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PubMed1996

An insertion/deletion polymorphism in the angiotensin converting enzyme gene is associated with both brain substance P contents and affective disorders.

Because of a potent action of angiotensin converting enzyme (ACE) to degrade substance P (SP) and an association of the insertion/deletion (I/D) polymorphism of the ACE gene with ACE activity, an association between the SP level and the ACE I/D polymorphism were examined using 20 human postmortem brain samples. The results showed a significant association between the polymorphism and SP levels in the basal ganglia and substantia nigra, where both ACE and SP concentrate, and a higher SP level in the subjects with the DD genotype than in those with the II genotype, with an intermediate level in heterozygotes. Associations of the polymorphism with schizophrenia and affective disorders were also investigated in 292 unrelated Japanese schizophrenics, 65 patients with affective disorders, and 579 controls. The D allele was significantly more frequent in the patients with affective disorders than in the controls (p < .02), and the DD genotype was significantly more frequent in the patients with affective disorders than in the controls (p < .002). There is no significant difference in the frequencies of the allele and the genotype between the controls and schizophrenics. These results suggest that the ACE I/D polymorphism is one of the genetic factors for an interindividual variability of brain SP levels, and that the ACE polymorphism may contribute to the susceptibility to affective disorders.

Adult↗
PubMed2000

Reducing conditions differentially affect the functional and structural properties of group-I and -II metabotropic glutamate receptors.

We have examined the influence of reducing conditions on the activity of group-I or -II metabotropic glutamate receptors. In cultured cerebellar granule cells or in hippocampal slices, the reducing agent dithiothreitol (DTT) inhibited the stimulation of polyphosphoinositide (PPI) hydrolysis elicited by group-I mGlu receptor agonists without affecting responses to norepinephrine or carbamylcholine. Similarly, DTT reduced the increase in intracellular free Ca(2+) induced by glutamate in HEK-293 cells expressing mGlu5 receptors. In adult hippocampal slices, the selective group-II mGlu receptor agonist, (2S,1'R,2'R,3'R)-2-(2, 3-dicarboxycyclopropyl)glycine (DCG-IV) had no effect per se on PPI hydrolysis, but potentiated the response to quisqualate. Although DTT substantially attenuated the action of quisqualate, it did not affect the potentiation by DCG-IV, suggesting that group-II mGlu receptors are resistant to extracellular reduction. Accordingly, DTT did not affect the inhibition of forskolin-stimulated cAMP formation induced by maximally effective concentrations of group-II mGlu receptor agonists in hippocampal slices or in CHO cells expressing mGlu2 receptors. At structural level, DTT differentially affected the aggregation state of mGlu1a, -2/3 or -5 receptors. In immunoblots performed under non-reducing conditions, mGlu1a, -2/3 or -5 antibodies labeled exclusively a high-molecular weight band, corresponding to receptor dimers. Under reducing conditions, mGlu1a or -5 receptors were detected as monomers, whereas a large proportion of mGlu2/3 receptors was still present in a dimeric form. We conclude that reducing conditions differentially influence the aggregation state of group-I and -II mGlu receptors and suggest that dimerization affects the functional activity of native mGlu receptors.

Amino Acids, Dicarboxylic↗
PubMed1996

Lipoprotein lipase activity of post-heparin plasma in Japanese black cattle affected with fat necrosis.

Post-heparin plasma (PHP) lipoprotein lipase (LPL) activity and serum lipoprotein concentration were examined in Japanese Black cows affected with fat necrosis. The PHP-LPL activity in the affected cows was significantly (P < 0.001) higher than in normal animals and tended to reduce 4 weeks after treatment with isoprothiolane. This finding indicates that affected cows have a predisposition to deposit more fat into adipose tissue than normal animals. The serum concentrations of triglyceride in beta-lipoprotein and of cholesterol, phospholipid and total lipid in alpha-lipoprotein were significantly (P < 0.05) lower in the affected cows. Elevated levels of phospholipid and total lipid in alpha-lipoprotein as well as decreased levels of non-esterified fatty acid (NEFA) were observed after medication. It is suggested that isoprothiolane produces an improvement in hepatic lipid metabolism including acceleration of plasma NEFA uptake and alpha-lipoprotein secretion in affected cows.

Animals↗
PubMed1997

Urine glycosaminoglycan concentrations in mucopolysaccharidosis VI-affected cats following bone marrow transplantation or leukocyte infusion.

Urinary glycosaminoglycan (GAG) concentrations were determined in nineteen normal cats (eleven kittens and eight adult cats), eighteen mucopolysaccharidosis VI (MPS VI)-affected untreated cats (ten kittens and eight adult cats), thirteen cats MPS VI-affected cats following bone marrow transplants (BMT), and two MPS VI-affected cats following intravenous infusion of leukocytes from normal cats. Mucopolysaccharidosis VI-affected cats treated with BMT had a precipitous decrease in urinary GAG by day 7 post-BMT, then a transient increase just prior to engraftment, followed by a sustained decrease to within, or near, the range of urinary GAG concentration established for normal cats. The pre-engraftment changes in urinary GAG excretion were reproduced by leukocyte infusion. After infusion of comparable members of normal peripheral blood leukocytes, a significant decrease in urinary GAG concentrations, specifically dermatan sulfate (DS), was seen with a nadir at day 5 post-infusion, followed by a return by day 9 to pre-infusion values. Post-engraftment, a continued low urinary GAG concentration with a specific decrease in DS can be utilized to document successful autologous engraftment in MPS VI-affected cats.

Animals↗
PubMedDate not supplied

The experience of basic emotions in schizophrenia with and without affective negative symptoms.

A diminished ability to experience emotion could be a key characteristic of the negative symptomatology in schizophrenia. We examined the frequency of basic emotions in everyday life as well as emotion control in various groups of chronic schizophrenic patients. Self-report questionnaires (Differential Emotions Scale [DES], Emotion Control Questionnaire [ECQ]) were provided to healthy controls and three groups of schizophrenia patients (n=88), i.e., affectively flat patients, anhedonic patients, and patients not suffering from affective negative symptoms. Patients with affective negative symptoms experienced the positive emotions interest and joy less frequently than healthy subjects or patients without affective negative symptoms. All schizophrenia patients felt fear more often and tended to feel disgust more frequently than healthy subjects. The frequency of guilt and anger experiences increased with the chronicity of the disease. Anhedonic patients manifested more emotion inhibition than healthy controls and exhibited an affectivity pattern consistent with Meehl's model of anhedonia.

Adult↗
PubMed1990

Mutants of pheV in Escherichia coli affecting control by attenuation of the pheS, T and pheA operons. Two distinct mechanisms for de-attenuation.

Two mutants of pheV, a gene coding for tRNA(Phe) in Escherichia coli, were previously isolated because they affect attenuator control of the pheS, T operon when the mutant pheV genes are carried by the plasmid pBR322. We show that the two mutants (A44 and A46) affect attenuator control by different mechanisms. The effect of mutant A44 on pheS, T expression can be progressively decreased by overproduction of Phe-tRNA synthetase, consistent with the mutant tRNA acting as a competitive inhibitor of the enzyme. By contrast, the effect on attenuation of mutant A46 increases with overproduction of Phe-tRNA synthetase, indicating that the mutant must be charged to affect attenuation; we propose that this mutant affects translation directly and causes derepression by competing with wild-type tRNA in translation of the attenuator region leader peptide. Mutant A46 but not mutant A44 leads to further de-attenuation in a miaA background. The presence of two different mechanisms for de-attenuation is further indicated by the finding that a second attenuator controlled by Phe codon translation, from the pheA operon, is affected quite differently by the mutant tRNAs. Finally, experiments involving the introduction of the mutations A44 and A46 into an amber suppressor derived from tRNA(Phe) suggest that both species can function in protein synthesis but with reduced efficiency; mutant A46 is less efficient than mutant A44, consistent with a defect in elongation.

Amino Acid Sequence↗
PubMed2000

Procedure-related miscarriages and Down syndrome-affected births: implications for prenatal testing based on women's preferences.

OBJECTIVE: To determine how pregnant women of varying ages, races, ethnicities, and socioeconomic backgrounds value procedure-related miscarriage and Down-syndrome-affected birth. METHODS: We studied cross-sectionally 534 sociodemographically diverse pregnant women who sought care at obstetric clinics and practices throughout the San Francisco Bay area. Preferences for procedure-related miscarriage and the birth of an infant affected by Down syndrome were assessed using the time trade-off and standard gamble metrics. Because current guidelines assume that procedure-related miscarriage and Down syndrome-affected birth are valued equally, we calculated the difference in preference scores for those two outcomes. We also collected detailed information on demographics, attitudes, and beliefs. RESULTS: On average, procedure-related miscarriage was preferable to Down syndrome-affected birth, as evidenced by positive differences in preference scores for them (time trade-off difference: mean = 0.09, median = 0.06; standard gamble difference: mean = 0.11, median = 0.02; P <.001 for both, one-sample sign test). There was substantial subject-to-subject variation in preferences that correlated strongly with attitudes about miscarriage, Down syndrome, and diagnostic testing. CONCLUSION: Pregnant women tend to find the prospect of a Down syndrome-affected birth more burdensome than a procedure-related miscarriage, calling into question the equal risk threshold for prenatal diagnosis. Individual preferences for those outcomes varied profoundly. Current guidelines do not appropriately consider individual preferences in lower-risk women, and the process for developing prenatal testing guidelines should be reconsidered to better reflect individual values.

Abortion, Spontaneous↗
PubMed2003

Food availability and photoperiod affect reproductive development and maintenance in the marsh rice rat (Oryzomys palustris).

To examine whether photoperiod and food availability interact to influence reproductive development (Experiment 1), we exposed juvenile male and female rice rats to 16L:8D or 14L:10D and to ad lib, 80% of ad lib, or 60% of ad lib food intake from 3 to 8 weeks of age and recorded body and reproductive organ masses. Absolute paired testis masses were similar in ad lib and 80% of ad lib groups but significantly different than the 60% of ad lib group in both photoperiods. Relative paired testis masses were significantly different in the 80% and 60% of ad lib groups on 16L:8D only. Absolute seminal vesicle masses (SVM) were directly dependent upon the level of food restriction in both photoperiods, but relative SVMs were different only in the 60% of ad lib group. Terminal body masses were also directly dependent upon the level of food restriction and were greater on 16L:8D than on 14L:10D at most levels of food availability. In juvenile females, absolute uterine mass was only affected in the 60% of ad lib group on 14L:10D, while absolute paired ovary masses were affected on both photoperiods in the 60% of ad lib groups only. There was no effect of photoperiod or food on relative uterine and paired ovary masses. Terminal body mass was affected by food intake in both photoperiods. Lastly, in adult males (Experiment 2), photoperiod and food restriction affected reproductive function. Within a photoperiod, there was no effect of food restriction (75% of ad lib) on the testes, seminal vesicles, or testosterone levels in animals housed on 16L:8D, but terminal body mass was significantly reduced. On 12L:12D, however, food restriction significantly decreased testes and SVMs relative to ad lib-fed controls. Testosterone levels were reduced regardless of food availability. There was no effect of food restriction on terminal body mass. These results suggest that multiple potential environmental cues can be utilized to affect gonadal status in both juvenile and adult marsh rice rats.

Animals↗
PubMed1999

Accumulation of heavy metals in sunflower and sorghum plants affected by the Guadiamar spill.

The collapse of a pyrite-mining, tailing dam on 25 April 1998 contaminated approximately 2000 ha of croplands along the Agrio and Guadiamar river valleys in southern Spain. This paper reports the accumulation of chemical elements in soil and in two crops--sunflower and sorghum--affected by the spill. Total concentrations of As, Bi, Cd, Cu, Mn, Pb, Sb, Tl and Zn in spill-affected soils were greater than in adjacent, unaffected soils. Leaves of spill-affected crop plants had higher nutrient (K, Ca and Mg for sunflower and N and K for sorghum) concentrations than controls, indicating a 'fertilising' effect caused by the sludge. Seeds of spill-affected sunflower plants did accumulate more As, Cd, Cu and Zn than controls, but values were below toxic levels. Leaves of sorghum plants accumulated more As, Bi, Cd, Mn, Pb, Tl and Zn than controls, but these values were also below toxic levels for livestock consumption. In general, none of the heavy metals studied in both crops reached either phytotoxic or toxic levels for humans or livestock. Nevertheless, a continuous monitoring of heavy metal accumulation in soil and plants must be established in the spill-affected area.

Accidents, Occupational↗
PubMed2001

Examining child sexual abuse evaluations: the types of information affecting expert judgment.

OBJECTIVE: There were two aims: First, to determine to what extent four variables, disclosure, doll play, affect and collateral information, affect the decision-making processes of child sexual abuse experts and lay persons when confronted with an abuse allegation, and second, to see how these two groups of raters might differ from one another. METHOD: A randomized block partially confounded factorial design was used. Participants made abuse likelihood and confidence ratings in response to six hypothetical cases of child sexual abuse, four of which had varying combinations of the four types of information and two of which were constant across all raters. Participants also completed attitudes and knowledge questionnaires. RESULTS: Disclosure and collateral information both had large effects on both rater groups. Doll play and affect had little or no effect on the decisions of either group. Experts were slightly more conservative in their judgments over all than students were. Experts also displayed more knowledge of the sexual abuse literature and more child-believing attitudes than their student counterparts. CONCLUSION: Concrete information such as disclosure statements and collateral information affected abuse decisions while inferential data such as doll play and affect did not. The goal of these evaluations may be the clarification of such concrete information and the inferential data may be used only to guide one's inquiry. This conclusion argues against the concern that experts might jump to conclusions of abuse merely based upon suggestive, symbolic material.

Adult↗
PubMed1989

X-linked progressive cone dystrophy. Clinical characteristics of affected males and female carriers.

The authors evaluated nine affected males and six female carriers from a four-generation family with X-linked cone dystrophy. As the affected males grew older, visual acuity deteriorated, central scotomas deepened, and macular changes became more prominent. There was granularity of the macula in younger individuals and bull's eye lesions and central geographic atrophy of the retinal pigment epithelium (RPE) in the older subjects. The retinas of some affected males had a bronze-green tapetal-like sheen. Color vision was impaired in all affected males and resembled an acquired type II defect (Verriest classification). One younger subject had paradoxical pupillary constriction to darkness. Visual-evoked potential (VEP) latencies were prolonged in some affected males, suggesting that photoreceptor degeneration caused transsynaptic degeneration of ganglion cells. All female carriers had visual acuities of 20/30 or better, but some showed mild ophthalmoscopic changes and abnormalities of color vision, electroretinograms (ERGs), and VEPs.

Adolescent↗
PubMed2001

Bone mineral density in pre-and post-menopausal women with affective disorder treated with long-term L-thyroxine augmentation.

BACKGROUND: Augmentation with TSH-suppressive L-thyroxine (T4) has been shown to improve the course of illness in otherwise refractory affective disorders. This collaborative study investigates whether T4 augmentation for a minimum of 12 months decreases bone mineral density (BMD) in 26 pre- and post-menopausal women with affective disorder. METHODS: We measured BMD at the femoral neck, Ward's triangle, trochanter and lumbar vertebrae (L1-L4) in 13 premenopausal and 13 postmenopausal women with affective disorder using dual energy X-ray absorptiometry. BMD was expressed as g/cm(2) and as a Z-score, calculated using bone density data from the international reference population standard. RESULTS: The Z-scores for the pre- and post-menopausal women were within the reference range of the age and sex matched population standard. BMD for the composite group also did not differ either from the population standard. BMD in the lumbar spine and hip did not differ significantly between the pre- and post-menopausal groups. However, there were a relatively high number of postmenopausal patients with BMDs one S.D. lower than the population standard. LIMITATIONS: This is a cross-sectional study with a relatively small sample size. CONCLUSIONS: The study demonstrates that T4 augmentation treatment does not reduce BMD to a clinically significant degree in many women with affective disorder. However, the resilience of bone structure to T4 treatment may vary with site and menopausal status. This study underscores the need for regular assessment of BMD during adjunctive thyroid treatments for affective disorder, especially in postmenopausal women.

Absorptiometry, Photon↗
PubMed2003

Increased risk of developing dementia in patients with major affective disorders compared to patients with other medical illnesses.

BACKGROUND: The association between affective disorder and subsequent dementia is unclear. Our aim was to investigate whether patients with unipolar or bipolar affective disorder have an increased risk of developing dementia compared to patients with other chronic illnesses. METHOD: By linkage of the psychiatric and somatic nation-wide registers of all hospitalised patients in Denmark, 2007 patients with mania, 11741 patients with depression, 81380 patients with osteoarthritis and 69149 patients with diabetes were identified according to diagnosis at first-ever discharge from a psychiatric or somatic hospital between 1 January 1977 and 31 December 1993. The risk of receiving a diagnosis of dementia on subsequent re-admission was estimated with the use of survival analyses. RESULTS: Patients with unipolar or bipolar affective disorder had a greater risk of receiving a diagnosis of dementia than patients with osteoarthritis or diabetes. Differences in age and gender and the effect of alcohol- or drug-abuse did not explain these associations. CONCLUSION: Patients with unipolar or bipolar affective disorder seem to have an increased risk of developing dementia compared to patients with other illnesses. LIMITATION: The study includes only patients who have been hospitalised at least once. CLINICAL RELEVANCE: Patients with unipolar or bipolar affective disorder may be at increased risk of developing dementia.

Adult↗
PubMed2003

Head injury as a risk factor for bipolar affective disorder.

BACKGROUND: Case reports have associated head injury with psychoses including affective disorders, but little is known regarding head injury as a risk factor for the onset of bipolar affective disorder. METHODS: The Danish Psychiatric Case Register and the Danish National Patients Register were linked together with the Danish Population Register, thus identifying 10,242 patients with bipolar affective disorder, and 102,420 matched controls. History regarding head injury was recorded from the National Patients Register data. Data were analysed using conditional logistic regression. RESULTS: Bipolar affective disorder was associated with an increased risk of a history of head injury (IRR=1.55; 95% CI 1.36-1.77). The increased risk was confined to head injury occurring less than 5 years before the first psychiatric admission. The finding could not be ascribed to increased accident proneness (as evaluated through the occurrence of other fractures not involving the skull). LIMITATIONS: In studies based on clinical diagnoses only and limited to patients who were hospitalised for psychiatric disorder, exposure was limited to injuries leading to admission to hospital. CONCLUSIONS: Head injury may be a contributing factor to the onset of bipolar affective illness. However, this factor is probably only relevant to a relatively small minority of cases.

Accidents↗
PubMed1998

A functional variant of the serotonin transporter gene in families with bipolar affective disorder.

BACKGROUND: The serotonin transporter protein (SERT) reuptakes serotonin from synapses and has been implied as the site of therapeutic action of many antidepressant drugs. SERT is one of the most relevant candidate genes for bipolar affective disorder. Recently a functionally important 44 basepair deletion in the regulatory region of the SERT gene was described. Association between this variant and affective disorder has been suggested. METHODS: The present study analysed this variation and another variation in the SERT gene and nearby DNA markers in order to test for linkage between SERT and bipolar affective disorder in two Danish families. RESULTS AND CONCLUSION: There was no evidence that variants in the SERT gene were a stronger dominant disease gene for the development of affective disorder in the families. The possibility of a recessive disease gene at or near SERT could not be excluded. LIMITATIONS: The present study cannot exclude if variations at or near the SERT gene were weak susceptibility genes or determine if they are important for other characteristics than presence or absence of disease. CLINICAL RELEVANCE: Further studies of the SERT gene in affective and other disorders, as well as in relation to treatment response to antidepressants are needed.

Bipolar Disorder↗
PubMed1998

Predictors of recurrence in affective disorder. A case register study.

BACKGROUND: The risk of recurrence in affective disorder is affected by socio-demographic variables such as gender, age at onset and marital status and by illness related factors as the length of previous episodes and the total duration of the illness. The present study investigated how the effect of these variables changed with the progression of the illness. METHOD: Using survival analysis, the risk of recurrence was estimated in a case register study including all hospital admissions with primary affective disorder in Denmark during 1971-1993. RESULTS: Totally, 20350 first admission patients had been discharged with a diagnosis of affective disorder, depressive or manic/circular type. Initially in the course of the illness, bipolar patients had a substantial greater risk of recurrence compared with unipolar patients. At this time, gender, age and marital status together with the total duration of the illness predicted the risk of recurrence in both unipolar and bipolar illness. Some variables had different predictive effect in the two types of illness. Later, especially the duration of the previous illness predicted the risk of recurrence. CONCLUSION: It seems as initially in the course of affective disorder socio-demographic variables such as gender, age at onset and marital status act as risk factors for further recurrence. Later, however, the illness itself seem to follow its own rhythm regardless of prior predictors. LIMITATION: The data relate to re-admissions rather than recurrence and the findings may be due to decreasing sample sizes during the course of illness. CLINICAL RELEVANCE: The study underscores the importance of the illness process itself.

Adult↗
PubMed1999

Flat affect and social skills in schizophrenia: evidence for their independence

Although flat affect and social skills deficits are generally considered to be distinct impairments in schizophrenia, flat affect is typically assessed via an interview - an inherently social context. To the extent that emotional expressivity is an important component of socially appropriate interaction, it is possible that schizophrenic patients' diminished expressiveness in a social situation is largely a function of their concurrent social skills deficit. In the present study, we examined the relation between social skills and flat affect by measuring flat affect in two contexts: during an interview (high social demand) and while participants watched emotional film clips alone (low social demand). Results showed that social skills were not significantly correlated with flat affect in either context, suggesting that the two constructs represent independent domains of functioning in schizophrenic patients.

Journal Article↗
PubMed1994

X-Linked hypophosphatemic rickets: a disease often unknown to affected patients.

X-Linked hypophosphatemic rickets (XLH) is an X-linked dominant disorder that is secondary to renal phosphate wasting. Affected individuals frequently present the following characteristics: short stature, lower-extremity deformity, bone pain, dental abscesses, enthesopathy, rickets, and osteomalacia. Since the disorder is characterized by evident phenotypic abnormalities, we hypothesized that there would be a high degree of knowledge about the disease in affected kindreds. Thus, we constructed a six-page, self-administered questionnaire to determine whether family members are, in fact, aware of their disease and properly diagnosed and treated. We also designed the survey to determine rates of symptoms thought to be associated with rickets/osteomalacia in a population with a lower referral bias than is usually seen in tertiary care centers. We administered the questionnaire to 234 study subjects (57 affected) who were members of one of three large kindreds. Although 62% of affected individuals knew they had some problem with their bones, only 22.6% were told by a physician that they had rickets or osteomalacia. This apparent lack of awareness occurred in spite of 61.1% of affected subjects complaining of bone or joint problems to their personal physician. Indeed, of those patients who had persistent complaints, only 34.5% were told they had rickets or osteomalacia. Only one patient was taking phosphate and vitamin D.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗