Orthotopic liver transplantation for primary hepatic cancer in rats.
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Biomedical subjects
Publications and source records attributed to Y Fukuda.
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We measured soluble interleukin-2 receptor (sIL-2R) levels in the cerebrospinal fluid (CSF) of patients with hematological malignancies especially, adult T-cell leukemia (ATL) and non-Hodgkin's lymphoma (NHL) with or without meningeal infiltration. CSF levels of sIL-2R were significantly higher in patients with ATL and NHL with meningeal infiltration than in patients with both diseases without meningeal infiltration. The sIL-2R levels in CSF were elevated in 4/4 ATL patients (100%) and 3/13 NHL patients (23%) with meningeal infiltration. CSF levels of sIL-2R from ATL patients with meningeal infiltration had a tendency to elevate in correlation with numbers of mononuclear cells and lactic dehydrogenase (LDH) in CSF. However, these had no correlation with serum levels of sIL-2R. Therefore, sIL-2 levels in CSF may be useful in the diagnosis of meningeal infiltration in patients with ATL, are probably specific markers for meningeal infiltration of ATL.
The efficacy of postoperative adjuvant chemo- and chemoimmunotherapy in non-small cell lung cancer was evaluated in a multicentric prospective randomized study. From September 1987 to June 1990, resected lung cancer patients were randomly stratified into three groups. Group A received 2 courses of chemotherapy with CDDP and VDS following operation. Group B was administered UFT daily for 1 year after 2 courses of CDDP. Group C received intrapleural administration of OK-432 after lung resection, then UFT and OK-432 once every 2 weeks for 1 year. Out of 94 cases, analyses were carried out on 87 of eligible cases. The five-year survival rate was 56.8% in stage I (43 cases), 73.3% in stage II (12 cases), 18.8% in stage IIIA (24 cases), 50% in stage IIIB (2 cases) and 33.3% in stage IV (6 cases). The five-year survival rate in group A was 32.2%, 55.2% in group B and 53.9% in group C, and no statistical difference was recognized between 3 groups. But in the cases of noncurative resection, the 5-year survival rate was significantly low in group A compared with Group B or C. Similarly, the cases with low-grade TP (<6.0 g/dl) or low response of PPD skin reaction (< 12mm) showed a significantly low 5-year survival rate only in group A. From these results, it was suspected that aggressive chemotherapy provides no benefit for postoperative lung cancer patients with advanced disease.
The efficacy of omeprazole, 20 mg once daily, in suppressing Helicobacter pylori colonization was studied in 33 patients with peptic ulcers. Omeprazole treatment produced a significant fall in the number of H. pylori colony-forming units in the antrum. This finding, together with the results of a meta-analysis of clinical trials of H. pylori eradication therapy, suggests that combinations of omeprazole and antibiotics may be useful as eradication therapy in patients with peptic ulcer disease and H. pylori infection.
Recent international consensus statements have concluded that Helicobacter pylori is a causal factor in peptic ulcer disease and a Group 1 carcinogen in humans, and that all patients with peptic ulcer associated with H. pylori infection should receive eradication therapy. There are marked differences in the presentation of peptic ulcer disease between Japanese patients and those from other countries, however, and thus a committee of the Japanese Society of Gastroenterology has been set up to develop guidelines for clinical trials in patients with gastric or duodenal ulcers associated with H. pylori. According to these guidelines, eradication therapy should normally consist of dual therapy with a proton pump inhibitor, such as omeprazole, and an antibiotic; a nitroimidazole can be added, however, if necessary. The diagnosis of H. pylori should be made on the basis of a positive culture of the organism or histological examination of gastric biopsies, together with a positive urease test or 13C-urea breath test. Eradication should be confirmed by the same means 4-6 weeks after treatment. Other research is investigating the relationship between H. pylori and gastric cancer, an important issue in view of the high incidence of this condition in Japan. There is evidence that the Mongolian gerbil may be a useful animal model to investigate this question.
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Here, we describe the clinical course of an adult patient who had living-related liver transplantation (LRLT) from a donor with Gilbert's syndrome and problems of living-related liver transplantation to adult patients. A 22-year-old woman had been diagnosed as having liver cirrhosis at the age of 5. She had undergone devascularization and transsection of the esophagus, and splenectomy for esophageal varices at the age of 8. Complications such as spontaneous bacterial peritonitis and nonspecific colitis sometimes appeared from 17 years old, and icterus and ascites had appeared on all such occasions. Such complications had frequently occurred from 21 years old. Total bilirubin was 5.5 mg/dl and direct bil. was 4.2 mg/dl. The patient and her family members were informed that LRLT might be possible, and they indicated that the patient's 57-year old father was willing to act as the donor. His liver function was examined. His hepatic function was normal except for hyperbilirubinemia (T. Bil. 2.3 mg/dl, D. Bil. 0.3 mg/dl). He was diagnosed with Gilbert's Syndrome because of an increase of unconjugated bilirubin levels during low caloric intake and nicotinic acid test. The standard liver volume for the patient was calculated to be 900 ml on the basis of body weight. Volumetric analysis with computed tomography revealed that the left lobe volume of the donor's liver was 512 ml, corresponding to 56% of the recipient standard liver volume. This proposal was submitted to the ethical committee of Tokushima University School of Medicine and was accepted. In March 28, 1995, the patient underwent LRLT with the donor's left lobe as the graft. The graft weight was 440 g and the graft corresponded to 49% of the recipient's standard liver volume. Volumetric analysis showed rapid enlargement of graft to 683 ml as early as one week after the operation. The donor has returned to work after discharge from the hospital. The recipient is well 11 months after surgery. Total bilirubin was 1.8 mg/dl and D. Bil 0.5 mg/dl. LRLT may become an option for adult recipients, if graft of more than 30% of the recipient standard liver volume is transplanted even from a donor with Gilbert's syndrome.
Two hundred Japanese panels were serologically typed for human leukocyte antigen (HLA) - DR to assign 65 HLA-DR8 haplotypes, which were then subdivided into two genotypes, i.e., DRB1*0802 and DRB1*0803, by a polymerase chain reaction (PCR)--based, simple, and practical method. The panels possessing DR8 specificity were firstly subjected to PCR with a couple of primers specifically to amplify their DR52 associated group--DRB1 genes. PCR products were then denatured in the presence of formamide, electrophoresed in a non-denaturing polyacrylamide gel, and visualized by silver staining. The same DRB1 products of these samples were also mixed with the DRB1*1302, and simultaneously analyzed by the same procedure. Electrophoretic mobilities of the samples were compared with those of the typing standards to genotype their DR8--DRB1 alleles by using the characteristic polymorphism in the single-stranded DNAs and the heteroduplexes. This method, designated PCR--DNA conformation polymorphism (DCP) analysis, allowed for genotyping of the DR8-DRB1 alleles without using sequence-specific oligonucleotide probes (SSOP) or restriction endonucleases. The entire process after PCR was completed within a few hours. The tested panels were also genotyped for DRB1 gene by the PCR-SSOP method for comparison with results obtained by the PCR-DCP method. Satisfactory coincidence was achieved and it represented how accurately the new system genotyped DRB1*0802 and DRB1*0803. PCR-DCP analysis was thus shown to be practical and useful for subtyping of serologically defined DR8 specificities.
Livers from fasted animals are believed to be more vulnerable to ischemic injury than those from fed donors. However, we have recently shown the opposite: livers from fasted rats were more tolerant to ischemic injury. Indeed, the survival rate of 60 min warm ischemic damaged livers increased from 0 to 90% if donor rats were fasted for three days. In this study, we examined how donor fasting affects the outcome of pancreas and heart preservation. BN rats were used as both donors and recipients, and recipients of pancreatic grafts were rendered diabetic prior to transplantation. Pancreatic or heart grafts were subjected to 90 min or 25 min of warm ischemia and were transplanted into the right side of the necks of recipients rats. The viability rate of hearts transplanted from fed donors into fed recipients was only about 11% (1/9) after transplantation. However, the viability rate with fasted donors was 75% (6/8). The rate of successful pancreatic grafting from fed donors into fed recipients was 28.6% (2/7), and that from fasted donors to fed recipients was 41.7% (5/12). These results confirm that the nutritional status of the donor is an important factor in the outcome of not only liver, but also pancreas and heart preservation during transplantation, although the effect of fasting on pancreatic graft is marginal.
The extracellular matrices and vascularization of the developing corpus luteum of adult female rats were studied with immunohistochemistry for laminin, type I, III and IV collagen and with electron microscopy. Ovaries were removed from Wistar-Imamichi rats that had a regular 4-day estrous cycle, 6 and 2 h before ovulation, immediately after ovulation, 6, 16 and 24 h after ovulation and at maturity of the corpus luteum and examined. The basement membrane of the follicles and capillaries of the theca interna started to break down around the entire circumference of the Graafian follicle 2 h before ovulation. More than 6 h after ovulation, dot-pattern positive reactions for type IV collagen and laminin were detected in the granulosa layer, and thin basement membrane structures appeared in association with the luteinizing granulosa cells. More than 16 h after ovulation, vascularization with the formation of capillary basement membrane was observed in the granulosa layer, and luteal mesenchymal cells with adjacent interstitial collagen components always appeared in close association with the newly formed capillaries. Our chronological observations revealed that both luteinizing cells and luteal mesenchymal cells are involved in the destruction and reconstruction of the follicular ECM, and that the luteal mesenchymal cells play an essential role in the neovascularization of the developing corpus luteum.
Ecabet sodium (ecabet), a new agent that has protective effects on the gastric mucosa has anti-Helicobacter pylori effects, binding with urease to inhibit H. pylori activity, and causing the bacterial to become non-viable. Ecabet monotherapy eradicates H. pylori infection in Japanese monkeys. We investigated a new regimen that included ecabet to eradicate H. pylori infection in gastric ulcer patients. Fifty-five H. pylori-positive patients with gastric ulcer were randomly assigned to one of two groups: group 1 received dual therapy with lansoprazole (30 mg o.d.) for 8 weeks plus clarithromycin (200 mg b.i.d.) or amoxicillin (250 mg q.i.d.) for 2 weeks. Group 2 received triple therapy with lansoprazole (30 mg o.d.) and ecabet sodium (1.0 g b.i.d.) for 8 weeks plus clarithromycin (200 mg b.i.d.) or amoxicillin (250 mg q.i.d.) for 2 weeks. Four weeks after the treatment was withdrawn, H. pylori status was evaluated by histological examination, rapid urease test, and culture. The eradication rate was 26% (7 out of 27 patients) in group 1 and 79% (22 out of 28 patients) in group 2. All patients completed the treatment. The addition of ecabet to the regimen increased the eradication rate of H. pylori infection, and there were no associated major side effects.
Eradication therapy for Helicobacter pylori is now common, since eradication of this organism reduces the recurrence rate of peptic ulcer. We evaluated the eradication of H. pylori 4 weeks after the cessation of eradication treatment, and encountered recolonization in patients in whom eradication had been confirmed. Using a urease probe, we analyzed the Ure B restriction fragment length polymorphism (RFLP) of the DNA of the recolonized H. pylori by Southern blotting and compared it with that of the H. pylori strain cultured before eradication therapy. RFLP patterns before and after the treatment were identical, indicating that the recolonization of H. pylori was an exacerbation of the primary infection, rather than a reinfection.
The optic nerve fibers of adult mammals, once injured, can not regenerate spontaneously. However, from recent studies it has become clear that when their extracellular environment is replaced with that of the peripheral nervous system, namely surrounded with Schwann cells, they can regenerate their axons through the grafted nerve. Previous studies on the optic nerve regeneration by peripheral nerve transplantation have been done mostly in rats or hamsters. With an expectation of clinical application in future, we studied the optic nerve regeneration of adult cats because a great deal of knowledge on the optic nerve fibers and retinal ganglion cells had been accumulated. From recent series of studies we have obtained following results. 1. Retinal ganglion cells that regenerated axons constitute 2--4% of the total population, and among several types of ganglion cells, alpha cells have the greatest capacity for axonal regeneration. The ability of alpha cells for axonal regeneration is related to their relative resistance to axotomy. 2. Retinal ganglion cells with regenerated axons preserve their original dendritic fields, but their axons are thinner than normal, and mostly unmyelinated. 3. Single unit activities recorded from teased fibers of regenerated axons revealed that the units have mostly normal receptive field properties, enabling us to classify them into Y, X or W cells. 4. Amplitude reduction of pattern reversed electroretinogram (ERG) after the optic nerve section was slowed, to some extent, by the peripheral nerve transplantation. How we can reconnect these regenerated optic nerve fibers to the target neurons in the central visual system is a matter for future study.