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PubMed1982

Cerebral ventricular enlargement in subtypes of chronic schizophrenia.

A computed tomographic study of the brain in 55 young men with chronic schizophrenia and 27 age- and sex-matched control subjects showed a significantly higher ventricle-brain ratio (VBR) in the patients with chronic schizophrenia. Using the Tsuang-Winokur criteria, the sample was classified into paranoid and nonparanoid-hebephrenic subtypes. Nonparanoid patients who did not fulfill the criteria for hebephrenia were grouped as a nonparanoid-undifferentiated subtype. All three groups of subtypes had a significantly higher mean VBR than control subjects. Among the schizophrenia subtypes, the paranoid and nonparanoid-hebephrenic groups were not different, and both had a significantly larger mean VBR than the nonparanoid-undifferentiated group. The results suggest that although the extent of ventricular enlargement varies among schizophrenia subtypes, they all show a significant enlargement compared with the control group. Also, in contrast with previous reports linking a high VBR with negative symptoms, poor prognosis, and impaired cognition, the data in this study show the largest mean VBR in the paranoid patients who generally have a good premorbid history, positive symptoms, less impaired cognition, and relatively better prognosis.

Adult↗
PubMed1999

Muscarinic receptor subtypes in the lateral geniculate nucleus: a light and electron microscopic analysis.

Neural activity in the dorsal lateral geniculate nucleus of the thalamus (DLG) is modulated by an ascending cholinergic projection from the brainstem. The purpose of this study was to identify and localize specific muscarinic receptors for acetylcholine in the DLG. Receptors were identified in rat and cat tissue by means of antibodies to muscarinic receptor subtypes, ml-m4. Brain sections were processed immunohistochemically and examined with light and electron microscopy. Rat DLG stained positively with antibodies to the m1, m2,and m3 receptor subtypes but not with antibodies to the m4 receptor subtype. The m1 and m3 antibodies appeared to label somata and dendrites of thalamocortical cells. The m1 immunostaining was pale, whereas m3-positive neurons exhibited denser labeling with focal concentrations of staining. Strong immunoreactivity to the m2 antibody was widespread in dendrites and somata of cells resembling geniculate interneurons. Most m2-positive synaptic contacts were classified as F2-type terminals, which are the presynaptic dendrites of interneurons. The thalamic reticular nucleus also exhibited robust m2 immunostaining. Cat DLG exhibited immunoreactivity to the m2 and m3 antibodies. The entire DLG stained darkly for the m2 receptor subtype, except for patchy label in the medial interlaminar nucleus and the ventralmost C laminae. The staining for m3 was lighter and was distributed more homogeneously across the DLG. The perigeniculate nucleus also was immunoreactive to the m2 and m3 subtype-specific antibodies. Immunoreactivity in cat to the m1 or m4 receptor antibodies was undetectable. These data provide anatomical evidence for specific muscarinic-mediated actions of acetylcholine on DLG thalamocortical cells and thalamic interneurons.

Animals↗
PubMed1999

Immunohistochemical distribution of the somatostatin receptor subtype 5 in the adult rat brain: predominant expression in the basal forebrain.

Somatostatin exerts its actions by means of a family of G protein-coupled receptors, five of which have so far been cloned. Whereas mRNAs for receptor subtypes sst(1)-sst(4) have been unequivocally localized in the brain, the data concerning the fifth subtype, sst(5), are contradictory. Moreover, whereas sst(1) and sst(2A) receptor proteins have been localized by immunohistochemistry, the distribution of sst(3)-sst(5) receptor proteins and/or subtype-specific binding remains to be determined in the central nervous system. In the present study, we investigated the distribution of immunoreactive sst(5) in adult rat brain and pituitary and demonstrated the presence of this receptor protein in the central nervous system by using an affinity-purified antibody generated against the C-terminus of the receptor. The specificity of the antibody for sst(5) was established by immunoblotting experiments on membranes prepared from cells transfected with cDNA encoding different somatotropin release inhibiting (SRIF) receptor subtypes as well as from anterior pituitary. In both systems, the antibody specifically recognized a band at approximately 50 kDa molecular mass, corresponding well to the reported size of the cloned receptor (48 kDa). Immunofluorescence in COS-7 cells transfected with individual SRIF receptor subtypes as well as in sections of rat pituitary demonstrated the antibody's applicability to the immunohistochemical detection of sst(5) receptors. In rat brain sections, sst(5) immunoreactivity was predominantly associated with neuronal perikarya and primary dendrites. Immunolabeling was most prominent in the olfactory tubercle, islands of Calleja, diagonal band of Broca, substantia innominata, and magnocellular preoptic nucleus of the basal forebrain as well as in the reticular nucleus of the thalamus. Other, less intensely labeled areas included the cerebral cortex, hippocampus, amygdala, preoptic area as well as the lateroanterior nucleus of the hypothalamus. The present findings provide the first characterization of the anatomic distribution of sst(5) receptors in the rat brain. They demonstrate a prominent expression of these receptors in the basal forebrain, suggesting that they may be involved in the mediation of somatostatin effects on the sleep-wake cycle through their association with cortically projecting subcortical systems.

Animals↗
PubMed1998

Cancer of the corpus uteri in white and black women in Michigan, 1985-1994: an analysis of trends in incidence and mortality and their relation to histologic subtype and stage.

BACKGROUND: Cancer of the corpus uteri occurs more commonly among white women in the U.S., yet survival is poorer for black women. This study examined whether this trend has changed and also examined the relation of age and histologic subtype to differences in stage. METHODS: This retrospective cohort study assessed incidence trends, mortality trends, and the relation of age and histologic subtype to stage for 12,079 incident cases and 2325 deaths registered between 1985 and 1994 in Michigan. Rate ratios compared incidence and mortality. Odds ratios quantified the contribution of age and histologic subtype to differences in risk for advanced stage, using Mantel-Haenszel univariate techniques and multivariate logistic regression. RESULTS: The overall incidence rate was 21.99 per 100,000, and the overall mortality rate was 3.82 per 100,000. Black women had a 40% lower risk (rate ratio [RR] =0.60) of developing cancer of the corpus uteri but had a 54% greater risk (RR=1.54) of dying from cancer of the corpus uteri. Black women were at greater risk of being diagnosed with either sarcoma or more aggressive adenocarcinoma. However, after adjustment for age and histologic subtype, black women still had an increased risk for advanced stage disease (2.63, 95% confidence interval=2.19-3.16). CONCLUSIONS: The disparity between white and black women persists in incidence and mortality trends for cancer of the corpus uteri. The greater frequency of more aggressive histologic subtypes experienced by black women accounts for only 10% of their excess risk for more advanced stage disease.

Adenocarcinoma↗
PubMed1998

Electrophysiological studies in the Guillain-Barré syndrome: distinguishing subtypes by published criteria.

Guillain-Barré syndrome (GBS) is recognized clinically by the presence of acute, rapidly progressive weakness, areflexia, and albuminocytological dissociation in cerebrospinal fluid. Although GBS was initially considered to be primarily an acute inflammatory demyelinating polyneuropathy (AIDP), several other subtypes have been recognized: acute motor axonal neuropathy (AMAN), acute motor-sensory axonal neuropathy (AMSAN), and Fisher syndrome (FS). Because each of these subtypes may have an independent immunopathogenesis and, therefore, may require selective treatments in the future, recognition of these subtypes is important. When using nerve conductions to classify the subtypes, the most easily and confidently identified subtype is AIDP. Therefore, most electrodiagnostic criteria have attempted to identify demyelination in this acute setting, in which physiology is constantly changing. In a single well-defined GBS population, we compared the various published criteria for demyelination in GBS. We reviewed charts of 43 patients with GBS between 1991 and 1996. Applying six available criteria sets, the number of patients categorized as having AIDP ranged from 21% to 72%. Until investigators can agree on a single set of criteria, considerable variability will continue to exist when identifying cases of AIDP.

Adolescent↗
PubMed1991

Flow cytometric DNA content analysis in neuroendocrine carcinoma of the lung. Correlation with survival and histologic subtype.

The DNA content of 53 primary and locally metastatic pulmonary neuroendocrine carcinomas was retrospectively determined by flow cytometric analysis of nuclei released from paraffin-embedded tissues and compared with histologic subtypes and clinical survival. Forty-one percent (9 of 22) of tumors classified as well-differentiated neuroendocrine carcinoma (WDNC) were aneuploid. In contrast, 85% (17 of 20) of small cell neuroendocrine carcinoma (SCNC), and 73% (8 of 11) of intermediate cell neuroendocrine carcinoma (ICNC) were aneuploid. DNA content was not a significant independent predictor of patient survival within each histologic subtype (P greater than 0.05 for all subtypes). Yet, when all cases were examined as a single group, diploid cases showed better clinical survival than cases with DNA aneuploidy (P less than 0.02). However, the survival advantage for diploid DNA content did not quite achieve statistical significance when only cases of limited stage disease were analyzed (0.10 greater than P greater than 0.05). Histologic subtype was also a prognostic indicator, with WDNC cases showing a significantly longer survival than either SCNC (P less than 0.05) or ICNC (P less than 0.02), for those cases with limited-stage disease. These results indicate information on clinical staging and the histologic subtype are important parameters to compare with DNA content analysis in determining independent prognostic factors in neuroendocrine or small cell carcinoma of the lung.

Adult↗
PubMed2000

Group I and group III metabotropic glutamate receptor subtypes provide enhanced neuroprotection.

Neuroprotection by the metabotropic glutamate receptor (mGluR) system has been linked to the modulation of both the free radical nitric oxide (NO) and programmed cell death (PCD). Because the cellular mechanisms that ultimately determine neuronal PCD rely upon the independent pathways of genomic DNA degradation, externalization of membrane phosphatidylserine (PS) residues, and the activation of associated cysteine proteases, we investigated the ability of the individual mGluR subtypes to modulate the distinct pathways of NO-induced PCD in primary rat hippocampal neurons. Membrane PS residue externalization occurred within the initial 3 hr after exposure to the NO donors (300 microM SNP or 300 microM NOC-9), preceded genomic DNA fragmentation, and was present in 80 +/- 2% of the neurons within a 24-hr period. NO exposure also led to the rapid induction of both caspase 1-like and caspase 3-like activities that were determined to be necessary, at least in part, for the generation of NO-induced genomic DNA degradation, but distinct from the detrimental effects of intracellular acidification. Yet, only caspase 1-like activity was necessary for the modulation of PS residue externalization. Activation of group I mGluR subtypes utilized an effective, "upstream" mechanism for the inhibition of cysteine protease activity that offered an enhanced level of neuroprotection through both the preservation of genomic DNA integrity and the maintenance of PS membrane asymmetry. Group II and Group III mGluR subtypes maintained DNA integrity and group III mGluR subtypes additionally prevented PS residue externalization through mechanisms that were targeted below the level of caspase activation. Our work elucidates the independent nature of the mGluR subtypes to not only provide discrete levels of protection against neuronal PCD, but also offer robust therapeutic strategies for neurodegenerative disease.

Animals↗
PubMed1999

A data-driven approach to the study of heterogeneity in idiopathic Parkinson's disease: identification of three distinct subtypes.

Idiopathic Parkinson's disease (IPD) has been subclassified on the basis of predominant motor symptomatology, age at disease onset, depressive affect, and cognitive performance. However, subgroups are usually arbitrarily defined and not reliably based on qualitatively distinct neuropathology. We explored heterogeneity in IPD in a data-driven manner using comprehensive demographic, motor, mood, and cognitive information collected from 176 patients with IPD. Cluster analysis revealed three subgroups of patients at a disease duration of 5.6 years and two subgroups at 13.4 years. The subgroups may represent the clinical progression of three distinct subtypes of IPD. The "motor only" subtype was characterized by motor symptom progression in the absence of intellectual impairment. Equivalent motor symptom progression was shown by the "motor and cognitive" subtype which was accompanied by executive function deficits progressing to global cognitive impairment. The "rapid progression" subtype was characterized by an older age at disease onset and rapidly progressive motor and cognitive disability. There was no relationship between the motor and cognitive symptoms in any subtype of IPD. We conclude that the clinical heterogeneity of IPD is governed by distinct neuropathologic processes with independent etiologic influences.

Aged↗
PubMed1990

Autoantibodies against different histone H1 subtypes in systemic lupus erythematosus sera.

The H1 histones represent the most heterogenous class of histone proteins. In this study, we analyzed the specificity of human antibodies against 6 H1 subtypes. H1 histones from rat organs were separated by reverse-phase high performance liquid chromatography and used as antigens in immunoblotting experiments. Sera containing anti-histone H1 antibodies were obtained from patients with systemic lupus erythematosus. Of the 9 sera tested, 2 reacted with only 1 H1 subtype. The other sera recognized different combinations of H1 subtypes. Only 1 serum reacted with all 6 H1 subtypes. Histones H1.5 and H1.1 were the subtypes most frequently recognized by the human autoantibodies. Our data indicate that human anti-H1 antibodies represent a heterogenous population, directed mainly against epitopes localized in the variable region of the H1 molecule.

Antibody Specificity↗
PubMed1993

Astrocyte subtypes in the rat olfactory bulb: morphological heterogeneity and differential laminar distribution.

Despite increased recognition of the importance and heterogeneity of astrocyte functions throughout the central nervous system (CNS) relatively little attention has been paid to morphological diversity among astrocytes. Recent studies have indicated that subsets of astrocytes are involved in glial-axonal interactions critical to both development and reinnervation of the rat olfactory bulb. Here, we have characterized the morphologies and distribution of astrocytes within anatomically and functionally distinct layers of the adult main olfactory bulb (MOB). Using a known immunohistochemical marker for astrocytes, glial fibrillary acidic protein (GFAP), and the classic gold sublimate method, we identified six astrocyte subtypes based on their morphology and distribution: (1) unipolar, (2) irregular, (3) wedge-shape, (4) circular, (5) semicircular, and (6) elongate. Unipolar, irregular and wedge-shape astrocytes have not been previously described in the CNS. The unipolar and irregular types are located exclusively in the olfactory nerve layer. Wedge-shape astrocytes are unique to, and are the major subtype in, the glomerular layer. These three morphologically unique astrocyte subtypes may correspond to olfactory nerve layer (ONL) and glomerular layer (GL) astrocytes, which express molecules that regulate axonal growth or synaptogenesis during development and/or regeneration of the olfactory nerve. In the glomerular layer, astrocytes are highly organized with respect to the glomeruli. Individual astrocytes are loyal to a single glomerulus. In the external plexiform layer, astrocytes are spaced relatively uniformly. In the granule cell layer, astrocytes appear to compartmentalize granule cell aggregates, recently shown to be coupled by tight junctions. The distribution and patterns of astrocyte processes and the density of GFAP immunoreactivity are distinctive for each of the layers of the olfactory bulb. The spacing of astrocytes and the organization of their processes may be important to compartmentalization of neuronal functions. High levels of GFAP immunoreactivity correlated with layers of high neuronal plasticity. The morphological diversity and differential distribution of astrocytes in the olfactory bulb reported here support growing evidence for functional diversity of astrocytes and important interactions among specific astrocyte and neuron subtypes. It is reasonable to hypothesize, therefore, that as for neurons, morphologically distinctive astrocyte subtypes may correspond to functionally specific classes.

Animals↗
PubMed2002

Generalizability and correlates of clinically derived panic subtypes in the population.

To determine the generalizability and population-based correlates of clinically derived panic attack subtypes among adults in the community. Data were drawn from the National Comorbidity Survey (n = 8,098), a representative sample of adults of age 18-54 years in the United States. Sociodemographic characteristics, psychiatric comorbidity, and panic symptomotology associated with three clinically derived panic subtypes (early-onset, agoraphobia, and dyspnea) were compared using two-way ANOVA and multivariate logistic regression analyses. Among those with panic attacks in the community, 51.2% had early-onset, 32.6% had agoraphobia, and 64.4% had dysthymia. Significant differences in sociodemographic characteristics, psychiatric comorbidity, and panic symptomotology emerged between the three groups. Early-onset panic was associated with significantly increased likelihood of bipolar disorder and substance dependence but was not distinguished from the other two subtypes by panic symptoms. Panic attack with agoraphobia was associated with significantly higher odds of several comorbid anxiety disorders, and panic with dyspnea was more common among married females with less education and high levels of comorbid alcohol and depressive disorders. These data suggest that clinically derived panic subtypes are generalizable and may be associated with several unique sociodemographic and psychiatric correlates in the general population. Observed differences between these subtypes may influence results from clinical samples.

Adolescent↗
PubMed2006

An open trial of paroxetine for the "offensive subtype" of taijin kyofusho and social anxiety disorder.

The taijin kyofusho (TKS) offensive subtype is thought to be a culture-bound syndrome similar to social anxiety disorder (SAD). In Western countries, such patients would be diagnosed as having delusional disorder, somatic subtype, or body dysmorphic disorder. Recently, open trials for the TKS offensive subtype and a randomized controlled trial for body dysmorphic disorder demonstrated that selective serotonin reuptake inhibitors (SSRIs) might be as effective in TKS as in SAD. This study investigated the efficacy of the SSRI paroxetine in patients with the TKS offensive subtype, both on anxiety and fears, as well as insight. This study was a 12-week open trial using paroxetine in 22 patients with TKS. Subjects were diagnosed based on the original diagnostic criteria for the TKS offensive subtype. Insight regarding TKS symptoms was assessed by the 11th supplement subscale "Insight into obsessions and compulsions" of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The Liebowitz Social Anxiety Scale (LSAS), the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), Rosenberg's Self-Esteem Scale, and the Interpersonal Distrust subscale of the Eating Disorder Inventory were also administered. Offensive anxiety was assessed by the original TKS offensive anxiety subscale (0-3 points). The primary efficacy variable was the Clinical Global Impression scale (CGI) global improvement item. Nineteen patients completed the study. Forty-seven percent (9/19) were responders to the drug treatment (scoring 2 or less on the CGI). Last observation carried forward (LOCF) analysis (N=22) demonstrated a statistically significant reduction in LSAS total score and offensive anxiety in TKS, and the insight scale score of the Y-BOCS also significantly improved. Interpersonal distrust showed a trend toward improvement.

Adult↗
PubMed2006

Evidence for respiratory and nonrespiratory subtypes in panic disorder.

Recently researchers have posited a "respiratory" subtype of panic disorder (PD), which differs from "nonrespiratory" subtypes in phenomenology and perhaps treatment response. This study was designed to further examine evidence for the existence of a respiratory subtype in PD. Individuals with PD with prominent respiratory symptoms (PD-R; n=10) and without prominent respiratory symptoms (PD-NR; n=23), as well as healthy controls (n=27), underwent a standardized 5% CO(2) rebreathing challenge. Ventilatory response and subjective sensation of suffocation were continuously recorded. The PD-R group exhibited greater subjective suffocation levels, rates of respiration, and propensity to terminate the procedure voluntarily than did the other two groups, which in turn did not differ on these measures. Findings are consistent with the existence of a respiratory subtype of PD, which differs from nonrespiratory subtypes in CO(2) sensitivity.

Adult↗
PubMed1997

Susceptibility to ankylosing spondylitis correlates with the C-terminal residue of peptides presented by various HLA-B27 subtypes.

Susceptibility to spondyloarthropaties is strongly associated with some HLA-B27 alleles. Evidence suggests a direct pathogenic role for the B27 molecules which possibly present an arthritogenic peptide to the T cells. If this hypothesis is true, B27 subtypes that differ structurally but are disease-associated ought to be capable of presenting such peptide(s), while non-disease-associated ones would not. We have recently described a B27 subtype, B*2709, and shown its absence in ankylosing spondylitis (AS) patients. Here, we show the elution and sequence of peptides from HLA-B*2709 molecules. Similar to other B27 subtypes, these peptides are mainly nonamers with an Arg at position P2. Comparison of the C-terminal anchors of peptides eluted from B*2702 and B*2705 with those eluted from B*2709 reveals that, while B*2702 and B*2705 have a broader specificity, B*2709 molecules appear to only accept C-terminal hydrophobic residues. A common feature shared by the two caucasoid AS-associated subtypes (B*2702 and B*2705) but different from B*2709, is the presence of a Tyr as peptide C-terminal anchor. The substitution of Val for Tyr at the C terminus in one of the eluted peptides greatly reduces the binding to B*2709 molecules. This finding suggests Tyr as a discriminative amino acid allowed at the C terminus of peptides bound to the AS-associated B27 subtypes, but not to those which are not associated with AS.

Amino Acid Sequence↗
PubMed1990

Haptoglobin subtyping with anti-haptoglobin alpha chain antibodies.

Specific antibodies against the human haptoglobin (HP) alpha chain were raised and used for immunoblotting after isoelectric focusing to determine Hp alpha subtypes in a reproducible and simplified manner. By eliminating the staining of the HP beta chain, HP alpha subtypes were visualized more precisely and simply than by previously reported methods. Subtypes of a total of 1211 sera, obtained from two different populations in Japan, were examined by the new method. Four HP alpha subtypes (HP 1S-1S,2FS-1S, 2FS-2FS and 2FS-2SS) and five subtypes combined with a new variant (HP 2FS-1V1, 2V1-1S, 2FS-2V1, 2FS-2V2 and 2FS-2V3) were observed. HP 1V1 belonged to HP alpha 1, and HP 2V1, 2V2 and 2V3 belonged to HP alpha 2, and their alleles were designated HP A*1V1, HP A*2V1, HP A*2V2 and HP A*2V3, respectively. The allele frequencies were calculated to be as follows: HP A*1S, 0.2597; HP A*1V1, 0.0004; HP A*2FS, 0.7333; HP A*2SS, 0.0008; HP A*2V1, 0.0045; HP A*2V2, 0.0008; and HP A*2V3, 0.0004. The allele frequency of HP A*2SS, which is common in the European population, is less frequent than HP A*2V1 in the Japanese population.

Alleles↗
PubMed1993

Calcium-mobilizing and electrophysiological effects of bradykinin on cortical astrocyte subtypes in culture.

The possible consequences of activating bradykinin (Bk) receptors on identified astrocyte subtypes derived from rat cortex have been investigated in terms of: 1) mobilization of intracellular Ca2+; and 2) electrophysiological response. Bk induced a rapid, transient rise in intracellular Ca2+ in 63% of cortical type-1-like astrocytes and 44% of type-2 astrocytes tested. Experiments involving Ca(2+)-free conditions suggested that the release occurred largely from internal stores in both astrocyte subtypes. Bk receptor activation resulted in an inward current in approximately 10% of each astrocyte subtype tested using the whole-cell patch clamp technique. The use of perforated patch recording confirmed a similar population of cells responsive to Bk. The Bk-induced current was associated with a decrease in membrane conductance. The reversal potential was close to the K+ equilibrium potential, consistent with the closure of K+ channels. The current demonstrated similar EC50 values and Hill coefficients and also a marked degree of desensitization for both astrocyte subtypes. Recordings from type-1-like astrocytes indicated that the receptor mediating the electrophysiological response was of the B2 subtype. The data were consistent with the functional translation of Bk receptor occupation to physiological responses in distinct sub-populations of cortical type-1-like and type-2 astrocytes.

Animals↗
PubMedDate not supplied

Virological significance of HBeAg subtypes (HBeAg/1 and HBeAg/2) in patients with type B hepatitis.

In order to establish the virological significance of HBeAg subtypes (HBeAg/1 and HBeAg/2) during hepatitis B virus infection, HBsAg, HBeAg and hepatitis B virus DNA in serum and HBcAg in liver were determined quantitatively in relation to the detection of HBeAg subtypes in agar gel diffusion. Thirty-eight chronic HBsAg carriers with HBeAg, including 16 non-specific reactive hepatitis, 8 chronic persistent hepatitis, 11 chronic active hepatitis and 3 liver cirrhosis, who were seen at Tohoku University Hospital from 1983 to 1985, were examined. Significantly larger amounts of HBsAg, HBeAg and hepatitis B virus DNA in serum and HBcAg in liver were found in patients positive for both HBeAg/1 and HBeAg/2 in serum than in those positive for only HBeAg/1 or negative for both subtypes. These results suggest that the presence of HBeAg/2 in serum may reflect the occurrence of active viral replication. When the detection pattern of HBeAg subtypes was examined during serial follow-up for at least 1 year, three groups of patients were classified with respect to the presence of HBeAg/2, i.e., Type I, consistently positive for HBeAg/2; Type II, consistently negative for HBeAg/2, and Type III, intermittently positive for HBeAg/2. More than 80% of Type I patients were histologically diagnosed having as nonspecific reactive hepatitis, while more than 80% of Type II and III patients had more progressive liver diseases such as chronic persistent hepatitis, chronic active hepatitis and liver cirrhosis. These results suggest that the serial examination of HBeAg subtypes in serum may be important for more detailed evaluations of type B hepatitis.

Adult↗
PubMedDate not supplied

Post-transcriptional regulation of interferon-alpha 4 subtype production by lymphoblastoid cells.

The constitutive production of interferon-alpha (IFN-alpha) subtypes by the lymphoblastoid cell lines, Namalwa, Daudi and Raji, was investigated using sensitive and semi-quantitative flow cytometric techniques. Further, we sought to determine whether the previously described failure of these cell lines to produce IFN-alpha-4 was a result of the deletion of the IFN A4 gene. Cytoplasmic production of IFN-alpha-2 and IFN-alpha-4 was assessed using IFN-alpha subtype-specific antipeptide antibodies and FITC-labelled secondary antibodies in indirect immunofluorescence-flow cytometry studies. The constitutive production of IFN-alpha-2 was detected in all three cell lines. Significant increases in fluorescence representing increased production of IFN-alpha-2 and possibly other IFN-alpha subtypes were detected after induction by Sendai virus. Approximately 100 per cent of cells in the Namalwa, Daudi and Raji cell populations contained IFN-alpha-2 before and after induction. However, no cells from the same cell populations contained the IFN-alpha-4 subtype. Analysis of genomic DNA isolated from the lymphoblastoid cells using the Polymerase Chain Reaction (PCR) and oligonucleotide primers specific for IFN A2 or IFN A4 confirmed the presence of the genes encoding both IFN-alpha subtypes. Furthermore, using reverse transcriptase-PCR amplification, mRNAs for both IFN-alpha-2 and IFN-alpha-4 were detected. Therefore, in contrast to some leukaemias and derived cell lines where IFN A genes have been deleted, these cell lines of B cell lineage exhibit selective expression of IFN A genes, as a result of altered transcriptional/translational control of IFN-alpha expression.

Antiviral Agents↗