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Biomedical subjects

C B Gilks

Publications and source records attributed to C B Gilks.

52 records · Page 3Linked to original sources

Progression of interleukin-2 (IL-2)-dependent rat T cell lymphoma lines to IL-2-independent growth following activation of a gene (Gfi-1) encoding a novel zinc finger protein.

During progression of Moloney murine leukemia virus (Mo-MuLV)-induced rat T cell lymphomas, growth selection results in the expansion of cell clones carrying increasing numbers of integrated proviruses. These new provirus insertions reproducibly contribute to enhanced growth, allowing the emergence of cell clones from the initially heterogeneous population of tumor cells. The Mo-MuLV-induced rat T cell lymphoma lines 2780d and 5675d, which are dependent on interleukin-2 (IL-2) for growth in culture (IL-2d), were placed in IL-2-free medium to select for IL-2-independent (IL-2i) mutants. Southern blot analysis of genomic DNA from these mutants, which was hybridized to a Mo-MuLV long terminal repeat probe, revealed that all mutants carried new provirus insertions (from one to four new proviruses per cell line). A locus of integration identified through cloning of the single new provirus detected in one of the IL-2i mutants, 2780i.5, was found to be the target of provirus insertion in 1 additional IL-2i cell line of 24 tested. A full-length cDNA of a gene (growth factor independence-1 [Gfi-1]) activated by promoter insertion in the 2780i.5 cells was cloned and shown to encode a novel zinc finger protein. Gfi-1 is expressed at low levels in IL-2d cell lines cultured in IL-2-containing medium and at high levels in most IL-2i cell lines, including the two harboring a provirus at this locus. Gfi-1 expression in adult animals is restricted to the thymus, spleen, and testis. In mitogen-stimulated splenocytes, Gfi-1 expression begins to rise at 12 h after stimulation and reaches very high levels after 50 h, suggesting that it may be functionally involved in events occurring after the interaction of IL-2 with its receptor, perhaps during the transition from the G1 to the S phase of the cell cycle. In agreement with this, Gfi-1 does not induce the expression of IL-2. Expression of Gfi-1 in 2780d cells following transfer of a Gfi-1/LXSN retrovirus construct contributes to the emergence of the IL-2i phenotype.

Amino Acid Sequence↗

T-cell receptor variable region gene expression in cutaneous T-cell lymphomas.

The cutaneous T-cell lymphomas (CTCL) are a group of diseases characterized by malignant proliferations of CD4 positive T-cells having monoclonally rearranged T-cell receptor (TCR) genes. A recent study using monoclonal antibodies to two TCR beta-chain variable (V) region gene products showed preferential expression of the V beta 8 gene product in these tumors. The finding of predominant usage of a single V beta gene would imply that selection by antigen is important in the etiology of these tumors. We have studied eight cases of cutaneous T-cell lymphoma and one cell line derived from a patient with mycosis fungoides/Sezary syndrome, using an extended panel of antibodies to V region gene products. Contrary to the previous report, in our study expression of the V beta 8 gene product by tumor cells was not observed in any of the cases of CTCL or in the tumor cell line studied; preferential use of any of the variable region genes recognized by the antibodies in the panel was not observed.

Adult↗

Papillary serous adenocarcinoma of the uterine cervix: a report of three cases.

Three cases of primary papillary serous adenocarcinoma of the uterine cervix, the first described in detail at this site, are reported. Two women, 32 and 33 years of age, presented with postcoital spotting. The third patient, a 69-year-old asymptomatic woman, had abnormal cells on a routine cervical Papanicolaou smear. There was no evidence of extracervical spread on physical examination in any of the cases, but computed tomographic scan of the abdomen revealed retroperitoneal lymphadenopathy in one patient. Two patients, one treated by preoperative radiation and cervicectomy and the other by radical hysterectomy and postoperative radiation, are alive and well 5 years later. The third patient underwent cone biopsy and is currently completing chemotherapy to be followed by radiation therapy. On gross examination, the tumors were indistinguishable from typical endocervical adenocarcinoma. Microscopic examination revealed high-grade papillary serous adenocarcinoma in each case; in one tumor, there was a minor admixed component of low-grade villoglandular papillary adenocarcinoma. Although none of the tumors was deeply invasive, pelvic nodal metastases were present in two cases. There was no evidence of endometrial, tubal, ovarian, or peritoneal tumor in any case. Papillary serous carcinomas should be distinguished from other papillary carcinomas of the cervix, particularly the recently described low-grade papillary villoglandular adenocarcinoma, a variant of endocervical adenocarcinoma with a good prognosis.

Adult↗

Mucinous tumors of the appendix associated with mucinous tumors of the ovary and pseudomyxoma peritonei. A clinicopathological analysis of 22 cases supporting an origin in the appendix.

Twenty-two cases in which mucinous tumors of the appendix were associated with mucinous tumors of the ovary are reported. The patients ranged from 23 to 83 (average 49) years of age and usually presented with increasing abdominal girth. The appendiceal and ovarian tumors were synchronous in 21 cases. Laparotomy typically disclosed large cystic ovarian tumors that averaged 16 cm in diameter and were usually multiocular, an appendix that was usually dilated and covered with mucus, and abundant intra-abdominal mucus. The ovarian tumors were bilateral in seven cases. The ovarian and appendiceal tumors were typically similar histologically, with features similar to those of ovarian mucinous cystadenomas and cystadenomas of borderline malignancy. In most of the ovarian tumors, mucin dissected through the ovarian stroma (so-called pseudomyxoma ovarii). Eight of the 20 patients with follow-up information were well when last seen, but the duration of follow-up was 3 years or less in six of them. Two patients died of pseudomyxoma peritonei 4 and 5.5 years after presentation. One patient died of a myocardial infarct shortly after laparotomy for recurrent pseudomyxoma peritonei at 11 years. The remaining patients had definite or probable recurrent or residual disease but were alive at the time of the last follow-up information. The typical synchronous presentation of the ovarian and appendiceal tumors, their histologic similarity, the frequency of bilaterality of the ovarian tumors, the predominance of right-sided ovarian involvement, and the usual presence of mucin and atypical mucinous cells on the ovarian surfaces all point toward the probable secondary nature of the ovarian tumors.

Adult↗

Intratumoral T lymphocytes from small cleaved follicular center cell lymphomas show unrestricted T-cell receptor alpha-chain variable region gene usage.

The relationship between the reactive T cells and neoplastic B cells of follicular center cell lymphomas is unclear. It is not known whether the T cells are recruited nonspecifically by the neoplastic B cells or are responding through the T-cell antigen receptor (TCR), to tumor-related antigen(s). This question was addressed by polymerase chain reaction analysis of TCR alpha chain variable (V) region gene expression in intratumoral T lymphocytes from three cases of small cleaved follicular center cell lymphoma. In all three cases studied, the tumor-associated T cells showed unrestricted expression of all 18 alpha-chain V region genes. These findings imply that the T cells admixed with the neoplastic B cells of small cleaved follicular center cell lymphomas are not recruited based on TCR recognition of a single or limited number of tumor-related antigens.

DNA↗

Serous psammocarcinoma of the ovary and peritoneum.

We report 11 cases of serous psammocarcinoma, a rare variant of serous carcinoma characterized by massive psammoma body formation and low-grade cytological features. The patients ranged in age from 36 to 76 (mean of 57) years. The tumors were stage three in every case (three stage IIIA, seven stage IIIB, and one stage IIIC). Eight of the patients had ovarian psammocarcinomas with ovarian tumors measuring 5-22 (mean of 11) cm in diameter; the other three patients had primary peritoneal psammocarcinomas. The surfaces of the ovarian tumors were smooth and intact in seven of eight ovarian psammocarcinomas. Cysts were present in six of eight ovarian tumors, and the solid portions were typically gritty or granular. Necrosis was not seen. Microscopically there was destructive invasion of ovarian stroma or vascular invasion in the ovarian tumors; the extraovarian tumor implants were invasive of intraperitoneal viscera in five cases. The epithelium was arranged in small nests with no areas of solid epithelial proliferation, and at least 75% of the epithelial nests were associated with psammoma body formation. No more than moderate nuclear atypicality was identified in any case. No mitotic figures were found in 10 of the tumors, with a single mitotic figure identified in the other tumor. Follow-up data for more than 1 year was available for six patients, with two patients lost to follow-up and three patients followed without evidence of recurrence for less than 1 year. One patient died of tumor 6 1/2 years after presentation, and five patients were alive without evidence of recurrent tumor 3-10 (mean of 8.3) years after presentation. Although based on a small number of cases, these data suggest that the clinical behavior of psammocarcinoma more closely resembles that of borderline serous tumors than of serous carcinomas of the usual type, following a protracted course and being associated with a relatively favorable prognosis.

Adenocarcinoma, Papillary↗

Recurrent endometrial adenocarcinoma: presentation as a splenic mass mimicking malignant lymphoma.

We report the case of a 72-year-old woman in whom the sole manifestation of recurrent endometrial adenocarcinoma was a large splenic mass. The clinical presentation mimicked that of malignant lymphoma. Although as many as 9% of carcinomas are associated with splenic metastases, such involvement is typically encountered only at autopsy and associated with widespread extrasplenic metastases. In contrast, we have found only three other reported cases of gynecological malignancy in which a splenic mass was the sole presenting manifestation of recurrent tumor.

Adenocarcinoma↗

Histochemical changes in cervical mucus-secreting epithelium during the normal menstrual cycle.

Recently developed specific histochemical techniques were applied to sections of human endocervix to investigate possible cyclic changes in stainable intracellular mucin glycoproteins. During the secretory phase, there is a decrease in the sialic acid/O-sulfate ester ratio, a decrease in the neutral sugar/acidic sugar ratio and increased amounts of O-sulfate ester, compared with during the proliferative phase. Endocervical epithelia from prepubertal, pregnant, and postmenopausal females also show decreased sialic acid/O-sulfate ester and neutral sugar/acidic sugar ratios, compared with during the proliferative phase. The authors conclude that proliferative phase mucin is chemically different from secretory phase mucin, and that this difference may be significant in allowing sperm penetration in the periovulatory period.

Carbohydrates↗

Trichoblastic fibroma. A clinicopathologic study of three cases.

Three cases of trichoblastic fibroma, a rare benign skin tumor of hair follicle origin, are reported. On clinical examination, solitary, mobile, subcutaneous nodules with normal overlying skin were found on the vulva (one case) and scalp (two cases) in women aged 57, 46, and 19 years, respectively. On microscopic examination, the tumors were composed of complex nests and strands of basaloid, focally keratinized epithelium arranged in a moderately cellular fibroblastic stroma. No connection with the overlying epithelium or adjacent adnexal structures was observed. Immunohistochemical staining supported a trichogenic origin for these tumors. Trichoblastic fibromas are histologically distinctive lesions that should be distinguished from other tumors of follicular origin and from keratotic basal cell carcinoma.

Adult↗

Adenoma malignum (minimal deviation adenocarcinoma) of the uterine cervix. A clinicopathological and immunohistochemical analysis of 26 cases.

We reviewed 26 examples of the rare variant of cervical adenocarcinoma that has been designated "adenoma malignum." The patients, three of whom had Peutz-Jeghers syndrome, ranged in age from 25 to 72 years (average, 42 years). The most common presenting symptom was menometrorrhagia, followed by vaginal discharge, postmenopausal bleeding, and abdominal swelling in decreasing order of frequency. In 12 of the patients, the diagnosis was established on the basis of the examination of a cervical biopsy specimen, endocervical curettage specimen, or both. In three of these cases, however, up to four biopsies were performed before the diagnosis was established. In the remaining 14 patients, the diagnosis was not made until the time of operation or pathologic examination of a hysterectomy specimen. On gross examination, the cervix usually appeared abnormal, but occasional specimens were considered unremarkable. The cervix was typically described as firm or indurated. Microscopic examination showed glands that were irregular in size and shape and lined predominantly by mucin-containing columnar epithelial cells with basal nuclei. The tumors typically exhibited deep invasion of the cervical wall, and a portion of the infiltrating tumor was associated with a stromal response in most cases. Minor foci of tumor with a less well-differentiated appearance were present in 15 of the 26 tumors. Argyrophil cells were present in six of 15 tumors. Five of the six tumors containing argyrophil cells stained immunohistochemically for serotonin and peptide hormones. Positive staining for serotonin was seen in four tumors; one of these also contained a few cells positive for neurotensin. Cytoplasmic staining of the tumor cells for carcinoembryonic antigen (CEA) was seen in five of six cases. CEA reactivity was very focal in two of the positive tumors. Microscopic features that were most helpful in distinguishing adenoma malignum from normal endocervix or benign endocervical glandular proliferations were the presence of markedly irregular, abnormally shaped glands; invasion of the cervical wall; a loose edematous or desmoplastic stromal response; foci of less well-differentiated tumor; vascular invasion; perineural invasion; and positive staining for CEA. Despite radical therapy in most of the cases, the prognosis was poor. Follow-up data were available for 22 patients. Thirteen of them died of recurrent tumor, four were alive with recurrent tumor at the time of last follow-up examination, and only three patients were disease free for 2 years or more.4+ tumor of the

Adenocarcinoma↗

Biological effects of biliary shock wave lithotripsy in swine.

Extracorporeal shock waves generated with an electromagnetic lithotriptor of the second generation were administered to the gallbladder or bile ducts of 24 domestic piglets. In six animals, fresh human cholesterol gallstones were implanted into the gallbladder two weeks before shock wave administration. Treatment with 3,000 shock waves resulted in fragmentation of the majority of the gallstones in all six animals. In the other animals, 3,000 shock waves (n = 12) or 6,000 shock waves (n = 6) were directed at the gallbladder or the bile ducts without previous stone implantation. Twelve of all 24 animals were killed immediately after shock wave treatment, the other 12 after one week. Autopsy in all 24 animals revealed no gross traumatic changes; the peritoneal fluid was clear in all 24 animals. Microscopically, acute hemorrhage was found in the gallbladder wall (3/12 animals) or in the portal fissure and right lung base (1/12 animals) in those animals who were killed immediately. After one week, resolving hemorrhage with scar formation was found in the right or left lung base in 2/12 animals.

Animals↗

A novel lymphocyte activation antigen present on allospecific primed lymphocytes and defined by the monoclonal antibody VG01.

This study describes VG01, a monoclonal antibody to a novel lymphocyte activation antigen. The cells reacting with VG01 were first characterized by indirect immunofluorescence and fluorescence-activated cell sorter analysis. The antigen defined by VG01 was expressed on circulating T lymphocytes (23.8 +/- 9.0) and on the majority of large granular lymphocytes and monocytes (greater than 90%), while granulocytes stained weakly. All other cells tested so far--thymocytes, hematological malignancies and several cell lines--were negative. Upon activation with mitogens or allogeneic cells more than 90% of the transformed lymphocytes became VG01-positive. The kinetic studies demonstrated that the antigen defined by VG01 lags the expression of the IL-2 receptor by 48 hr and remains present for up to 18 days after stimulation in culture. Thus, this antigen does not seem to be involved in the initial steps of T cell activation and its expression continues after cell division has stopped. Assays with purified sorted populations showed that lymphocyte proliferation to mitogens and in mixed lymphocyte culture came primarily from the VG01- population. The responding cells became VG01+ during activation--and when alloantigen-primed lymphocytes were sorted and restimulated with the original stimulators, all the in vitro memory response came from the VG01+ population. Thus, VG01 antibody is efficient in selecting for alloreactive T lymphocytes in vitro and has potential for selective modulation of immune responses. Its reactivity with activated T cells and NK cells may also help define a common functional program for these two cell types, adding to the understanding of their mechanism of action and/or their origin.

Antibodies, Monoclonal↗

Simple procedure for assessing relative quantities of neutral and acidic sugars in mucin glycoproteins: its use in assessing cyclical changes in cervical mucins.

A simple histochemical procedure for assessing relative amounts of neutral and acidic sugars in mucin glycoproteins, and its application in the study of cyclical changes of human cervical mucins, is described. This procedure, the saponification/selective periodate oxidation/borohydride reduction/alcian blue pH 2.5/periodic acid Schiff (KOH/PA*/Bh/Ab 2.5/PAS) method, uses a selective oxidation step to remove the PAS positivity of sialic acid; thus only neutral sugars stain positively with PAS, and acidic sugars (O-sulphate esters and carboxyl groups) stain with alcian blue. This differs from the KOH/Ab/PAS technique which stains sialic acid residues with both alcian blue and PAS. Applying the KOH/PA*/Bh/Ab 2.5/PAS technique to the study of cyclical changes of human cervical mucins, a decreased neutral:acidic sugar ratio in the secretory phase mucins compared with those of the proliferative phase was found. This difference was not seen with KOH/Ab/PAS staining in the same cases. The techniques and reagents used in this procedure can be easily applied in a clinical histopathology laboratory.

Animals↗

Inflammatory pseudotumor of the uterus.

The clinical and pathological features of two cases of inflammatory pseudotumor of the uterus are reported, a lesion previously undescribed in this site. In Case 1, a 6-year-old girl presented with abdominal pain, distension, and a suprapubic mass on physical examination. The lesion in Case 2 was an incidental finding in a 30-year-old woman at the time of hysterectomy. In both cases, solitary leiomyoma-like masses, measuring 12.5 and 4.5 cm in maximum diameter respectively, involved the myometrium. On histological examination the lesions were characterized by an admixture of spindle-shaped cells and a mixed inflammatory infiltrate rich in plasma cells. The spindle cells were positive for actin with immunoperoxidase staining, and in Case 1, exhibited the ultrastructural features of myofibroblasts. Both patients are alive with no evidence of disease at postoperative intervals of 5 and 4 1/2 years, respectively. The literature pertaining to other inflammatory and reactive tumor-like lesions within the female genital tract is reviewed.

Adult↗

Colo-ovarian fistula: a report of two cases.

We report two patients with a colo-ovarian fistula which produced a granulomatous oophoritis. Both patients presented with an adnexal mass and abdominal discomfort; in each case the preoperative diagnosis was a probable neoplasm. The patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy; the colo-ovarian fistula was not recognized intraoperatively in either case. Both patients required reoperation in the early postoperative period because of the development of a colovaginal and a colocutaneous fistula, respectively. Intraoperative recognition of colo-ovarian fistula is important for the selection of the appropriate surgical procedure. The differential diagnosis of granulomatous oophoritis is discussed.

Adult↗