October 2001: 40-year-old Xhosa male with back pain and leg weakness

A 40-year-old Xhosa male presented with progressive upper lumbar back pain and weakness At examination he was emaciated and had enlarged lymph nodes in the groin and axilla. Both lower limbs were severely atrophic and weak. Sensation to touch and pain was decreased below L3 bilaterally. MR of the spine showed a discrete, contrast-enhancing epidural mass. A T10-T12 laminectomy revealed an soft, vascular extradural tumor dorsal to the cord. The mass was loosely applied to the dura and easy to remove. The operative specimen consisted of a sausage-shaped (3.5 x 2.0 x 1.2 cm), thinly-encapsulated mass of reddish-brown tissue. The cut surface had a mottled, vaguely nodular, yellowish-brown appearance. Microscopic examination revealed sheets of hematopoeitic elements, including myeloid, red cell and megakaryocytic lines, the latter showing Factor 8-related positivity. The final diagnosis was extramedullary hematopoiesis (EMH). A bone marrow biopsy performed as a result of the diagnosis showed a myeloproliferative disease and polycythemia vera. EMH in the spinal epidural space is a rare but treatable cause of progressive paraparesis in patients with a variety of hematological disorders. Since 1956 there have been more than 50 reported cases, most of which occurred in association with thalassaemia. In spinal cord compression secondary to EMH, the lesions are commonly localized to the mid-lower thoracic region.     

Atypical squamous epithelium in cytologic specimens from the pancreas: cytological differential diagnosis and clinical implications

Atypical squamous epithelium is an uncommon finding in cytologic specimens obtained from pancreatic lesions. A variety of pathologic conditions can result in the presence of these cells, including primary or metastatic carcinomas, chronic pancreatitis, and squamous metaplasia related to pancreatic or biliary duct stent placement. Primary adenosquamous and squamous-cell carcinomas of the pancreas are rare, representing 3.4% and 1.4 % of pancreatic carcinomas, respectively. Cytologic separation of these malignancies from less ominous metaplasias has immense clinical importance. We reviewed Indiana University Hospital's and Duke University's experiences with atypical squamous epithelium occurring within pancreatic aspirates. Study cases were identified using a computer to search the cytology records of these two institutions. Nine cases with a diagnosis of squamous-cell carcinoma, adenosquamous carcinoma, or atypical squamous epithelium were retrieved from the two institutions' Department of Pathology files. One case of pure squamous-cell carcinoma occurred in a patient with a known pulmonary primary; a single case of adenosquamous carcinoma was diagnosed in a patient with a coexistent endometrial primary; a single sample of adenocarcinoma with squamous differentiation was diagnosed in a patient without other known disease; and four primary squamous-cell carcinomas of the pancreas were detected. In addition, a single case of atypical squamous metaplasia associated with a stent was identified, and one case of atypical squamous epithelium associated with chronic pancreatitis was diagnosed. Despite the reactive atypia present in the examples of metaplastic squamous epithelium, separation of these cases from true squamous-cell carcinoma and adenosquamous carcinoma was achievable by cytologic evaluation. No cytologic criteria aided in separating primary pancreatic carcinomas with squamous differentiation from metastatic lesions. In this study, we report our findings in a series of nine cases where cytology disclosed atypical squamous epithelium in the aspirates derived from pancreatic lesions.     

Cytogenetic studies of primary cultures of esophageal squamous cell carcinoma

Cytogenetic analysis was performed on primary cultures of 21 squamous cell carcinomas of the esophagus (SCCE). Seven cases exhibited mosaic clonal chromosome abnormalities distributed as follows: two contained tetraploid cell populations, one with t(3;7)(p21;q11); two showed loss of the Y chromosome, one with double minutes; single cases demonstrated der(11)t(4;11)(q?27;q23); add(1)(p35) and del(4)(p12); and del(7)(p13), del(7)(q22q34), and der(11)t(7;11)(p?15;p?13). The remaining 14 cases had apparently normal karyotypes, possibly derived from stromal elements. These results demonstrate numerical abnormalities and the multiple occurrence of rearrangements involving chromosomes 7 and 11 in SCCE.     

Bi-directional modulation of T cell-dependent antibody production by prostaglandin E(2).

T cell-dependent Ig production involves interaction between T cells and B cells. This study evaluated the effects of prostaglandin (PG) E(2) on Ig production in a system in which B cells were co-cultured with autologous CD4(+) T cell clones non-specifically activated by anti-CD3. The effects of PGE(2) on T cell-dependent Ig production differed substantially, depending on the T cells employed. We selected six T cell clones that were able to enhance Ig production (resistant T cell clones) and six T cell clones that inhibited Ig production in the presence of PGE(2) (sensitive T cell clones) for comparison. The resistant T cells produced high levels (>1000 pg/ml) of IL-2 and/or IL-4, and expressed high CD40L, OX40 and CD45RA, and low CD45RO. In contrast, sensitive T cells secreted low IL-2 (<500 pg/ml) and IL-4 (<200 pg/ml), and expressed low CD40, OX40 and CD45RA, and high CD45RO. Adding supernatant derived from resistant T cell clones restored Ig production inhibited by PGE(2), while removing IL-2, IL-4 or IL-10 using specific antibodies inhibited Ig production. In addition, we demonstrated a direct effect of PGE(2) on B cells to enhance Ig production. Consistently, in the presence of resistant T cells, PGE(2) increased B cell proliferation and differentiation. In conclusion, the effects of PGE(2) on Ig production consist of its indirect effects through T cells and its direct effects on B cells. The outcome of the effects can be up-regulatory or down-regulatory, depending whether resistant or sensitive T cells are involved.     

Lateral visual pathway of giant barnacle

1. We have studied the responses to light, conduction down the axons, and anatomical projections of the photoreceptors of the lateral eye in the giant barnacle, Balanus nubilus. By recording intracellularly from ganglion cells that respond to visual input, we have described convergence of the lateral and median visual pathways. 2. Each lateral eye contains three photoreceptor cells, two large and one small. Cobalt filling of single large lateral receptor axons demonstrated that they end in a restricted ovoid bush on the ipsilateral side of the ganglion in approximately the same region in which the median receptors arborize. 3. The lateral receptors have dark resting potentials and responses to light similar to those previously described for the receptors of the median eye. Like the median receptors, the lateral receptors conduct visual signals decrementally, although their axons may be twice as long (14-25 mm). 4. Passing current of either polarity into either of the large receptors produced no detectable voltage change in the other cell. Action potentials elicited in either cell by stimulating it in the presence of tetraethylammonium ion were not detected in the other cell. Light-induced membrane noise in one cell did not correlate with noise in the other. Thus, like the receptors of the median eye, the large receptors of the lateral eye are not electrically coupled. 5. By shadowing each ocellus individually, we have shown that the signals from the median and lateral photoreceptors converge at the level of the second-order cells described for the median pathway. Shadowing the median or a lateral eye gave rise to synergistic responses in second-, third-, and all higher order ganglion cells studied. No cells were found that were driven solely by the lateral eyes. Thus, the lateral and median visual pathways are highly convergent.     

Screening of selected male blood donors for p24 antigen of human immunodeficiency virus type 1. The Transfusion Safety Study Group

BACKGROUND. The p24 antigen of human immunodeficiency virus type 1 (HIV-1) is sometimes detected before antibody (anti-HIV-1) is detectable in the serum of recently infected persons. This has led to the consideration of p24-antigen testing for routine screening of blood donors. METHODS. To estimate how many HIV-infected seronegative donors would be identified if p24-antigen screening was introduced, we tested selected donations from a repository of 200,000 serum samples from voluntary donors that was established in late 1984 and early 1985. The 8597 serum samples selected for p24-antigen screening were chosen because their donors had demographic characteristics known to be associated with a high prevalence of seropositivity. RESULTS. The prevalence of anti-HIV-1 antibodies in the 1984-1985 serum samples selected for p24-antigen screening was 1.54 percent--more than 100 times the 0.012 percent prevalence in present-day donations in the United States. The antigen was detected in 15 of 132 serum samples (11.4 percent) from donors who had already been confirmed as seropositive. No instance of confirmed positivity for p24 antigen was found among the 8465 seronegative serum samples. CONCLUSIONS. These data indicate that the yield of screening for p24 antigen in volunteer donors to identify HIV-1 carriers would be negligible. We therefore recommend against routine screening with currently available p24-antigen assays.     

HER2 protein overexpression in estrogen receptor-positive ductal carcinoma in situ of the breast: frequency and implications for tamoxifen therapy.

Recent clinical data have suggested that the efficacy of tamoxifen in reducing the risk of local recurrence following lumpectomy and radiation therapy in patients with ductal carcinoma in situ (DCIS) is limited to patients with estrogen receptor (ER)-positive lesions. However, it is currently not known if HER2 protein overexpression might be associated with reduced tamoxifen benefit in patients with ER-positive DCIS, as has been suggested in patients with ER-positive invasive breast cancer and in preclinical models. Moreover, the frequency of HER2 overexpression in ER-positive ductal carcinoma in situ has not been previously evaluated in detail. To address this issue, we studied ER expression and HER2 overexpression in 148 cases of DCIS using a sensitive double immunostaining technique and assessed the frequency of ER expression and HER2 overexpression in relation to each other and in relation to DCIS grade. Overall, ER expression was seen in 114 cases (77%) and HER2 protein overexpression was seen in 42 cases (28%). Of 114 ER-positive ductal carcinoma in situ, 14 (12%) showed concurrent HER2 protein overexpression, and all 14 of these DCIS lesions were of high nuclear grade. In addition, in all 14 ER-positive DCIS cases that showed HER2 overexpression, double immunostaining demonstrated that ER and HER2 protein were coexpressed by the same neoplastic cells. We conclude that a subset of ER-positive DCIS show concomitant overexpression of HER2 protein. Whether or not HER2 overexpression is associated with a diminished response to tamoxifen in patients with ER-positive DCIS will require investigation in clinical outcome studies.     

Receptor-mediated recognition of Cryptococcus neoformans.

Cryptococcus neoformans, a facultative intracellular pathogen of macrophages, is unique among medically important fungi in its possession of a polysaccharide capsule. Capsule represents the organism's major virulence factor. In the absence of opsonins, binding of encapsulated C. neoformans to macrophages is minimal. Following incubation in serum, C. neoformans potently activates complement, resulting in surface deposition of the third component of complement. Macrophages bind and phagocytose opsonized C. neoformans via three major complement receptors (CR) for C3 fragments, designated CD35 (CR1), CD11b/CD18 (CR3), and CD11c/CD18 (CR4). Antibody in normal human serum generally lacks opsonic activity, although vaccination can elicit anticapsular antibodies that are opsonic. The major component of cryptococcal capsule, glucuronoxylomannan (GXM), is shed from the fungus and circulates in the blood and cerebrospinal fluid of patients with cryptococcosis. Cellular receptors defined for GXM include CD14, toll-like receptor-2, toll-like receptor-4, and CD18. GXM binding to macrophage receptors triggers activation of nuclear factor-kB, but not mitogen-activated protein kinases. This results in no proinflammatory gene expression or release. C. neoformans also secretes mannoproteins, which are recognized by mannose receptors as well as by mannose-binding lectin, perhaps in conjunction with CD14. Strategies directed at modulating how intact C. neoformans and its released components are recognized by phagocytes could lead to novel approaches to treating cryptococcosis     

Temporal effects of a COX-2-selective NSAID on bone ingrowth

The effects of a short course of a COX-2 inhibitor on bone healing when the drug is discontinued are unknown. We examined the effects of rofecoxib on bone ingrowth over a 6-week period using a well-defined animal model. The Bone Harvest Chamber was implanted bilaterally in mature rabbits. After osseointegration of the chamber, the following treatments were given for 6 weeks each, followed by a harvest in each case: control-no drug; oral rofecoxib (12.5 mg/day) for the first 2 of 6 weeks; washout period-no drug; oral rofecoxib for the last 2 of 6 weeks; washout period-no drug; rofecoxib given continuously for all 6 weeks. Harvested specimens were snap-frozen, cut into serial 6-microm sections, and stained with hematoxylin and eosin and alkaline phosphatase (osteoblast marker), and processed using immunohistochemistry to identify the vitronectin receptor (osteoclast-like cells). Rofecoxib given continuously for 6 weeks yielded statistically less bone ingrowth compared to the control treatment. Rofecoxib given during the initial or final 2 weeks of a 6-week treatment did not appear to interfere with bone ingrowth. This suggests that the effects of COX-2 inhibitors on bone are less profound when the drug is administered for a short period of time.     

Quantitative enzyme cytochemistry of leukaemic cells

A new technique for the quantitative estimation of glycolytic and respiratory enzyme activity in intact and unfixed bone marrow and peripheral blood cells is described. The method gives a two- to three-fold increase in demonstrable enzyme activity per cell compared with existing techniques using fixed marrow film preparations, and is particularly applicable to the study of relatively fragile cells such as the leukaemic lymphoblast.