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M Osborn

Publications and source records attributed to M Osborn.

At least 91 records · Page 5Linked to original sources
PubMed1990

Cells of the cellular immune and hemopoietic system of the mouse lack lamins A/C: distinction versus other somatic cells.

Almost all somatic cells in adult murine tissues express all three nuclear lamins (A, B, C). Here we demonstrate that cells of the hemopoietic system of the adult mouse are an exception in that they express only lamin B. Thus T and B lymphocytes as well as granulocytes and monocytic cells directly isolated from spleen, thymus, blood or bone marrow do not express lamin A/C but only lamin B. In agreement with this observation the murine hemopoietic cell lines EL4, BW5147, HK22, 70Z/3, SP2/0 and PAI express only lamin B. In immunoblotting experiments used to confirm the immunofluorescence data no lamin A/C expression was detected. However, we noticed that murine lamin B occurs in two isoforms, which can be distinguished immunologically. These results reinforce the idea that a functional nuclear lamina can be formed from lamin B alone. They also pose the question of whether cells lacking lamin A/C are more plastic in their developmental programs than those that express all three lamins.

Animals↗
PubMed1990

Keratin 7 is a marker for a subset of trophoblastic cells in human germ cell tumors.

Human testicular germ cell tumors were studied immunohistochemically with the monoclonal antibody to the 54-kd keratin polypeptide (keratin 7) to determine whether this antibody could be used selectively to identify trophoblastic cells. The antibody reacted with the intermediate filaments in the cytoplasm of some cells in choriocarcinoma cell lines, and in trophoblastic cells in mixed germ cell tumors and a seminoma. It did not react with classic seminoma cells, embryonal carcinoma, yolk sac carcinoma, or somatic tissues of mixed germ cell tumors. On the basis of these data we conclude that monoclonal antibody to keratin 7 is a marker for a subset of trophoblastic cells in human germ cell tumors.

Adult↗
PubMed1990

On the nature of serological tissue polypeptide antigen (TPA); monoclonal keratin 8, 18, and 19 antibodies react differently with TPA prepared from human cultured carcinoma cells and TPA in human serum.

A panel of monoclonal antibodies which recognize the rod domains of human keratin 8, 18, or 19 was tested for its capacity to replace TPA antiserum as anchoring antibody in a two-site TPA immuno-radiometric assay kit. All six antibodies could anchor a TPA preparation, with varying efficiencies, when iodinated TPA antiserum monitored antigen binding. Conversely, the soluble keratin 8, 18, and 19 rod complex could efficiently replace the TPA preparation as antigen when TPA antiserum anchored and detected antigen binding. Moreover, in immunoblots the TPA antiserum recognized the rod domains of human keratins 8, 18, and 19. In contrast to the general reaction of the keratin antibodies with a TPA preparation, the reactions with TPA in human serum were antibody and sample dependent. A keratin 19- and a keratin 8-specific antibody anchored TPA in all sera consistently and efficiently, while the other 4 antibodies anchored serological TPA inefficiently. TPA in human serum was found in immunoblots to be somewhat more heterogeneous in size than the standard TPA preparation. The data presented here indicate that TPA in patients' sera is a degradation product of keratins 8, 18, and 19. The significance of these findings is discussed.

Antibodies, Monoclonal↗
PubMed1990

Vimentin expression appears to be associated with poor prognosis in node-negative ductal NOS breast carcinomas.

Vimentin expression in tumors from 83 node-negative and 112 node-positive patients with infiltrative ductal not otherwise specified (NOS) breast carcinomas has been compared with 5-year survival. For node-negative, but not for node-positive patients, there was a significant inverse relation between vimentin expression and survival. Five-year survival of node-negative patients with vimentin-positive tumors was significantly worse compared with vimentin-negative tumors (P less than 0.0001). In the node-negative group, only 36% of patients with vimentin-positive tumors but 82% of patients with vimentin-negative tumors survived 5 years. Tumors of all eight node-negative patients with ductal NOS cancer who died in the first 27 months expressed vimentin. Multivariate analysis of the node-negative group showed a strong correlation of vimentin expression and overall survival, but weak and not significant correlation between histologic grade or size and overall survival at 5 years. Thus vimentin expression seems to be a strong indicator of poor prognosis in node-negative ductal NOS breast carcinomas.

Biopsy↗
PubMed1990

Vimentin is preferentially expressed in human breast carcinomas with low estrogen receptor and high Ki-67 growth fraction.

Vimentin expression, growth fractions (GF), and estrogen receptor (ER) levels were determined for 90 untreated primary breast carcinomas. Coexpression of keratin and vimentin was found in approximately 20% of the tumors regardless of menopausal status. Vimentin was expressed preferentially in tumor cells of high-grade ductal breast carcinomas (15 of 28 histologic grade 3 vs. 0 of 40 grades 1 and 2). Vimentin expression was found preferentially in tumors with high GF (greater than 15% Ki-67 positive by immunoperoxidase staining) and low ER levels (less than 60 fmols/mg protein by a monoclonal enzyme immunoassay). Sixty-eight percent of tumors in this group were vimentin positive and 88% of all vimentin-positive tumors fell into this category. More than 50% of the tumor cells coexpressed vimentin and keratin. Thus, vimentin expression may be helpful in identifying a substantial subset of ER-independent breast carcinomas with poor prognostic indicators.

Antigens, Surface↗
PubMed1990

Vimentin is preferentially expressed in high-grade ductal and medullary, but not in lobular breast carcinomas.

Two hundred sixty-two invasive breast carcinomas dating from 1979 to 1984 were tested for vimentin and keratin on formaldehyde-fixed paraffin-embedded sections. None of 26 lobular carcinomas expressed vimentin. Vimentin expression in 10% or more of tumor cells was found in 78% of medullary (14 of 18), in 16% of ductal not otherwise specified (NOS) (35 of 214), and in two of four mucinous carcinomas. A further seven tumors showed vimentin expression in less than 1% to 10% of the cells. Vimentin was expressed in tumor cells of 30% (28 of 93) of grade III invasive ductal NOS carcinomas versus 7% (7 of 105) of grade II and 0% of grade I carcinomas (0 of 10). Vimentin was found to be preferentially expressed in tumors growing in broad, often anastomosing bands or sheets with extensive necrosis, scanty supportive stroma, high nuclear grade, and numerous mitoses. The authors conclude that vimentin is not detected in lobular carcinomas, but is preferentially expressed in medullary and in high-grade ductal NOS breast carcinomas.

Biomarkers↗
PubMed1989

Diagnosis of major tumor categories in fine-needle aspirates is more accurate when light microscopy is combined with intermediate filament typing. A study of 403 cases.

Intermediate filament (IF) typing of tumor cells with monoclonal antibodies was applied to 403 fine-needle aspirates. In 271 cases specific cytologic diagnosis of tumor type was apparent from clinical data and light microscopic study alone. Intermediate filament typing confirmed the tumor type in 262 cases and changed an erroneous cytologic diagnosis of major tumor type in nine cases. In a second group of 132 difficult cases, where the tumor type could not be revealed with certainty, IF typing confirmed the cytologic suggestion of tumor type in 50 cases, changed it in nine cases, and helped resolve ambiguities in cytologic diagnosis in 59 cases. It did not help in 14 cases. Thus IF typing adds independent objective differentiation specific information to descriptive tumor typing currently used in aspiration cytologic study. When combined with the morphologic analysis of tumor cells and clinical information it can refine the cytologic diagnosis of major tumor types and prevent error.

Adolescent↗
PubMed1989

Myogenesis in the mouse embryo: differential onset of expression of myogenic proteins and the involvement of titin in myofibril assembly.

Antibodies to muscle-specific proteins were used in immunofluorescence to monitor the development of skeletal muscle during mouse embryogenesis. At gestation day (g.d.) 9 a single layer of vimentin filament containing cells in the myotome domain of cervical somites begins to stain positively for myogenic proteins. The muscle-specific proteins are expressed in a specific order between g.d. 9 and 9.5. Desmin is detected first, then titin, then the muscle specific actin and myosin heavy chains, and finally nebulin. At g.d. 9.5 fibrous desmin structures are already present, while for the other myogenic proteins no structure can be detected. Some prefusion myoblasts display at g.d. 11 and 12 tiny and immature myofibrils. These reveal a periodic pattern of myosin, nebulin, and those titin epitopes known to occur at and close to the Z line. In contrast titin epitopes, which are present in mature myofibrils along the A band and at the A-I junction, are still randomly distributed. We propose, that the Z line connected structures and the A bands (myosin filaments) assemble independently, and that the known interaction of the I-Z-I brushes with the A bands occurs at a later developmental stage. After fusion of myoblasts to myotubes at g.d. 13 and 14 all titin epitopes show the myofibrillar banding pattern. The predominantly longitudinal orientation of desmin filaments seen in myoblasts and in early myotubes is transformed at g.d. 17 and 18 to distinct Z line connected striations. Vimentin, still present together with desmin in the myoblasts, is lost from the myotubes. Our results indicate that the putative elastic titin filaments act as integrators during skeletal muscle development. Some developmental aspects of eye and limb muscles are also described.

Actins↗
PubMed1989

Differential timing of nuclear lamin A/C expression in the various organs of the mouse embryo and the young animal: a developmental study.

In mouse embryos, acquisition of the nuclear lamin polypeptides A/C varies according to developmental stage and tissue type. In order to determine the precise time points and cell types in which lamin A/C are first observed, we have used two monoclonal antibodies in immunofluorescence studies of different tissues of developing mouse embryos and of young mice. One antibody (mAB346) is specific for lamins A and C, while the other (PKB8) detects lamins A, B and C. Dividing uterine development into three phases--germ layer formation, organogenesis and tissue differentiation--our results show that lamin A/C expression in the embryo proper is not observed until the third phase of development. Lamin A/C first appears at embryonic day 12 in muscle cells of the trunk, head and the appendages. Three days later it is also seen in cells of the epidermis where its appearance coincides with the time of stratification. In the simple epithelial of lung, liver, kidney and intestine, as well as in heart and brain, lamins A/C do not appear until well after birth. Embryonal carcinoma (EC) cells express lamin B but not lamin A/C. Lamin A/C expression is noted in some EC cells after they are induced to differentiate and in several differentiated teratocarcinoma cell lines. Our results suggest that commitment of a cell to a particular pathway of differentiation (assayed by cell-type-specific expression of intermediate filament proteins) usually occurs prior to the time that lamin A/C can be detected. Thus lamin A/C expression may serve as a limit on the plasticity of cells for further developmental events.

Animals↗
PubMed1989

Repetitive titin epitopes with a 42 nm spacing coincide in relative position with known A band striations also identified by major myosin-associated proteins. An immunoelectron-microscopical study on myofibrils.

A direct titin-thick filament interaction in certain regions of the A band is suggested by results using four new monoclonal antibodies specific for titin in immunoelectron microscopy. Antibodies T30, T31 and T32 identify quasi-repeats in the titin molecule characterized by a 42-43 nm repeat spacing. These stripes seem to coincide with striations established by others on negatively stained cryosections of the A band. Antibodies T30 and T32 recognize epitopes matching five or two of the seven striations per half sacromere known to harbor both the myosin-associated C-protein and an 86K (K = 10(3) Mr) protein. Antibody T31 labels two stripes in the P zone, which correspond to the two positions where decoration is seen with 86K protein, but not with C-protein. The single titin epitope defined by antibody T33 is located 55 nm prior to the center of the M band. This position seems to coincide with the M7 striation defined by others on negatively stained A bands. The T33 epitope position proves that the titin molecule, which is known to be anchored at the Z line, also penetrates into the complex architecture of the M band. The titin epitopes described here enable us to begin to correlate known ultrastructural aspects of the interior part of the A band with the disposition of the titin molecule in the sarcomere. They raise the question of whether there is a regular interaction pattern between titin and the thick filaments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Coexpression of intermediate filaments in squamous cell carcinomas of upper aerodigestive tract before and after radiation and chemotherapy.

Frozen sections of 48 squamous cell carcinomas and seven undifferentiated carcinomas of the upper aerodigestive tract were investigated immunohistochemically with monoclonal antibodies specific for keratin, vimentin, desmin, neurofilaments, and glial fibrillary acidic proteins. In nine squamous cell carcinomas (19%) and six undifferentiated carcinomas (86%) obtained before treatment coexpression of keratin and vimentin was detected in some tumor cells by double immunofluorescence studies. Nine squamous cell carcinomas expressed neurofilaments in scattered tumor cells. Coexpression of vimentin or neurofilaments was seen especially in the peripheral cell layer of the tumor nests and did not seem to correlate with the degree of differentiation. Three undifferentiated carcinomas additionally expressed desmin, and one tumor contained neurofilaments. Glial fibrillary acidic proteins were not detected. Increased coexpression of keratin with vimentin, desmin, or neurofilaments was seen in some tumors that were studied before and after radiation/chemotherapy, suggesting that the intermediate filament profile of tumor cells can be altered by external influences.

Carcinoma, Squamous Cell↗
PubMed1989

[Vasculitis of the kidney].

Panarteritis nodosa, Wegener's granulomatosis and idiopathic necrotizing glomerulonephritis, regarded by some as a vasculitis restricted to the glomerulus, are those forms of primary vasculitis most often encountered in renal biopsy. The histopathologic differential diagnosis can be difficult and has to rely on the finding of vascular inflammation in preglomerular vessels and of granulomata. In a majority of renal biopsies only a necrotizing and crescentic glomerulonephritis without inflammation of arteries or arterioles can be seen. Also the clinical manifestation of these three diseases can be very similar. A new impetus for the differential diagnosis of vasculitis was the discovery of antineutrophilic cytoplasmic antibodies (ANCA). In alcohol fixed leukocytes a cytoplasmic immunofluorescence (c-ANCA) represents an autoantibody to a serine protease of 29 kD - probably Protease 3-, and a perinuclear stain (p-ANCA), often a reaction against myeloperoxidase. ANCA antibodies seem to be a useful marker for the diagnosis of Wegener's granulomatosis, although ANCA positive tests have also been obtained in microscopic panarteritis nodosa and seemingly even in lupus nephritis. ANCA autoantibodies apparently are a reliable parameter to assess activity of the vasculitic process, and may thus be helpful in therapeutic decisions. Despite of current aggressive immunosuppressive therapy long term survival of patients or their kidneys still is rather bleak, in case a severe renal vasculitic process is diagnosed. Extracapillary proliferation (crescents) in more than 50% of glomeruli is also associated with an increased mortality.

Diagnosis, Differential↗
PubMed1989

Leukocyte-common antigen and vimentin are reliable adjuncts in the diagnosis of non-Hodgkin's lymphoma in fine needle aspirates.

Alcohol-fixed fine needle aspirates of 82 non-Hodgkin's malignant lymphomas (NHLs) were tested for the presence of vimentin and leukocyte-common antigen (LCA) by means of monoclonal antibodies (MAbs) and indirect immunofluorescence. All NHLs stained positively for vimentin; the staining was strong in all except three cases. Of the 69 NHLs tested for LCA, 1 (a large cell T-cell lymphoma) was negative while the staining was weak in 6. Thus, vimentin and LCA MAbs are sensitive, specific and reliable complementary diagnostic adjuncts that are useful in the definitive diagnosis of NHLs in alcohol-fixed fine needle aspirates. Their presence in the aspirate confirmed a cytologic diagnosis of NHL in 47 cases, helped to diagnose NHL in 31 cases in which a cytologic differential diagnosis with small cell anaplastic carcinoma could not be made with confidence and helped to change the initial cytologic diagnosis of anaplastic carcinoma to NHL in 4 cases.

Antigens, Differentiation↗
PubMed1989

Endothelial cells help in the diagnosis of primary versus metastatic carcinoma of the liver in fine needle aspirates. An immunofluorescence study with vimentin and endothelial cell-specific antibodies.

Fine needle aspirates of 5 primary hepatocellular carcinomas and 24 carcinomas metastatic to the liver were studied using vimentin and endothelial cell-specific monoclonal antibodies. Numerous endothelial cells dispersed and in bundles overlying clumps of tumor cells were positively stained by both antibodies in smears of primary hepatocellular carcinomas while such cells were rare or absent in metastatic carcinomas, with the exception of clear cell carcinoma of the kidney. It is concluded that endothelial cells, if present in large numbers in fine needle aspirates of a hepatic carcinoma and arranged in bundles that envelope the clumps of tumor cells, can (1) suggest the presence of a primary hepatocarcinoma and (2) narrow the differential diagnosis with the most common metastatic cancers to renal cell carcinoma.

Antibodies, Monoclonal↗
PubMed1988

Sexual dysfunction among middle aged women in the community.

In a community survey of women aged 35-59 sexual functioning was studied in the 436 women with partners. One third of these women had operationally defined sexual dysfunction: impaired sexual interest was identified in 17% of women (68/406), vaginal dryness in 17% (73/434), infrequency of orgasm in 16% (60/379), and dyspareunia in 8% (30/379). Sexual dysfunctions were statistically significantly associated with increasing age and also with psychiatric disorder, neuroticism, and marital disharmony. One in 10 women regarded themselves as having a sexual problem. These women were no older than women with sexual dysfunction who did not regard themselves as having a sexual problem. Nevertheless, they differed from the rest of the sample in having more psychiatric disorder, neuroticism, marital disharmony, and (in women still menstruating) psychological symptoms of the premenstrual syndrome. In the whole sample 16 women (4%) said that they would like help for a sexual problem. The prevalence of sexual dysfunction in this series of women suggests that general practitioners should increase their alertness to the problem in their patients.

Adult↗
PubMed1988

Villin, intestinal brush border hydrolases and keratin polypeptides in intestinal metaplasia and gastric cancer; an immunohistologic study emphasizing the different degrees of intestinal and gastric differentiation in signet ring cell carcinomas.

Gastric carcinomas have been assayed for the presence of villin and for the small intestinal hydrolases aminopeptidase N and sucrase isomaltase. These proteins seem not to be present in normal stomach epithelium. However intestinal metaplasia in stomach, and tumour cells in the glandular patterns of gastric carcinoma were positive for all three markers, showing characteristic apical positivity. In contrast, in diffuse gastric carcinomas the percentage of signet ring cells positive for these markers varied from 10-100% with each marker showing a similar percentage of positive cells. Testing of gastric carcinomas with antibodies specific for different keratin polypeptides showed that while all 7 tumours were positive for keratins 8 and 18.2 were also positive for keratin 7. In the keratin 7 positive tumours all tumour cells were keratin 7 positive. The keratin 8 antibody also reacted on routinely fixed specimens. Thus gastric carcinomas reveal different degrees of gastric and intestinal differentiation.

Adenocarcinoma, Mucinous↗