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Biomedical subjects

J K Larsen

Publications and source records attributed to J K Larsen.

At least 73 records · Page 4Linked to original sources

Altered modulation of prefrontal and subcortical brain activity in newly diagnosed schizophrenia and schizophreniform disorder. A regional cerebral blood flow study.

To measure prefrontal and subcortical activity during a cognitive task, we examined 19 newly diagnosed schizophrenics and patients with schizophreniform psychosis. Seven healthy volunteers served as controls. The patients were drug naive or had received neuroleptics for a few days only. Cerebral blood flow distribution was depicted by single photon emission computed tomography at rest and during activation with the Wisconsin Card Sorting Test. A significant relative activation deficit in the left inferior-prefrontal region was revealed during the Wisconsin Card Sorting Test in the patient group. Furthermore, the patients had impaired striatal suppression on the left side during the cognitive task. The test performance was significantly impaired in the patients. The inability to reduce striatal activity may be due to a lack of corticostriatal feedback during prefrontal activation.

Adult↗

Washless double staining of unfixed nuclei for flow cytometric analysis of DNA and a nuclear antigen (Ki-67 or bromodeoxyuridine).

Washless methods for double staining of nuclear antigen and DNA in unfixed nuclei were compared with established methods for staining of fixed cells. The methods were tested on phytohemagglutinin (PHA)-stimulated normal human blood lymphocytes for the double staining of 1) Ki-67 antigen and DNA and 2) bromodeoxyuridine (BrdUrd) and DNA, in continuously BrdUrd-labeled cells. With respect to the discrimination between antigen-positive and -negative subpopulations, there was no statistically significant differences between the results from direct (Ki-67) or indirect (Ki-67 or BrdUrd) washless staining of unfixed nuclei and the results from staining of fixed cells. Washless staining of unfixed nuclei was found to be rapid and simple and resulted in greater precision of the DNA analysis and in less aggregation and loss of cells.

Bromodeoxyuridine↗

Moclobemide in depression: a randomized, multicentre trial against isocarboxazide and clomipramine emphasizing atypical depression.

Moclobemide was compared with isocarboxazide and clomipramine in patients with depression. A total of 167 outpatients were allocated to daily treatment with 300 mg moclobemide, 30 mg isocarboxazide or 150 mg clomipramine for 6 weeks. Moclobemide was slightly inferior to clomipramine, whereas isocarboxazide had an intermediate position. There was no interaction between treatment and atypical or nonatypical depression. Anticholinergic symptoms and orthostatic hypotension were most pronounced in the clomipramine group.

Adult↗

Hydatidiform mole and fetus with normal karyotype: support of a separate entity.

Repetitive hydatidiform mole was observed in four pregnancies. The pregnancies presented with heavy bleeding and vomiting, but the post-evacuation courses were uncomplicated, with rapid regression of serum hCG levels. Cytogenetic investigations, analyses of restriction fragment length polymorphisms, and flow cytometry in three pregnancies were consistent with diploid, biparental conception as the origin of fetal tissue and molar and nonmolar villi. In one pregnancy, the analyses of cytogenetic markers suggested the coexistence of two different cell lines of dizygotic, biparental origin, whereas DNA analysis was consistent with a single conception. With incomplete genetic information, a hydatidiform mole with coexistent normal fetus is generally considered to result from dizygous twinning comprising an androgenetic complete mole and a normal conception. In the present gestations, the results based on several techniques applied on numerous samples from different tissues render this possibility unlikely. Some of the contradictions between histologic and cytogenetic classifications of hydatidiform mole may be explained by diploid, biparental partial mole, which seems to constitute a separate subgroup within hydatidiform mole. Following chorionic villus sampling or amniocentesis, continued pregnancy may be considered, depending on prenatal diagnosis including genetic marker analysis.

Adult↗

Correlation between in vitro tetraploidy in skin fibroblasts and development of sporadic colorectal carcinomas.

In vitro tetraploidy (IVT) in skin fibroblasts cultures measured by flow cytometry was compared with histological type and degree of dysplasia in 22 patients with adenomas of the colon and rectum. Furthermore, IVT was compared with stage and differentiation in 36 patients with carcinoma of the colon and rectum. In vitro tetraploidy in skin fibroblasts was correlated to type as well as dysplasia in adenomas and differentiation in carcinomas but was not correlated to Dukes' stage in carcinomas. Skin fibroblast genetic instability, expressed as increased IVT (IVT+), has been reported to reflect a genetic predisposition to colorectal cancer in the hereditary nonpolyposis colorectal cancer syndrome. Because IVT+, which appears to be associated with the progression of adenomas to carcinomas, also is found in many of the non-syndrome colorectal cancers, we suggest that development of colorectal cancer is considerably influenced by the constitutive genetic instability of the autosomal dominant colorectal cancer syndromes.

Adenoma↗

Plasma ratio tryptophan/neutral amino acids in relation to clinical response to paroxetine and clomipramine in patients with major depression.

The pretreatment plasma ratio of tryptophan (Trp) to other large neutral amino acids (LNAA), thought to reflect brain serotonin formation, was determined in 44 inpatients with major depression, who were subsequently treated double-blind on a fixed-dose schedule for 4 weeks with the selective serotonin uptake inhibitor paroxetine (n = 27) or clomipramine (n = 17). The study took place at four clinical centers. Endogenous and non-endogenous depressives were comparable with respect to the ratio Trp/LNAA and clinical improvement and were therefore analyzed together. The clomipramine group showed a significant inverse correlation between ratio Trp/LNAA and improvement, and patients with a ratio Trp/LNAA below the mean showed a trend towards greater improvement than patients with a higher ratio but with comparable serum drug levels. The improvement in the paroxetine group was significantly inversely correlated with the Trp concentration but not with the ratio Trp/LNAA. The findings accord with previous trials of various antidepressant treatments, in which about 25% of the variance in therapeutic response associates with pretreatment plasma amino acid profiles.

Adult↗

Quantifying depressive symptomatology: inter-rater reliability and inter-item correlations.

In this study an evaluation of the inter-rater reliability of the Hamilton Depression Rating Scale, the Melancholia Scale and the Montgomery-Asberg Depression Rating Scale has been carried out. Furthermore, the inter-item correlations of these scales have been investigated in relation to diagnostic ratings. It was found that the quantitative scales had satisfactory inter-rater relationship. Only low agreement was found between the quantitative and diagnostic scales, as expected, while there was high agreement between the quantitative scales. The relevance of introducing new scales and the definition of major depression are discussed.

Adult↗

Human-human hybridoma producing monoclonal antibodies against colorectal cancer-associated antigens.

Lymphocytes from lymph nodes draining the tumor region in patients with colorectal cancer were fused with two different human B-lymphoblastoid cell lines, LICR-LON-HMy-2 (HMy-2) and WI-L2-729-HF2 (729-HF2), to generate hybridomas synthesizing antibodies reacting with tumor-associated antigens. In this way 220 hybridomas were obtained which produce antibody reacting with colon cancer cells. All established clones produced IgM. Four human monoclonal antibodies have been further analyzed. The cell lines producing these antibodies are all hybrids based on DNA analysis. Three of the antibodies (G4146, B9165 and D4213) showed binding to differentiation antigens by immunocytochemical analysis on different cancer cell lines and normal human leucocytes and by immunohistochemical analysis on sections of frozen malignant and normal tissues, while the fourth (F11348) showed a reaction with all cells and tissues tested. Western blots of tumor extracts showed binding of G4146 to two components from colon cancer cells with Mr of 59 K and 61 K, while B9165 bound to a 43 K component and F11348 to several components with Mr from 30 to 200K. D4213 showed no binding in this analysis. The results obtained demonstrate the successful application of hybridoma technology to produce human monoclonals with reactivity to differentiation antigens.

Antibodies, Monoclonal↗

Flow cytometric DNA analysis of lesions from 18 children with langerhans cell histiocytosis (histiocytosis x).

The DNA content in 26 formalin-fixed, paraffin-embedded histologic specimens from 18 children with Langerhans cell histiocytosis (LCH) was analyzed by flow cytometry. In two cases, the propidium iodide fluorescence histograms showed small (5 and 3% of the analyzed nuclei) but significant aneuploid subpopulations with DNA indices of approximately 1.5. This was confirmed by analysis of unfixed, frozen material in one patient. Both patients had disseminated disease without organ dysfunction and were treated with prednisone. Currently, they are without signs of disease activity after 1 and 10 years. DNA histograms were normal from a patient who died from disseminated disease and from two patients with disseminated disease who experienced several relapses and various chemotherapeutical regimens. The histograms were also normal in lesions from four patients with unifocal bone involvement. Our results show that DNA aneuploidy occurs in LCH lesions in the pediatric age group. Further investigation is necessary to reveal whether DNA aneuploidy is restricted to disseminated LCH or its presence has any value in predicting the course and outcome of the disease.

Adolescent↗

[Preoperative ultrasonic diagnosis of maldescended testis].

In 30 boys with a total of 35 maldescended testicles, the present authors found that ultrasonic examination was a useful aid in the diagnosis of maldescended testicles, including intraabdominal testicles. Ultrasonic examination is recommended preoperatively in boys with non-palpable testicles in order to provide optimal surgical intervention.

Adolescent↗

Genetically different cell subpopulations in hydatidiform moles. A study of three cases by RFLP, flow cytometric, cytogenetic, HLA, and morphologic analyses.

Most investigators find a good correlation between the morphologic and cytogenetic classification of hydatidiform moles (HM), but exceptions have been noted. We have examined three cases of HM, using chromosome marker analysis on cultured cells, human leukocyte antigen typing on cultured and uncultured tissue, and restriction fragment length polymorphism (RFLP) analysis and flow cytometry on uncultured cells. In one morphologically partial mole, only one cell population (triploid) was found and data obtained by the above-mentioned techniques were concordant. The other two moles, which were classified morphologically as complete, consisted of several cell subpopulations differing in DNA content. In both cases only one cell population was disclosed by cytogenetic investigation. In one case, the cytogenetic analysis indicated that the cultured cells were near triploid with paternal chromosomes exclusively, whereas RFLP analysis showed that maternal X chromosomal alleles were present in the mole. The present findings demonstrate that some HMs contain cellular subpopulations with differing DNA content. One explanation for discordance between cytogenetic and morphologic classification may thus be the detection of only one cell subpopulation when karyotyping.

Chromosome Aberrations↗

Human skin fibroblast in vitro tetraploidy. Flow cytometric DNA assay used to confirm metaphase assay in patients with various colonic diseases.

One hundred twenty-two patients with various colon pathologies (43 colorectal carcinoma patients exclusive of the known autosomal dominant colorectal cancer syndromes, 31 patients with solitary colorectal adenomas, 27 patients with ulcerative colitis, and 21 controls with no evidence of colorectal cancer) were investigated for in vitro tetraploidy in dermal fibroblasts cultures using a metaphase assay for determination of numerical chromosomal alterations. Later, stationary cultures of these skin fibroblasts were investigated with DNA flow cytometry. There was good correlation between the percentage of tetraploid metaphase cells and the percentage of nuclei with a flow cytometric DNA index of 2. Using a linear discrimination function to classify the flow cytometric data, the peak with DNA index of 2 was the most important parameter, supplemented by the region with DNA index greater than 2, whereas the region with DNA index between 1 and 2 probably represented a different subpopulation. We have thus demonstrated that only the region with a DNA index of 2 or greater is suitable in determining in vitro tetraploidy in stationary skin fibroblast cultures.

Colitis, Ulcerative↗

Fatal cutaneous T cell lymphoma in a child with atopic dermatitis.

The development of a fatal cutaneous T cell lymphoma in a child with atopic disease is presented. From very early childhood the patient had classic atopic dermatitis, and at age 13 developed lymphoma-like skin tumors. The diagnosis--based on immunohistologic criteria--was initially difficult to establish, but cytogenetic and DNA studies of the dermal infiltrate supported the clinical suspicion of malignancy. In addition, the T cell receptor beta chain gene showed a clonal rearrangement pattern both in skin and in lymph node, suggesting malignancy. Whether the malignant evolution in our patient took place primarily in the skin or in the lymph nodes is difficult to decide. Further examination of the association between atopic dermatitis and cutaneous T cell lymphoma may lead to insights into both disorders.

Adolescent↗

DNA analysis by flow cytometry in cutaneous T-cell lymphomas.

DNA histograms of skin and blood specimens from 64 patients with known or suspected cutaneous T-cell lymphoma (CTCL) have been examined and compared with normal blood mononuclear cells and skin biopsy samples from 50 patients with various benign cutaneous conditions (i.e. patch test infiltrates, eczema, psoriasis, lichen planus, atopic dermatitis) in an attempt to establish whether DNA measurements by flow cytometry may improve the early recognition of CTCL. The results indicate that right-skewed G0/G1 peaks are seen frequently in both benign disorders and known and suspected CTCL. Such peaks may reflect increased stainability of DNA due to chromatin dispersion during cell activation and/or cell proliferation and do not constitute reliable evidence of malignancy. In contrast, discrete aneuploid DNA peaks are confined to malignant lesions, but are seen almost exclusively in the advanced stages in which the diagnosis can be established easily based on routine histological criteria. These data indicate that DNA measurements by flow cytometry is of only limited help in the early recognition of CTCL and support the view that the lymphoid infiltrate in early CTCL may be reactive (rather than neoplastic) or alternatively may contain only minor reactive (rather than neoplastic) or alternatively may contain only minor populations of abnormal (malignant) cells which cannot be detected by currently available DNA measurement techniques.

Adult↗

Specific depletion of mature T lymphocytes from human bone marrow.

An effective method for specific depletion of mature T lymphocytes from human bone marrow mononuclear cells (BMMC) with preservation of prethymic T cells and natural killer (NK) cells is presented. The BMMC were incubated with F101.01, a monoclonal antibody recognizing an epitope of the T-cell receptor-CD3 complex, and subsequently with immunomagnetic beads. Flow cytometric analysis demonstrated that mature T cells were efficiently depleted and that NK cells and prethymic T cells were preserved in the BMMC. Furthermore, T cell-mediated immune reaction as measured by thymidine incorporation after stimulation with phytohaemagglutinin was abolished, whereas NK activity as measured by 51Cr release using K562 as target cells was preserved. Recovery of colony-forming units of granulocyte-macrophages was 60-70%.

Bone Marrow↗