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Structure/function analysis of the domains required for the multimerisation of phenylalanine hydroxylase.

Phenylalanine hydroxylase (PAH) exists as an equilibrium of dimers and tetramers. However, there is little information concerning the inter- or intra-molecular interactions required for enzyme quaternary structure. It is predicted that the formation of a PAH tetramer will require at least two points of contact per enzyme subunit. Sequence analysis has suggested the existence of a C-terminal domain with characteristics of a leucine zipper or a variant of this called a coiled-coil. By deletion of 24 amino acids from the C-terminus or conversion of leucine 448 to an alanine residue, we have shown that this putative leucine zipper/coiled-coil domain is involved in the assembly of an active enzyme tetramer from dimers. The removal of this C-terminal domain of PAH reduces enzyme activity but does not abolish it. Furthermore, we report that an alanine 447 to aspartate mutation associated with phenylketonuria may affect subunit assembly which suggests the formation of enzyme tetramers is physiologically relevant. Our analysis of subunit interactions in vivo, show that in the absence of the C-terminal coiled-coil domain, dimers can form and this is only possible when the N-terminal domain is present. This provides the first evidence that N-terminal domain is required for multimerisation. We propose that the N-terminal regulatory domain in conjunction with the C-terminal coiled-coil domain, mediates the formation of fully active enzyme tetramers.

Amino Acid Sequence↗

Two distinct mechanisms of fibroblast adhesion.

The adhesion of cells to the connective tissue matrix is commonly thought to be governed by fibronectin, a pericellular glycoprotein with binding sites for cell surfaces, collagen and glycosaminoglycans. Here we report evidence that Chinese hamster ovary (CHO) cells possess an alternative mechanism for adhesion which is independent of fibronectin. Cells of a variant CHO clone called ADvF11 are defective in their ability to adhere to fibronectin-coated substrata, but can adhere to a substratum coated with SAM (substrate-attached material), a pericellular material produced by fibroblasts. The adhesion of wild-type CHO cells to fibronectin-coated substrate and adhesion of ADvF11 cells to SAM-coated substrata are differentially sensitive to proteolytic treatment. This suggests that there are two distinct adhesion mechanisms for CHO cells, only one of which is dependent on fibronectin.

Animals↗

Mutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure.

Antenatal Bartter syndrome (aBS) comprises a heterogeneous group of autosomal recessive salt-losing nephropathies. Identification of three genes that code for renal transporters and channels as responsible for aBS has resulted in new insights into renal salt handling, diuretic action and blood-pressure regulation. A gene locus of a fourth variant of aBS called BSND, which in contrast to the other forms is associated with sensorineural deafness (SND) and renal failure, has been mapped to chromosome 1p. We report here the identification by positional cloning, in a region not covered by the human genome sequencing projects, of a new gene, BSND, as the cause of BSND. We examined ten families with BSND and detected seven different mutations in BSND that probably result in loss of function. In accordance with the phenotype, BSND is expressed in the thin limb and the thick ascending limb of the loop of Henle in the kidney and in the dark cells of the inner ear. The gene encodes a hitherto unknown protein with two putative transmembrane alpha-helices and thus might function as a regulator for ion-transport proteins involved in aBS, or else as a new transporter or channel itself.

Animals↗

Urinary free cortisone and the assessment of 11 beta-hydroxysteroid dehydrogenase activity in man.

OBJECTIVE: Two isoforms of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) catalyse the interconversion of cortisol to hormonally inactive cortisone; defects in the 11 beta-HSD2 isoform result in hypertension. The kidney, expressing high levels of 11 beta-HSD2, is the principal source of cortisone in man. We have validated the measurement of urinary free cortisone (UFE) excretion in normals and in patients with disorders of the pitultary-adrenal axis in an attempt to more accurately measure the activity of 11 beta-HSD2 in vivo. SUBJECTS: Forty-one normal adults, 12 normal children < 12 years of age, 15 patients with Cushing's syndrome, 12 with hypopitultarism on replacement hydrocortisone, 12 with the syndrome of apparent mineralocorticoid excess (AME) and 7 volunteers consuming liquorice. MEASUREMENTS: A complete 24-hour urine collection was analysed by gas chromatography/mass spectrometry for "A-ring' reduced cortisol and cortisone metabolites, i.e. tetrahydrocortisols (THF and allo-THF) and tetrahydrocortisone (THE). In addition, urinary free cortisol (UFF) and urinary free cortisone were quantified using deuterium-labelled internal standards. RESULTS: In normal adults and children, UFE excretion exceeded that of UFF (UFF 30.4 +/- 2.4 micrograms/24h (mean +/- SE), UFE 54.6 +/- 4.1 micrograms/24h, adults) (for conversion to nmol/24h multiply E by 2.78 and F by 2.76 respectively). Thus the normal UFF/UFE ratio was 0.54 +/- 0.05 in contrast to the (THF + allo-THF)/THE ratio of 1.21 +/- 0.06. UFE excretion was normal in hypopituitary patients on replacement hydrocortisone. Although UFE was elevated in all forms of Cushing's syndrome, the UFF/UFE ratio was grossly elevated in patients with the ectopic ACTH syndrome (14.0 +/- 6.7, n = 6). UFE was below the lower limit of the assay (< 1 microgram/24h) in most patients with the so-called type 1 variant of AME and significantly reduced in 4 patients described as having the type 2 variant of AME (10.5 +/- 3.5 micrograms/h, P < 0.05) and in 7 volunteers consuming liquorice (26.8 +/- 10.0 micrograms/24h, P < 0.01). In ectopic ACTH syndrome, AME, and liquorice ingestion the UFF/UFE ratio was more deranged than the (THF + allo-THF)/THE ratio. CONCLUSION: In normals the discrepant THF + allo-THF/ THE and UFF/UFE ratio suggests that much more of the UFE is derived from the kidney. Reduction in UFE excretion is seen following liquorice ingestion and in both variants of AME, though it is more profound in AME1. The high UFF/UFE ratio in the mineralocorticoid excess state seen in the ectopic ACTH syndrome is compatible with substrate-saturation of renal 11 beta-HSD2. The measurement of UFE and the UFF/UFE ratio is a significant advance in the analysis of human 11 beta-HSD activity in vivo; in particular, the UFF/UFE ratio appears to be a more sensitive index than the (THF + allo-THF)/THE ratio of renal 11 beta-HSD2 activity.

11-beta-Hydroxysteroid Dehydrogenases↗

Leiomyosarcoma of the heart and its pulmonary metastasis, both with prominent osteoclast-like multinucleated giant cells expressing tartrate-resistant acid phosphatase activity.

An autopsy case of cardiac leiomyosarcoma and its pulmonary metastasis, both with osteoclast-like multinucleated giant cells (OMGC) mimicking the so-called giant cell variant of malignant fibrous histiocytoma (MFH), is reported. The patient, a 70-year-old male, was admitted for sudden dyspnea. Extensive work-up established only a left atrial tumor mass. Three months after admission, the patient developed multiple intracranial and pulmonary metastases, followed by a worsening clinical course characterized by semicoma and dyspnea, and subsequently died 6 months after the onset of his symptoms. At subsequent autopsy, the left atrial polypoid tumor was found to have invaded destructively to the left half of the cardiac wall. Histology of the cardiac tumor revealed a bimorphic sarcoma in which a poorly differentiated leiomyosarcoma comfirmed by histologic and immunohistochemical findings was juxtaposed to a small nodule with features closely mimicking giant cell MFH. The pulmonary metastatic nodules exhibited features that were entirely indistinguishable from giant cell MFH except for the fact that a minority of polymorphic cells manifested myogenic differentiation. We believe that such a MFH-like pattern represents a pleomorphic form of leiomyosarcoma rather than a dedifferentiated one. The OMGC within the MFH-like component coexpressed CD68 and tartrate-resistant acid phosphatase activity.

Acid Phosphatase↗

Pituitary adenylate cyclase-activating polypeptide triggers dual transduction signaling in CATH.a cells and transcriptionally activates tyrosine hydroxylase and c-fos expression.

We used a catecholaminergic neuron-like cell line (CATH.a cells) as a model system to investigate the likelihood that pituitary adenylate cyclase-activating polypeptide (PACAP) may participate in the regulation of specific gene expression in catecholaminergic neurons. Analysis by reverse transcriptase-PCR amplification revealed the presence in these cells of type I PACAP receptors, with a short isoform, together with a heavier so-called Hop splice variant. PACAP38 and PACAP27 enhanced, in a dose-dependent manner, both cyclic AMP formation and phosphoinositide breakdown, with EC50 values of, respectively, 0.6 x 10(-10) and 2 x 10(-9) M. These peptides, in addition, also elevated [Ca2+]i by mobilizing intracellular calcium pools. Vasoactive intestinal peptide (VIP) was approximately 1,000-fold less potent in stimulating cyclic AMP (with EC50 = 2 x 10(-7) M) and failed to change the turnover of phosphoinositides and to alter [Ca2+]i. Both forms of PACAP, as well as forskolin, stimulated transcriptional induction of tyrosine hydroxylase (TH) and c-fos promoters fused to a chloramphenicol acetyltransferase (CAT) reporter gene in transiently transfected cells (p < 0.01 vs. controls). Induction of CAT activity linked to both TH and c-fos promoters was obliterated upon coexpression of a dominant inhibitory mutant (Mt-RAB) of cyclic AMP-dependent protein kinase. We conclude that CATH.a cells do express functional PACAP type I receptors, the activation of which impinges on TH and c-fos transcription according to a process that is primarily dependent on the cyclic AMP-PKA pathway.

Adenylyl Cyclases↗

Gitelman's syndrome revisited: an evaluation of symptoms and health-related quality of life.

BACKGROUND: Gitelman's syndrome (GS), also called Gitelman's variant of Bartter's syndrome, is an autosomal recessive renal disorder characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalciuria. GS is caused by inactivating mutations in the thiazide-sensitive sodium chloride cotransporter gene (NCCT). It is also known as the "milder" form of Bartter's syndrome, as patients with GS are usually diagnosed in adulthood during routine investigation. Symptoms reported in the literature range from asymptomatic, to mild symptoms of cramps and fatigue, to severe manifestations such as tetany, paralysis, and rhabdomyolysis. This is the first systematic evaluation of a large group of patients with genetically defined GS. METHODS: We evaluated the symptoms and quality of life (QOL) in 50 adult GS patients with confirmed mutations in NCCT, using a standardized questionnaire. This cohort was compared with 25 age- and sex-matched controls. RESULTS: GS patients were significantly more symptomatic than controls. The most common symptoms were salt craving, with musculoskeletal symptoms such as cramps, muscle weakness, and aches and constitutional symptoms such as fatigue, generalized weakness and dizziness, and nocturia and polydipsia. Forty-five percent of GS patients consider their symptoms a moderate to big problem. Measures of health-related QOL were significantly lower in GS patients compared with controls, particularly in terms of role limitations caused by physical health, emotion, level of energy, and general health perception. CONCLUSIONS: This descriptive study indicates that GS is not an asymptomatic disease and adversely affects QOL in these patients. Further studies are needed to assess the impact of therapy on symptoms and QOL.

Adolescent↗

[Significance of intermittent slow waves with right posterior accentuation in the EEG's of psychiatric patients].

The study was based on the frequent occurrence of intermittent slow waves right-posterior accentuation (IRP) in the EEGs of psychiatric patients. With regard to the EEG-phenomenon we present a detailed morphological and functional description as well as an evaluation from a developmental point of view. According to case histories a clinico-psychopathological characterization of the patients with IRP is given. The IRP-phenomenon can be interpreted electrogenetically against the background of and in connection with the so-called slow alpha variant rhythms as well as the posterior slow waves characteristic of children and adolescents. These patterns have in common a certain tendency to right-sided accentuation. In accord with a hypothesis (which has been derived from other observations and considerations) of a "maturation gradient" which favours the left hemisphere, we try to explain the IRP-phenomenon as an expression of a maturation deficit. Whereas the slow alpha variant rhythms and the posterior slow waves characteristic of children and adolescents appear bilaterally for the most part, IRP by definition, limited to the right hemisphere, may be considered as a less pronounced form in comparison. Deriving from clinico-psychopathological assessment the relationships are as follows: Patients with IRP account for about 5% of the in-patients in our psychiatric hospital. The IRP phenomenon seems to be closely linked to the male sex. Although a clear relationship with nosological categories (ICD) could not be proved, it seems that patients suffering from schizophrenic psychoses (ICD No. 295) are more frequently represented among the patients with the IRP-phenomenon than others. For the group of schizophrenic patients with IRP we found in contrast to a control group of schizophrenics without IRP a tendency to earlier onset of their disease. Compared with the control group it is found that the IRP groups consists of younger patients at the time of conducting this study. The two comparative groups of schizophrenics with and without IRP can be characterized by differences in the more or less pronounced manifestation of a fairly large number of AMDP items. Whereas for the IRP group a symptom pattern emerges with a hypermotoric -expansive accentuation, the control group seems to tend more towards a syndrome with depressive shading. The slight tendencies towards increased hereditary disposition as well as towards increased perinatal complications among the schizophrenic IRP patients necessitate further studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Human hypoxanthine (guanine) phosphoribosyltransferase: an amino acid substitution in a mutant form of the enzyme isolated from a patient with gout.

We have investigated the molecular basis for a deficiency of the enzyme hypoxanthine (guanine) phosphoribosyltransferase (HPRT; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) in a patient with a severe form of gout. We reported in previous studies the isolation of a unique structural variant of HPRT from this patient's erythrocytes and cultured lymphoblasts. This enzyme variant, which is called HPRTLondon, is characterized by a decreased concentration of HPRT protein in erythrocytes and lymphoblasts, a normal Vmax, a 5-fold increased Km for hypoxanthine, a normal isoelectric point, and an apparently smaller subunit molecular weight. Comparative peptide mapping experiments revealed a single abnormal tryptic peptide in HPRTLondon. Edman degradation of the aberrant peptide from HPRTLondon identified a serine-to-leucine amino acid substitution at position 109. This substitution can be explained by a single nucleotide change in the codon for serine-109 (UCA leads to UUA). Thus a mutation at the HPRT locus has now been defined at the molecular level.

Amino Acid Sequence↗

The N-terminal end of Bax contains a mitochondrial-targeting signal.

The translocation of Bax alpha, a pro-apoptotic member of the BCL-2 family from the cytosol to mitochondria, is a central event of the apoptotic program. We report here that the N-terminal (NT) end of Bax alpha, which contains its first alpha helix (Eta alpha 1), is a functional mitochondrial-addressing signal both in mammals and in yeast. Similar results were obtained with a newly described variant of Bax called Bax psi, which lacks the first 20 amino acids of Bax alpha and is constitutively associated with mitochondria. Deletion of Eta alpha 1 impairs the binding of Bax psi to mitochondria, whereas a fusion of the N terminus of Bax alpha, which contains Eta alpha 1 with a cytosolic protein, results in the binding of the chimeric proteins to mitochondria both in a cell-free assay and in vitro. More importantly, the mitochondria-bound chimeric proteins inhibit the interaction of Bax psi with mitochondria as well as Bax-apoptogenic properties. The mutations of the Eta alpha 1, which inhibit Bax alpha and Bax psi translocation to mitochondria, also block the subsequent activation of the execution phase of apoptosis. Conversely, a deletion of the C terminus does not appear to influence Bax alpha and Bax psi mitochondrial addressing. Taken together, our results suggest that Bax is targeted to mitochondria by its NT and thus through a pathway that is unique for a member of the BCL-2 family.

Amino Acid Sequence↗

Impaired functioning of thermolabile methylenetetrahydrofolate reductase is dependent on riboflavin status: implications for riboflavin requirements.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR; EC 1.7.99.5) supplies the folate needed for the metabolism of homocysteine. A reduction in MTHFR activity, as occurs in the homozygous state for the 677C-->T (so-called thermolabile) enzyme variant (TT genotype), is associated with an increase in plasma total homocysteine (tHcy). OBJECTIVE: In vitro studies suggest that the reduced activity of thermolabile MTHFR is due to the inappropriate loss of its riboflavin cofactor. We investigated the hypothesis that MTHFR activity in the TT genotype group is particularly sensitive to riboflavin status. DESIGN: We studied tHcy and relevant B-vitamin status by MTHFR genotype in a cross-sectional study of 286 healthy subjects aged 19-63 y (median: 27 y). The effect of riboflavin status was examined by dividing the sample into tertiles of erythrocyte glutathionine reductase activation coefficient, a functional index of riboflavin status. RESULTS: Lower red blood cell folate (P = 0.0001) and higher tHcy (P = 0.0082) concentrations were found in the TT group than in the heterozygous (CT) or wild-type (CC) groups. However, these expected relations in the total sample were driven by the TT group with the lowest riboflavin status, whose mean tHcy concentration (18.09 micromol/L) was almost twice that of the CC or CT group. By contrast, adequate riboflavin status rendered the TT group neutral with respect to tHcy metabolism. CONCLUSIONS: The high tHcy concentration typically associated with homozygosity for the 677C-->T variant of MTHFR occurs only with poor riboflavin status. This may have important implications for governments considering new fortification policies aimed at the prevention of diseases for which this genotype is associated with increased risk.

Adult↗

Marfan's disease and Erdheim's cystic medionecrosis. A study of their pathology.

Differentiation between Marfan's disease, or its forme fruste counterpart and Erdheim's cystic medionecrosis can be made in cases of aortic dilatation or dissection. This study examined the morphological features at light microscopy of aortic tissue, removed at surgery in 10 patients with Marfan's disease. A separate group consisted of 24 patients who did not express the complete Marfan phenotype but had family members who displayed the full and typical features of the disease. This group represented the so-called 'forme fruste' variant. These two groups were compared with 12 patients in whom a histopathological diagnosis of Erdheim's cystic medionecrosis had been made. Finally normal aortic tissue from post-mortem subjects were made available representing controls. In each case the degree of elastic fragmentation and cystic change of the aortic media was assessed and tabulated. The results indicate that severe fragmentation of elastic is similarly identifiable in both Marfan and Marfan forme fruste groups and that differentiation is easy pathologically from subjects with the comparatively modest fragmentation seen in Erdheim's cystic medionecrosis. Although cystic change was encountered in all groups, its severity tended to parallel the age of the subject, and we consider from our study that Erdheim's cystic medionecrosis represents no more than an exaggerated age-related change.

Adolescent↗

Encephalomyocarditis virus and diabetes mellitus: studies on virus mutants in susceptible and non-susceptible mice.

The so-called M-variant (especially subtype D) of encephalomyocarditis virus (EMCV) induces a diabetes-like syndrome in certain mouse strains which may serve as a model of insulin-dependent diabetes mellitus (IDDM) in man. The development and course of diabetes was influenced by a number of virus and host factors, among these being virus strain, virus dose, mouse strain, age, sex, and the host's immunological status. In a D-variant stock of EMCV, we found a virus plaque variant (PV 2) diabetogenic for DBA/2 mice, and at least one variant (PV 7) that did not affect carbohydrate metabolism. Although the diabetogenicity of PV 2 proved to be a genetically stable characteristic after further passages in vivo and in vitro, the incidence of diabetes varied somewhat (mean value 65% in 10-week-old DBA/2 mice infected with 10(5) p.f.u.). Both lower (10(1) or 10(3) p.f.u.) and higher (10(7) or 10(8) p.f.u.) virus doses led to a diminished incidence and severity of diabetes. In younger animals (5 weeks) transient hyperglycaemia often appeared, whereas in older animals (20 weeks) there was a higher rate of mortality. Histological examination of the islets of Langerhans in diabetes-susceptible (DBA/2) and resistant (C57BL/6) mice revealed that EMCV-induced hyperglycaemia appeared to develop in parallel to islet cell damage. Even in diabetic animals, some unaffected islets were regularly found. This study demonstrates that EMCV mutants may have completely different biological effects and produce diabetes only in special circumstances. Host factors play a significant role in the development of diabetes.

Age Factors↗

Two approaches for estimating disease prevalence from population-based registries of incidence and total mortality.

Two approaches are described for estimating the prevalence of a disease that may have developed in a previous restricted age interval among persons of a given age at a particular calendar time. The prevalence for all those who ever developed disease is treated as a special case. The counting method (CM) obtains estimates of prevalence by dividing the estimated number of diseased persons by the total population size, taking loss to follow-up into account. The transition rate method (TRM) uses estimates of transition rates and competing risk calculations to estimate prevalence. Variance calculations are described for CM and TRM as well as for a variant of CM, called counting method times 10 (CM10), that is designed to yield more precise estimates than CM. We compare these three estimators in terms of precision and in terms of the underlying assumptions required to justify the methods. CM makes fewer assumptions but is typically ess precise than TRM or CM10. For common diseases such as breast cancer, CM may be preferred because its precision is excellent even though not as high as for TRM or CM10. For less common diseases, such as brain cancer, however, TRM or CM10 and other methods that make stabilizing assumptions may be preferred to CM.

Adult↗

The Sup35 domains required for maintenance of weak, strong or undifferentiated yeast [PSI+] prions.

The Sup35 protein can exist in a non-infectious form or in various infectious forms called [PSI+] prion variants (or prion strains). Each of the different [PSI+] prion variants converts non-infectious Sup35 molecules into that prion variant's infectious form. One definition of a 'prion domain' is the minimal fragment of a prion protein that is necessary and sufficient to maintain the prion form. We now demonstrate that the Sup35 N region (residues 1-123), which is frequently referred to as the 'prion domain', is insufficient to maintain the weak or strong [PSI+] variants per se, but appears to maintain them in an 'undifferentiated' [PSI+] state that can differentiate into weak or strong [PSI+] variants when transferred to the full-length Sup35 protein. In contrast, Sup35 residues 1-137 are necessary and sufficient to faithfully maintain weak or strong [PSI+] variants. This implicates Sup35 residues 124-137 in the variant-specific maintenance of the weak or strong [PSI+] forms. Structure predictions indicate that the residues in the 124-137 region form an alpha-helix and that the 1-123 region may have beta structure. In view of these findings, we discuss a plausible molecular basis for the [PSI+] prion variants as well as the inherent difficulties in defining a 'prion domain'.

Animals↗

An additional exon in the human vinculin gene specifically encodes meta-vinculin-specific difference peptide. Cross-species comparison reveals variable and conserved motifs in the meta-vinculin insert.

We have analyzed the structure, origin and expression of the high-molecular-mass muscle-specific variant of vinculin, called meta-vinculin. The meta-vinculin-specific inserts from the human and avian molecules have been isolated and sequenced and the sequences confirmed via cloning of the corresponding cDNA. Comparison of the human, avian and determined porcine sequences revealed cross-species identity in the C-terminal half of the insert. Human and porcine meta-vinculin were highly similar in the insert region, showing only five amino acid exchanges; avian meta-vinculin showed 22 exchanges in the same region compared to human meta-vinculin and exhibited, in addition, one extra amino acid, making 69 in all. Each insert was flanked by characteristic KWSSK motifs. Evidence for two vinculin mRNA species in human uterus smooth muscle was provided by reverse transcription combined with the polymerase chain reaction, as well as by ribonuclease-mapping analysis of cDNA/mRNA hybrids. One of the mRNA species contained an additional 204-nucleotide insert that precisely encoded the meta-vinculin-specific peptide. Sequence analysis of the appropriate portion of the human vinculin gene showed that the section coding for the meta-vinculin-specific insert is present as a discrete exon. Thus, meta-vinculin and vinculin mRNA are generated by alternative splicing.

Amino Acid Sequence↗

Psychological aspects of weekend headache sufferers in comparison with migraine patients.

Sometimes the relaxation after stress may trigger a migraine attack. This is the principle that underlies that particular variant of migraine called "weekend headache". We hypothesize the presence in weekend headache prone subjects of a particular psychological background, different from that of common migraine sufferers. In order to detect possible differences supporting our hypothesis, we studied 104 new outpatients: 46 patients suffering from headache only on weekends (23 males and 23 females) and 58 matched common migraineurs (26 males and 32 females) with no weekend predilection. The psychological assessment was performed using the following psychometric tools: MMPI, BDI, STAIX1-X2. A clinical assessment of each patient was also carried out. Significant differences were found after statistically analyzing the test results. Most of the MMPI scales were found to be more elevated in both male and female weekend headache sufferers. From a clinical point of view, the weekend headache attacks proved to be similar to those of common migraine, but with a significantly higher incidence of concomitant symptoms. Our study confirms the important role that psychological factors play in the pathogenesis and clinical development of migraine and leads us to conclude that a psychic tension component is associated with the vascular one in weekend headache.

Adult↗

Use of a serologically distinct strain of Thermoactinomyces vulgaris in the diagnosis of farmer's lung disease.

During investigations into farmer's lung disease it was noticed that Micropolyspora faeni (MF) was isolated and identified with ease, but difficulty was encountered in the identification of Thermoactinomyces vulgaris (TV), although an organism resembling TV was frequently isolated. Extracts prepared from the isolates resembling TV (called Thermoactinomyces vulgaris variant, TVV) when tested against the standard TV antiserum by double diffusion, did not produce any precipitin lines. When TVV extracts were tested against the serum of a patient from whom TVV had been isolated from the sputum, +++ precipitin lines were observed. With the TVV extracts the authors have demonstrated the existence of a serologically distinct strain of TV, and also that it would be a useful addition to the routine testing of antibodies to farmer's lung disease.

Dust↗