Red blood cell (RBC) carbonic anhydrase-I isozyme (CAI) and zinc concentrations were measured in patients with various thyroid diseases. Both concentrations were decreased in patients with hyperthyroid Graves' disease, and the RBC CAI concentration significantly (r = 0.95) correlated with the RBC zinc concentration. After treatment, the normalization of RBC CAI and zinc lagged 2 months behind normalization of plasma T4 and T3 levels. Furthermore, the highest correlation coefficients were observed between RBC CAI and zinc levels and plasma thyroid hormone levels measured 8 weeks earlier. These results indicate that both RBC CAI and zinc levels reflect the integrated plasma thyroid hormone levels over the previous few months. Transient thyrotoxicosis due to destructive (subacute or painless) thyroiditis did not cause significant changes in the RBC CAI and zinc concentrations. Therefore, the measurement of RBC CAI and zinc concentrations may be useful in differentiating patients with Graves' disease from those with transient thyrotoxicosis. T3 at a physiological free concentration significantly decreased CAI concentrations in erythroleukemic YN-1 cells and burst forming unit-erythroid-derived cells obtained by culturing peripheral blood mononuclear cells. These cells may be useful in vitro models for investigations of thyroid hormone action in human erythroid cells.
To clarify the role of thromboxane A2 (TxA2), endothelin-1 (ET-1) and endothelin-3 (ET-3) in the progression of glomerular injury in accelerated nephrotoxic serum nephritis (NTN) in the rat, we studied the expression of ET-1 and ET-3 at the kidney by immunohistochemical method and examined the effect of a novel TxA2 receptor antagonist, S-1452. The S-1452- treated group showed significantly lowered 24-hr proteinuria and milder glomerular cell proliferation and lobulation than the non-treated group (NT group) on experimental day 10. There was no significant difference in the glomerular polymorphonuclear cell (PMN) exudation between the 2 groups. Immunofluorescent findings revealed that ET-1 and ET-3 were seen along the glomerular capillary wall and partly in the mesangial area in all rats of the NTN group. The degree and positive rate of ET-1 and ET-3 staining were significantly higher in the NTN group than in the S-1452 group. These findings suggest that TxA2 may be an important mediator in the development of NTN, and that TxA2 receptor antagonist may be useful for the reduction of glomerular injury in this type of nephritis. In addition, local production of ET may contribute to the development of this nephritis.
Rush immunotherapy (RIT) with house dust extract was given to 15 patients with mild extrinsic or mixed asthma. Every patient was strongly positive for IgE on the radioimmunosorbent test and sensitive to house dust extract on the scratch skin test. Nine patients were positive on the bronchial provocation test to house dust extract and 6 could not be examined. All patients did not drop out and got to house dust extract solution 10−1 within 1 week. The symptom-medication scores decreased significantly after RIT. During RIT 1 patient developed a mild asthmatic attack and 3 patients developed generalized skin reaction. Eight weeks later, the threshold for house dust-provoked bronchoconstriction increased in 9 patients, but did not in 3 patients. The blood eosinophil count and blood histamine level significantly decreased. We conclude that RIT is able to raise antigen concentrations for a short periods and effective but not risky for mild asthma.
We analyzed expression of transforming growth factor (TGF)-α, epidermal growth factor (EGF) and their receptor, EGF receptor (EGFR), by immunohistochemistry in the human testis to determine the possible roles of these growth factors in human testicular function. Specimens were obtained from 17 patients including 9 patients with infertility, 4 patients with prostatic carcinoma and 4 patients with contralateral testicular tumor. EGF immunoreactivity was positive in the hyperplasic Leydig cells of one patient but negative in the other cases. On the other hand, strong TGF-α immunoreactivity was observed in Leydig cells, with weak staining in Sertoli cells and germ cells in cases with normal spermatogenesis. EGFR immunoreactivity was observed in the Leydig and peritubular cells, appearing as membrane staining. Marked immunoreactivity for TGF-α was observed in the Sertoli cells in testes with decreased spermatogenesis, especially in the Sertoli-cell-only syndrome. This finding may indicate a compensatory increase of TGF-α expression in the Sertoli cells accompanying a decrease in spermatogenesis. No significant correlation was found between the degrees of spermatogenesis and immunolocalization of the EGF receptor. These findings suggest that TGF-α is a locally produced growth factor that is involved in spermatogenesis in the human testis via an autocrine and/or paracrine mechanism.
The IL-2 receptor (IL-2R) γchain is shared among receptors for IL-4, IL-7, IL-9 and IL-15 as well as IL-2. In order to clarify the functional role of these cytokines interacting with the common γchain in human early hematopoiesis, we studied expression of the IL-2R γchain on purified CD34 positive cells from bone marrow and cord blood. Broad populations of bone marrow mononuclear cells were all found to express the IL-2R γchain. CD34 positive cells were purified by CD34 monoclonal antibodies and immunomagnetic beads as representative hematopoietic progenitor cells. It was established that only 38±10% of CD34 positive bone marrow cells (n = 5) and 35±12% of CD34 positive cord blood cells (n =11) expressed the IL-2R γchain. CD34(+) IL-2R γchain(+) and CD34(+) IL-2R γchain(−) cells fractionated by cell sorting were subjected to clonogenic assays that showed granulocyte-macrophage colony-forming cells (CFU-GM) were present evenly in both fractions, whereas erythroid burst-forming cells (BFU-E) were enriched in the CD34(+) IL-2R γchain( fraction approximately two- to six-fold as compared with CD34(+) IL-2R γchain(+) fraction. Such clonogenic features did not differ between the bone marrow and cord blood cases. These results indicate that CD34(+) IL-2R γchain(−) cells contain immature cells already committed to the erythroid lineage.
The existence of ryanodine-sensitive Ca2+ stores and their role in the Ca2+ entry mechanism were examined in the rat submandibular gland acinar cells, using the microfluorimetry of intracellular Ca2+ concentration ([Ca2+]i). In the presence of thapsigargin, a Ca2+-ATPase inhibitor of inositol (1, 4, 5) triphosphate (InsP3)- sensitive Ca2+ stores, caffeine caused an increase in [Ca2+]i, which was inhibited by treatment with ryanodine (a ligand to the Ca2+-induced Ca2+ release channels). In the cells treated with ryanodine, 1 mM Ca2+ addition to a Ca2+-free solution caused a marked increase in [Ca2+]i, which was eliminated by application of Ni2+ or SK & F 96365, suggesting a Ca2+ entry triggered by ryanodine. The maximal change in the net increase in [Ca2+]i caused by the ryanodine-coupled Ca2+ entry, was 104.0± 16.0 nM, which intense was caused by 10 μM ryanodine. Emptying the InsP3-sensitive stores by treatment with thapsigargin also caused Ca2+ entry, which maximally changed [Ca2+]i by 349.6± 15.1 nM. Ten μmol/liter ryanodine was confirmed to cause a release of 45Ca2+ from the parotidic microsomal fraction enriched in endopaismic reticulum. We propose that ryanodine-sensitive Ca2+ stores are present in rat submandibular gland acinar cells. We further propose that release of Ca2+ from the ryanodine-sensitive stores, which means eventually depletion of the ryanodine-sensitive Ca2+ stores, can activate the Ca2+ entry. The ability for Ca2+ entry coupled with the ryanodine-sensitive Ca2+ stores seems to be about 30% of the ability for Ca2+ entry coupled with the thapsigarginsensitive Ca2+ stores.
P815 murine mastocytoma cells were separated to plastic-adherent and -nonadherent cell populations by repetitive in vitro selections. Their abilities of experimental and spontaneous metastases were investigated in the syngeneic DBA/2 mice. While the plastic-adherent populations were found to be liver-metastatic, the plastic-nonadherent populations were liver-nonmetastatic. The inability of plastic-nonadherent P815 cells to metastasize to the liver did not mean that these cells were not tumorigeneic because they could metastasize to tissues and/or organs other than the liver. Hence it could be looked as inability for liver specific metastasis resulted from, or related to, the loss of plastic adhesiveness. By limiting dilution of plastic-adherent and -nonadherent P815 cells, two series of well comparable P815 clones were established: (1) plastic-adherent, livermetastatic clone and (2) plastic-nonadherent, liver-nonmetastatic one. Since these two series of P815 clone are originated from a common parent line, they might be valuable in the study of the molecular mechanisms of liver specific metastasis and of the relations between liver metastasis and cell adhesiveness.
We investigated the changes in the ability of adenosine triphosphate (ATP) synthesis in the inner mitochondrial membrane with the acute and chronic liver injuries by carbon tetrachloride (CCL4) in rats. The ability of ATP synthesis was evaluated by measuring the activity of proton ATPase and the ability of oxygen consumption using isolated mitochondria. In the acute liver injury, the ability of ATP synthesis at 6 hr after injection was preserved relatively well in spite of hepatocyte injuries. On the other hand, at 12 hr after CCL4 injection, the necrosis of hepatocyte was widely recognized. In the chronic liver injury, severe fibrosis was induced but the ability of ATP synthesis was kept as well as that in the normal liver. These results suggest that the mitochondria have some resistivity against radicals produced by CCL4.
We report a case of a 19-year-old male with an extradural granulocytic sarcoma at T5/6 to T7 demonstrated by MRI. He recovered from paraplegia that had progressed rapidly after excision of the tumor as an emergency operation. Histopathological studies disclosed granulocytic sarcoma. Both peripheral blood and bone marrow examinations revealed acute myelogenous leukemia. The karyotype of the bone marrow showed 45, X, -Y, t (8;21) (q22;q22).
An autopsy case of double cancer is reported. The patient had undergone right hemicolectomy for colon carcinoma in 1982, and the second cancer was detected in the pancreas in April 1989, which was diagnosed as intraductal papillary adenocarcinoma that is known for its favorable prognosis after surgical resection. However, as the patient did not consent to the operation, she died in August 1994, five years after the diagnosis of the second cancer. Histopathological study revealed neither recurrence nor metastasis of colon carcinoma. The pancreatic carcinoma metastasized to the lung, liver, and peritoneum. DNAs were extracted from paraffin-embedded tissue for molecular pathological examinations. Different mutations were found at codon 12 of the K-ras gene by nucleotide sequencing analysis: one in the colon and the other in the pancreas and lung. Over-expression of p53 protein was also detected in the colon by immunostaining. Replication error was not observed in these three tumors suggesting that a factor(s) other than genetic instability was playing a role in the development of double cancer in this patient.
An anonymous unlinked HIV antibody test was conducted on 1632 Chlamydia trachomatis (C. trachomatis) antibody positive women from 10 institutes of 7 prefectures in Japan. All the sera were negative for both HIV-1 and HIV-2 antibodies. The result may support the suggestion that HIV prevalence is low among general population in Japan. Such a test as this study will be useful not only for developing a reliable HIV surveillance system but also for the study of sexual behavior of general population, since C. trachomatis infection is sensitive to reflect sexual contact.