potential using cellular smoke exposure technology (CSET). CSET includes a computer controlled 30-port AMESA/Battelle-Geneva smoke generator which exposes cultured mammalian Chinese hamster ovary cells (CHO) to whole smoke. Cytotoxicity was assessed using the neutral red assay and genotoxicity was assessed using the sister chromatid exchange (SCE) assay. Compared on a per cigarette basis, mainstream smoke from 1R5F and the TOB-HT cigarette was significantly less cytotoxic and genotoxic than the smoke from the 1R4F cigarette. The cytotoxic and genotoxic activity of smoke from the TOB-HT cigarettes was slightly greater than the smoke from the ultra-low "tar" Kentucky 1R5F reference cigarettes. In conclusion, in these assays mainstream whole smoke of the TOB-HT cigarette had slightly greater cytotoxic and genotoxic potential compared with an ultra-low "tar" 1R5F Kentucky reference cigarette and significantly less activity compared with the whole mainstream smoke from a low "tar" 1R4F Kentucky reference cigarette, representative of the US market average cigarette for FTC yields of "tar", CO and nicotine.

Animals↗
PubMed1997

Evaluation of the genotoxic and cytotoxic potential of mainstream whole smoke and smoke condensate from a cigarette containing a novel carbon filter.

A novel carbon filter has been developed which primarily reduces the amount of certain vapor phase constituents of tobacco smoke with greater efficiency than the charcoal filters of cigarettes currently in the market. In vitro indicators of genotoxic and cytotoxic potential were used to compare the cigarette smoke condensate (particulate phase) or whole cigarette smoke (vapor phase and particulate phase) from cigarettes containing the novel carbon filter with smoke condensate or whole smoke from commercial or prototype cigarettes not containing the novel carbon filter. Ames bacterial mutagenicity, sister chromatid exchange (SCE) in Chinese hamster ovary (CHO) cells, and neutral red cytotoxicity assays in CHO cells were utilized to assess the genotoxic and cytotoxic potential of the cigarette smoke condensates. SCE and neutral red cytotoxicity assays were utilized to assess the genotoxic and cytotoxic potential of the whole smoke. As expected, the novel carbon filter did not significantly affect the genotoxic or cytotoxic activity of the smoke condensate, although we did observe that the use of low-nitrogen tobacco reduced the mutagenicity of the condensate in Salmonella typhimurium strain TA98. However, the whole smoke from cigarettes containing the novel carbon filter demonstrated significant reductions in genotoxic and cytotoxic potential compared to cigarettes without the novel carbon filter. The toxicity of the smoke was correlated (r = 0.7662 for cytotoxicity and r = 0.7562 for SCE induction) to the aggregate mass of several vapor phase components (acetone, acetaldehyde, acrolein, acrylonitrile, 1,3-butadiene, ammonia, NOx, HCN, benzene, isoprene, and formaldehyde) in the smoke of the cigarettes utilized in this study. In conclusion, this novel carbon filter, which significantly reduced the amount of carbonyls and other volatiles in mainstream cigarette smoke, resulted in significant reductions in the genotoxic and cytotoxic activity of the smoke as measured by these assays.

Animals↗
PubMed1996

Human pharmacokinetics and tolerability of L-365,260, a novel cholecystokinin-B antagonist.

A study was conducted to examine the tolerability and pharmacokinetics of single and multiple oral doses of L-365,260, a novel antagonist for type B cholecystokinin (CCK) receptors and to quantify effects of selective blockade of type B CCK receptors through treatment with L-365,260 on measures of anxiety, hunger, and cognitive performance. Healthy volunteers were given single oral doses of up to 50 mg of L-365,260 and multiple oral doses of up to 25 mg every 6 hours for 10 days. Plasma concentrations of L-365,260 were quantified by means of high-performance liquid chromatography. Anxiety and hunger were assessed by visual analog scale and the Spielberger State Anxiety Index. Cognitive testing was used to evaluate attention level and short-term memory. L-365,260 was rapidly absorbed and a biphasic pattern of elimination was demonstrated with a terminal half-life (t1/2) of 8 to 12 hours. The mean (n = 6) values for peak plasma concentration (C(max)) and time to peak concentration (t(max)) of L-365,260 were 503 ng/mL and 1.25 hours, respectively, after a single 50-mg oral dose. Accumulation of L-365,260 plasma concentrations was seen after the prescribed multiple-dose regimens. Steady state was achieved after 3 days of oral administration. L-365,260 had an acceptable tolerability profile after oral administration. No changes in measures of anxiety, hunger, or short-term memory were observed at doses of L-365,260 shown to have antagonist activity at the CCK-B receptor.

Administration, Oral↗
PubMed1996

Diagnosis and six-month stability of negative symptoms in psychotic disorders.

Negative symptoms were examined in 150 primarily first-admission patients diagnosed with schizophrenia, schizoaffective disorder, psychotic depression, psychotic bipolar disorder, and 'other' psychoses. The analysis focused on patients who were rated on the Scale for the Assessment of Negative Symptoms (SANS) within 45 days of admission and at follow-up 6 months later. Significantly more schizophrenics had moderate to severe negative symptoms at each time point compared with other psychotic patients. The SANS scores were found to be relatively stable over time in all five diagnostic groups. Although the DSM-IV includes alogia, affective flattening, and avolition in the A criterion for schizophrenia, only alogia and affective flattening were found to be specific to this disorder. Our results point to the existence and enduring quality of negative symptoms in the early phase of psychosis and its specificity to schizophrenia even at this early stage.

Adolescent↗
PubMed1995

Gender, premorbid characteristics and negative symptoms in schizophrenia.

The interrelationships among gender, premorbid functioning, and negative symptoms were examined in a first-admission inpatient sample with DSM-III-R schizophrenia. Fifty-two subjects were assessed with the Schedule for the Assessment of Negative Symptoms (SANS) at baseline and 6-month follow-up. Three indicators of premorbid functioning were examined: the Premorbid Adjustment Scale, the Quick Test, and the GAF for the best month in the year prior to the baseline interview. Men and women had relatively similar ratings on each of the 5 SANS global subscales at both times; they were also relatively similar on most of the indicators of premorbid functioning. The men and women were categorized into low vs moderate-high negative symptom groups at baseline, and no differences in premorbid functioning were detected. When the sample was classified into those with and without consistent negative symptoms at baseline and 6-month follow-up, the enduring negative men and women had significantly poorer premorbid functioning in several areas than the consistently non-negative patients. Our findings support the importance of assessing negative symptoms longitudinally and suggest that gender is not strongly associated with negative symptoms and premorbid functioning in patients ascertained at early stages of schizophrenia.

Adult↗
PubMed1992

Alzheimer's disease and feeling-of-knowing for knowledge and episodic memory.

The metamemory (knowledge of the veracity of memories) of moderately impaired Alzheimer's patients was compared to that of aged controls. Despite their profoundly impaired recall of information from both long-term (knowledge) and recent (episodic) memory, Alzheimer's patients were as accurate as controls in assigning confidence ratings related to the probability that their recalls were correct. They were impaired, however, at predicting the likelihood that they would subsequently recognize correct answers (feeling-of-knowing) to knowledge memory questions which they had been unable to recall correctly. Nevertheless, their performance on this task did exceed chance. Thus, the moderately impaired Alzheimer's patient demonstrates intact awareness of the veracity of recall from knowledge and episodic memory but shows impaired feeling-of-knowing for knowledge memory.

Aged↗
PubMed1992

A strategy of "combination chemotherapy" in Alzheimer's disease: rationale and preliminary results with physostigmine plus deprenyl.

Although the central cholinergic deficits are still considered to be of primary importance in Alzheimer's disease, there is great need for an expansion of the pharmacological approach in this illness beyond the simple cholinergic replacement hypothesis. This report focuses on the concept of "combination chemotherapy" in Alzheimer's disease as the next generation of therapeutic strategies. Based on earlier positive findings in Alzheimer patients with the monoamine oxidase B inhibitor, 1-deprenyl, the authors speculate that a combination of physostigmine, the short-acting cholinesterase inhibitor, and 1-deprenyl might be more beneficial than either agent alone. The authors outline a sample paradigm for such combination studies, report preliminary data on the first 16 Alzheimer subjects to have received an initial combination of physostigmine and deprenyl, and point to other possible "combination chemotherapy" strategies for future study.

Aged↗