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Biomedical subjects

S Lake

Publications and source records attributed to S Lake.

At least 37 records · Page 2Linked to original sources
PubMed1994

Cloning of the rat and human prostaglandin F2 alpha receptors and the expression of the rat prostaglandin F2 alpha receptor.

We have cloned the FP receptor from rat corpus luteum and human uterus cDNA libraries, respectively. The coding DNA sequence in the rat cDNA is 1101 bp and is similar to the mouse cDNA coding for a receptor protein of 366 amino acids. The human sequence shows a 5 bp deficiency in the 3' region, truncating the coding sequence to 359 amino acids. Northern blot analysis indicates highest expression in the ovary. Cell lines have been established giving stable expression of the FP receptor. Activation of the cloned FP receptor gave an increase in intracellular calcium, indicating signaling via phospholipase C-mediated phosphoinositide turnover. Using [3H]PGF2 alpha, binding of PGs showed the rank order of fluprostenol > PhXA70 > PGF2 alpha > or = PhXA85 > PGD2 > PGE2.

Amino Acid Sequence↗
PubMed1994

A comparison of multiplex and simplex families with Alzheimer's disease/senile dementia of Alzheimer type within a well defined population.

A study was made on 150 clinically demented patients presenting at autopsy at Umeå University Hospital in Sweden. In 90 of the cases dementia was considered to be primary in nature and of these forty six per cent (41 cases), fulfilled both the clinical and histopathological criteria for the diagnosis of Alzheimer's disease/Senile dementia of Alzheimer type (AD/SDAT). The families of these 41 AD/SDAT cases were then studied, and a family history obtained through interviews with multiple family informants and from civil and medical records. Additional diseased family members suffering from progressive dementia (multiplex families) were observed in 12 probands out of 41 (29%). Multiplex families exhibited similar clinical and histopathological characteristics as simplex families containing a single affected individual. The secondary cases in the multiplex families exhibited similar demographic and clinical characteristics as the probands. 39% of the multiplex and 14% of the simplex cases had an early age of onset of the disease, that was under 65 years. The overall prevalence of progressive dementia disorders in the 41 families was 5.9%. The prevalence of a progressive dementia disorder was 11% in the multiplex families (14% for the early onset cases) and 3.5% in the simplex families (2% for the early onset cases). The prevalence of progressive dementia disorder for family members who had passed the mean age of the onset of the disease for their family, was 45% for multiplex and 18% for simplex families. Furthermore the incidence rate for dementia was significantly higher (p < 0.005) in multiplex families (5.5 per 1,000 person years) when compared to simplex families (2.5 per 1,000 person years). No differences could be seen in parental age at birth of the diseased when comparing the two sets of families. However in multiplex families the duration of the disease was significantly (p < 0.025) shorter, in subjects with parental age at birth over 35 years compared to those with a parental age under 35 years. The multiplex families contained significantly (p < 0.025) larger sibships; and showed a significantly lower age of onset for the disease (p < 0.001), and a significantly longer duration of disease (p < 0.05) compared to the simplex families. A significant intra familial correlation of age at disease onset was observed in both sets of the families.

Age of Onset↗
PubMed1993

Screening of amyloid precursor protein gene mutation (APP 717 Val-->Ile) in Swedish families with Alzheimer's disease.

Screening for the APP 717 Val-->Ile mutation in the amyloid precursor protein (APP) gene in 34 Swedish families with familial Alzheimer's disease (FAD), 16 sporadic cases of Alzheimer's disease and five patients with Down's syndrome (DS) failed to identify further cases of the mutation. These results suggests that the mutation is rare among Swedish families with Alzheimer's disease. In addition, we summarize present reports of the frequency of the mutation.

Aged↗
PubMed1993

Management of pseudophakic retinal detachment with various intraocular lens types.

In the last five years, 25 cases of retinal detachment (RD) after intraocular lens implantation were treated in the University Eye Clinic of Thessaloniki. The incidence of RD was lower with posterior chamber intraocular lens (PC-IOL, 0.46%) implantation than in the cases with anterior chamber IOL (AC-IOL, 2.6%) implantation. The successful reattachment rate was higher with PC-IOL (100%) than in cases with AC-IOL where the low success (87%) rate was caused by proliferative vitreoretinopathy. Therefore, the eyes with AC-IOL required reoperation more frequently, and the ultimate failure rate (despite multiple operations) was higher in the AC-IOL group. Conventional surgical techniques were used in the first procedure. In the reoperated cases, the most advanced techniques were used, such as vitrectomy combined with gas or silicone oil injection.

Cataract Extraction↗
PubMed1992

[Alzheimer's disease--an amyloid disease of the brain].

During recent years, Alzheimer's disease (AD) has attracted increasing interest among clinicians and neuropathologists throughout the world. The amyloid core of the neuritic plaques found in the brains of individuals with the disease has been shown to be composed of a distinct peptide formed through proteolytic degradation of a large precursor protein, the Alzheimer amyloid precursor protein (APP), which exists in at least three isoforms differing from each other in the splicing of the primary transcript from which they derive. Although the physiological function of APP remains unknown, it has been suggested to function as a protease inhibitor and to be important to the blood coagulation system. The gene encoding APP is located on the long arm of chromosome 21. Individuals with Down's syndrome (trisomy 21) often develop AD in early middle age, suggesting that the 50 percent increase in APP, gene expression may promote the development of the disease. Mutations in the APP gene have also been shown to be associated, probably pathogenetically with familial forms of AD. The conclusions drawn from these studies include (i) that the amyloidosis associated with AD is probably a central pathogenetic factor and (ii) that the development of drugs capable of inhibiting amyloidosis might be an appropriate strategy for the treatment of AD.

Alzheimer Disease↗
PubMed1991

Effect of pancreatectomy on plasma activities of amylase, isoamylase, lipase and trypsin-like immunoreactivity in dogs.

The contribution of the pancreas to the plasma activities of amylase, isoamylase, lipase and the concentration of trypsin-like immunoreactivity (TLI) in the dog was examined by measuring the activities of these enzymes before and after total pancreatectomy. Pancreatectomy was followed by a decrease in the concentration of TLI (from 6.2 +/- 0.3 micrograms litre-1 to 1.2 +/- 0.3 micrograms litre-1; P less than 0.001) and activity of isoamylase peak 4 (from 1257 +/- 105 iu litre-1 to 894 +/- 171 iu litre-1; P less than 0.05). Though significantly reduced, the activities of peak 4 isoamylase were still within the normal range for control dogs. Pancreatectomy did not significantly alter the activities of amylase, lipase or isoamylase peaks 1, 2 and 3. These findings provide strong evidence that the pancreas is not the sole source of circulating amylase, isoamylase and lipase activities. In contrast the marked reductions in TLI to values close to the limits of assay sensitivity suggest that TLI is derived from the pancreas alone. The results indicate that assay of circulating TLI provides a more sensitive and specific indicator of pancreatic exocrine mass than plasma amylase, lipase or isoamylase activities.

Amylases↗
PubMed1985

Flow cytometric determination of the proportions of X- and Y-chromosome-bearing sperm in samples of purportedly separated bull sperm.

A rapid assay for determining the proportions of X- and Y-chromosome-bearing sperm in semen samples would benefit research aimed at sex ratio control through sperm separation. It also would be of value for quality control should a separation technique be developed. Flow cytometric methods capable of measuring sperm DNA content precisely enough to resolve and quantify the X and Y populations in many mammalian species have been developed. They are effective for fresh and cryopreserved sperm of most domestic animals. Results are reported of flow cytometric analyses of bull sperm samples from seven commercial and academic sources after processing with procedures purported to separate the X and Y populations. In no case was enrichment of either sperm population observed. Breeding trials carried out by the sources of two of the sets of samples showed these procedures were ineffective in altering the sex ratio.

Animals↗
PubMed1984

Estimation of the frequency of malformed sperm by slit scan flow cytometry.

We have investigated the utility of Slit Scan Flow Cytometry (SSFCM) for measuring the frequencies of malformed sperm heads in control and mutagen treated B6C3F1/CRL mice. In SSFCM, fluorescence profiles of sperm heads stained with the DNA-specific fluorescent dye acriflavine were recorded for sperm flowing lengthwise through a 2.5-microns-thick laser beam. Malformed sperm were detected as having fluorescence profiles that differed substantially from an average fluorescence profile for sperm from untreated mice. Specifically, a sum of squared difference (SSD) value was calculated for the fluorescence profile of each sperm according to the equation (Formula: see text) where c(i) and t(i) are the ith values for the fluorescence profiles from control and test sperm, respectively. Profiles whose SSD exceeded a threshold value of 20 were considered to be from malformed sperm. We measured fluorescence profiles for 500 sperm per mouse from five control mice, five mice injected intraperitoneally daily for 5 days with a total of 375 mg/kg of body weight methyl methane sulfonate (MMS), and for 30 mice injected intraperitoneally daily for 5 days with total doses of procarbazine ranging from 125 mg/kg to 1,250 mg/kg. Sperm were collected from the caudae epididymides 35 days after the last injection. Frequencies of malformed sperm in these samples were also estimated by visual analysis. All samples were analyzed in double blind fashion. The visual and SSFCM malformed sperm frequencies for the samples from control, MMS-treated, and procarbazine-treated mice were correlated (r = 0.83). A dose effect was seen with both the visual and SSFCM estimates for the sperm from the procarbazine-treated mice.

Animals↗
PubMed1983

Quantification of the X- and Y-chromosome-bearing spermatozoa of domestic animals by flow cytometry.

The relative content of DNA in spermatozoa presumed to be the X- and Y-chromosome-bearing gametes from bulls, boars, rams and rabbits and the amount of DNA in spermatozoa of cockerels was determined by flow cytometry. Differences in the relative content of DNA and proportions of the presumed X- and Y-sperm populations in cryopreserved semen from Holstein, Jersey, Angus, Hereford and Brahman bulls were also determined. Spermatozoa were washed by centrifugation using a series of dimethyl sulfoxide solutions made in isotonic sodium citrate, fixed in ethanol, treated with papain and dithioerythritol to loosen the chromatin structure and remove cellular organelles, and stained quantitatively for DNA with the fluorochrome 4'-6-diamidino-2-phenylindole (DAPI). Approximately 5000 stained sperm nuclei, which were nonviable due to the removal of other cellular organelles during the washing procedure, were measured for DNA in an epi-illumination flow cytometer. A single distinct peak for cockerel spermatozoa and two symmetrical, overlapping peaks for species with X- and Y-spermatozoa were seen. This and other evidence strongly supports the interpretation that the peaks represent the X- and Y-sperm populations. The content of DNA in sperm nuclei from cockerels, bulls, boars, rams and rabbits, as determined by fluorescence flow cytometry, corresponded to biochemical estimates of DNA per sperm cell. Analyses of the bimodal histograms by computer-fitting two Gaussian distributions to the data showed the means of the peaks differed by 3.9, 3.7, 4.1 and 3.9% for bulls, boars, rams and rabbits, respectively. In four replicate analyses of semen from 25 bulls representing 5 breeds, the average population of sperm nuclei in the Y-peaks ranged from 49.5 to 50.5% for all breeds. The X-Y peak differences did not vary within each breed, but were significantly different when the breeds were compared. Spermatozoa from Jersey bulls had larger X-Y peak differences (P less than 0.001) than spermatozoa from Holstein, Hereford, and Angus bulls; spermatozoa from Brahman bulls had smaller X-Y differences (P less than 0.004). It is suggested from the evidence obtained in these studies that flow cytometry can be used to assess the proportion of X- and Y-spermatozoa in semen of domestic animals and is thereby applicable to verification of the effectiveness of enrichment techniques for X- or Y-spermatozoa.

Animals↗
PubMed1983

Radiation-induced DNA content variability in mouse sperm.

Mouse sperm collected from the cauda epididymidis 35 days after acute testicular X-ray exposure and fluorescently stained for DNA show dose-dependent increases in the coefficient of variation (CV) of flow cytometrically obtained fluorescence distributions. By comparing dose-response curves obtained with three protocols which overcome the optical and cytochemical difficulties of sperm measurement in different ways we conclude the response is due to X-ray-induced DNA content variability. In the range between 0 and 600 rad the dose dependence of the square of CV of the DNA content variability, delta CV2D, is described by delta CV2D = Bx + Cx2, with 0 less than or equal to B less than or equal to 0.23 X 10(-2) and C = (0.44 +/- 0.06) X 10(-4). The dose x is measured in rad and delta CVD is expressed in percent. Computer modeling of the shapes of the fluorescence distributions show that at 600 rad 30 to 40% of the sperm have abnormal DNA content. Some have errors as large as two whole chromosomes, but it is not clear whether they are due to whole chromosome nondisjunction or a finer fragmentation of the genome. Exposures to benzo(a)pyrene and mitomycin C cause no detectable DNA content variability. We conclude mouse sperm DNA content measurements are not sensitive to small amounts of aneuploidy and as such will only be useful in detecting agents that produce substantial DNA content variability. Another animal with a smaller number of chromosomes might be more favorable. These sperm measurement techniques may find additional application in other areas of reproductive biology, such as the determination of the relative numbers of X and Y chromosome-bearing sperm in semen that may be artificially enriched in one population.

Animals↗
PubMed1982

Sex preselection in mammals? Separation of sperm bearing Y and "O" chromosomes in the vole Microtus oregoni.

The two sex determining sperm populations of the vole Microtus oregoni were separated according to DNA content by use of flow sorting instrumentation. Although the sperm were not viable, they should be useful for addressing the question of haploid expression of genes linked to sex chromosomes and for efficiently searching for biochemical markers that differentiate the two populations.

Animals↗
PubMed1982

Quantification of mammalian sperm morphology by slit-scan flow cytometry.

The head shapes of mammalian sperm have been measured by slit-scan flow cytometry (SSFCM). In this approach, the distribution of fluorescence along acriflavine stained mammalian sperm is recorded and used as a measure of head shape. Fluorescence profiles were measured for sperm from mice, rabbits, hamsters, and bulls, and for sperm from mice exposed to testicular x-irradiation from 0 to 900 rads. The profiles for sperm from nonirradiated animals were characteristic of each species and were reproducible from sperm to sperm. Some of the fluorescence profiles for sperm from the irradiated mice differed significantly from the profiles usually measured for sperm from exposed mice. An algorithm was developed to determine the frequency of these sperm. The estimated frequencies of atypical profiles correlated well (r = 0.99) with the frequencies of abnormally shaped sperm determined by microscopic scoring. The maximum SSFCM sensitivity (minimum detectable dose = 199 rad) was not as high as that for the visual assay (minimum detectable dose = 116 rad). However, only 100 profiles were measured by SSFCM at each dose while at least 500 sperm were scored visually at each dose. The sensitivity of the SSFCM assay should be increased substantially by measuring more profiles. The objective nature of SSFCM couple with the high correlation with results from the visually based assay of morphology suggests the use of SSFCM to measure frequencies of misshapen sperm when testing for mutagens or monitoring for effects of environmental contaminants.

Animals↗
PubMed1982

High resolution DNA content measurements of mammalian sperm.

The high condensation and flat shape of the mammalian sperm nucleus present unique difficulties to flow cytometric measurement of DNA content. Chromatin compactness makes quantitative fluorescent staining for DNA difficult and causes a high index of refraction. The refractive index makes optical measurements sensitive to sperm head orientation. We demonstrate that the optical problems can be overcome using the commercial ICP22 epiillumination flow cytometer (Ortho Instruments, Westwood, MA) or a specially built cell orientating flow cytometer (OFCM). The design and operation of the OFCM are described. Measurements of the angular dependence of fluorescence from acriflavine stained rabbit sperm show that it is capable of orienting flat sperm with a tolerance of +/- 7 degrees. Differences in the angular dependence for the similarly shaped bull and rabbit sperm allow discrimination of these cells. We show that DNA staining with 4-6 diamidino-2-phenylindole (DAPI) or an ethidium bromide mithramycin combination allows resolution of the X and Y populations in mouse sperm. They have also been successful with sperm from the bull, ram, rabbit, and boar. Reliable results with human sperm are not obtained. The accuracy of the staining and measurement techniques are verified by the correct determination of the relative DNA content of these two populations in sperm from normal mice and those with the Cattanach [7 to X] translocation. Among the potential uses of these techniques are measurement of DNA content errors induced in sperm due to mutagen exposure, and assessment of the fractions of X and Y sperm in semen that may have one population artifically enriched.

Acriflavine↗
PubMed1982

[Clinical experience with A- and B-scan ultrasonographie (author's transl)].

Ultrasonography, and especially the combined use of A- and B-scan echography, is one of the most important methods of clinical investigation in ophthalmology, It was employed on 1000 patients with opaque media. In 158 cases the examination confirmed the diagnosis of pathologic changes, while in the rest the echograms were normal. The most frequent finding was retinal detachment. Echography is also the most important examination for selection and preoperative examination of candidates for vitrectomy.

Eye Diseases↗