Cognitive functioning and depression in patients with chronic fatigue syndrome and multiple sclerosis.

OBJECTIVE: To assess cognitive function in patients with chronic fatigue syndrome (CFS) and multiple sclerosis (MS) and to evaluate the role of depressive symptoms in cognitive performance. DESIGN: Case-control. All subjects were given a neuropsychological battery, self-report measures of depression and fatigue, and a global cognitive impairment rating by a neuropsychologist "blinded" to clinical diagnosis. Patients with MS and CFS were additionally evaluated with a Structured Clinical Interview for DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition) disorders. SETTING: Institutional and private neurological practices and the community at large. PATIENTS: Twenty patients with CFS diagnosed in accord with the Centers for Disease Control and Prevention-revised criteria who had cognitive complaints; 20 patients with clinically definite MS who were ambulatory and were matched for fatigue severity, age, and education to CFS subjects; and 20 age- and education-matched healthy controls. RESULTS: Patients with CFS had significantly elevated depression symptoms compared with patients with MS and healthy controls (P < .001) and had a greater lifetime prevalence of depression and dysthymia compared with MS subjects. Patients with CFS, relative to controls, performed more poorly on the Digit Symbol subtest (P = .023) and showed a trend for poorer performance on logical memory (P = .087). Patients with MS compared with controls had more widespread differences of greater magnitude on the Digit Span (P < .004) and Digit Symbol (P < .001), Trail Making parts A (P = .022) and B (P = .037), and Controlled Oral Word Association (P = .043) tests. Patients with MS also showed a trend of poorer performance on the Booklet Category Test (P = .089). When patients with CFS and MS were directly compared, MS subjects had lower scores on all measures, but the differences reached significance only for the Digit Span measure of attention (P = .035). CONCLUSIONS: Patients with CFS compared with MS have more depressive symptoms but less cognitive impairment. Relative to controls, a subset of CFS subjects did poorly on tests of visuomotor search and on the logical memory measure of the Wechsler Memory Scale-revised. Poor performance of logical memory in CFS appears to be related to depression, while visuomotor deficits in CFS are unrelated. Cognitive deficits in patients with MS are more widespread compared with those in patients with CFS and are independent of depressive symptoms.

Politics, science, and the emergence of a new disease. The case of chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) emerged as a diagnostic category during the last decade. Initial research suggested that CFS was a relatively rare disorder with a high level of psychiatric comorbidity. Many physicians minimized the seriousness of this disorder and also interpreted the syndrome as being equivalent to a psychiatric disorder. These attitudes had negative consequences for the treatment of CFS. By the mid-1990s, findings from more representative epidemiological studies indicated considerably higher CFS prevalence rates. However, the use of the revised CFS case definition might have produced heterogeneous patient groups, possibly including some patients with pure psychiatric disorders. Social scientists have the expertise to more precisely define this syndrome and to develop appropriate and sensitive research strategies for understanding this disease.

Symptom patterns in long-duration chronic fatigue syndrome.

OBJECTIVE: Our objective was to evaluate symptom patterns in patients with chronic fatigue syndrome (CFS) who were ill for 10 or more years. METHODS: This cross-sectional self-report study compared patient groups with long-duration (median = 18 years; n = 258) and short-duration (median = 3 years; n = 28) CFS to a group of healthy significant others (n = 79) on symptomatic, neurocognitive, and psychological variables. Data were gathered from a 574-item postal questionnaire. RESULTS: A principal-components analysis of CFS symptom data yielded a three-factor solution: cognitive problems; flu-like symptoms; and neurologic symptoms. Compared with the short-duration CFS group, the long-duration group had significantly higher CFS symptom severity scores (p < 0.04), largely attributable to increased cognitive difficulties. A subgroup comparison of subjects ill for < 3 years versus those ill 4-7 years suggested that denial coping strategies were more likely in those participants with the shorter illness duration. Significant differences between both CFS groups and healthy controls were found in a number of comorbid disorders. Participants with CFS most often endorsed immune/viral abnormalities and persistent stress as important perceived causes of their illness. CONCLUSION: Participants with long-duration CFS reported a large number of specific cognitive difficulties that were greater in severity than those reported by participants with short-duration CFS. The pattern of comorbid disorders in the CFS groups was consistent with hypersensitivity and viral reactivation hypotheses.

Species comparison of calmodulin sequences.

No amino acid substitutions can be located when the calmodulin produced in various vertebrate species (human, rat, chicken, toad) are compared. However, multiple substitutions exist in calmodulin derived from non-vertebrates. Here, we have determined the residues for which no alterations in sequence are allowed. The protein from each species exhibits a sequence identity from residue 27 to residue 53, i.e., residues spanning a small part of the Ca2+ binding loop I and the adjacent interloop region. The analogous sequence (residues 100 to 129) abutting the Ca2+ binding loop III also exhibits only a few differences. Furthermore, negatively charged side chains at residues 82-84 in the central alpha-helix are conserved.

Accuracy of indirect estimates of maternal mortality: a simulation model.

A simulation model was developed to test the accuracy of indirect estimates of maternal mortality (the sisterhood method). The model generated a first generation of grandmothers, a second generation of mothers (with brothers and sisters), and a third generation of children (births). In the second generation, maternal mortality was introduced. Empirical values for the parameters of fertility and mortality were taken from a prospective survey in Senegal (Niakhar). Results based on 100 simulations of the same situation revealed several limitations of the sisterhood method: The indirect estimates could fall as far as 33 percent from the true values on individual cases; the indirect estimates tended to be systematically higher than the direct estimates; their range was wider, as were their confidence intervals; and biases were particularly strong for the younger age groups of respondents. Reasons for these biases are explored.

PIP: A simulation method was used to assess the accuracy of indirect estimates of maternal mortality (sisterhood method). The model generated a first generation of grandmothers, a second generation of mothers (with brothers and sisters), and a third generation of children (births). Maternal mortality was introduced in the second generation. Fertility and mortality parameters for the simulations were derived from a prospective study conducted in Niakhar, Senegal, in 1983-89. Results based on 100 simulations of the same situation revealed several limitations of the sisterhood method. The indirect estimates were as far as 33% from the true values on individual cases, despite the assumed perfect quality of the data. The indirect estimates tended to be systematically higher than the direct estimates, with wider ranges and confidence intervals. Biases were especially marked for the younger age group (15-39 years). The only justification for use of indirect rather than direct estimates seems to be the avoidance of questions about age differences between the respondent and the sister and the age of the sister at time of death, when applicable. Recommended, instead of indirect estimates, are two methods of computing direct estimates of maternal mortality: 1) direct computation of the maternal mortality quotient, followed by conversion to the maternal mortality rate through use of the total fertility rate, and 2) use of information on parity by age from maternity histories to compute the maternal mortality rate in each age group directly.

Cloning and characterization of the beta-amylase gene from Bacillus polymyxa.

The gene for beta-amylase was isolated from Bacillus polymyxa by molecular cloning in B. subtilis. B. subtilis cells containing this gene express and secrete an amylase which resembles the B. polymyxa beta-amylase and barley beta-amylase in terms of the products it generates during carbohydrate hydrolysis. Starch hydrolysis with this beta-amylase produces maltose, not glucose, whereas maltotriose and cycloheptaose are resistant to the action of this beta-amylase. The enzyme has a molecular weight of approximately 68,000. Restriction endonuclease mapping demonstrated that the DNA inserted in pBD64 and containing the gene is approximately 3 kilobases in length.

Segments of amino acid sequence similarity in beta-amylases.

In alpha-amylases from animals, plants and bacteria and in beta-amylases from plants and bacteria a number of segments exhibit amino acid sequence similarity specific to the alpha or to the beta type, respectively. In the case of the beta-amylases the similar sequence regions are extensive and they are disrupted only by short interspersed dissimilar regions. Close to the C terminus, however, no such sequence similarity exist.

Sequence of cyanogen bromide fragments D and E of B. amyloliquefaciens alpha amylase.

Alpha amylase (Sigma type IIA) was cleaved by cyanogen bromide. The sequences of two fragments, D which contains 88 amino acids and E which contains 56, are presented. By applying the Chou-Fasman rules, D is predicted to have 32% beta sheet and 37% alpha helix, and E is predicted to exhibit 11% beta sheet and 71% alpha helix.

Sequence of the N-terminal half of Bacillus amyloliquefaciens alpha-amylase.

Bacillus amyloliquefaciens alpha-amylase (1,4-alpha-D-glucan glucanohydrolase. EC 3.2.1.1), which is commercially supplied as 'Bacillus subtilis alpha-amylase' does not cross-react immunologically with B. subtilis alpha-amylase. This enzyme (from B. amyloliquefaciens) was cleaved by treatment with CNBr into seven fragments. Peptide A was selected for sequence determination. It is the longest one, containing 185 amino acids (i.e. approx. 50% of the total molecule) and connects to the hexapeptide of the N-terminus. Its primary structure was aligned by use of various proteolytic enzymes. The sequence of amino acids 181-184 is identical with that of amino acids 14-17 of the alpha-amylase isolated from B. subtilis (except that amino acid 183 is asparagine rather than aspartic acid).

Sequence motifs for calmodulin recognition.

Calmodulin (CaM) is recognized as a major calcium sensor and orchestrator of regulatory events through its interaction with a diverse group of cellular proteins. Many investigations have focused on defining the region of interaction between CaM and its cellular targets and the action of CaM on target protein function. Because CaM can bind with high affinity to a relatively small alpha-helical region of many proteins, success in clearly defining the essential elements of CaM binding motifs seems feasible and should provide a means of identifying CaM binding proteins. Three recognition motifs for CaM interaction are discussed in the context of experimental investigations of a variety of CaM target proteins. A modified version of the IQ motif as a consensus for Ca2+-independent binding and two related motifs for Ca2+-dependent binding, termed 18-14 and 1-5-10 based on the position of conserved hydrophobic residues, are proposed. Although considerable sequence diversity is observed among the different binding regions, these three classes of recognition motifs exist for many of the known CaM binding proteins.

Multiple mRNAs encoding human calmodulin.

In humans, as in rats, four distinct molecular weight species of mRNA encoding calmodulin exist, i.e. 1.6 Kb for L, 1.4 Kb for T2 and 2.5 and 1.0 Kb for T1. They result from the expression of three genes. Each of these mRNAs codes for a calmodulin identical in amino acid sequence. The 5' and 3' untranslated regions of these mRNAs, however, differ extensively, and oligonucleotide probes specific to these regions were used in this study. The poly A+ mRNA was isolated from human erythroleukemia cells and also from human B cells infected with EBV.

Molecular weight of B. subtilis alpha-amylase derived from chemical studies.

Bacillus subtilis alpha-amylase was cleaved with cyanogen bromide and the amino terminal sequences of the purified products were determined. The molecular weights of the cyanogen bromide fragments were ascertained on an agarose column equilibrated with 6 M guanidine hydrochloride. The molecular wieghts of these fragments were also calculated from their amino acid compositions. The data obtained bzyme monomer as 48,000.