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J S Gronowitz

Publications and source records attributed to J S Gronowitz.

46 records · Page 3Linked to original sources
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↗
PubMed1980

Optimized assay for thymidine kinase and its application to the detection of antibodies against herpes simplex virus type 1- and 2-induced thymidine kinase.

An optimized assay for herpes simplex virus type 1- and 2-induced deoxythymidine kinase (dTk) is described which used [125I]iododeoxyuridine (IUdr) as a substrate. Values for Km and Vsat were determined for both viral and cellular dTK, using either deoxythymidine or IUdR as a substrate. A comparison between the two substrates revealed that higher reaction velocities and lower Km values were obtained with IUdR. A standard assay was designed which uses 10(-7) M IUdR as a substrate. This assay can detect herpes simplex-induced dTK from as few as two infected cells and is several orders of magnitude more sensitive than conventional dTK assays which use 10(-5) M dT as a substrate. An easily detectable blocking activity, which was shown to be mainly confined to the immunoglobulin G antibody class, was found in most human sera which were positive for complement-fixing antibody against herpes simplex virus.

Antibodies, Viral↗