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Biomedical subjects

C F Källander

Publications and source records attributed to C F Källander.

At least 37 records · Page 2Linked to original sources
PubMed1987

Serum deoxythymidine kinase correlates with peripheral lymphocyte thymidine uptake in chronic lymphocytic leukemia.

The serum thymidine kinase (S-TK) and proliferative activity of the leukemic cells were determined in 27 untreated patients with chronic lymphocytic leukemia (CLL). A significant positive correlation between S-TK and proliferation expressed as a proliferative index (PI) was found (r = 0.70, p less than 0.001). Additionally, PI (r = 0.59, p less than 0.01) and S-TK (r = 0.47, p less than 0.05) correlated to peripheral blood lymphocyte count. When different variables and combinations of variables were studied in order to define their capacity for discriminating between progressive and indolent CLL, S-TK activity and PI proved to be powerful indications. In longitudinal studies, both S-TK and PI paralleled disease activity. A model where a combination of S-TK and PI gives information of the degree of localized disease is proposed.

Adult↗
PubMed1986

Serum deoxythymidine kinase in small cell carcinoma of the lung. Relation to clinical features, prognosis, and other biochemical markers.

Thymidine kinase (s-TK), lactate dehydrogenase (LDH), and carcinoembryonic antigen (CEA) were determined in pretreatment serum from 125 patients with small cell carcinoma of the lung. The distribution of marker levels into three ranges, when including all patients were as follows: s-TK less than 5 units 49%, 5-less than 10 units 25%, greater than or equal to 10 units 26%; LDH less than 6.7 mukat 31%, 6.7-less than 13.4 mukat 48%, greater than or equal to 13.4 mukat 21%; CEA less than 7.5 micrograms/l 51%, 7.5-less than 15 micrograms/l 25%, greater than or equal to 15 micrograms/l 24%. The percentages of patients with limited and with extensive disease within each range were s-TK less than 5 82/18, 5-less than 10 29/71, greater than or equal to 10 9/91; LDH less than 6.7 76/24, 6.7-less than 13.4 51/49, greater than or equal to 13.4 21/79; CEA less than 7.5 70/30, 7.5-less than 15 39/61, greater than or equal to 15 23/77. Analyses in relation to metastases present showed that patients with skeletal and bone marrow metastases had significantly higher s-TK and LDH than those without, while this was not the case for CEA. A strong correlation between s-TK and LDH level, a weaker correlation between CEA and s-TK, and no correlation between CEA and LDH level, was found. Both the level of s-TK and LDH correlated to the patients' performance, as defined by the Karnofsky index. These correlations were mainly confined to the patients with extensive disease. Analyses of the prognostic capacity of variables showed that s-TK, stage, and Karnofsky index could divide the patients into groups with highly significant difference in survival time, while LDH and CEA were of less value. Longitudinal studies showed that the serum markers mirrored the disease activity, with the exception that highly increased s-TK was found during remission induction for some patients. It was concluded that the expression of pathologic levels for the serum markers were dependent on different biological parameters. Of the serum markers, only s-TK was judged useful for estimation of disease spread and prognosis of the individual patient.

Actuarial Analysis↗
PubMed1986

Mothers of children with Down syndrome have higher herpes simplex virus type 2 (HSV-2) antibody levels.

The antibody response to herpes simplex virus (HSV) was studied in 53 mothers of children with Down syndrome (Ds) and compared with that in 154 controls, using sera sampled during pregnancy or at delivery. Conventional analysis of HSV complement fixing antibodies showed the same frequency of positivity for the two groups (70%). When the levels of IgG antibodies to an HSV-1 and an HSV-2 antigen preparation were determined by an enzyme-linked immunosorbent assay (ELISA) technique, it was found that the Ds and control mothers had similar levels of IgG antibodies to HSV-1, whereas the level of IgG antibodies to HSV-2 was significantly (P less than 0.001) higher in Ds mothers. The ratio of HSV-2 to HSV-1 ELISA IgG was calculated for each mother and the distribution of these ratios also differed significantly between the control and Ds mothers. The differences found were not due to differences in age distribution in the control and Ds groups. For comparison a third procedure, measurement of thymidine kinase blocking antibody (TK ab), was used. With this procedure the mothers were divided into groups estimated to be positive for HSV-1, HSV-2, or both. Statistical analyses showed a good correlation between the type found in TK ab analyses and the ratio found in the ELISA HSV test. The results clearly demonstrated an overrepresentation of HSV-2 antibody positivity among Ds mothers, though not of sufficient magnitude to imply that HSV-2 can be the major cause of Ds. It is discussed whether HSV-2 might be related to the recently increased birthrate of children with Ds among young mothers in Sweden or to localized geographical clustering of Ds births, or whether the increased HSV-2 antibody positivity merely indicates that factors following the same epidemiological pattern are involved in the aetiology of Ds.

Adolescent↗
PubMed1986

Thymidine kinase in extracts of human brain tumours.

Deoxythymidine kinase (TK) is an enzyme involved in DNA synthesis. It can be used as a marker of cell proliferation. TK was measured in extracts of human brain tumours and non-neoplastic brain tissue. In astrocytomas the mean TK activity increased with increasing grade of malignancy. Oligodendrogliomas showed higher TK activity than astrocytomas. The highest activities were noted in menigiomas, of which the recurrent ones exceeded the primary in TK activity. In non-neoplastic brain tissue lower TK activity was found. It is concluded that TK can be measured in human brain tumour extracts, and is potentially of use for studies on tumour cell proliferation.

Astrocytoma↗
PubMed1986

Acyclic guanosine analogs as substrates for varicella-zoster virus thymidine kinase.

This study was performed to obtain information on the enzymatic background to the antiviral activity of acyclic guanosine analogs. Five acyclic guanosine analogs, the (R)- and (S)-enantiomers of 9-(3,4-dihydroxybutyl)guanine, 9-(4-hydroxybutyl)guanine, 9-[(2-hydroxyethoxy)methyl]guanine, and 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine, were compared in enzyme kinetic experiments using purified varicella-zoster virus and human placenta mitochondrial thymidine kinase (TK). All analogs showed competitive patterns of inhibition in the phosphorylation of thymidine by varicella-zoster virus TK, but only low affinities and phosphorylation rates were observed. No affinity for the mitochondrial TK was observed for any of the analogs.

Guanosine↗
PubMed1986

Deoxythymidine kinase, a possible marker for monitoring activity of cytomegalovirus infection after renal transplantation.

Measurement of deoxythymidine kinase activity (S-TK) in serum is used as a marker for cytomegalovirus (CMV) infection following transplant surgery. A case is presented where a kidney transplant patient suffered a fatal CMV infection. The new antiviral drug Foscarnet was used to treat the infection. Retrospective analysis of S-TK showed a good correlation with the course of the disease, its treatment, recurrence and final outcome.

Antiviral Agents↗
PubMed1986

Serum thymidine kinase in transplant patients: its relation to cytomegalovirus activity, renal transplant rejection and its use for monitoring of antiviral therapy.

Twenty patients, cadaveric renal transplant recipients, were retrospectively analysed for serum levels of deoxythymidine kinase. Special reference was made to the thymidine kinase level in relation to rejection, and viral infection. Seven of the patients experienced clinically suspected cytomegalovirus infection. All these patients had elevated levels of serum thymidine kinase during the period of clinical disease. Usually the thymidine kinase level parallelled the severity of the disease. All patients with irreversible rejection had increased levels of serum thymidine kinase, but normally not as high, as seen in patients with severe cytomegalovirus infection. There was also some correlation between clinically suspected rejection, that lead to rejection treatment, and moderate increase in thymidine kinase. However, not all rejection episodes were accompanied by a thymidine kinase increase. Serum thymidine kinase was analysed and compared in patients with self-healing cytomegalovirus disease, and those treated with phosphonoformate. A rapid decline in thymidine kinase level was found in connection with successful antiviral therapy, when compared to the decline in untreated patients. Some bone marrow transplanted patients were also included in this analysis.

Adult↗
PubMed1985

Evaluation of serum deoxythymidine kinase as a marker in multiple myeloma.

A recently developed deoxythymidine kinase assay utilizing 125I-iododeoxyuridine as substrate was used in an investigation of sera from 122 untreated patients with multiple myeloma. Most patients had slightly elevated or normal serum deoxythymidine kinase activity (S-TK), although in some patients values increased by more than forty-fold were found. S-TK correlated with the haemoglobin level but did not correlate with sex, age, erythrocyte sedimentation rate, nor with the serum concentrations of creatinine, beta 2-micro-globulin, Ca or M-component. The distribution of S-TK values in IgG, IgA and pure Bence-Jones myeloma did not differ significantly. Patients with IgG and IgA myeloma excreting light-chain immunoglobulin in the urine had significantly higher S-TK than non-excreters. There was a significant correlation between S-TK values and tumour cell mass as determined by clinical staging. A high pretreatment S-TK (greater than 5.1 units) also distinguished a group of patients with a significantly shorter survival time. Patients with no response to initial therapy had significantly higher S-TK values than those who did respond. In longitudinal studies of 11 patients, S-TK was found to increase when the disease became more aggressive. The possibility of diagnosing disease progression at an early stage by an elevation of S-TK is discussed.

Adult↗
PubMed1984

Serum deoxythymidine kinase gives prognostic information in chronic lymphocytic leukemia.

A recently developed deoxythymidine kinase assay, utilizing iodine-125-iodo-deoxyuridine as substrate and capable of detecting enzyme activity in serum from healthy humans, was used in an investigation of sera from 55 untreated patients with chronic lymphocytic leukemia (CLL). When confined to the study, the patients were classified as having progressive or indolent disease and according to Rai stage. The results showed a significant correlation between serum deoxythymidine kinase activity (S-TK) and disease status, i.e., higher values were found in patients with progressive disease, compared to those with indolent disease. S-TK also correlated with Rai stage. S-TK values of more than 40 times the normal value were found in some patients. All patients with S-TK greater than 8.4 units had a disease that was or became progressive during the observation period. Within the patient group with indolent disease two groups that differed with regard to prognosis could be distinguished according to their initial S-TK values. In longitudinal studies of 18 patients with indolent disease, S-TK was found to exceed 8.4 units only on one occasion during an observation period of up to 68 months. In patients with indolent disease, a transition to progressive disease was parallelled by an increase in S-TK. Studies of S-TK levels in 18 patients receiving treatment showed that S-TK decreased during successful therapy. S-TK was also found to increase when the disease was reactivated. From these results it is concluded that S-TK could be used as a prognostic marker for the individual CLL patient. Furthermore, S-TK seems to be useful for longitudinal follow-up studies of disease status, both in indolent disease and in progressive disease during treatment.

Adult↗
PubMed1984

Deoxythymidine-kinase in cerebrospinal fluid: a new potential "marker" for brain tumours.

A recently developed method for deoxythymidine kinase (dTK) determination was applied to cerebrospinal fluid (CSF) and serum samples, derived from "healthy" individuals and from patients with non-neoplastic or neoplastic disorders of the brain. No dTK activity could be detected in the CSF of healthy individuals or in patients with hydrocephalus or cranio-cerebral trauma. dTK levels ranging from detectable to high were found in the CSF of patients with malignant primary brain tumours or secondary brain tumours, while in some cases of low grade primary brain tumours dTK could not be detected in the CSF. CSF samples taken before and after treatment were available both in some patients with CNS involvement of malignant lymphomas and in some with primary brain tumours. The dTK activity rapidly declined after chemotherapy intrathecally and irradiation, as well as after surgery. Enhanced CSF dTK was not only a feature of malignant CNS processes, but was also found in patients with cerebral haemorrhage penetrating into the CSF. The origin of dTK in CSF and the practical use of quantifying it is discussed.

Astrocytoma↗
PubMed1983

The use of serum deoxythymidine kinase as a prognostic marker, and in the monitoring of patients with non-Hodgkin's lymphoma.

A recently developed enzyme assay, utilizing [125I]-iododeoxyuridine as substrate, and capable of detecting normal levels of serum deoxythymidine kinase (s-dTk), was used in an investigation of sera from 155 untreated patients with non-Hodgkin's lymphoma (NHL). The patients were classified at the discovery of disease, both according to spread (stages I-IV according to the Ann Arbor classification) and to tumour histology (the Kiel classification). The results showed a significant correlation between s-dTk level and the extent of disease, as well as to the malignancy; i.e. the more advanced the disease or the more aggressive the tumour, the higher the s-dTk values. Greater than 100-fold increases in s-dTk levels were found in some patients compared to those reported for healthy individuals. A high pretreatment level of s-dTk for patients in stages III-IV correlated with a poor prognosis for the patient in terms of survival. This was consistent even when only patients in stages III-IV with "high-grade" malignant lymphomas were included in the analysis. Longitudinal studies of s-dTk levels in 19 NHL patients showed that s-dTk increases with progression of the disease, decreases during successful therapy, and finally increases during relapse. It is concluded that s-dTk could be used both as a prognostic marker and to monitor the effect of therapy in NHL patients.

Adolescent↗
PubMed1983

Rapid diagnosis of varicella-zoster virus infection by detection of viral deoxythymidine kinase in serum and vesicle fluid.

A sensitive enzyme assay utilizing [125I]iododeoxyuridine as the substrate and CTP as the phosphate donor in combination with isozyme-specific antisera was used for direct detection and typing of herpesvirus deoxythymidine kinase (dTk) in clinical specimens. An investigation of 16 coded vesicle fluid specimens, taken in connection with varicella-zoster virus (VZV) and herpes simplex virus infections, revealed viral dTk activity in 14 samples. All positive samples except one were taken within 5 days after the onset of illness. Serological typing of the dTk activities easily established whether the vesicles were caused by VZV, herpes simplex virus type 1, or herpes simplex virus type 2. The results were obtainable within 5 h and were in agreement with the results achieved by immunofluorescence tests or by virus isolation when positive. Acute- and convalescent-phase sera from patients with VZV infections were analyzed with regard to dTk isozyme composition. All sera collected within 5 days after the onset of varicella were found to contain elevated levels of dTk activity. By the use of isozyme-specific antisera and gel electrophoresis, it was possible to show the presence of both cellular and VZV dTk's. Among the 13 acute-phase sera from zoster patients, only 2 were found to be VZV dTk positive. Convalescent sera, in most cases collected 15 days or more after the onset of illness, were also found to be devoid of VZV dTk. The relevance of the results and the possible use of these methods for viral diagnostics are discussed.

Clinical Enzyme Tests↗
PubMed1982

Human serum antibodies to varicella-zoster virus thymidine kinase.

The conditions required for the production of varicella-zoster virus (VSV)-induced deoxythymidine kinase (dTk) have been studied. Extracts from Vero cells harvested 62 h after VZV infection were found to contain VZV-induced dTk activity, with a minimal contribution from the cellular dTk activity. VZV dTK was shown to have a broad substrate specificity phosphorylating both deoxythymidine, deoxycytidine, and iododeoxyuridine. Deoxythymidine triphosphate inhibition studies revealed an intermediate deoxythymidine triphosphate sensitivity when compared with that of the cellular cytosolar enzyme and the deoxythymidine triphosphate-insensitive herpes simplex virus dTk. An assay for VZV dTk-blocking antibodies was developed, with [125I]iododeoxyuridine as a substrate in the presence of a deoxythymidine triphosphate concentration which selectively blocked the dTK of host cell origin. A total of 79 serum samples were studied; these included serum pairs from patients with varicella or herpes zoster and single sera from immune and nonimmune adults. VZV dTk blocking antibodies were detected exclusively in sera from patients with herpes zoster. All serum pairs showing VZV dTK seroconversion also showed a parallel conversion of complement fixation titers. The VZV dTk antibodies were found to be of the immunoglobulin G class. The immunological specificity of VZV dTK was investigated, and no cross-reactivity with herpes simplex virus type 1 or 2 dTk was found.

Adolescent↗
PubMed1982

Rapid typing of herpes simplex virus based on immunological specificity of viral thymidine kinase and typing according to sensitivity to iododeoxyuridine.

We describe two methods for typing of herpes simplex virus (HSV). One procedure is based on the finding that the multiplication of HSV type 1 strains in primary rabbit kidney cells is inhibited by 2 x 10(-5) M iododeoxyuridine, whereas growth of HSV type 2 strains is considerably less affected. Forty-nine different HSV isolates were typed according to this method. For all isolates except two the results were found to be in agreement with results obtained by another typing procedure, the counterimmunoelectroosmophoretic method (S. Jeansson, Appl. Microbiol. 24:96-100, 1972). One HSV type 1 isolate behaved as a type 2 strain and was found to be a deoxythymidine kinase-negative mutant strain. The other deviant strain exhibited an intermediate iododeoxyuridine sensitivity, thus being impossible to type with this method. Another, faster typing procedure which is based on the immunological difference between HSV type 1 and 2 deoxythymidine kinase is also presented. This assay, in combination with the conventional methods for isolation, enables the detection of deoxythymidine kinase-negative therapy-resistant HSV strains. Finally, we report the detection and typing of HSV deoxythymidine kinase present in vesicle fluids.

Animals↗
PubMed1982

The use of herpes virus induced dTk as a marker for serological and direct identification of herpes virus infection in man.

This report summarizes the essential features of a sensitive deoxythymidine kinase (dTk) assay, which can be used for the diagnosis of Herpes virus infections. A type specific antibody response towards the different Herpes virus dTk isozymes, the Herpes simplex virus (HSV) type 1, type 2, and Varicella Zoster virus (VZV), was found in human sera. The occurrence of dTk antibody in relation to complement fixing (cf) antibody and the state of infection, was found to differ between HSV and VZV. The VZV dTk antibody was only found in patients with Herpes Zoster, while most HSV cf positive individuals had HSV dTk antibody. Absence of dTk in HSV cf positive individuals was related to a "recent primary infection". The type specificity of the dTk isozymes makes these antigens suitable for typing of isolates, and this in combination with the sensitivity of the assay, made it possible to verify and type HSV infection by direct analysis of blister secrete without previous virus isolation. Such results can be obtained within five hours. Combined with conventional isolation procedures the dTk typing assay also detects dTk negative "therapy resistant" strains. The use of the dTk assay for diagnostic purposes is discussed.

Antibodies↗
PubMed1981

Occurrence of antibodies against herpes simplex virus thymidine kinase in human sera.

The occurrence of antibodies in human serum that block herpes simplex virus (HSV) type 1 and 2 deoxythymidine kinase (dTK) has been investigated. The antibodies were detected by means of a sensitive assay technique using [125I]iododeoxyuridine as a substrate [Gronowitz and Källander, 1980]. A total of 213 sera was studied. They included pairs of serum from patients with an acute HSV infection, individual sera from persons not suspected of a HSV infection, as well as sera from patients from whom HSV had been isolated. The HSV complement fixing (cf) titer was determined for each serum and subsequently used as a reference. None of the HSV cf negative sera contained HSV dTK blocking antibodies, whereas all cf positive sera did, however, all excepting those that were collected in connection with primary infections. by following the serum titer after a primary infection, we have found that 12 out of 19 persons studied had detectable dTK antibodies after an average time of 179 days. The results indicate a low degree of cross-reactivity between HSV type 1 and 2 dTK blocking antibodies.

Antibodies, Viral↗