Biomedical subjects

S Othman

Publications and source records attributed to S Othman.

At least 19 recordsLinked to original sources

PubMed2006

Clinical outcome of unicompartmental knee arthroplasty and influence of alignment on prosthesis survival rate.

INTRODUCTION: Various factors that affect the longevity of unicompartmental knee arthroplasty (UKA) include patient activity level, habitus, competence of cruciate ligaments, postoperative alignment, implant positioning and ligament balancing. The purpose of this study was to evaluate the clinical outcome of the open standard UKA and establish the influence of radiological alignment on the survivorship of the prosthesis. METHODS: We consecutively reviewed the results of 20 open standard UKAs performed in 17 patients between 1996 and 2000. A single implant type, the Press Fit Condylar Unicompartmental Knee System (DePuy, Leeds, UK), was used in all patients. All patients were evaluated clinically using the Knee Society Rating. Implant positioning and limb alignment were recorded in the standing long leg anteroposterior and lateral radiographs, and various angles were measured. RESULTS: The alignment of the prosthesis was found to be good in 19 out of 20 operated knees. One knee with malalignment of prosthesis had to be revised at 23 months follow-up. There was a significant increase in Knee Society Rating of all patients, at a follow-up of 4-8 years. The Kaplan-Meier survival rate using revision to total knee arthroplasty as an endpoint was 91.7 percent. CONCLUSION: The long-term outcome of UKA is influenced by positioning and alignment of the prosthesis. With proper patient selection and surgical technique, the outcome of UKA can be definitely improved.

Adult↗

PubMed1999

Distinct structures and environments for the three hemes of the cytochrome bc1 complex from Rhodospirillum rubrum. A resonance Raman study using B-band excitations.

The B-band excited resonance Raman (RR) spectra (100-1700 cm-1) of the bacterial cytochrome bc1 complex purified from Rhodospirillum rubrum are reported. Four redox states, i.e., the persulfate-oxidized, "as prepared", and ascorbate- and dithionite-reduced states of the complex, were investigated with the laser excitations at 406.7, 413.1, and 441.6 nm. Following the different absorption properties of the b- and c-type hemes and the different resonance enhancements of the vibrational modes of oxidized and reduced hemes, RR contributions from the b- and c-type hemes were characterized. For the nu2, nu10, and nu8 porphyrin vibrational modes, individual contributions of hemes c1, bH, and bL were determined. The data show that the macrocycle conformation of the three hemes of the cytochrome bc1 complex is different. In particular, the frequencies assigned to ferrous heme bL (1580, 1610, and 352 cm-1, respectively) reveal that its porphyrin is more strongly distorted than that of ferrous heme bH (1584, 1614, and 344 cm-1, respectively). The frequencies of the nu11 modes (1543, 1536, and 1526 cm-1 for ferrous heme c1, heme bH, and heme bL, respectively) confirm that the axial histidylimidazole ligands of heme bL have a marked anionic character. Strong differences in the peripheral interactions of the three hemes with the proteins were also detected through the frequency differences of the nu5, nu13, nu14, and nu42 modes. Considering that hemes bH and bL are inserted into a four-helice bundle, the RR data are interpreted in the frame of a strong protein constraint on heme bL.

Electron Transport Complex III↗

PubMed1999

Purification, redox and spectroscopic properties of the tetraheme cytochrome c isolated from Rubrivivax gelatinosus.

The tetraheme cytochrome c subunit of the Rubrivivax gelatinosus reaction center was isolated in the presence of octyl beta-D-thioglucoside by ammonium sulfate precipitation and solubilization at pH 9 in a solution of Deriphat 160. Several biochemical properties of this purified cytochrome were characterized. In particular, it forms small oligomers and its N-terminal amino acid is blocked. In the presence or absence of diaminodurene, ascorbate and dithionite, different oxidation/reduction states of the isolated cytochrome were studied by absorption, EPR and resonance Raman spectroscopies. All the data show two hemes quickly reduced by ascorbate, one heme slowly reduced by ascorbate and one heme only reduced by dithionite. The quickly ascorbate-reduced hemes have paramagnetic properties very similar to those of the two low-potential hemes of the reaction center-bound cytochrome (gz = 3.34), but their alpha band is split with two components peaking at 552 nm and 554 nm in the reduced state. Their axial ligands did not change, being His/Met and His/His, as indicated by the resonance Raman spectra. The slowly ascorbate-reduced heme and the dithionite-reduced heme are assigned to the two high-potential hemes of the bound cytochrome. Their alpha band was blue-shifted at 551 nm and the gz values decreased to 2.96, although the axial ligations (His/Met) were conserved. It was concluded that the estimated 300 mV potential drop of these hemes reflected changes in their solvent accessibility, while the reduction in gz indicates an increased symmetry of their cooordination spheres. These structural modifications impaired the cytochrome's essential function as the electron donor to the photooxidized bacteriochlorophyll dimer of the reaction center. In contrast to its native state, the isolated cytochrome was unable to reduce efficiently the reaction center purified from a Rubrivivax gelatinosus mutant in which the tetraheme was absent. Despite the conformational changes of the cytochrome, its four hemes are still divided into two groups with a pair of low-potential hemes and a pair of high-potential hemes.

Cytochrome c Group↗

PubMed1999

Features of hepatic cavernous hemangioma on planar and SPECT Tc-99m-labeled red blood cell scintigraphy.

PURPOSE: To determine the value and diagnostic accuracy of planar and SPECT Tc-99m-labeled red blood cell (Tc-99m RBC) scintigraphy in the investigation of suspected hepatic cavernous hemangioma as found on ultrasound. PATIENTS AND METHODS: One hundred patients, 89 women (89%) and 11 men (11%), between 22 and 67 years old (mean age, 38 years) were evaluated for liver masses found on abdominal ultrasound. All the patients had previous Tc-99m RBC scintigraphy. The size of the lesions ranged from 1 to 9 cm. The final diagnosis was reached through cytologic biopsy, or histopathologic tests (or all of these). RESULTS: One hundred thirty lesions were found. With regard to the distribution of the lesions, 116 (89%) were single; 14 (3%) were multiple, with 118 (91%) in the right lobe and 12 (9%) in the left lobe; 83 (64%) were posterior; and 47 (36%) were anterior. With respect to the pattern of radioactivity fill-in, 86 (66%) lesions were typical and 44 (34%) were atypical. The results of Tc-99m RBC scintigraphy showed sensitivity, specificity, and positive and negative predictive and accuracy values of 97%, 83%, 98%, 77%, and 96% respectively. The use of SPECT improved the sensitivity value by 11% for lesions of 1 to 2 cm. CONCLUSIONS: Tc-99m RBC scintigraphy is the noninvasive technique most helpful in the diagnosis of hepatic hemangioma, especially in those at risk for lesion rupture or bleeding. SPECT should be performed whenever planar imaging fails to show the lesion by 2 hours. The use of ultrasound should precede scintigraphy for two important reasons: the size and the location of the lesion. Location of the lesion (anterior or posterior) is important for optimal gamma camera acquisition parameters. Lesions less than 1 cm are cannot be detected because they are beyond the limit of spatial resolution of the gamma camera we used.

Adult↗

PubMed1997

Influence of conserved amino acids on the structure and environment of the heme of cytochrome c2. A resonance Raman study.

Resonance Raman spectra using Soret excitations of oxidized and reduced Rhodobacter capsulatus cytochrome c2 at pH 7.5 were studied. The spectra of oxidized cytochrome c2 show three components for the v10 mode at 1638, 1633, and 1629 cm(-1). The intensities of these components are sensitive to the excitation wavelength. This effect is explained in the context of a conformational equilibrium of the ferriheme between a nearly planar structure and two ruffled structures. In the case of reduced cytochrome c2, the absolute frequencies as well as the excitation-dependent frequency dispersion of the v10 mode (1618-1621 cm(-1)) indicate a displacement of the conformational equilibrium of heme toward the more planar structures. To measure the influence of some key amino acid residues on the heme-protein interaction of cytochrome c2, four site-directed mutants of Rb. capsulatus cytochrome c2 have been studied by resonance Raman spectroscopy and their spectra compared with the spectra obtained for the wild type cytochrome. The mutants studied are K14E/K32E, P35A, W67Y, and Y75F. The spectral changes induced by the mutations are interpreted in terms of alterations in the structure and/or environment of the cytochrome c2 heme in the framework of the expected role of the different amino acid residues in the stability and redox potential.

Amino Acids↗

PubMed1997

Hemiconvulsion-hemiplegia-epilepsy syndrome. A clinical, electroencephalographic and neuroradiological study.

Six patients (4 boys and 2 girls) with hemiconvulsion-hemiplegia-epilepsy (HHE) syndrome are described. They had prolonged seizures, lasting from 30 min to 12 h, at ages 1-4 years. These took the form of hemiconvulsion in three of the children and generalized tonic-clonic seizures in the others, being preceded by hemifacial twitching or head and eye deviation in two. They were followed by hemiplegia, which cleared with time in five patients, apart from subtle pyramidal tract signs. One child had spastic quadriparesis, choreiform movements, contracture deformities and severe mental retardation following repeated status epilepticus. Subsequent epilepsy developed in five patients and was satisfactorily controlled with carbamazepine and/or phenobarbitone. Cerebral hemiatrophy was documented in all patients by cranial computed tomography and/or magnetic resonance imaging. Single photon emission computed tomography (done in 4 patients) showed ipsilateral hypoperfusion (of the damaged hemisphere). Electroencephalography showed ipsilateral slowing and low voltage of background activity. Epileptiform discharges were found on the ipsilateral side in two cases and the contralateral side (the undamaged hemisphere) in one.

Atrophy↗

PubMed1997

Serotypes of group A streptococci isolated from healthy schoolchildren in the United Arab Emirates.

Group A streptococci (GAS) are the most frequent cause of pharyngitis in children and are a common cause of emergency room or paediatric clinic visits worldwide. This study determined the representative M and T types of GAS, and their distribution, among schoolchildren in the United Arab Emirates. Throat swabs were taken and cultured for GAS isolates during the winter of 1994-95 from 1000 children aged 5-7 years attending nine schools. Of the isolates obtained, 100 were serotyped using standard techniques. Nearly all these isolates (91%) were T typable, falling into 15 T types; the commonest being type 1 (n = 17), type 6 (n = 15), type 11 (n = 10), type 2 (n = 8), type 12 (n = 8), and type 28 (n = 8). A total of 76% of the isolates were typable for M protein, falling into 14 M types, with type 1 (n = 17), type 6 (n = 15), type 2 (n = 8), type 22 (n = 5), type 28 (n = 7), and type 75 (n = 5) predominating. Serotype clusters were found in certain classes or schools, although the number of isolates examined was too small to allow definitive epidemiological conclusions to be drawn. The ease of serotyping these isolates suggests that GAS strains in the United Arab Emirates are similar, but not necessarily related, to those commonly found in the USA and Europe, and that these may be the most prevalent strains worldwide. The relative prevalence of M type 1 is significant, as this GAS serotype is associated with serious diseases such as rheumatic heart disease, a recognized problem in the United Arab Emirates, and toxic shock syndrome, which has not yet been reported from this area. Knowledge of the prevalence of GAS serotypes, and further research on the epidemiology of streptococcal disease, will be useful should streptococcal vaccines become available.

Age Factors↗

PubMed1996

Evidence for a proximal histidine interaction in the structure of cytochromes c in solution: a resonance Raman study.

Soret-excited resonance Raman (RR) spectra of oxidized and reduced cytochromes ć from Rhodospirillum molischianum and Rhodobacter sphaeroides, in solution, are reported. The spectra of the type I ferricytochromes ć in both species contain different extents of two forms. One of these is readily assignable to a "normal" five-coordinated high-spin heme. The second species with v3 and v10 modes at 1502 and 1635 cm-1, respectively, is attributed to a five-coordinated intermediate-spin heme. The RR data show that the equilibrium between these two forms is species-dependent at neutral pH and 20 degrees C. The v(Fe-His) mode of the a form of reduced cytochromes ć is assigned to a band at 228-231 cm-1, indicating that the proximal His has a strong electronegative character. X-ray crystallographic data on R. molischianum ferricyt ć show that the proximal His has no interaction with either the protein or water molecules [Finzel, B.C., Weber, P.C., Hardman, K.D., & Salemme, F.R.(1985) J. Mol. Biol. 186, 627-643]. Considering that the absence of H bonding at the coordinated histidine corresponds to a low frequency for the v(Fe-His) mode (195-205 cm-1), the structure and/or environment of the proximal histidine appears different for cyt ć (III) in the crystal and cyt ć (II) in aqueous solution. To account for the elevated frequency of the v(Fe-His) mode of cyt ć (II), several possibilities have been examined. Among these, we propose that a conserved Lys residue, located in the protein sequence three residues before the His ligand, can form an electrostatic interaction with the (His)N1 atom, directly or through a water molecule. It is further suggested that this electrostatic interaction could also play a role in the high-spin <--> intermediate-spin equilibrium of oxidized cytochromes ć.

Amino Acid Sequence↗

PubMed1996

The role of complement in the pathogenesis of postpartum thyroiditis: ultrasound echogenicity and the degree of complement-induced thyroid damage.

Postpartum thyroiditis (PPT) is a transient autoimmune thyroiditis occurring during the postpartum year that is characterized by circulating antithyroid antibodies, abnormal thyroid ultrasound echotexture, and episodes of hyperthyroidism, hypothyroidism, or both. In this study we examined the relationship between lymphocytic thyroiditis, as indicated by echotexture changes, and complement-activating thyroid autoantibodies. Thyroid ultrasound echotexture, thyroid function, and bioactive (complement-activating) thyroid peroxidase (TPO) antibodies have been measured in a group of 63 TPO antibody-positive women during the postpartum year. When the maximum bioactive TPO antibody activity recorded was compared with echogenicity and thyroid status, there was a correlation between hypoechogenicity, elevated antibody activity, and abnormal thyroid status (r = 0.72, p < 0.001). However, 7 cases showed severe ultrasound changes in the absence of any thyroid dysfunction (3 of these cases showed normal bioactive antibody activity), while 4 (all hyperthyroid PPT) showed thyroid dysfunction in the absence of any ultrasound changes. Within the euthyroid ultrasound normal group, bioactive TPO antibody activity remained low throughout the postpartum year. Antibody activity in the hypoechogenic euthyroid women was significantly elevated (p < 0.001) compared with the echo normal group, but was indistinguishable from the activity curve obtained in women whose PPT included a hypothyroid phase. The determination of echotexture by thyroid ultrasonography gives a useful, noninvasive measure of the degree of thyroiditis in these women. However, as a significant number of cases with severe changes in echotexture remained euthyroid, we conclude that the development of thyroid dysfunction is not an inevitable consequence of lymphocytic thyroiditis during the postpartum and suggests that other factors must also be involved in progression to overt thyroid dysfunction.

Autoantibodies↗

PubMed1996

The clinical spectrum of postpartum thyroid disease.

The clinical and biochemical features of postpartum thyroid disease were analysed in 152 antithyroid peroxidase antibody-positive (anti-TPO+ve) women and compared with 239 anti-TPO-ve age-matched control postpartum women. All were assessed monthly for up to 12 months postpartum. Seventy three anti-TPO+ve women developed postpartum thyroiditis (PPT): 19.2% hyperthyroid alone, 49.3% hypothyroid alone, and 31.5% characterized by hyper- followed by hypothyroidism. None of the antibody-negative women developed any thyroid dysfunction. A significant increase in many of eleven symptoms of hypothyroidism and some of eight symptoms of hyperthyroidism compared to control women was observed in all anti-TPO+ve women, independent of thyroid status. This was particularly seen in women who later developed PPT when they were euthyroid, but was also observed in euthyroid anti-TPO+ve women who showed no decline of thyroid function during the postpartum period. Although PPT is usually transient, this condition, and the euthyroid antibody-positive state, may be associated with significant symptomatology, including an increased incidence of minor to moderate depression. Early recognition of this syndrome by antenatal screening of thyroid antibodies may contribute to improved management of women during the postpartum period.

Adult↗

PubMed1996

Major histocompatibility complex class II and complement polymorphisms in postpartum thyroiditis.

The objective was to re-evaluate the association between class II HLA-DR and DQ MIIC antigens and postpartum thyroiditis (PPT) and to determine the prevalence of the class III complement allotypes of Properdin factor B (Bf), C4A and C4B in this condition. Two hundred and sixty-five (of 2897) pregnant women screened positive for thyroid autoantibody activity took part. Further blood samples were obtained for HLA class II (185) and complement (193) typing. The severity of the ensuing PPT was assessed by measuring thyroid function during the postpartum year. The HLA-DR and DQ phenotypes were assigned from restriction fragment length polymorphism analysis, and Bf, C4A and C4B allotypes were determined by immunofixation with anti-Bf or anti-C4 antibodies after electrophoresis. A weak association between the HLA class II antigens and PPT, as indicated by a reduced frequency of DR15 and DQ6 together with an increased frequency of-DR5 and DQ7, was confirmed. However, only the change in DR5 frequency remained significant after correction (corrected p < 0.05). Postpartum thyroiditis was also associated with frequency disturbances in BI and C4A allotypes but not C4B allotypes. Whilst this study has not provided evidence of a strong marker gene for PPT, it does not preclude the involvement of the MIIC in this condition. These data show disturbances in complement allotype frequencies, suggesting that the class III region may provide a useful focus for further study of this pathology.

Complement C4a↗

PubMed1995

Cognitive function, thyroid status and postpartum depression.

Impairment of cognitive function can occur with thyroid disorder and also with depression. Since depression occurs in conjunction with postpartum autoimmune thyroiditis, the question arises as to whether any impairment of cognitive function in postpartum women is related to change in thyroid status or to depressed mood. A total of 242 women (110 thyroid antibody-positive and 132 antibody-negative) were assessed at 8, 12, 20 and 28 weeks postpartum in the outpatients of a district general hospital. Thyroid antibody levels (antimicrosomal and antithyroglobulin) were monitored at monthly intervals, together with plasma T3, T4 and thyroid-stimulating hormone. The main outcome measures were Research Diagnostic Criteria for depression, the 17-item Hamilton Depression Rating Scale and the Edinburgh Postnatal Depression Scale, together with reaction time and digit span. Subjects with postnatal depression showed detectable cognitive impairment independent of thyroid antibody status and actual thyroid dysfunction.

Antibodies↗

PubMed1995

Role of complement in the pathogenesis of postpartum thyroiditis: relationship between complement activation and disease presentation and progression.

The aim of this study was to assess whether the presentation and progression of autoimmune postpartum thyroiditis (PPT) was related to the degree of thyroid peroxidase autoantibody (TPO-ab)-mediated activation of the complement cascade. One hundred and forty-eight thyroid autoantibody-positive women have been followed during their postpartum year. Seventy-five women remained euthyroid during this time whilst the remaining 73 showed one or more episodes of thyroid dysfunction. Fourteen women showed hyperthyroid PPT, 23 showed a biphasic PPT and the remaining 36 showed hypothyroid PPT. Hyperthyroid PPT was always transient but 29 of the 59 women with hypothyroidism remained hypothyroid or still required thyroxine replacement therapy at the conclusion of the study. Thyroid autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA), free triiodothyronine and free thyroxine by the Amerlex M methods and thyrotrophin by the Amerlite TSH (monoclonal) assay. Complement component C3b, immobilized as a result of classical complement pathway activation in the presence of TPO/TPO-ab complexes in vitro, was measured by ELISA. Bioactive TPO-ab were calculated as the product of the C3 index and TPO-ab level. Basal levels of complement C3 activation were seen in the euthyroid TPO-ab-positive women (C3 index 0.06 at delivery rising to 0.36 at 12 months postpartum; bioactive TPO-ab activity 0.4 kIU/l at delivery rising to 10.4 kIU/l at 12 months' postpartum (N = 75). These parameters were elevated progressively as the severity of the clinical syndrome increased. In 14 hyperthyroid PPT women the C3 index was 0.47 at 8 months' postpartum (bioactive TPO-ab activity = 20 kIU/I; p vs euthyroid group, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

PubMed1994

Resonance Raman investigation of imidazole and imidazolate complexes of microperoxidase: characterization of the bis(histidine) axial ligation in c-type cytochromes.

In order to evaluate the steric and electronic influences of the heme axial ligands on the vibrational modes of heme c, various ferric and ferrous six-coordinate heme c compounds have been prepared from microperoxidase-8 (MP8) and different extrinsic ligands. In this paper, the absorption and Soret-excited resonance Raman (RR) spectra of imidazole, imidazolate, 1-methylimidazole, and histidine complexes of MP8 are presented. The absorption characteristics of the unligated forms, either aggregated or monomeric, as well as of the ligated forms of MP8(III) and MP8(II) have been determined as a function of pH, the presence of a cationic detergent, and the ligand concentration. Spectrophotometric titrations have shown that MP8(III) and MP8(II) can bind one or two molecules of exogenous ligand, forming monoligated or bisligated complexes. The latter form, observed with large excesses of ligand, results from the displacement of the intrinsic proximal His of MP8 by an exogenous ligand. Several structural marker bands have been detected in the high- and low-frequency regions of RR spectra. The high-frequency RR spectra of the ImH compounds of MP8(III) exhibit a v10 mode sensitive to ligand deprotonation(s). Moreover, the replacement of His by an exogenous ImH in MP8(III) complexes induces the upshift of the v10 mode frequency (1637-1641 cm-1), indicating that the porphyrin skeleton is less distorted when the internal coordination of proximal His to heme is broken. A similar dependence of the out-of-plane porphyrin distortion is suggested for the low-frequency mode v8 (343-347 cm-1). As far as the ferrous compounds are concerned, the mode most sensitive to the ImH deprotonation is v11, which is downshifted from 1539 to 1527 cm-1. Comparisons of the low-frequency regions of the RR spectra of imidazole-type ligated MP8(III) and MP8(II) complexes, as well as observations based on isotopic substitutions of the corresponding 1-methylimidazole complexes (MeIm-->MeIm-d6), allow the assignment of two bands in the 184-197 and 400-409 cm-1 regions to modes involving the symmetric and asymmetric stretches of the axial ligands, respectively. Two other bands in the 343-347 and 359-362 cm-1 regions, sensitive to the mass and/or deprotonation states of the axial ligands, have been tentatively assigned to v(Fe-N(pyrrole)) modes coupled to either a deformation mode of axial bonds or an internal mode of the bound imidazole(s).(ABSTRACT TRUNCATED AT 400 WORDS)

Cytochrome c Group↗

PubMed1994

The role of complement in the pathogenesis of postpartum thyroiditis.

Postpartum thyroiditis (PPT) affects half of the 10% of women who have elevated circulating thyroid autoantibodies during the postpartum year. Because of the similarities between PPT and Hashimoto's thyroiditis, the pathogenic role of complement in PPT has been investigated. Complement fixation by thyroid peroxidase antibodies (TPO Abs) (expressed as log reciprocal titer) in serum from euthyroid TPO Ab-positive women (n = 29) was 0.91 at 1 month postpartum and increased to 1.45 by 12 months postpartum; complement C3 activation, measured by enzyme-linked immunosorbent assay, in a similar group of women (n = 75) was 0.05 at delivery and increased to 0.33 by 6 months postpartum. In women with PPT, there was greater TPO Ab-related complement activation during the postpartum year; complement fixation increased from 1.00 at 1 month postpartum to 1.48 at 4 months postpartum (P < 0.005) (n = 25), and C3 activation increased from 0.11 at delivery to 0.63 at 6 months postpartum (P < 0.005) (n = 73). Bioactive TPO Ab (TPO Ab x C3 index) was significantly higher in PPT women (55 kilo international units of activity (kIU)/L at 6 months postpartum) (Hashimoto range, 30-108 kIU/L) compared with euthyroid TPO Ab-positive women (< 9 kIU/L at all time points; P < 0.005). Serum samples from TPO Ab-negative control women showed no interaction with complement in either assay at any time during the postpartum year (complement fixation < 0.7; complement C3 activation index < 0.01). This detailed examination of the role of complement in the pathogenesis of PPT shows that TPO Ab-driven complement fixation is a marker for thyroid dysfunction in TPO Ab-positive women. The levels of bioactive TPO Ab in PPT fall within the range seen in Hashimoto's thyroiditis, suggesting similarities in their pathology.

Autoantibodies↗

PubMed1993

A heme c-peptide model system for the resonance Raman study of c-type cytochromes: characterization of the solvent-dependence of peptide-histidine-heme interactions.

The visible absorption and Soret-excited resonance Raman spectra of ferrous microperoxidase-8 [MP8(II)], an octapeptide containing a heme c, are reported. These spectroscopies indicate that MP8(II), dissolved in aqueous buffered solutions, forms low-spin six-coordinated complexes in the 7-14 pH range. Intermolecular bonding interactions of MP8(II) in water account for this behavior. On the contrary, when the hemopeptide is dispersed in aqueous solutions containing detergent or an alcohol, the spectroscopic data show that the iron atom of MP8(II) is essentially high-spin five-coordinated in accordance with a monomeric structure of MP8(II). In addition to a high-spin signature to the heme skeletal modes, the high-frequency regions of resonance Raman spectra characterize an electronic influence of the thioether bridges on the frequency of stretching modes of C beta-C beta bonds (nu 2, nu 11, and nu 29). On the other hand, the low-frequency Raman spectra of monomeric MP8(II) at pH 7.5 present significant differences in the 150-250-cm-1 regions depending upon the solvent composition (pH, presence or absence of detergent, alcohol). These effects are attributed to frequency variations of the Fe-N(His)-involving mode which indicate changes in the H-bonding interactions of the axial His and therefore solvent-dependent changes of the octapeptide conformation. Our resonance Raman data further show that the axial His of monomeric MP8(II) could be totally deprotonated in aqueous cetyltrimethylammonium bromide solution at very alkaline pH (pKa = 13.3). The vibrational data (100-1700 cm-1) obtained for the various monomeric forms of MP8(II) are expected to be useful for determining the heme structure and environment in reduced c'-type cytochromes. Comparisons of resonance Raman data with X-ray crystallographic data available for different hemoproteins allow us to evaluate the ionization and H-bonding states of the His bound to the high-spin five-coordinated hemes. These data are discussed in terms of proximal influence of protein-His-heme interactions on the determination and the regulation of a particular biological function.

Amino Acid Sequence↗

PubMed1992

Association between postpartum thyroid dysfunction and thyroid antibodies and depression.

OBJECTIVE: To define the relation between mood and autoimmune thyroid dysfunction during the eight months after delivery. DESIGN: Double blind comparison of the psychiatric status of women positive and negative for thyroid antibodies. Clinical examination and blood sampling for free triiodothyronine and thyroxine, thyroid stimulating hormone, and thyroid antibody concentrations at four weekly intervals. Psychiatric assessment at six, eight, 12, 20, and 28 weeks post partum. SETTING: Outpatient department of district hospital. PATIENTS: 145 antibody positive women and 229 antibody negative women delivering between August 1987 and December 1989. MAIN OUTCOME MEASURES: Thyroid status. Number of cases of mental ill health by the general health questionnaire, research diagnostic criteria, Hamilton 17 item depression scale, hospital anxiety and depression scale, and Edinburgh postnatal depression scale. RESULTS: Six weeks after delivery the general health questionnaire showed 62 (43%) antibody positive women and 65 (28%) antibody negative women had mental ill health (chi 2 = 8.18, p less than 0.005). Follow up of 110 antibody positive and 132 antibody negative women showed significantly greater depression by research diagnostic criteria in antibody positive women (47%) than antibody negative women (32%) regardless of thyroid dysfunction. Antibody positive women showed higher mean scores for depression on the Hamilton (6.01 v 3.89, p = 0.0002), Edinburgh (7.45 v 5.92, p = 0.031), and hospital depression scales (4.95 v 3.79, p = 0.003). CONCLUSION: Depressive symptoms are associated with positive thyroid antibody status in the postpartum period.

Autoantibodies↗

PubMed1992

The sonographic appearances in postpartum thyroiditis.

During the postpartum period about 50% of women with circulating thyroid autoantibodies develop a transient autoimmune thyroiditis. To determine the sonographic appearances in postpartum thyroiditis (PPT), serial ultrasound (US) scans of the thyroid were performed in 135 postpartum women who were divided into three clinical groups: Group 1, 37 antibody positive subjects who developed PPT; Group 2, 28 antibody positive subjects in whom thyroid function remained normal; Group 3, 70 antibody negative controls. Thyroid hypoechogenicity was observed in 14/31 patients (45%) who were scanned between 4 and 8 weeks postpartum and who subsequently developed PPT (Group 1) compared with 4/24 patients (17%) in Group 2 (P less than 0.05) and 1/65 patients (1.5%) in Group 3 (P less than 0.001). In antibody positive patients, the positive predictive value of an abnormal scan during this period was 78%. Between 15 and 25 weeks postpartum thyroid hypoechogenicity was present in 32/37 patients (86%) in Group 1 compared with 11/28 patients (39%) in Group 2 (P less than 0.001) and 2/70 patients (3%) in Group 3 (P less than 0.001). Sonographic abnormality persisted beyond 32 weeks postpartum in 36/41 antibody positive patients (87%) who had exhibited thyroid hypoechogenicity earlier during the study and who had late scans. The characteristic US appearance in PPT is thyroid hypoechogenicity. The role of sonography in the prediction, diagnosis and follow up of patients with PPT is discussed.

Autoantibodies↗