Histopathological studies on experimental marine toxin poisoning--4. Pathogenesis of experimental maitotoxin poisoning

Repeated injections of 45 ng/kg of maitotoxin into the peritoneal cavities of male ICR mice resulted in marked atrophy of lymphoid tissues, a reduction of lymphocytes in the circulating blood, reduced immunoglobulin M in serum, and an increase of calcium content in the adrenal glands. A single injection of 200 ng/kg of maitotoxin induced a marked increase in total calcium content of the adrenal glands as well as in plasma cortisol concentration (about seven times control) within 1 hr. In contrast, mice pretreated with CoCl2, a calcium channel inhibitor, and/or adrenalectomized mice, showed no discernible changes in the lymphoid tissues after repeated injections of maitotoxin. It is thus suggested that maitotoxin first stimulates calcium influx in the adrenal glands, which then causes the release of cortisol into the blood. The excess amount of cortisol in serum produces acute involution of the thymus and other lymphoid tissues.     

Predicting recurrence time of esophageal carcinoma through assessment of histologic factors and DNA ploidy

Cytophotometric analysis of nuclear DNA content was done in 128 patients with squamous cell carcinoma of the esophagus. The relationship among histopathologic features, DNA distribution pattern, and survival time was investigated from the standpoint of recurrence. Of 128 patients, 77 (60.1%) died of recurrence within 2 years after surgery: 16 (12.5%) from 2 to 5 years and two (1.6%) over 5 years. The rate of death of recurrence within 2 years was higher in patients with T4 or N1 than T1, T2, and T3 or N0 (P less than 0.01). Survivors over 5 years more frequently possessed type II DNA pattern than types III and IV (P less than 0.05). The rate of death of recurrence within 2 years was 34.4% in type II, which was lower than the 59.6% rate in type III (P less than 0.05) and the 76.6% rate in type IV (P less than 0.01). Survivors from 2 to 5 years were higher in type III than in type IV (P less than 0.05), and recurrence over 5 years was found only in type II. This inclination was more apparent in those with curative resection. In the patients with type II, careful follow-up may be needed over 5 years for late recurrence. However, in those with type IV, no recurrence over 2 years could be regarded as healed because most of their recurrences occur within 2 years. These findings suggest that the growth rate of esophageal carcinoma should reflect DNA aneuploidy, and the DNA analysis of esophageal carcinoma should be a valuable parameter for postoperative follow-up planning.     

PFK inhibition test for cancer detection: clinical applications and mechanisms of PFK inhibition

A newly established cancer marker, the PFK inhibition test, has been further examined for its capacity to detect malignant neoplasms irrespective of the organs in which cancer cells start proliferating. We tested 1,160 sera from cancer patients and compared them with 756 normal sera, using histograms and normal paper for analysis of accumulated frequency. PFK activity through the influence of normal sera showed normal distribution, and cancerous sera shifted to the inhibitory site with an irregular shape. From these analyses, the patients were classified into the following types: normal range: PFK greater than SD (standard deviation of PFK activity in normal sera); suspicious range: SD greater than PFK greater than 2SD, must be given the PFK test again; and dangerous range: PFK less than 2SD, further examination must be carried out to detect cancer. Fifty percent of the sera from all the cancer patients inhibited PFK beyond 2 SD of normal sera. We also analyzed organ-associated PFK distribution, eg, gastric, colorectal, and mammary cancer. In gastric cancer, PFK inhibition was stronger in accordance with how far a particular stage of cancer had progressed. However, 50% of sera from stage I gastric cancer patients was positive beyond the cut-off line of 2 SD. We examined 104 sera from patients diagnosed as benign prostatic hypertrophy and found malignant cells in 10 patients whose sera tended to be positive in PFK inhibition. The PFK inhibitory factor in the body fluids of cancer patients was fractionated by Sephadex G-75 gel filtration and DEAE ion exchange chromatography. The approximate molecular weight of this factor was 13,000 daltons. The factor was resistant to heat and acid (0.1 N HCl and H2SO4) and was sensitive to 0.1 N NaOH and phosphate buffer. Diluted sulfuric acid and ammonium sulfate made an inactive NaOH-treated sample active when lyophilized following dialysis against distilled water. PFK inhibition by cancerous sera was eliminated by fructose-2,6-bisphosphate (the strongest activator of PFK) in a dose-dependent manner. PFK attached to agarose beads was found to be reversible even after being inhibited by cancerous body fluids and ATP water solution. Although PFK is apt to decay in a low pH range, the established procedure did not destroy PFK, but induced a direct inhibition of PFK by ATP through the ATP inhibition site on the PFK molecule. The PFK inhibitor may possibly function as a proton carrier and release protons to activate the ATP inhibition site.(ABSTRACT TRUNCATED AT 400 WORDS)     

Non-hormonal adrenocortical adenoma with oncocytoma-like appearances

We report a case of non-hormonal adrenocortical adenoma. The tumor was removed en block with the adrenal gland. The specimen was 5.0 X 4.5 X 3.0 cm, weighed 30 g and was solid. Histologically, this tumor had an oncocytoma-like appearance. However, as there is no concept of oncocytoma in connection with adrenocortical adenoma, this case was diagnosed as adrenocortical adenoma. A case with such histological findings has never been reported.