Biomedical subjects

L I Larsson

Publications and source records attributed to L I Larsson.

At least 19 recordsLinked to original sources

PubMed2002

A comparison of the effects on intraocular pressure of latanoprost 0.005% and the fixed combination of dorzolamide 2% and timolol 0.5% in patients with open-angle glaucoma.

PURPOSE: To compare the effects on intraocular pressure (IOP) of latanoprost 0.005% and the fixed combination of dorzolamide 2% and timolol 0.5%. METHODS: Overall, 226 patients whose IOP was insufficiently controlled by timolol alone were randomized to receive either latanoprost once daily or the fixed combination of dorzolamide plus timolol twice daily. Intraocular pressure was measured at 10:00 am and 5:00 pm at baseline and after 3 months of treatment. RESULTS: Mean IOP was reduced from baseline in both groups (p < 0.001), with a mean +/- SEM reduction of - 4.3 +/- 0.3 mmHg (19%) for the latanoprost treatment group and - 4.0 +/- 0.3 mmHg (17%) for the dorzolamide plus timolol treatment group. The two therapies were similarly effective in lowering IOP levels (mean difference in reduction: - 0.4 +/- 0.4; 95% confidence interval: - 1.1, 0.4). CONCLUSIONS: Monotherapy with latanoprost once daily was as effective in reducing mean IOP as the fixed combination of dorzolamide plus timolol twice daily in patients with IOP insufficiently controlled by timolol alone.

Adult↗

PubMed2001

Aqueous humor flow in normal human eyes treated with brimonidine and timolol, alone and in combination.

OBJECTIVE: To compare the effect on aqueous humor flow and intraocular pressure (IOP) of topically applied 0.2% brimonidine tartrate with topically administered 0.5% timolol maleate, alone and in combination. DESIGN: A randomized, double-masked, placebo-controlled study of 20 human subjects was carried out. The topical drugs were instilled twice daily the day before and again on the morning of the day of the measurements. Aqueous humor flow was measured by clearance of topically applied fluorescein with a fluorophotometer, and IOP was measured with an applanation tonometer. RESULTS: Brimonidine reduced the aqueous humor flow by 33.1%; timolol, by 49.9%; and the combination of brimonidine and timolol, by 58.9%. Brimonidine reduced the IOP by 20.3%; timolol, by 22.9%; and the combination of brimonidine and timolol, by 34.7%. CONCLUSIONS: Brimonidine suppressed aqueous humor flow, but not as effectively as timolol. However, the effects on the IOP of both drugs separately were comparable. The short-term effect of brimonidine was partly additive to timolol, and the combination treatment caused a further reduction in aqueous humor flow and IOP. The IOP reduction by timolol could be explained solely by aqueous humor flow reduction. Much of the IOP reduction caused by brimonidine, but not all, could be explained by suppression of the aqueous humor flow, suggesting an additional mechanism for the ocular hypotensive effect of brimonidine.

Administration, Topical↗

PubMed2001

Expression of SMAD signal transduction molecules in the pancreas.

Members of the TGF-beta superfamily of cytokines have been implicated in pancreatic cancer, pancreatitis and in regulation and differentiation of pancreatic endocrine and exocrine cells. Different TGF-beta members signal through phosphorylation of different signal transduction proteins, which eventually form oligomers with SMAD 4 and translocate to the nucleus. Reverse transcriptase-polymerase chain reaction showed that SMADs 1, 2 and 4 are expressed in pancreatic islets. Immunostaining revealed that SMAD 1 and 4 predominantly were expressed by islet insulin and glucagon cells. Since SMAD 1 is known to transduce signals from receptors binding bone morphogenetic protein (BMP) these results indicate a previously unknown role of BMP-like ligands in islet function.

Animals↗

PubMed2001

Intraocular pressure over 24 hours after repeated administration of latanoprost 0.005% or timolol gel-forming solution 0.5% in patients with ocular hypertension.

PURPOSE: To compare the effect on intraocular pressure (IOP) over 24 hours after 4 weeks of treatment with latanoprost 0.005% and timolol gel 0.5%. DESIGN: Randomized, open, crossover single-center study. PARTICIPANTS: Twenty-seven patients with ocular hypertension. METHODS: The patients were randomly assigned to 4 weeks of latanoprost 0.005% once daily or timolol gel 0.5% once daily, with a 4-week washout period before switching therapy. MAIN OUTCOME MEASURES: Measurement of IOP during 24 hours of hospitalization. Blood pressure and heart rate were also measured repeatedly over the 24 hours. Daytime mean IOP, nighttime mean IOP, and 24-hour mean IOP were calculated as IOP area under the curve (AUC) divided by time in hours. RESULTS: The mean IOP during daytime (7 AM to 10 PM) was 13.5 +/- 0.4 mmHg (daytime IOP, AUC/15 hours, least square mean +/- standard error of the mean [SEM]) in the latanoprost group, and 14.8 +/- 0.4 mmHg in the timolol gel group. This difference of 1.3 +/- 0.3 mmHg was statistically significant in favor of latanoprost (P < 0.001; 95% confidence interval [CI], 0.7, 2.0). The mean IOP at night (10 PM to 7 AM) was 13.7 +/- 0.4 mmHg for latanoprost (nighttime IOP, AUC/9 hours, least square mean +/- SEM) and 15.9 +/- 0.5 mmHg for timolol gel, with a difference of 2.2 +/- 0.3 mmHg (P < 0.001; 95% CI, 1.5, 2.8). At every measured time point during the 24 hours, latanoprost reduced IOP more than timolol. There was no difference between the two treatment groups regarding blood pressure and heart rate. CONCLUSIONS: Latanoprost reduced mean 24-hour IOP, mean daytime IOP, and mean nighttime IOP statistically significantly more than timolol. Also, latanoprost reduced IOP more effectively at every measured time point over the 24 hours compared with timolol gel.

Aged↗

PubMed2001

The effect on diurnal intraocular pressure of the fixed combination of latanoprost 0.005% and timolol 0.5% in patients with ocular hypertension.

PURPOSE: To measure the effect on intraocular pressure (IOP) after single-dose administration of the fixed combination of latanoprost 0.005% and timolol 0.5%. METHODS: A randomized, double-masked placebo-controlled parallel-group study was carried out. Twenty patients with ocular hypertension received the fixed combination of latanoprost+timolol, while 10 received placebo eyedrops. On baseline day no eyedrops were given, but IOP was measured repeatedly between 8.00 a.m. and 8.00 p.m. On Day 7 the eyedrops were given at 8.00 a.m., and IOP measured as on baseline day. On Day 8 and Day 9, IOP was again measured at 8.00 a.m. RESULTS: There was no difference in IOP in the placebo group. In the latanoprost+timolol group maximal IOP reduction (12.4+/-2.8 mmHg; mean+/-standard deviation) occurred 6.4 hours after drug administration (5.2--7.7 hours; 95% confidence interval [CI]). The mean IOP reduction after 24 hours was 9.8 mmHg (7.4--12.2 mmHg; 95% CI; p<0.001), and after 48 hours 5.7 mmHg (3.4--8.1 mmHg; 95% CI; p<0.001). CONCLUSIONS: The fixed combination of latanoprost+timolol statistically significantly reduced IOP after single-dose administration. The maximal effect was noted after about 6 hours, and the IOP reduction was still pronounced after 48 hours.

Adrenergic beta-Antagonists↗

PubMed2001

Increased permeability of the blood-aqueous barrier after panretinal photocoagulation for proliferative diabetic retinopathy.

PURPOSE: To measure the permeability of the blood-aqueous barrier before and after panretinal photocoagulation (PRP) in patients with proliferative diabetic retinopathy. METHODS: Twenty patients with diabetic proliferative retinopathy in one eye and background retinopathy in the other eye were included. PRP was performed in the proliferative eye, while the other eye served as control. Aqueous flare intensity was measured with a laser flare cell meter before, 10 and 90 days after treatment. RESULTS: The flare was stable in the control eye with a flare of 4.5+/-2.3, 4.4+/-2.4, and 4.5+/-1.7 photon counts/ms (mean+/-standard deviation) on Day 0, 10 and 90. In the laser treated eye corresponding figures were 5.2+/-2.4, 9.6+/-3.3, and 7.1+/-2.8 photon counts/ms, with a significant increase in aqueous flare at 10 days (p<0.001) and 90 days (p=0.002). CONCLUSION: A significant increase in aqueous flare was found 10 days after PRP, indicating a breakdown of the blood-aqueous barrier after retinal laser treatment. The breakdown was still present, however, less pronounced, after 3 months.

Adult↗

PubMed2001

Intraocular pressure over 24 hours after single-dose administration of latanoprost 0.005% in healthy volunteers. A randomized, double-masked, placebo controlled, cross-over single center study.

PURPOSE: To measure the effect on intraocular pressure (IOP) over 24 hours after single-dose administration of latanoprost 0.005%. PATIENTS AND METHODS: A randomized, double-masked placebo-controlled cross-over study was carried out. Twenty healthy volunteers were randomly assigned to receive a single drop of latanoprost 0.005% or placebo, with a 2-week wash-out period before switching therapy. After hospitalization, the IOP was measured repeatedly over 24 hours, and again after 36 and 48 hours. RESULTS: The maximum IOP reduction for latanoprost occurred 12 hours after the dose with IOP 11.7+/-0.5 mmHg (least square mean+/-standard standard error of the mean [SEM]) for latanoprost and 13.5+/-0.5 mmHg for placebo. The difference of 1.8+/-0.6 mmHg was statistically significantly in favor of latanoprost (p=0.01; ANCOVA, confidence interval (CI) [-3.1; -0.5] mmHg). The average time to onset of action, defined as 50% of the maximal IOP reduction, was 6.0 hours for latanoprost. Latanoprost consistently reduced IOP over 24 hours after drop application with a difference in IOP reduction of 1.1+/-0.5 mmHg (p=0.03, CI [-2.1, 0.1]) at 24 hours. The corresponding IOP difference at 36 hours was 0.7+/-0.5 mmHg (p=0.20, CI [-1.7, 0.3]), and at 48 hours 0.8+/-0.5 mmHg (p=0.04, CI [-1.5, 0.0]). CONCLUSIONS: Latanoprost applied as a single dose reduced IOP over 24 hours in healthy subjects compared with placebo. The IOP reduction was still present, however, less pronounced, 48 hours after drug application.

Adult↗

PubMed2001

Effect on intraocular pressure during 24 hours after repeated administration of the fixed combination of latanoprost 0.005% and timolol 0.5% in patients with ocular hypertension.

PURPOSE: To measure the effect on intraocular pressure (IOP) for 24 hours after repeated administration of the fixed combination of latanoprost 0.005% and timolol 0.5%. METHODS: A randomized, double-masked placebo-controlled crossover study including 20 patients with ocular hypertension was carried out. Patients were randomized to treatment with the fixed combination of latanoprost and timolol or with placebo. The eyedrop was taken at 8 AM. After 2 weeks of treatment, the patients were hospitalized, and the IOP was measured at 8 AM, and thereafter every other hour until midnight, and also at 3 AM, 6 AM, and 8 A.M. After a washout period of 4 weeks, they switched to the other eyedrop, and after 2 weeks of treatment were hospitalized and the IOP measurements were repeated at the same intervals. RESULTS: The mean 24-hour IOP was 14.7 +/- 0.3 mm Hg (mean +/- standard error of the mean) for latanoprost and timolol and 19.4 +/- 0.3 mm Hg for placebo. This corresponds to a significant IOP difference of 4.7 +/- 0.4 mm Hg (95% confidence interval 3.8-5.8; P < 0.001) between the two treatments in favor of the combination. At all measured time points, except at 3 AM, the mean IOP was lower with latanoprost and timolol than with placebo. During daytime measurements the mean IOP was 13.9 +/- 0.7 mm Hg for the fixed combination and 19.5 +/- 0.7 mm Hg for the placebo. Corresponding figures at nighttime were 16.1 +/- 0.7 mm Hg and 19.2 +/- 0.7 mmHg, respectively. CONCLUSIONS: The fixed combination of latanoprost and timolol significantly reduced IOP after administration once daily for 2 weeks in patients with ocular hypertension. A reduction of IOP during a 24-hour period was seen, with a greater IOP reduction during daytime compared with nighttime. The fixed combination applied once daily could be a convenient alternative to concomitant therapy with its individual components.

Adrenergic beta-Antagonists↗

PubMed2001

Quantitative and qualitative immunofluorescence studies of neoplastic cells transfected with a construct encoding p53-EGFP.

The p53 protein is a major regulator of cell cycle progression and apoptosis. We used a p53-enhanced green fluorescent protein (EGFP) construct for transfections into human breast cancer (MCF-7) cells. Cells expressing p53-EGFP showed an increased apoptotic index compared to cells transfected with EGFP alone. Interestingly, apoptotic cells showed localization of p53-EGFP to both nuclei and cytoplasm, whereas non-apoptotic cells usually only showed nuclear localization of p53-EGFP. This result is in agreement with the hypothesis that p53 induces apoptosis by interaction with both nuclear and cytoplasmic targets. Transfected p53-deficient osteosarcoma cells were used for immunofluorescence quantitation. The intensity of immunofluorescence for either p53 or EGFP showed excellent linear correlation to the EGFP autofluorescence, proving that measurements of immunofluorescence intensities can be used for determining endogenous protein levels.

Fluorescent Antibody Technique, Indirect↗

PubMed2000

Developmental biology of gastrin and somatostatin cells in the antropyloric mucosa of the stomach.

Gastrin is a hormone regulating gastric acid secretion and the growth of the gastrointestinal epithelium. It is expressed by endocrine tumors and by adenocarcinomas of the gastroenteropancreatic region and may represent an autocrine tumor growth factor. Gastrin is also implicated in the genesis of peptic ulcer disease both in conjunction with H. pylori infections and with gastrin-producing tumors. The secretion and expression of gastrin are under the paracrine control of somatostatin, produced by D cells situated in close contact with gastrin-producing G cells. D cells also contain neuronal nitric oxide synthase and appear to regulate apoptosis of G cells by paracrine release of nitric oxide. Both G and D cells are derived from a common multihormonal precursor cell present in the regenerative (isthmus) region of the gastric units. The precursor cells have been suggested to undergo asymmetrical divisions resulting in gastrin- and somatostatin-producing daughter cells that remain in paracrine contact during their migration into the glands. The precursor cells also give rise to the third main antropyloric endocrine cell type; the serotonin-producing EC cell. The maturation of all of these cell types is regulated by a number of transcription factors containing homeobox motifs (Pdx-1, Pax 4 and 6, Isl-1, Nkx6.1). Many of these also regulate the development of the central nervous system and the pancreas. The use of different combinations of these factors for regulating the expression of different hormones may explain the phenomenon of abberant hormone expression during development and carcinogenesis and the occurrence of multihormonal cells.

Animals↗

PubMed2000

Development of hormonal peptides and processing enzymes in the embryonic avian pancreas with special reference to co-localisation.

Studies on the developing mammalian pancreas have suggested that insulin and glucagon co-exist in a transient cell population and that peptide YY (PYY) marks the earliest developing endocrine cells. We have investigated this in the embryonic avian pancreas, which is characterised by anatomical separation of insulin and glucagon islets. Moreover, we have compared the development of the endocrine cells to that of processing enzymes involved in pancreatic hormone biosynthesis. PYY-like immunoreactivity occurred in islet cells from the youngest stages examined: it increased in amount from approximately 5 days of incubation and was co-localised with glucagon and to a lesser extent with insulin. Insulin and glucagon cells were numerous: co-existence of the two peptides in the same cells was but rarely observed. From the youngest stages examined, prohormone convertase (PC) 1/3-like immunoreactivity was detected in insulin cells and PC2-, 7B2- and carboxypeptidase E-like immunoreactivity in both glucagon and insulin cells. We conclude that: (1) PYY-like immunoreactivity occurs in avian islet cells but generally in lesser amounts than in mammals at the earlier stages, (2) the paucity of cells co-expressing insulin and glucagon indicate that all avian insulin cells do not pass through a stage where they co-express glucagon and (3) the early expression of the enzymes responsible for the processing of prohormones suggests that this process is initiated soon after islet cells first differentiate.

Animals↗

PubMed2000

Absence of a PDX-1 mutation and normal gastroduodenal immunohistology in a child with pancreatic agenesis.

Pancreatic agenesis is a rare condition, of which only a limited number of cases have been described. One recent paper reported a homozygous mutation in the pancreatic duodenal homeobox gene 1 (PDX-1) in a child with pancreatic agenesis. We report a 6-year-old boy with pancreatic agenesis, treated medically, without abnormalities in the PDX-1 gene coding sequence and with normal gastroduodenal endocrine cell distribution. Genes other than PDX-1 also appear to be involved in human pancreatic agenesis.

Biopsy↗

PubMed2000

Apoptosis in rat gastric antrum: evidence that regulation by food intake depends on nitric oxide synthase.

The turnover of the epithelium of the gastrointestinal tract is regulated by a balance between cell multiplication and cell loss. We examined the effects of starvation on apoptosis in endocrine and other epithelial cells of rat antropyloric mucosa. Apoptosis was determined by the TUNEL reaction combined with immunocytochemical staining for gastrin and somatostatin. Apoptotic cell morphology was determined by bisbenzimide staining for DNA. Both gastrin and somatostatin cells showed a significantly lower apoptotic index than the general epithelium. This agrees with the longer turnover kinetics of gastric endocrine cells. On starvation, the apoptotic index of the general epithelium and of the gastrin but not of the somatostatin, cells increased significantly. This was prevented by the nitric oxide synthase (NOS) inhibitor L-NAME but not by its inactive stereoisomer D-NAME. Immunoreactive neuronal NOS was present in somatostatin cells, in nonendocrine cells predominating in the surface and pit epithelium, and in rare nerve fibers. Endothelial cell NOS was present in vessels, whereas the inducible isoform was barely detectable. Thus, endogenous NOS isoforms participate in regulating antropyloric epithelial apoptosis during starvation. The close paracrine relation between somatostatin cells and gastrin cells suggests that the former regulates apoptosis of the latter through release of NO.

Animals↗

PubMed2000

Immunocytochemical evidence suggesting that diamine oxidase catalyzes biosynthesis of gamma-aminobutyric acid in antropyloric gastrin cells.

gamma-Aminobutyric acid (GABA) is a neurotransmitter that also occurs in a few non-neuronal cell types, where it may serve as a paracrine modulator. GABA is biosynthesized from glutamate by glutamate decarboxylase (GAD) and from putrescine via diamine oxidase (DAO). GAD is demonstrable in several GABA-positive cell types but is undetectable in the GABA-containing gastrin cells and somatostatin cells of the antropyloric mucosa of the stomach. Using two antisera raised against synthetic peptides corresponding to two different regions of rat DAO, we now demonstrate strong reactivity for DAO in gastrin-positive cells of the rat antropyloric mucosa, whereas somatostatin-positive cells as well as other structures of the antrum are unreactive. Western blotting analysis of antrum and colon demonstrate that both antisera react with a single band of 85 kD, consistent with the predicted molecular weight of DAO. Expression of DAO mRNA in the antrum is demonstrated by reverse transcriptase polymerase chain reaction (RT-PCR). Our results strongly indicate that gastrin cells produce GABA via DAO-catalyzed oxidation of putrescine, and experimental data moreover suggest that the biosynthesis of GABA is regulated by the prandial state. Because GABA modulates release of somatostatin, these results point to a new mechanism of paracrine interaction between gastrin cells and somatostatin cells.

Amine Oxidase (Copper-Containing)↗

PubMed1999

Endogenous endothelial cell nitric-oxide synthase modulates apoptosis in cultured breast cancer cells and is transcriptionally regulated by p53.

Nitric oxide can both stimulate and suppress apoptosis. By reverse transcriptase-polymerase chain reaction and sequencing we show that human breast cancer (MCF-7) cells express endothelial cell nitric-oxide synthase (ecNOS), but not other nitric-oxide synthase isoforms. Inhibition of ecNOS activity in MCF-7 cells increased tumor cell apoptosis, and this effect was also seen following treatment with an NO scavenger. In addition, low concentrations of the NO donor sodium nitroprusside inhibited, whereas high concentrations stimulated MCF-7 cell apoptosis. The ecNOS promoter was found to contain a specific binding site for the apoptosis-regulating protein p53. In co-transfection studies wild-type, but not mutant, p53 down-regulated transcription of an ecNOS promoter-luciferase reporter gene construct. In addition, NO donors up-regulated p53 protein levels in MCF-7 cells. These data point to a previously unrecognized p53-dependent regulation of ecNOS expression that may be important both for regulating apoptosis and for avoiding the generation of genotoxic quantities of NO.

Apoptosis↗

PubMed1999

Pax6 and Pdx1 form a functional complex on the rat somatostatin gene upstream enhancer.

The somatostatin upstream enhancer (SMS-UE) is a highly complex enhancer element. The distal A-element contains overlapping Pdx1 and Pbx binding sites. However, a point mutation in the A-element that abolishes both Pdxl and Pbx binding does not impair promoter activity. In contrast, a point mutation that selectively eliminates Pdx1 binding to a proximal B-element reduces the promoter activity. The B-element completely overlaps with a Pax6 binding site, the C-element. A point mutation in the C-element demonstrates that Pax6 binding is essential for promoter activity. Interestingly, a block mutation in the A-element reduces both Pax6 binding and promoter activity. In heterologous cells, Pdx1 potentiated Pax6 mediated activation of a somatostatin reporter. We conclude that the beta/delta-cell-specific activity of the SMS-UE is achieved through simultaneous binding of Pdx1 and Pax6 to the B- and C-elements, respectively. Furthermore, the A-element appears to stabilise Pax6 binding.

3T3 Cells↗

PubMed1999

Retinopathy in diabetic patients aged 15-50 years in the county of Umeå, Sweden.

PURPOSE: To examine the prevalence of diabetic retinopathy and its relation to certain risk factors (glycosylated hemoglobin, blood pressure, serum creatinine, proteinuria, smoking) in a population-based study on a specific age-group of patients with diabetes mellitus in the county of Umeå, Sweden. METHODS: All diabetic patients aged 15-50 years living in the county of Umeå were invited to the study. A standard clinical and eye examination was performed, and seven-field stereoscopic photographs were taken of each eye. Blood and urine samples were collected. Univariate and multivariate statistical analyses were performed. RESULTS: Of the eligible 395 patients 285 (91%) participated in the study. 285 patients (79%) had diabetes mellitus type 1, 71 (20%) subjects had diabetes mellitus type 2, and 3 patients (1%) had secondary diabetes. In the statistical analysis performed on patients with type 1 diabetes mellitus, duration, presence of hypertension, systolic blood pressure, plasma glucose, glycosylated hemoglobin, serum creatinine, proteinuria and smoking all were significantly related to increasing degree of retinopathy when a univariate model was applied. However, when a multivariate analysis was performed only duration, proteinuria, glycosylated hemoglobin and male gender were statistically significantly associated with severeness of retinopathy. CONCLUSION: Increased duration of diabetes, inadequate metabolic control as measured by glycosylated hemoglobin, proteinuria and male gender are factors that are associated with a higher incidence of diabetic retinopathy in diabetes mellitus type 1.

Adolescent↗

PubMed1999

The association of hyperlipidemia with retinopathy in diabetic patients aged 15-50 years in the county of Umeå.

PURPOSE: To study possible associations between serum lipid levels and degree of retinopathy in a population-based study on a specific age-group of patients with diabetes mellitus in the county of Umeå, Sweden. METHODS: All patients with diabetes mellitus aged 15-50 years living in the county of Umeå were invited to the study. The participating subjects had a standard clinical examination and an eye examination performed. Seven-field stereoscopic photographs were taken of each eye, and the photos were sent to Grading Center, Hammersmith Hospital, London, U.K. for grading of the retinopathy. Blood samples were drawn for analysis of lipoprotein(a), high density lipoprotein (HDL) cholesterol, cholesterol and triglycerides. Univariate and multivariate statistical analyses were performed. RESULTS: In the present study only patients with type 1 diabetes mellitus were included, and 285 of the invited 308 diabetic subjects (93%) took part. When univariate analysis was applied we found statistically significant associations between higher lipoprotein(a) levels, higher triglyceride levels, higher cholesterol levels, lower HDL cholesterol/total cholesterol ratios and increasing severeness of retinopathy. However, in the multivariate analysis triglyceride levels lost their importance while all other significant associations were still present. CONCLUSION: Associations were found between higher levels of serum total cholesterol, declining ratios of high density lipoprotein (HDL) cholesterol/total cholesterol, higher levels of serum lipoprotein(a) and more severe retinopathy in diabetes mellitus type 1. No such association was found between serum triglycerides and degree of retinopathy.

Adolescent↗