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Biomedical subjects

H Seki

Publications and source records attributed to H Seki.

At least 199 records · Page 11Linked to original sources

Lymphokine production by human melanoma tumor-infiltrating lymphocytes.

Lymphokine production by human melanoma tumor-infiltrating lymphocytes (TIL) was studied. Uncultured TIL produced interferon gamma (IFN gamma), but not interleukin-2 (IL-2) or IL-4, in response to anti-CD3 mAb or IL-2. In bulk cultures, IL-2-activated TIL displaying autologous tumor-specific cytotoxicity (CTL-TIL) produced IFN gamma in culture with medium alone, whereas IL-2-activated noncytotoxic TIL did not. Addition of anti-CD3 mAb or autologous tumor cells up-regulated IFN gamma production in IL-2-activated TIL from 10 of 12 or 6 of 12 cases respectively. Those from 4 of 12 cases (2 CTL-TIL and 2 noncytotoxic TIL) produced IL-2 in culture with medium alone. At the clonal level, 5 (4 CD4+ and 1 CD8+) of 7 autologous tumor-specific CTL clones derived from TIL and 3 (2 CD4+ and 1 CD8+) of 7 noncytotoxic TIL clones produced IFN gamma in culture with medium alone, which was up-regulated by adding anti-CD3 mAb. Two IFN gamma-producing CTL clones tested produced IL-2 in 4x-concentrated supernatants from a 3.5-h culture with medium alone. Furthermore, 2 IFN gamma-producing CTL clones tested expressed mRNA for both IFN gamma and IL-2. IL-2 production and its mRNA expression were up- or down-regulated, respectively, by adding anti-CD3 mAb or autologous tumor cells. IL-4 production was not observed in culture either with medium alone or with IL-2 in any of the cells described above. Anti-CD3 mAb was required for IL-4 production in 3 of 12 IL-2-activated TIL, 2 of 6 CTL clones, and none of 5 noncytotoxic TIL clones. In summary, IFN gamma production was characteristic of melanoma TIL. Some autologous tumor-specific CTL in TIL are suggested to be productive of IL-2 and IFN gamma under unstimulated conditions, both being required for self-activation in an autocrine loop.

Antibodies, Monoclonal↗

[Analysis of kinesthetic sensation: the influence of m. deltoid, m. forearm extensor and flexor on sensory information of reproductive elbow movements].

The effect of muscle vibration during voluntary self-paced elbow movements were studied in normal human subjects. Vibrations (10Hz, 30Hz, 50Hz, 70Hz) were applied to the m. deltoid, m. forearm extensor and flexor: vibration was turned off between movements. During non-visually guided (eyes closed) movements (reproductive movements), an undershoot of the required movement was observed in cases where vibration (30Hz, 50Hz, 70Hz) was applied to the m. forearm extensor and flexor. On the contrary, no effect was observed in cases where vibration (80Hz) was applied to the m. deltoid. These findings suggest that sensory information from the m. forearm extensor and flexor might play a role in reproductive elbow extension and flexion movements.

Elbow↗

[Studies on the function of mast cells infiltrating in nasal polyps].

The function of nasal polyp mast cells has not been elucidated despite the large number of these cells observed in tissues. We examined these mast cells histochemically, immunohistologically and functionally. Ninety-three percent of collagenase dispersed cells in a nasal polyp were formalin-sensitive. These dispersed cells released histamine in reaction to calcium ionophore A23187 in a dose dependent manner, but not in response to C5a, Compound 48/80 or Substance P. From these results, dispersed mast cells from nasal polyps were considered to be analogous to dispersed mast cells from the human lung and nasal mucosa but not those from human skin. On the other hand, in the reaction with anti-human IgE, dispersed mast cells from a non allergic nasal polyp could not be seen to release histamine. In only 2 of 7 patients, could histamine release in response to Japanese red cedar antigen, from mast cells sensitized passively with the serum of Japanese red cedar pollinosis, seen. Using small tissue samples from polyps, histamine was released by anti-human IgE in allergic patients but not in non allergic patients. Immunohistologically in allergic nasal polyps, some IgE positive mast cells could be seen, whereas in non allergic polyps these cells were absent. These observations suggest that mast cells which had accumulated in nasal polyps both with and without allergy were capable of functional histamine release, whereas in the nasal polyps of allergy patients but not in non-allergic patients these cells are involved in IgE mediated reactions.

Adolescent↗

[Localization of androgen receptor in male sex organ, accessory sex organs and external genital skin].

Previously, we established an anti-androgen receptor (AR) monoclonal antibody. Using the antibody, we investigated immunohistological AR localization in human testes, epididymides, seminal vesicles and scrotal skins. The testes, epididymides and scrotal skins were obtained from a prostate cancer patient without pre-hormonal therapy undergoing bilateral orchiectomy. The seminal vesicles were obtained from a bladder cancer patient undergoing radical cystectomy. The tissues were immediately frozen in liquid nitrogen and kept at -80 degrees C until used. Cryostat-frozen sections were cut at 5 microns and stained by an indirect method. We obtained the following results. 1) In the testes, nuclei of Leydig cells were stained though Sertoli cells were not stained. AR localization in Leydig cells which produce testosterone suggests autocrine or intracrine mechanism in the testis. 2) In the epididymides, nuclei of epithelial cells of epididymal ducts were stained, while muscles and connective tissues were not stained. In the seminal vesicles, nuclei of glandular epithelial cells were stained. 3) In the scrotal skins, the cells of squamous cell layer have positive stainings. The cells in the upper portion of squamous cell layer were stained more intensely than the cells in the lower portion. The basal layer was not stained. The cells of the outer root sheath of hair follicles in the scrotal skins were also stained. 4) In androgen target organs, AR-positive cells and AR-negative cells were mixed in the epithelium of a glandular duct, which suggests heterogeneity of AR localization in the androgen target organs.

Animals↗

[A case of lung cancer with specific calcification].

A 67-year-old male was admitted for detailed investigation of an abnormal chest roentgenogram showing a tumor shadow about 3 cm in diameter in the left S1+2. The shadow was surrounded by minute granular and striate shadows. Small cell carcinoma of the lung was diagnosed and chemotherapy was commenced, but without effect. Hypercalcemia and superior vena caval syndrome followed. Autopsy indicated highly specific calcinosis present in the left upper lobe peripheral to the primary disease. This calcinosis was observed subepithelially in bronchi and bronchioles, in the tunica intima of the veins, and in the alveolar septa. It could not be detected in the tumor or arterial or lymphatic systems. The calcinosis had been present prior to the development of hypercalcemia, and the density of the calcinosis was greatest close to the tumor, gradually decreasing with increased distance from the tumor. The calcinosis appeared to have been caused by some substance, and to have been accelerated by venous congestion, resulting in its unique distribution.

Aged↗

[Study on the pharmacokinetics of cefepime (I)].

The pharmacokinetics of 14C-cefepime dihydrochloride (14C-CFPM), were studied in rats upon both single and repeated intravenous administration. 1. Blood level of radioactivity was 59.27 micrograms eq./ml at 5 minutes after single intravenous administration at a dose of 20 mg/kg, and declined biexponentially thereafter. The values of AUC and T 1/2 were 70.1 micrograms eq..hr/ml and 38.0 hours, respectively. 2. Blood level of radioactivity was 59.41 micrograms eq./ml at 5 minutes after administration on the 7th day of repeated intravenous administration at a daily dose of 20 mg/kg, and declined more slowly as compared to the case of single administration. The values of AUC and T 1/2 after repeated administration were 159.7 micrograms eq..hr/ml and 44.5 hours, respectively. 3. Urinary and fecal excretion rates after single administration were 93.3% and 3.3%, respectively. 4. Urinary and fecal excretion rates were almost constant throughout the repeated administration; 88.4-90.7% and 2.3-3.7%, respectively. 5. 14C-CFPM distributed rapidly to the whole body except to the central nervous system. Although the radioactivity was removed rapidly from tissues, high levels of radioactivity remained in the kidney and the spleen as compared to other tissues. 6. Tissue concentrations of radioactivity at 5 minutes after the final dose of repeated administration were about the same as those after single administration but they declined more slowly than those after single administration. High levels of radioactivity were found in the kidney and the spleen as were found upon single administration. The ratios of these levels between repeated and single dosing were 4.3 and 2.6 for kidney and spleen, respectively. 7. Data obtained with autoradiograms of the whole body were consistent with measured tissue distribution obtained in both cases of single and repeated administration.

Animals↗

[Study on the pharmacokinetics of cefepime (II)].

The pharmacokinetics of 14C-cefepime dihydrochloride (14C-CFPM), was studied in dogs after single intravenous administration at a dose of 20 mg/kg. Protein binding was also investigated both in vitro and in vivo. 1. Blood level of radioactivity was 83.53 microns eq./ml at 5 minutes after single intravenous administration and declined biexponentially thereafter. The values of AUC and T1/2 were 229 microns eq.(.)hr/ml and 90 hours, respectively. 2. Urinary and fecal excretion rates were 95.1% and 2.7%, respectively. 3. The in vitro protein binding at 1 to 100 microns/ml of drug concentration was 7.9 to 12.7% in rat, 12.4 to 18.6% in human, and 12.5 to 14.5% in dog. In vivo protein binding, which increased with time after administration, was 10.8 to 92.9% in rat and 17.5 to 64.9% in dog at 5 minutes to 6 hours.

Animals↗

[Relationship between Ga-67 uptake and radiotherapeutic response of primary lung cancer (squamous cell carcinoma)].

This investigation was undertaken to evaluate the relationship between Ga-67 uptake and radiotherapeutic response to primary lung cancer (squamous cell carcinoma), Ga-67 uptake of tumor was estimated on 16 patients with untreated primary lung cancer (squamous cell carcinoma). Ga-67 uptake was then compared with the response to radiation therapy (tumor reduction ratio). There was statistically significant inverse correlation between Ga-67 uptake and response to radiation therapy (r = -0.701, p less than 0.01). The fewer the Ga-67 accumulation in the tumor, the more effective radiotherapy in reducing tumor size. In conclusion, Ga-67 scintigraphy appears to be able to predict the response of primary lung cancer (squamous cell carcinoma) to radiation therapy.

Carcinoma, Squamous Cell↗

Role of prostaglandins in pregnancy-induced hypertension.

Enzymes involved in prostaglandin I2 (PGI2) and thromboxane A2 (TXA2) synthesis were studied in maternal and fetal platelets and venous endothelium from normotensive pregnant controls (n = 70), women with mild preeclampsia (MP, n = 45), and severe preeclampsia (SP, n = 34). Activities of phospholipase A2 (PHA2), cyclooxygenase (PGHS), and PGI2 synthetase (PGIS) or TXA2 synthetase (TXAS) were determined in platelets and in endothelial cells. The PGHS enzyme was studied further by immunoblot methodology. In maternal platelets: Vmax (per 10(-10) mol/mg protein) and Michaelis-Menten constant (Km) (10(-7) mol, mean +/- SEM) of PHA2 were 3.0 +/- 0.8, 3.0 +/- 0.7, and 31.7 +/- 10.9* maximum velocity (Vmax) and 1.8 +/- 0.3, 2.0 +/- 0.8, and 0.8 +/- 0.2 (Km) in normal control (NC), mild preeclampsia (MP), and severe preeclampsia (SP), respectively (*P less than 0.05 against NC). The apparent overall PGHS plus TXAS activity was 10.2 +/- 1.8, 23.8 +/- 7.1, and 68.8 +/- 18.8* (Vmax) and 3.2 +/- 1.3, 5.4 +/- 1.4, and 6.9 +/- 1.2* (Km, *P less than 0.05 against NC). TXA synthesis in fetal platelets demonstrated PHA2 activity of 6.4 +/- 1.4, 12.0 +/- 1.3, and 17.2 +/- 3.2* (Vmax) and 3.5 +/- 0.9, 2.2 +/- 1.5, and 0.7 +/- 0.3* (Km, *P less than 0.05 against NC), respectively, whereas an apparent overall PGHS plus TXAS activity was 18.5 +/- 2.8, 87.5 +/- 12.5*, and 3.6 +/- 0.1* (Vmax) and 4.8 +/- 1.0, 8.8 +/- 1.2, and 0.8 +/- 0.3* (Km, *P less than 0.05 against NC).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗

Efficacy of endoscopic retrograde cholecystoendoprosthesis (ERCCE) for cholecystitis.

Fourteen patients with cholecystitis were treated by endoscopic placement of an endoprosthesis into the cystic duct. In these patients the administration of antibiotics had failed to change the clinical picture of cholecystitis. Clinical and ultrasonographic findings before and two months after stenting were compared. There was an improvement in abdominal pain in 9 out of 14 cases (64%); fever, present in 5 patients, disappeared in all. No clinical complications were observed. Sonographic findings in terms of gallbladder wall thickening and sludge present within the gallbladder improved in 57% and 88%, respectively. Our results indicate that this endoscopic procedure may be effective in the treatment of cholecystitis.

Aged↗

Diagnosis of biliary diseases via a naso-biliary catheter.

Nasobiliary double contrast radiography and nasobiliary cytological diagnosis via nasobiliary catheter were performed in 30 patients with biliary diseases to assess the diagnostic usefulness and limitations of the procedures. The results showed that the contour and fine mucosal pattern of the extrahepatic bile duct could be demonstrated adequately (88%) by nasobiliary double contrast radiography. In contrast, the intrahepatic bile duct could not be fully demonstrated (56%) by nasobiliary double contrast radiography because of its anatomical structure. On the other hand the fine reticular pattern of the mucosa was defined in each section of the gallbladder by nasobiliary double contrast radiography. This procedure is thus a valuable method for detection of mucosal lesions of the extrahepatic bile duct and gallbladder, especially carcinoma. The cell collection rate was not as high (59%) using conventional nasobiliary cytological diagnosis. Brush cytology via a nasobiliary catheter was shown to be a useful adjunct to other diagnostic procedures.

Barium Sulfate↗

Changes in nasal metachromatic cells during allergen immunotherapy.

We have investigated changes of nasal metachromatic cell number, nasal symptoms and nasal provocation at the third and sixth month during allergen immunotherapy. Twenty-five subjects with perennial allergic rhinitis (house dust (23), Alternaria (2) were divided into two groups: an immunotherapy-treated group (n = 14) and a control group (n = 11). At the first visit nasal symptom scores, nasal provocation reactions and the number of metachromatic cells in nasal mucosal epithelial scrapings were not significantly different between groups. At the third and sixth month after immunotherapy nasal symptom scores, nasal provocation and the metachromatic cells in epithelial scrapings were significantly reduced (P less than 0.05) compared with the pretreatment values in the immunotherapy group, but unchanged in the control group. These results suggest that the reduction in metachromatic cell number at the nasal mucosal surface may be one of the mechanisms which could explain the improvement of nasal allergic symptoms by immunotherapy.

Adolescent↗

Immunological treatment of cough occurring in dogs with dirofilariosis.

A persistent, spasmic and productive cough known as filarial cough often occurs in dogs with dirofilariosis, and has been considered to be the consequence of an allergic response to Dirofilaria immitis. Twenty-one dogs with filarial cough were subcutaneously injected with worm antigen (200 micrograms of protein concentration) extracted from adult D. immitis once a day for 5 days. These injections were effective for 17 (81%) of the dogs, resulting in a complete cure for 7 dogs and marked improvement for 10 dogs.

Animals↗

Hybridoma-derived human suppressor factors: inhibition of growth of tumor cell lines and effect on cytotoxic cells.

With the objective of developing human T-T cell hybrids producing B-cell growth factor, we fused concanavalin A-activated T lymphocytes with cells of the Jurkat T cell line. The hybrids were selected on the basis of their ability to form colonies in soft agar, whereas the parent Jurkat T cell line did not. T-T cell hybrids were HLA-typed, screened by functional tests, and recloned by limiting dilution. In addition to obtaining B-cell growth factor-producing hybrids, we also obtained certain other T-T cell hybrids (as determined by HLA-typing) producing suppressor factors inhibiting proliferative responses and antibody production by human lymphocytes. Subsequently, a suppressor factor with similar inhibitory properties was identified in supernatants of the Jurkat T cell line. However, the Jurkat factor exhibited different biochemical and functional properties than the hybridoma-derived suppressor factors. Using two-parameter cell cycle analysis and the metachromatic fluorochrome acridine orange, we found that the hybridoma-derived 160 and 169 suppressor factors arrested phytohemagglutinin-induced proliferative of peripheral blood mononuclear cells in the G0/G1 phase of the cell cycle, whereas the Jurkat suppressor factor arrested proliferation in the S phase. Incubation of peripheral blood mononuclear cells with the 160, 169, or Jurkat suppressor factors for 24 hr at 37 degrees C, followed by washing, did not alter their cell cycle progression (or RNA content) in response to stimulation with phytohemagglutinin. The hybridoma-derived 160 and 169 suppressor factors and the Jurkat factor inhibited the growth but not the viability of cells from the following human tumor cell lines: A673 sarcoma cell line, SK-LC-6 and SK-LC-14 lung cell lines, SB, Raji, and Daudi lymphoblastoid cell lines, and FARR malignant melanoma cell line. In contrast, it did not affect the growth of murine L1210 cells and FS-4 normal human diploid fibroblasts. The hybridoma-derived 160 suppressor factor was selected to investigate its effect on cell-mediated cytotoxicity. The 160 suppressor factor did not inhibit natural killer cytotoxicity or its augmentation by interferon alpha or interleukin 2 or the generation of lymphokine-activated killer cells. However, this factor partially inhibited the generation of specific T cell-mediated cytotoxicity.

Cell Cycle↗

[The concentration of endothelin in maternal vein, umbilical vein and artery of normal pregnancy and pregnancy-induced hypertension].

The concentrations of endothelin (ET) in maternal vein (MV), umbilical vein (UV) and artery (UA) of normal pregnancy (N) and severe pregnancy-induced hypertension (sPIH) were measured to investigate the significance of ET in the maternal and feto-placental circulation of normal pregnancy and PIH. 1) The concentrations of ET (pg/ml blood: mean +/- S.E.M.) in MV of a normal non-pregnant group, 1st, 2nd and 3rd trimester of N were 1.00 +/- 0.19 (n = 2), 0.55 +/- 0.16 (n = 4), 0.45 +/- 0.14 (n = 4) and 0.89 +/- 0.09 (n = 10), respectively. The concentration of ET in MV of 3rd trimester of sPIH was 2.76 +/- 1.21 (n = 7), and significantly (p less than 0.05) higher than in MV of 3rd trimester of N. 2) The concentrations of ET in UV and UA of N and UV of sPIH were 1.53 +/- 0.05, 1.29 +/- 0.06, 2.12 +/- 0.46, respectively. The concentrations of ET in UV and UA of N were significantly (p less than 0.01) higher than in MV of N. 3) The concentrations of ET in MV of N and sPIH correlated significantly (p less than 0.05) with diastolic blood pressure of N (r = 0.53). It was concluded that the synthesis of ET during pregnancy was suppressed until the 2nd trimester, and that the increased ET in MV of sPIH might be one of the factors that caused the pathogenesis of PIH. And the high concentration of ET in UV and UA was supposed to operate play a role in feto-placental circulation.

Adult↗

Modified rotational acetabular osteotomy (RAO) for advanced osteoarthritis of the hip joint in the middle-aged person. First report.

Classical methods for pelvic osteotomy, such as those of Salter, Pemberton, Chiari, and Wagner, have been developed for reconstruction of the subluxed hip joint in children and young adults. Regarding pelvic osteotomy involving a middle-aged patient, however, there are not as many operation methods to consider, and it is difficult to choose the most suitable technique for alleviating advanced osteoarthritis. Based on current practice, total hip replacement (THR) seems the accepted method, though it presents problems such as loosening, sinking, and infections; because of these factors physicians hesitate to recommend THR surgery, particularly if the patient is otherwise healthy and appears to have many good years ahead of him. As an alternative, we have been developing and improving the acetabular osteotomy, based on Tagawa's rotational acetabular osteotomy (RAO) and Wagner's acetabular osteotomy (type II). In this paper we present the results of a modified RAO operation performed on 50 middle-aged patients with an average age of 42 years and 2 months (31-61). The average follow-up was 3 years and 3 months (1-9 years). In 82% of patients the result was satisfactory (41 of 50 cases). A similar osteotomy technique has been used by Eppright and Wagner. We feel that our method achieves a more favorable result for an older patient with severe osteoarthritis, since both the surgery and the follow-up rehabilitation are more comprehensive. A modified acetabular osteotomy should not be regarded as merely an alternative to total hip replacement, but as the preferred choice for hip-joint reconstruction.

Adult↗

Purine nucleoside modulation of functions of human lymphocytes.

The accumulation of endogenous substrates in patients with adenosine deaminase deficiency or purine nucleoside phosphorylase deficiency is believed to be responsible for the immunodeficiency observed in these patients. To identify the lymphocyte populations that are most susceptible to these substrates, we investigated the effect of their nucleoside analogs on a number of T and B cell functions of human lymphocytes. We found that tubercidin (Tub), 2-chloro 2'deoxyadenosine (2CldA), 2-fluoro adenine arabinoside-5'phosphate (FaraAMP), and 9-beta-D-arabinosyl guanine (AraGua) inhibited the proliferative responses of human peripheral blood mononuclear cells (PBMC) to polyclonal activators (PHA, OKT3 mab) or to allogeneic PBMC in mixed lymphocyte cultures (MLC). Addition of recombinant IL-2 from the beginning of the culture did not alter the inhibition by Tub of the proliferative responses of PBMC. These purine nucleoside analogs also inhibited the proliferative responses of purified human peripheral blood CD4+ and CD8+ T cells to PHA and of purified B cells to SAC. The concentrations of these nucleosides required to achieve a given degree of inhibition of proliferative responses of T lymphocyte subpopulations or B cells was similar, suggesting that these analogs do not exhibit any selectivity for these purified lymphocyte populations. Tub and FaraAMP, respectively, inhibited and enhanced, at the effector phase, both NK cytotoxicity and specific T cell-mediated cytotoxicity. In contrast to these findings, LAK cytotoxicity at the effector phase was not significantly inhibited by Tub, and was not enhanced by FaraAMP. Both analogs inhibited rIL-2-induced proliferative responses of PBMC, but did not affect the generation of LAK cytotoxicity (induction phase) against the K562 targets when added at the beginning of the culture. This suggests that DNA synthesis is not required for LAK cell induction. Both Tub and FaraAMP inhibited immunoglobulin production (IgG and IgM) by PBMC in the PWM-induced system. These results demonstrate that purine nucleoside analogs significantly inhibited a number of functions of human lymphocytes. Although selectivity for T lymphocyte subpopulations and B cells was not observed, a differential effect of Tub and FaraAMP on LAK cytotoxicity versus NK cytotoxicity and specific T cell cytotoxicity was found.

B-Lymphocytes↗