Search PubMed⌕ Search

Biomedical subjects

A Lin

Publications and source records attributed to A Lin.

At least 127 records · Page 7Linked to original sources
PubMed1997

Defective expression of gp180, a novel CD8 ligand on intestinal epithelial cells, in inflammatory bowel disease.

Previous studies support a role for intestinal epithelial cells (IEC) as antigen-presenting cells in mucosal immune responses. T cells activated by IEC are CD8+, suppressor in function, and dependent upon CD8-associated p56lck activation. A 180-kD glycoprotein (gp180) recognized by mAbs B9 and L12 has been identified and shown to be important in CD8+ T cell activation by IEC. Since IEC derived from patients with inflammatory bowel disease (IBD) are incapable of activating CD8+ T cells, we asked whether this correlated with gp180 expression. While frozen sections of normal bowel revealed bright gp180 staining on all IEC, both inflamed and uninflamed ulcerative colitis (UC) specimens showed patchy staining. In Crohn's disease (CD), staining was faint to absent. Flow cytometry confirmed immunohistochemical data. The staining patterns correlated with the ability of IEC to activate CD8-associated p56lck. Normal IEC induced phosphorylation of p56lck in CD8alpha but not CD4+ transfectants. In contrast, both UC and CD IEC activated CD4 and, to a much lesser extent, CD8-associated p56lck. Thus, gp180 expression by IBD IEC appears to be altered, and correlates with a functional alteration of lck activation. This defect may reflect a more proximal event in the pathogenesis of IBD.

CD8 Antigens↗
PubMed1997

Identification of c-Jun NH2-terminal protein kinase (JNK)-activating kinase 2 as an activator of JNK but not p38.

c-Jun NH2-terminal protein kinase (JNK), a distant member of the mitogen-activated protein (MAP) kinase family, regulates gene expression in response to various extracellular stimuli. JNK is activated by JNK-activating kinase 1 (JNKK1), a dual specificity protein kinase that phosphorylates JNK on threonine 183 and tyrosine 185 residues. Here we show that JNKK2, a novel member of the MAP kinase kinase family, was phosphorylated and activated by MEKK1, a MAP kinase kinase kinase in the JNK signaling cascade. JNKK2 activity was also stimulated by constitutively active forms of Rac and Cdc42Hs, members of the Rho small GTP-binding protein family. Unlike JNKK1 that activates both JNK and p38 MAP kinases, JNKK2 stimulated only JNK. Transient transfection assays demonstrated that JNKK2 potentiated the stimulation of c-Jun transcriptional activity by MEKK1. The existence of multiple JNK-activating kinases may contribute to the specificity of the JNK signaling cascade.

Amino Acid Sequence↗
PubMed1997

Structure-function studies of p38 mitogen-activated protein kinase. Loop 12 influences substrate specificity and autophosphorylation, but not upstream kinase selection.

Several mitogen-activated protein kinase (MAPK) cascades have been identified in eukaryotic cells. The activation of MAPKs is carried out by distinct MAPK kinases (MEKs or MKKs), and individual MAPKs have different substrate preferences. Here we have examined how amino acid sequences encompassing the dual phosphorylation motif located in the loop 12 linker (L12) between kinase subdomains VII and VIII and the length and amino acid sequence of L12 influence autophosphorylation, substrate specificity, and upstream kinase selectivity for the MAPK p38. Conversion of L12 of p38 to an "ERK-like" structure was accomplished in several ways: (i) by replacing glycine with glutamate in the dual phosphorylation site, (ii) by placing a six-amino acid sequence present in L12 of ERK (but absent in p38) into p38, and (iii) by mutations of amino acid residues in loop 12. Two predominant effects were noted: (i) the Xaa residue in the dual phosphorylation motif Thr-Xaa-Tyr as well as the length of L12 influence p38 substrate specificity, and (ii) the length of L12 plays a major role in controlling autophosphorylation. In contrast, these modifications do not result in any change in the selection of p38 by individual MAPK kinases.

Amino Acid Sequence↗
PubMed1997

The niacin challenge test: clinical manifestation of altered transmembrane signal transduction in schizophrenia?

Several lines of evidence implicate altered phospholipid-dependent signal transduction (PDST) in the pathophysiology of schizophrenia. Niacin induces vasodilation through mechanisms requiring intact PDST. Thus, an altered response to a challenge dose of niacin may reflect disturbances in these signalling processes in this disorder. In the present study, niacin-induced vasodilation was estimated quantitatively in schizophrenic and comparison bipolar affective disorder and healthy subjects using thermocouple sensors to measure the change in skin temperature relative to core body and ambient room temperature. Twelve (42.9%) of 28 schizophrenic subjects did not vasodilate in response to a 200-mg niacin challenge dose, whereas only 1 of 18 (6%) bipolar disorder subjects and none of 28 controls showed impaired response (Fisher's Exact Test, p < .0001). These findings support the notion that the schizophrenic syndromes are biochemically heterogeneous and suggest the existence of a subgroup of schizophrenic subjects in whom phospholipid-dependent signalling responses may be impaired.

Adolescent↗
PubMed1997

The neuroimaging findings in Sotos syndrome.

We reviewed the neuroimaging studies of 40 patients with classic Sotos syndrome. The studies consisted of CT scans only in 4 patients and one or more MRI scans in 36 patients. The diagnosis of Sotos syndrome was made using well-established clinical criteria. The neuroimaging studies of each patient were evaluated subjectively by visual inspection and the chief findings were tabulated and grouped into five categories: 1) ventricular abnormalities, 2) extracerebral fluid spaces, 3) midline abnormalities, 4) migrational abnormalities, and 5) others. The most common abnormality of the cerebral ventricles was prominence of the trigone (90%), followed by prominence of the occipital horns (75%) and ventriculomegaly (63%). The supratentorial extracerebral fluid spaces were increased for age in 70% of the patients and the fluid spaces in the posterior fossa were increased in 70% also. A variety of midline abnormalities were noted but anomalies of the corpus callosum were almost universal. Gray matter heterotopias occurred in only 3 (8%) of 36 patients. Periventricular leukomalacia, presumably the result of prenatal or perinatal difficulties and unrelated to the basic condition, was the most common of the miscellaneous other abnormalities noted. The neuroimaging findings of Sotos syndrome are distinct enough to allow differentiation of this syndrome from other mental retardation syndromes with macrocephaly.

Abnormalities, Multiple↗
PubMed1997

Characterization of a new ribotoxin gene (c-sar) from Aspergillus clavatus.

A new ribotoxin, c-sarcin, was isolated from a culture of Aspergillus clavatus. A full-length genomic DNA (c-sar) coding for c-sarcin was cloned and sequenced. The deduced amino acid sequence showed a high homology to restrictocin and alpha-sarcin. The native toxin as well as the recombinant protein hydrolysed ribosomes and naked RNA. The genomic structure of the c-sar gene had an intron located between the coding sequences for secretory signal peptide and the mature protein. The intron contained a stretch of 38 adenines. The intron sequence of c-sar was different from that of restrictocin but resembled that of alpha-sarcin. There was 34% identity between the intron of c-sarcin and alpha-sarcin, and this similarity was further increased to 83% if the stretch of polyadenine was omitted.

Aspergillus↗
PubMed1997

mRNA and protein expression of nitric oxide synthase and adrenoceptor alpha 1 in young and old rat penile tissues.

OBJECTIVE: To investigate alterations of neuronal structure and the mRNA expression of nitric oxide synthase (NOS) and adrenoceptor alpha 1 in young and old rat penile tissues, and assess the importance of these factors in erectile dysfunction (ED) associated with ageing. MATERIALS AND METHODS: NOS was determined in the pelvic ganglia of 32 rats using nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase staining. Adrenergic neurons were identified by histofluorescence staining. The gene expression for NOS and for adrenoceptor alpha 1 was investigated in corporal tissue by differential reverse transcriptase-polymerase chain reaction (RT-PCR) using specific oligonucleotide primers. b-actin was used as an internal standard in each tube to quantify the baseline gene expression. RESULTS: The following changes occurred in old rats: (i) an increase of lipofuscin and a decrease in both bNOS-containing neurons and fluorescent adrenergic neurons in the pelvic ganglia; (ii) significantly less expression of NOS mRNA than in young rat penile tissues; and (iii) no significant alteration in adrenoreceptor alpha 1 mRNA expression. CONCLUSIONS: The fewer adrenergic and NOS-containing neurons and neurotransmitters in pelvic ganglia from old rats may explain the enhanced penile smooth muscle tone previously reported in older impotent men. Furthermore, lower mRNA expression of NOS may be associated with structural and functional changes associated with ageing penile tissue.

Age Factors↗
PubMed1997

Risk factors associated with hepatocellular carcinoma notified to the Anti-Cancer Council of Victoria in 1991-1992.

The study aimed to estimate the prevalence of risk factors for liver disease, particularly hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, in a population-based series of hepatocellular carcinoma, and to assess the feasibility of retrospective surveys in determining risk factors for hepatocellular carcinoma. A survey of all cases of hepatocellular carcinoma diagnosed in 1991 and 1992 documented the high contribution of alcoholic cirrhosis, particularly in Australian-born men. Low levels of testing for HBV and HCV made their contribution to hepatocellular carcinoma uncertain. No cases of hepatocellular carcinoma due to HBV or HCV were reported in Australian-born subjects. Higher rates of HBV carriage in those tested were found in Asian and Mediterranean immigrants. Testing for HCV was known to have occurred for less than a quarter of subjects, and assessment for multiple aetiological risk factors was rare. The burgeoning epidemic of HCV will require improved surveillance for the sequelae of long-term infection. Satisfactory surveillance will require cooperation from clinicians in regard to the completeness of medical records and adequate resources for cancer registries to supplement their passive reporting system with exposure data.

Adult↗
PubMed1996

The tumor promoter arsenite stimulates AP-1 activity by inhibiting a JNK phosphatase.

Trivalent arsenic (As3+) is highly carcinogenic, but devoid of known mutagenic activity. Therefore, it is likely to act as a tumor promoter. To understand the molecular basis for the tumor-promoting activity of As3+, we examined its effect on transcription factor AP-1, whose activity is stimulated by several other tumor promoters. We found that As3+, but not As5+, which is toxic but not carcinogenic, is a potent stimulator of AP-1 transcriptional activity and an efficient inducer of c-fos and c-jun gene expression. Induction of c-jun and c-fos transcription by As3+ correlates with activation of Jun kinases (JNKs) and p38/Mpk2, which phosphorylate transcription factors that activate these immediate early genes. No effect on ERK activity was observed. As5+, on the other hand, had a negligible effect on JNK or p38/Mpk2 activity. Biochemical analysis and co-transfection experiments strongly suggest that the primary mechanism by which As3+ stimulates JNK activity involves the inhibition of a constitutive dual-specificity JNK phosphatase. This phosphatase activity appears to be responsible for maintaining low basal JNK activity in non-stimulated cells and its inhibition may lead to tumor promotion through induction of proto-oncogenes such as c-jun and c-fos, and stimulation of AP-1 activity. The same phosphatase may also regulate p38/Mpk2 activity.

Arsenites↗
PubMed1996

Genetic variant near cytosolic phospholipase A2 associated with schizophrenia.

Two studies were undertaken to determine a possible genetic basis for alterations in phospholipid metabolism in schizophrenia. Initial results demonstrated an association in 65 schizophrenics compared with a matched normal control population. A follow-up haplotype relative risk study of 44 triads (mother, father, affected offspring), confirmed the results seen in the association study. Results suggest that a genetic variant near the promotor region of the gene for cytosolic phospholipase A2, the rate-limiting enzyme in the synthesis of prostaglandins from arachindonic acid, is associated with schizophrenia.

Female↗
PubMed1996

Substrate specificity of monomeric and dimeric alpha-sarcin.

The substrate specificity of monomeric and dimeric forms of alpha-sarcin was investigated by membrane blotting procedures. Dimeric alpha-sarcin fails to inactivate ribosomes as well as to hydrolyze mini-stem-loop RNA, whereas monomeric alpha-sarcin catalyzes both substrates. Both monomeric and dimeric alpha-sarcin are effective ribonucleases that are displayed by in situ RNA-impregnated gel electrophoresis. The same purine base specificity was detected for both dimeric and monomeric forms. alpha-Sarcin is also an effective deoxyribonuclease to supercoiled DNA. The action of alpha-sarcin as deoxyribonuclease and ribonuclease is inhibited by the presence of SDS (3.5 x 10(-6) M); the inhibition on ribonuclease, but not on deoxyribonuclease, is reversible if the proteins are renatured.

Animals↗
PubMed1996

The niacin challenge test in schizophrenia: past, present and future.

Schizophrenia, a complex, heterogeneous illness, represents a diagnostic challenge in that defining the clinical subtypes of this illness remains equivocal. Moreover, a scarcity of research has focused on the integration of the biochemical and clinical aspects of schizophrenia. Therefore, there is a need to approach the subtyping of schizophrenia with attention to potential clinical manifestations of underlying biochemical disturbances. In an attempt to subtype schizophrenia, we review some of the clinical and biochemical evidence for alterations in phospholipid function in schizophrenia.

Niacin↗
PubMed1996

Phospholipases: in search of a genetic base of schizophrenia.

Evidence from a variety of clinical and biochemical sources indicates alterations in phospholipid synthesis and activity in schizophrenia. We review a recent study which suggests that a genetic variant near the promotor region of the gene for cytosolic phospholipase A2, the rate-limiting enzyme in the synthesis of prostaglandins from arachidonic acid (AA), is associated with schizophrenia. These findings are consistent with a extensive body of literature which suggests alterations in membrane phospholipids in schizophrenia.

Alleles↗
PubMed1996

Targeting and function in mRNA export of nuclear pore complex protein Nup153.

Nup153 is a large (153 kD) O-linked glyco-protein which is a component of the basket structure located on the nucleoplasmic face of nuclear pore complexes. This protein exhibits a tripartite structure consisting of a zinc finger domain flanked by large (60-70 kD) NH2- and COOH-terminal domains. When full-length human Nup153 is expressed in BHK cells, it accumulates appropriately at the nucleoplasmic face of the nuclear envelope. Targeting information for Nup153 resides in the NH2-terminal domain since this region of the molecule can direct an ordinarily cytoplasmic protein, pyruvate kinase, to the nuclear face of the nuclear pore complex. Overexpression of Nup153 results in the dramatic accumulation of nuclear poly (A)+ RNA, suggesting an inhibition of RNA export from the nucleus. This is not due to a general decline in nucleocytoplasmic transport or to occlusion or loss of nuclear pore complexes since nuclear protein import is unaffected. While overexpression of certain Nup153 constructs was found to result in the formation of unusual intranuclear membrane arrays, this structural phenotype could not be correlated with the effects on poly (A)+ RNA distribution. The RNA trafficking defect was, however, dependent upon the Nup153 COOH-terminal domain which contains most of the XFXFG repeats. It is proposed that this region of Nup153, lying within the distal ring of the nuclear basket, represents a docking site for mRNA molecules exiting the nucleus.

Animals↗
PubMed1996

[Treatment of recurrent anterior dislocation of the shoulder with pectoralis minor muscle-bone flap].

We treated 10 patients with recurrent anterior dislocation of the shoulder by transplantation of pectoralis minor muscle-bone flap transplanted to the upper part of the humerus. All patients were followed-up for an average 31 months and no recurrent was found. We consider that the muscle beily exerts a protective effect like a barrier on the weak anterio inferior region of the shoulder and increases the force for extending the shoulder and lifting the arm. The operation is based on biomechanics. Meanwhile, suturing the laxative joint capsule and repairing the weak anteroinfeior region of the shoulder is more beneficial to prevent from redislocation of the humerus head.

Adult↗
PubMed1995

Selective activation of the JNK signaling cascade and c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs.

The Rho subfamily of GTPases is involved in control of cell morphology in mammals and yeast. The mammalian Rac and Cdc42 proteins control formation of lamellipodia and filopodia, respectively. These proteins also activate MAP kinase (MAPK) cascades that regulate gene expression. Constitutively activated forms of Rac and Cdc42Hs are efficient activators of a cascade leading to JNK and p38/Mpk2 activation. RhoA did not exhibit this activity, and none of the proteins activated the ERK subgroup of MAPKs. JNK, but not ERK, activation was also observed in response to Dbl, an oncoprotein that acts as a nucleotide exchange factor for Cdc42Hs. Results with dominant interfering alleles place Rac1 as an intermediate between Ha-Ras and MEKK in the signaling cascade leading from growth factor receptors and v-Src to JNK activation. JNK and p38 activation are likely to contribute to the biological effects of Rac, Cdc42Hs, and Dbl on cell growth and proliferation.

3T3 Cells↗