Biomedical subjects

S Teichberg

Publications and source records attributed to S Teichberg.

At least 73 records · Page 4Linked to original sources

PubMed1989

Morphologic and functional alterations in absorptive epithelial cells during L-tryptophan induced inhibition of net sodium and fluid absorption in the rat ileum.

L-Tryptophan (L-Trp) has been reported to suppress jejunal fluid and electrolyte transport in vitro, at a 20 mM concentration, whereas other amino acids enhance that absorption at the same concentration. The effect of L-Trp, glycine (Gly) and L-phenylalanine (L-Phe) on in vivo ileal and jejunal fluid and sodium transport, and their morphologic correlates, were investigated in the rat. In the ileum, morphology as well as fluid and sodium transport were more readily altered by L-Trp than in the jejunum. The ileal effects were rapid; morphologic and transport changes were seen within 2.5 minutes. The changes were stereospecific; they occurred only with the levo, but not with the dextro isomer of Trp. There was a concentration dependence; 20 mM levels of L-Trp were required, whereas lower concentrations of the amino acid often stimulated net absorption. Morphologic alterations produced by L-Trp were restricted to absorptive epithelial cells, whereas goblet cells appeared unaffected. Morphologically, L-Trp treatment led to the formation of clear basal vacuoles in ileal absorptive epithelial cells at 2.5 minutes, and extensive vacuolization and loss of the lumenal permeability barrier to macromolecules at 30 minutes. Since L-Trp can be hydroxylated in the small intestine, we assessed the effects of L-5 = OH tryptophan and 5-hydroxytryptamine on small intestinal transport and morphology in this experimental system. L-5-OH tryptophan inhibited fluid transport and produced some epithelial cell vacuolization. However, 5-hydroxytryptamine, which most severely decreased transport, had none of the morphologic effects of L-Trp. We hypothesize that L-Trp may inhibit transport as a result of its intracellular accumulation in absorptive epithelial cells.

Animals↗

PubMed1988

Protozoal infections in the acquired immunodeficiency syndrome.

Several protozoa have emerged as the major opportunistic infections and cause of death in patients with acquired immunodeficiency syndrome (AIDS). Pneumocystis carinii pneumonia is the leading cause of death in AIDS patients. Electron microscopy (EM) usually shows numerous trophozoites and cysts of Pneumocystis filling up the entire alveolar space, while only cysts are seen under the light microscope. The focal thickening of cyst wall of Pneumocystis, as demonstrated by EM and manifested as a "parentheses" shaped structure with silver stain, serves as a diagnostic marker for Pneumocystis. Freeze-fracture EM has demonstrated the intimate contact between Pneumocystis trophozoites and the type I pneumocytes, which may contribute to the alveolar-capillary block, leading to severe respiratory distress. However, EM is seldom needed for the diagnosis of this infection. Toxoplasma encephalitis, which is an unusual clinical manifestation in cases of toxoplasmosis reported previously, has become a common complication and one of the major causes of death in patients with AIDS. Because subclinical infection by Toxoplasma is common, serologic tests usually offer no definite answers as to whether the infection is acute or chronic, active or past. The small size and its non-specificity in both morphology and tissue affinity make light microscopic diagnosis of toxoplasmosis difficult. Only immunologic staining, such as immunoperoxidase and immunofluorescence, can help to achieve a definite positive identification of the organism. When special antibodies or facility for such staining is not available, EM is the final resort for identifying Toxoplasma by showing the apical complex with the characteristic sausage-shaped rhoptries. Cryptosporidiosis, practically unknown before the AIDS outbreak, has become one of the most common intestinal protozoa in both immunocompromised and immunocompetent patients. The protracted and sometimes fatal course of cryptosporidiosis in immunocompromised patients can be explained by the presence of autoinfective oocysts (thin-walled oocysts), as detected by EM, and by recycling of first-generation schizonts observed experimentally. While diagnosis of cryptosporidiosis can be made by detection of oocysts in stools in most cases, EM is still the last resort for a definitive identification of Cryptosporidium species. While the incidence of isosporiasis is still low, it has been found more frequently in patients with AIDS than in the general population. The parasite, Isospora belli, being a coccidian as is the Cryptosporidium species, is similar to the latter in its life cycle and clinical manifestations.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗

PubMed1988

Oral hydration solutions in experimental osmotic diarrhea: enhancement by alanine and other amino acids and oligopeptides.

Improvement of sodium absorption during the administration of oral hydration solutions (OHS) could increase the efficacy of formulations used in the treatment of infantile diarrhea. To test this hypothesis, selected protein breakdown products were evaluated as absorption enhancers in OHS of different osmolalities and Na-to-glucose ratios in an animal model of osmotic diarrhea induced by cathartics. A very significant increase in water and Na absorption occurred in rats with diarrhea when they were perfused with a 90-mmol/L-Na, 111-mmol/L-glucose OHS containing 30 mmol/L of L-alanine (Ala). The same effect on Na retention was observed with a protein hydrolysate (PrH) in rats with diarrhea. Glycine was not effective. Other experimental OHS were ineffective in rats with diarrhea. The data indicate that in this animal model of chronic diarrhea Na transport enhancers, such as Ala and a PrH, are most efficacious in the presence of higher Na concentration.

Absorption↗

PubMed1988

Alveolar enlargement in obesity-induced hyperplastic lung growth.

Structural changes underlying obesity-induced pulmonary cellular hyperplasia were evaluated by lung morphometry and stereology in 8-wk-old male Long-Evans rats made obese by nursing in small litters with subsequent feeding of a high-fat diet. Control animals were raised in normal-sized litters and then fed standard rat chow. Compared with controls, obese rats had significant elevations in body weight (31%), fat pad weight (158%), fat pad weight-to-body weight ratio (97%), snout-to-anus length (8%), snout-to-tail length (7%), serum insulin concentration (64%), fixed lung volume (56%), and the ratios of lung volume to body weight (18%) and lung volume to body length3 (24%). Lungs of obese rats had enlarged alveoli, with significant increases in mean (182%) and total (71%) alveolar volume, mean chord length (28%), and mean (89%) and total (25%) alveolar surface area. Surface density (24%), surface-to-volume2/3 ratio (24%), and numerical density (43-53%) of alveoli in obese rats were significantly diminished compared with lungs of control rats. Unchanged were total alveolar number and alveolar volume density. Measurements of perihilar and subpleural alveoli within the obese and control groups were indistinguishable. These results indicate the presence of alveolar enlargement with relatively diminished respiratory surface area in lungs of young rats made obese by diet. This relative decrease in gas-exchanging area may contribute to physiological and functional alterations present in obesity.

Animals↗

PubMed1987

Quantitative alterations in the structural development of jejunal absorptive epithelial cells and their subcellular organelles in protein-energy-malnourished rats: a stereologic analysis.

The effect of protein-energy malnutrition (PEM) on the structural development of rat jejunal absorptive epithelial cells was evaluated. Stereologic characteristics of jejunal histologic subcompartments, epithelial cell surfaces and volumes, and volumes of key subcellular organelles (nuclei, mitochondria, Golgi apparatus, lysosomes) in crypt and villus mid and tip cells were determined by morphometric analysis of light and electron micrographs in well-nourished rats and rats with PEM. In rats with PEM there were developmental alterations in cells migrating on villi that were not seen in crypt cells. The amplification of the apical microvillus surface between mid and tip levels in well-nourished rats (679-1085 micron2/cell) failed to occur in rats with PEM (807-729 micron2/cell). This resulted in an estimated 60% reduction of total jejunal absorptive surface, from 10,070 cm2 in well-nourished rats to 3975 cm2 in rats with PEM. In contrast, the development of the basolateral surface, which requires much less membrane accrual, was unaffected by PEM. Villus mid and tip cells of rats with PEM also had increased cell volume and mitochondrial volumes. Microvillus surface area per cell appears dependent on the number of microvilli per cell, which equals the cell flat surface times the microvillus numerical density (number of microvilli per square micrometer) in well-nourished rats. However, this relationship was not demonstrable in rats with PEM.

Animals↗

PubMed1987

Correlation of absent inner dynein arms and mucociliary clearance in a patient with Kartagener's syndrome.

Recent experimental studies have demonstrated extensive biochemical differences between the outer and inner dynein arms of cilia. The inner dynein arms are now emerging as the "prime movers" for ciliary clearance. We studied ciliary motility as evidenced by radioisotope mucociliary clearance, and the ultrastructure of respiratory cilia in a patient with Kartagener's syndrome. Cilia exhibited complete absence of only the inner dynein arms, while retaining outer arms, and mucociliary clearance was totally absent. We also studied neutrophil chemotaxis and other immunologic functions in our patient and found them to be normal. Our findings demonstrate an association between the structural abnormality of absent inner dynein arms alone and ciliary immotility in Kartagener's syndrome. The neutrophil migration abnormalities may have a different mechanism which needs further study.

Adenosine Triphosphatases↗

PubMed1986

Hepatitis in children with acquired immune deficiency syndrome. Histopathologic and immunocytologic features.

Hepatic morphology and immunocytology were evaluated in 4 children with clinical and immunologic characteristics of the acquired immune deficiency syndrome or acquired immune deficiency syndrome related complex. All 4 children had hepatomegaly and increased serum alanine and aspartate aminotransferase activity. Both lobular and portal changes were noted. Lymphocytic infiltration, piecemeal necrosis, hepatocellular and bile duct damage, sinusoidal cell hyperplasia, and endothelialitis were prominent. Vesicular rosettes in sinusoidal lymphocytes and tubuloreticular structures in sinusoidal endothelial cells were demonstrated by electron microscopy. The lymphocytic infiltrate in both the lobular and portal spaces was characterized by a relative increase of cytotoxic/suppressor (T8) cells. Hepatitis may be a common feature of pediatric acquired immune deficiency syndrome and acquired immune deficiency syndrome-related complex. Although the histopathologic changes are consistent with chronic active hepatitis, the specific pathogenesis remains to be determined.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Cancer family syndrome: marker studies.

Individuals from kindreds with the cancer family syndrome (CFS) have an increased hereditary risk for the development of adenocarcinoma of the colon in childhood and early adulthood. Previous studies have suggested that this high occurrence of adenocarcinoma may be due to a genetic defect in the control of colonic epithelial proliferation. Others have suggested that these families may have an underlying abnormality in immunologic tumor surveillance. We have investigated these possibilities in 15 cancer-free, at-risk individuals (10 children, ages 3-15 yr, and 5 adults) from two unrelated CFS kindreds. Colonic mucosal proliferative activity was studied by in vitro autoradiography after tritiated thymidine labeling in 7 subjects. The mean labeling index (12.7 +/- 0.9%) was comparable to that in controls, as was the distribution of thymidine labeling. Immunologic evaluation revealed depressed lymphocyte culture responses to stimulation by microbial antigens, but not to that by mitogens. Mixed lymphocyte culture responses were depressed in 4 of 8 subjects, but became normal in 2 of these after filtration through a Sephadex G10 column. Natural killer cell cytotoxicity was significantly depressed in 5 of 13 subjects, and borderline normal in another 3 subjects. These data suggest that many cancer-free members of CFS kindreds have a spectrum of in vitro cell-mediated immunologic defects that might interfere in vivo with the recognition or killing of incipient tumor cells.

Adenocarcinoma↗

PubMed1986

Alterations in jejunal transport and (Na+-K+)-ATPase in an experimental model of hypoxia in rats.

Hypoxia was induced by exposing rats to an atmosphere of 93% N2, 7% O2 for 4-48 hr. The animals became hypoxic as indicated by a decreased blood PaO2 (mean +/- SEM: 48 +/- 10 mm Hg). Hypoxia was accompanied by metabolic acidosis (pH 7.22 +/- 0.02) and decreased serum bicarbonate levels (9.0 +/- 4.0 meq/liter). Hypoxic rats also showed evidence of tissue hypoxia; liver tryptophan oxygenase levels were increased to 21 +/- 2 nmole/min/mg protein. In the hypoxic animals there was decreased jejunal mucosal (Na+-K+)-ATPase activity and an inhibition of active intestinal transport of sodium, glucose, 3-O-methylglucose, galactose, tyrosine, phenylalanine, and glycine as determined by in vivo perfusion studies. Jejunal fructose transport, which has a large passive component, was unaffected by hypoxia. The electrolyte, carbohydrate, and amino acid transport alterations produced by hypoxia were seen in the absence of an effect on jejunal cell number, DNA synthesis, or cell turnover. There was also no evidence of histological or ultrastructural damage. Furthermore, studies with a luminal macromolecular tracer, horseradish peroxidase, indicated that the jejunal lumen-to-blood barrier to macromolecules was also unaltered in these hypoxic animals. In vitro local oxygenation of the jejunum, by bubbling of 95% O2:5% CO2, markedly improved sodium and glucose (but not 3-O-methylglucose) absorption in hypoxic rats and control rats. The (Na+-K+)-ATPase activity of the jejunal mucosa of hypoxic rats was significantly enhanced by the local bubbling of 95% O2:5% CO2. Overall, our data indicate that during relatively mild conditions of hypoxia there is an inhibition of jejunal (Na+-K+)-ATPase activity and related transport processes that is prevented by in situ oxygenation.

Amino Acids↗

PubMed1985

Cyclic AMP-mediated jejunal secretion in lactose-fed malnourished rats.

We evaluated the effects of a hyperosmolar lactose load on the functional properties of the jejunal mucosa of protein-energy malnourished rats. Malnourished animals exposed to an oral lactose load showed an enhanced loss of DNA, protein, and sodium into the intestinal lumen as compared to well nourished controls exposed to the same lactose load. Only the jejunum of lactose-fed malnourished rats showed increased levels of 3'-5' cyclic adenosine monophosphate (cAMP), that appeared principally due to an enhancement of adenyl cyclase. Overall, our data strongly suggest that the intestinal mucosa in malnutrition is more sensitive and responds to an osmotic stress by enhanced secretion.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1984

Experimental focal segmental glomerulosclerosis: correlation with protein excretion, glomerular filtration rate, and renal plasma flow.

A rat model of focal segmental glomerulosclerosis (FSGS) produced by repeated injections of aminonucleoside (AMN) of puromycin was used to evaluate the relative roles of hemodynamic alterations and AMN-induced glomerular visceral epithelial cell injury in the development of FSGS. Twenty rats received three intraperitoneal injections of AMN on days 1, 21, and 28 and developed significant proteinuria. On day 50, 14 rats (group 1) underwent selective left renal perfusion with AMN and six rats (group 2) received left renal perfusion with saline. At sacrifice on day 70 or 110, group 2 rats had similar values in left and right kidneys for glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and the amount of FSGS (13.1 +/- 5.6% in left and 12.9 +/- 7.8% in right). In contrast, group 1 rats manifested a significantly higher amount of FSGS in right kidneys as compared to left kidneys (3.1 +/- 1.3% in left and 6.3 +/- 2.0% in right, as well as significantly diminished GFR and ERPF in left as compared to right kidneys. A higher degree of FSGS was seen in kidneys with a higher GFR and ERPF. A positive correlation was observed between the mean 24-h protein excretion of the rats and the percentage of FSGS in left and right kidneys (r = 0.66, p less than 0.01).

Animals↗

PubMed1983

Morphologic and clinical observations in human infection with Babesia microti.

On admission to the hospital, a splenectomized man was found to have 85% of his erythrocytes parasitized by Babesia microti. His extensive parasitemia allowed for direct study of the morphology and ultrastructure of this organism as it appears in human infection; the need for animal inoculation and rescue techniques was thus eliminated. Positive characteristics (other than the tetrad form) that are diagnostic for babesiosis were identified. By transmission and scanning electron microscopy, parasite-induced changes in the erythrocyte membrane were observed; these alterations may explain the hemolysis seen in babesiosis. Factors that may have allowed the patient to sustain such high-level parasitemia are considered. The experience with this patient confirms that exchange transfusion is a reliable, rapid method for reduction of the parasite load in serious infection with B microti.

Animals↗

PubMed1983

Altered jejunal macromolecular barrier induced by alpha-dihydroxy deconjugated bile salts.

The effect of deconjugated bile salt hydroxy group position and numbers on the ability of these agents to alter the normal lumen-to-blood jejunal barrier to intact protein penetration was analyzed. Only in vivo jejunal perfusion with 0.5 mM alpha-dihydroxy deconjugated bile salts chenodeoxycholate and deoxycholate led to increased penetration of the 40,000-molecular-weight protein horseradish peroxidase (HRP). This increased absorption of HRP with 0.5 mM chenodeoxycholate and deoxycholate was detectable biochemically, as well as by light and electron microscopic cytochemistry, and occurred in the absence of demonstrable histological or ultrastructural damage to the epithelium. Conjugation of chenodeoxycholate with glycine, epimerization of chenodeoxycholate from 7 alpha-hydroxy to 7 beta-hydroxy as in ursodeoxycholate, or addition of a third hydroxyl group as in cholate all eliminated the increase in jejunal HRP penetration and led to HRP absorption levels like those in bile salt-free preparations. The effect of chenodeoxycholate and deoxycholate on HRP absorption was paralleled by their production of net jejunal water secretion. The observations suggest that the naturally occurring alpha-dihydroxy bile salts may lead to an increase in intact antigen or toxin absorption during bacterial stasis syndromes.

Animals↗

PubMed1983

Disaccharide feedings enhance rat jejunal macromolecular absorption.

Disaccharide feedings to post-weaning rats alters their jejunal barrier to macromolecular absorption. Penetration of horseradish peroxidase (HRP) across the jejunum was enhanced after short-term high concentration gavage (30 g . kg-1 . day-1) of lactose that produces weight loss, osmotic diarrhea, and jejunal mucosal damage. HRP absorption was also increased by longer term feedings of lower levels of disaccharide that did not produce body weight alterations, diarrhea, or cell damage. Rats without diarrhea and gavaged with 7.5 g . kg-1 . day-1 of either lactose or maltose showed an increase in lumen to blood HRP absorption after 21 days of feedings. Also, lactose or maltose in the solid food diet at 30 g . kg-1 . day-1 for 21 days did not lead to diarrhea but produced an increase in jejunal lumen to blood HRP absorption. Rats having no diarrhea and receiving 15 g . kg-1 . day-1 of lactose or maltose in the drinking water for 21 days, showed an increase in jejunal HRP absorption. When rats were fed either lactose or maltose for 21 days glucose absorption became totally dependent upon the sugar concentration in the perfusion medium. The kinetics of this glucose absorption are compatible with a decrease in the "unstirred" layer. Disaccharide-induced HRP absorption may be mediated by transport from endocytotic vesicles across the jejunal epithelium.

Animals↗

PubMed1983

Selective fetal malnutrition: the effect of in vivo ethanol exposure upon in vitro placental uptake of amino acids in the non-human primate.

In vitro uptake (45 and 90 minutes) of amino acids, alpha-amino isobutyric (AIB) and valine (VAL), was measured in six placentae from the nonhuman primate, Macacca fascicularis. Three of the pregnant primates were chronically treated with ethanol before and throughout pregnancy (CHR); one during the last trimester only (LT); and two were controls (C). Compared to the C placentae, the LT placenta had significantly decreased uptake only for AIB at 45 min: 33.4 +/- 6.8% reduction (mean +/- S.E.) (P less than 0.05). In contrast, the CHR placentae demonstrated significantly reduced uptake (P less than 0.01) for both amino acids at both time points. Percent reduction at 45 and 90 min: AIB, 35.2 +/- 6.5% and 32.6 +/- 5.6% and VAL, 38.7 +/- 2.9% and 22.1 +/- 4.1%. The results indicate that chronic in vivo ethanol exposure impairs the in vitro placental uptake of two actively transported amino acids, using an animal with a placenta almost identical to the human.

Aminoisobutyric Acids↗

PubMed1983

Jejunal transport in experimental nephrotic syndrome.

In vivo jejunal transport of amino acids, monosaccharides, sodium, and electrolytes were studied in rats made nephrotic with puromycin aminonucleoside (PAN) and in pair-fed controls. Studies were performed 14 days after a single intravenous dose of PAN when rats were no longer edematous, but were still hypoproteinemic. There was decreased absorption of glucose, 3-0-methyl glucose, glycine, phenylalanine, histidine, water, and sodium in the nephrotic animals but transport of fructose, lysine and potassium was similar in the nephrotic and control animals. Enzyme kinetic studies for glucose transport showed a mixed type of inhibition affecting both Vm and Km. The jejunal mucosa of nephrotic and control rats had similar ATP content and enzyme activity for lactase, sucrase, maltase and (Na-K)-ATPase and the ratios of RNA to DNA were similar in the nephrotic and control rats. No abnormality of the jejunum was detected by light or electron microscopy. The data suggest that the impairment of absorption is a result of decreased activity of jejunal membrane carrier mechanisms. The altered transport may be secondary to effects related to the metabolic consequences of nephrotic syndrome and does not appear to be related to acute purine aminonucleoside toxicity, edema or malnutrition.

3-O-Methylglucose↗

PubMed1982

Burkitt's leukemia: a re-evaluation.

Two patients who presented with acute leukemia of Burkitt's cell type are discussed. Although one patient died within four months of diagnosis, the other has maintained a one year clinical complete remission. The clinical and morphologic picture of Burkitt's leukemia is nonspecific and therefore requires complementary studies including cytochemistry, transmission electron microscopy, cell surface markers and cytogenetics studies to establish diagnosis. Serial bone marrow aspirations with marker analyses may detect relapse at an earlier stage than conventional cytology, allowing therapy to be modified prior to overt clinical relapse.

Adult↗

PubMed1982

Glycerol-induced hypoglycemia: a syndrome associated with multiple liver enzyme deficiencies. Clinical and in vitro studies.

A 4 10/12 yr-old white male presented with a history of occasional grand mal seizures and hypoglycemic episodes after overnight fasting. Upon evaluation, he became hypoglycemic after 1 g/kg oral glycerol challenge (plasma glucose: 31 mg/dl in 45 min), but had normal glucose, alanine and fructose tolerance tests. He responded well to a glucagon challenge after 11 hr fast but he became hypoglycemic and could not normalize his blood glucose after a 2nd glucagon stimulation test after 17 hr of fasting. Studies conducted on a percutaneous liver biopsy, and compared with 3 non-hypoglycemic controls, showed reduced activities (20%-30% of normal) of alpha-glycerophosphate dehydrogenase, alpha-glycerophosphate oxidase and fructose-1,6-diphosphatase. Alpha glycerophosphate in the patient's liver was elevated. Two types of electrophoresis showed absence of one enzymatically active zone and overall decrease of staining intensity for alpha-glycerophosphate dehydrogenase. Other liver enzymes tested were normal. The 50% inhibition of the patient's liver fructose-1,6-diphosphatase by alpha-glycerophosphate occurred, in vitro, or lower concentration than in controls (11 versus 22-40 mM). Electron microscopy revealed hepatocytes with moderately swollen mitochondria that very occasionally contained dense inclusions in the inner mitochondrial matrix. After discharge from the hospital, the patient followed a normal course, with a regimen of multiple snacks and avoidance of high-fat food in the morning.

Child, Preschool↗