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1.
Neuroreport ; 12(4): 761-5, 2001 Mar 26.
Article in English | MEDLINE | ID: mdl-11277580

ABSTRACT

Expression of monocarboxylate transporter MCT1 was studied in archival tissues from human CNS using antibodies to the carboxyl-terminal end of MCT1. Sections of neocortex, hippocampus and cerebellum of brains from 10 adult autopsy patients who died from other than CNS disease, and from archival surgical biopsy specimens of 83 primary CNS and eight non-CNS tumors were studied. MCT1 immunoreactivity was present in microvessels and, ependymocytes of normal CNS tissues similar to that reported for MCT1 expression in rat brains. MCT1 immunoreactivity was strongest in ependymomas, hemangioblastomas and high grade glial neoplasms, and weakest in low grade gliomas. Increased MCT1 expression in high grade glial neoplasms may provide a potential therapeutic target for treatment of some CNS neoplasms.


Subject(s)
Brain Chemistry , Brain Neoplasms/metabolism , Carrier Proteins/analysis , Glioblastoma/metabolism , Antibodies , Astrocytoma/metabolism , Astrocytoma/pathology , Blotting, Western , Brain Neoplasms/pathology , Carrier Proteins/biosynthesis , Carrier Proteins/immunology , Glioblastoma/pathology , Humans , Immunohistochemistry , Monocarboxylic Acid Transporters , Oligodendroglioma/metabolism , Oligodendroglioma/pathology
2.
Int J Hyperthermia ; 16(2): 159-70, 2000.
Article in English | MEDLINE | ID: mdl-10763744

ABSTRACT

Male Fischer rats were surgically castrated through a lower midline incision and a 5-8 cm long segment of small intestine was fixed to the interior of the right scrotum. Two weeks after the surgery, the herniated intestine was heated by immersing the scrotum into a water bath at different temperatures and the blood flow in the intestine was measured with the radioactive microsphere method. The blood flow in the herniated intestine increased 1.5-2.0 times when the scrotum was heated with 42.5 and 43.5 degrees C water baths for 60-90 min, but began to decrease when heated longer, although the blood flow after heating for 120 min at these temperatures was still slightly larger than the blood flow before heating. Upon heating the scrotum with 44.5 degrees C water bath, the blood flow in the herniated intestine increased to 3-fold of control by 90 min and then rapidly recessed. Massive histological damage was observed 24 h after heating with 44.5 degrees C water bath for 60 min. The blood flow in the intestine measured 1 day after 60 min heating with 43.5 degrees C and 44.5 degrees C water bath was found to be only slightly decreased. Given the relatively small decrease in blood flow, the severe damage in the intestine 24 h after heating may be attributed to direct damage to parenchymal cells.


Subject(s)
Hyperthermia, Induced , Intestine, Small/blood supply , Animals , Blood Pressure , Cardiac Output , Male , Rats , Rats, Inbred F344 , Regional Blood Flow , Scrotum/blood supply
3.
Ann Clin Lab Sci ; 29(1): 78-85, 1999.
Article in English | MEDLINE | ID: mdl-10074970

ABSTRACT

Desmoplastic small round cell tumors (DSRCT) are highly aggressive tumors typically involving the serosal surfaces of the peritoneum. Patients often present with abdominal pain, an abdominal mass, ascites or signs of intestinal obstruction. Cytogenetic and molecular studies have identified a characteristic t(11;22)(p13;q12) translocation within the tumor cells. The fused gene product apparently aligns the NH2-terminal domain (NTD) of the EWS gene to the zinc finger DNA-binding domain of the WT1 gene. This product could lead to loss of the tumor suppressor effect of the WT1 gene as well as to an increase in EWS driven expression of growth factors normally repressed by WT1. We investigated this latter possibility by performing immunohistochemical studies on formalin fixed tissue from 10 cases of DSRCT and five Wilms' tumors using antibodies to insulin-like growth factor (IGF)-II, the latency associated peptide of transforming growth factor (TGF)-beta1, platelet-derived growth factor (PDGF)-AB chain and PDGF-alpha receptor, respectively. In general, tumor cells were strongly positive for these growth factors in DSRCT, while stromal cells were negative for IGF-II and positive for the other growth factors in parallel with the tumor cells. Wilms' tumor cells were essentially negative for PDGF-AB chains, but positive for IGF-II, and the latency associated peptide of TGF-beta1 and variably positive for PDGF-alpha receptor. These findings support the proposed molecular mechanism of tumorigenesis for DSRCT and may help explain this tumor's poor prognosis.


Subject(s)
Abdominal Neoplasms/metabolism , Abdominal Neoplasms/pathology , Carcinoma, Small Cell/metabolism , Carcinoma, Small Cell/pathology , Autocrine Communication/physiology , Growth Substances/metabolism , Humans , Immunohistochemistry , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Paracrine Communication/physiology , Wilms Tumor/metabolism , Wilms Tumor/pathology
4.
Ann Clin Lab Sci ; 28(6): 386-93, 1998.
Article in English | MEDLINE | ID: mdl-9846206

ABSTRACT

Desmoplastic small round cell tumors (DSRCT) are highly aggressive tumors typically involving the serosal surfaces of the peritoneum. Patients often present with abdominal pain, an abdominal mass, ascites or signs of intestinal obstruction. Cytogenetic and molecular studies have identified a characteristic t(11;22)(p13;q12) translocation within the tumor cells. The fused gene product apparently aligns the NH2-terminal domain (NTD) of the EWS gene to the zinc finger DNA-binding domain of the WT1 gene. This product could lead to loss of the tumor suppressor effect of the WT1 gene as well as to an increase in EWS driven expression of growth factors normally repressed by WT1. We investigated this latter possibility by performing immunohistochemical studies on formalin fixed tissue from 10 cases of DSRCT and five Wilms' tumors using-antibodies to insulin-like growth factor (IGF)-II, the latency associated peptide of transforming growth factor (TGF)-beta 1, platelet-derived growth factor (PDGF)-AB chain and PDGF-alpha receptor, respectively. In general, tumor cells were strongly positive for these growth factors in DSRCT, while stromal cells were negative for IGF-II and positive for the other growth factors in parallel with the tumor cells. Wilms' tumor cells were essentially negative for PDGF-AB chains, but positive for IGF-II, and the latency associated peptide of TGF-beta 1 and variably positive for PDGF-alpha receptor. These findings support the proposed molecular mechanism of tumorigenesis for DSRCT and may help explain this tumor's poor prognosis.


Subject(s)
Abdominal Neoplasms/chemistry , Carcinoma, Small Cell/chemistry , Growth Substances/analysis , Immunohistochemistry , Peptide Fragments , Protein Precursors , Adult , Humans , Insulin-Like Growth Factor II/analysis , Kidney Neoplasms/chemistry , Male , Platelet-Derived Growth Factor/analysis , Proteins/analysis , Receptors, Platelet-Derived Growth Factor/analysis , Transforming Growth Factor beta1 , Wilms Tumor/chemistry
5.
Cryobiology ; 34(1): 42-69, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9028916

ABSTRACT

This study investigates cryodestruction of the Dunning AT-1 rat prostate tumor at the single cell, tissue slice, and in vivo levels. The thermal history around a 3-mm-diameter cylindrical cryosurgical probe was predicted by solving the bioheat equation in a one-dimensional cylindrical geometry. At various radial positions in the iceball this thermal history was approximated by a constant cooling rate and a final, steady-state temperature (or end-temperature). The predicted cooling rates and end temperatures ranged from > or = 1000 degrees C/min to 5 degrees C/min and -196 degrees C to -20 degrees C, respectively. These cooling rates and end-temperatures were then imposed on single AT-1 cells, AT-1 tissue slices in vitro and AT-1 tumors in vivo. The single cells and tissue slices were frozen by LN2 immersion, copper block slam-freezing, or controlled cooling on a cryomicroscope or a directional solidification stage. LN2 immersion is lethal to AT-1 cells (presumably due to intracellular ice formation), while cooling at 5-100 degrees C/min leaves some viable cells (at end-temperatures ranging between -20 and -40 degrees C). AT-1 tumor slices show extensive intracellular ice formation due to slam cooling, extensive dehydration at 100 degrees C/min, and total dehydration at rates < or = 10 degrees C/min to end temperatures below -10 degrees C. Postfreeze culture and histology of the AT-1 tissue show that extensive intracellular ice formation is lethal, while cellular dehydration and vascular engorgement leave viable cells (at end-temperatures between -20 and -40 degrees C). Based solely on the single cell and in vitro tissue damage achieved by cooling rates and end-temperatures, a sizable portion of a cryosurgically frozen tumor would be expected to survive. However, in vivo cryosurgery performed on AT-1 tumors demonstrated that the tissue was damaged throughout the cryolesion, even at the periphery where the thermal history would be expected to allow single cells and tissue slices to survive in vitro. Taken together, these results suggest that damage mechanisms other than those due to cooling rate and end-temperature may be responsible for the increased cellular destruction at the periphery of the iceball in vivo and that cooling rate is less important than end-temperature in determining cryosurgical damage in AT-1 tumors. Experiments are ongoing to determine if the time held at an end temperature, thawing rate, vascular response, or other mechanisms are primarily responsible for the enhanced destructive capability in vivo.


Subject(s)
Cryosurgery/methods , Neoplasms, Experimental/surgery , Prostatic Neoplasms/surgery , Animals , Cell Survival , Male , Models, Theoretical , Neoplasms, Experimental/pathology , Prostatic Neoplasms/pathology , Rats , Tumor Cells, Cultured
6.
Clin Transplant ; 9(6): 450-3, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8645887

ABSTRACT

Nephrotoxicity remains a concern for patients on long-term cyclosporine. We have previously reported on renal function in a cohort of kidney transplant recipients followed up to 10 years posttransplant. The current study extends the analysis to 12 years. We find no evidence of cyclosporine-induced renal failure.


Subject(s)
Cyclosporine/adverse effects , Kidney Transplantation , Kidney/drug effects , Cohort Studies , Creatinine/metabolism , Cyclosporine/pharmacology , Graft Rejection , Humans , Kidney/physiology
7.
Transplantation ; 55(4): 857-65; discussion 865-6, 1993 Apr.
Article in English | MEDLINE | ID: mdl-8475561

ABSTRACT

Complement (C) activation is thought to be critical for the hyperacute rejection of xenografts. We investigated the role of C in the rejection of discordant cardiac xenografts by studying outcome in recipients depleted of C, using a highly purified form of cobra venom factor (CVF) in both a small (guinea pig [GP]-to-rat) and large (pig-to-baboon) animal model. A single dose of 30 or 60 units CVF given i.v. to rats completely abrogated hemolytic C activity for up to 72 hr. The lack of hemolytic C activity correlated with nearly undetectable serum levels of C3. Doses of 30 U/kg daily or 60 U/kg every other day over a 7-day period sustained C depletion without morbidity or mortality. Rats receiving GP cardiac xenografts during CVF therapy had significantly prolonged xenograft survival (88 +/- 10 hr in CVF-treated rats vs. 18.6 +/- 7.2 min in control rats, P < 0.001). Rats that rejected GP xenografts at 4 days posttransplant had higher levels of anti-GP antibodies than control rats, without hemolytic C activity at rejection. This rise in xenoreactive Ig reflected an increase in circulating IgG and IgM against GP antigens recognized before transplantation. Histologic analysis of GP cardiac xenografts taken from CVF-treated rats revealed leukocyte and monocyte margination along blood vessels, beginning at 12 hr posttransplant. Progressive cell infiltration, interstitial hemorrhage, and necrosis were observed over the next 72 hr. Rejected GP xenografts showed diffuse deposition of IgM and fibrin within blood vessels but no evidence of C3 deposition. A nonspecific pattern of IgG deposition was noted. CVF was tested in baboons. Complete C depletion was achieved with a dose of 60 U/kg, and was not associated with any morbidity or mortality. Xenotransplantation of a pig heart was performed in one baboon receiving CVF, 60 U/kg/day, for 2 consecutive days. Xenograft survival was prolonged to 68 hr, compared with 90 +/- 30 min in control baboons. Lack of hemolytic activity was noted during engraftment and at rejection. Histology showed evidence of vascular rejection. Immunopathology showed diffuse deposition of IgM, fibrin, and C4, and absence of C3 or membrane attack complex. We conclude that highly purified CVF can achieve marked C depletion with minimal morbidity and no associated fatalities. CVF alone can significantly prolong discordant cardiac xenograft survival. In the GP-to-rat model, the improvement in graft survival achieved with CVF was better than with conventional immunosuppression or isolated acute antibody depletion.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Complement System Proteins/immunology , Heart Transplantation/immunology , Transplantation, Heterologous/immunology , Animals , Antibodies/analysis , Complement Activation , Complement C3/analysis , Complement C4/analysis , Complement System Proteins/drug effects , Elapid Venoms/pharmacology , Graft Rejection/pathology , Graft Rejection/physiopathology , Graft Survival/drug effects , Graft Survival/immunology , Guinea Pigs , Hemolysis/drug effects , Immunoglobulin G/analysis , Immunoglobulin M/analysis , Papio , Rats , Rats, Inbred Lew , Swine , Transplantation, Heterologous/pathology
9.
Cancer ; 70(6): 1564-7, 1992 Sep 15.
Article in English | MEDLINE | ID: mdl-1516007

ABSTRACT

BACKGROUND: Therapeutic options for patients with bilateral renal cancer or cancer in a solitary kidney are limited to partial nephrectomy or bilateral radical nephrectomy with subsequent renal transplantation or dialysis. The outcome after partial nephrectomy is well documented, but few reports discuss the long-term survival of patients receiving chronic dialysis or after renal transplantation. Information regarding the long-term prognosis for these patients is important when deciding on the appropriate treatment. METHODS: The authors retrospectively evaluated the long-term prognosis of 23 patients who lost renal function because of surgery for renal cell carcinoma or Wilms' tumor between 1970 and 1990. RESULTS: Twelve patients had renal transplantation (Tx group), and 11 had chronic dialysis (DS group). In the Tx group, four patients had Wilms' tumor and eight had renal cell carcinoma (Stage I, 5 patients; Stage II, 2 patients; Stage III, 1 patient). In the DS group, three patients had Wilms' tumor, and eight had renal cell carcinoma (Stage I, 5 patients; Stage III, 2 patients; Stage IV, 1 patient). Unexpectedly, 9 of 11 (82%) patients from the DS group died of cancer, compared with 1 of 12 (8%) patients who had transplantation (P = 0.0133) despite comparable stages of renal cell carcinoma and Wilms' tumor in the two groups. CONCLUSIONS: For patients who have had bilateral nephrectomy or removal of a solitary kidney, the authors recommend waiting at least 12 months, during which time the patient receives dialysis, before proceeding with transplantation if there is no evidence of recurrent tumor.


Subject(s)
Kidney Neoplasms/therapy , Kidney Transplantation , Renal Dialysis , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Kidney Neoplasms/surgery , Male , Middle Aged , Retrospective Studies , Survival Analysis , Treatment Outcome
10.
Blood ; 79(12): 3116-29, 1992 Jun 15.
Article in English | MEDLINE | ID: mdl-1375841

ABSTRACT

A highly aggressive human CALLA+C mu+ pre-B acute lymphoblastic leukemia (ALL) cell line (NALM-6-UM1) causes disseminated and invariably fatal leukemia in CB.17 mice with severe combined immunodeficiency (SCID). We used this SCID mouse model of human pre-B ALL to evaluate and compare, in a total of 434 SCID mice, the antileukemic efficacy of B43 (anti-CD19)-pokeweed antiviral protein (PAP) immunotoxin and cyclophosphamide (CPA) as individual reagents and as combined immunochemotherapeutic regimens. B43-PAP plus CPA was superior to either the immunotoxin or drug alone, and combined immunochemotherapy markedly improved the event-free survival (EFS) of SCID mice challenged with NALM-6-UM1 pre-B ALL cells. Notably, 90% to 100% of SCID mice challenged with 1 x 10(6) leukemia cells and then treated with B43-PAP plus CPA combined immunochemotherapy regimens became long-term survivors, a result not achieved with B43-PAP alone or CPA alone. The advantage was particularly evident in mice inoculated with 5 x 10(6) leukemia cells. While neither 15 micrograms B43-PAP (median survival, 58 days) nor 1 mg CPA (median survival, 49 days) resulted in long-term EFS of SCID mice challenged with 5 x 10(6) NALM-6-UM1 pre-B ALL cells, the probability of EFS at 6 months was 50% +/- 16% for SCID mice treated with 15 micrograms B43-PAP plus 1 mg CPA (median survival, greater than 180 days) (P less than .0001). The probability of long-term EFS was only 14% +/- 7% for mice treated with 30 micrograms B43-PAP and 0% +/- 0% for mice treated with 1 mg CPA, but 40% +/- 16% for mice treated with 30 micrograms B43-PAP plus 1 mg CPA (P less than .0001). Similarly, the probability of EFS at 6 months was 40% +/- 16% for mice treated with 2 mg CPA alone, 70% +/- 15% for mice treated with 2 mg CPA plus 15 micrograms B43-PAP, and 70% +/- 15% for mice treated with 2 mg CPA plus 30 micrograms B43-PAP. Ten SCID mice in the B43-PAP plus CPA combined immunochemotherapy arms surviving long term after the inoculation of 5 x 10(6) NALM-6-UM1 pre-B ALL cells were electively killed at 174 to 181 days to assess their leukemia burden. We found no evidence of leukemia in any of the bone marrow specimens by two-color immunofluorescence and multiparameter flow cytometry.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Cyclophosphamide/therapeutic use , Immunotoxins/therapeutic use , N-Glycosyl Hydrolases , Plant Proteins/therapeutic use , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Animals , Antibodies, Monoclonal/therapeutic use , Antigens, CD/immunology , Antigens, CD19 , Antigens, Differentiation, B-Lymphocyte/immunology , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Base Sequence , Chromosome Aberrations , Cyclophosphamide/administration & dosage , DNA, Neoplasm/chemistry , Humans , Immunoglobulin mu-Chains/analysis , Immunophenotyping , Mice , Mice, SCID , Molecular Sequence Data , Neoplasm Transplantation , Plant Proteins/administration & dosage , Polymerase Chain Reaction , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Ribosome Inactivating Proteins, Type 1
11.
Blood ; 79(9): 2201-14, 1992 May 01.
Article in English | MEDLINE | ID: mdl-1373967

ABSTRACT

A highly aggressive subclone of the human CALLA+C mu+ pre-B acute lymphoblastic leukemia (ALL) cell line NALM-6 (designated NALM-6-UM1) caused disseminated and fatal leukemia in CB.17 mice with severe combined immunodeficiency (SCID). An intravenous challenge with 1 x 10(6) (NALM-6-UM1 cells caused 15 of 27 (56%) SCID mice to become paraplegic at 31 +/- 2 days (median = 33 days) and 27 of 27 (100%) mice to die of disseminated leukemia at 38 +/- 1 days (median = 39 days). We used this SCID mouse model of aggressive human pre-B ALL to evaluate the in vivo antileukemic efficacy of B43 (anti-CD19)-pokeweed antiviral protein (PAP) immunotoxin. A 3-day treatment with nontoxic doses of B43-PAP markedly reduced the incidence of paraplegia and improved event-free survival (EFS) in SCID mice challenged with 1 x 10(6) NALM-6-UM1 pre-B ALL cells, as reflected by significantly higher cumulative proportions of mice free of paraplegia or alive at 1 to 7 months, as compared with phosphate-buffered saline (PBS) treated control mice. The Kaplan-Meier estimates and standard errors of the probability of developing paraplegia after inoculation of 1 x 10(6) NALM-6-UM1 cells was 64% +/- 10% for PBS-treated mice (median time to paraplegia = 37 days) (N = 27), 18% +/- 8% for mice treated with 15 micrograms B43-PAP (5 micrograms/mouse/d x 3 days) (N = 23) and 5% +/- 5% for mice treated with 30 micrograms B43-PAP (10 micrograms/mouse/d x 3 days) (N = 21). While 27 of 27 PBS-treated control SCID mice died of leukemia at 38 +/- 1 days (range = 24 to 54 days), only 16 of 44 B43-PAP-treated mice developed leukemia at 74 +/- 12 days (range = 30 to 182 days), consistent with greater than or equal to 6 logs kill of clonogenic NALM-6-UM1 cells in 64% of SCID mice. The Kaplan-Meier estimates and standard errors of the probability of long-term EFS after inoculation of 1 x 10(6) NALM-6-UM1 cells were 65% +/- 10% for mice treated with 15 micrograms B43-PAP and 60% +/- 11% for mice treated with 30 micrograms B43-PAP with a median survival time of greater than 7 months for both groups. In contrast, neither unconjugated B43 monoclonal antibody nor the anti-T-cell immunotoxin G17.2 (anti-CD4)-PAP decreased the incidence of paraplegia or improved EFS.(ABSTRACT TRUNCATED AT 400 WORDS)


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antigens, CD/immunology , Antigens, Differentiation, B-Lymphocyte/immunology , Antineoplastic Agents, Phytogenic/therapeutic use , Burkitt Lymphoma/therapy , Immunotoxins/therapeutic use , N-Glycosyl Hydrolases , Plant Proteins/therapeutic use , Animals , Antigens, CD/analysis , Antigens, CD19 , Antigens, Differentiation/analysis , Antigens, Neoplasm/analysis , Burkitt Lymphoma/genetics , Chromosome Aberrations , Histocompatibility Antigens/analysis , Humans , Leukocyte Common Antigens , Mice , Mice, SCID , Neprilysin , Ribosome Inactivating Proteins, Type 1
14.
Transplantation ; 53(2): 316-23, 1992 Feb.
Article in English | MEDLINE | ID: mdl-1738925

ABSTRACT

Although the nephrotoxic side effects of cyclosporine are well known, the impact of long-term CsA on renal transplant function is uncertain. We studied 5-10-year renal function in 347 CsA-treated patients, and in 64 randomly selected non-CsA-treated patients who had a minimum of 55 months of graft function. Non-CsA patients had a lower creatinine (Cr) level at one year than CsA patients (P = .001), with no change in renal function over time (P = .6). In CsA-treated patients there was also no suggestion of progressive renal damage, as evidenced by no change in Cr or 1/Cr. Simple linear regression models of 1/Cr vs. time for the first 10 years posttransplant were fit to the data for each patient. Analysis of the Y-intercept estimates from these regressions showed that age (P = .001), sex (P = .001), cyclosporine toxicity (P = .024), and initial cyclosporine dosage (P = .016) significantly affected the one-year serum Cr. Variables not affecting one-year Cr included donor source, early rejection episodes, late rejection episodes, ATN, diabetes, transplant number, HLA ABDR mismatch (for cadaver transplants), maximum PRA, and PRA at transplant. Analysis of the slope estimates from the regressions revealed that only age (P = .001) and late rejection episodes (P = .001) significantly affected the rate of change in 1/Cr over time. We conclude that, in long-term renal transplant patients, there is no evidence of progressive deterioration in renal function due to CsA nephrotoxicity.


Subject(s)
Cyclosporine/therapeutic use , Kidney Transplantation/physiology , Creatinine/blood , Female , Graft Rejection/drug effects , Graft Survival/drug effects , Humans , Kidney Transplantation/immunology , Male , Multivariate Analysis , Prospective Studies , Risk Factors , Time Factors
15.
Int J Gynecol Pathol ; 11(1): 2-10, 1992.
Article in English | MEDLINE | ID: mdl-1373414

ABSTRACT

We studied seven examples of the solid variant of adenoid cystic carcinoma of the uterine cervix in postmenopausal women who presented with vaginal bleeding and a large ulcerated or polypoid cervical mass. The tumors lacked the characteristic cribriform pattern of conventional adenoid cystic carcinoma. The neoplastic cells were small, undifferentiated, or basaloid and grew in cords, nests, trabeculae, and nodules. Foci of squamous cell carcinoma were seen in three tumors and areas of necrosis in four. A characteristic feature was the production of abundant periodic acid-Schiff's procedure (PAS)-positive basement membrane material that was immunoreactive for collagen IV and that in some areas compressed tumor cells. Electron microscopy on three cases showed globules and cylinders of redundant basal lamina. The tumor cells were joined by desmosomes and contained bundles of tonofilaments. Material similar to basement membrane material appeared to be intracytoplasmic in two tumors. No neurosecretory granules or myoepithelial cells were found. Four deaths were tumor related. Two patients are currently alive, but with local recurrence or metastases; another is alive and well 19 months after surgery. We believe that the solid variant of adenoid cystic carcinoma of the cervix is a distinctive neoplasm that should be separated from small cell carcinomas with or without endocrine features, adenoid basal cell carcinoma, and squamous cell carcinoma.


Subject(s)
Carcinoma, Adenoid Cystic/pathology , Uterine Cervical Neoplasms/pathology , Aged , Basement Membrane/pathology , Cell Nucleus/pathology , Collagen/analysis , Cytoplasm/pathology , Female , Humans , Immunoenzyme Techniques , Keratins/analysis , Membrane Glycoproteins/analysis , Microscopy, Electron , Middle Aged , Mucin-1 , Necrosis , Staining and Labeling
16.
Pancreas ; 6(4): 479-88, 1991 Jul.
Article in English | MEDLINE | ID: mdl-1876604

ABSTRACT

Pancreas transplantation is usually performed in patients with denovo type I diabetes, who have advanced secondary complications. We report a case in which whole pancreaticoduodenal transplantation, with enteric drainage, was performed to correct both endocrine and exocrine deficiencies in a patient with hyperlabile diabetes and steatorrhea, unresponsive to oral enzyme replacement therapy, following staged total pancreatectomy for idiopathic or familial chronic pancreatitis. The transplant was performed one year after completion of native pancreatectomy and immediately established an insulin-independent euglycemic state, with normal oral and intravenous glucose tolerance test results and correction of steatorrhea. Beginning one year posttransplant, the patient had intermittent episodes of steatorrhea, associated with mild elevation of blood sugar levels, which were presumed to be due to rejection and, indeed, responded to antirejection treatment with antilymphocyte globulin and temporary increases in steroids dosages. At 20 months posttransplant, steatorrhea did not respond to antirejection treatment and an acute abdomen developed. Laparotomy revealed a perforated graft duodenum, which was resected; pathology showed transmural necrosis secondary to chronic rejection. The pancreas graft itself was left in situ, disconnected from the intestinal tract. The patient remained normoglycemic after graft duodenectomy but resumed oral enzyme replacement therapy in an attempt to combat recurrence of severe steatorrhea. However, his overall situation remained improved compared to pretransplant, since the exocrine deficiency was tolerable in the absence of a diabetic state. Ten months postgraft duodenectomy (38 months posttransplant), elevations in blood sugar levels were treated with another course of antirejection treatment and levels temporarily declined. At 14 months postgraft duodenectomy (42 months posttransplant), graft endocrine function again declined and exogenous insulin was resumed. Six months later, four years after the original transplant, a new enteric-drained pancreaticoduodenal graft was placed, once again resulting in an insulin-independent, steatorrheafree state. With improvements in immunosuppression, pancreas transplantation could be offered to selected patients with hyperlabile diabetes, following total pancreatectomy for benign disease; if the enteric drainage technique is used, in the absence of rejection, exocrine deficiency could be corrected as well.


Subject(s)
Duodenum/transplantation , Pancreas Transplantation , Pancreatitis/surgery , Adult , Chronic Disease , Drainage , Duodenum/surgery , Humans , Male , Pancreas/surgery
17.
Pancreas ; 6(4): 398-403, 1991 Jul.
Article in English | MEDLINE | ID: mdl-1715083

ABSTRACT

Human pancreas contains two cholinesterase isoenzymes: acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In the present study, binding potency of two organophosphates for human cholinesterases were compared by the Ellman method. Echothiophate was found to have much greater potency than iso-OMPA for both cholinesterases. Using Karnovsky histochemical stains on human pancreatic tissue, the same results were confirmed. Dose-response studies with acetylcholine were done on viable pancreas fragments from nine human donors, without pancreatic disease (group I). Cold-preservation time was less than 30 h. Pancreas was minced into fragments, after the technique of Scheele and Palade, placed in Eagle's medium, and gassed with O2. Amylase release was measured by the Phadebas Method and corrected for basal release. There was a dose-dependent response to acetylcholine at 1 and 2 h, with a shift in peak amylase release to the left, when fragments were preincubated in 10(-4) M echothiophate. This indicated a 100-fold increase in sensitivity to acetylcholine. In three patients with chronic pancreatitis (Group II), there were variable patterns of response of amylase release to acetylcholine, and higher basal outputs. In Group III, prolonged storage conditions of over 40 h were tested for 4 pancreas donor tissues. There was no response to acetylcholine. These studies show that for up to 30 h cold storage, fragments of pancreas from human organ donors respond to acetylcholine in dose-dependent manner. An organophosphate, echothiophate (10(-4) M) which inhibits both cholinesterases, increases pancreatic sensitivity to acetylcholine, and these results are similar to findings from canine pancreas fragments, which also showed increased sensitivity.


Subject(s)
Acetylcholine/pharmacology , Organophosphorus Compounds/pharmacology , Pancreas/drug effects , Amylases/metabolism , Cholinesterases/metabolism , Dose-Response Relationship, Drug , Echothiophate Iodide/metabolism , Echothiophate Iodide/pharmacology , Humans , Organophosphorus Compounds/metabolism , Pancreas/enzymology , Pancreas/metabolism , Pancreatitis/chemically induced , Tetraisopropylpyrophosphamide/metabolism , Tetraisopropylpyrophosphamide/pharmacology
19.
J Urol ; 142(6): 1478-82, 1989 Dec.
Article in English | MEDLINE | ID: mdl-2585620

ABSTRACT

We reviewed retrospectively the medical records of 58 patients treated for squamous cell carcinoma of the penis who were followed for more than 3 years or until they died. Tissue sections from all patients were reviewed. Of 15 patients with stage I disease 11 underwent partial penectomy, and 4 underwent partial penectomy and immediate ilioinguinal lymphadenectomy; none died of cancer. Nine patients with stage II and 9 with stage III disease underwent partial or total penectomy and immediate ilioinguinal lymphadenectomy, and 5-year survival was 100 and 75%, respectively. Of 20 patients with clinical stage II disease who did not undergo immediate ilioinguinal lymphadenectomy 18 had metastasis to the groin. Of these 18 patients 12 underwent delayed ilioinguinal lymphadenectomy but only 1 survived more than 5 years. We evaluated the possible significance of the degree of histological differentiation of the primary tumor to the course of the disease. Of the 23 cases of carcinoma in situ or well differentiated disease only 1 became metastatic, while of the 35 cases of moderately to poorly differentiated disease 31 metastasized to the groin. Vascular invasion of cancer cells in the primary tumor was another indicator for poor prognosis.


Subject(s)
Carcinoma, Squamous Cell/pathology , Lymph Node Excision , Penile Neoplasms/pathology , Aged , Carcinoma in Situ/mortality , Carcinoma in Situ/pathology , Carcinoma in Situ/surgery , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/surgery , Follow-Up Studies , Groin , Humans , Lymph Nodes/pathology , Male , Middle Aged , Neoplasm Staging , Penile Neoplasms/mortality , Penile Neoplasms/surgery , Penis/surgery , Prognosis , Retrospective Studies , Risk Factors , Time Factors
20.
J Urol ; 141(5): 1107-10, 1989 May.
Article in English | MEDLINE | ID: mdl-2540348

ABSTRACT

A total of 62 patients with retroperitoneal or genitourinary sarcoma was treated at our institutions during the last 46 years. Of the patients 51 were followed for at least 5 years or until they died (median followup 11 years); 5 patients were lost to followup. The most common site was the retroperitoneum. Liposarcoma, leiomyosarcoma and malignant fibrous histiocytoma were the most common tumors (74 per cent). Tumors were completely resected in 42 patients (68 per cent) and incompletely resected in 11, while a biopsy only was performed in 9. Some patients also received adjuvant radiation therapy and/or chemotherapy. There were no long-term survivors among patients with unresectable tumors. Over-all 3 and 5-year survival rates were 68 and 39 per cent, respectively. The histological type of the tumor appeared to have prognostic significance. The highest 5-year survivals were for liposarcoma (70 per cent), malignant fibrous histiocytoma (33 per cent) and leiomyosarcoma (13 per cent). The mean survival for patients after adjuvant radiation therapy or chemotherapy was similar to that after a radical operation alone. The primary cause of treatment failure was local recurrence (45 per cent of the patients), which was detected within 3 years of complete resection in most cases (82 per cent). Complete extirpation that provided adequate margins free of tumor was the most effective initial treatment and provided the best chance for cure.


Subject(s)
Histiocytoma, Benign Fibrous/therapy , Leiomyosarcoma/therapy , Liposarcoma/therapy , Retroperitoneal Neoplasms/therapy , Urogenital Neoplasms/therapy , Combined Modality Therapy , Female , Histiocytoma, Benign Fibrous/mortality , Humans , Leiomyosarcoma/mortality , Liposarcoma/mortality , Male , Middle Aged , Prognosis , Retroperitoneal Neoplasms/mortality , Retrospective Studies , Urogenital Neoplasms/mortality
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