[Evaluation of the anticancer effect of cisplatin and etoposide against nude mice transplanted urological malignant tumors].
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Animals↗
Biomedical subjects
S Kitazawa
Publications and source records attributed to S Kitazawa.
Parathyroid hormone-related protein in gastric cancers with heterotopic ossification.
BACKGROUND: Parathyroid hormone-related protein (PTHrP) has been regarded as one of the substances causing humoral hypercalcemia of malignancy. METHODS: The immunohistochemical localization of PTHrP was investigated in 33 cases of gastric cancer (4 with heterotopic ossification and 29 without heterotopic ossification) to clarify the role of PTHrP in heterotopic ossification by using the anti-PTHrP monoclonal antibody, 4B3. RESULTS: The four cases with heterotopic ossification showed positive staining at primary or metastatic sites, and in one case fibroblasts in the stroma surrounding the heterotopic ossifying foci also showed positive. On the other hand, of the 29 cases without heterotopic ossification, only 5 showed positive staining. CONCLUSIONS: The presence of PTHrP in ossifying gastric carcinomas at a relatively high rate indicates that PTHrP also might be related to heterotopic ossification associated with malignancies. It is speculated that PTHrP would contribute to heterotopic ossification by facilitating the process of mineralization.
Adenocarcinoma↗
Common expression of parathyroid hormone-related protein and no correlation of calcium level in renal cell carcinomas.
BACKGROUND: Parathyroid hormone-related protein (PTHrP) is the predominant cause of humoral hypercalcemia of malignancy (HHM). METHODS: Using a PTHrP-specific monoclonal antibody (MoAb), 4B3, the authors investigated the immunohistochemical localization of PTHrP in formalin-fixed and paraffin-embedded sections of normal human kidney tissues and tissues from 42 human renal cell carcinomas obtained at operation or autopsy. RESULTS: In normal renal tissues, the distal tubules and collecting ducts showed positive immunostaining. PTHrP was detected in 40 of 42 renal cell carcinoma tissues (95%). Histopathologically, the granular cell subtypes of renal cell carcinomas tended to be more strongly positive than the clear cell subtypes. There was no significant correlation between the level of immunostaining and each patient's serum calcium level. CONCLUSION: PTHrP was commonly observed in renal cell carcinomas, and no significant correlation was seen between the intensity of PTHrP staining and the serum calcium level.
Antibodies, Monoclonal↗
Candidate premotor neurones of skin reflex pathways to T1 forelimb motoneurones of the cat.
This study explored the locations and input-output properties of a large population of putative premotor neurones of skin reflex pathways in the cat. These neurones, interneurones excited by forelimb skin afferents and antidromically from the T1 motor nucleus (MN) and/or the lateral funiculus (LF, C8/T1 border), termed antidromic cells, were extracellularly recorded at C6-8. Selection of this site was based on data showing that cells retrogradely HRP labelled from the T1 MN were most numerous in C6-8 and the observation that transection of LF at the C8/T1 border abolished most skin-evoked postsynaptic potentials of T1 motoneurones. Antidromic cells were located in laminae IV-V, VI and VII. The latencies of antidromic excitation ranged from 0.4 to 1.8 ms, with a tendency for laminae IV-V cells to show longer latencies than laminae VI and VII cells. Latency of skin-evoked excitation ranged from 0.6 ms (IV-V cells), 0.8 ms (VI) and 1.4 ms (VII) to greater than 5 ms. The sum of the ortho- and antidromic latencies (estimated central latency) of individual cells explained the central latencies of skin-evoked postsynaptic potentials in T1 motoneurones. Skin-evoked firing responses (average of eight to ten cells) were earliest and largest in laminae IV-V antidromic cells, and latest and smallest in lamina VII cells. The antidromic cells who received inputs from muscle afferents and descending tracts. The following three results support the suggestion that the sampled antidromic cells are mostly premotor neurones. (1) Projection to the T1 MN via LF was verified in six laminae IV-VII antidromic cells, as tested with threshold mapping for antidromic excitation. (2) Three skin-excited axons of the middle LF projected to T1 MN, as revealed by intra-axonal staining (HRP). (3) PHA-L injection in laminae I-V of C8 anterogradely labelled terminals in lamina IX and LF axons at T1. It is suggested that last-order neurones of skin reflex pathways to T1 motoneurones are widely distributed in laminae IV-VII of C6-8 and consist of a variety of neurones with different locations and input patterns.
Animals↗
A membrane-bound metallo-endopeptidase from rat kidney: its immunological characterization.
The structure and location of a membrane-bound metallo-endopeptidase, previously purified from rat kidney [Yamaguchi et al. (1991) Eur. J. Biochem. 200, 563-571], were examined by immunochemical and immunohistochemical methods with a rabbit polyclonal antibody against the purified enzyme. On treatment with endoglycosidase F, the subunit of the purified enzyme (molecular mass = 88 kDa) was converted to a smaller form (78.5 kDa), indicating that the enzyme contained at least 11% N-linked carbohydrate. Treatment of kidney membranes with papain resulted in release of the enzyme, as shown by Western blotting analysis of the solubilized fraction. Immunoassays of rat tissues showed that only the kidney, and small and large intestine expressed significant amounts of the antigen. Moreover, immunohistochemical studies showed that the antigen was confined to the luminal surfaces of the proximal renal tubules and the intestinal villi. Thus, like another kidney membrane metallo-endopeptidase, meprin [Kounnas et al. (1991) J. Biol. Chem. 266, 17350-17357], the purified enzyme is shown to be a glycoprotein that is probably anchored in the plasma membrane, and located in the luminal surface of microvillar membranes of the kidney and intestine. These results indicate that our enzyme and meprin have clear structural and topological similarities.
Animals↗
Introduction of a series of alkyl thiomaltosides, useful new non-ionic detergents, to membrane biochemistry.
We synthesized a series of non-ionic detergents, alkyl thiomaltosides, and investigated their properties and usefulness. We solubilized membrane proteins of Vibrio parahaemolyticus using the detergents. With octyl thiomaltoside, nonyl thiomaltoside, decyl thiomaltoside, or undecyl thiomaltoside, we observed satisfactory solubilization of the membrane proteins. Alkyl thiomaltosides possessing longer alkyl chains showed better solubilization than ones possessing shorter chains. H(+)-translocating ATPase (F0F1), which is localized in the cytoplasmic membrane (inner membrane), was solubilized with the detergents, and the solubilized enzyme showed much higher specific activity than that solubilized with octyl glucoside or heptyl thioglucoside, other useful non-ionic detergents. 5'-Nucleotidase, which seems to be an outer membrane protein, was also efficiently solubilized with the alkyl thiomaltosides. Membrane proteins of Escherichia coli were also efficiently solubilized with the detergents. Octyl thiomaltoside and nonyl thiomaltoside were removed fairly rapidly on dialysis. Decyl thiomaltoside was removed slowly, and undecyl thiomaltoside and dodecyl thiomaltoside were difficult to remove by dialysis.
5'-Nucleotidase↗
Long-term effect of acarbose on glycaemic control in non-insulin-dependent diabetes mellitus: a placebo-controlled double-blind study.
The efficacy and safety of acarbose therapy (100 mg tds for 24 weeks) was investigated in a placebo-controlled double-blind study in patients with non-insulin dependent diabetes mellitus who could not achieve satisfactory glycaemic control by diet alone. In the acarbose group, the 2 h postprandial blood glucose and haemoglobin A1 levels decreased significantly from 14.0 mmol l-1 to 11.3 mmol l-1 and from 11.1% to 9.7%, respectively. In the placebo group, the 2 h postprandial blood glucose (14.4 mmol l-1 to 14.2 mmol l-1) and the hemoglobin A1 level (10.3% to 9.9%) showed no significant changes. A 75 g oral glucose tolerance test was performed before and after the study, the difference not being significant in either the acarbose group or the placebo group. The incidence of side-effects (mainly gastrointestinal symptoms such as flatulence and abdominal distension) was high at 78.9% in the acarbose group and 61.1% in the placebo group. However, there was no significant difference between the groups, and side-effects in the acarbose group tapered during the trial, suggesting that some at least were not related to the drug. From these findings, it was concluded that acarbose is an effective new treatment for diet treated non-insulin-dependent diabetic patients.
Acarbose↗
Structure determination of N-terminal-blocked peptide from hog kidney aldose 1-epimerase by tandem mass spectrometry.
The blocked-N-terminal structure of hog kidney aldose 1-epimerase (mutarotase, EC 5.1.3.3) was determined to be Ac-Val-Ser-Val-Thr-Arg-Ser-Val-Phe-Gly-Asp... by a coupling of conventional methods (enzymatic digestion, amino acid analysis, and Edman sequencing) and tandem mass spectrometry. The side-chain fragmentations observed in the high-energy product ion spectra gave unambiguous sequence information about the arginine-containing N-terminal structure.
Amino Acid Sequence↗
In situ hybridization using bromodeoxyuridine labelled DNA probe and RNase H.
We developed a modified in situ DNA-RNA hybridization technique and demonstrated c-myc proto-oncogene transcripts in nodular sclerosis type Hodgkin's disease (HD-NS). A hybridization probe was prepared by metabolic labelling of bromodeoxyuridine (BrdU). The hybridized probe was detected with anti-BrdU monoclonal antibody after incubation with ribonuclease H (RNase H), which specifically degrades RNA from DNA-RNA hybrids. In HD-NS, c-myc protooncogene transcripts were demonstrated in the cytoplasm of lacuna cells and a few surrounding lymphoid cells. This modified hybridization method was sensitive and applicable to the study of oncogene expression at a single cell level.
Adult↗
In situ hybridization at the electron microscopic level using a bromodeoxyuridine labeled DNA probe.
A bromodeoxyuridine (BrdU) labeled DNA probe was used for in situ hybridization at the electron microscopic (EM) level. A BrdU labeled DNA probe was hybridized in situ to cryostat sections of paraformaldehyde fixed OCT compound embedded cultured HL-60 cells. After hybridization, some sections were incubated with FITC-conjugated anti-BrdU monoclonal antibody for fluorescence microscopy (FM), and others were embedded in Quetol for electron microscopy (EM). The ultrathin sections of Quetol-embedded specimens were incubated with the anti-BrdU monoclonal antibody and the immunoglobulin: gold colloid. In both FM and EM studies, the signals were concentrated in the rough endoplasmic reticulum. Moreover, some label was arranged from the nucleus to the cytoplasm at the EM level. Relatively simple methods using the BrdU labeled DNA probe for the detection of the defined nucleic acid sequence with reasonable tissue preservation and high resolution are described here. This method may be useful for developmental and disease related studies of specific mRNA in cells and tissues.
Antibodies, Monoclonal↗
[Establishment and characterization of a new human testicular germ cell tumor cell line (TCam-2)].
A new human testicular cancer cell line (TCam-2) was established. The original material of TCam-2 was a primary lesion of a left testicular seminoma (typical pure type seminoma) from a 35 aged male patient. TCam-2 produced neither AFP nor beta-HCG, It showed strong immunoreactivities for 5G9 (anti testicular cancer MoAb), 4B3 (anti PTHrP MoAb) and PALP (placental alkaline phosphatase). The chromosomal analysis revealed 92 modal number and loss of Y chromosome. Histochemical, morphological and chromosomal analysis supported that TCam-2 is from classical seminoma. TCam-2 was transplanted subcutaneously to the back of 6 weeks old scid mice (CB-17 strain), and grew a classical seminomatous tissue.
Adult↗
[A case of acute myeloblastic leukemia invaded uterine cervix-diagnosed by changes in peripheral blood after G-CSF administration].
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Antineoplastic Combined Chemotherapy Protocols↗
[Studies on initiating activity of secondary bile acids for rat hepatocarcinogenesis].
The initiating potential of the secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA), was investigated using the development of preneoplastic lesions in the rat liver as a marker. In a short-term assay in which DCA and LCA were given in the diet for 3 weeks in conjunction with partial hepatectomy midway followed by the selection regimen, DCA dose-dependently induced gamma-glutamyltranspeptidase (gamma-GTP)-positive foci, but the results for LCA were less unequivocal and no dose-dependency was evident. In another experiment, I extended the period of observation and examined whether the gamma-GTP-positive foci thus induced by the secondary bile acids can develop into hepatic tumors after a latent period of 52 weeks with or without the administration of phenobarbital (PB), a promoter of experimental hepatocarcinogenesis. Whereas significantly high numbers of hyperplastic liver nodules developed in the DCA-treated rats irrespective of PB promotion, no such increase was evident in the LCA-treated rats. In contrast, both DCA and LCA treatments enhanced the development of glutathione S-transferase placental form (GST-P)-positive foci with or without subsequent PB promotion. The present data indicate that a short period of administration of DCA and LCA in the initiation stage in conjunction with partial hepatectomy results in enhanced development of preneoplastic liver lesions under selection pressure conditions with or without subsequent PB promotion. This suggests that these secondary bile acids possess possible initiating activity for rat hepatocarcinogenesis.
Animals↗
Expression of parathyroidlike protein in normal, proliferative, and neoplastic human breast tissues.
Parathyroidlike peptide (PLP), or parathyroid hormone-related protein, is a protein of uncertain biological function that is structurally homologous to parathyroid hormone. Immunohistochemical studies have identified aminoterminal epitopes of PLP in breast carcinomas, but not in normal breast. In the present studies, immunohistochemistry and in situ hybridization were performed to evaluate further expression of PLP in normal, proliferative, and neoplastic breast tissues. Using a polyclonal antibody that recognizes epitopes within the middle and carboxyl-terminal domains of PLP, immunoreactive protein was detected within the cytoplasm of lobular and ductal epithelial cells in all normal and fibrocystic breast tissues from 74 patients. The intensity of cytoplasmic staining was increased in association with lactation, adenosis, and simple or atypical ductal hyperplasia and decreased in atrophic lobules. Cytoplasmic reactivity was also observed in 69% (56 of 81) of breast adenocarcinomas. Expression of immunoreactive PLP was inversely correlated with tumor stage and extent of nodal involvement at the time of diagnosis. However, there was no significant correlation with tumor grade, patient age, or hormone receptor status. In situ hybridization studies confirmed the epithelial expression of PLP messenger RNA in PLP-positive normal and neoplastic breast tissue. Interestingly, tumor-associated calcifications were identified in 43% of PLP-positive carcinomas, but in only 12% of PLP-negative carcinomas (P < 0.007). Our results suggest that PLP plays some role in the normal differentiated function of mammary epithelial cells and are consistent with the hypothesis that expression of this protein influences local calcium metabolism.
Adolescent↗
[Immunohistological evaluation of parathyroid hormone-related protein in breast cancer with and without calcification on mammography].
PTHrP is the main factor of humoral hypercalcemia of malignancy. PTHrP produces the same effect on renal and osteoblast membrane in vitro and on calcium and inorganic phosphate fluxes in vivo as human PTH. Physiologically, PTHrP is produced by rat mammary tissue during lactation. It is suggested that PTHrP correlates to the metabolism of calcium in the mammary gland. Using anti-PHTrP (1-34) monoclonal antibody 4B3, we investigated the correlation of PTHrP and calcification in breast cancer. All the breast cancers with calcification on mammography showed positive immunostaining. Most cases without calcification, on the other hand, showed negative. Positive PTHrP staining was not related to the any clinical parameter. It is suspected that PTHrP is also one of the main factors of calcification in breast cancer.
Adult↗
Immunohistochemical evaluation of parathyroid hormone-related protein (PTHrP) in the uterine cervix.
We investigated the immunohistochemical localization of parathyroid hormone-related protein (PTHrP), a major factor responsible for the humoral hypercalcemia of malignancy, in uterine cervical lesions. Formalin-fixed paraffin-embedded specimens from 16 cases of normal and reactive conditions, 45 cases of cervical intra-epithelial neoplasm (CIN) and 63 cases of invasive cancer were studied immunohistochemically by the avidine-biotin-peroxidase method, using an anti-PTHrP monoclonal antibody (MAb), 4B3. In normal and reactive conditions, PTHrP was positive in parabasal cells, squamous metaplasia, and hyperplastic reserve cells. In neoplastic conditions, 96% (43/45) of invasive squamous-cell carcinomas were positive for PTHrP, regardless of the patients' serum calcium levels. Two cases with hypercalcemia were strongly positive for PTHrP and showed prominent stromal interaction of the scirrhous type. In CIN, including koilocytic atypia, 76% (32/42) of cases were positive for PTHrP. In contrast, 91% (10/11) of adenocarcinomas were negative for PTHrP. In conclusion, we found, first, that in non-neoplastic conditions, the presence of PTHrP was correlated with the transformation of progenitor cells into squamous epithelia and with the maturation of keratinocytes and, second, that in squamous-cell carcinoma, the degree of keratinization and stromal interaction was higher in direct proportion to the apparent incidence of detectable PTHrP.
Animals↗
The expression of parathyroid hormone-related protein (PTHrP) in normal parathyroid: histochemistry and in situ hybridization.
The expression and localization of parathyroid hormone-related protein (PTHrP), a major factor responsible for humoral hypercalcemia of malignancy (HHM), was investigated in 14 cases of surgically resected normal parathyroid glands. For light microscopic immunohistochemistry, formalin-fixed and paraffin-embedded specimens were stained with avidin-biotin-peroxidase complex (ABC) using the anti-PTHrP monoclonal antibody (MoAb), 4B3. Four percent paraformaldehyde (PFA)-fixed and OCT compound-embedded specimens were used for pre-embedded immunoelectron microscopy. For in situ hybridization, 4% PFA-fixed, frozen sections were studied using a bromodeoxyuridine (BrdU)-labeled PTHrP cDNA probe. Immunohistochemically, 12 of the 14 cases were positive for PTHrP, which was observed mainly in the oxyphil and transitional oxyphil cells. The chief and clear cells, on the other hand, were faintly positive. Electron microscopically, secretory granules positive for PTHrP were observed in cells containing abundant mitochondria. Consistent with the PTHrP immunoreactivity, transcripts of PTHrP were observed also in the oxyphilic cells by in situ hybridization. Thus the production and secretion of PTHrP was shown by the oxyphil cell lineage in the normal parathyroid glands.
Histocytochemistry↗
Different origin of leiomyoblastoma by immunohistochemical study.
Leiomyoblastoma has been regarded as a neoplasm of smooth muscle origin. With recent progress in immunohistostaining techniques, many clinicopathological discrepancies have been pointed out about the origin of leiomyoblastoma. It has been claimed that gastrointestinal non-epithelial tumors should be regarded as stromal tumors in order to study their origin. In the present study, we performed various forms of immunohistostaining in seven cases of leiomyoblastoma to determine their origin. One case expressed desmine and muscle specific actin and was considered to be derived from smooth muscle. Four neoplasms expressed X-100 protein (two cases were also NSE positive) and were thought to be derived from the nerve. Two cases were of unknown derivation. These results suggest that the cells of leiomyoblastoma may arise from a primitive to totipotential cell of neural lineages that may anomalously express smooth muscle filaments.
Actins↗