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Biomedical subjects

K Jacobsen

Publications and source records attributed to K Jacobsen.

At least 19 recordsLinked to original sources
PubMed1992

Highly restricted expression of a stromal cell determinant in mouse bone marrow in vivo.

B lymphocyte precursor cells in mouse bone marrow develop in close association with stromal cells which provide essential growth signals. To identify molecules that may normally play a role in this interaction we have examined the in vivo binding of a new monoclonal antibody (mAb) (KMI6) that recognizes a determinant on a bone marrow stromal cell line (BMS2) in vitro. Flow cytometric and radioautographic evaluations revealed that the antigen recognized by KMI6 is represented on the surface of an extremely small number of cells in bone marrow cell suspensions from adult mice. An apparent molecular mass of 110 kD was obtained by surface labeling of a stromal cell clone and immunoprecipitation. Purified mAb KMI6 labeled with 125I was then given intravenously to young C3H/HeJ mice. Unbound mAb was washed out by cardiac perfusion and femoral bone marrow was examined by light and electron microscope radioautography. KMI6 labeling was heavy on the plasma membrane of many stromal cells, especially those located towards the outer subosteal region. The KMI6-labeled stromal cells were usually associated with cells of lymphoid morphology which they often completely surrounded. The labeling was restricted to areas of stromal cell plasma membranes in contact with lymphoid cells. The lymphoid cells themselves, as well as macrophages and other hemopoietic cells, failed to bind mAb KMI6 significantly. Stromal cells in bone marrow depleted of hemopoietic cells by gamma-irradiation (9,5 Gy) bound mAb KMI6 at reduced intensity. The results demonstrate that the KMI6 determinant, a 110-kD protein, is expressed on bone marrow stromal cells in vivo. Its restriction to areas of interaction with lymphoid cells suggests a role in forming microenvironmental niches of B lymphopoiesis. The surface membrane of individual stromal cells may thus be functionally polarized towards interacting B cell precursors and other hemopoietic cells.

Animals↗
PubMed1992

Dynamics and localization of early B-lymphocyte precursor cells (pro-B cells) in the bone marrow of scid mice.

Mice homozygous for the scid (severe combined immunodeficiency) mutation are generally unable to produce B lymphocytes, a condition attributed to defective rearrangement of immunoglobulin genes in precursor B cells. Some early B-lineage cells are present in the bone marrow (BM), however. In scid mice, we defined three subsets of early progenitor B cells lacking mu heavy chains (pro-B cells) based on the expression of terminal deoxynucleotidyl transferase (TdT) and B220 glycoprotein: (a) early pro-B cells (TdT+B220-), (b) intermediate pro-B cells (TdT+B220+), and (c) late pro-B cells (TdT-B220+). Double immunofluorescence labeling of BM cell suspensions has shown normal numbers of early and intermediate pro-B cells, substantially reduced numbers of late pro-B cells, and an absence of pre-B cells and B cells. Early and intermediate pro-B cells accumulated in metaphase in near-normal numbers after intraperitoneal (IP) vincristine administration. B220+ pro-B cells have been localized in BM sections by the binding of intravenously (IV) administered 125I monoclonal antibody (MoAb) 14.8, detected by light and electron microscope radioautography. Many B220+ cells were located peripherally in the bone-lining cell layers associated with stromal reticular cells. More centrally located B220+ cells were frequently associated with macrophages containing prominent cytoplasmic inclusions. Occasional B220+ cells were present in venous sinusoids. These results demonstrate that many pro-B cells in scid mice occupy microenvironments in the BM near the surrounding bone. The pro-B cells maintain normal rates of production during stages of presumptive mu heavy-chain gene rearrangement, apparently unaffected by the absence of a mature B cell pool. Nearly all defective cells then abort at the late pro-B cell stage and are deleted, apparently by macrophages. The findings contribute to models of in vivo differentiation, regulation, localization, and selection of early B-lineage cells in the BM.

Animals↗
PubMed1992

Acute and habitual caffeine ingestion and metabolic responses to steady-state exercise.

This study compared the exercise catecholamine and metabolic responses to a caffeine challenge in trained subjects before and after a 6-wk period of increased caffeine ingestion. Trained subjects (n = 6) were challenged with 500 mg of caffeine followed by prolonged exercise before and after 6 wk of increased caffeine ingestion (500 mg ingested before each daily run). A control group (n = 6) of trained subjects followed the same protocol except for caffeine ingestion. Acute caffeine ingestion resulted in increased plasma epinephrine and decreased respiratory exchange ratio (RER) during exercise. After 6 wk of caffeine supplementation, the epinephrine response to exercise or caffeine plus exercise was decreased, although the latter still resulted in a lower RER value compared with exercise without caffeine ingestion. Activity of key metabolic enzymes (hexokinase, citrate synthase, phosphorylase, and 3-hydroxyacyl-coenzyme A dehydrogenase) from biopsies of the gastrocnemius showed no response to 6 wk of this increased adrenergic receptor stimulation and, on the basis of the lower RER, enhanced fat metabolism. This study suggests that caffeine ingestion by trained subjects causes increases in plasma epinephrine and reduces the RER during exercise. However, habitual stimulation results in a general dampening of the epinephrine response to caffeine or exercise. There was no indication that increased adrenergic stimulation and fat oxidation caused any adaptation in the activity of metabolic enzymes.

Adult↗
PubMed1991

[Vision tests for the severely handicapped].

The methods available for acuity assessment of multi-handicapped persons are limited by lack of verbal, manual and locomotor response indicators. However, eye activity itself, can provide a clue to what is seen. The results in the present study suggest that the preferential looking technique, using gratings as stimuli and eye movements as response indicators, is a useful tool for assessing the acuity of multi-handicapped people. However, acuity testing of multi-handicapped people was very time consuming, and called for many individual adaptations.

Blindness↗
PubMed1990

[Selective screening for hypercholesterolemia. Results from a screening model in general practice].

At present, it appears to be probable that both dietary changes and medicinal treatment can reduce the risk of development of coronary disease in middle-aged men with moderately to severely raised blood cholesterol values. Internationally, the limits for cholesterol intervention are considerably lower than in Denmark. Extensive cholesterol screening is, however, very expensive and the identified persons with high cholesterol values will frequently be found in sex and age groups where the beneficial effect of intervention is probably limited. A model for selective cholesterol screening in high risk groups in general practice is described here. In 20 general practices, all of the men aged 45-59 years belonging to the practice were invited to examination of cholesterol and blood pressure. Plasma cholesterol was measured by means of a Reflotron (results are available within three minutes) and the blood pressure and tobacco consumption were registered. After this, the patient's own general practitioner calculated with each of the persons the risk for development of myocardial infarction within the next ten years and intervention could be commenced immediately. 41% of those invited came for examination. Out of these, 29% had cholesterol values greater than or equal to 7.0 mmol/l (Danish limiting value), 44% greater than or equal to 6.5 mmol/l (limiting value in the remainder of Western Europe), and 5% greater than or equal to 9.0 mmol/l (severe hypercholesterolaemia) while only 18% had completely normal cholesterol less than 5.2 mmol/l. In every practice, two patients on an average were found with severe hypercholesterolaemia greater than or equal to 9.0 mmol/l. 28% of the participants had at least two of the three risk factors investigated. (ABSTRACT TRUNCATED AT 250 WORDS)

Denmark↗
PubMed1990

[Formalized dietary advice in hypercholesterolemia. Results in 110 men diagnosed by selective screening in general practice].

In connection with a screening investigation for high blood cholesterol in middle-aged men in general practice in the Municipality of Copenhagen, all participants with cholesterol values greater than or equal to 7.5 mmol/l were given brief advice by their own general practitioner and were invited to come for fasting blood lipid tests approximately ten days later. In cases with continued cholesterol greater than or equal to 6.8 mmol/l, the participants together with wives or partners were invited to formalized dietary advice in small groups. Already before the formalized dietary advice, an average decrease in serum cholesterol of 10% was observed. This was attributed to biological variation, absence of fasting, the degree of error between the measuring methods and also a genuine decrease on the basis of the brief dietary advice by the general practitioner. On control after dietary advice, a further decrease in cholesterol of 15% was observed while low density lipoprotein cholesterol fell by 20% and triglycerides by 23%. These decreases must be considered to result mainly from the dietary advice. It is concluded that a single but professional session of dietary advice in small groups and with involvement of the wives or partners is an effective method of treatment in hypercholesterolaemia. If the decrease in cholesterol obtained can be maintained, the literature suggests that the risk of development of ischaemic heart disease during the subsequent 5-7 years is reduced by 20-30%.

Denmark↗
PubMed1990

[Measurement of blood cholesterol, decentralized, using a Reflotron, or centralized in a laboratory. A comparison].

In connection with an extensive screening programme for blood cholesterol, the cholesterol values in 105 participants were measured on a sample of capillary blood employing a Reflotron and, simultaneously, samples of venous blood were examined by conventional enzymatic analysis in a laboratory. Whereas the day-to-day variation and the scatter involved were quite limited in the laboratory, the variation scatter between the two methods of measurement was 0.65 mmol/l. This figure was, however, no greater than that described between different laboratories in USA. Nevertheless, it is an important problem with the Reflotron method that even slight deviations from the recommended procedure of withdrawing blood involve a systematic risk for erroneously low cholesterol results.

Blood Chemical Analysis↗
PubMed1990

[Screening for cardiovascular risk factors in a large workplace].

A screening investigation was carried out in a large industry in the Copenhagen region and 1,472 of the employees were offered examination of blood cholesterol and measurement of blood pressure. At this examination the employees completed a one-page questionnaire about other cardiovascular risk factors. 45% of those invited participated in the investigation, the poorest participation was among women and the greatest among the male officials. On account of the limited number of female employees, the majority of results were only calculated for men. Over 1/3 of these had hypercholesteremia (greater than or equal to 7.0 mmol/l) and nearly 1/3 had, simultaneously, at least two cardiovascular risk factors in addition to age and male sex. Extensive occupational investigations under the auspices of WHO have demonstrated that energetic intervention at the place of work aimed at the cardiovascular risk factors can reduce the risk of development of coronary heart disease and death within a six-year follow-up period. It is therefore emphasized that similar interventions are very necessary also in Denmark.

Adult↗
PubMed1990

Microenvironmental organization and stromal cell associations of B lymphocyte precursor cells in mouse bone marrow.

B lymphocyte precursor cells expressing B220 glycoprotein have been examined in mouse bone marrow (BM) by the in vivo binding of monoclonal antibody (mAb) 14.8 visualized by light and electron microscope radio autography. Young mice were injected intravenously with 125I-labeled mAb 14.8 and then perfused to remove unbound antibody. Quantitative analysis of radioauto graphic sections of femoral BM revealed many labeled mAb 14.8-binding cells which were situated both singly and in groups throughout the extravascular BM parenchyma. Groups of large 14.8+ cells were located in patchy areas in the peripheral regions of the BM near the endosteum. These cells were shown to include proliferating precursor B cells by using mice given vincristine sulfate to stop cells in metaphase and mice treated from birth with anti-IgM antibodies to delete mature B lymphocytes. Electron microscopy revealed clusters of 14.8+ cells intimately associated with the processes of stromal reticular cells. Other 14.8+ cells were in close contact with macrophages; in some instances the intervening cell membranes were indistinct and the macrophages contained 14.8+ material in their cytoplasm. In addition, 14.8+ small lymphocytes were highly concentrated within the lumen of some sinusoids. The present method of detecting B lineage precursor cells in situ has led to a working model of the microenvironmental organization of primary B cell genesis in vivo. The model proposes (a) a centrally directed sequence of differentiation initiated by early precursor cells situated peripherally near the surrounding bone; (b) close associations between precursor B cells and stromal reticular cells; (c) deletion of ineffective B cells by macrophages, and (d) an intravascular maturation phase before B lymphocytes are finally delivered into the blood stream.

Animals↗
PubMed1990

Opioid-like immunoreactants in human cervical cancer.

Cervical carcinoma cell lines produce several polypeptide hormones. While screening human cervical cancers for such factors we have found many tumors to be immunoreactive for opioid peptides. The tumors were collected at surgery or prior to actinotherapy, fixed in buffered formalin, paraffin-embedded, and immunocytochemically stained using the PAP method. The localization of opioid-like immunoreactivity was investigated using a primary antiserum recognizing the Tyr-Gly-Gly-Phe sequence common to all known opioid peptides. The presence of neuropeptide Y (NPY) and peptide histidine methionine (PHM), both known to be present in normal human cervical tissue, was also investigated using specific antisera. Controls included staining controls and absorption controls, using Sepharose-coupled antigen and were all negative. Out of 40 cervical carcinomas, 27 displayed varying numbers of opioid-immunoreactive cells. In 12 normal cervical specimens no specific staining was observed. None of the tumors displayed any NPY-like or PHM-like immunoreactivity. The growth of cervical carcinoma seems therefore to be accompanied by a destruction of the local peptidergic innervation of blood vessels and smooth muscle cells. The demonstration of opioid-like immunoreactants and the known immunoregulatory properties of these peptides, indicate that opioid peptides may be important in the regulation of growth of human cervical carcinoma.

Adult↗
PubMed1990

Correlation of abdominal ultrasound and computed tomography scans with second- or third-look laparotomy in patients with ovarian carcinoma.

To determine the best noninvasive means of evaluating response in patients with advanced ovarian carcinoma, 50 abdominal ultrasound (US) and computed tomography (CT) scans were performed in clinically disease-free ovarian cancer patients. The scans were correlated with the results obtained at a subsequent second- or third-look laparotomy. CT and US were not complementary, and only metastases larger than 2 cm were detected. The overall positive predictive value of nonconcordant scans was 57% compared with 100% for concordant CT and US (95% confidence limits: 18.4-90.1 and 29.2-100%, respectively). The corresponding negative predictive values were 45 and 47% (30.2-59.9 and 30.4-61.2%, respectively), if undetected microscopic disease was classified as a false-negative result. The negative predictive value of US and CT increased only to 60% in both cases, if undetected microscopic disease was registered as a true-negative result. Compared with the pelvic examination CT and US added positive information for 4 of 22 (18%) patients with macroscopic residual disease. In this study neither CT nor US was sensitive enough to preclude second-look laparotomy.

Abdomen↗
PubMed1990

HMG I-like proteins from leaf and nodule nuclei interact with different AT motifs in soybean nodulin promoters.

Three different nuclear factors recognizing short AT-rich DNA sequences were identified in different organs of soybean. One factor (NAT2) was found to be present in mature nodules, another factor (NAT1) was detected in roots and nodules, and a third one (LAT1) was only observed in leaves. All three factors recognized several DNA sequences in the promoter region of the soybean nodulin N23 gene. Footprinting, deletion, and point mutation analyses revealed different binding properties for all three factors and further showed that even single base pair substitutions had a dramatic effect on binding affinity. The LAT1 and NAT1 factors were released from chromatin by extraction with a low-salt buffer and were soluble in 2% trichloroacetic acid, implying a relationship to high-mobility group (HMG) proteins. DNA binding studies further indicated a functional relationship of these factors to the human HMG I protein. Purification of the LAT1 factor from leaf nuclei revealed the presence of two polypeptides with molecular masses of 21 kilodaltons and 23 kilodaltons, respectively, binding the same DNA sequence with equal affinity.

Base Sequence↗
PubMed1990

Early B-lymphocyte precursor cells in mouse bone marrow: subosteal localization of B220+ cells during postirradiation regeneration.

The localization of early B-lymphocyte precursor cells in the bone marrow of young mice has been studied during recovery from sublethal whole body gamma-irradiation (150 rad). Initial studies by double immunofluorescence labeling of the B-lineage-associated cell surface glycoprotein, B220, and of mu heavy chains in bone marrow cell suspensions, demonstrated a sequential wave of regeneration of early B precursor cells, pre-B cells, and B cells. Early B precursor cells expressing B220 but not mu chains were enriched at 1-3 days following irradiation. After in vivo administration of 125I-labeled monoclonal antibody 14.8 to detect B220+ cells in situ, light and electron microscope radioautography of femoral bone marrow sections revealed concentrations of labeled B220+ cells located peripherally near the cortical bone at 1-3 days following irradiation, increasing in numbers in more central areas by 5-7 days. Proliferative B220+ precursor cells were found within layers of bone-lining cells and in a subosteal area characterized by a prominent electron-dense extracellular matrix, often associated with stromal reticular cells. The results demonstrate that the precursor cells that are active in the bone marrow early in the recovery of B lymphopoiesis after gamma-irradiation are located both within and near the endosteum of the surrounding bone. The distinctive extracellular matrix and stromal cell associations noted in this region may contribute to a supportive local microenvironment for early hemopoietic progenitor cells.

Animals↗
PubMed1978

Demonstration of rotatory instability in injured knees by stress radiography.

Rotatory instability of injured knees may be demonstrated by stress radiography by recording the different movements of the medial and lateral tibial condyle at pull or push with the knee in 90 degrees flexion. The displacements of the condyles are expressed in millimetres, not degrees. Comparison with the healthy knee is always used. The displacement of a tibial condyle has to exceed 3.0 mm in relation to the healthy knee to be defined as pathological. If the movements of both condyles exceed the movements in the healthy knee by more than 3.0 mm in the same direction a drawer sign is present--if only one of them moves, an abnormal rotation is present. When a drawer sign is present there may still be a greater displacement of one of the tibial condyles which means a rotatory instability added to the drawer sign, designated a complex rotatory instability. All types of rotatory instabilities, simple and complex, are defined and discussed, in relation to the classification of Nicholas, Trickey and Slocum & Larson. Forty-one cases of abnormal rotation were demonstrated in this series by stress radiography. The direction of rotation and the type of instability are described and compared with the operative findings. The findings are in agreement with those of the above-mentioned authors and the experimental work of Warren et al.

Humans↗
PubMed1977

A clinical and stress radiographical follow-up investigation after Jones' operation for replacing the anterior cruciate ligament.

Measurements have been made on knee radiographs exposed during stress displacement by controlled hydraulic forces using a specially designed apparatus. This accurately records the amount of anterior and posterior tibial displacement (drawer sign) and the degree of medial and lateral collateral ligament laxity on radiographs. The findings in 25 patients have been analysed following the Jones' procedure for the repair of the anterior cruciate ligaments. The operative results were judged to be completely successful in 72% of patients and the value of stress radiographic measurements is discussed.

Adolescent↗