Membrane-fusing capacity of the human immunodeficiency virus envelope proteins determines the efficiency of CD+ T-cell depletion in macaques infected by a simian-human immunodeficiency virus.

The mechanism of the progressive loss of CD4+ T lymphocytes, which underlies the development of AIDS in human immunodeficiency virus (HIV-1)-infected individuals, is unknown. Animal models, such as the infection of Old World monkeys by simian-human immunodeficiency virus (SHIV) chimerae, can assist studies of HIV-1 pathogenesis. Serial in vivo passage of the nonpathogenic SHIV-89.6 generated a virus, SHIV-89.6P, that causes rapid depletion of CD4+ T lymphocytes and AIDS-like illness in monkeys. SHIV-KB9, a molecularly cloned virus derived from SHIV-89.6P, also caused CD4+ T-cell decline and AIDS in inoculated monkeys. It has been demonstrated that changes in the envelope glycoproteins of SHIV-89.6 and SHIV-KB9 determine the degree of CD4+ T-cell loss that accompanies a given level of virus replication in the host animals (G. B. Karlsson et. al., J. Exp. Med. 188:1159-1171, 1998). The envelope glycoproteins of the pathogenic SHIV mediated membrane fusion more efficiently than those of the parental, nonpathogenic virus. Here we show that the minimal envelope glycoprotein region that specifies this increase in membrane-fusing capacity is sufficient to convert SHIV-89.6 into a virus that causes profound CD4+ T-lymphocyte depletion in monkeys. We also studied two single amino acid changes that decrease the membrane-fusing ability of the SHIV-KB9 envelope glycoproteins by different mechanisms. Each of these changes attenuated the CD4+ T-cell destruction that accompanied a given level of virus replication in SHIV-infected monkeys. Thus, the ability of the HIV-1 envelope glycoproteins to fuse membranes, which has been implicated in the induction of viral cytopathic effects in vitro, contributes to the capacity of the pathogenic SHIV to deplete CD4+ T lymphocytes in vivo.

Malignant Sertoli cell tumor of the ovary metastatic to the lung mimicking neuroendocrine carcinoma: report of a case.

A Sertoli cell carcinoma of the ovary with lung metastases mimicking neuroendocrine carcinoma is presented. Lung metastases frequently occur. Primary and secondary tumors may exhibit similar growth patterns and differentiating primary from secondary tumors may be troublesome. This process may be more difficult when metastases occur from a tumor in which metastases are uncommon and morphologically resemble only a small portion of the primary tumor. We report the case of a 52-year-old woman who underwent resection of a 4,550-g Sertoli cell tumor of the ovary. Histologically, in addition to the characteristic tubular pattern of growth, 5% of the tumor consisted of poorly differentiated areas with tumor cells in sheets, a high mitotic rate, and areas of necrosis. Eleven months after this surgery she presented at a different institution with multiple pulmonary nodules. Microscopic examination of a subsequently resected lung nodule showed histologic findings similar to those of the poorly differentiated areas of the ovarian tumor and initial immunohistochemical studies showed positive staining for cytokeratin, neuron-specific enolase, and focal positivity for synaptophysin. Without knowledge of the ovarian tumor the lung lesion was interpreted as large-cell neuroendocrine carcinoma. On review of the clinical history and comparison with the previous surgical material, however, both tumors showed similar light microscopy and immunohistochemical reactivity, and a final diagnosis of metastatic Sertoli cell tumor was made. Immunohistochemical staining for inhibin revealed weak positivity in the poorly differentiated areas of the ovarian tumor but not in the lung metastasis. This is one of the rare reports of ovarian Sertoli cell tumor metastasizing to the lungs and it emphasizes the importance of complete clinical histories, ancillary studies, appropriate sampling, and review of archival material in such unusual cases.

Usefulness of certain red blood cell indices in diagnosing and differentiating thalassemia trait from iron-deficiency anemia.

Iron-deficiency anemia and thalassemia are among the most common microcytic anemias. Differentiating these anemias by means of hemogrant indices is imprecise. Powerful statistical computer programming now enables sensitive discriminant analyses to aid in the diagnosis. Laboratory results from 383 adults were examined retrospectively and grouped according to their original diagnoses: normal (n = 78); beta-thalassemia (n = 134); alpha-thalassemia (n = 106); and iron-deficiency anemia (n = 65). Statistical analysis of results evaluated only RBC indices: RBC count, hemoglobin level, mean corpuscular volume, mean corpuscular hemoglobin, and RBC distribution width. Stepwise multivariate discriminant analysis determined those indices that best differentiated the 4 groups. The Fisher linear discriminant function for each group was calculated and tested casewise. Discriminant analysis identified mean corpuscular hemoglobin, RBC count, mean corpuscular volume, and RBC distribution width as the best set of indices for differentiating the 4 diagnoses. Casewise testing of the calculated Fisher linear discriminant function resulted in mean-weighted sensitivity of 80.4%. The present study demonstrates that a set of linear discriminant functions based on routine hemogram data can effectively differentiate between alpha-thalassemia, beta-thalassemia, and iron-deficiency anemia, with a high degree of accuracy.

Acanthamoeba infection presenting as skin lesions in patients with the acquired immunodeficiency syndrome.

Acanthamoeba organisms are a well-known, although rare, cause of central nervous system infection in immunodeficient hosts, including those with the acquired immunodeficiency syndrome. Extracerebral acanthamebiasis, with the exception of contact lens-associated keratitis, is reported but little emphasized in the literature. We describe two patients with the acquired immunodeficiency syndrome in whom skin lesions were the primary manifestations of Acanthamoeba infection. Central nervous system disease was proved in one patient and suspected, but unproved, in the other. The skin lesions exhibited an intact epidermis with suppurative inflammation of the subcutis, associated with numerous amebic cysts and trophozoites. The amebic cyst walls stained with periodic acid-Schiff and Gomori's methenamine-silver stains, creating confusion with Blastomyces dermatitidis yeast in one instance. Immunofluorescence studies and culture identified the organisms as an Acanthamoeba species. Preliminary studies in one of the cases suggested a previously undescribed Acanthamoeba species as the etiologic agent. Our experience emphasizes that skin lesions may be the presenting sign of disseminated Acanthamoeba infection in patients with the acquired immunodeficiency syndrome.

Bronchoscopy specimens in adults with AIDS. Comparative yields of cytology, histology and culture for diagnosis of infectious agents.

Bronchoscopy specimens from 183 known/suspected acquired immunodeficiency syndrome patients were evaluated for pathogens. In each case, transbronchial biopsies were evaluated and bronchoalveolar lavage material was cultured for viruses, fungi and mycobacteria and examined cytologically. A specimen was considered positive for a pathogen if detected by any one of the methods (TBB or BALC or culture). BALC was more sensitive for Pneumocystis carinii than TBB (90 of 92 vs 67 of 80 cases). TBB and BALC had poor sensitivities for cytomegalovirus detection (six of 79 and ten of 91 cases, respectively): 80 of 91 CMV cases were detected by culture only. Nineteen of 26 MB cases were positive by culture only: BALC and TBB detected only three of 26 and five of 23 cases, respectively. Three cryptococcosis cases were detected by culture only. One coccidioidomycosis case was positive by BALC and culture. Culture and BALC in combination detected 212 of 216 all significant pathogens. We believe that TBB is not routinely necessary in AIDS-related bronchoscopies in the absence of suspicion of neoplasia.

Retention indices by wide-bore capillary gas chromatography with nitrogen-phosphorus detection.

The use of wide-bore capillary columns in gas chromatography (GC) with nitrogen-phosphorus detectors (NPD) is gaining popularity in the toxicology laboratory. Though the preferred method to achieve reproducible results and to make interlaboratory comparisons of GC data is by retention index (RI), the selectivity of the NPD has relegated its users to calculations of relative retention time. The present study utilizes a set of drugs as reference standards under temperature programmed conditions and presents a unique method of RI calculation. RI calculations are highly reproducible with this technique (day-to-day variations range from 0.3 to 3.4 RI units) and are comparable to packed column, FID generated reference data. A program, written in Basic, calculates RI values based on daily injections of the reference standards and searches a library of over 100 basic and acidic drugs.

Peliosis hepatis in the acquired immunodeficiency syndrome.

We report two cases of peliosis hepatis in patients with acquired immunodeficiency syndrome. Hepatic tissue, obtained by needle biopsy from one patient and at postmortem examination from a second patient, demonstrated lesions grossly and microscopically consistent with previous descriptions of peliosis. Peliotic lesions were also identified in the spleen and porta hepatis lymph nodes in the second case. In at least one of the cases, peliosis was thought to play a significant role in the patient's morbidity and ultimate demise. Peliosis hepatis should be included in the differential diagnosis of hepatic disease among patients with acquired immunodeficiency syndrome.

Solitary extramedullary plasmacytoma of the breast with serum monoclonal protein: a case report and review of the literature.

A case of a solitary extramedullary plasmacytoma of the breast in a 73-year-old woman is reported. This is the second case of solitary breast plasmacytoma reported in the world literature. Plasmacytomas of the breast are extremely rare, especially those that are not associated with myelomatosis or disseminated disease. An associated monoclonal protein was present in the serum and was immunologically identical to the immunoprotein found in the tumor cells. The subject of extramedullary plasmacytomas in the breast is reviewed and discussed.

Tissue sources of elevated serum alkaline phosphatase activity in hyperthyroid patients.

Total alkaline phosphatase (ALP) and its isoenzymes were studied in the sera of 72 hyperthyroid patients and 24 age- and sex-matched controls. Eighty-nine per cent of thyrotoxic patients had elevated total serum ALP activity. Both liver (LALP) and bone (BALP) isoenzymes were present in the sera of 75% of patients. Women (43%) most frequently had elevated levels of LALP and BALP. Men (41%) most often had elevated levels of BALP and normal levels of LALP. The units of BALP present, but not of LALP, were related to measures of thyroid function. Levels of the activity of the aminotransferases and lactic dehydrogenase were usually normal. Gammaglutamyl transferase activity was elevated in nearly 40% of both sexes. The data presented, when correlated with previously reported information, suggest that elevations of serum LALP activity may be due to hepatocellular necrosis with leakage of preformed enzyme into the serum.

Malignant fibrous histiocytoma of the maxillary sinus. Case report and literature review.

A case of malignant fibrous histiocytoma of the maxillary sinus, which to our knowledge is the third such report, involved a patient who was seen initially with nasal obstruction, swelling of the face, and visual disturbances. Three months after partial excision of the tumor and radiotherapy and chemotherapy, the patient died of bone and liver metastases. These tumors usually manifest initially with symptoms directly referable to the involved sinus. If there is any evidence of metastatic disease, the prognosis appears to be poor.

Heterotopic ossification in the pulmonary metastases of gastric adenocarcinoma: report of a case and review of the literature.

A case of heterotopic ossification in the pulmonary metastases of an adenocarcinoma of the stomach is presented. This report represents the second known case in the world literature. Three cases with ossification in the primary tumor of the stomach and three cases of colorectal adenocarcinoma with ossification in the pulmonary metastases have been reported. The findings in these reports are reviewed and compared with those in the present case. The observations in these cases are consistent with the theory that heterotopic ossification in tumors and/or their metastases is due to metaplasia of fibroblasts induced by the presence of malignant cells.

Effects of storage in the cold on activity of gamma-glutamyltransferase in serum.

Sera from patients with hepatobiliary disorders were selected to represent a wide range of activity of gamma-glutamyltransferase (EC 2.3.2.2). Samples were stored at 4 degrees C and periodically tested for as long as nine weeks, others at -6 degrees C for as long as 40 weeks. The frozen-stored samples were thawed and then frozen again after each testing. The activity of the enzyme was essentially unchanged under both conditions of storage. These results are consistent with comments in the literature on the enzyme's stability.

Primary neonatal hyperparathyroidism. Report of a case and review of the literature.

The seventh case in the world literature of primary hyperparathyroidism in a neonate is reported. This is the fifth case in which an autopsy was performed. The clinical and anatomic findings in all seven cases are reviewed and compared. Neonates with primary hyperparathyroidism show diffuse hyperplasia of the parathyroid glands. The bones show disturbed osteogenesis, bone resorption, and widespread fibrosis of the marrow cavities. Bony cysts are not appreciated. Pathologic fractures are common. Marked hypercalciuria or hyperphosphaturia is usually not observed, perhaps because the immature renal tubules fail to respond to the influence of excess parathormone. Aminoaciduria and anemia are commonly observed. The prognosis is grave, and the etiology of this syndrome remains unexplained.