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Biomedical subjects

J C Mattson

Publications and source records attributed to J C Mattson.

32 records · Page 2Linked to original sources

Polymerase chain reaction: amplification of DNA from fixed tissue.

The polymerase chain reaction (PCR) allows the analysis of DNA from biologic samples containing only nanogram quantities of DNA. We used DNA purified from fresh or frozen peripheral blood (PB) leukocytes and formalin, or B-5 fixed bone marrow aspirate clots (BM). A sequence of the beta-globin gene was amplified via the PCR then hybridized with allele specific oligonucleotide probes for hemoglobin A, S, and C. All DNA preparations, including formalin and B-5 fixed BMs, were successfully amplified; the hybridization of the amplified products resulted in patterns consistent with the hemoglobin phenotype for all patients. PCR can be used on DNA from many sources; retrospective studies using paraffin embedded fixed tissue are possible because extremely small amounts of DNA present in fixed tissue can be successfully amplified.

Adult↗

Defective contact activation of platelets from dogs with basset hound hereditary thrombopathy.

Basset Hound Hereditary Thrombopathy (BHT) is an autosomally inherited disorder of platelet function characterized by a thrombasthenia-like defect in aggregation but normal clot retraction. Glycoprotein IIb-IIIa (GP IIb-IIIa) is detectable in BHT platelets but may be functionally defective. In order to further characterize this potential model for human Glanzmann's thrombasthenia, contact reactivity of BHT platelets was studied by whole mount electron microscopy. Gel filtered BHT platelets, after 30 minutes of contact activation, attached poorly to a formvar substrate. There was an 8 fold difference in the number of adherent BHT platelets and normal platelets. In addition, contact induced shape change was inhibited when compared to control dogs. Almost 95% of control platelets reached fully dendritic or spread forms after 30 minutes of contact; in contrast only 63.7% of BHT platelets reached this degree of activation. The addition of 8.2 uM ADP to BHT platelets induced nearly a 4 fold increase in the number of spread forms and a 5 fold increase in the number of adherent BHT platelets, but did not cause aggregate formation. Both the defect in adhesion and shape change and the ability of ADP to stimulate both adhesion and contact-induced shape change in BHT platelets are similar to recent observations in our laboratory in patient's with type II Glanzmann's thrombasthenia.

Adenosine Diphosphate↗

Use of scanning electron microscopy to study structural-functional relationships in normal and diseased platelets.

This paper reviews the contribution of scanning electron microscopy (SEM) to our understanding of platelet physiology and pathology. Observations of platelet shape changes which accompany activation and the ability to visualize and analyze platelet aggregation and adhesion in three dimensions make this experimental medium an important tool in the evaluation of healthy and diseased platelets. While SEM adds a valuable third dimension to the study of morphology and ultrastructure, its greatest contribution is realized when studies are correlated directly with light and/or transmission electron microscopic observations and with studies of functional capacity.

Adenosine Diphosphate↗

Clinicopathological correlations of disseminated intravascular coagulation in patients with head injury.

To try to define the significance of disseminated intravascular coagulation (DIC) in head-injured patients, we correlated clinical, laboratory, and pathological findings in 16 patients with head injury as their main problem who had DIC, who died within 4 days of injury, and who were examined postmortem. Patients were ranked according to the number of abnormal laboratory screening tests for DIC and the severity of these abnormalities. The most frequently abnormal laboratory tests were the fibrinogen degradation products and fibrinogen, followed in order by the activated partial thromboplastin time, prothrombin time, and thrombin time. The platelet count was the least abnormal value. The patients with the fewest abnormalities had the least abnormal computed tomographic scans. Autopsy reports revealed necrosis and bleeding in the brain and in a number of other organs, particularly the lungs. Microthrombi were not reported in the original autopsy reports. However, when these cases were reevaluated and their slides were stained with an immunoperoxidase technique using rabbit anti-human fibrinogen antiserum, microthrombi were seen frequently. Large microthrombi were more common in patients who had died within less than 24 hours, suggesting a relationship to death or to less time for lysis. In order of frequency, the brain/spinal cord, liver, lungs, kidneys, and pancreas were most commonly affected, and the liver, pituitary gland, pancreas, thymus, brain/spinal cord, large intestine, kidneys, and lungs had the greatest density of microthrombi. Pulmonary dysfunction had been a frequent problem in these patients, which may have been related to the high incidence of microthrombi and bleeding found in the lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation Tests↗

The Bernard-Soulier platelet: I. Correlation of adhesion defects with abnormalities of surface glycoproteins.

Bernard-Soulier disease, an inherited human platelet disorder, is characterized by decreased adhesion of platelets to the subendothelium. A review of the clinical features, laboratory diagnostic features and glycoprotein abnormalities is presented. The glycoprotein composition of platelets from patients with Bernard-Soulier disease was compared with normal using 3H-labeling of surface glycoproteins followed by two-dimensional gel electrophoresis. Decreased amounts of 3H-labeling of glycoprotein IIa as well as absence of the specific surface glycoprotein Ib was observed in Bernard-Soulier platelets. Studies of Bernard-Soulier platelets affords an opportunity to understand the mechanisms of platelet adhesion responses in the interactions of platelets with blood vessels.

Blood Platelet Disorders↗

The Bernard-Soulier platelet: II. A comparative study of changes in platelet morphology and cytoskeletal architecture following contact activation.

Platelet adhesion is a critical, early event in hemostasis. It is a complex process which involves platelet sticking, activation, granule release, and a series of morphologic changes which appear to enhance contact. The membrane glycoprotein (GP) Ib, which is thought to play an important role in adhesion, is missing in the Bernard Soulier Syndrome (BSS) and platelets in this syndrome have a structural defect which results in giant size on peripheral smear. Correlative SEM/TEM studies on adherent BSS platelets were used to address two questions: 1) Does the absence of GP Ib in BSS platelets result in abnormalities in the morphologic changes which ordinarily accompany adhesion to formvar? and 2) Is the giantism seen in BSS platelets related to or reflected in abnormalities in organization of the cytoskeletons of adherent platelets?

Blood Platelet Disorders↗

The effects of aluminum on microtubular integrity using in vitro and in vivo models.

Since neuronal lesions produced by aluminum (Al) are morphologically similar to lesions produced by microtubule inhibitors, the effect of aluminum on microtubule integrity was investigated. Aluminum inhibited microtubule formation at concentrations as low as 0.1 mM. This approaches the aluminum concentrations found in brains of patients with several disorders which result in progressive dementia.

Aluminum↗

Effects of asphyxia on cardiac output and organ blood flow in the newborn piglet.

Experiments were performed on newborn piglets 6--96 hr of age. When the respiratory dead space was increased arterial pO2 decreased and pCO2 increased. During this time cardiac output was unchanged (Fig. 1), while heart rate, respiratory rate, and blood pressure increased (Figs. 2 and 3). After 90 min of asphyxia blood flow to the stomach and small and large intestines decreased. Changes in blood flow were associated with dilatation of segments of the small and large intestine with scattered areas of hemorrhage. Pathologic examination revealed scattered areas of mucosal necrosis (Fig. 6).

Animals↗

Additive summation following intradimensional discrimination training.

Rats were exposed to intradimensional composite stimuli presented on the response lever that varied in both light intensity and flicker rate. For all subjects, pressing the lever was reinforced when it was illuminated at a high intensity and flickered at a low rate (I + f) or when it was illuminated at a low intensity and flickered at a high rate (i + F). For half the subjects, lever responding was not reinforced when it was illuminated at a low intensity and flickering at a low rate (i + f). For the remaining subjects, lever presses were not reinforced when the lever was illuminated at a high intensity and flickered at a high rate (I + F). When the composite stimulus composed of the light intensity and flicker rates that had been associated only with reinforced responding was displayed (I + F for half the subjects and i + f for the remaining subjects), it controlled the highest response rate of all stimuli (additive summation). The results demonstrated that similar attentional processes control intra- and interdimensional composite-stimulus discriminations in a manner consistent with Weiss' (1972) analysis of summation.

Journal Article↗

Microfollicular thyroid carcinoma with amyloid rich stroma, resembling the medullary carcinoma of the thyroid (MCT).

A human thyroid tumor is described which, on light microscopy, exhibited the features of medullary carcinoma of the thyroid (MCT). The cells were arranged in solid lobules or trabeculae, and the stroma was abundant and gave positive reaction for amyloid as assessed by congo red, crystal violet and thioflavin T stains. However, there was microfollicular differentiation in certain portions of the tumor even where the tumor was invasively growing. On electron microscopy, numerous microfollicles were identified even where unsuspected by light microscopy. There were junctional complexes, the cells possessed well developed rough endoplasmic reticulum, prominent Golgi and numerous dense bodies obviously derived from the Golgi vesicles, which were of the same morphology as "secretory" granules described previously by some authors in MCT. However, we find this kind of cytology typically in microfollicular thyroid carcinomas. Presence of about 100 A thick fibrils in the stroma was consistent with histochemically positive amyloid. The biochemical data were compatible with the differentiated follicular cell origin of the tissue. The homogenate contained poorly iodinated thyroglobulin, and thyroid peroxidase activity. Calcitonin was undetectable by a sensitive radioimmunoassay. It is concluded that this tumor was follicular thyroid carcinoma with amyloid rich stroma. The presence of amyloid and dense bodies with homogenous electron dense contents is insufficient for making conclusions about histogenesis of thyroid tumors. The so called MCT with amyloid stroma probably represents a heterogenous group of thyroid tumors, at least some of them derived from follicular epithelium.

Adenocarcinoma↗

Fixation of platelets for scanning and transmission electron microscopy.

A double fixation method of preparing platelet suspensions for both scanning and transmission electron microscopy is outlined. Prefixation in 0.1% glutaraldehyde allows for immediate preservation of morphologic characteristics induced by experimental procedures, but does not completely destroy platelet surface stickiness. Preservation of surface stickiness allows subsequent production of a platelet pellet for processing for transmission electron microscopy. This pelleting cannot be achieved when higher initial concentrations of glutaraldehyde are used for prefixation. Prefixation in 0.1% glutaraldehyde is also an appropriate initial step for preservation of platelets in suspension for scanning electron microscopy.

Blood Platelets↗