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Biomedical subjects

V Petersen

Publications and source records attributed to V Petersen.

At least 19 recordsLinked to original sources
PubMed2001

The impact of parental divorce for adolescents: a consideration of intervention beyond the crisis.

The effects of divorce on children and adolescents remain a major public health issue. Over the last three decades, there has been ongoing debate among researchers and mental health and legal professionals who counsel divorcing families as to whether the effects are acute but time-limited or more enduring. This chapter looks at the tasks of normal adolescent psychosocial development and how divorce complicates those tasks. It suggests ways that pediatricians and other health professionals can intervene effectively with divorcing families within the context of their role. Divorce-specific resources and services are explained.

Adolescent↗
PubMed1998

Analysis of autoantibody epitopes on steroid 21-hydroxylase using a panel of monoclonal antibodies.

A panel of five mouse monoclonal antibodies (MAbs) to human recombinant steroid 21-hydroxylase (21-OH) were produced, characterized, and used to study the interaction of 21-OH autoantibodies (AAbs) with different epitopes on human 21-OH. AAbs in patients with isolated autoimmune Addison's disease, autoimmune polyglandular syndromes types I and II, and 21-OH antibody-positive patients without overt Addison's disease (25 patients in total) were studied. Four MAbs were IgG1 subclass, one was IgG2a, and all had kappa light chains. The affinities of four of the antibodies were in the range 2.0 x 10(8) M(-1) to 7.0 x 10(8) M(-1), and the affinity of the other was 2.3 x 10(7) M(-1) 21-OH MAbs did not cross-react with 17alpha-hydroxylase (17alpha-OH)) or P450 side chain cleavage enzyme. Studies using a series of 21-OH fragments allowed the identification of short stretches of amino acids (AA) that were involved in forming the MAb binding sites. AA 391-405, defined as epitope region (ER) 1, were found to be important for binding of M21-OH1 and M21-OH2, AA 406-411 (ER2) were important for M21-OH3 and M21-OH4 binding, and AA 335-339 (ER3) for M21-OH5 binding. In addition, MAb Fab or F(ab')2 fragments were used to study 21-OH AAb epitopes in competition experiments. These investigations demonstrated that 21-OH AAbs recognize similar epitopes to the MAbs, with ER2 and ER3 being part of two distinct major epitopes, and ER 1 being part of a minor epitope. Mixtures of M21-OH antibody Fab or F(ab')2 fragments caused almost complete inhibition (80%-95%) of AAb binding in 24 out of 25 sera, and in the case of the remaining serum, the effect was marked but incomplete (67% inhibition). There were no major differences between the binding characteristics of AAbs from patients with different forms of autoimmune adrenal disease. All five 21-OH MAbs reacted with human adrenal tissue in an immunofluorescence test, but only M21-OH1 and M21-OH2 reacted with bovine adrenal tissue in these experiments. None of the MAbs reacted with human ovarian tissue in an immunofluorescence test. Overall, these studies indicate that 21-OH AAbs bind to at least three different epitopes in the C-terminal part of 21-OH, and two of these epitopes appear to be human 21-OH specific.

Addison Disease↗
PubMed1996

Glutamic acid decarboxylase autoantibody assay using 125I-labelled recombinant GAD65 produced in yeast.

We describe a new method for measuring autoantibodies (Ab) to the 65 kDa isoform of glutamic acid carboxylase (GAD65). In particular, GAD65 without the hydrophobic N-terminal region has been produced in yeast, purified, labelled with 125I and reacted with GAD65 Ab. Antibody bound 125I-GAD65 is then precipitated by the addition of solid phase protein A. With the assay, GAD65 Ab were detected in 59 of 71 (83%) islet cell antibody (ICA) positive IDDM patients and in 8 of 23 (35%) ICA negative IDDM patients (overall 67 of 94 (71%) of IDDM patients). Low concentrations of GAD65 Ab were also detected in 2/98 (2%) healthy blood donors and 1/27 (4%) Graves' disease patients had a high level of antibody. GAD65 Ab were not detected in any of 10 Hashimoto's thyroiditis, 20 Addison's disease or 19 myasthenia gravis sera. There was good agreement between the 125I assay and the current reference method based on 35S-labelled full-length GAD65 (produced by in vitro transcription/translation reaction) and solid phase protein A (r = 0.91, n = 108). Overall, our 125I assay showed sensitivity, precision and disease group specificity at least as good as any assay so far described. These features, combined with a simple assay protocol and the convenience of 125I counting and handling indicate that the method is suitable for routine GAD65 Ab measurements.

Adult↗
PubMed1996

Effects of the antiparkinsonian drug budipine on central neurotransmitter systems.

Budipine is a novel antiparkinsonian drug which is particularly beneficial in the treatment of parkinsonian tremor. The mechanism of action of budipine is not fully understood. To study whether budipine has dopaminergic activity in vivo, we used the 6-hydroxydopamine rotational model of Parkinson's disease. Budipine (0.78-12.5 mg/kg i.p.) did not induce ipsilateral or contralateral rotations, suggesting that it does not possess direct or indirect dopaminergic activity. This conclusion is further supported by the observation that budipine (10 mg/kg) i.v. did not facilitate striatal dopamine release measured in vivo by brain microdialysis. To investigatate possible antimuscarinic and N-methyl-D-aspartic acid (NMDA) antagonistic properties of budipine, we compared budipine with the antimuscarinic antiparkinsonian drug biperiden and the NMDA receptor antagonist 3-[(+/-)-2-carboxypiperazine-4-yl]-propyl-1-phosphonic acid (CPP). In receptor-binding assays, budipine inhibited thienylcyclohexylpiperidyl-3,4-[3H](n) ([I3H]TCP) (2.5 nM)-binding with an IC50 of 36 microM and [3H]3-quinuclidinol benzilate-binding with an IC50 of 1.1 microM. The respective values for biperiden were 170 and 0.053 microM. In line with these findings, budipine and CPP increased the threshold for NMDA-induced seizures in mice with an ED50 of 10.2 and 4.4 mg/kg, respectively, whereas biperiden was not effective. In 6-hydroxydopamine-lesioned rats, budipine (3.13-12.5 mg/kg) and CPP (0.1-0.39 mg/kg) increased the number of contralateral rotations induced by apomorphine, whereas biperiden was not effective. The present data suggest that budipine acts by blocking muscarinic and NMDA transmission while facilitation of dopaminergic transmission does not appear to contribute to its in vivo action. In comparison to biperiden, which has also antimuscarinic and NMDA receptor antagonistic properties, the anti-NMDA action of budipine is more prominent.

Animals↗
PubMed1996

Pharmacology and regional distribution of the binding of 6-[3H]nitro-7-sulphamoylbenzo[f]-quinoxaline-2,3-dione to rat brain.

6-Nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione (NBQX) is a competitive antagonist selective for alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. Here we report the pharmacological characteristics and anatomical distribution of [3H]NBQX binding to rat brain. The association rate of [3H]NBQX to rat cerebrocortical membranes was rapid, with peak binding occurring within 10 min at 0 degree C. The off-rate was also rapid, with near-complete dissociation of the radioligand within 5 min of addition of 1 mM unlabelled L-glutamate. [3H]NBQX bound to a single class of sites with KD and Bmax values of 47 nM and 2.6 pmol mg-1 of protein, respectively. The rank order of inhibition of [3H]NBQX binding by AMPA receptor ligands was NBQX > > 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) > or = (S)-5-fluorowillardiine > or = AMPA > > L-glutamate. The chaotrope KSCN had no effect on the IC50 value of unlabelled NBQX displacement of [3H]NBQX binding. The kainate receptor-selective ligands NS102 and kainate were only very weak displacers. It is interesting that NBQX and CNQX displaced significantly more [3H]NBQX than any of the agonists tested. Autoradiographic analysis of the binding of [3H]NBQX to coronal sections showed a distribution compatible with that of [3H]AMPA binding. These data indicate that [3H]NBQX provides a useful novel tool to characterise the antagonist binding properties of AMPA receptors.

Animals↗
PubMed1995

Cellular uptake of albumin from lungs of anesthetized rabbits.

Resolution of alveolar edema depends on clearance of serum protein, as well as liquid from the alveolar space. Protein clearance is slower than liquid clearance and may take days to weeks. Our earlier studies presented evidence for the importance of paracellular removal of soluble protein from the air spaces. However, long-term protein clearance may also depend on uptake by alveolar epithelial cells or macrophages. This study examined cellular uptake of soluble human albumin and insoluble colloidal gold-albumin from the lungs of anesthetized rabbits. Native albumin was endocytosed by both alveolar type I and type II cells and appeared in vesicles and endosomes. Neither cell type took up colloidal gold-albumin over periods as long as 8 h. Alveolar macrophages took up native albumin and colloidal gold-albumin to a greater extent and more rapidly than alveolar epithelial cells. The tracer proteins were found in vesicles, endosomes, and phagolysosomes. Similarly, cultured alveolar macrophages took up native albumin more rapidly than cultured type II cells. Thus macrophages may be important in clearing precipitated protein from the air spaces, and they may have a role in completing the clearance of soluble protein. The potential for transepithelial transport of soluble alveolar protein exists, but based on this work and our prior studies, it appears to be a low-capacity pathway.

Animals↗
PubMed1995

Monoclonal thyroglobulin autoantibodies: variable region analysis and epitope recognition.

A panel of human monoclonal thyroglobulin (Tg) autoantibodies (TgAAb) has been used to analyze autoantigenic determinants on human Tg and to investigate the relationship between variable (V) region gene sequences and epitope specificity. Two monoclonal TgAAb bound to the same (or closely related) epitope on Tg, and these were defined as type I TgAAb. Three other monoclonals bound to a different site and were defined as type II TgAAb. Inhibition studies with mixtures of type I and type II monoclonal TgAAb (Fab)2 preparations indicated that a mixture of the (Fab)2s almost completely inhibited (> 75%) labeled Tg binding to intact TgAAb in the sera of apparently healthy blood donors and patients with autoimmune thyroid disease (AITD). Type I TgAAb predominated in apparently healthy blood donors' sera, whereas type II TgAAb predominated in AITD sera. Analysis of V region gene sequences of the TgAAb indicated that a range of light chain and heavy chain genes from different gene families was used. Furthermore, the same germline genes that are used by TgAAb are also well represented in the genes coding for other self- and nonself-reactive antibodies. No homology in terms of light chain and heavy chain gene families, germline gene usage, or complementarity determining region sequences was observed in TgAAb directed to the same or closely related epitopes. Our studies show that TgAAb are directed to two major conformational epitopes on the Tg molecule and that the proportion of TgAAb directed to these epitopes in apparently healthy blood donors and that in patients with AITD appear to be different. TgAAb derived from different germline genes and with different complementarity determining region sequences can display similar epitope specificity, and this indicates that AAb directed to the same or a closely related epitope show considerable heterogeneity at the molecular level.

Amino Acid Sequence↗
PubMed1991

Subcellular distribution and life cycle of Epstein-Barr virus in keratinocytes of oral hairy leukoplakia.

The authors investigated the life cycle of Epstein-Barr virus (EBV) in keratinocytes of oral hairy leukoplakia by combining immunohistochemistry. DNA in situ hybridization, and lectin histochemistry with electron microscopy. Diffuse-staining components of the EBV early antigen complex (EA-D), EBV 150-kd capsid antigen (VCA), EBV membrane antigen (gp350/220), and double-stranded DNA were labeled with monoclonal antibodies. An EBV-DNA probe was used to locate EBV DNA. Wheat-germ agglutinin (WGA) was employed to distinguish Golgi-associated compartments. The authors found EBV proteins and EBV DNA only in keratinocytes with apparent viral assembly. In situ hybridization showed EBV DNA in free corelike material and in electron-dense cores of mature nucleocapsids. Monoclonal antibodies to nonspecific double-stranded DNA attached to the same structures and to marginated chromatin. Components of EA-D were dispersed throughout the nuclei but accumulated near condensed chromatin and in 'punched-out' regions of the chromatin. Epstein-Barr virus 150-kd capsid antigen was found only in the nuclei, where it appeared preferentially on mature nucleocapsids. As yet unexplained arrays of intranuclear particles that remained unlabeled with all EBV-specific probes reacted intensely with an antiserum against common papillomavirus antigen. Gp350/220 was detectable in various cellular membrane compartments and was highly concentrated on EBV envelopes in peripheral Golgi-associated secretory vesicles. It was less abundant on the extracellular EBV, indicating that viral membrane antigen partly dissociates from the mature virus. Combined lectin-binding histochemistry and electron microscopy demonstrated for the first time that EBV is processed in the Golgi apparatus, which eventually releases the virus by fusion with the plasma membrane. These results provide insight into the biologic events that occur during complete EBV replication in vivo.

Adult↗
PubMed1990

Efficacy of desciclovir in the treatment of Epstein-Barr virus infection in oral hairy leukoplakia.

The efficacy of desciclovir, an analog of acyclovir, in eliminating lesions of oral hairy leukoplakia (HL) and suppressing Epstein-Barr virus (EBV) infection was evaluated in a double-blind, placebo-controlled study of 14 patients. Patients were randomized to receive either the active drug, 250 mg three times a day for 14 days, or placebo. In all eight patients receiving desciclovir, lesions of HL were either completely resolved or significantly reduced during the treatment period, whereas lesions in patients receiving placebo showed no change. The histological features of HL were significantly diminished in patients on desciclovir, and cytochemical, in situ hybridization, and ultrastructural studies showed that EBV infection was eliminated or dramatically reduced in the desciclovir group only. Four patients on desciclovir reported side effects, but none required withdrawal from the study. The reappearance of HL in all eight subjects on desciclovir within 1-4 months after therapy was discontinued suggests the need for additional study.

Acyclovir↗
PubMed1989

Fine structure of EBV-infected keratinocytes in oral hairy leukoplakia.

We evaluated biopsy specimens of 42 cases of clinically suspected oral hairy leukoplakia for the pattern and frequency of ultrastructural alterations specific to epithelial cells infected with Epstein-Barr virus. Some structures could clearly be identified as Epstein-Barr virus at different stages of assembly, but other intranuclear and cytoplasmic alterations were not conclusively identifiable as any known structure. Keratinocytes producing Epstein-Barr virus contained intranuclear particles of different size and shape; some of them were arranged in a monodispersed pattern and others formed arrays. In contrast, both lesional keratinocytes not producing virus and keratinocytes in uninvolved mucosa contained intranuclear particles reminiscent of perichromatin granules. The nuclei of productive cells also contained marginated chromatin, tubular structures, and, occasionally, crystalline and fibrillar formations as well as enveloped virus. Formations of electron-dense bilayers were seen on both sides of the nuclear membrane. In the cytoplasm of productive cells we observed aggregates of parallel tubules and enveloped electron-dense bodies. Although many of these observations are of diagnostic and pathobiological significance, the morphogenesis, composition, and function of alterations with uncertain morphological identification remain unclear.

Adult↗
PubMed1987

Operative treatment of chronic acromioclavicular dislocation.

Six patients (median age 35 years) were reviewed at an average of 24 months after operation for chronic acromioclavicular dislocation. The operation consisted of resection of the lateral part of the clavicle and transference of the coracoacromial ligaments as a substitute for the coraco-clavicular ligament. The ligament was secured by an AO screw for 6 weeks. In five patients the reasons for operation were pain, when working and sleeping, and, in one patient, pressure on the skin. Three of the patients complained of weakness. At follow-up the results were excellent in four patients and good in two. Three patients had mild pain when lying on the shoulder and three had complaints where the flake of bone attached to the transferred ligament was inserted into the clavicle. We now recommend a modification of the method, omitting the flake of bone.

Acromioclavicular Joint↗
PubMed1987

Absence of Langerhans cells in oral hairy leukoplakia, an AIDS-associated lesion.

Oral hairy leukoplakia (HL) is a recently described manifestation of human immunodeficiency virus (HIV) infection in which Epstein-Barr virus (EBV) has been shown to replicate. To seek evidence for a local defect in mucosal immunity, we assessed the presence of epithelial Langerhans cells (LC) in these lesions and in autologous nonlesional mucosa. We used monoclonal antibodies against HLA-DR, HLA-DQ, and T6 antigens to identify LC in biopsy specimens of HL from 23 homosexual men. In all lesion specimens, LC either were not detected or were present only in greatly reduced numbers with at least 1 of the antibodies. In nonlesional oral mucosa from the same patients, LC were detected with all 3 antibodies in 11/12 specimens (92%) and were found in approximately normal numbers with at least 1 antibody. There was close correlation between the absence of LC and positive staining for EBV, human papillomavirus antigens, and candidal hyphae in the epithelium. We conclude that LC are absent or greatly reduced in the lesions of HL. Absence of normal LC function may be important in the pathogenesis of HL and may reflect an event in the pathogenesis of other features of the acquired immune deficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Replication of Epstein-Barr virus within the epithelial cells of oral "hairy" leukoplakia, an AIDS-associated lesion.

We conducted a study to identify the viruses in tissue specimens of oral "hairy" leukoplakia, a lesion that is found in immunosuppressed male homosexuals and that is associated with the subsequent development of the acquired immunodeficiency syndrome. When stained for papillomavirus core antigen, 49 of 67 biopsy specimens (73 per cent) yielded positive results in epithelial-cell nuclei. Electron microscopy showed papillomavirus-like particles in all of 25 specimens, and the herpes-type virus described in a previous report was seen in 23 of the 25 specimens. Three specimens had both types of particle in the same individual epithelial cells. Immunofluorescence for herpes simplex virus, varicella-zoster virus, and cytomegalovirus gave negative results in all cases, but 19 of 20 specimens showed intense nuclear staining in epithelial cells for the viral capsid antigen of Epstein-Barr virus (EBV). DNA hybridization using EBV probes in Southern blots demonstrated EBV DNA in all of 13 specimens and found 200 or more viral DNA molecules per cellular genome in 11 of the 13. The whole EBV genome was also demonstrated in the specimens and found to be in linear virion form. We conclude that EBV replicates within the epithelial cells in hairy leukoplakia.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Oral "hairy" leucoplakia in male homosexuals: evidence of association with both papillomavirus and a herpes-group virus.

An outbreak of a new form of oral leucoplakia, found principally on the lateral borders of the tongue, is reported in male homosexuals in the San Francisco area. Many of the patients showed evidence of immunosuppression, and candida was often found in the lesions. The characteristic histology is similar to that of the flat wart of skin. There was immunocytochemical evidence of papillomavirus core antigen in 77% of 30 biopsy specimens, but no papillomaviruses were detected by electron microscopy in samples from 6 randomly selected patients. In 5 of these 6 patients there was evidence of a herpes-type virus. Pneumocystis carinii pneumonia has developed in 8 of 37 patients in a 33-month period. This leucoplakia may presage AIDS, may be associated with both papillomavirus and a herpes-type virus, and may offer clues to the pathogenesis of other forms of oral epithelial hyperplasia and dysplasia.

Acquired Immunodeficiency Syndrome↗