Rat as a potential model for hearing loss in biotinidase deficiency.

Biotinidase deficiency is an inborn error of metabolism that is transmitted as an autosomal recessive disorder. Symptoms include hearing loss, ataxia, blindness, mental retardation, and seizures. The metabolic defect is an inability to recycle the vitamin biotin, which is an important cofactor in key enzymes. We therefore sought to develop an animal model for this disorder by inducing biotin deficiency. Rat pups were divided into control and experimental groups. Control rats were fed a normal diet whereas experimental animals were given a diet deficient in biotin. Animals from both groups underwent brain stem auditory evoked potential testing at various ages. Wave I thresholds at various ages were similar in both groups. Latencies for wave I, however, and interpeak latencies (I-IV) were prolonged in the biotin-deficient groups compared to controls. Scanning electron microscopy of the organ of Corti in biotin-deficient animals showed no significant hair cell loss. The biotin-deficient developing rat appears to acquire functional changes in the auditory brain stem. These effects may be caused by defective myelination, since biotin is important in fatty acid metabolism.

The effect of maternal smoke exposure on the ultrastructure of fetal peripheral blood vessels in the mouse.

Ultrastructural changes have been found in umbilical blood vessels, placental blood vessels, and peripheral blood vessels of human fetuses whose mothers smoked during pregnancy. This study was undertaken to determine if similar changes could be found in peripheral blood vessels of mice fetuses whose mothers were exposed to cigarette smoke during pregnancy. Breeding mice of the C57BL/KsJ strain were placed in a smoking box similar to that described by Younoszai and exposed to cigarette smoke intermittently. This produces carbon monoxide levels in the adult mice similar to that found in human adults smoking one pack of cigarettes per day. Similarly caged mice of the same strain were used as controls. The female mice were not removed from their cage from pre-conception time until after delivery. Upon delivery each pup was sacrificed via neck fracture and the entire pup was immersed in a solution of 2.5% glutaraldehyde in 0.1 M cacodylate buffer at pH 7.3. While still under solution, the rear leg muscles were dissected free, sliced, and immersed in the same preservative for four to five hours. They were then placed in fresh 2.5% glutaraldehyde mixture overnight. The tissues were post-fixed in osmium ferrocyanide and en-block stained with uranyl acetate in a graded series of alcohol. The tissues were infiltrated with and embedded in Spurr. Sections were taken via an ultramicrotome and post-stained with uranyl acetate and lead citrate. The sections were examined in a Philips 201 electron microscope at 60 KV. In the peripheral vessels of the fetuses from smoke-exposed mothers, endothelial blebbing (both surface-type and vacuole-type) was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Ultrastructural changes in neonatal sciatic nerve tissue: effects of passive maternal smoking.

The dangers of cigarette smoking having already been recognized, this study attempts to delineate findings from a passive smoking study at the ultrastructural level. The project utilized a model of mice subjected to cigarette smoke and encompassed the electron microscopic examination of neonatal tissue for morphological abnormalities. Study of sciatic nerve tissue taken from the offspring of passively smoked females revealed definite toxic effects on the neonatal tissue. This investigation, which concentrated on morphological changes, indicates that passive maternal smoke inhalation may result in abnormal changes to the fine structure of fetal tissue although further investigation in this area is necessary to broaden our knowledge and understanding of the mechanisms involved.

Ultrastructural changes in neonatal liver tissue: effects of maternal drinking.

There is already sufficient evidence in the literature that alcohol abuse during pregnancy has a toxic effect upon the developing fetus; however, previous studies have not revealed any morphological changes in fetal or newborn liver specimens from animals exposed to alcohol in utero. As it is known that alcohol freely crosses the placental barrier, this investigation was an attempt to demonstrate that structural abnormalities can indeed be identified in neonatal mouse liver specimens from pups exposed to alcohol in utero. Chosen as a model for this study was the C57BL/KsJ mouse strain as this particular animal demonstrates an alcohol preference paralleling that of the human alcoholic. Findings appear to indicate the presence of abnormal changes on the morphological level in these study animals.

Ultrastructural changes in preputial neural tissues: effects of maternal drinking.

Peripheral nerves in the prepuces of eight newborns were studied in this investigation. The mothers of four of these newborns were alcohol abusers but did not smoke or take coffee. The other four mothers did not drink alcohol or coffee, nor did they smoke. Using a transmission electron microscope, the peripheral nerves in preputial specimens were studied for pathological changes. In samples taken from the prepuces of those newborns with drinking mothers, the neuropathological changes seen were mainly in the unmyelinated axons. These demonstrated increased vesicular and tubular elements of agranular endoplasmic reticulum and dense bodies not found in the specimens taken from the non-drinking group. Other significant findings in the fetal preputial specimens from the alcohol group were aggregations of mitochondria and collagen entrapment.

Ultrastructural changes in preputial neural tissues: effects of maternal smoking.

The fetal prepuce was studied for neural changes due to maternal smoking during pregnancy. Prepuces from 10 newborns whose mothers smoked throughout pregnancy and from 4 newborns of nonsmoking mothers were examined by transmission electron microscope. Significant ultrastructural changes were seen in the neural tissues of the newborns of smoking mothers. The ultrastructural changes observed were: (1) local aggregation of mitochondria; (2) many myelin bodies, and (3) dilated Golgi apparatus and dilated endoplasmic reticulum of the Schwann cell. Similar changes have been reported in neuropathies due to various drugs, chemicals and deficiency states. These findings suggest adverse effects on fetal preputial neural tissue due to maternal smoking.

Cyclic AMP-induced morphological transformation of cells infected by temperature-sensitive mouse sarcoma virus. Expression of transformation-associated markers.

Normal rat kidney (NRK) cells infected with a temperature-sensitive (ts) mutant of mouse sarcoma virus (NRK [MSV-1b]) express the transformed phenotype when grown under permissive conditions, but acquire the normal phenotype when grown under restrictive conditions. Addition of 3', 5' cyclic adenosine monophosphate (cAMP) to NRK (MSV-1b) cells grown at the restrictive temperature results in morphological transformation. To determine whether other markers associated with the transformed phenotype were coordinately expressed after cAMP exposure, concanavalin A (Con A) agglutinability, hexose transport rate, and incorporation of radioactively labeled fucose into fucolipid III and fucolipid IV (FL III and FL IV ) of the cells were examined. NRK cells transformed by wild-type MSV or NRK(MSV- 1b) grown under permissive conditions were agglutinated by low concentrations of Con A and exhibited relatively high maximal agglutination levels which were specifically inhibited by alpha-methyl-D-mannoside. In contrast, NRK (MSV-1b) cells grown under restrictive conditions were weakly agglutinated by Con A and exhibited reduced maximal agglutination levels, similar to uninfected NRK cells. Treatment of NRK (MSV-1b) cells at the restrictive temperature with cAMP resulted in morphological transformation and a change in the pattern of incorporation of labeled fucose inot FL III and FL IV to one comparable to that of NRK (MSV-1b) cells at the permissive temperature or to NRK cells transformed by wild-type MSV. In contrast, cAMP treatment resulted in no increase in Con A agglutinability or 2 deoxy-D- [(3)H]glucose transport relative to mock treated cultures. The results demonstrate that cAMP-induced morphological transformation and altered fucolipid composition of NRK (MSV-1b) cells are not correlated with alterations in hexose transport rate or Con A agglutinability.