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Interstitial lung lesions were induced in mice by high-dose methotrexate with high frequency. They appeared early after treatment; their onset, evolution and recovery parallelled those of lesions to the hemopoietic tissues and the intestine. The pathogenesis of methotrexate lung toxicity in mice is discussed. Leucovorin rescue was ineffective in preventing the lung lesions induced by high-dose methotrexate.

In this study, different groups of mice were treated with a single high-dose of methotrexate or with a leucovorin-methotrexate association, and the changes in structure and cell types of the small intestine were studied histologically. The results suggested that leucovorin rescue diminished the degree of mitotic abatement induced by methotrexate in the first days after treatment, with better preservation of enteric structures and the cell type ratio.

In vitro infection of human cord blood lymphocytes (CBL) with human T-cell leukemia/lymphoma virus type I (HTLV-I) was found to be reduced by suramin treatment at a concentration ranging from 10-100 micrograms/ml. At higher concentrations (500 micrograms/ml) suramin was toxic to the cells and even resulted in an increased percentage of cells positive for the p19 viral core protein. Suramin treatment at the onset of the CBL coculture with a lethally irradiated HTLV-I donor cell line (MT-2) reduced virus transmission, evaluated as number of p19+ cells, and the consequent amount of integrated provirus in the host genome. The amount of viral RNA transcripts was not reduced in CBL cocultures. On the other hand, suramin affected HTLV-I replication in infected MT-2 cells, when used at a concentration of 50 micrograms/ml, and this might contribute to the reduced infectivity of suramin-treated MT-2 cells. In addition to its antiviral effects, suramin exerted a modest positive regulation on the natural killing activity of CBL and their early proliferative response in mixed lymphocyte/tumor cell culture.

Several yeast species in the genera Candida, Saccharomyces and Cryptococcus showed powerful immunoadjuvant, chemotherapy-synergic effects against a histocompatible, virus-induced murine lymphoma. Sensitizing and booster intraperitoneal injections of 2 x 10(7) yeast cells on days -14 and +1 (with respect to tumor challenge on day 0) followed by treatment with antiblastic drugs (on day +5) were required to elicit optimum activity. The antitumor effect was not markedly influenced by the morphological growth form of merthiolate-inactivated C. albicans nor by the nature of the carbon source in the growth medium, except for C. albicans cells grown in a medium containing stearic acid, which were not effective. These cells had a higher ratio of soluble to insoluble cell wall components, as compared to glucose-grown cells, but this finding alone could hardly explain the lack of antitumor effects. Previous observations, suggesting that the alkali-acid insoluble beta-glucan (in the form of cell wall ghosts) is the only component of yeast cell walls endowed with antitumor activity comparable to that of whole cells, were confirmed and extended; the soluble mannan and glucan-protein fractions were unable to replace whole cells and glucan ghosts even as sensitizers or as boosting agents.

The appendectomy specimens submitted to surgical pathology exhibit a wide variety of morphological appearances. We have evaluated the activities of acid phosphatase, alpha-naphthyl esterase, and leucineaminopeptidase in 100 human appendixes divided into six age groups in order to ascertain whether any histochemical pattern was related to the age group rather than to pathological condition. Our findings support that the submucosal fibrosis is unrelated to the patient's age, as well as appendiceal obliteration. It is noteworthy that the mucosa of the appendix may retain its lymphoid constituents at any age and that young subjects may already show appearances of involution up to lumen obliteration.

Histopathology may serve a wide spectrum of diagnostic purposes in tropical medicine other than for infectious and parasitic diseases. In addition, it is essential in defining new pathological entities and collecting statistical data on morbidity and mortality. It should also constitute a basic support for advancement and research in tropical diseases. For practical purposes, both histopathology and cytopathology are often more effective than clinical chemistry and microbiology in providing the clinician with a final diagnosis. They do not rely on complicated and delicate equipment, and the few reagents they require can be stored indefinitely. Formalin fixation permits most histological methods to be used, including special stains and immunohistochemistry. Formalin-fixed material can be examined several days after excision. Implementing pathology laboratories in tropical countries may constitute a practical, cost-effective approach to the planning of diagnostic services at the regional or district level. A fraction of the medical graduates in developing countries should be devoted to the staffing of these laboratories.

At the autopsy of a 64-year-old man, a small ectopic liver lobe without biliary drainage was found in the retroperitoneum. Both the liver and the ectopic lobe showed micronodular cirrhosis. In the latter, biliary hyperplasia and bile plugs were also seen.

The accuracy and usefulness of the score classifications most currently in use to assess testicular biopsies for infertility were comparatively evaluated in 40 consecutive specimens of the years 1979-1982. Our results suggested that score methods should be rejected and a comprehensive estimate of the morphological characteristics of the testis should be given, if no specific cause of damage can be recognized.

Lesions of the central nervous system were seen in 13/22 autopsies of Italian subjects affected by the acquired immune deficiency syndrome and including 19 intravenous drug addicts. Multinucleated cells similar to those originally described by Sharer et al. [1985] in response to direct central nervous system lesions by the human immune deficiency virus were seen in five subjects. Isolated or multiple opportunistic infections of the brain including cerebral toxoplasmosis (7 cases), progressive multifocal leukoencephalopathy (4), cytomegalovirus encephalitis (3), and tuberculous meningoencephalitis (2) were recognized. Finally, three cases of primitive cerebral lymphoma of large round cells were found. The central nervous system is a target, like the lymphoid tissue, of direct damage for the human immune deficiency virus, and it is frequently affected by opportunistic infections due to the immunological impairment sustained by the acquired immune deficiency syndrome.

The volume of the adenomatous mucosa (V), the area of the surface epithelium (Ss), the area of the glandular epithelium (Sg), and the Sg: Ss ratio were calculated in a series of 14 adenomatous polyps (APs) of a case of multiple polyposis of the colon. The equation of simple allometry was used to study the relative growth of the four series of values. Ss grew isometrically with size; Sg overgrew Ss and accounted for most of the increase in V. The Sg:Ss ratio increased with Sg and V.

This work is concerned with the morphometric analysis of 19 subcutaneous hemangiomas of capillary and cavernous types, to investigate their evolution. Our results suggest that hemangiomas in adults are of malformative nature, and that there is no clear-cut separation between the above types, which only designate extreme patterns of non-intermittent series. Cavernous changes are probably due to blood flow and intravascular pressure in originally capillary hemangiomas.

The ultrastructure of the nervous tissue in a benign ovarian teratoma is described. This tissue was organized into areas having both "meningeal" and "ependymal" surfaces, between which were found astrocytes, ependymal cells, neurones with synapses and microglia. These cells all had ultrastructural similarities to their normal counterparts in the nervous system. In addition, some signs of degenerative change--due possibly to the abnormal location of the nervous tissue--were observed. Oligodendrocytes and myelin were absent, possibly because of vascular insufficiency.

Five cases of melanosis of the larynx, verified by biopsy, are reported. All occurred in male patients. Melanocytes and melanin-laden epithelial cells were microscopically seen in the laryngeal mucosa. In one case squamous carcinoma coexisted. Current theories on melanin pigmentation at atypical sites are reviewed.

This work is concerned with a morphometric analysis of cystadenolymphoma (CAL, Warthin's tumor), a growth generally found in the parotid gland. CAL is composed of various amounts of epithelium-lined cysts and of lymphoid stroma. Our results support the notion that the epithelium is the proliferating component in CAL. They also challenge the idea that CAL is a tumor, because its growth is slow and self-limiting, and occurs in a restricted space.

An increased prevalence of nocardiosis has been reported in patients receiving immunosuppressive therapy, or affected by immunodeficiency disorders and autoimmune diseases. A case of severe Nocardia lung infection with pleurisy and hematogenous spread to the

The results of Grimelius' silver impregnation method and of two immunohistochemical methods for the demonstration of the sites of storage of parathyroid hormone (PTH) were compared in a series of parathyroid glands from 39 patients affected by either hyperplasia or adenoma and from 10 normal subjects. An indirect immunoperoxidase method using an anti-bovine PTH serum gave unsatisfactory results. In contrast a biotin-streptavidin immunoperoxidase method using an antibody against the 44-68 amino acid sequence of human PTH yielded similar results to those with Grimelius' silver impregnation method. This supports the view that argyrophil granules correspond to the secretory granules of PTH. The degree of silver impregnation, however, varied considerably in duplicate sections, probably because of difficulties in standardization of the Grimelius' method. The biotin-streptavidin method appeared more sensitive and was reproducible. The immunohistochemical demonstration of PTH may prove useful in defining the sites of hormone storage in normal and pathological conditions.

Two degenerations of the mitral valve apparatus, namely myxoid degeneration of the mitral cusps and necrosis with subsequent calcification of the annulus fibrosus, are extensively reviewed and discussed. Both lesions are mainly noticed in elderly patients, with the possible exception of systemic dystrophies of the connective tissue associated with metabolic disorders. The clinicopathological correlations of several cases are reported, with special emphasis on modern diagnostic procedures and their wide anatomic spectrum.

Two cases of granular cell tumour of the oesophagus and one case of granular cell tumour of the larynx are reported. The light and electron microscope findings are discussed, as well as the much debated histogenesis of such tumours.

Whereas the numbers of nerve cells in several areas of the cerebral cortex are reported to decrease with aging, the fate of the neurons of the subcortical nuclei is controversial. This work is concerned with a morphometric study of the nerve cell population of the putamen through cell counting in 24 subjects aged 62 to 90 years. Our data suggest that there is no significant decline in the small-cell density with aging, nor any differences according to sex. No conclusions on the functions of the aging brain should be inferred from cell counting alone, since other signs of functional damage, such as impairment of the synapses or decrease in their number probably precede cell loss.

The ultrastructural appearances of preneoplastic liver nodules induced in male Wistar rats through sequential treatment with diethylnitrosamine (DENA) and 2-acetylaminofluorene (2-AAF) followed by partial hepatectomy were investigated. Although separately non-specific, the lesions reported represented altogether a fairly characteristic pattern consistent with previous observations in tumors and in preneoplastic nodules induced by long-term treatment with single carcinogens. Such data support the view that sequential treatment followed by partial hepatectomy is a reliable method to study early phenotypic changes in hepatocarcinogenesis. Such treatment is also advisable because it requires only a short period of latency in comparison to other in vivo screening tests of potential carcinogens.

Pathologic findings in 25 autopsies of AIDS. The common and severe changes of the central nervous system, lungs, adrenals, heart, kidneys and gonads are reviewed in a series of autopsies of AIDS. In the brain, HIV infection induces directly inflammatory infiltrates including the typical multinucleated giant cells described by Sharer. In addition, primary lymphomas are seen as well as reactive and inflammatory lesions that are caused by opportunistic infections, such as those of poliomavirus, Cytomegalovirus and Toxoplasma gondii. In the lung, interstitial inflammation prevails, which may be related to direct HIV infection and include rare multinucleated giant cells like the ones described by Sharer. Opportunistic infections are often associated, and are commonly sustained by Cytomegalovirus and Pneumocystis carinii. A peculiar findings is the evolution from septal inflammation to fine fibrosis and hyaline degeneration, either focal or diffuse. We believe that the severe respiratory insufficiency that is commonly seen in the advanced stages of AIDS could be related to the interstitial damage. In the adrenal gland, the most common change is Cytomegalovirus infection affecting both the cortex and the medulla, and inducing massive necrosis in the cortex with little or no reaction. Again, adrenal involvement should be related to adrenal functional insufficiency, which may be over-looked clinically because of the preponderant lesions of other sites. In the heart, myocarditis is often discrete, and may be complicated by perivascular fibrosis and rare foci of myocytolysis; in some cases primary lymphomas may also develop. In the kidney, several histological lesions are found, including glomerular damage with segmental necrosis, cortical areas of hyporeactive necrosis, and mild interstitial inflammation. In the gonads, the changes are partly induced by drug abuse, and consist of atrophy with secondary hypoplasia of the germ cells and interstitial fibrosis. In conclusion, the most important abnormalities consist of opportunistic infections, hyporeactive necrosis, fibrotic evolution of the inflammatory infiltrates and neoplasias (Kaposi's sarcoma and lymphomas). In this work, the changes of the lymphoid organs are only mentioned, for they have been widely reviewed elsewhere.

The volume fraction of the sinusoids (Vv), the sinusoidal surface:total volume ratio (Sv), and the sinusoidal length:total volume ratio (Lv) were evaluated morphometrically in twelve biopsy specimens with cirrhosis and in eleven control specimens. The Sv, which is directly related to the radius of the sinusoids, was significantly (0.01 greater than P greater than 0.001) greater in the cirrhotic group than in the controls. In contrast, the Lv, which is directly related to the length of the sinusoids, and the Vv did not vary significantly in the same groups. These data support the concept that changes of the sinusoids do not contribute to portal hypertension in cirrhosis.

Argyrophil cells and melanocytes were sought with Grimelius' and Fontana-Masson's techniques in 43 specimens of laryngeal mucosa. In 7 cases, melanocytes were found in the squamous epithelium: in only 2 cases, rare argyrophil cells were found in the respiratory epithelium. The demonstration of argyrophil cells in the laryngeal mucosa constitutes the anatomic rationale for the insurgence of carcinoids and oat-cell carcinomas at this site.

Using an ammoniacal silver nitrate stain, we have demonstrated typical microglial cells in three teratomas. Microglia appeared identical to their counterparts in the mature human brain, both resting and slightly hypertrophic types being present in differentiated nervous tissue, which also comprised astrocytes, neurones and ependyma. The implications of the presence of microglia with ectodermal derivatives in teratomas are discussed.