Felice Caramia

Analysis of the effects of the antiserum to the nerve growth factor in adult mice.

Abstract The effect of the nerve growth factor antiserum (NGF-AS) on adult mice has been studied at morphological and biochemical levels. A 5-day treatment of 3-month-old mice results in a marked volume reduction of sympathetic chain ganglia. This decrease in volume appears to be due in part to cell death, but to a major extent to atrophy of residual neurons. A severe impairment of the sympathetic function also obtains, as indicated by a marked decrease of catecholamine uptake and content in peripheral organs. A few weeks after the end of treatment, a gradual and progressive recovery of the sympathetic function ensues, and the nerve cells regain their normal appearance. These results are described in connection with the problem of the site of action of NGF antibodies in immature and in fully differentiated sympathetic neurons.

The ultrastructural basis for the identification of cell types in the pancreatic islets

SummaryThe pancreatic islets of rabbit, dog and opossum have been studied by light and electron microscopy. Silver-positive cells in the rabbit are predominantly sandwiched between the peripheral A and central B cells, and by electron microscopy are identified as D cells. Pancreatic islets in the tail of the dog pancreas have A, B, and D (silver-positive) cells, but the islets in the uncinate process of the dog pancreas lack phosphotungstic acid hematoxylin-positive A cells. By electron microscopy the characteristic D cells are found in both tail and uncinate process, but A cells are confined to the tail islets, confirming the identification of cell types. A unique cell type termed the F cell is found in the dog uncinate islets and it is characterized by secretory granules of angular profiles. In the opossum, the A cells contain considerable amounts of glycogen demonstrable by both light and electron microscopy. A unique cell type is also present in the opossum islets termed an E cell (Thomas, 1937), which has large secretory granules (400–500 mμ). The physiological implications of a multiplicity of cell types in pancreatic islets is discussed.

Ultrastructure of mouse submaxillary gland: I. Sexual differences

Normal male and female mouse submaxillary glands have been studied by light and electron microscopy. The female gland is characterized by the presence of secretory granules in the intercalated duct nearest the acinus and a striated secretory tubule, i.e., a tubule with basal mitochondria similar to a striated duct but also containing secretory granules in the apical cytoplasm. The striated secretory tubule is found following the intercalated duct. The male has a very prominent secretory tubule in which two types of cells are present, one relatively clear, the other the dark cell of Pfluger. A striated secretory tubule is absent in the male. The male secretory tubule is also characterized by the presence of intracellular canaliculi.

In vitro effects of the nerve growth factor on the fine structure of the sensory nerve cells

Summary Dorsal root ganglia from 8-day chick embryos were explanted in semisolid media with or without a specific nerve growth factor (NGF). The ganglia were incubated for a period of 4 and 12 h and examined with the electron microscope. The presence of the NGF in the culture medium calls forth striking and rapid changes in the fine structure of the neurons. The nuclei develop an irregular contour and denser clumped chromatin in comparison with the controls. In the cytoplasm the Golgi apparatus is dilated; in some cells there is a massive increase in ribosomes associated with increased number of membranous elements of endoplasmic reticulum. Neurofilaments and neurotubules, sparse in control cultures, are already prominent after 4 h of incubation in the presence of the NGF. After 12 h, the cytoplasm of most ganglionic cells is packed with large masses of neurofilaments.

The ultrastructural basis for the identification of cell types in the pancreatic islets. I. Guinea pig.

SummaryThe pancreatic islets of the guinea pig have been studied by light and electron microscopy. The B granules in glutaraldehyde-fixed tissue often are cup-shaped with an indentation visible on one side of the granule. Phosphotungstic acid hematoxylin (PTAH) positive cells have been characterized by electron microscopy as three subtypes based on the size of the secretory granules. Aa cells are the most common and have secretory granules around 200 mμ in diameter. Ab cells have large secretory granules around 300 mμ in diameter and are relatively infrequent. Ac cells are the least common and have small (160 mμ) granules. Characteristic D cells are identifiable by electron microscopy and, on the basis of the subsequent study (Munger, Caramia, and Lacy, 1965), are identified as the silver positive cells observed by light microscopy.

Alterations in the fine structure of nucleoli in sympathetic neurons following NGF-antiserum treatment.

Summary Antiserum to the nerve growth factor (NGF) produces a severe cytotoxic effect on sympathetic nerve cells when injected into newborn mice. The early cytological lesions were studied by electron microscopy in superior cervical ganglia of 1-day-old mice 12 and 24 h after antiserum treatment. In line with previous observations, early and marked ultrastructural changes were observed in the nuclear compartment. Alterations in the fine structure of nucleoli of the nerve cells are very prominent by 12 h after the As injection. The early alterations consist of condensation and disarrangement of the nucleolar components, which become progressively more severe in the following hours. Distinct dense bodies form from the separation and condensation of the nucleolar material and eventually the nuclear envelope breaks down and cytoplasmic and nuclear material mix. In later stages, marked disorganization of ribosomes and mitochondria is apparent in the cell cytoplasm. Incorporation experiments show that RNA synthesis is markedly reduced in the experimental ganglia already 12 h after the As injection.

Ultrastructural changes in sympathetic neurons of newborn and adult mice treated with nerve growth factor

Purified nerve growth factor (NGF) induces a marked hypertrophy of the sympathetic chain ganglia when injected into newborn and adult mice. A 5-day treatment of newborn or adult mice with daily injections of NGF (20 μ g/g body weight) results in both instances in a striking increase in wet weight of sympathetic ganglia. When examined at the electron microscope, the NGF—treated neurons appear very enlarged: the endoplasmic reticulum and free ribosomes are very abundant. The cytoplasmic area is filled with the interlacing bundles and threads of neurofilaments. This extraordinary production of neurofilaments and neurotubuli appears to be the most striking feature of the NGF—treated neurons.

Structural and ultrastructural changes in developing sympathetic ganglia induced by guanethidine

Abstract Injections of guanethidine into newborn mice and rats result in progressive and irreversible lesion of sympathetic ganglia and in a complete sympathectomy similar to that obtained with a specific antiserum to the nerve growth factor (NGF) (immunosympathectomy) and with 6-hydroxydopamine (chemical sympathectomy). Studies at the optical microscope performed in the first days after administration of guanethidine show the progressive disappearance of immature neurons and a marked increase of glial and satellite cells. Two months after discontinuation of the treatment the sympathetic ganglia are reduced to sclerotic nodules barely detectable at the dissection microscope. The nerve cell population of para- and prevertebral chain ganglia is reduced to 3–5% of that of controls. Studies at the electron microscope performed toward the end of the first week of treatment on the superior cervical ganglion show, in some neurons, mitochondrial lesions and in others dilation and disruption of the endoplasmic reticulum. The destructive effects caused by guanethidine are discussed and compared with those caused by 6-hydroxydopamine and bretylium tosylate.

A glycogen body in liver nuclei

A new aspect of nuclear glycogenosis has been investigated by electron microscopy in liver biopsies from two patients. This consists of a round agglomerate (1–2 μ in diameter) of packed glycogen particles enclosed by a relatively dense halo. In many instances, the surrounding halo contained one or several very dense particles separate from the glycogen deposit. Outside this zone, depending on the extent of glycogen deposition, glycogen particles also were scattered diffusely in the nucleoplasm.

Ultrastructure of mouse submaxillary gland: II. Effect of castration in the male

Male mouse submaxillary glands have been studied by electron microscopy at 1, 2, and 3 months following castration. The secretory tubules were reduced in volume and secretory granules reduced in number. The intracellular canaliculi became enlarged in the apical cytoplasm, and some appeared to be greatly distended. The dark cell of Pfluger could not be identified. Tubules similar to striated secretory tubules characteristics of the female gland occasionally were found. Castration does not result in the male gland becoming female in type—rather the gland of a male castrate is characteristic in appearance.