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Biomedical subjects

R Kalb

Publications and source records attributed to R Kalb.

At least 37 records · Page 2Linked to original sources

[Anxiety attacks and epileptic seizures. Determining similarities based on a case report].

A patient suffering from panic attacks without any other clinical signs of epilepsy showed epileptic-form activity in sleep-deprivation EEG. After therapy with carbamazepine, the intensity and number of the panic attacks dropped significantly, whereas therapy with a tricyclic antidepressant had had no effect. Thus, even isolated panic attacks may have an epileptogenic background and should be taken into account in differential diagnosis.

Adult↗

[Comparison of serologic typing and DNA typing of platelet alloantigens].

Platelet alloantigens of the Zw, Ko, Bak und Br systems were determined by restriction fragment length polymorphism (RFLP) analysis of appropriate PCR products in 98 unselected patients. Results were compared with serological typing by monoclonal antibody immobilization of platelet antigens (MAIPA) and platelet agglutination.

Agglutination Tests↗

[Molecular biologic clarification of Br alloantigens in human platelets and its application in DNA typing].

Alloimmunization against the platelet alloantigen Br (HPA-5) is the second most common cause of neonatal alloimmune thrombocytopenia (NAIT) in Caucasian populations. We have recently shown that a single-base polymorphism at position 1648 on platelet mRNA coding for GPIa results in an amino acid substitution at position 505 on the mature glycoprotein Ia which is associated with the two serologically defined Br phenotypes. To establish DNA-based genotyping for the Br system we elucidated the genomic organization of the GPIa gene adjacent to the polymorphic base. Using PCR of blood cell DNA we have identified a 144 bp exon encoding the Br polymorphic base. A PCR primer based on the 3' intron sequence of this exon in combination with an exon-primer was used to amplify a 274 bp fragment of the GPIa gene. Restriction analysis using the endonuclease Mnl I leads to a Br-specific restriction fragment length polymorphism (RFLP) which perfectly correlates with serological phenotyping.

Antigens, Human Platelet↗

[A single base substitution is responsible for the origin of "private" platelet Sra antigens affects molecular weight polymorphism of glycoproteins IIIa].

Some of the genetic polymorphisms of the platelet membrane glycoproteins (GP) IIIa are known to be responsible for alloantibody formation (Zw, Yuk). These antibodies may be involved in neonatal alloimmune thrombocytopenia, posttransfusion purpura, and sometimes in the state of refractoriness to platelet transfusion. Recently we described the first 'private' alloantigen on platelets residing on the 66-kDa membrane-bound fragment of GP IIIa. Further molecular genetic studies showed that the Sr polymorphism is associated with a C to T substitution at base 2004 in the GP IIIa gene resulting in an Arg/Cys amino acid dimorphism at position 636. Transfection of COS cells with recombinant forms of GP IIIa cDNA demonstrated that this amino acid dimorphism is responsible for the formation of the Sra epitope. Furthermore, the Sra variant of GP IIIa showed a slightly increased molecular weight which is presumably caused by different glycosylation.

Antigens, Human Platelet↗

[RNA typing of granulocyte NA antigens by means of PCR-RFLP analysis].

An RNA-based method was developed for genotyping of the granulocyte-specific alloantigens NA1 and NA2, mRNA was isolated from neutrophils and reversely transcribed into cDNA. To avoid coamplification of Fc-gamma receptor III-2 in the polymerase chain reaction (PCR), a Fc-gamma receptor III-1 sequence-specific primer was employed. Restriction analysis using Taq I led to NA-specific restriction fragment length polymorphism (RFLP) of PCR-amplified cDNA. The results of the PCR-RFLP typing were in good concordance with serological phenotyping by granulocyte immunofluorescence test and the antigen capture assay MAIGA.

Granulocytes↗

[Presence of alternatively spliced messenger RNA for HLA-A, -B and -C in platelets].

Recently we demonstrated that platelets contain specific messenger RNA (mRNA) encoding for the transmembrane HLA class I molecule (44 kDa). In this study we analyzed lymphocytes as well as platelets for the presence of alternatively spliced mRNA with deleted transmembrane domain resulting in soluble HLA class I antigens (39 kDa). PCR amplification of lymphocyte RNA led to a product specific for alternatively spliced cDNA corresponding to the presence of soluble HLA in plasma, while this product could not be obtained from platelet mRNA. These results suggest that platelets in contrast to lymphocytes are unable to synthesize soluble HLA antigens via alternative splicing.

Alternative Splicing↗

A deletion in the second exon of an HLA-DRB1 allele found in a DR2-negative narcolepsy patient.

In this report, we describe a new allele of the HLA-DRB 1 gene carrying a form of mutation that has not been observed before. It appeared in an HLA-DR2-negative narcolepsy patient who, besides HLA-DR4, revealed a serologic HLA-DR blank segregating with HLA-DQ1. Oligotyping showed that the new allele belongs to the HLA-DR8 group. Restriction analysis and DNA sequencing revealed the deletion of 12 bp as well as the substitution of 9 flanking base pairs between codons 36 and 43. The expression of the mutated gene was demonstrated by the presence of its messenger RNA and a few positive reactions with DR8 sera. Without interrupting the reading frame, the mutation leads to a gene product composed of a modified amino acid sequence. We anticipate that the mutation influences the conformation of the molecule with possible consequences concerning immune response.

Alleles↗

The presence of messenger RNA for HLA class I in human platelets and its capability for protein biosynthesis.

In order to determine whether platelets contain specific messenger RNA encoding for HLA class I molecules, polymerase chain reaction (PCR) was performed with RNA from different platelet donors. Two amplified 300 bp and 279 bp cDNA fragments were obtained which encompassed sequences from 321 to 620 and from 795 to 1073. The 300 bp fragment encodes exon 2 and exon 3, the 279 bp encodes a portion of exon 4, exon 5, exon 6 and a portion of exon 7. A 300 bp nested PCR product from one donor, that encoded for the highly polymorphic region alpha 2, was cloned and sequenced. The resulting nucleotide sequences fitted to the expected sequence for HLA B*3801 of this donor. Sequence analysis of the 279 bp PCR product demonstrated the presence of exon 5 encoding for the 117 bp transmembrane domain. In addition, de novo protein biosynthesis was studied by radioimmunoprecipitation of HLA class I molecules from 35S-methionine metabolically labelled platelet lysates with a monoclonal antibody (mab) w6/32 specific for a monomorphic epitope on the heavy chain of HLA class I antigens. Analysis of the immunoprecipitates on SDS polyacrylamide gel electrophoresis showed a specific band with apparent molecular weight (M(r)) of 44 kD corresponding to integral membrane HLA protein. On the basis of these results, we conclude that platelets contain specific messenger RNA encoding for HLA class I molecules and have the capability to synthesize the integral HLA membrane protein.

Base Sequence↗

The human platelet alloantigens Br(a) and Brb are associated with a single amino acid polymorphism on glycoprotein Ia (integrin subunit alpha 2).

The human GPIa/IIa complex, also known as integrin alpha 2 beta 1, serves as a major receptor for collagen in platelets and other cell types. In addition to its role in platelet adhesion to extracellular matrix, GPIa/IIa is also known to bear the clinically important Br(a) and Brb alloantigenic determinants, which can result in antibody-mediated platelet destruction. Immunochemical studies showed that the Br antigenic epitopes reside solely on the GP Ia subunit and do not depend on sialic acid residues. To define the polymorphism responsible for the Br alloantigen system platelet RNA PCR technique, was used to amplify GPIa mRNA transcripts. Nucleotide sequence analysis of the amplified platelet GPIa cDNA from Br(a/a) and Brb/b individuals revealed a single A<-->G polymorphism at base 1648. MnlI RFLP analysis of cDNA from serologically determined individuals confirmed that this polymorphism segregates with Br phenotype. This single base change results in a substitution of Lys (AAG) in Br(a) to Glu (GAG) in Brb at amino acid residue 505 In spite of the reversal in charge at this position, however, we found no difference in the ability of Bra and Brb homozygous platelets to adhere to collagens types I, III, or V, nor did anti-Bra or anti-Brb alloantibodies interfere with platelet adhesion to any of these fibrillar collagens. The identification of the nucleotide substitution that defines the Bra/Brb alloantigen system will now permit both pre- and postnatal diagnosis for Br phenotype.

Antigens, Human Platelet↗

[Self-instruction expert systems in medicine. Presentation of knowledge, acquisition of knowledge, prediction of suicide as an example].

AIMS: 1. Description of how self-learning expert systems work, and 2. comparison of various algorithms for the establishment of a data base for suicide prediction. POINTS DISCUSSED: from exemplary patient data, self-learning expert systems obtain their expert knowledge which they subsequently employ to establish the diagnosis in new patients. Various possibilities of storing knowledge may be employed, for example the decision tree, classes of rules or neuronal networks. The various forms of representing knowledge are also presented. Taking the prediction of suicidal risk as an example, the effectiveness of the algorithm is tested with the aid of a patient questionnaire. CONCLUSIONS: Different fields of application require different systems. The diagnosis of such expert systems can at least prompt the care-providing physician to reconsider his own diagnosis.

Artificial Intelligence↗

[Suicidal acts in advanced age].

Geriatric suicides and attempted suicides differ from those of other age groups in a number of major characteristics: the suicide rate increases with age, while attempted suicides decrease; the lethality of the method selected increases with advancing age; the motivations of the elderly differ from those of younger suicides; psychiatric problems are more severe in the aged. Our own investigations were based on the data on suicide in West Germany collected between 1979 and 1987. Possible explanations for these findings are discussed, and conclusions drawn on how to prevent suicide and how to treat attempted suicides in the aged.

Aged↗

[A clarification system for completing suicidal thoughts].

To improve the prediction of suicidal risk one has to understand the suicidal thoughts in individuals. We formalized these ideas and integrated them into an understanding system. In such a system the ideas concerning suicide cooperate in such a way so that the suicidal attempt appears to be the optimal solution for this patient. We discuss the question whether such an idiographic understanding system may help to understand other patients too.

Expert Systems↗

Creutzfeldt-Jakob disease probably acquired from a cadaveric dura mater graft. Case report.

A case of Creutzfeldt-Jakob disease (CJD) is reported in a 28-year-old woman who had received a cadaveric dural graft 19 months earlier after resection of a cholesteatoma. The circumstances of the case point to the graft as the most likely source of the disease. Cadaveric dura should be added to the list of materials that may transmit CJD, and it must be very carefully screened if it is used at all for grafting. Autologous tissue should be considered whenever possible.

Adult↗

Cutaneous infection at dog bite wounds associated with fulminant DF-2 septicemia.

Severe DF-2 sepsis with disseminated intravascular coagulopathy developed following dog bites in two patients who had undergone prior splenectomy. Eschariform lesions developed at the site of the animal bite in both patients. DF-2 is an unusual animal-borne slow-growing gram-negative rod that can cause fulminant sepsis in splenectomized patients. Splenectomized patients should be aware of the hazards from a dog bite. The presence of eschariform lesions in such patients should provide a clinical clue to the presence of DF-2 infection.

Adult↗

Factors associated with unemployment of patients with multiple sclerosis.

As part of a larger study of psychosocial aspects of chronic disease, the employment status of 79 male and 233 female multiple sclerosis patients was evaluated by interview to identify: (1) the relationship between degree of disability and employment status and (2) other determinants of employment status. Seventy-seven per cent of the patients were unemployed. Disability level, age, sex, and level of education accounted for 14% of the differences in employment status, with less disabled, older, more educated males being the most likely to be employed. Employment status was unrelated to marital status or type of occupation. Case histories are presented to illustrate psychosocial and environmental factors which might further account for the differences in employment status.

Adolescent↗