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Biomedical subjects

K Inai

Publications and source records attributed to K Inai.

At least 55 records · Page 3Linked to original sources
PubMed1998

Microsatellite instability in breast cancers with special reference to patients' age and bilaterality.

We examined breast cancers from 67 female patients to ascertain the possible correlation between RER or LOH status, age and bilaterality using eight microsatellite markers on chromosomes 2p, 3p, 16q, 17p and 17q. The frequencies of RER in young patients (25-35 years old), patients with double primary disease (43-77 years old) and patients with contralateral metastases (46-72 years old) were 35%, 63%, and 80%, respectively, while that in elderly patients (60-81 years old) was 0%. In contrast, there were no statistically significant differences in the frequency of LOH between these groups. Our results suggest that RER might play an important role in the occurrence of breast cancer at a younger age and in bilateral breast cancer.

Adult↗
PubMed1997

Differentiation induction in non-lymphocytic leukemia cells upon treatment with mizoribine.

Inosine-5'-monophosphate (IMP) dehydrogenase catalyzes the rate-limiting reaction of guanine nucleotide biosynthesis and has been implicated in the reaction of cell growth and differentiation. We examined the ability of mizoribine, an IMP dehydrogenase inhibitor, to induce differentiation in HL-60 and U937 cells as well as in fresh leukemic blast cells from patients with non-lymphocytic leukemia. Treatment with mizoribine reduced intracellular GTP levels and induced morphologic and functional differentiation in these two cell lines in a dose-dependent manner. HL-60 and U937 cells developed polymorphic nuclei and macrophage-like cytoplasm, respectively, as well as expression of CD11b and CD14 antigens and the ability to oxidize NBT. These changes became evident when intracellular GTP levels decreased to approximately 30% of untreated controls and were abrogated by addition of guanosine to the media. However, in fresh leukemic cells, the cells showing maturation in response to mizoribine were limited in those derived from two of ten patients having non-lymphocytic leukemia. These findings suggest mizoribine could induce differentiation in HL-60 and U937 cells through a decrease of intracellular GTP levels. Further study is required to determine its clinical use in patients with acute non-lymphocytic leukemia.

Adult↗
PubMed1997

Solitary fibrous tumor of the prostate.

A case of solitary fibrous tumor of the prostate is reported. A 42-year-old man had been complaining of difficult voiding and constipation for 8 years. Urological and radiological examinations showed a large prostatic mass, and a total cystectomy and prostatectomy were performed. The tumor was 14 x 13 x 11 cm in size, solid with a fibromuscular capsule, and gray-tan in color. Histologically, the tumor was composed of short spindle-shaped and polygonal cells with mild to moderate nuclear atypia, predominantly arranged in the so-called 'patternless pattern' in a fibrocollagenous background. Mitoses were occasionally seen. Vascular invasion was also observed. Immunohistochemically, these cells were strongly positive for CD34 and vimentin, and occasionally for desmin. The maximum Ki-67 labeling index of the tumor cells was 4.5%. These findings are consistent with a solitary fibrous tumor. To our knowledge, this is the first report of a solitary fibrous tumor of the prostate in the English medical literature.

Adult↗
PubMed1996

Expression of bcl-2 Protein in Breast Carcinoma with Correlation to Expression of p53 Protein and Clinicopathological Factors.

Expression of bcl-2 gene product was examined in 204 breast carcinomas in order to ascertain its clinicopathological significance. The bcl-2 protein was detected by immunohistochemistry on paraffin embedded tissue sections and its presence was confirmed by Western blot analysis of whole cell lysates. A strong positive correlation was noted among expression of bcl-2 protein in carcinoma cells, positivity of progesterone receptor (PR) and expression of p53 protein. However, no correlation could be observed among expression of bcl-2 protein, histological type of carcinoma, tumor size, lymph node metastasis and positivity of estrogen receptor (ER).

Journal Article↗
PubMed1996

Multicentric Breast Carcinoma: Evaluation of Clinicopathological and Immunohistochemical Characteristics.

Multicentric breast carcinomas not diagnosed clinically, were examined by serial step-cut sectioning of the whole breast, and multicentric carcinoma cases were compared with single carcinoma cases with regard to histological and clinicopathological findings. In 7(3.7%) out of 187 surgically resected breasts, latent carcinomas apart from the main carcinoma were noted. The size of the latent carcinoma varied from 0.2 to 5 cm in diameter. The histological type was noninvasive ductal carcinoma in six cases and invasive ductal carcinoma in one case. When the main carcinoma was small in size (less than 2.5 cm in diameter), and showed papillotubular carcinoma as the histological type or had estrogen receptor (ER) by the dextran-coated charcoal (DCC) method, the incidence of latent carcinoma was high. In 5 of 6 cases with latent carcinoma examined by immunohistochemistry, latent carcinomas showed expression of ER. Concerning Ki-67, proliferating cell nuclear antigen (PCNA) and p53 protein, there was no significant difference between the main and latent carcinomas, as well as with other clinicopathological factors.

Journal Article↗
PubMed1996

Differentiation effect of acyclic retinoid on acute promyelocytic leukemia cells.

Acyclic retinoid (all-trans-3, 7, 11, 15-tetramethyl-2, 4, 6, 10, 14-hexadecapentaenoic acid) binds cellular retinoic acid-binding protein with an affinity similar to that of all-trans retinoic acid and induces differentiation of human hepatoma cell lines and a human acute myelogenous leukemia cell line (HL-60). We investigated the in vitro efficacy of acyclic retinoid to induce the differentiation of acute promyelocytic leukemia (APL) cells using primary cultured cells obtained from 11 APL patients. Five days' incubation with acyclic retinoid effected a dose-dependent induction of differentiation. Cells from eight patients showed maximum differentiation at 10(-6) M acyclic retinoid. Cells from one patient required 10(-5) M for maximum differentiation, while those from two patients exhibited moderate differentiation at 10(-5) M. Five days' incubation with acyclic retinoid (10(-7) approximately 10(-5) M) did not affect the viability or number of cells from any patient except one, whose cells showed a slight decrease in viability at 10(-5) M. Thus, we conclude that acyclic retinoid induced the differentiation of primary cultured APL cells at concentrations of 10(-6) approximately 10(-5) M, a range at which it is not toxic.

Antineoplastic Agents↗
PubMed1996

Endoscopic resection of intraventricular ependymal cyst presenting with psychosis.

BACKGROUND: Intracranial ependymal cysts are rare lesions generally located in the cerebral parenchyma, juxtraventricular region, or subarachnoid space; but no case of a purely intraventricular ependymal cyst has been reported. CASE REPORT: A case of intraventricular ependymal cyst presenting with symptoms of psychosis is reported. The patient's symptoms resolved almost completely following endoscopic resection of the cyst. The embryologic basis of the development of an ependymal cyst inside the ventricle and its histologic characteristics are discussed. Possible mechanism of psychosis in this case is also discussed. CONCLUSION: Minimally invasive techniques, as in this case, may be useful in refractory psychotic cases with cystic lesions.

Adult↗
PubMed1996

Effects of K-ras gene mutations in the development of lung lesions induced by 4-(N-methyl-n-nitrosamino)-1-(3-pyridyl)-1-butanone in A/J mice.

The relationship between the development of peripheral lung lesions induced by tobacco-specific 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and K-ras gene mutation in A/J mice, and the correlations between histological alterations and the course of lung lesion development after NNK treatment and K-ras gene mutation were investigated. The acquisition of a selective growth advantage by the lung lesions with mutations was also examined using immunohistochemical labeling with bromodeoxyuridine. Thirty female 5 weeks old A/J mice were each injected intraperitoneally with a single dose of NNK (100 mg/kg body weight) and subdivided into 6 groups according to the time after NNK treatment. The lung lesions were characterized histologically as alveolar/bronchiolar hyperplasia, adenoma and adenocarcinoma, and point mutations in codons 12 and 61 of the K-ras gene were detected by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) and dideoxy sequencing methods. K-ras gene mutations were identified in 7 (58.3%) of 12 hyperplasias, 42(75.0%) of 56 adenomas and 3 (75.0%) of 4 adenocarcinomas. The most frequent K-ras gene mutation was a G-to-A transition at the second base of codon 12 and this accounted for 86.5% of all the mutations detected. Neither the frequency of activation of this gene nor the specific mutation was affected by the time after NNK treatment and there was no positive correlation between the proliferative activity of lung lesions and the presence of K-ras gene mutations. Thus, K-ras gene mutation is closely associated with the development of NNK-induced peripheral lung lesions in A/J mice, but it plays no role in the selective growth advantage of these lesions.

Animals↗
PubMed1996

p16/CDKN2 gene and p53 gene alterations in Japanese non-smoking female lung adenocarcinoma.

Primary lung adenocarcinomas in non-smoking females are increasing in the USA and Japan. Environmental factors such as passive smoking, asbestos, domestic radon, and hormonal effects have been implicated, but the etiology is still uncertain. We therefore analyzed point mutations of p16 gene, a newly characterized tumor suppressor gene, and compared the results with alterations of p53 gene in 28 primary lung adenocarcinomas in non-smoking Japanese females. There were no cases with somatic point mutation of p16 gene, except for one case with two germline mutations (silent mutations). In contrast, six out of 16 informative cases showed loss of heterozygosity of p53 gene using a TP53 microsatellite marker and 19 out of 28 cases showed expression of oncoprotein using DO-7 immunohistochemistry. These findings suggest that p16 gene alteration is a rare event in primary lung adenocarcinomas in Japanese non-smoking females, compared with alterations of the p53 gene.

Adenocarcinoma↗
PubMed1996

Alteration of the p53 gene of lung carcinomas with sarcomatous transformation (spindle cell carcinoma): analysis of four cases.

Lung carcinoma with sarcomatous transformation (LCST) is highly aggressive and characterized by local invasion and/or distant metastasis, which leads to a shorter survival than ordinary lung carcinomas. Therefore, to elucidate whether the malignant potential of the spindle cell element in LCST is associated with the alteration of the p53 gene, four cases were examined by analyses of overexpression of the p53 oncoprotein, mutation of the p53 gene and loss-of-heterozygosity (LOH) at chromosome 17p. In two cases overexpression of the p53 oncoprotein of the spindle cell component showed a higher degree of staining than that of the carcinoma component; LOH was identified in both carcinoma and sarcomatous components in one case, while in contrast, another case showed LOH in the sarcomatous component only. Mutations were clearly detected in two cases; one showed a CTT to CGT transversion in codon 194 of exon 6 in both components, whereas the other showed a CTG to CAG transversion in codon 265 of exon 8 in the sarcomatous component only. On the basis of these observations, it suggested that the sarcomatous component shows a higher frequency of p53 gene abnormalities in comparison to the carcinoma component. These results also suggested that the acquisition of malignant potential in the sarcomatous component, or the morphological alteration of carcinoma cells, is correlated with abnormalities associated with the p53 gene.

Adenocarcinoma↗
PubMed1996

Primary carcinoid tumor of the kidney with special reference to its histogenesis.

A case of primary carcinoid tumor of the kidney occurring in a 66-year-old woman is reported. The tumor was 10 x 10 x 9 cm in size, solid, yellowish-white in color, and associated with massive hemorrhagic necrosis. Histologically, it was composed of trabecular and anastomosing ribbon-like nests. The tumor cells showed argyrophilicity with the Grimelius stain and cytoplasmic positivity for neuroendocrine markers, (including chromogranin A, neuron-specific enolase, synaptophysin and Leu-7), prostatic acid phosphatase, keratin and vimentin. Numerous cytoplasmic neurosecretory granules were demonstrated ultrastructurally. These histologic and immunohistochemical findings are consistent with the theory that this tumor has a common phenotype with that of carcinoid tumor arising from the hindgut or cloaca.

Acid Phosphatase↗
PubMed1996

[Anomalous origin of the left coronary artery from the pulmonary trunk with myocardial infarction and severe left ventricular dysfunction in infancy--assessment of myocardial damage using SPECT studies with 201TlCl and 123I-BMIPP].

A 4-month-old male infant with Bland-White-Garland (BWG) syndrome complicated myocardial infarction was reported. Signs included tachypnea, coughing, and failure to thrive. However, there was no sign of myocardial infarction. A chest radiograph revealed cardiomegaly (CTR = 65%) and electrocardiogram showed abnormal Q waves in I, aVL, V6 leads. Cardiac catheterization and angiography revealed marked dilatation of left ventricle (end-diastolic volume = 384 ml/m2) and extremely depressed ejection fraction (16%), confirming the diagnosis of BWG syndrome. A 201TlCl-myocardial SPECT demonstrated apical defect and hypoperfusion in the anterolateral, inferoposterior walls, whereas 123I-beta-methyl-p-iodophenylpentadecanoic-acid (123I-BMIPP) SPECT showed a wider defect area. SPECT studies with 201TlCl and 123I-BMIPP, are useful to assess myocardial viability more accurately in BWG syndrome.

Coronary Vessel Anomalies↗
PubMed1995

Telomerase activity in small-cell and non-small-cell lung cancers.

BACKGROUND: Telomerase is an enzyme that adds hexameric TTAGGG nucleotide repeats onto the ends of vertebrate chromosomal DNAs (i.e., telomeres) to compensate for losses that occur with each round of DNA replication. Somatic cells do not have telomerase activity and stop dividing when the telomeric ends of at least some chromosomes have been shortened to a critical length. It has been suggested that immortalized cells (including some, but probably not all, cancer cells) continue to proliferate indefinitely because they express telomerase. PURPOSE: To investigate whether expression of telomerase is a prerequisite for the development of naturally occurring human cancers, we assayed the levels of telomerase activity in specimens of human lung tumor and adjacent normal tissue. METHODS: Using a polymerase chain reaction-based assay, we examined telomerase activity in 136 primary lung cancer tissues and 68 adjacent noncancerous tissues obtained by surgical resection. We also studied telomerase activity in four primary and 23 metastatic lesions obtained through biopsy, (two patients) or autopsy (10 patients). Relative telomerase activity levels were estimated by serial dilutions of extracts prepared from the specimens. Telomerase activity was also assayed in extracts of cells present in pleural fluids from three patients with adenocarcinoma of the lung. RESULTS: Among surgically resected samples, telomerase activity was detected in 109 (80.1%) of 136 primary lung cancer tissues and in three (4.4%) of 68 normal adjacent tissues. All 11 surgically resected specimens of primary small-cell lung cancer (from 11 patients) revealed high levels of telomerase activity, whereas the activity ranged from undetectable to high levels in the 125 surgically resected specimens of primary non-small-cell lung cancer tissue (from 125 patients). Generally, high levels of telomerase activity were observed in metastatic lesions and tumors with altered telomere length. A few primary and, surprisingly, some metastatic tumors did not appear to have detectable telomerase activity. Telomerase activity was, however, detected in cells present in all tested pleural fluids obtained (from three patients with adenocarcinoma of the lung). CONCLUSION: The subset of non-small-cell lung cancers that exhibits only low or undetectable levels of telomerase activity may contain primarily mortal cancer cells. Cancers that exhibit high levels of telomerase activity, such as all of the small-cell lung cancers examined in this study, are likely to consist mainly of immortal cells. IMPLICATIONS: Telomerase activity may be useful both as a diagnostic marker to detect the existence of immortal lung cancer cells in clinical materials and as a target for therapeutic intervention.

Base Sequence↗
PubMed1995

Alterations in telomeric repeat length in lung cancer are associated with loss of heterozygosity in p53 and Rb.

In the two-stage model of controlling cellular senescence in cultured human fibroblasts, retinoblastoma (Rb) and p53 proteins may be key factors regulating the mortality stage 1 mechanism. In addition, the critical loss of telomeric DNA due to the end-replication problem may result in the mortality stage 2 mechanism. Cells which acquire telomerase activity can overcome the M2 mechanism by stabilizing telomere length and thus become immortal (telomere hypothesis). At present it is known whether cellular immortality is a prerequisite for all human cancers. To investigate this question and the applicability of the two-stage model to human cancers, we analysed the relationship between alterations of telomere length and other genetic changes in lung cancer. Among 60 primary lung cancer tissues, telomere length alterations were observed in 16 tumors (26.7%) including 14 with short and two with elongated telomeres. Ten of them revealed allelic loss of both p53 and Rb genes, and remaining six showed no abnormalities in both genes. We propose that inactivation of both p53 and Rb genes may promote cell divisions causing telomere shortening in lung cancer as in the two-stage model, while there may be another pathway to overcome both M1 and M2 mechanisms, especially for adenocarcinoma.

Base Sequence↗
PubMed1995

Role of point mutation of the K-ras gene in tumorigenesis of B6C3F1 mouse lung lesions induced by urethane.

In order to elucidate the role of point mutation of the K-ras gene in the tumorigenetic process of lung tumors, an experimental model of lung lesions in mice induced by the administration of urethane was used. A total of 135 B6C3F1 male mice, 6 weeks old, were given urethane in the drinking water at 0, 6, 60, 600 or 1200 ppm, and were then killed after varying periods of time. The lung lesions were histologically characterized as hyperplasia, adenoma and adenocarcinoma. Point mutations in codons 12 and 61 of the K-ras gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and confirmed by using dideoxy sequencing analysis. K-ras gene mutation was identified in 9 (23.7%) of 38 lesions classified as hyperplasia, 31 (46.3%) of 67 adenomas, and 3 (50%) of 6 adenocarcinomas. The most frequent mutation was an AT-to-TA transversion at the second base of codon 61 and this pattern accounted for 65% of the three mutant forms observed. These results suggest that the point mutation of K-ras gene is involved in all stages of mouse lung tumorigenesis, i.e., activation of this gene can also influence the later stages of lung lesions.

Adenocarcinoma↗
PubMed1995

[A case of erythroleukemia associated with lung aspergilloma successfully treated with continuous drip infusion of amphotericin B].

In September 1990, a 55-year-old female with erythroleukemia was treated with enocitabine, mitoxantrone, vincristine, and etoposide. Despite prophylaxis of infectious diseases by oral administration of 2,400 mg/day amphotericin B (AMPH), 600 mg/day ofloxacin, and 1,500 mg/day kanamycin, pneumonia with refractory pyrexia appeared and developed cystic lesions with air crescent signs thereafter. Finally, the cystic one formed fungus balls. The pneumonia was diagnosed as aspergillus pneumonia by fungus growth in the tissue in the transbronchial lung biopsy specimens and by an elevation of serum anti-Aspergillus antibody. The patient had continuously been administered with AMPH for 16 days, increasing the drug doses every 2 days. The maximum plasma level of AMPH rose up to 0.78 micrograms/ml, the total amount up to 166 mg. The fungus balls disappeared completely without adverse effects except a transient decrease of plasma potassium level. Pharmacological studies had been reported that tissue AMPH levels elevated more than twice as much as that of the plasma. Although the maximum plasma level was less than that of MIC for Aspergillus, the lung tissue drug level was suspected to have been maintained higher by continuous drip infusion. These findings indicate that continuous drip infusion of AMPH is one of the useful treatment for lung aspergillosis.

Amphotericin B↗
PubMed1995

[The proliferative activity in epithelial hyperplasia of the breast].

Epithelial hyperplasia of the breast has been recognized as an indicator of the risk for occurrence of invasive ductal carcinoma. In the future, however, its biological nature as well as precancerous potency remains unclear. Therefore, in order to elucidate a part of its biological nature, we attempted to evaluate proliferative activity in 62 lesions of epithelial hyperplasia of the breast, by means of immunohistochemistry of Ki-67 and silver stain of nuclear organizer region (NOR). Consequently, the labelling index (LI) of Ki-67 and the number of AgNOR became larger according to the increased grade of stratification, but cellular atypia without significant stratification also showed large LI of Ki-67 and number of AgNOR. Moreover, it was suggested from the discrepancy in the results of Ki-67 and AgNOR that AgNOR and Ki-67 reflected different phenomena.

Breast↗