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Biomedical subjects

J A Terzakis

Publications and source records attributed to J A Terzakis.

At least 19 recordsLinked to original sources

Malignant granular cell tumor.

We report a case of malignant granular cell tumor present in the left medial mid-thigh of a 69-year-old black male. The lesion was grossly fungating, partially ulcerated and measured 14 cm in largest diameter. Light microscopy, electron microscopy and immunohistochemistry techniques were used to confirm the preliminary cytologic diagnosis of malignant granular cell tumor. Diagnostic criteria of malignancy for such lesions are reviewed. Immunohistochemical and ultrastructural analyses support a neural or Schwann cell origin for the tumor. Clinical outcome for such lesions is discussed.

Aged

Activation of c-Ki-ras in human gastrointestinal dysplasias determined by direct sequencing of polymerase chain reaction products.

Activation of c-Ki-ras by point mutation within exon 1 was studied in 33 specimens of dysplastic gastrointestinal lesions or of cancers presumed to arise from dysplasia. Samples were obtained from patients with underlying ulcerative colitis or Barrett's esophagus, two diseases associated with dysplasia and increased rates of colonic or esophageal adenocarcinoma, respectively. Genomic DNA was amplified using primers bounding this exon in the polymerase chain reaction. Polymerase chain reaction products were analyzed by direct dideoxy sequencing. Three point mutations in codon 13 of c-Ki-ras were found, all in colonic specimens (two high-grade dysplasias and one adenocarcinoma arising in ulcerative colitis). No point mutations were observed in the second exon of c-Ki-ras or in and around codons 12, 13, and 61 of c-N-ras and C-Ha-ras in a partial sampling of the specimens. These data indicate that ras family protooncogene activation is an uncommon event at this level of malignant progression in these disease states. Carcinogenesis in ulcerative colitis and Barrett's esophagus may proceed via different pathways than in sporadic colon cancer, perhaps involving loss or inactivation of suppressor genes.

Adenocarcinoma

Ultrastructural features of epithelial cell degeneration in rectal crypts of patients with AIDS.

Focal crypt epithelial cell degeneration (apoptosis) of the rectum is a characteristic pathologic feature in AIDS. The presence of apoptosis usually implies cell-mediated cytolysis, which would be an unexpected finding in this disease. We investigated the ultrastructural features of apoptosis in rectal biopsies from five AIDS patients (three homosexual males and two females with i.v. drug abuse), three heterosexual controls, and two homosexual male controls. Apoptosis was found in all AIDS patients and, to a lesser extent, in one heterosexual control. Ultrastructurally, vacuolization of several adjacent cells, leading to extrusion of cellular debris through the basal lamina and phagocytosis by macrophages, was seen. No intracellular or extracellular viral particles were detected in the regions containing apoptotic bodies, in epithelial cells near the crypt bases, in intraepithelial lymphocytes, or in macrophages. In summary, apoptosis in the rectal crypts of patients with AIDS has the same ultrastructural features as in other conditions, which suggests that its pathogenesis is related to immune rather than infectious factors. If this process occurs on a chronic basis in multiple cell types, it would promote general tissue depletion, which has been demonstrated to occur in AIDS. The presence of apoptosis in AIDS is not explained by current concepts of disease pathogenesis.

Acquired Immunodeficiency Syndrome

Bronchial adenocarcinoid tumor metastatic to skin.

A pulmonary neoplasm, evident initially as a metastatic nonpruritic skin rash in a 51-year-old man, progressed during a period of four months, leading to the patient's death. Histologic and histochemical studies of the skin metastasis, which were confirmed by transbronchial biopsy, demonstrated an adenocarcinoid tumor. Further ultrastructural studies of the skin metastasis showed that many tumor cells contained neurosecretory granules, although histochemical analyses had revealed the presence of only a few such tumor cells. Furthermore, in some cells both mucin and neurosecretory granules were present in the cytoplasm, confirming a previous observation in normal human segmental bronchi. These findings support the endodermal origin of such neoplasms.

Adenocarcinoma, Mucinous

Compartment syndrome caused by a traumatized vascular hamartoma.

A case report is presented of a traumatized vascular hamartoma producing a forearm flexor compartment syndrome; such a case has not been reported previously. The role of minor trauma in this case was important. There is a need for a high degree of suspicion in order to make an early, accurate diagnosis. Delayed surgical decompression and resection of the pathologic muscle resulted in a dramatic improvement in sensibility and digital mobility.

Adult

X-ray microanalysis of crystalline material in the liver of a narcotics user.

A 22-year-old athlete, who had had intravenous injections of narcotics in the past, developed a viral hepatitis with markedly altered liver enzyme values. Studies revealed evidence of a virtual cure of hepatitis B virus and a current infection with delta agent. Liver biopsy showed a mixed-cell portal inflammation and doubly refractile crystalline particles. These particles were shown by energy-dispersive x-ray microanalysis to contain calcite, silica, talc, and a variety of elements including Al, P, S, Cl, K, Ti, Cr, Fe, Ni, Br, Yb, Os, Ir, and a trace U. The predominance of Ca-containing compounds suggested that the foreign material was present as a result of the chemical preparation of the narcotic or as a narcotic diluent. The potential for pathologic alteration by the various substances is discussed. These observations support the idea of particulate-induced hepatic disease advanced previously by others.

Adult

Pheochromocytoma producing immunoreactive ACTH with Cushing's syndrome.

A 42-year-old female with clinical and endocrine indications of Cushing's syndrome, as well as periodic hypertension and increased urinary catecholamines and their metabolites, benefitted from removal of a pheochromocytoma. Adrenocortical hyperplasia was present. Electron microscopy showed catecholamine-type granules in the tumor cells; in addition, immunoreactive ACTH, leu-enkephalin, somatostatin, and serotonin were identified. Such studies were performed for the first time in this unusual condition.

Adrenal Gland Neoplasms

Widespread foreign-body granulomas and elevated serum angiotensin-converting enzyme.

A patient had extensive foreign-body granulomatous inflammation of multiple skin sites and of the inguinal lymph nodes with splenomegaly, cutaneous anergy to common skin antigens, and peripheral blood eosinophilia. The patient had an elevated serum angiotensin-converting enzyme level. Histologically, the granulomas were of the foreign-body type with lymphocytes, histiocytes, eosinophils, and giant cells, some that contained doubly refractile crystalline material. Electron-probe x-ray microanalysis identified silicon, magnesium, iron, calcium, phosphorus, zinc, titanium, and chromium in the crystalline material. These findings suggest talc, cement, and inorganic pigment as possible sources of the crystals. This case is reported for its unusual clinical, laboratory, and morphologic features.

Biopsy

Direct infection of hepatocytes by sporozoites of Plasmodium berghei.

To identify the unknown liver cell type initially invaded by sporozoites of mammalian malaria, young rats were inoculated intravenously with large numbers of Plasmodium berghei sporozoites obtained from infected Anopheles stephensi mosquitoes. Fine structural studies of liver specimens obtained from the rats within 2 min after inoculation demonstrated the presence of morphologically unaltered sporozoites in the cytoplasm of hepatocytes. Many sporozoites were also observed undergoing cytolysis within the lysophagosomes of Kupffer cells, as well as other phagocytic cells. These observations strongly suggest direct infection of the hepatocyte by the sporozoite.

Animals

Exoerythrocytic merozoites of Plasmodium berghei in rat hepatic Kupffer cells.

Liver biopsies of white rates infected by Plasmodium berghei sporozoites were examined by electron microscopy. Intrahepatocytic schizont development was confirmed. In addition, at 60 and 70 h after sporozoite inoculation, exoerythrocytic merozoites were noted in Kupffer cells of liver sinusoids. Although it is theoretically possible that this observation may be of merozoite development in Kupffer cells, the authors suspect that this example of phagocytosis would be one of the host's natural defenses against sporozoite-transmitted malaria.

Animals

Neuroendocrine cells in dysplastic bronchi: ultrastructural observations and quantitative analysis of secretory granules and the golgi complex.

Ultrastructural and biochemical studies have suggested that bronchopulmonary carcinoids and oat cell carcinomas may be derivatives of neuroendocrine cells; their amine and/or peptide secretory capabilities may at times be reflected in clinical hormonal syndromes. This investigation was prompted by the hypothesis that dysplastic neuroendocrine bronchial cells may also exhibit structural and functional aberrations of their secretory apparatus. Surgical specimen samples from 5 human dysplastic bronchi were studied ultrastructurally; 7 normal bronchi served as controls. Golgi complexes of dysplastic cells were distinctly less prominent than those of the controls. Moreover, the Golgi vesicles of dysplastic cells appeared significantly smaller than their counterparts in normal cells (P less than 0.01). Also, dysplastic neuroendocrine cells displayed significantly fewer secretory granules per cell than the controls (P less than 0.05). These findings indicate structural abnormalities in the secretory apparatus of neuroendocrine cells in dysplastic bronchi and correlate with experimental observations of aberrant hormonal production associated with bronchial dysplasia. Thus, the possibility arises that bronchial epithelial dysplasias may be detected and monitored through laboratory determinations of their secretory products.

Bronchi

Viruslike particles in malaria parasites.

The ultrastructural appearance of viruslike particles in several malaria parasites at different times in sporogony is described in detail. Emphasis is placed on particle size, 42 to 52 nm, density and the presence or absence of geometric configuration of particle aggregations in P. berghei ookinetes, and P. gallinaceum early oocysts. This particle appearance is compared with that noted in later oocysts of P. berghei, P. gallinaceum, and P. c. bastianelli and with negatively-stained particles obtained by fractionation of A. stephensi mosquito medguts heavily infected by P. berghei oocysts. Although particles are dispersed in later oocysts, particle size and shape is similar to that noted in the aggregates found in early forms. Aggregations of particles in a geometric configuration in ookinetes and early oocysts is associated with a particle of smaller diameter and the absence of a limiting membrane or envelope. This suggests an incomplete or nascent virus particle form. The observations of such particles in malaria and other blood parasites is compared with the present findings.

Animals

Squamous differentiation and basal lamina deposition in endometrial adenoacanthoma.

Eleven endometrial adenoacenthomas were studied ultrastructurally. Special emphasis was placed on patterns of squamous metaplasia and the appearance of the basal laminae. Tonofibrils, irregular keratohyaline, abundant desmosomes, and foci of frank keratinization were observed. However, the granule population was small, with relatively scanty keratohyaline and no definite membrane coating granules. These features resemble squamous metaplasia observed in various epithelia; experimental models utilizing estrogens also resulted in similar changes. This observation appears pertinent in view of the possible etiologic role played by high estrogen levels in the development of human endometrial carcinoma. Most tumor cell clusters were surrounded by a well-defined basal lamina; focal basal lamina reduplication was also observed. These observations suggest a high level of differentiation in respect to synthetic capabilities and cell surface recognition. They correlate well with the relatively favorable prognosis generally observed in endometrial adenoacanthomas. However, these conclusions are tempered by the finding of occasionally absent or defective basal lamine, indicative of partial dedifferentiation of some neoplastic cells.

Adenocarcinoma