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Biomedical subjects

A Bergström

Publications and source records attributed to A Bergström.

At least 19 recordsLinked to original sources

Response rate to mailed epidemiologic questionnaires: a population-based randomized trial of variations in design and mailing routines.

Although self-administered questionnaires are major sources of information in epidemiology, comparatively little has been done to study practical aspects of design and mailing. The objective of this study was to evaluate various measures taken to increase the response rate. A questionnaire was mailed in July 1995 to a random sample (n = 2,000) of the Swedish population aged 20-79 years. Using a randomized factorial study design, the questionnaire and mailing procedures were changed in three ways: preliminary notification, length of the questionnaire, and mention of telephone contact. The overall questionnaire retrieval rate was 49%. Preliminary notification (adjusted odds ratio of receiving a completed questionnaire = 1.30, 95% confidence interval (CI) 1.08-1.56 relative to the absence of preliminary notification) and short length of the questionnaire (odds ratio = 1.24, 95% CI 1.04-1.48 relative to a long questionnaire) were both independently associated with a higher retrieval rate. Of eight possible combinations, the one comprising preliminary notification, a short questionnaire, and no mention of telephone contact gave the highest retrieval rate, 56%. The lowest retrieval rate, 40%, was observed for the combination of no preliminary notification, a long questionnaire, and mention of telephone contact. Young age, male sex, and urban residence significantly lowered the retrieval rate. Although there was a positive association between the questionnaire retrieval rate and partial nonresponse (missing answers in retrieved questionnaires), the marginal losses due to the latter did not cancel the gains by optimized mailing routines. Old age was the strongest determinant of partial nonresponse. The data provide evidence that design and mailing strategies, as well as demographic characteristics, may greatly influence the response rate of mailed epidemiologic questionnaires.

Adult

Immediate assessment of HbA1c under field conditions in Tanzania.

In Tanzania, assessment of blood glucose is the most frequently used method for evaluating glycaemic control in diabetic patients. The patients' metabolic control is often poor and the determination of glycated haemoglobin (HbA1c) for long-term control could be a valuable tool to better manage the treatment. The aim of this study was to determine whether an immediate assessment method for HbA1c (DCA 2000 analyzer) gives reliable results in the warm and moist climate of east Africa. The study was performed in two parts. One equipment test in Sweden where blood samples from 65 diabetic patients were analysed in a DCA 2000 kept at room temperature and in another kept in a climate chamber. The samples were also analysed with HPLC as a reference method. In the second part HbA1c was analysed in 159 Tanzanian diabetic patients with a DCA 2000 and with HPLC combined with a filter paper technique (HbA1c via Post). The study showed that the DCA 2000 gives reliable results at 85% humidity and a temperature not exceeding +31 degrees C. The correlation with the HPLC analysis varied between 0.94 and 0.98. The conclusion is that the DCA 2000 analyzer can be used in Tanzania during the winter but has to be placed in an air-conditioned room if the temperature exceeds +31 degrees C.

Adult

Confirmation of nosocomial transmission of hepatitis C virus by phylogenetic analysis of the NS5-B region.

Four hepatitis C virus transmission chains at three dialysis units were disclosed by limited sequencing; three of these were disclosed by analysis of the NS5-B region of the genome. Dialysis on the same shift as that during which infected patients were dialyzed was the common factor for seven patients in two chains. Two nurses exposed to needle sticks and their sources of infection constituted two other chains. The strains of three chains belonged to subtype 1a and formed clusters with an intrachain variability of 0 to 6 nucleotides compared to 8 to 37 nucleotides for unrelated strains within this subtype. The clusters were supported by bootstrap values ranging from 89 to 100%.

Cross Infection

Outcome of clinical foot examination in relation to self-perceived health and glycaemic control in a group of urban Tanzanian diabetic patients.

Diabetic foot complications were studied in 153 patients at the university clinic in Dar es Salaam (56 insulin treated, 77 treated with oral agents and 20 with diet only). Neuropathy disability and symptoms scores were used to diagnose peripheral neuropathy (PN). Peripheral vascular disease (PVD) was classified as ankle/brachial pressure index less than one. The degree of metabolic control was assessed by glycated haemoglobin (HbA1c) and self-perceived health was measured with SF-36. PN was present in 28.1% of patients and 12.5% had PVD. Patients with PN had higher age and later onset of diabetes in comparison with patients without food complications. Patients with PVD had longer duration of diabetes and higher systolic and diastolic blood pressure compared with those free from PVD. HBA1c and body mass index did not seem to influence the occurrence of PN or PVD. Patients with PN had significantly poorer self-perceived health, whilst PVD-patients had health scorings equal to patients without any foot complications. PN, but not PVD, appeared to have a negative influence on patients self-perceived health. In comparison with studies from the industrial world, foot problems are as common in diabetic patients living in a developing country.

Adult

Influence of technique and transplantation site on rosette formation in rabbit retinal transplants.

In order to determine mechanical and host-graft related interactions in the histogenesis of retinal transplants, a new technique for transplanting flat and comparatively large pieces of embryonic rabbit retina into adult rabbit eyes was elaborated. With the procedure, free-floating grafts in the epiretinal space survive, develop and differentiate largely without rosette formation, suggesting that the dissection and transplantation procedure is adequate for obtaining a normal development. On the other hand, subretinal transplants mature at an apparently faster pace than epiretinal transplants, but do not become regularly laminated. Outer segments do not develop well in the epiretinal transplants, whereas they do so in the subretinal ones, suggesting host-graft interactions by means of yet unknown diffusible factors.

Animals

High prevalence of GB virus C strains genetically related to strains with Asian origin in Nicaraguan hemophiliacs.

The presence of hepatitis GB virus C (GBV-C), also known as hepatitis G virus (HGV), and hepatitis C virus (HCV) were investigated in sera from 45 hemophiliacs from nine locations in Nicaragua using a nested polymerase chain reaction (PCR). Primers used to detect GBV-C and HCV derived from the helicase region and 5'UTR, respectively. Seventeen (38%) patients were positive for GBV-C RNA in serum by PCR. Twelve (27%) patients were positive for HCV RNA by PCR. Six (13%) of these were coinfected with GBV-C. Anti-HCV was detected in all the 12 HCV RNA positive hemophiliacs and in another 14 (31%) individuals, in whom GBV-C RNA was found in 2. Ten patients (22%) lacked markers for both GBV-C and HCV. The mean age of the patients positive for GBV-C but negative for HCV by PCR was significantly lower than for those negative for GBV-C but positive for HCV by PCR (P < 0.05; Student's t-test), indicating that the risk for this group of hemophiliacs to acquire GBV-C infection is higher as compared to the risk of acquiring HCV infection. Eleven GBV-C strains were sequenced in the 5'UTR. Sequence comparison to previously published GBV-C strains revealed that all 11 strains were more similar to Asian strains than to strains of European and African origin. Sequences in the NS5-B region were available for 8 HCV strains, all of which were found to belong to genotype 1a. The similarity of the Nicaraguan GBV-C strains to strains from Asia indicates that the GBV-C strains in the region presumably have an Amerindian origin. It is also considered that the HTLV II strains in the New World aboriginal populations are ancient and brought there by the ancestral Amerindian populations from Asia. Further, the genotype F of hepatitis B virus, known to represent the strains in populations with Amerindian background, predominates in Central American populations with Hispanic background. It remains to be clarified why Amerindian strains of GBV-C as well as of HBV predominate also in populations with mixed ethnic background in Central America.

Adolescent

Comparisons of studies on diabetic complications hampered by differences in GHb measurements.

OBJECTIVE: To compare glycated hemoglobin (GHb) values of the relationship between glycemic control and complications of diabetes from laboratories involved in long-term studies (Steno, Oslo, Stockholm, Diabetes Control and Complications Trial, and Linköping.) RESEARCH DESIGN AND METHODS: Blood samples were collected from 25 subjects selected to represent the clinically relevant measurement range. Fresh whole-blood samples were distributed and analyzed within 4 days of sample collection. Pretreatment of samples and analyses of GHb were performed according to the routine method of each study's central or reference laboratory. Results from each laboratory were compared with the group mean, i.e., the mean of all results for each sample. RESULTS: Regression analyses with the group mean values as independent variables and results from each laboratory as dependent variables showed that Oslo's result had a slope significantly different from the group mean. Laboratories used by the DCCT, Oslo, and Steno studies gave, on average, 0.4, 0.4, and 0.7% higher HbA1c readings than the group mean, respectively, while HbA1c results from Linköping and Stockholm were, on average, 0.6 and 1.0% lower, respectively. CONCLUSIONS: There were large differences in GHb values among laboratories participating in studies of diabetic complications. The present data offer a guide to the comparison of results from the studies and underscores the need for standardization of GHb measurements.

Diabetes Complications

The membrane glycoprotein G1 of Uukuniemi virus contains a signal for localization to the Golgi complex.

Members of the Bunyaviridae family acquire their envelopes by budding into the Golgi complex (GC). The accumulation of the membrane glycoproteins G1 and G2 in the GC probably determines the site of maturation. Here we have studied the intracellular transport and targeting to the GC of G1 and G2 of Uukuniemi virus, a member of the Phlebovirus genus, and report on their expression from cloned cDNAs either together or separately by using a T7 RNA polymerase-driven vaccinia virus expression system. When G1 and G2 were expressed together from a full-length cDNA as the p110 precursor, both proteins were localized to the Golgi complex, as evidenced by colocalization with the Golgi marker enzyme mannosidase II. Immunofluorescent staining indicated that G1 expressed alone also localized to the GC. However, pulse-chase experiments showed that G1 remained endoglycosidase H sensitive. G2 expressed alone remained associated with the endoplasmic reticulum (ER). G2 could be rescued from the ER and transported to the GC by coexpression with G1 from separate mRNAs. Coexpression also increased the efficiency of G1 transport to the GC. With none of the constructs could the glycoproteins be observed on the cell surface. These results show that efficient export of G1 and G2 from the ER requires coexpression of both proteins, in conformity with our previous results showing that G1 and G2 form heterodimeric complexes in the ER. Since G1 expressed alone is retained in the GC, we conclude that G1 contains a retention signal for localization to the GC. G2 might thus become associated with the GC indirectly via its interaction with G1.

Biological Transport

Co-transplantation of embryonic retina and retinal pigment epithelial cells to rabbit retina.

The retinal pigment epithelium (RPE) is important for normal development of the neural retina. We sought to investigate whether cografting RPE cells affected the differentiation and survival of retinal grafts. Pigmented embryonic day 16 (E16) rabbit retina was dissected either with or without attached RPE and injected into a lesion site in retinas of young adult rabbit hosts. Each host obtained a pure retina graft in one eye and a retina/RPE cograft in the other. Animals were sacrificed after 4, 8 and 12 weeks. After 4 weeks, grafts (1-2 mm in diameter) were seen in both experimental groups at the lesion site or in the subretinal space. However, 8 and 12 weeks after transplantation, the graft survival rate decreased. The grafts developed cell layers in folded sheets and many rosettes (a rosette consists of photoreceptors and cells of other retinal layers around a central lumen defined by an outer limiting membrane). Cografts of retina with RPE had areas of more distinct cell lamination than transplants of pure retina. Grafted RPE cells were organized in clusters of cells surrounded by extracellular matrix and often associated with blood vessels. If the extracellular matrix of RPE cell clusters was outside the rosettes close to inner retinal layers in the graft, transplant Müller cell endfeet developed an inner limiting membrane. Müller cell endfeet could also be observed in subretinal transplants attached to the denuded Bruch's membrane of the host. In 12-week grafts, when RPE cell clusters were inside rosettes, the surrounded photoreceptors survived better. No RPE effect could be seen if single RPE cells were dispersed among retinal donor cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Reversed ratio of color-specific cones in rabbit retinal cell transplants.

Recently, we have reported on the emergence of various retinal cell types in embryonic rabbit retina transplanted to adult rabbits. When comparing the relative numbers of the spectrally different cone types in the transplants to those in the host or age-matched control retinas, a surprising shift was observed. While in the normal rabbit retina the middle-wavelength-sensitive (M) cones are considerably more abundant than the short-wave-sensitive (S) cones, the S/M cone ratio was found to be the opposite in the graft. The number of rosettes containing only S-cones in high density was found to be considerably higher than that of M-cone rich rosettes. The number of S-cones also exceeded that of the M-cones in each rosette that contained both cell types. Our results were obtained from the systematic immunocytochemical analysis of 15 different transplants derived from transplantations of embryonic rabbit retinas into adult hosts of the same species. The emergence and proportion of the two cone types were followed between 14 and 63 days after transplantation (between 29 and 78 postconceptional days of the donor tissue). Sections from various parts of the transplants were reacted with the monoclonal antibodies COS-1 and OS-2, specific for the middle- and short-wavelength-sensitive cones, respectively. The explanation for the reverse cone ratio in these transplants is not known yet, however, the observed phenomenon may indicate differences between the specification of the two basic cone types.

Animals

Development of cell markers in subretinal rabbit retinal transplants.

Retinas from embryonic rabbits at day E15 were transplanted to the subretinal space in adult rabbits. After survival times between 7 and 193 days, the rabbits were killed, and the transplants were processed for immunohistochemistry. The results show that subretinal transplants from embryonic rabbit retinas develop many, if not all, retinal neuronal types. The cells show approximately normal morphology and express a variety of cell-type-specific markers: photoreceptor cells express visual pigment proteins as identified by antibodies against rhodopsin (R2-15), color-specific cone pigments (COS-1, OS-2) and the cone specific antigen 50-1B11, rod bipolar cells express PKC, horizontal cells HPC-1 antigen and neurofilament 160 kDa, amacrine cells HPC-1 antigen, GABA and neurofilament 160 kDa, and glial cells express vimentin and glial fibrillary acidic protein. The high degree of rosette formation seen in many young grafts, diminishes with time; many transplant cells disappear, and the remaining cells present a less prominent formation of rosettes.

Animals

Interphotoreceptor matrix components in retinal cell transplants.

To further investigate the functional potential of retinal transplants we have used immunocytochemistry to study the distribution of four different interphotoreceptor matrix (IPM)-specific components in rabbit retinal transplants. The different components were: interphotoreceptor retinoid-binding protein (IRBP), chondroitin-6-sulfate, F22 antigen and peanut agglutinin (PNA) binding structures. IRBP acts as a retinoid-transport protein between the neural retina and the retinal pigment epithelium. Chondroitin-6-sulfate is a glycosaminoglycan and a part of the insoluble IPM skeleton. The identity and role of the F22 antigen is not known. However, it is a 250 kDa protein localized to specific extracellular compartments such as teh IPM. PNA is a lectin with a high binding affinity for D-galactose-beta (1-3) N-acetyl-D-galactosamine disaccharide linkages and binds to IPM domains surrounding cones, but not rods. The transplants (15-day-old embryonic rabbit retina) were placed between the neural retina and retinal pigment epithelium in adult hosts. The transplants developed the typical rosette formations with photoreceptors toward the center. IRBP labeling was distinct in the IPM in the host retina. However, no IRBP labeling could be detected in the transplants. The chondroitin-6-sulfate and F22 antibodies strongly labeled the IPM in the host retina and corresponding structures in the center of rosettes. A cone-specific labeling with PNA could be seen in the host retina. In the transplants, however, PNA labeling appeared in association with many more photoreceptors than in the host retina. There is no previous study available on the IPM in retinal cell transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Embryonic rabbit retinal transplants survive and differentiate in the choroid.

Retinal allotransplants to intraocular locations usually survive well, partly because of the relative immune privilege provided by the blood-ocular barriers. The choroid, however, is located outside the barriers, and is therefore usually considered not to be immunologically privileged. This study was performed to investigate if transplants could survive in the choroid, and, if so, if they develop some sort of blood transplant barrier. Embryonic retinas from pigmented rabbits at stage E 15 (embryonic day 15) or E 22 were dissected and transplanted into the choroid of 29 adult animals of the same strain. As controls, a similar retinal transplant was placed in the subretinal space in six animals and in the subconjunctival space in another six animals. The animals were killed at intervals up to 8 weeks and the eyes were analysed by light microscopy, immunohistochemistry and morphometry. Some of the animals received Evan's Blue intravenously before termination. Eighty-three per cent of the choroidal transplants survived until termination. All six subretinal but none of the six subconjunctival transplants survived. Both choroidal and subretinal grafts developed rosettes, i.e. rounded formations of retinal cells organized in layers. The different retinal cells developed normal reactivity for the intracellular markers rhodopsin, neurofilament 160 kDa, vimentin and GFAP. Evan's Blue and endogenous serum albumin were used as markers for the patency of the blood-ocular barriers. Evan's Blue was not excluded from the transplants in the early phase up to day 8 after the transplantation. The Evan's Blue content diminished with longer survival times, and after 40 days almost no Evan's Blue was present in the transplants.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Complementary cone fields of the rabbit retina.

PURPOSE: Complementary cone fields have been considered a unique feature of the mouse retina. In an attempt to map the arrangement of the color-specific cones in other mammals, the authors investigated the rabbit, a commonly used experimental animal for vision research. METHODS: For the identification of the different cone types immunocytochemistry was used with two monoclonal antibodies, each specific to the middle- to long-wave (red-green) and short-wave (blue) sensitive visual pigments, respectively. RESULTS: The major part of the retinal surface, including the visual streak, exhibited a dominance of M (middle-wave sensitive) cones (6 to 13,000/mm2) versus S (short-wave sensitive) cones (1 to 2,500/mm2). In contrast, the lower 5% to 6% of the total retinal area showed a complete lack of green cones and a high density of blue cones (11,000/mm2). The authors designate this crescent-like area the blue streak of the rabbit retina. CONCLUSION: In addition to the visual streak primarily abundant in green cones, there is a specialized area of the rabbit retina that is densely and exclusively populated with blue cones. Although the relative extension of this peculiar cone field is considerably smaller than the S-field of the mouse retina, its position is similar in that it occupies the lowermost part of the retina. The functional implication of this area is unknown.

Animals

Transplantation of embryonic retina to the subretinal space in rabbits.

Embryonic rabbit retina can be transplanted to the subretinal space of adult rabbit with a new method, which gives a high rate of successful short-term transplants. Embryonic (stage E 15) neural retina cells were injected through an incision just behind the sclerocorneal border with a thin (inner diameter 0.15-0.4 mm, outer diameter 0.3-0.5 mm) plastic tube attached to a specially designed instrument, by which the length of the protruding plastic tip could be controlled. The retina was penetrated from the vitreous side and the donor tissue was injected into the subretinal space. The cells survived in the host for at least 5 months, although the long-term survival rate tended to decrease. The transplanted cells matured and differentiated, forming an approximation of the layered, retinal structure with some anomalies (e.g. rosettes). The subretinal location offers an interesting and convenient way of studying the development of retinal cell transplants in rabbits. Large transplants can be produced, and the risk for failures due to erroneous vitreous placement is small.

Animals

Ultrastructure of human retinal cell transplants with long survival times in rats.

Human fetal retinas (6-12 weeks post-conception) were obtained from elective abortions, transplanted to rat retinas and examined by electron microscopy. The oldest transplants that form the basis of this report were obtained 40 and 41 total weeks post-conception. The host rats were immunosuppressed with cyclosporin A. The transplants developed according to their intrinsic, genetically determined timetable. The development was heterogeneous with some parts showing almost normal differentiation and others, little. Both rods and cones developed with inner and outer segments and synaptic terminals. In regions corresponding to the inner plexiform layer, bipolar cell processes were seen in the typical dyad arrangement. Likewise, amacrine cell processes formed typical conventional synapses. Serial synapses were seen, engaging amacrine cell synapses as well as a few reciprocal synapses at the bipolar cell dyads. Monad-type synaptic complexes, a sign of immaturity, were common in bipolar cell processes. Similarly, incompletely differentiated synapses of both the amacrine and bipolar cell types were often observed. Ganglion cell processes could not be identified with certainty. A structure with morphological characteristics similar to the inner limiting membrane was noted to form inside the transplant. Both epi-retinal and sub-retinal transplants were obtained. Transplant cells touched host photoreceptor cells or pigment epithelium without any obvious specializations. The host pigment epithelium microvilli were absent adjacent to the graft. However, graft cells did appear in the host retina, and nerve cell processes were observed to cross the membrane separating the transplant and host.

Animals