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Biomedical subjects

G Jacobsen

Publications and source records attributed to G Jacobsen.

At least 109 records · Page 6Linked to original sources
PubMed1990

Localization of virus and antibody response in mice infected persistently with MHV-JHM.

Suckling mice infected intranasally with MHV-JHM and nursed by immunized dams develop a late onset demyelinating encephalomyelitis. Analysis by in situ hybridization revealed that MHV-JHM entered the central nervous system (CNS) via the olfactory and trigeminal nerves and spread over the next two weeks to the spinal cord, prior to amplification at this site. Serial measurements of neutralizing antibody titers showed that the late onset disease developed in some mice at levels of antibody which protected mice from the fatal, acute encephalitis, supporting the notion that cell-mediated and not humoral immunity is important in protecting mice from MHV-JHM persistence.

Animals↗
PubMed1990

Identification of the spinal cord as a major site of persistence during chronic infection with a murine coronavirus.

After intranasal inoculation, mouse hepatitis virus (MHV) gains entry into the central nervous system (CNS) via the olfactory and trigeminal nerves. Under the appropriate conditions, some mice develop clinically apparent demyelinating encephalomyelitis several weeks later, with virus always present in the spinal cord. To determine the pathway by which virus reaches the cord, brains and spinal cords of infected, asymptomatic mice were analyzed by in situ hybridization. Viral RNA was always detected in the anterior part of the upper spinal cord. A similar analysis of mice with the recent onset of hindlimb weakness showed that viral RNA was detected in the same location. The results suggest that MHV is transported to the spinal cord via well-defined neuroanatomic pathways and that viral amplification with resultant clinical disease occurs from this site of persistence in the anterior spinal cord. This process of viral amplification may involve the generation of viral variants as has been described for MHV-infected rats. No major changes in viral RNA or protein could be detected when MHV isolated from mice with hindlimb paralysis was analyzed. The data suggest that the generation of viral variants is not important in the pathogenesis of the late onset of neurological disease induced by MHV in mice.

Animals↗
PubMed1990

Variability of symphysis-fundus height measurements: an experimental study among general practitioners.

With the aim of evaluating the impact of supervised training during a postgraduate course in obstetrics and gynaecology, the variability of symphysis-fundus (SF) height measurements was studied by a group of general practitioners (GPs), all of whom provided primary antenatal care. A nested analysis of variance was used. The SF height measurements of the group differed significantly from those of a senior obstetrician and the course training had no impact on the variability. Similar studies should evaluate measurement variability in the light of pregnancy outcome.

Adult↗
PubMed1990

Multiparametric deoxyribonucleic acid and cell cycle analysis of breast carcinomas by flow cytometry. Clinicopathologic correlations.

Using intact ethanol-fixed cytokeratin monoclonal (CAM 5.2) and propidium iodide dual-stained cells, we have performed two-color multiparametric flow cytometric (FCM) DNA analysis and S-phase fraction (SPF) determination on 165 mechanically dissociated breast carcinomas. Sixty-seven patients were axillary node positive, 33 patients node negative; 59 had biopsy only and in 8, FCM was performed on tissue from metastatic lesions. Overall, 62% of the tumors contained aneuploid cell populations. Abnormal cellular DNA content (aneuploidy) was significantly correlated with high nuclear grade (p less than 0.001), lack of estrogen receptors (p less than 0.001), presence of vascular invasion (p less than 0.04), high histologic grade (p less than 0.04), and tumor size (p less than 0.03) but not with patient age (p greater than 0.07) or axillary node status (p greater than 0.50). SPF values derived from ungated histograms had a positively skewed frequency distribution (range 2 to 30%, N = 152) with an overall median of 11% (diploid, 8.9%; aneuploid, 15.7%). Higher SPF values were significantly correlated with aneuploidy (p less than 0.001), presence of necrosis (p less than 0.001), lack of estrogen receptor (p less than 0.0001), high nuclear grade (p less than 0.001), vascular invasion (p less than 0.003), tumor size (p less than 0.006), and high histologic grade (p less than .004) but not the presence of lymph node metastases (p greater than 0.56). Mean SPF values were significantly higher when calculated from cytokeratin gated DNA histograms (14.1% versus 11.5%, p less than 0.001), probably due to exclusion of contaminating stromal/inflammatory cells; and significantly lower when calculated from debris subtracted histograms (7.8% versus 11.4%). Cytokeratin gated and debris subtracted SPF values both had a greater degree of correlation than ungated values with clinicopathologic factors of known prognostic significance.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1990

The frequency of aneuploidy in cultured lymphocytes is correlated with age and gender but not with reproductive history.

The clinical significance of low numbers of aneuploid cells in routine cytogenetic studies of cultured lymphocytes is not always clear. We compared the frequencies of chromosome loss and gain among five groups of subjects whose karyotypes were otherwise normal; these groups were (1) subjects studied because of multiple miscarriages, (2) parents of live borns with autosomal trisomy, (3) subjects studied because they had a relative with Down syndrome, (4) an age-matched control group of phenotypically normal adults studied for other reasons (e.g., parent of a dysmorphic child or member of a translocation family), and (5) other mostly younger and phenotypically abnormal subjects who could not be assigned to the first four groups (e.g., individuals with multiple congenital anomalies or mental retardation). No significant age, sex, or group effects were observed for autosomal loss (hypodiploidy) or gain (hyperdiploidy). Autosomal loss was inversely correlated with relative chromosome length, but autosomal gain was not. Sex-chromosome gain was significantly more frequent in females than in males, but sex-chromosome loss was not significantly different between the sexes. Significant age effects were observed for both gain and loss of sex chromosomes. When age and sex were accounted for, the frequencies of sex-chromosome loss and gain were not significantly different among the five clinical groups. In general, low numbers of aneuploid cells are not clinically important when observed in blood chromosome preparations of subjects studied because of multiple miscarriages or a family history of autosomal trisomy.

Abortion, Spontaneous↗
PubMed1989

Relationship of spontaneous regional lymph node metastases to dose of local irradiation of primary B16 melanomas.

We evaluated the effects of local X-irradiation on microscopic or small macroscopic primary melanomas in the feet of C57BL/6 mice and the subsequent development of spontaneous femoral lymph node (LN) metastases. Doses of 30, 40, 55, 62.5, or 72.5 Gy often cured the foot tumor and metastases to regional femoral lymph nodes were relatively uncommon. Doses of 3.75, 7.5, 10, 15, and 20 Gy were associated with a dose-dependent regrowth delay of the foot tumor treated at microscopic size. Foot melanomas that were not cured spread to regional femoral LNs more frequently (P less than 0.001). The relative risk of developing femoral LN metastasis increased 2.55 times for each 1-mm increase in the anteroposterior diameter of the primary foot tumor in mice with 20 days of primary tumor exposure and increased 4.87 times for each 1-mm increase in mice with 100 days of primary tumor exposure. Although tumors treated with subcurative doses of irradiation had a longer period of time to metastasize to regional LNs for each 1-mm increase in primary tumor size, this variable alone did not account for the increased incidence of metastasis seen with irradiation.

Animals↗
PubMed1989

Spread of a neurotropic murine coronavirus into the CNS via the trigeminal and olfactory nerves.

The route of entry into the central nervous system (CNS) of most neurtropic viruses has not been established. The coronavirus, mouse hepatitis virus strain JHM (MHV-JHM), causes acute encephalomyelitis and acute and chronic demyelinating diseases and is an important model system for virus-induced neurological disease. Suckling C57BL/6 mice infected intranasally with MHV-JHM develop either the acute encephalomyelitis or a late onset, symptomatic demyelinating encephalomyelitis, depending on whether they are nursed by unimmunized or immunized dams. Analysis by in situ hybridization was used to determine the route of entry of MHV-JHM into the CNS in these mice. At early times, viral RNA was detected only in the trigeminal and olfactory nerves and in their immediate connections in all mice. A few days later, MHV-JHM RNA was found throughout the brain in mice dying of the acute encephalomyelitis, but remained confined to the entry sites in mice which did not develop acute disease. These results suggest that MHV-JHM enters the CNS via an interneuronal route in all mice, but that the presence of maternal antibody prevents the dissemination of virus via extracellular fluid. In addition, MHV-JHM may establish low-level persistence in the trigeminal or olfactory nerve or in one of its connections in mice that do not develop acute encephalomyelitis.

Acute Disease↗
PubMed1989

Developing retina and PNS segments for transplantation into the adult host eye: reconstruction of the mammalian visual system. 1. Methodology.

Various techniques have been explored to determine the uses and limitations of techniques that enable the adult CNS to regenerate, but relatively little attention has been given to the consideration of a "reconstructed" visual system. Using this approach, one can design experiments to study the uses of exogenous tissues in reestablishing neuronal circuits that have been damaged. Toward this end, experiments were designed to determine whether embryonic retinal ganglion cells can project axons into a grafted PNS "bridge", and enter adult host targets that were partially deafferented. Embryonic eyes of E11, E14, E18 and E21 rats were sutured to peripheral nerve segments which served as bridges between the host eye and frontal cortex. Projections between the developing retina and the host brain could then be evaluated using HRP tracing techniques. From a methodological standpoint, the preparations are 65% effective; i.e., a viable bridge results between the embryonic eye and the host forebrain. The results presented in the accompanying paper demonstrate that the technique can yield results indicative of embryonic retinal development and axonal projection through the graft and into the host brain. This partial reconstruction of the visual system may prove a useful tool in understanding the uses and limitations of grafting in the CNS.

Animals↗
PubMed1989

Developing retina and PNS segments for transplantation into the adult host eye: reconstruction of the mammalian visual system. 2. Results.

The previous companion paper detailed a technique which allowed embryonic retinal ganglion cell axons to grow from the anterior eye chamber across a PNS bridge, and enter the adult host forebrain. Embryonic eyes of E11, E14, E18 and E21 animals were sutured to a PNS bridge, the embryonic eye implanted into an adult host eye, and the distal end of the bridge implanted into the host forebrain. Results indicate that when eyes of all ages are used for implantation, axons could be observed to grow from the embryonic retina, through the bridge and into the adult host forebrain. The axons extend for long distances in the host brain, reach various layers of the cortex and in a few animals enter the caudate/putamen complex. Control studies show that the bridge is used exclusively as the conduit to the brain, as opposed to the degenerated host optic nerve. Thus, the results presented in this paper indicate that successful grafting and transplantation is possible using the aforementioned technique. The results suggest that the described visual system reconstruction technique can be used for the study of development and transplantation in this system.

Animals↗
PubMed1989

Role of endogenous brain kinins in the cardiovascular response to intracerebroventricular melittin.

Intracerebroventricular infusion of the peptide melittin increases immunoreactive kinins in the cerebrospinal fluid of anesthetized dogs, probably secondary to activation of brain or cerebrospinal fluid kininogenases. Intracerebroventricular melittin also increases blood pressure and heart rate, possibly mediated by brain kinins, since intracerebroventricular bradykinin also increases blood pressure and heart rate. We tested whether the effects of centrally administered melittin on blood pressure and heart rate could be blocked by simultaneous infusion of a kinin receptor antagonist, [DArg0]Hyp3-Thi5,8[DPhe7]bradykinin, in normotensive awake rats. In the controls, intracerebroventricular infusion of kinin receptor antagonist given for 1 hour at a rate of 10 micrograms/hr blocked bradykinin-induced increases in blood pressure and heart rate by 80%. Basal blood pressure and heart rate were not affected by the kinin receptor antagonist alone. After a 30-minute infusion of melittin (8 micrograms/30 min), cerebrospinal fluid kininogenase activity (n = 17) rose from 0.13 +/- 0.05 to 0.43 +/- 0.1 ng/ml/min (p less than 0.02). Although cerebrospinal fluid kinins increased from below sensitivity (0.02 ng/ml, n = 12) to 0.19 +/- 0.1 ng/ml (n = 17), this change was due to drastic increases in three rats, whereas in 12 of them kinins were below sensitivity. Incubation of bradykinin (10 ng) with 0.1 ml rat cerebrospinal fluid for 5 minutes destroyed 70% of kinins, suggesting that rapid destruction may have made detection of increased CSF kinins difficult.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Preliminary results from the Collaborative Alabama and Scandinavian Study of Successive Small-for-Gestational Age Births.

The study "Successive Small-for-Gestational Age Births" (SGA study) was initiated and is sponsored by the National Institutes of Health (N.I.H.) in the U.S.A. Its purpose is to describe and characterize the different types of intra-uterine growth retardation and their consequences, to assess the associated risk factors, and to provide a basis for preventive measures. Starting in 1986, it runs concurrently in Bergen and Trondheim (Norway), Uppsala (Sweden) and Birmingham, Alabama (U.S.A.), recruiting pregnant para 1 and 2 mothers at high risk of having an SGA birth and a random (control) sample of the total pregnant population. Data collection will end in late 1989, when the last-born children have reached 13 months of age. At the present symposium, investigators from all four study centers and the N.I.H. described the study design and discussed problems of methodology. Strict standardization of parameters to determine gestational age (ultrasound, menstrual dates) is a prerequisite for comparison of results over time and between study centers. Some preliminary results were presented.

Alabama↗
PubMed1989

Antenatal care in general practice, Trondheim, Norway.

In this study from the city of Trondheim during 1979-81 nulliparae were found to be younger, higher educated, and more actively working outside the home than parous women. Most women were examined by their GP during the first trimester, and were seen about 10 times on average during the pregnancy. Women who smoked tended to consult later in pregnancy than the non-smokers. Drugs were prescribed for 33% of the women during their pregnancy, 10% during the first trimester. Medication was most frequently prescribed for genitourinary disorders. Sick leave was often the result of low-back-pain and lasted on average 5 weeks longer in parous women. Hospitalization was most often due to hypertension and threatened premature labour and lasted on average longer among nulliparae. Controlled trials are needed to evaluate future antenatal care provision in the light of pregnancy outcome.

Absenteeism↗
PubMed1988

Regional localization of virus in the central nervous system of mice persistently infected with murine coronavirus JHM.

Suckling C57BL/6 mice infected with mouse hepatitis virus strain JHM (MHV-JHM) develop either a fatal acute encephalomyelitis or a late onset demyelinating disease, depending on whether they are nursed by unimmunized or immunized dams. To determine the localization of virus-specific RNA, serial sections of brains from infected and uninfected mice were annealed with a 35S-labeled antisense RNA probe and analyzed by film autoradiography. In the mice with acute encephalomyelitis, viral RNA was present in the mesencephalon, hypothalamus, hippocampus, basal ganglia, subcortical white matter, and thalamus. Viral RNA was detected in the spinal cords of all mice with the late onset, demyelinating encephalomyelitis, but was distributed into three different patterns in the brains of these mice, even though all had the same clinical disease. In the first group, viral RNA was detected only in the brainstem. In the second group, viral RNA was detected in the brainstem, thalamus, and cerebral grey matter. This distribution was consistent with viral spread along well-defined tracts connecting these parts of the brain. In the third group, viral RNA could be detected both in the brainstem and in several white matter tracts within close physical proximity to the optic chiasm. This distribution was consistent with viral spread by an extracellular route from one white matter tract to other tracts which were physically close, but which were not part of the same pathways. These results suggest that MHV-JHM spreads through the central nervous system both along well-defined neuronal pathways and by spread from contiguous structures, but also suggest that viral replicates preferentially in a limited number of areas of the brain. The technique of in situ hybridization with film autoradiography should be generally useful for analyzing macroscopic movements of virus within infected organs.

Animals↗
PubMed1988

The effect of practical training in obstetrics among medical students: symphysis-fundal height measurements.

In a study to evaluate the repeatability of symphysis-fundal (SF) height measurements by medical students, and the effect of practical training in obstetrics on this repeatability eight medical students and an obstetrician initially measured the SF height three times each in six pregnant women. The students were then split into two groups: a training group and a control group. After a training period at the University Hospital in Trondheim, another series of measurements were taken on another group of pregnant women. For comparison of results analysis of variance was used. Within and between observer variation are presented, and the results showed that the practical training had a positive effect on the repeatability of SF height measurements.

Education, Medical, Undergraduate↗