A new Epstein-Barr virus nuclear antigen (EBNA) negative cell line SKW 4 has been established in vitro from a patient with diffuse histiocytic lymphoma. The SKW 4 seems to be an authentic human tumour cell line as evidenced by its EBV negativity, monoclonality and aneuploidy tested during early in vitro passage. The cell line expresses surface mu and kappa-chains, HLA-DR antigen, C3 and Fc receptors and B-cell lineage antigens. The karyotypic analyses demonstrated many numerical and structural aberrations. No Burkitt lymphoma associated translocations (t8;14, t2;8, t;22) were detected, but most of the markers found are those commonly associated with various types of human cancer. The SKW 4 thus represents the most common type of 'histiocytic lymphoma', that with a B-lymphoid cell phenotype, but is unique among HL derived lymphoma lines in its strong expression of a Helix pomatia A agglutinin binding surface glycoprotein of an apparent molecular weight of 75 000 daltons.

Antibodies, Monoclonal↗

PubMedDate not supplied

Glucocorticoid receptors, DNA synthesis, membrane antigens and their relation to disease activity in chronic lymphatic leukemia.

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Animals↗

PubMedDate not supplied

Preventing cross infection of blood borne viruses on haemodialysis.

A chronic haemodialysis patient acquired hepatitis C. It was thought certain that this had occurred while dialysing in a satellite dialysis unit. The incident initiated a review of current measures in place to prevent the transmission of blood-borne viruses (BBV) on haemodialysis, with an analysis of current literature on the topic. It was found that the author's unit and several additional local units had no written protocols on prevention of BBV during haemodialysis, and methods of prevention were largely verbally communicated. A review of the literature gave conflicting opinions on the effectiveness of different measures to prevent cross-infection. Following the assessments and literature review, the appropriateness of certain preventative measures was looked at in more detail. A local protocol was subsequently developed and implemented at the author's Trust, which will significantly change practice in the haemodialysis unit.

Blood-Borne Pathogens↗

PubMedDate not supplied

Plasma homocysteine is a sensitive marker for tissue deficiency of both cobalamines and folates in a psychogeriatric population.

The concentration of blood folates was decreased and the concentration of plasma homocysteine was increased in a psychogeriatric population, whereas the concentrations of methylmalonic acid or serum cobalamins were not changed compared with healthy subjects. The highest frequency of abnormal values was shown by plasma homocysteine concentration, which was increased in 88 of 168 patients. In 29 of these 88 patients increased concentration of plasma homocysteine could possibly be attributed to tissue cobalamin deficiency. One patient had only a lowered concentration of blood folate. Thirteen patients had elevated concentrations of serum creatinine which could explain increased plasma homocysteine concentration. Even if the remaining patients (n = 45) had normal vitamin levels in circulation, the increased plasma homocysteine concentration in most cases must be attributed to tissue deficiency of cobalamins and/or folates. Thus, many patients with increased plasma homocysteine concentrations need further vitamin supplementation despite their normal vitamin levels in serum and blood. Copyrightz1999S.KargerAG,Basel

Aged↗

PubMedDate not supplied

Apolipoprotein-E genotyping in Alzheimer's disease and frontotemporal dementia.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are characterized by progressive neuronal loss and microvacuolization, although with different distributions of cortical involvement. In contrast to AD there is no amyloid, senile plaques or tangles in FTD. The involvement of chromosome 19 in AD has been associated with apoliprotein E (ApoE) and the epsilon 4 gene frequency has been related to increased risk and early onset of AD. Our analysis of frequency of the ApoE alleles in 38 patients with AD, 21 patients with FTD and 29 normal controls indicates an association of both AD and FTD with an increased frequency of the epsilon 4 allele and in AD also with homozygosity for epsilon 4. Our results might indicate that ApoE epsilon 4 is an important aggravating and pathoplastic factor in the presence of genetic and other determinants for the development of AD or FTD. A significantly higher epsilon 2 frequency in our FTD material compared to AD and normals might also indicate a connection with the distribution of cortical degeneration.

Adult↗

PubMedDate not supplied

Long-term effects of tacrine on regional cerebral blood flow changes in Alzheimer's disease.

UNLABELLED: Regional cerebral blood flow (rCBF) was studied in patients with Alzheimer's disease (AD) before and after 14 months of tacrine treatment. The treated group was compared with an identical reference group of untreated AD patients. At baseline the two groups showed an identical rCBF and mean hemispheric blood flow. After 14 months the tacrine-treated patients showed a stable rCBF level and a significant increase in rCBF in the central-parietal regions, compared to the untreated reference group, who showed typical AD reductions in rCBF in these regions. CLINICAL OUTCOME: 7 of 9 patients in the tacrine group were clinically unchanged or slightly improved during the study time. In the untreated group 8 of 11 patients had deteriorated in clinical assessments and none had improved. Long-term tacrine treatment in Alzheimer's disease may delay the progression of symptoms.

Aged↗

PubMedDate not supplied

Oral tetrahydroaminoacridine treatment of Alzheimer's disease evaluated clinically and by regional cerebral blood flow and EEG.

Neurochemical evidence indicates that cognitive impairment in dementia of Alzheimer type (DAT) is related to degeneration of cholinergic neurons in the brain. A pharmacological approach is treatment with a cholinesterase inhibitor such as tetrahydroaminoacridine (THA). THA treatment of 17 patients with DAT was studied with a double-blind crossover design with three types of treatment, THA + lecithin, THA + placebo and placebo + placebo. Each treatment period was 6 weeks with wash out periods of 2 weeks. The treatment was evaluated with clinical ratings, psychometric testing, EEG and regional cerebral blood flow (rCBF) measurements. No significant clinical differences between treatment periods were found in the total sample, but marked individual differences were observed. The patients were subdivided into three outcome groups based on four clinical measures: 6 patients improved (responders), 5 patients were mainly unchanged, and 6 patients showed further deterioration during the trial period of 26 weeks. Pretreatment rCBF in responders differed significantly from that of the deteriorated patients. EEG showed more high frequency activity among responders. Hepatotoxic side effects were observed in several cases. Three subjects showed marked increases of liver enzymes, with normalization following dose reduction. The majority of patients who improved or remained unchanged during the study chose to continue THA treatment in an open trial.

Aged↗

PubMedDate not supplied

Local tissue effects of surface-applied ENT drugs.

Local tissue effects caused by a selected group of topically applied ENT-drugs are analysed. By means of a testing system consisting of vital mircoscopy, infrared thermography and microangiography applied to hamsters and rabbits, an evaluation of the varying degree of tissue injury is made. According to the degree of tissue damage the tested substance could be graded in three groups (I-III). The drugs belonging to group I show fairly little microcirculatory disturbance, while those belonging to group III cause tissue necrosis. Our conclusion is that topically applied drugs should be used with caution, especially on previously injured tissues.

Angiography↗

PubMedDate not supplied

The tracheal mucosa microvasculature and microcirculation. Intravital microscopic observations in rabbits and a histologic study in man.

A method for the intravital microscopic study of the tracheal mucosal microcirculation in the rabbit is described. A low tracheostomy is performed for ventilation, while a hole cut in the ventral portion of the trachea cranial to the tracheostomy is used for observations. The trachea is immobilized by a fixation device. Microscopic observations are made with a Leitz stereo microscope. The microvasculature of the rabbit tracheal mucosa is characterized by centripetally arranged arterioles which subdivide into a fairly sparse capillary network at the mucosal surface. The capillaries drain into venular networks at different levels of the mucosa and collect finally into circumferentially arranged veins which run mainly between the cartilages. For comparative purposes the microvasculature of the human tracheal mucosa has been analysed in clarified (Spalteholz) preparations. This investigation shows that the microvascular architecture is principally the same in the human and rabbit tracheal mucosa. There is, however, a much denser capillary network in the human tracheal mucosa.

Adult↗

PubMedDate not supplied

Neuron-specific enolase in small-cell carcinoma of the lung: the value of combined immunocytochemistry and serum determination.

The value of neuron-specific enolase (NSE) as a marker for small-cell carcinoma of the lung has been the subject of several reports. Taken together, about 70 per cent of patients with small-cell carcinoma had a raised serum concentration of NSE, and in a majority of patients NSE could be detected immunocytochemically in tumor biopsy speciments. This study examined the diagnostic value of combined immunocytochemical detection and serum determination of NSE in 96 unselected patients with small-cell carcinoma. Seventy-one patients had raised serum concentrations and in 69 a positive immunoreaction for NSE was demonstrated in the biopsy cells. However, for 87 (91%) of the patients, both or either of the NSE assays were positive. The combined use of immunocytochemistry and serum determinations thus gave better information on tumor NSE expression than either method alone. When patients with small or mechanically maltreated biopsy specimens were excluded, the accuracy of the combined assays was even higher (47/49, 96%). We therefore conclude that NSE, although not a specific marker for small-cell carcinoma of the lung, is useful as a complement to conventional diagnostic procedures and, when assayed both in biopsy material and in patient sera, tumor NSE expression can be demonstrated with a high precision.

Biomarkers, Tumor↗

PubMedDate not supplied

Early ionic events associated with phorbol ester induced differentiation and inhibition of cell growth in hematopoietic tumor cell lines.

The effects of 12-O-tetradecanoylphorbol-13 acetate (TPA) on DNA synthesis, phenotypic expression, cytoplasmic Ca2+ (Ca2+i), intracellular pH (pHi) and membrane potential were studied in the monoblastic U-937 and the erythroleukemic K-562 cells. In both cell lines DNA synthesis was inhibited and in the U-937 cells this was accompanied by the appearance of macrophage differentiation markers. The erythroid characteristics of K-562 cells, on the other hand, were markedly suppressed. Intracellular pH (pHi) was increased by TPA treatment; however, while the alkalinization of K-562 cells was dependent on the presence of extracellular Na+, the response of U-937 cells was unaffected by the removal of this cation. In each cell type the protein kinase C (PKC) inhibitor H-7 largely attenuated the TPA induced increase of pHi. Moreover, the alpha-stereoisomer of TPA, which does not activate PKC, had no effects. TPA caused a dose-dependent decrease in Ca2+i which was more pronounced in U-937 cells. Measurements of membrane potential revealed a marked TPA depolarization of the K-562 cells, but no such effects were observed in the U-937 cell line. The depolarizing response of K-562 cells could be abolished by substituting extracellular Na+ with choline+, indicating the presence of a TPA sensitive Na+ permeability. The results show that the phorbol ester TPA, which inhibits proliferation and causes phenotypic modulation, also induced a number of early, apparently PKC dependent and cell type specific, changes of intracellular ion activities. The possible role of intracellular ion fluxes in the regulation of cell growth and differentiation is discussed.

Calcium↗

PubMedDate not supplied

Surface-glycoprotein patterns of established human lung cancer cell lines and primary cultures.

The cell surface glycoprotein (GP) profiles of cell lines representing the four major histopathological lung cancer entities, squamous cell (SQC)-, small cell (SCC)-, adeno (ADC)-, and large cell carcinoma (LCC), and two primary cultures of SCC and LCC, respectively, have been examined by the galactose-oxidase tritiated sodium-borohydride cell surface labelling method, The SCC specimens (five cell lines and one biopsy) had a characteristic pattern of major surface GPs, with common GPs at apparent molecular weights (MWs) of 54 -kilo (k) Daltons (D) and 88 kD, which was discriminative from the group of non-SCC (SQC, ADC and LCC). The non-SCC group constantly expressed GPs at apparent MWs of 80 kD and 110 kD, both as established cell lines and in the primary LCC culture. The GP patterns of the SCC cell lines and the LCC cell line were retained in comparison to corresponding primary biopsy material. The propagation of an established SCC cell line without supplementation of serum did not alter the GP expression at the cell surface. Taken together, the surface GP patterns for SCC versus non-SCC appear to be reliable and reproducible markers for these tumor entities, both in biopsy material and in established cell lines.

Adenocarcinoma↗