Biomedical subjects

H Hiratsuka

Publications and source records attributed to H Hiratsuka.

At least 19 recordsLinked to original sources

PubMed2001

Intravenous 1alpha, 25[OH]2 vitamin D3 (calcitriol) pulse therapy for bone lesions in a murine model of chronic cadmium toxicosis.

The aim of the present study was to clarify the therapeutic effects of 1alpha, 25[OH]2 vitamin D3 (calcitriol) pulse injection on bone lesions induced in a rat model of chronic cadmium toxicosis. Ovariectomized (OVX) and control-operated (sham-OVX) rats were given repeated intravenous injections of 0.5 mg/kg/day CdCl2 for 70 weeks. The rats were then treated intravenously with 0.02 microg/kg/day calcitriol 3 days per week for 8 weeks. CdCl2 treatment induced increases in osteoid volumes of the femur cortex and trabecula. This change was accompanied by an increase in the volume of iron deposition at the mineralization front of the trabeculae and a reduction in mineral density. Abnormalities of bone metabolic parameters, which were increases in the blood calcium, inorganic phosphorous, bone-specific alkaline phosphatase, parathyroid hormone (PTH) and osteocalcin levels, and in the urine deoxypyridinoline (D-PYR) level, were also induced. Calcitriol treatment increased the blood calcium and inorganic phosphorous levels, and reduced the blood PTH level. Decreases in blood tartrate-resistant acid phosphatase and urine d-PYR levels were also induced indicating that bone resorption was suppressed. The findings indicated that the increased osteoid volume of the cortex and Fe-deposition volume of the trabecula were improved. These effects or improvements were observed in the sham-OVX rats but not in the OVX rats.

Acid Phosphatase↗

PubMed2001

Polyvinyl alcohol as a useful indicator on iodometry: volumetric and spectrophotometric studies on iodine-PVA and iodine-starch complexes.

Iodometry is one of the easiest, most rapid and accurate methods for the determination of a relatively small amount of oxidizing agent, such as residual chlorine. Starch has long been used as a useful color indicator in iodometry. However, we found that PVA (polyvinyl alcohol with partially saponificated; e.g., saponification degree of 88%) is a more useful color indicator than starch. For example, at 20 degrees C, the PVA indicator gave similar profiles of iodine concentration vs. titration efficiencies (percent recoveries) to those of starch at 0 degrees C. At 0 degrees C, the PVA indicator detected 1.1 mg I2/L (11 microg I2: with 10 mL sample volume) with a high percentage of recovery (=95%). Furthermore, at 20 degrees C an iodine concentration of 0.36 mg/L (which corresponds to a residual chlorine concentration of 0.1 mg Cl2/L) could be detected using PVA color indicator assuming an appropriate correction.

Chlorine↗

PubMed2001

Relationship between toxicity and cadmium accumulation in rats given low amounts of cadmium chloride or cadmium-polluted rice for 22 months.

To clarify toxic effects of long-term oral administration of low dose cadmium (Cd) on the liver and kidney, six groups of female Sprague-Dawley rats were fed a diet containing Cd-polluted rice or CdCl2 at concentrations up to 40 ppm, and killed after 12, 18, and 22 months. With toxicological parameters, including histopathology, there was no evidence of Cd-related hepato-renal toxicity, despite a slight decrease of mean corpuscular volume and mean corpuscular hemoglobin of red blood cells with 40 ppm CdCl2. Dose-dependent accumulation of Cd was observed in the liver and kidneys with peak levels of 130 +/- 42 micrograms/g and 120 +/- 20 micrograms/g, respectively, at 18 months in animals treated with 40 ppm CdCl2. A dose-dependent increase in urinary Cd levels became evident with time. Induction of metallothionein (MT) was also observed in the liver and kidney with a high correlation to the corresponding Cd levels. In the proximal renal tubular epithelia of 40 ppm CdCl2-treated rats at 22 months, prominent accumulation of Cd was observed in secondary lysosomes associated with MT deposits in their exocytotic residual bodies. The results demonstrated that, in contrast to the case with high-dose Cd-administration, renal toxicity is not induced by long-term oral administration of low amounts of Cd, although tissue accumulation does occur. Possible protective mechanisms may be operating.

Animals↗

PubMed2000

Assessment of renal toxicity by analysis of regeneration of tubular epithelium in rats given low-dose cadmium chloride or cadmium-polluted rice for 22 months.

To determine whether low-dose oral administration of cadmium (Cd) induces renal toxicity, six groups of female Sprague-Dawley rats were fed a diet containing low amounts of CdCl2 or Cd-polluted rice at concentrations up to 40 ppm, and were killed after 12, 18, and 22 months (experiment 1). In addition to the determination of cortical Cd levels and histopathological assessment of kidneys, labeling indices (LIs) for proliferating cell nuclear antigen (PCNA) in the renal cortical tubular epithelium of Cd-treated rats were determined as a measure of regenerative activity. For comparison, the kidneys of rats given diets containing small to large amounts of CdCl2 up to 600 ppm for 4 months were similarly examined (experiment 2). Animals in experiment 1 demonstrated spontaneous chronic nephropathy and fluctuation in the tubular PCNA LI, but these findings were not correlated with renal Cd levels at 22 months. PCNA LI on the other hand, appeared to be linked to the severity of chronic nephropathy. In experiment 2, levels of CdCl2 of 200 ppm or more clearly induced degeneration and apoptosis of proximal tubules with high correlations between renal Cd levels, PCNA LI, and the severity of tubular degeneration. The results demonstrated that, in contrast to high-dose Cd administration, treatment with 40 ppm or less for 22 months did not influence tubular regeneration as a component of nonspecific chronic nephropathy, suggesting that long-term oral administration of low levels of Cd does not injure renal tubules in female rats.

Animals↗

PubMed2000

Comparative study of oral squamous cell carcinoma in Okinawa, Southern Japan and Sapporo in Hokkaido, Northern Japan; with special reference to human papillomavirus and Epstein-Barr virus infection.

In Okinawa, a subtropical island in Southern Japan, the incidence of oral squamous cell carcinoma is 1.5 times higher than that in mainland Japan. Sixty cases of oral squamous cell carcinoma from 1993 to 1996 in Okinawa and 42 cases over the same period in Sapporo were examined histologically. Human papillomavirus (HPV) and Epstein-Barr virus (EBV) were detected by polymerase chain reaction (PCR) amplification with primers specific for HPV and EBV. In situ hybridisations of the viruses were also carried out. In the case of Epstein-Barr virus, in situ PCR was also performed. Thirty-five (58.3%) Okinawan tumours were well-differentiated in type, but in Sapporo, 18 (42%) were of such type. In Okinawa, tumours of the mouth floor (10 cases, 16.7%) and oropharynx (12 cases, 20%) were frequently observed, whereas in Sapporo only five cases (12%) of each were found. HPV was demonstrated in 78% of Okinawan cases and 26.2% of Sapporon cases by PCR or non-isotopic in situ hybridisation (NISH). There were 76.6% (46 cases) of Okinawan and 38.1% (16 cases) of Sapporo cases positive for EBV by PCR. In only 12 Okinawan cases and 4 Sapporon cases, were positive signals demonstrated by in situ PCR on the cancer cells themselves. EBV was demonstrated in the large number of infiltrating lymphocytes, most of which were CD3+, and a few were CD19+. In Okinawa, HPV might be an important causative factor of oral squamous cell carcinoma and EBV a less important factor, whereas in Sapporo HPV and EBV might play only a small part in the aetiology of the tumour.

Adult↗

PubMed1999

Tissue distribution of cadmium in rats given minimum amounts of cadmium-polluted rice or cadmium chloride for 8 months.

To investigate the relationship between cadmium (Cd) toxicity, intestinal absorption, and its distribution to various tissues in rats treated orally with minimum amounts of Cd, 14 female rats per dose group per time point were given diets consisting of 28% purified diet and 72% ordinary rice containing Cd-polluted rice (0. 02, 0.04, 0.12, or 1.01 ppm of Cd) or CdCl(2) (5.08, 19.8, or 40.0 ppm of Cd) for up to 8 months. At 1, 4, and 8 months after the commencement of Cd treatment, seven rats per group were euthanized for pathological examinations to determine the Cd concentrations in the liver and kidneys and metallothionein (MT) in the liver, kidneys, intestinal mucosa, serum, and urine. One week before each period of 1, 4, and 8 months, the remaining seven rats in each group were administered a single dosage of (109)Cd, a tracer, to match the amounts of the designated Cd doses (about 1.2 to 2400 microg/kg body wt). They were euthanized 5 days later to determine the distribution of Cd to various tissues. No Cd-related toxic changes were observed. The concentrations of Cd in the liver and kidneys at any time point and MT in the liver, kidney, serum, and urine at 4 and 8 months increased dose-dependently, whereas MT in the intestinal mucosa did not alter markedly at any time point. The distribution rates of Cd to the liver increased dose-dependently (40% at lower doses to 60% at higher doses), whereas those to the kidney decreased dose-dependently (20% at lower doses to 10% at higher doses). The Cd retention rates 5 days after (109)Cd administration (amounts of Cd in various tissues/amounts of Cd administered) ranged from 0.2 to 1. 0% at any time point. These results suggest that the distribution of Cd to the liver and kidneys after the oral administration vary depending on the dosage levels of Cd. The difference of the distribution pattern of Cd to the liver and kidney is probably due to the difference in the form of the absorbed Cd, i.e., free ion or Cd-MT complex, although not closely related to the MT in the intestinal mucosa.

Administration, Oral↗

PubMed1999

Anatomical structure and surface epithelial distribution in the nasal cavity of the common cotton-eared marmoset (Callithrix jacchus).

To validate use of the common cotton-eared marmoset (Callithrix jacchus) in inhalation toxicity studies, its nasal morphology was examined. The nasal turbinates each consisted of one maxilloturbinate and one ethmoturbinate: these were more planar in structure than the comparable structures of rodents or dogs. The nasal cavity epithelia comprised squamous epithelium (SE), nasal transitional epithelium (NTE), respiratory epithelium (RE) and olfactory epithelium (OE), listed in order of occurrence from anterior to posterior positions. NTE was distributed as a narrow band lying between SE and RE. OE was limited to the dorsal part of the cavity, which was structurally similar to that of the macaque or man. Overall, this study revealed structural the similarity of the whole nasal cavity in the marmoset to that of macaques or humans. Prediction of nasal cavity changes in man based on extrapolation from experimentally induced changes in the common marmoset therefore seems likely to be feasible, making it a useful animal model for inhalation studies.

Animals↗

PubMed1998

Oral malignant melanoma: long-term follow up in three patients.

Three patients with oral malignant melanoma, who survived for at least ten years after initial examination, are presented. The depth of tumor invasion was 5 mm or less in all patients. The first patient received surgery and postoperative immunotherapy and she had no recurrence more than 18 years after treatment. The second patient underwent surgery but had local recurrence after 11 years. He underwent resection and postoperative chemotherapy and was still alive more than 14 years after initial examination. The third patient received radiotherapy and had metastasis nine months after treatment. Resection and radiotherapy were performed and the patient was alive more than 14 years after first presentation.

Aged↗

PubMed1998

Cadmium accumulation in rats treated orally with cadmium chloride for 8 months.

To investigate the accumulation pattern of cadmium (Cd) in the liver and kidney following Cd intake from diet, female SD rats were fed cadmium chloride (CdCl2)- contained diets (1.24 and 4.96 ppm Cd) for 2 or 4 months. The other rats were fed CdCl2-contained diets (8, 40, 200, and 600 ppm Cd) for 2, 4 or 8 months. The control rats were given diet without Cd addition (lower than 0.01 ppm Cd). The concentrations of Cd in the liver and kidney derived from all rats were determined. The concentrations of Cd in the liver and kidney increased depending on the dosage of Cd. The concentrations of Cd in the liver did not reach plateau level even in the 200 and 600 ppm groups. On the other hand, the concentrations of Cd in the kidney in the 200 and 600 ppm groups reached a plateau level, which was approximately 250 micrograms/g. In the 600 ppm group, the concentrations of Cd in the kidney reached 250 micrograms/g at 2 months, but did not exceed that level at 4 months. In the 200 ppm group, the concentrations of Cd in the kidney increased to nearly the level of 250 micrograms/g at 8 months. The ratio of the concentrations of Cd in the kidney versus liver decreased as the dosage of Cd increased, suggesting that a low dosage of Cd was distributed preferentially to the kidney, but a high dosage of Cd was distributed to the liver. The relation curves between total amounts of Cd intake and Cd levels in the kidney in the 2-, 4-, and 8-month groups showed a parabola. The curves were shifted in parallel in the direction of higher levels of ingested Cd in order of length of Cd exposure period. These results suggested that when Cd is ingested over a long time at low concentrations, the amount of Cd accumulation in the kidney is small even for equal amounts of total ingested Cd.

Administration, Oral↗

PubMed1998

[Successful management for chemorefractory testicular cancer with brain and lung metastases. A case report].

This is a report of successful management for a far advanced, chemorefractory testicular cancer patient. A 29-year-old male was referred to our hospital for the treatment of progressive lung metastases with elevated hCG level, which had recurred after complete remission following 3 courses of BEP chemotherapy and progressed after transient partial regression following 2 courses of intensified EP chemotherapy. In addition, a 3 cm in diameter, solitary brain metastasis was detected on CT. First, we performed wedge resection of bilateral pulmonary lower lobe for chemorefractory pulmonary metastases. Histological examination revealed viable embryonal carcinoma identical to the primary one. Thereafter, whole brain irradiation in combination with VIP chemotherapy (etoposide 100 mg/m2, cisplatin 20 mg/m2 and ifosfamide 1200 mg/m2 daily for 5 consecutive days) was carried out to treat brain metastasis. By 2 cycles of VIP therapy and irradiation (36 Gy), partial tumor regression and normalization of hCG level were achieved, leading to salvage surgery of the brain metastasis which histologically proved to be necrosis. Following an additional cycle of VIP therapy, the patient has been free of recurrence 24 months after completion of the treatment.

Adult↗

PubMed1997

Multivariate analysis of occult lymph node metastasis as a prognostic indicator for patients with squamous cell carcinoma of the oral cavity.

BACKGROUND: The biologic aggressiveness of squamous cell carcinoma of the oral cavity is reflected in its ability to metastasize to regional cervical lymph nodes. Patients with clinically negative cervical lymph nodes are believed to have a good prognosis; however, the prognosis of patients with lymph node metastasis occurring after excision or radiotherapy of the primary tumor is poor. METHODS: Univariate and multivariate analyses for occult lymph node metastasis (ONM) in 172 patients with clinically negative cervical lymph nodes were performed by the authors to elucidate the clinical and histologic tumor risk factors to enhance their ability to predict ONM. A multivariate Cox proportional hazards model and Hayashi's quantification theory type II were used to analyze prognostic factors and to determine the probability of ONM. RESULTS: Using Cox's proportional regression model, the factors linked to cancer specific survival were selected: tumor differentiation (P = 0.0330), mode of carcinoma invasion (P = 0.0175), and ONM (P = 0.0433). Pathologically identified metastatic lymph nodes were found in 21.5% of the cases studied (37 of 172 cases). The 5-year cancer specific survival was 94.0% for patients without lymph node metastasis, and 51.0% for patients with ONM (P < 0.0001, log rank test). The most significant predictors for ONM of each of the clinical and histologic factors, in descending order, were: mode of carcinoma invasion, intensity of lymphocytic infiltration, degree of differentiation, number of mitotic figures, and type of growth by means of Hayashi's quantification theory type II. The presence or absence of ONM in 147 of 172 patients (85.5%) was correctly predicted by the score at the point of intersection of the two curves, which was -0.03. Further investigation revealed that 28 of 32 new cases were differentiated accurately by means of this diagnostic system. CONCLUSIONS: The results of the current study suggest that this method of analysis can establish a reliable predictor of ONM, thereby facilitating correct choices for surgical procedures to enhance the survival rates of patients with clinically negative cervical lymph nodes.

Adult↗

PubMed1997

Iron deposition at mineralization fronts and osteoid formation following chronic cadmium exposure in ovariectomized rats.

To investigate whether chronic exposure of cadmium (Cd) chloride induces osteomalacic lesions similar to Itai-itai disease (IID), ovariectomized rats were injected intravenously with the cadmium at doses of 0.05 and 0.5 mg/kg/day, 5 days per week, for 50 weeks. In six rats in the 0.5 mg/kg group, the administration was continued for up to 70 weeks. In the 0.5 mg/kg group, the plasma concentration of calcium was similar in the treatment and control groups throughout the treatment period. The urinary excretion of calcium increased from 20 weeks and the increase became marked from 40 weeks. Histopathologically, osteoid seams in the femur, tibia, and humerus were increased from 50 weeks, and these changes became prominent at 70 weeks. Hypertrophy and hyperplasia of chief cells in the parathyroid were also observed from 50 weeks. The osteoid morphometry of the trabecular bone of the femur and sternum revealed a dose-dependent increase in osteoid/bone volumes. Roentgenographs of the antebrachial and metacarpal bones taken at 70 weeks showed so-called paper bone. The bone Cd content markedly increased until 25 weeks, but thereafter decreased linearly for up to 70 weeks. In contrast to the Cd content, the iron content decreased until 25 weeks, but thereafter increased until 70 weeks. Undecalcified section of the humerus showed the deposition of iron and formation of osteoid at mineralization fronts. Our data suggest that osteomalacic lesions were caused by chronic Cd intoxication, and that iron, as well as Cd, was involved in osteoid formation.

Animals↗

PubMed1996

Chronic cadmium exposure-induced renal anemia in ovariectomized rats.

Cadmium (Cd) chloride was intravenously injected at doses of 0.05 and 0.5 mg/kg/day in ovariectomized rats for 50 weeks, and the chronic Cd exposure-induced nephrotoxicity and anemia were investigated. The rats treated with 0.05 mg/kg Cd showed no apparent hematological, urinary, and histopathological abnormalities. In the 0.5-mg/kg group, renal tubular disorders became marked at 16 weeks, and cortical fibrosis with glomerular dysfunction appeared at 50 weeks. Anemia occurred at 12 weeks in the 0.5-mg/kg group and became increasingly marked with time. The mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were decreased at 12 and 25 weeks; however, the decreases of MCV and MCH disappeared at 50 weeks. A slight decrease in mean corpuscular hemoglobin concentration was noted at 50 weeks. The blood chemistry from the same group revealed a decrease in plasma iron levels and an increase in total iron binding capacity throughout the administration period. The erythropoietin (EPO) level was increased as the hemoglobin level decreased at 12 weeks, whereas the EPO level was not elevated even when the hemoglobin level was decreased at 50 weeks. These findings showed that renal anemia also occurred in addition to the iron deficiency anemia at 50 weeks.

Anemia↗

PubMed1995

Two cases of tongue cancer treated with intra- and peri-tumoral injection of recombinant interleukin-2 alone: immunohistochemistochemical considerations to clinical tumor response.

SUBJECTS AND METHODS: Two cases with stage II tongue cancer who exhibited different responses to intra- and peri-tumoral administration of rIL-2 alone are presented. Special consideration is given to the relationship between tumor responses to rIL-2 and clinicopathological and immunohistopathological findings. RESULTS: The patient who responded completely to treatment showed an exophytic tumor growth pattern, low-grade cancer invasion, and predominant infiltration of CD8+ lymphocytes over CD4+ lymphocytes in cancer cell nests. The non-responder showed endophytic tumor growth, high-grade cancer invasion, and uniform distribution of both CD4+ and CD8+ lymphocytes in cancer cell nests. CONCLUSIONS: Distribution of adequate amounts of T lymphocytes subsets may be necessary in order for good tumor response to biotherapy with rIL-2; other clinical and histopathological variables predicting the effect for cancer chemotherapy remain to be identified.

Aged↗

PubMed1995

[Distribution and origin of corpola amylacea in the vestibulocochlear nerve].

The distribution of the corpora amylacea in the vestibulocochlear nerve is very limited. We studied the relation between the number of corpora amylacea in the cochlear nerve and the aging of cochlea and developed some hypotheses on the origin of corpora amylacea. This study involved 11 subjects, 14 samples. The results were as follows. There was no relationship between the number of corpora amylacea in the cochlear nerve and aging of the cochlea. Corpora amylacea probably have no relation to cochlear disorders. However, it was reported that corpora amylacea were produced more than 10 years after the organ's obstruction. There is a possibility that corpora amylacea increased 10 years after disorders developed in the cochlear nerve. There is a neurilemma-Schwann sheath junction (NSS junction) in the vestibulocochlear nerve. Corpora amylacea characteristically exist only in the central portion of the vestibulocochlear nerve on one side of the NSS junction. There are 3 possibilities regarding the origin of corpora amylacea which include consideration of the hypothesis that the NSS junction is the point where the vestibulocochlear nerve pierces the encephal dura mater. 1) Supposing that the origin of the corpora amylacea is the vestibulocochlear nerve itself, we would expect that the oligodendrocytes which are components of the vestibulocochlear nerve to be the origin of the corpora amylacea because they exist only in the central portion of the nerve, but not in peripheral portions of the nerve. 2) Supposing that the origin of the corpora amylacea is not the vestibulocochlear nerve itself, we would expect that the perineurium from the encephal dura mater to be the origin of corpora amylacea.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Cadmium-induced osteomalacic and osteopetrotic lesions in ovariectomized rats.

The effects of long-term administration of cadmium (Cd) chloride on the bone were studied using ovariectomized rats. The rats were injected iv with the compound at doses of 1.0 and 2.0 mg/kg, 5 days a week, for 13 weeks. The serum concentrations of calcium and inorganic phosphorus were significantly increased from 8 weeks in the 2.0 mg/kg group. The bone Cd content was gradually increased for 13 weeks in a dose-dependent manner. Calcium and phosphorus contents in the bone, and serum levels of parathyroid hormone and osteocalcin, were not significantly different between Cd-treated and control rats. Histopathologically, chronic Cd nephropathy such as tubular atrophy and interstitial fibrosis was observed with clinical polyuria and increased enzymuria. The skeletal changes were detected mainly in the femur and tibia. In the metaphysis of Cd-treated rats, cancellous bone mass increased with time. This change was detected as an increased opacity by a roentgenogram. In the cortical bone of the midshaft haversian canals were dilated with clearly bordered osteoid seams and showed a motheaten pattern in rats in the 2.0 mg/kg group at 13 weeks. In the present study, we report Cd nephropathy and osteomalacic changes in ovariectomized rats with iv injection of CdCl2 for 13 weeks. Although an involvement of the indirect action of Cd through renal failure could not be ruled out in this experiment, our biochemical and pathological data suggested that osteomalacia was induced by a direct action of Cd on the bone through abnormal calcium homeostasis.

Animals↗

PubMed1993

Ovariectomy enhances cadmium-induced nephrotoxicity and hepatotoxicity in rats.

The toxicity of cadmium (Cd) chloride was studied in ovariectomized (OX) female rats and non-OX female rats after intravenous administration of the compound at doses of 2.0 and 3.0 mg/kg for 14 days. Mild hypochromic microcytic anemia developed in all rats treated with Cd, but growth retardation in the OX rats was more prominent than that in the non-OX rats. There was an increase of AST and ALT and a decrease of total cholesterol and the A/G ratio in both OX and non-OX rats treated with Cd. The hepatic and renal Cd concentrations increased in a dose-dependent manner, and the concentrations in both organs on Day 14 were comparable in the 3.0 mg/kg OX group (liver, 270.0 +/- 39.6 micrograms/g; kidney, 121.3 +/- 10.1 micrograms/g) and non-OX group (liver, 277.0 +/- 29.9 micrograms/g; kidney, 100.8 +/- 1.3 micrograms/g). Hepatocyte necrosis developed only in OX rats treated with Cd, and the nephrotoxicity of Cd was also notably enhanced by ovariectomy, since Cd nephropathy affected the proximal convoluted epithelium more severely and more frequently in OX rats than in non-OX rats. BrdU-labeled cells in the renal cortex were increased by approximately 2.7-fold in OX rat (7.4 cells/mm2) over those in the renal cortex in non-OX rat (2.7 cells/mm2). In conclusion, the present study demonstrated that ovariectomy enhanced Cd-induced nephrotoxicity and hepatotoxicity in rats.

Animals↗

PubMed1993

Variation in K-ras codon 12 point mutation rate with histological atypia within individual colorectal tumors.

To elucidate genetic alteration in relation to morphology and also to confirm more directly the proposed adenoma-carcinoma sequence, we analyzed thirty-eight colorectal "cancer in adenoma" lesions exhibiting areas of different atypia, in terms of K-ras codon 12 point mutation. The mutation incidence was 26.3% (10/38) for all cancerous areas. Well-differentiated and very well-differentiated carcinoma exhibited values of 17.6% (3/17) and 30.4% (7/23), respectively (statistically not significant). Positive cases of adenoma with severe atypia and adenoma with moderate or slight atypia were 26.7% (8/30) and 8.3% (3/36) respectively (statistically significant). Thus, K-ras point mutation, as indicated previously, may play an important role in the early stages of colorectal tumorigenesis. As for the nature of the mutation, GGT(Gly) to GAT(Asp) was the most frequent (80%). Eight cases had mutations concurrently in different areas of the same tumor and in all of these the mutation was homogeneous (6 cases to GAT, 1 case to TGT and 1 case to GTT). This provides genetic support for the "adenoma-carcinoma sequence" theory proposed on the basis of morphological considerations. All lesions with a mutation were of polypoid type, and no mutation was found in the flat type.

Adenocarcinoma↗