Hepatic artery reconstruction during liver transplantation.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to A S Klein.
Explore the source record for details and available documents.
Fungal infections are characteristic of severely immunocompromised patients. Noncandidal yeasts represent a growing proportion of such infections. Risk factors for developing fungal infections include the use and abuse of central venous catheters. Two patients with gynecologic malignant neoplasms became fungemic with Hansenula anomala, a yeast of the Ascomycetes class, after insertion of central venous catheters. Frequent catheter manipulation and prolonged use favored the development of fungemia in both patients. A review of the literature revealed 19 additional cases over the course of four decades, all in hosts with underlying diseases. Thirteen of these cases have been described in the last 18 months, suggesting either increased recognition or increased frequency of infection with this organism. All tested isolates have been susceptible to amphotericin B. Patients have generally responded to catheter withdrawal and amphotericin B administration. Hansenula anomala is an opportunistic pathogen, whose clinical behavior resembles that of Candida species.
Perforation of esophageal malignancy secondary to instrumentation is an uncommon but catastrophic complication. Esophageal perforation at the site of an obstructing esophageal malignancy precludes simple operative repair and mandates esophageal resection with reestablishment of gastro-intestinal tract continuity. In the past the standard surgical approach has involved transthoracic esophageal resection via thoracotomy. We have successfully treated four patients with perforated esophageal neoplasms by transhiatal esophagectomy and cervical esophagogastrostomy, thus avoiding thoracotomy in high-risk patients. We consider transhiatal esophagectomy an advantageous alternative in the management of selected cases of instrumental esophageal perforation adjacent to an esophageal malignancy.
Forty-five patients with biliary atresia were accepted for orthotopic liver transplantation. Nine patients died awaiting transplantation, and 36 underwent transplantation. A portoenterostomy had been performed in 28 of these 36 patients, and its presence did not significantly affect the intraoperative blood loss (5.6 vs 4.1 blood volumes), the need for retransplantation (21% vs 12%), biliary complications (21% vs 12%), postoperative infections (36% vs 25%), or survival (82% vs 63%). These results indicate that early portoenterostomy is appropriate early therapy for biliary atresia; however, prompt referral to a liver transplant center for evaluation at the first sign of cholestasis is needed to attain optimal results for transplantation. Revisions of the portoenterostomy prior to transplantation did not improve the longevity of the procedure but did substantially increase complications and death after orthotopic liver transplantation.
The classical types of generalized autoimmune disease in man are systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Several murine strains which develop SLE and sometimes RA-like diseases are now available. They should help in the understanding of the etiopathology of SLE and RA. Basically two main therapeutic strategies which use solely irradiation have been tried; one being sublethal whole-body irradiation (WBI) and the other fractionated total lymphoid irradiation (TLI). Other protocols which combine lethal WBI and stem cell transplantation have often been attempted. It was regularly found that the bone marrow transplant (BMT) dictates the immune status of the recipient. This paper reviews the data published about NZB, NZB/W, BXSB and MRL mice in this context.
The Ds-controlled allele, bz-m4 Derivative 6856 [bz-m4 D6856], is reported to have an altered temporal- and tissue-specific pattern of gene expression. We have cloned this allele and have characterized it at the molecular level. The mutation was caused by the insertion of a complex transposon-like structure 36 base pairs downstream from the Bz mRNA cap site. The insert is 6.7-kbp long. Ds elements, each approximately 2 kbp in length, are at both ends of the insert. The sequence between the Ds elements is a partial duplication of flanking sequences from the 3' end of the Bz gene. These data suggest that Ds initially inserted near the 3' end of the gene and mobilized adjacent sequences as it transposed.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Renal calculus disease is an infrequent, but not insignificant, occurrence during pregnancy. Fortunately, the majority of symptomatic calculi that present during pregnancy pass spontaneously. However, 20 to 30 per cent of patients do require intervention for stones, posing a diagnostic and therapeutic challenge. Delay in treatment may jeopardize the pregnancy. Traditional methods of intervention for renal calculus disease have been supplanted by advanced, less invasive techniques; however, their application for the pregnant patient has not been addressed adequately. The varied presentation of urolithiasis during gestation and the use of newer methods of treatment in each is discussed.
Thymostimulin (TS), a partially purified thymic factor, has a significant impact on tumor development in C57B1/6 mice inoculated with Lewis lung carcinoma (3LL) cells, as judged by its effect on time of tumor appearance after tumor cell transplantation. In a previous study, we determined the conditions under which survival rate of the tumor-bearing mice can be significantly increased by TS treatment. In the study communicated here we analyzed host defense mechanisms that are modified by TS treatment in the tumor-bearing mice. In general, immune parameters that were increased or stimulated by the presence of the tumor were further increased in the TS-treated animals (number of lymphoid spleen cells, their response in mixed lymphocyte tumor cultures, their natural killer cell activity, and their ability to produce colony-stimulating factor), or reached earlier maximum levels (spontaneous [3H]thymidine incorporation, a reflection of in vivo spleen cell activation). Responses which reflect tumor-induced immunosuppression (proliferative response induced by phytohemagglutinin or concanavalin A stimulation) were restored to normal level by TS. Specific tumor-related reactions (specific cell-mediated cytotoxicity) were preserved in the TS-treated animals. The wide spectrum of TS effects had, nevertheless, certain elements of selectivity; e.g. colony-stimulating factor, but no interferon production is enhanced by TS in the tumor-bearing mice in diametric contrast to TS effect in Mengo virus-infected mice. The spectrum of TS effects was also dependent on the type of tumor cell used. The results indicate that the significant effect of TS on 3LL tumor development in mice is associated with a strong, multifaceted effect of TS on the immune system.
Renal cell carcinoma extends into the inferior vena cava in 5% of patients undergoing exploratory surgery for this malignancy. If the tumor is left unresected, death within 1 year is certain. In addition, caval occlusion may result in massive lower extremity edema, ascites, hepatic failure, and pulmonary embolus. During the past 17 years, 12 patients with renal cell carcinoma extending into the inferior vena cava were treated at a single institution by radical nephrectomy and caval tumor extraction. There were 10 men (83%) and ages ranged from 50 to 78 years (mean 63 years). There was one operative death (8%) caused by refractory coagulopathy. Long-term follow-up was achieved for all survivors. One- and 3-year survival rates by life-table method were 73% and 27%, respectively. Mean survival time after resection was 32 months. Careful preoperative planning is essential. The optimal approach for venacaval tumor extraction or resection is dictated by the cephalad extent of tumor seen on preoperative thoracoabdominal CT scan, ultrasound, or inferior venacavography. Disease limited to the infrahepatic vena cava is best approached with a thoracoabdominal incision through the eighth intercostal space. Extension of tumor to the hepatic veins or right atrium requires median sternotomy in combination with an abdominal incision for complete removal. An ellipse of vena cava around the origin of the renal vein is excised with the specimen. The resultant incision is closed by lateral phleborrhaphy. Late sequelae of the mild caval narrowing were not observed. An aggressive multispecialty surgical policy for caval extraction and resection of renal cell carcinoma resulted in extended patient survival and excellent palliation.
Inbred C57BL/6 mice were inoculated intraperitoneally (i.p.) with mengo virus. The activity of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells were measured during the first 22 days following infection. The CTL response began 7 days after virus inoculation, persisted for at least 22 days and was related to the dose of the virus inoculated. NK cell activity was elevated within 24 hr, reached its peak level on the fourth day and declined to normal levels on the eleventh day after exposure to the virus. These results suggest that NK cells represent the first cellular immune response to restrict mengo virus spread while specific CTL appear later and are probably responsible for further restriction, elimination and prevention of the viral disease.
A partially purified thymic factor, thymostimulin (TS), significantly increased the survival rate of adult, immune-intact mice infected with the neurotropic Mengo virus. TS treatment was begun after virus inoculation by daily i.p. injections. In untreated C57BL/6 mice, LD50 was reached with 1 X 10(4) PFU, but 10-fold more virus (i.e., 1 X 10(5) PFU) was needed to reach LD50 in TS-treated animals. TS effect on survival, though, could be observed with several virus doses (1 X 10(3) to 1 X 10(6) PFU) (p less than 0.001). A significant effect on survival was also observed with outbred ICR mice (p less than 0.005). Serum interferon (IFN) levels in the Mengo virus-infected mice were relatively low (average peak 300 U/ml), but were significantly increased (two- to ninefold) in the TS-treated mice. Peak serum levels were reached earlier in TS than in control animals (24 hr and 72 hr, respectively). Both acid-labile and acid-stable type I IFN production were augmented by TS in the Mengo virus-infected mice. Natural killer activity was also enhanced by TS, in particular on the second day after virus inoculation. In addition, MP-virus was used as a second, unrelated virus challenge. This virus caused a nonlethal infection, with relatively high levels of serum IFN (average peak 10,000 U/ml). TS increased IFN levels (two- to eight-fold) also in this challenge system. In conclusion, TS causes a nonspecific enhancement of endogenous production of IFN and has a significant effect on the survival of lethally infected mice. The data indicate a potential application of thymic factors for the treatment of viral infections.
The alkylating agent 1(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) caused a prolonged suppression of antibody response to sheep red blood cell challenge in mice. Two phases of suppression could be observed, an early (first three weeks after CCNU administration) and late phase (4-10 weeks). The late immunosuppression was more severe than the early one. Treatment by the thymic extract thymostimulin (TP-1R) caused a complete recovery of antibody response, with overshoot, during early phase, but only partial recovery during late phase. It is suggested that the known CCNU induced damage to stem cells, manifested at late phase, reduces the responding pool for the restorative effect of thymostimulin.
Transposition of a receptor element (Rs) for the suppressor-mutator (Spm) has generated the first Spm-controlled mutable allele of the bronze-1 (bz) locus in maize (Zea mays L.). In the absence of Spm, bz-m13 conditions full anthocyanin pigmentation in the aleurone but has a markedly decreased level compared to wild type of the gene product, UDPglucose:flavonol 3-O-glucosyltransferase (UFGT; EC 2.4.1.91). This UFGT activity appears to be qualitatively similar to the wild-type enzyme. Throughout endosperm development, the amount of a crossreactive material far exceeds the amount of detectable UFGT activity. This and other observations suggest that this insertion of Rs leads to the production of two polypeptides from the bz-m13 allele.
The effect of treatment with the thymic factor thymostimulin (TP-1) on the survival rate of tumor-bearing mice was studied, using C57BL/6 mice inoculated with 1 x 10(5) Lewis lung carcinoma (3LL) cells. TP-1 given from inoculation day (4 mg/kg, twice weekly) caused a delay in the appearance of primary tumor [14.4 +/- 1.1 (S.E.) days in control; 18.5 +/- 1.4 days in TP-1-treated animals; p less than 0.05], without changing ultimate survival rate. When primary tumor was resected, the incidence of fatal lung metastasis increased as a function of tumor size on resection day. TP-1 given after resection (same dose schedule) significantly increased survival rate as compared to resection only, provided that resected tumor diameter was less than 1.7 mm. The combination of TP-1 and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU; single i.p. injection, 50 mg/kg) was effective in either resected or nonresected primary tumor. Without resection, TP-1 with CCNU cured (more than 6 months free of tumor; untreated animals died within 30 to 44 days) 55% of the animals, as compared to 23% cured by CCNU alone (p less than 0.01). With resection animal cure rates were: resection (resected tumor diameter, 0.7 to 1.7 mm) alone, 42% cured; resection with CCNU, 47% cured; resection with TP-1, 70% cured; resection with CCNU and TP-1, 100% cured (last two groups significantly different from resection only). The results indicate a profound effect of TP-1 in prolonging life and increasing cure of tumor-bearing mice. This effect was manifested when tumor load was small and was apparently more pronounced on metastatic than on primary tumor.
Explore the source record for details and available documents.
The athymic nude mouse is a useful animal model for assaying the neoplastic growth potential in vivo of animal cells transformed in vitro. Despite the demonstrated absence of thymus-dependent immunological functions, however, the nude mouse has now been shown to reject transplants of certain highly malignant heterologous tumors. In addition, a few transformed mammalian cell lines that exhibit all or most of the cellular phenotypes usually associated with malignancy fail to grow as tumors when injected into nude mice. In a continuing study to identify the in vitro phenotypes associated with tumor-forming ability in vivo, we investigated the role of cellular susceptibility to the naturally occurring, thymus-independent lymphocytes (natural killer or NK cells) in determining tumor induction by animal cells in nude mice. A representative collection of animal cells (ranging from normal human diploid cell strains to highly tumorigenic clonal cell lines, either transformed in vitro or derived from experimental tumors) was tested to see if the ability of cells to form tumors is consistently correlated with their susceptibility to NK cell-mediated lysis measured in vitro with splenic leukocytes from nude mice. If the physiological role of the NK cells in vivo were to recognize, and possibly to destroy, incipient tumor cells in situ, a direct association between cellular tumorigenicity and susceptibility to NK activity, might be expected. If, on the other hand, the formation of growing tumors by animal cells in nude mice depended on their ability to escape the cytolytic activity of NK cells, cellular tumorigenicity would be associated with cellular resistance to NK cells. Results obtained in this study failed to confirm either of these associations. Thus, cellular suscepbibility to NK cells, at least as determined by direct cytotoxicity assay in vitro, is not a useful predictive indicator of cellular tumorigenicity in nude mice.