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Biomedical subjects

T Hatano

Publications and source records attributed to T Hatano.

At least 145 records · Page 8Linked to original sources
PubMed1994

Cytokine production and cytotoxicity of lymphocytes in patients on maintenance short- or long-term haemodialysis.

The lymphocyte-mediated cytotoxicity and cytokine production of patients under maintenance haemodialysis were studied. The patients were subdivided into two groups; 27 patients receiving haemodialysis treatment for up to 3 years (group 1) and 27 patients for longer than 10 years (group 2). Twenty-six healthy volunteers (group 3) were used as controls. The immunological parameters assayed were NK cell and lymphokine-activated killer (LAK) cell activities, and production of both interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha by either peripheral blood mononuclear cells (PBMC) cultured with IL-2 or LAK cells. In group 1 both NK- and LAK-cell-mediated cytotoxicities were significantly suppressed as compared to those in group 3. The titre of IFN produced by LAK cells was also less than that in group 3. On the contrary there were no significant differences in cytokine production by PBMC in all three groups. Percentage of the cases with suppressed cytokine production seemed higher in group 1 than group 3. In addition there was a close correlation between the value of IFN-gamma and of TNF-alpha produced by PBMC in the patients on haemodialysis. Both the type of dialysis membranes used and the primary diseases did not significantly influence the results in group 1 and group 2. From these results it could be speculated that there are more patients with impaired immune function in group 1 than in group 3. In contrast there was no significant difference in the immune function tested between group 2 and group 3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Treatment of advanced renal cell carcinoma using regional arterial administration of lymphokine-activated killer cells in combination with low doses of rIL-2.

We investigated the usefullness and problems of arterial administration of lymphokine activated killer (LAK) cells in combination with systemic IL-2 in the treatment of metastatic renal cell carcinoma (RCC). Ten nephrectomized patients with extrapulmonary and/or nonresectable metastases were treated with arterial infusions of LAK cells and systemic rIL-2 (5 x 10(5) IU twice a day) for 1-12 weeks. Leukapheresis was carried out once or twice a week, and two LAK cell populations generated from two gravity subtypes of peripheral blood lymphocytes were administered separately. Five of 15 metastases treated showed appreciable regression of metastatic sites including bone, muscle and lymph nodes. Two of 15 showed a minor response. Local pain due to metastasis was relieved or disappeared in 6 patients. There was no correlation between the response of the patients and the number of LAK cells used. The 24- and 56-month survival rate was 50 and 25%, respectively. No serious side effects were experienced during treatment. We conclude that regional arterial administration of LAK cells in combination with a low dose of IL-2 is worthwhile as an alternative treatment modality to conventional therapy for a selected group of patients with advanced RCC.

Adult↗
PubMed1994

Primary leiomyosarcoma of the ureter.

Malignant tumors of the ureteral smooth muscle are rare and the prognosis is not clear. This is a report of a patient with primary leiomyosarcoma of the ureter surviving 9 years and 9 months postoperatively without any evidence of recurrence. Malignancy of the ureter was suspected on the basis of angiography and radical nephro-ureterectomy was performed without positive cytology results.

Adult↗
PubMed1994

Tannins of theaceous plants. V. Camelliatannins F, G and H, three new tannins from Camellia japonica L.

Two new complex tannins, camelliatannins F (3) and G (4), were isolated from the leaves of Camellia japonica L. (Theaceae), and their structures, each consisting of an epicatechin unit and a C-glucosidic ellagitannin moiety, were elucidated. A new dimeric hydrolyzable tannin, named camelliatannin H (5), was isolated from the fruits of this plant. Camelliins A (6) and B (7), and camelliatannin A (1) and 3 were also isolated from the fruits.

Carbohydrate Sequence↗
PubMed1994

Simple monitoring system for R-mediated site-specific recombination on chromosomes in Saccharomyces cerevisiae.

A simple measuring system for the frequency of recombinant clones generated by R-protein mediated recombination was constructed. By applying the system, the frequencies of recombinant clones due to site-specific recombination between two loci on one or two different nonhomologous chromosome(s) were monitored during cultivation. Subsequently, it was found that the frequencies increase nearly in proportion to the culture period and are different among the individual two selected loci. Thus, the system is thought to be a candidate for analyzing physicochemical situations, such as folding and localization, of chromosomes in the nucleus.

Bacterial Proteins↗
PubMed1994

[Prognostic factors in patients with stage 4B renal cell carcinoma following nephrectomy].

We studied on prognostic factors in 106 patients with stage 4B renal cell carcinoma having distant metastases at the diagnosis. In this study, we excluded patients who died after nephrectomy within 30 days and those who died without cancer. As the result, significant differences were observed upon the 8 factors in those patients as summarized bellow: 1) The histological malignancy (grade): there observed an improved survival in patients with grade II compared to those with grade III and IV. 2) The opportunity of diagnosis: we classified the patients into 4 types: patients with urinary symptoms, those with non-urinary symptoms, those with metastatic symptoms and those with tumours found incidentally. There observed an improved survival in patients with tumours found incidentally compared to those with urinary symptoms and non-urinary symptoms. 3) The number of 5 laboratory findings such as anaemia, positive reaction of C-reactive protein (CRP), elevation of erythrocyte sedimentation rate (ESR), elevation of alpha 2-globulin and immunosuppressive acidic protein (IAP): there observed an improved survival in patients with less than 2 abnormal laboratory findings compared to those with more than 3. 4) The regional lymph node metastasis: there observed an improved survival in patients without lymph node metastasis compared to those with lymph node metastasis. 5) The number of metastatic organ: there observed an improved survival in patients with one organ metastasis compared to those with more than two. 6) The treatment modality: there observed an improved survival in patients receiving interferon (IFN) therapy/IFN plus chemotherapy than those receiving chemotherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[The results of long-term bladder cancer patient follow-up. The role of TUR in stage T1b and T2 bladder cancers].

We evaluated transurethral resection of bladder tumor (TUR) for stage T1b & T2 bladder cancers by reviewing our long-term results from 181 patients. All were followed for a minimum of 5 years or until death. In 29 patients with a stage T1b tumor treated by TUR, the 5- & 10-year survival rates were 82.5 +/- 7.1 and 73.4 +/- 8.8. Bladders were successfully preserved in 16 patients, whereas seven patients died of cancer, all of whom experienced tumor recurrence and progression at the same site as the initial lesion (true local recurrence). Conservative treatment is supposed to be indicated for a stage T1b tumor because more than half could be treated successfully by TUR. However, considering the true local recurrence, for which incomplete resection of primary lesion seems responsible, we believe that re-TUR (a second resection of the primary lesion area) is essential to evaluate the residual tumor. Radical cystectomy should subsequently be considered after re-TUR proved residual tumor because conservative treatment no longer appears reasonable and places the patients at undue risk regarding serious disease progression. As for eight patients with a stage T2 tumor treated by TUR, only one had no recurrence. The others died of recurrence of invasive tumors. In contrast, the 5- & 10-year survival rates of the patients treated by cystectomy were both 63.6 +/- 14.5%. Based on these data, radical cystectomy should be required as initial treatment for a stage T2 tumor.

Adult↗
PubMed1994

[Clinical experience with modified Studer's bladder substitute].

We modified Studer's bladder substitute technique and constructed continent urinary reservoir for 7 patients with bladder tumors after transprostatic cystoprostatectomy. Studer's bladder substitute technique is characterized by both a tubular isoperistatic proximal limb of 20 cm of the ileum in continuity with the pouch constructed using the detubularized ileum and the ureters reimplanted into the proximal part of the limb using a simple lateral anastomosis of the ureters to the end of the limb. Our modifications, transprostatic resection, was that distal one third or fourth of the prostate was left after cystoprostatectomy followed by either enucleation of the whole residual prostatic tissue including the urethra (type II) or sharp resection of the tissue leaving the urethra (type III). A small hole in the lowest part of the pouch was anastomosed either to the residual prostatic capsule (type II) or to the residual prostatic urethra (type III). Our modified Studer's technique was simple, easy to perform, and had low risk of massive bleeding especially from the central vein overlying the appex of the prostate. Clinical results were as follows; 1) all patients were satisfied with the passing of their urine per urethra without any cutaneous stoma, 2) no patients had clinical signs of pyelonephritis after discharge, 3) urine was not infected.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Novel inhibitors of poly(ADP-ribose) glycohydrolase.

The inhibitory effects on poly(ADP-ribose) glycohydrolase purified from human placenta of three classes of chemically defined tannins; gallotannins, ellagitannins and condensed tannins, were examined in vitro. Oligomeric ellagitannins were found to be most potent inhibitors of poly(ADP-ribose) glycohydrolase, their potencies increasing with increasing number of monomeric residues (dimer < trimer < tetramer). Monomeric ellagitannins and gallotannins were less inhibitory. Condensed tannins, which consist of an epicatechin gallate oligomer without a glucose core, were not appreciably inhibitory. A structure-activity study showed that higher-order conformations of the conjugates with glucose of hexahydroxydiphenoyl and valoneoyl groups, which are unique components of ellagitannins, cooperatively potentiated the inhibitory activity.

Enzyme Inhibitors↗
PubMed1993

Bovine serum albumin-doxorubicin conjugate overcomes multidrug resistance in a rat hepatoma.

A bovine serum albumin-conjugated doxorubicin via the glutaraldehyde bridge (BSA-DXR conjugate) showed potent dose-dependent inhibition of cell growth against daunorubicin-resistant AH66 (AH66DR) cells as well as parental AH66 (AH66P) cells in vitro as compared to treatment with DXR or BSA-glutaraldehyde conjugate without DXR (BSA-GA). In the culture of AH66DR with BSA-DXR conjugate, drug accumulation in the AH66DR cells increased as a function of time up to 24 h reaching approximately the same drug level as AH66P cells treated with DXR. The intracellular accumulation of the BSA-DXR conjugate was inhibited by the addition of ammonium chloride, while that of DXR alone was not inhibited. Intracellular DXR was effluxed rapidly from AH66DR cells, but BSA-DXR conjugate or pharmacologically active DXR adduct remained in the cells at a relatively high concentration over a 36-h time period. The life-prolonging effect of the conjugate was assessed using rats inoculated i.p. with AH66P or AH66DR. The rats were treated with the BSA-DXR conjugate, DXR, a mixture of DXR with BSA, or BSA-GA by either the i.p. or i.v. route. Treatment with DXR had no significant surviving effect as compared to that with saline in AH66P-bearing rats. By contrast, BSA-DXR conjugate showed a significant life-prolonging effect as compared with DXR alone in the same degree both in AH66P- and AH66DR-bearing rats. BSA-GA did not show any toxicity in vivo as well as in vitro. These results indicate that the BSA-DXR conjugate allows DXR to escape from the multidrug resistance mechanism.

Animals↗
PubMed1993

Tenascin staining positivity and the survival of patients with invasive breast carcinoma.

Tenascin immunohistochemical staining was investigated in 82 patients with primary invasive breast carcinoma followed for at least 5 years after surgery; the staining was analyzed in relation to clinicopathological factors. An intense tenascin staining pattern was noted in 59 patients (72%), but no definite correlation was found between tenascin positivity and clinical stage, lymph node metastasis, or estrogen receptor status. However, tenascin-positive patients had a significantly better prognosis than tenascin-negative patients. Tenascin staining may therefore be a useful marker for predicting the survival of breast cancer patients.

Breast Neoplasms↗
PubMed1993

Chemotherapeutic efficacy of the protein-doxorubicin conjugates on multidrug resistant rat hepatoma cell line in vitro.

In vitro studies were initiated to study the antitumour effect of protein-doxorubicin (DXR) conjugate on the growth of the multidrug resistant rat ascites hepatoma cell line, AH66DR. The 50% inhibitory concentration (IC50) for DXR in AH66DR cell line was 16 mumol l-1 (AH66 parental cell line, AH66P, IC50 was 0.08 mumol l-1). Treatment of AH66P and AH66DR cells with various concentrations of DXR or conjugates at equivalent concentrations of DXR was performed. The two types of conjugates used were bovine serum albumin (BSA)-DXR conjugate and immunoglobulin G (IgG)-DXR conjugate. Both of these conjugates showed potent dose-dependent inhibition of cell growth against AH66DR cells as compared with the cells treated with DXR or other controls. The IC50 for BSA-DXR and IgG-DXR conjugates in AH66DR cell line was 0.05 (equivalent DXR) mumol l-1 and 0.07 (equivalent DXR) mumol l-1, respectively. These values were similar to that of the AH66P treated with DXR. Cellular uptake and accumulation of DXR or BSA-DXR conjugate was also quantitated in both cell lines. The cellular concentration of DXR in AH66DR cells was 2-fold lower than that of AH66P cells throughout the experiment. In contrast, by the treatment of AH66DR cells with BSA-DXR conjugate, the intracellular drug concentration increased as a function of time up to 24 h (639.1 +/- 41.8, equivalent DXR, ng 10(-5) cells) and reached the same drug level as AH66P cells treated with DXR (617.9 +/- 17.3 ng-5 cells). Ammonium chloride treatment inhibited the effects of the conjugates but did not inhibit the free drugs. Intracellular DXR was effluxed rapidly from AH66DR cells, but BSA-DXR conjugate remained in the cells at relatively high concentration for a long time. These results indicate that by chemically modifying DXR, such as by conjugation of the drug with proteins, it may be possible to overcome multidrug resistance.

Animals↗
PubMed1993

Antitumor activity of oenothein B, a unique macrocyclic ellagitannin.

The antitumor effect of oenothein B, a macrocyclic ellagitannin from Oenothera erythrosepala Bordas, on rodent tumors was studied. Oenothein B exhibited a strong antitumor activity against MM2 ascites tumors upon intraperitoneal administration to the mice before or after the tumor inoculation. The tannin also inhibited the growth of Meth-A solid type tumor in mice. This antitumor effect of the tannin could not be attributed to its direct cytotoxic action on tumor cells, because the cytotoxicity was very weak in the presence of serum protein. When oenothein B was injected into the peritoneal cavity of mice, peritoneal exudate cells, including cytostatic macrophages, were induced. Furthermore, in the in vitro treatment of macrophages from mice and humans, the tannin stimulated release of an interleukin 1 (IL-1)-like activity and IL-1 beta from the cells. These results suggest that oenothein B exerts its antitumor effect through potentiation of the host-immune defense via activation of macrophages.

Animals↗
PubMed1993

Cytotoxic effect of the protein-doxorubicin conjugates on the multidrug-resistant human myelogenous leukemia cell line, K562, in vitro.

In vitro studies were performed to examine the antitumor effect of protein-doxorubicin (DXR) conjugate on the growth of the multidrug-resistant human chronic myelogenous leukemia cell line, K562/DXR. The 50% inhibitory concentration (IC50) for DXR in the K562/DXR cell line was 20 nM (in the K562 parental cell line, IC50 was 3.2 nM). Treatment of both types of cells with various concentrations of DXR or conjugates at equivalent concentrations of DXR was carried out. One type of the conjugates used was human serum albumin (HSA)-DXR conjugate and human transferrin (Tf)-DXR conjugate via a glutaraldehyde bridge (HSA-ga-DXR, Tf-ga-DXR, respectively) and another type used was HSA-DXR conjugate with a dextran bridge (HSA-dex-DXR). All of these conjugates showed potent dose-dependent inhibition of cell growth against the K562/DXR cells as compared with the cells treated with DXR or other controls. IC50 for HSA-ga-DXR, Tf-ga-DXR and HSA-dex-DXR conjugates in the K562/DXR cell line was 2.4, 3.6 and 1.0 (equivalent DXR) nM, respectively, which were approximately similar to the value of the K562 treated with DXR. Through the treatment of K562/DXR cells with HSA-DXR conjugate, the intracellular drug concentration increased as a function of time up to 24 h compared with the cells treated with DXR. Intracellular DXR effluxed rapidly from K562/DXR cells, but HSA-ga-DXR as well as HSA-dex-DXR conjugates remained in the cells at a relatively high concentration for a long time. These results indicate that it may be possible to overcome multidrug resistance by chemically modifying DXR, such as by conjugation of the drug with proteins.

Cell Survival↗
PubMed1993

Antitumor activities of ellagitannins against sarcoma-180 in mice.

Forty-five ellagitannins and related compounds were intraperitoneally injected into mice once, 4 d before intraperitoneal inoculation of S-180 cells, and their antitumor activities were evaluated. When an antitumor-active tannin was defined as one producing a 70% increase or more in the mean life span of mice or one regressor out of six mice, twenty-one ellagitannins were active. Among monomeric ellagitannins, tellimagrandin II was most active. Most of the oligomeric ellagitannins, consisting of tellimagrandins I and II as the monomer unit, had a significant antitumor activity. Macrocyclic ellagitannins were all active. Oenothein B, among them, had the most potent antitumor activity. In contrast, ellagitannins containing a casuarictin or potentillin moiety in their molecules, except for extensively oligomerized ones, showed very low or negligible activity. These results suggest that tannins need the ellagitannin monomer units, having galloyl groups at the O-2 and O-3 positions on the glucose core(s), such as tellimagrandins, in order to exhibit a strong antitumor activity.

Animals↗