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Biomedical subjects

G Nyberg

Publications and source records attributed to G Nyberg.

At least 127 records · Page 7Linked to original sources

Erythrocyte gangliosides act as receptors for Neisseria subflava: identification of the Sia-1 adhesin.

Neisseria gonorrhoeae was recently shown to bind to a subset of lactose-containing glycolipids (N. Strömberg, C. Deal, G. Nyberg, S. Normark, M. So, and K.-A. Karlsson, Proc. Natl. Acad. Sci. USA 85:4902-4906, 1988). A number of commensal Neisseria strains were also shown to be lactose binders. In addition, Neisseria subflava bound to immobilized gangliosides, such as hematoside and sialosyl paragloboside, carrying the NeuAc alpha 2-3Gal beta 1-4Glc sequence. To a lesser extent, N. gonorrhoeae also bound to this receptor in vitro. In N. subflava GN01, this binding property mediated agglutination of human erythrocytes in a neuraminidase-sensitive fashion. Nitrosoguanidine-induced nonhemagglutinative mutants of N. subflava GN01 had lost the ability to bind hematoside and sialosylparagloboside but remained able to bind lactosylceramide and gangliotetraosylceramide. These mutants fell into three classes with respect to their outer membrane protein profiles in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Class 1 mutants were identical to the parent strain save for the loss of a 27-kilodalton (kDa) protein. Class 2 mutants showed an outer membrane protein profile identical to that of the wild type, whereas mutants belonging to class 3 showed a number of changes, including the apparent absence of the 27-kDa protein. The 27-kDa protein from N. subflava GN01 was purified from the supernatant. A polyclonal antiserum to the purified Sia-1 protein as well as a Sia-1-specific monoclonal antibody inhibited hemagglutination by strain GN01. The purified Sia-1 protein in the presence of diluted anti-Sia-1 antiserum mediated a neuraminidase-sensitive hemagglutination. The purified Sia protein from a class 2 mutant was not able to hemagglutinate when cross-linked with antibodies, suggesting that it is a mutant form of Sia-1 affected in the receptor-binding site. Immunoelectron microscopy with a Sia-1-specific monoclonal antibody revealed that the adhesin was nonfimbrial in nature, with aggregates of the adhesin extended out from the cells in a patchy fashion.

Agglutination Tests↗

Transplantation in patients with diabetic nephropathy. Outcome of combined pancreas and kidney transplantation compared with kidney transplantation only.

Detailed results of 12 combined pancreas and kidney transplantations (Comb) were compared with those of two matched diabetic controls per patient--one living donor kidney recipient (LD) and one cadaveric donor kidney recipient (CD--who, though eligible for pancreas transplantation also, preferred kidney transplantation only. Mean follow-up was 22, 23, and 21 months in the three groups. There was no mortality in the LD group, but two CD and one Comb patient died from cardiovascular disease. Two kidneys were lost in both the Comb and the LD group, compared to five in the CD group. Ten major vascular events occurred and three of them were lethal. The only LD case was one below-knee amputation; the other nine were equally distributed in the Comb and CD groups. The time spent in the hospital was shorter for the LD group. Thus, in the short run, LDs confer the best results, whereas in the long term the better metabolic control in the Combs may prove favorable.

Adult↗

Renal transplantation in patients with systemic lupus erythematosus: increased risk of early graft loss.

The outcome of primary renal transplantation in 31 SLE patients was evaluated in relation to two contemporary controls per patient, matched for age, sex and immunosuppressive therapy. The proportion of living donors was one third in both groups. Patient survival did not differ, but graft survival at 6 and 12 months post transplantation was significantly reduced in SLE patients (p less than 0.001). When divided into groups using either azathioprine and steroids or combinations including cyclosporin A (14 and 17 SLE patients in each group), graft survival was significantly reduced for the azathioprine-treated SLE patients, 36% vs. 82% for their controls at one year. For cyclosporin-treated SLE patients, one-year graft survival was 59% vs. 85% for their controls, and 6 out of 17 grafts in the cyclosporin-treated group were lost within the first month vs. only 4 out of 34 controls. These differences were, however, not statistically different. Most failed grafts were lost from rejection, with a high proportion of acute vascular rejection, isolated or in combination with cellular rejection. There was no apparent association between rejection and HLA-matched or presence of HLA antibodies. Retransplantation was successful in 6 out of 7 cases. We conclude that SLE patients have an increased risk of early graft rejection, but that this may be overcome by more powerful immunosuppressive therapy.

Adolescent↗

Tubulointerstitial nephritis caused by the antiviral agent foscarnet.

The antiviral agent foscarnet has long been used in our unit to treat cytomegalovirus (CMV) infections in renal transplant patients. The clinical effect has been convincing and, apart from changes in serum calcium levels, very few side effects have been noted. We have, however, observed a nephrotoxic reaction in a series of patients with initially good renal function who therefore received high doses of foscarnet. Transplant biopsies performed in five of those patients revealed degenerative changes in the tubular epithelial cells as well as tubular calcium deposits and an infiltration of the interstitium by mixed mononuclear and polymorphonuclear leucocytes. Renal insufficiency was accompanied by high fever. After withdrawal of the drug, the temperature rapidly normalized, whereas serum creatinine continued to rise for about 3 days and then fell back towards previous levels. We conclude that transplant biopsies are of great value in distinguishing between a foscarnet nephrotoxic effect and CMV nephritis, various forms of rejection, and other causes of impaired renal function.

Adult↗

Morphology of diabetic glomerulopathy and relationship to hypertension.

The mutual relationship between elevated blood pressure and structural changes in the kidney is still an area with more open questions than clear answers. Indirect evidence is available concerning one aspect: When hypertension is present it has a significant impact on the further progression of the structural changes. This evidence is available only in terms of the effect of antihypertensive treatment on the preservation of renal function. Since it has been shown that the demise in renal function in long-term diabetics is closely related to the development of advanced diabetic glomerulopathy, it seems likely that normalization of the blood pressure leads to a slowing of this development. Structural studies to elucidate these interactions are, however, not available. An intriguing question is whether the relationship is interactive also in the other direction. Focusing on the alterations within the glomeruli, the fact is that the glomerulopathy develops over several years before it come to the stage when clinical signs appear. Thus, diabetics with "incipient nephropathy" clearly demonstrate basement membrane (BM) accumulation, showing as increased BM-thickness and increase in mesangial matrix volume. Since this is the most likely point of time for hypertension to develop the necessary condition obtains, that the development of hypertension might be triggered by structural abnormalities in the kidney. The mechanisms of action at this point of time remain speculative. The relationship between structural parameters characterizing diabetic glomerulopathy and the blood pressure level was studied in a series of 14 IDDM patients, representing a span of renal functional impairment. Mean blood pressure in the group was 117 mmHg, with a range from 87-122 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

Representation of the forepaw in the feline cuneate nucleus: a transganglionic transport study.

The projection of forelimb nerves innervating the paw to the cuneate nucleus was studied in the cat by the transganglionic transport method. Exposure of a single digital nerve to the tracer (a conjugate of horseradish peroxidase to wheat-germ agglutinin) resulted in a longitudinal sequence of labeled patches throughout the extent of the nucleus. In the middle region the labeled patches coincided with the location of the cell clusters that are characteristic of this part of the nucleus. A very precise somatotopic termination pattern was found in the middle region of the nucleus. Afferent fibers from the palm were represented superficially close to the dorsal rim. The digits were represented in a mediolateral sequence, with the first digit in the dorsolateral part of the nucleus and the fifth digit in the dorsomedial part. The ventral surfaces of the digits were represented superficial to the dorsal surfaces. The dorsum of the paw was represented close to the center of the nucleus. A similar somatotopic organization, but much less detailed, was found in the rostral and caudal regions of the cuneate nucleus. These dissimilarities in somatotopic detail between the different cytoarchitectonic regions of the cuneate nucleus probably reflect differences in function between these regions.

Animals↗

Long-term morbidity in patients where the initial suspicion of myocardial infarction was not confirmed.

The morbidity and mortality during a 5-year follow-up in patients admitted to the coronary care unit with chest pain presenting an initial suspicion of acute infarction, but in whom the diagnosis could not be confirmed, is reported. They were divided into four groups: Possible myocardial infarction (29%), angina pectoris (24%), chest pain of uncertain origin (32%), and nonischemic cause of chest pain (15%). The overall 5-year mortality rate was 13.3% and did not differ substantially between the four groups. During the 5-year follow-up a confirmed myocardial infarction developed in 28% and 22% among patients with the diagnosis possible infarction and angina pectoris, respectively, and in about 10% of the remaining patients. Stroke developed in 4% of patients with possible infarction and in 2-3% in the remaining subgroups. In all, 59% of the patients were rehospitalized for a mean duration of 30 days in hospital. Among survivors at 5 years, 54% reported chest pain equivalent to angina pectoris and 25% had chest pain daily. A high prevalence of angina pectoris, a high frequency of rehospitalization due to chest pain, and a high consumption of cardiovascular drugs could be found in all four groups.

Adult↗

A strong correlation between glomerular filtration rate and filtration surface in diabetic nephropathy.

Quantitative structural studies were performed in kidney biopsy specimens from 24 long-term Type 1 (insulin-dependent) diabetic patients with persistent albuminuria due to diabetic glomerulopathy. Ten patients were receiving antihypertensive treatment, and among the remaining patients the mean blood pressure was 142/91 mm Hg (SD = 11/9). The urinary albumin excretion rate showed a range from 100 to 5494 micrograms/min (geometric mean 688 micrograms/min.) Glomerular filtration rate also showed a wide range, from supranormal to markedly decreased values (128 to 28 ml.min-1. (1.73 m2)-1, mean 75). The filtration surface (interface between capillary and urinary space) per total number of nephrons (open + occluded) was estimated by combined light-and electron microscopy. The percentage occluded glomeruli as well as structural quantities in the open glomeruli were taken into account in this estimate. A highly significant correlation was seen between glomerular filtration rate and filtration surface per nephron (r = 0.77, p less than 10(-4). The percentage occluded glomeruli contributed significantly to the variation in glomerular filtration rate (for this relationship tested separately r = -0.78, p less than 10(-5). The volume of open glomeruli was even larger than that seen in early diabetic glomerular hypertrophy and tended to increase with the percentage of glomerular closure, indicating that a compensatory hypertrophy might have taken place. In the open glomeruli the filtration surface constituted a smaller percent of total capillary surface (the remaining part facing the mesangial regions) than in early diabetic patients and control subjects. Our study has demonstrated that reduced glomerular filtration surface is closely associated with reduced glomerular filtration rate in Type 1 diabetic patients with diabetic nephropathy.

Adult↗

Haemodynamic, anti-anginal and anti-ischaemic effects of sublingual nitroglycerin: dose-response, duration and time of onset of action.

To establish the time of onset of action and magnitude of response to the quickest disintegrating sublingual nitroglycerin tablet available in Scandinavia (Nitromex), nine patients with stable exercise-induced angina were studied whilst performing bicycle exercise tests. In the first session, placebo, 0.25, 0.50 and 0.75 mg sublingual nitroglycerin (Nitromex) was given in a double-blind cross-over fashion on different days. In the second session (1 h after Session 1), nitroglycerin 0.5 mg (Nitromex), placebo and 0.5 mg of a different brand of nitroglycerin were compared for the time of onset of attenuation of ST-segment depression when administered during exercise. In Session 1, there was a dose-dependent fall in systolic blood pressure and a concordant rise in heart rate whilst sitting at rest prior to exercise. Exercise time and ST-segment depression were dose-dependently prolonged, significantly by the two higher doses, (mean 20 and 26%, respectively) which did not differ from one another. In Session 2, nitroglycerin (Nitromex) caused ST-segment reversal after a mean of 123 s after administration, which was shorter than after ordinary nitroglycerin (mean 157 s) and placebo (two tests, 186 and 192 s). It is suggested that when nitroglycerin is administered during exercise, chest pain and ischaemic ECG-changes are largely improved through coronary vasodilatation and reduced afterload rather than through increased venous pooling and reduction in preload.

Aged↗

Identification of carbohydrate structures that are possible receptors for Neisseria gonorrhoeae.

Different strains and isogenic variants of Neisseria gonorrhoeae were assayed for their ability to bind glycolipids extracted from various sources. Among a large number of reference glycolipids, binding was observed only to lactosylceramide [Gal(beta 1-4)Glc(beta 1-1)Cer], isoglobotriaosylceramide [Gal(alpha 1-3)Gal(beta 1-4)Glc(beta 1-1)Cer], gangliotriaosylceramide [GalNAc(beta 1-4)Gal(beta 1-4)Glc(beta 1-1)Cer], and gangliotetraosylceramide [Gal(beta 1-3)GalNAc(beta 1-4)Gal(beta 1-4)Glc(beta 1-1)Cer]. The latter two glycolipids bound gonococci with the highest affinity. Lactosylceramide and gangliotriaosylceramide were found in glycolipid preparations from ME180 cells, an epithelial cell line derived from a human cervical carcinoma, and thus are possible receptors for gonococci. The gonococcal surface component that bound the above glycolipids is a protein distinct from pilin and protein II.

Animals↗

Abrupt withdrawal of isosorbide-5-mononitrate in Durules (Imdur) after long term treatment in patients with stable angina pectoris.

In a single-blind study of 6 weeks' duration, 32 patients with stable angina pectoris, who had been receiving controlled-release, Durules, isosorbide-5-mononitrate (Imdur) 60 to 180 mg daily for at least 1 year, were assessed after abrupt withdrawal of the nitrate. After 2 weeks of placebo treatment nitrate therapy was re-instituted, and the patients followed for another 2 weeks. The possibility of development of tolerance and rebound phenomena was also investigated. Three patients experienced severe anginal symptoms necessitating hospitalization when controlled-release isosorbide-5-mononitrate was withdrawn abruptly. Patients complained of more severe anginal symptoms during the placebo period, experienced more frequent anginal attacks and used more glyceryl trinitrate tablets than during active treatment. ST segment changes during exercise were more pronounced with placebo. After controlled-release isosorbide-5-mononitrate was re-introduced, these variables indicated significant improvement. On the other hand, no deterioration occurred in exercise performance during the placebo phase. Responsiveness to glyceryl trinitrate was maintained, as shown by comparisons of exercise tests performed after the long term treatment and during the placebo phase. Controlled-release isosorbide-5-mononitrate retains a beneficial effect in patients with angina pectoris during prolonged use, although some attenuation of the effect is seen. Abrupt withdrawal of the drug is not recommended because of the possibility of severe exacerbation of anginal symptoms, although no clearcut rebound phenomena were seen.

Acute Disease↗