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K Haller

Publications and source records attributed to K Haller.

At least 19 recordsLinked to original sources
PubMed2006

The N-terminus of rodent and human MAD1 confers species-specific stringency to spindle assembly checkpoint.

The spindle assembly checkpoint (SAC) guards against chromosomal mis-segregation and the emergence of aneuploidy. SAC in higher eukaryotes includes at least 10 proteins including MAD1-3, BUB1-3, and Msp1. A long-standing observation has been that rodent cells are more tolerant of microtubule toxins than primate cells indicating that SAC function is more relaxed in the former than the latter. Here, we report on an unexpected functional difference between the rodent and human MAD1 component of the respective SAC. Ectopic expression of human MAD1 in mouse and hamster cells corrected a relaxed SAC to a more stringent form. Our findings posit MAD1 as a species-specific determinant which influences the stringency of cellular response to microtubule depolymerization and spindle damage.

Amino Acid Sequence↗
PubMed2004

Type 1 diabetes is insulin -2221 MspI and CTLA-4 +49 A/G polymorphism dependent.

BACKGROUND: Several studies have demonstrated an association of type 1 diabetes with specific alleles of HLA class II molecules, as with polymorphisms of insulin gene region. The aim of our study was to evaluate the interaction of insulin -2221 MspI polymorphism to type 1 diabetes susceptibility in connection with autoimmunity associated gene--CTLA-4 polymorphism. MATERIALS AND METHODS: Insulin -2221 MspI C/T and CTLA-4 +49 A/G polymorphisms were detected by restriction fragment-length polymorphism analysis or oligonucleotide hybridization in type 1 (n = 69), type 2 diabetes (n = 301) patients and 158 healthy controls. Regression model adjusted for age, gender and gene polymorphisms was studied. RESULTS: C-allele of insulin -2221 MspI and G-allele of +49 CTLA-4 were significant risk factors for type 1 diabetes (crude OR 3.53 and 1.59, respectively) and this impact increased in the homozygous form of both alleles. The regression model supported the idea of insulin CC and CTLA-4 GG genotypes for an independent and clearly significant risk for developing type 1 diabetes. We could not detect any significant correlation between investigated polymorphisms and type 2 diabetes. CONCLUSIONS: There exists a significant association between the C-allele of -2221 MspI in the insulin gene and type 1 diabetes. The CTLA-4 G-allele is also positively correlated with type 1 diabetes. According to the regression model the investigated gene polymorphisms are independent risk factors for development of type 1 diabetes in the Estonian population. We propose that -2221 MspI is a good marker for evaluation of risk of insulin gene haplotype in type 1 diabetes patients.

Aged↗
PubMed2000

Tax-dependent stimulation of G1 phase-specific cyclin-dependent kinases and increased expression of signal transduction genes characterize HTLV type 1-transformed T cells.

Human T cell leukemia virus protein induces T cells to permanent IL-2-dependent growth. These cells occasionally convert to factor independence. The viral oncoprotein Tax acts as an essential growth factor of transformed lymphocytes and stimulates the cell cycle in the G(1) phase. In T cells and fibroblasts Tax enhances the activity of the cyclin-dependent kinases (CDK) CDK4 and CDK6. These kinases, which require binding to cyclin D isotypes for their activity, control the G(1) phase. Coimmunoprecipitation from these cells revealed that Tax associates with cyclin D3/CDK6, suggesting a direct activation of this kinase. The CDK stimulation may account in part for the mitogenic Tax effect, which causes IL-2-dependent T cell growth by Tax. To address the conversion to IL-2-independent proliferation and to identify overexpressed genes, which contribute to the transformed growth, the gene expression patterns of HTLV-1-transformed T cells were compared with that of peripheral blood lymphocytes. Potentially overexpressed cDNAs were cloned, sequenced, and used to determine the RNA expression. Genes found to be up-regulated are involved in signal transduction (STAT5a, cyclin G(1), c-fgr, hPGT) and also glycoprotein synthesis (LDLC, ribophorin). Many of these are also activated during T cell activation and implicated in the regulation of growth and apoptosis. The transcription factor STAT5a, which is involved in IL-2 signaling, was strongly up-regulated only in IL-2-independent cells, thus suggesting that it contributes to factor-independent growth. Thus, the differentially expressed genes could cooperate with the Tax-induced cell cycle stimulation in the maintenance of IL-2-dependent and IL-2-independent growth of HTLV-transformed lymphocytes.

Apoptosis↗
PubMed1998

Brefeldin A affects synthesis and integrity of a eukaryotic flagellum.

Eukaryotic flagella and cilia are highly dynamic organelles. In green algae like Chlamydomonas reinhardtii, flagella absorption and resynthesis is a normal process during the vegetative cell cycle. Rapid regeneration also occurs after stress-induced shedding of flagella. Ca2+ ions, protein synthesis, and a kinase activity are the main factors known to affect resynthesis. Recently, we have detected that certain small G proteins (Ypt/Rab) and a GTPase regulator (GDP dissociation inhibitor), known as regulatory elements of intracellular vesicle transport, are present in flagellar membranes of green algae, raising the possibility that the organelle's synthesis and/or integrity depends on functional membrane traffic. In this study, we examined the effect of brefeldin A (BFA), an inhibitor of intracellular membrane flow and Golgi function in animal and plant cells, on flagella regeneration in the colonial green alga Gonium pectorale. We show that low BFA concentrations (< 1 microgram/ml) inhibit flagella out-growth, while higher amounts cause dose-dependent deflagellation and cell death. Our findings provide experimental evidence for a direct connection between intracellular transport and eukaryotic flagella synthesis.

Brefeldin A↗
PubMed1995

Differentiation-dependent transcription of the epidermodysplasia verruciformis-associated human papillomavirus type 5 in benign lesions.

Human papillomavirus type 5 (HPV 5) induces cutaneous lesions and persists in skin carcinomas of patients with epidermodysplasia verruciformis (EV). We investigated the expression pattern of HPV 5 in biopsies from benign skin lesions of EV patients by cDNA analysis and in situ hybridization. Nine different cDNAs could be generated from total RNA of one of these lesions by reverse transcription and PCR amplification with HPV 5-specific primers. We could identify two major splice donors: one was found in the E6-proximal part of the noncoding region (NCR), and the other just downstream of the first ATG codon of ORF E1. Each of the characterized transcripts was processed at one or the other donor site and the two corresponding leader exons were found in combination with both 3'-early and late exons. Two transcripts appear to be specific for EV-associated papillomaviruses: one species might encode an E1--E2C fusion protein, and the other mRNA (NCR/E2) is probably encoding for the full-length E2 protein. According to the results of the cDNA analysis, riboprobes were designed for in situ hybridization experiments to study the cell differentiation-dependent expression of the different exons. Only the E7/E1 and E4 probes led to strong signals almost throughout the epithelium. The signals generated by the 5'-E2 and E1 probe increased with cell differentiation and were mainly confined to the nucleus. The NCR, E6, E7, L2, and L1 probes yielded more or less strong signals in the terminally differentiated epidermal layers. The difference in the cell differentiation-dependent expression of the 5'-early region exon (probe E7/1) and L2/L1 exons may point to a differentiation-dependent processing of transcripts.

Base Sequence↗
PubMed1994

More talk, less paper: predicting the accuracy of substituted judgments.

PURPOSE: To study the accuracy of substituted judgments regarding life-sustaining therapies and other therapies made by surrogate decision makers and to investigate factors associated with more accurate predictions. PATIENTS AND METHODS: A total of 50 pairs of ambulatory patients and surrogates, chosen according to a legal hierarchy, underwent separate interviews in which surrogates were asked to predict the preferences of patients for eight modes of medical therapy in three clinical scenarios, given only yes or no as response options. Patient preferences, their surrogates' predictions, and the extent of agreement between the two were measured. The total number of correct predictions constituted the Surrogate Accuracy in Matching Patient Preferences Scale (SAMPPS). Sociodemographic factors associated with agreement were also assessed. RESULTS: Agreement between patients and surrogates ranged from 57% to 81%. The mean SAMPPS score was 17 of 24 correct. Kappa (k) coefficients, which measure inter-rater concordance, were positive for 23 of 24 items and were 0.3 or greater (P < 0.05) for 14 of 24 items. Rates of agreement were not related to whether the surrogate interviewed (surrogate determined by state law) was the person the patient would have chosen as a surrogate or whether the patient had an advance directive. In multiple linear regression analysis, both prior discussions of preferences and nonchurchgoing behavior were significantly associated with patient-surrogate agreement, independent of religious denomination and race. CONCLUSION: When pressed to choose, surrogates can predict the preferences of patients for life-sustaining therapies with an imperfect accuracy that nonetheless significantly exceeds the agreement expected due to chance alone. Exhorting surrogates to give their "best estimate" and encouraging prior discussions may improve accuracy. Houses of worship might be important target sites for campaigns to improve public awareness about advance directives.

Adult↗
PubMed1988

Coexistence of antigen-specific and idiotype-specific suppressor T cells in mice injected neonatally with a mixture of antigen and anti-idiotype antibody.

Specific tolerance to phosphorylcholine (PC) can be induced in BALB/c mice by neonatal injection with either pneumococcal C-polysaccharide (PnC) containing PC or anti-TEPC-15 idiotype (T15id) antibody which recognizes the predominant idiotype of anti-PC antibody of BALB/c mice. Suppressor T cells (Ts) induced after treatment with anti-T15id antibody react with the T15id and PnC-induced Ts cells appear to recognize PC. A brief incubation of anti-id-induced, T15id-specific Ts with PnC-induced, PC-reactive Ts resulted in complete cancellation of their suppressor functions. However, both types of Ts were present in mice neonatally injected with mixtures of PnC and anti-T15id antibody. Neutralization experiments using either PnC-induced or anti-id-induced suppressor T cells strongly suggest that only one of the Ts cell types is functionally dominant in those mice: most frequently, T15id-specific Ts cells. The suppressor function of the other population is detectable only when the predominant Ts cell population is removed by anti-id or monoclonal IgM anti-PC (SP45) plus complement. However, both suppressor activities are completely eliminated when one of the Ts populations is removed by adherence to either antigen or T15id. These results suggest that mice neonatally injected with a mixture of antigen and anti-id antibody possess both types of suppressor T cells, yet only one type is functionally dominant.

Animals↗
PubMed1976

[Behaviour of serum concentrations of glucose, immunoreactive insulin and potassium ions in newborns after long term or crash treatments with Partusisten or Partusisten in combination with Isoptin (author's transl)].

The investigation was done on 50 infants born of metabolic healthy mothers. A group of 10 women received short term treatment with Partusisten and Isoptin. Another 10 were treated over the same period with Partusisten only. A further group of 15 received long term treatment (more than 7 days) with Partusisten and Isoptin and a final group of 15 mothers received placebos. Serum concentrations of glucose, immunoreactive insulin and potassium, together with acid-base-status and other important blood chemistry were determined in mothers and newborns directly postpartum. Blood sugar, immunoreactive insulin and potassium were further determined in the newborns 30 minutes, 60 minutes, 2 hours and 6 hours after birth. The results showed that a temporary relative hypoglycaemia occured in the newborns in short term as well as long term treatment with Partusisten or Partusisten in combination with Isoptin. Temporary derangements in insulin-glucose equilibrium were also seen in newborns from mothers receiving long term treatment. It was also demonstrated that approximately 1 hour post-partum, blood sugar and immunoreactive insulin of the newborn attained values compatible with normal carbohydrate metabolism. From these results it is indicated that infants born of mothers, who received tocolytic treatments with Partusisten or Partusisten in combination with Isoptin, should be given sodiumbicarbonate and glucose directly after birth.

Acid-Base Imbalance↗