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M Koss

Publications and source records attributed to M Koss.

At least 37 records · Page 2Linked to original sources
PubMed1997

The potential role of BAX and BCL-2 expression in diffuse alveolar damage.

Apoptosis of type II pneumocytes has been identified in diffuse alveolar damage (DAD), is associated with p53 and WAF1 expression, and may be of pathogenetic importance. BAX, a homologue of BCL-2, is induced by p53 and is a promoter of apoptosis. The proapoptotic effect of BAX is negatively regulated by its binding with BCL-2. In this study, we sought to investigate that role of BAX and BCL-2 in DAD. We hypothesized that alterations in BAX and BCL-2 expression may be important in determining the susceptibility of type II pneumocytes and interstitial cells to apoptosis. Twenty-eight cases of DAD and 16 control cases (i.e., lung tissues adjacent to resected tumors) were retrieved from the files of the University of Utah and the Armed Forces Institute of Pathology. Immunohistochemical stains were performed with antigen retrieval by microwave using antibodies recognizing BAX and BCL-2. The percentage of positively staining pneumocytes and interstitial cells was estimated in each case to the nearest 10%. BAX expression was markedly increased in pneumocytes and interstitial cells in DAD compared with control lung tissues. In DAD, BAX was identified on an average of 80% of alveolar pneumocytes (range 30 to 100%) and 70% of interstitial cells (range 20 to 90%). In control lungs, BAX was identified on an average of 10% of pneumocytes (range 0 to 20%) but not in interstitial cells. Focal BCL-2 staining was identified in interstitial myofibroblasts in 7 of 25 cases of DAD but was only identified in bronchiolar epithelium of control lungs. These results suggest that the induction of BAX in DAD may enhance the susceptibility of alveolar epithelial cells to apoptosis, whereas BCL-2 expression may contribute to the absence of apoptosis in interstitial myofibroblasts. Expression of BCL-2 in interstitial myofibroblasts may contribute to the development of pulmonary fibrosis in some patients.

Adult↗
PubMed1996

Analysis of p53, K-ras-2, and C-raf-1 in pulmonary neuroendocrine tumors. Correlation with histological subtype and clinical outcome.

Neuroendocrine tumors of lung, including typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC) constitute a spectrum of malignancies in which the pathologist at times has difficulty in discerning tumor subtype and aggressiveness in a reproducible fashion. Therefore, 59 primary neuroendocrine lung tumors including 10 TCs, 26 ACs, 15 LCNECs, and 8 SCLCs were selected from cases collected from 1976 to 1988 and immunostained for p53 protein. All of these tumors were also genotyped for specific point mutational damage affecting p53 (exons 5, 7, and 8; with ACs additionally sequenced for p53 exon 6); 13 tumors for K-ras-2 (exon 1); and 31 tumors for c-raf-1 (exon 15) growth-regulatory genes. Genotyping was performed on topographically selected, minute tumor samples removed from unstained formalin-fixed, paraffin-embedded tissue sections (topographic genotyping) using polymerase chain reaction and direct sequencing. The distribution of p53 immunohistochemical staining had four patterns: negative in TCs, one-half of ACs, 3 of 15 LCNECs, and 1 of 8 SCLCs; less than 10% but more than five tumor cells per 10 high power fields (focal) in a subset (7 of 26) of aggressive ACs; 10 to 49% of tumor cells (patchy) in a subset (6 of 26) of ACs with a higher grade of aggressiveness; and 50 to 100% of tumor cells (diffuse), exclusively seen in LCNECs (12 of 15) and SCLCs (7 of 8). Three patterns of immunohistochemical staining intensity of p53 protein were seen: negative, weak or mild, and moderate to marked. SCLCs and LCNECs accounted for cases of moderate to marked staining and were the only ones to have mutations in p53 exons 5, 7, or 8. No mutations were found in AC and TC, showing absent to weak staining and no staining, respectively. The difference in distribution and staining intensities between LCNEC and SCLC compared with AC and TC was statistically significant (P < 0.001). Patients having AC with patchy p53 immunostaining usually had survival limited to 3 years, whereas those having AC with focal p53 immunostaining subsequently developed metastatic or recurrence of AC disease (P < 0.05). The absence of point mutations in cases with patchy or focal immunostaining suggests increased expression of wild-type p53 tumor suppressor protein likely in response to growth deregulation in a more aggressive subtype of AC. A novel hypothesis is presented in regard to these findings. K-ras-2 and c-raf-1 gene sequence analysis showed no evidence of point mutational change in any of the tumors studied. The TC and AC categories are therefore genetically distinct from the higher grade neuroendocrine SCLC and LCNEC. Immunohistochemistry for p53 on AC lung tumors may be helpful to delineate cases at higher risk for aggressive behavior. Additionally, although LCNEC is categorized as a non-small-cell carcinoma, it is more akin genetically and immunohistochemically to SCLC.

Carcinoid Tumor↗
PubMed1996

Association of p53 and WAF1 expression with apoptosis in diffuse alveolar damage.

Little is known about alterations in cell cycle regulatory proteins such as p53 and WAF1 in diffuse alveolar damage (DAD). We hypothesized that up-regulation of p53 and WAF1 in type II pneumocytes in DAD is associated with underlying DNA damage and apoptosis. Twenty cases of DAD and twenty control specimens of lung adjacent to resected tumors were studied. Immunohistochemical stains with antibodies recognizing p53 and WAF1 were performed, and apoptosis was assessed in sixteen cases by the nick end-labeling method. We identified p53 expression and apoptosis in all cases of DAD but not in any of the control lungs. We detected WAF1 expression in nineteen of twenty cases of DAD and in sixteen of twenty control lungs. In general, the distribution and intensity of WAF1 staining were greater in DAD than in control lungs. Staining for both p53 and WAF1 and labeling of apoptotic cells in DAD were usually focal ( < 10% of cells) and predominantly localized in type II pneumocytes. We conclude that increased p53 and WAF1 expression in DAD reflects normal physiological up-regulation in response to cellular and DNA damage and is associated with apoptosis of type II pneumocytes. p53-dependent apoptosis may contribute to the pathogenesis of this disease.

Adolescent↗
PubMed1996

Low-grade B-cell lymphomas of lung and lymphomatoid granulomatosis.

The last decade has seen major advances in our knowledge of the clinical and biologic behavior of lymphomas of lung. These advances have in turn led to intriguing hypotheses that attempt to explain the origin of these lesions. In this chapter, the authors summarize the background and evolution of these intriguing lymphomas.

Humans↗
PubMed1996

Update on lymphoid interstitial pneumonitis.

Lymphoid interstitial pneumonitis (LIP) involves a clinicopathologic pattern of pulmonary disease characterized by diffuse interstitial reactive lymphoid infiltrates. In adults, it occurs most commonly in autoimmune diseases, such as Sjögren's syndrome (0.9% of these patients) and primary biliary cirrhosis, whereas in children it is usually seen in HIV infection. Dysproteinemias (hyper- and hypogammaglobulinemia) are found in more than 60% of patients. Children can show CD8-lymphocytosis in bronchoalveolar lavage fluid, lung tissue, peripheral blood, and salivary gland, associated with HLA-DR5 haplotype. Radiographically, most patients with LIP have reticulonodular infiltrates, with or without patchy areas of consolidation. CT scans can show both small nodular and ground glass patterns, patterns that are diagnostically nonspecific. Reduced lung volumes and diffusing capacities are consistent and sensitive indicators of disease in LIP. In an experimental model, diffusing capacity was the single most sensitive functional index of disease progression. Microscopically, LIP is part of a spectrum of pulmonary lymphoid proliferations, ranging from follicular bronchitis-bronchiolitis and pulmonary lymphoid hyperplasia (the latter in AIDS patients), proliferations largely limited to airways, to low-grade malignant lymphoma. These patterns may be difficult to differentiate from each other. It appears that LIP sometimes evolves to lymphoma; the frequency of this evolution is probably low but is difficult to assess because low-grade lymphomas may mimic LIP. A relatively high frequency of LIP patients have Epstein-Barr virus DNA in their lungs but not all patients with LIP show this finding, suggesting other possible etiologies.

Adult↗
PubMed1995

Renal afferent denervation prevents the progression of renal disease in the renal ablation model of chronic renal failure in the rat.

Rats with 5/6 nephrectomy develop hypertension and progressive deterioration in renal function. Several mechanisms may contribute to hypertension and to progressive renal disease in these rats. We have shown that increased activity of the sympathetic nervous system may contribute to hypertension in rats we chronic renal failure. However, the role of the sympathetic nervous system activity in the progression of renal disease has not been investigated. We have evaluated whether neurogenic factors contribute to the progression of renal disease in the renal ablation model of chronic renal failure in the rat. Sprague-Dawley rats underwent 5/6 nephrectomy and dorsal rhizotomy or sham rhizotomy (CRF). Age-matched normal rats were used as controls. Six weeks after surgery, rats with chronic renal failure and dorsal rhizotomy had lower blood pressure and serum creatinine than rats with sham rhizotomy. In addition, kidneys from rats with 5/6 nephrectomy and rhizotomy manifested less severe glomerulosclerosis than kidneys from rats without dorsal rhizotomy. These studies have demonstrated in rats with renal ablation. Although normalization of blood pressure may definitely play a role, the data raise the possibility that neurogenic impulses to the kidneys may contribute to the progression of renal disease.

Animals↗
PubMed1995

The clinical impact of reported variance in potency of antipsychotic agents.

There is significant disagreement on the clinical equivalence (or potency) of antipsychotic agents, with up to 500% variance reported in texts. To address the extent and consequences of these discrepancies, we took a random sample of 18 common psychiatry, psychopharmacology and pharmacology texts for antipsychotic equivalence tables. We found a marked variation in stated equivalences for the majority of antipsychotics. Most affected were the high potency (haloperidol, fluphenazine) and newer (molindone) drugs, which had a 500% variance. This variation inadvertently contributes to the misuse of these agents. For instance, high-potency antipsychotics are prescribed in far larger doses than necessary, leading to decreased efficacy and increased side effects. Steps to simplify and rationalize the use of these agents are recommended.

Antipsychotic Agents↗
PubMed1995

Pathways involved in PTH-induced rise in cytosolic Ca2+ concentration of rat renal proximal tubule.

Parathyroid hormone (PTH) raises cytosolic Ca2+ concentration ([Ca2+]i) in isolated or cultured renal proximal tubule cells. The pathways through which this action is mediated are not fully delineated. This study explored these pathways utilizing fura 2. [Ca2+]i of freshly prepared renal proximal tubular cells increased from 150 +/- 3.6 to 281 +/- 9.0 nM after the exposure to 10(-7) M angiotensin II, which served as a positive control. Both PTH-(1-84) and PTH-(1-34) produced a dose-dependent rise in [Ca2+]i. The effects of both moieties were similar up to 10(-7) M, but with higher doses the rise in [Ca2+]i with PTH-(1-84) was greater (P < 0.01) than with PTH-(1-34). This effect of the hormone occurred in the presence or absence of calcium in the media, but the rise in [Ca2+]i was significantly greater in the presence of calcium. The PTH-induced rise in [Ca2+]i was markedly inhibited by PTH antagonist [Nle8,18,Tyr34]bPTH-(7-34)-NH2 (bPTH is bovine PTH), verapamil, or nifedipine. 12-O-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C, increased [Ca2+]i of cells, but its effect was less than PTH. Staurosporine abolished the TPA effect and partially inhibited that of PTH. A G protein activator raised [Ca2+]i, whereas a G protein inhibitor and pertussis toxin partially blocked the effect of PTH. Sodium or chloride channel blockers or sodium-free media did not modify the effect of PTH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Multifocal micronodular pneumocyte hyperplasia: a distinctive pulmonary manifestation of tuberous sclerosis.

We report a peculiar multifocal micronodular proliferation of pneumocytes occurring in a 24-yr-old woman with tuberous sclerosis and lymphangioleiomyomatosis. A computed tomographic scan of the chest demonstrated multiple minute nodules present throughout both lung fields. Histologically, the nodules were well demarcated, measured up to 1.6 mm in diameter, and were composed of thickened, fibrotic, alveolar septa lined by pleomorphic, type II pneumocytes. Positive immunohistochemical stains for keratin, BER-EP4, and surfactant, and negative immunohistochemical staining with an antibody recognizing Clara cells support an epithelial origin from type II pneumocytes. The absence of immunohistochemical staining for HMB45 suggests a histogenesis separate than the lesions of lymphangioleiomyomatosis. We failed to detect estrogen or progesterone receptors in either the lesions of lymphangioleiomyomatosis or the micronodular proliferations. Recognition of these unique lesions facilitates their distinction from other epithelial proliferations, particularly atypical bronchioloalveolar cell hyperplasia. This lesion appears to be a distinctive manifestation of tuberous sclerosis. It is probably hamartomatous.

Adult↗
PubMed1994

Pulmonary lymphomatoid granulomatosis. Evidence for a proliferation of Epstein-Barr virus infected B-lymphocytes with a prominent T-cell component and vasculitis.

Similarities have been noted in the histologic patterns of lymphomatoid granulomatosis and Epstein-Barr virus associated lymphoproliferative disease involving the lung. Epstein-Barr virus has also been identified by polymerase chain reaction in most cases of lymphomatoid granulomatosis; however, the precise cellular localization of Epstein-Barr virus sequences has not been extensively studied. We analyzed 10 cases of lymphomatoid granulomatosis involving the lung by immunohistochemistry and combined immunohistochemistry with in situ hybridization for Epstein-Barr virus, CD20, and CD45RO. All cases were selected from the files of the Armed Forces Institute of Pathology and met the clinical and histologic criteria for the diagnosis of lymphomatoid granulomatosis, grades 1 through 3. In all 10 cases, immunohistochemistry showed that most of the cells--small to medium-sized lymphocytes--were T cells (CD45RO+); however, a much smaller population of medium-sized to large atypical cells were B cells (CD20+). In each case, combined immunohistochemistry and in situ hybridization confirmed the presence of Epstein-Barr virus sequences within B (CD20+) cells and the absence of Epstein-Barr within T-cells (CD45RO+). Polymerase chain reaction analysis for immunoglobulin heavy-chain gene rearrangement identified a monoclonal pattern in six of nine cases tested, whereas analysis for T-cell receptor gamma-chain gene rearrangements was negative in three cases tested. On the basis of these findings, we hypothesize that most cases of lymphomatoid granulomatosis involving the lung represent a proliferation of Epstein-Barr virus infected B-cells with a prominent T-cell reaction and vasculitis, distinguishing these cases from angiocentric "T-cell lymphomas" in other sites, such as the head and neck.

Adult↗
PubMed1993

Body size and shape characteristics of personal ("in search of") ads.

This study investigated sociocultural norms for height, weight, and body shape by analyzing 481 personal ads in a large metropolitan city magazine to determine self-report characteristics of males and females seeking companionship as well as the desired height, weight, and shape characteristics of the person being sought. Seventy percent of ads specified weight, shape, or height characteristics and of those ads most were heterosexual Caucasian males and females. Male searchers described themselves as tall, fit, and athletic, but of average weight. Female searchers described themselves as petite or tall and fit with body weight as significantly less (89.4%) than the ideal body weight. Male searchers sought females 5 years younger, thin, fit, petite or tall. Women seekers sought men 3 years older, tall, fit, and athletic. These ads confirmed the use of stereotyped and highly athletic body size and shape for self-descriptions and for characteristics of companions sought.

Adult↗
PubMed1993

Antidepressant side effects and physician prescribing patterns.

We studied the following questions: (1) Do physicians preferentially prescribe antidepressants (ADs) with the least side effects (SEs) of sedation, orthostatic hypotension, and anticholinergic activity; (2) Have there been any recent changes in prescribing patterns; and (3) Do patterns differ for psychiatrists and nonpsychiatrists. Data on psychiatrist and non-psychiatrist outpatient prescribing of specific ADs were obtained from the National Prescription Audit (NPA) for 1986 and 1989. In 1986, physicians did not minimize the use of ADs with the most of these SEs. The 1989 data indicate that psychiatrists made a major change toward prescribing more low SE ADs and less ADs with the most SEs. The data for nonpsychiatrists also suggest some movement in this direction. The availability of fluoxetine and the concomitant focus on SEs may have contributed to this shift. Further investigation is needed to clarify factors that influence physicians' choices of ADs.

Antidepressive Agents↗
PubMed1992

Pseudomesotheliomatous adenocarcinoma: a reappraisal.

Adenocarcinomas of or in lung that clinically and pathologically mimic diffuse pleural mesotheliomas are rare. We reviewed selected clinical and pathologic features of 15 autopsy/surgical cases previously reported in the medical literature and of 15 additional cases from the files of the Armed Forces Institute of Pathology (AFIP). Ninety percent of the patients were men. The median age was 61 years. Sixty-three percent of the patients smoked, 17% of them had possible or definite occupational exposure to asbestos, and one patient had microscopically proven asbestosis. Most patients had chest pain, shortness of breath, or cough, and had unilateral pleural effusion in the chest x-ray. At thoracotomy or at autopsy, numerous nodules, plaques, or a continuous rind of tumor was present over the pleural surface. Microscopically, the tumors showed simplified glands, nests, cords, papillary, tubulopapillary or biphasic patterns of growth. The neoplasms contained mucin that stained with diastase-predigested periodic acid-Schiff (PAS), mucicarmine, and alcian blue (with or without hyaluronidase predigestion). All patients died with/of tumor, with a mean survival of 4.7 months for those reported in the medical literature and of 7 months for those in the AFIP files. These adenocarcinomas therefore mimic pleural mesothelioma not only in their clinical and gross and microscopic appearance, but also in their prognosis.

Adenocarcinoma↗
PubMed1991

Bilateral renal cortical necrosis in two patients with Neisseria meningitidis sepsis.

Two patients who developed bilateral renal cortical necrosis as a consequence of Neisseria meningitidis infections are described: 1 patient had meningococcemia and the other had meningococcal meningitis. Both patients developed a Shwartzman-like reaction, disseminated intravascular coagulation and irreversible renal failure. Renal biopsy showed sclerosis of the majority of glomeruli; some glomeruli showed capillary congestion, thrombosis and an increased number of neutrophils; the intralobular arterioles showed thrombotic occlusions.

Adult↗
PubMed1991

Pulmonary blastoma with germ cell (yolk sac) differentiation: report of two cases.

Pulmonary blastoma is a rare lung neoplasm of disputed histogenesis and variable biologic behavior. Typical cases contain both epithelial and mesenchymal tissues, and a variety of patterns of differentiation have been described. While expression of oncofetal antigens in these tumors has been noted rarely, a coexisting component of germ cell tumor has not been reported previously. We describe the clinical and pathologic features of two cases of pulmonary blastoma having alpha-fetoprotein production and histologic areas of yolk sac tumor. We also report the finding of immunohistochemical staining of fetal lung tissue for alpha-fetoprotein.

Adult↗
PubMed1989

Extrarenal renin-secreting tumors: insights into hypertension and ovarian renin production.

Although renin-secreting tumors are rare, they must be considered in the differential diagnosis of hypertension associated with hypokalemia, which occurs commonly in the hypertensive population. The finding of an ovarian renin-secreting tumor emphasizes the potential importance of the ovary as an extrarenal source of renin; the local ovarian renin-angiotensin system may play a key role in reproductive function by regulating vascular reactivity, local blood flow, steroidogenesis and other physiologic effects. In the illustrative case presented, a renin-secreting ovarian leiomyosarcoma was obtained from a women who presented with hypertension and hypokalemia. Plasma prorenin levels were markedly elevated. Tumor excision was quickly followed by a fall in prorenin levels and tumor recurrence was accompanied by an increase in prorenin levels. Active renin concentration in the tumor homogenates was similar to that found in kidney homogenates while the tissue prorenin concentration was approximately 20 times that found in kidney tissue. When cultured for up to 4 weeks, ovarian tumor cells secreted greater than 95% prorenin. Immunoblot analysis demonstrated that tumor renin had a molecular weight of 47,000, similar to that of human recombinant prorenin. Immunohistochemical staining of tumor tissue with antibodies against human renal renin at the electron microscopic level demonstrated the presence of renin primarily in membrane-bound vesicles and rarely in dense-core secretory granules. These findings suggest that prorenin in this ovarian tumor was secreted by the constitutive pathway, which is mediated by these amorphous vesicles.

Aged↗