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.     

Ultrastructural study of the motor end-plate in botulism and Lambert-Eaton myasthenic syndrome

The motor end-plate fine structure was studied in 3 patients with type A botulism and compared with that in 4 patients with Lambert-Eaton myasthenic syndrome (LES). In the botulism cases a biopsy of the biceps brachii muscle was performed at the chronic stage. The skeletal muscle showed a neurogenic change. The nerve terminal area had decreased and the postsynaptic regions had been denuded of their nerve terminals in 16% of the regions (9.8% in control). No highly simplified postsynaptic regions were observed. The findings are consistent with those observed at the motor end-plates in motoneuron diseases. By contrast, in LES no changes were observed in the presynaptic region. In the postsynaptic region, the postsynaptic membrane length and membrane density decreased and hypertrophy of the junctional folds was not observed.     

Increased 5-HT-2 receptor function as measured by serotonin-stimulated phosphoinositide hydrolysis in platelets of depressed patients.

1. The present study was undertaken to examine whether or not 5-HT-induced inositol monophosphate (IP-1) accumulation in human platelets is mediated by 5-HT-2 receptors and to assess 5-HT-2 receptor function as measured by 5-HT-stimulated IP-1 accumulation in platelets from normal controls and depressed patients before drug treatment. 2. In platelets prelabeled with 3H-myo-inositol, in Ca ion free HEPES buffer containing 10 mM LiCl, 5-HT caused a dose-dependent accumulation of IP-1 during 15 min incubation. A maximal increase in IP-1 formation was observed at 30 microM of 5-HT and its EC50 value was 4 microM. 3. Ketanserin, a selective 5-HT-2 antagonist, was a potent inhibitor of 5-HT-stimulated IP-1 accumulation with a Ki value of 12 nM, but (-)propranolol (10 microM), a 5-HT-1 antagonist, failed to block the 5-HT response. 4. The potencies of various compounds tested to inhibit 5-HT-stimulated IP-1 accumulation in human platelets correlated positively with the affinities to 5-HT-2 receptor as defined by radioligand binding in rat cerebral cortex. 5. In a group of unmedicated patients with major depressive disorder matched for age with normal control group, we found a significant increase in 5-HT (100 microM)-induced accumulation of IP-1 (150 +/- 7% of basal for depressed patients, 132 +/- 3% for controls).     

Direct measurement of the lambda of the lumped constant of the deoxyglucose method in rat brain: determination of lambda and lumped constant from tissue glucose concentration or equilibrium brain/plasma distribution ratio for methylglucose

Steady-state distribution spaces of 2-[14C]deoxyglucose ([14C]DG), glucose, and 3-O-[14C]methylglucose at various concentrations of glucose in brain and plasma ranging from hypoglycemic to hyperglycemic levels have been determined by direct chemical analyses in the brains of conscious rats. The hexose concentrations were measured chemically in freeze-blown brain extracted with ethanol to avoid the degradation of acid-labile products of [14C]DG back to free [14C]DG that has been found to occur with the more commonly used perchloric acid extraction of brain. Corrections were also made for nonphosphorylatable, labeled products of [14C]DG found in the nonacidic fractions of the brain extracts, which were previously included with the assayed [14C]DG, and for the contribution of the hexose contents in the blood in the brain, which was found to be particularly critical for the determination of the glucose distribution space, especially in hypoglycemic states. From the measured contents of the hexoses in brain and plasma, the relationships of the tissue concentrations and distribution spaces of each of the hexoses and of the lambda (i.e., ratio of tissue distribution space of DG to that of glucose) of the DG method to the tissue glucose concentration were derived. The lambda was then quantitatively related to the measured equilibrium ratio for [14C]methylglucose over the full range of brain and plasma glucose levels. By combining these new data with the values for the lumped constant, the factor that converts the rate of DG phosphorylation to glucose phosphorylation, previously determined in rats over the same range of plasma glucose levels, the phosphorylation coefficient was calculated and the lumped constant graphed as a function of the measured distribution space in brain for [14C]methylglucose.     

A seromuscular stripping method to create a nipple valve without metal stapling for continent urinary reservoir

Urinary continence with a Kock or Mainz pouch is achieved by a nipple valve of the invaginated ileum which is usually fixed with metal staples. However, metal staples can cause various complications as a foreign body. The seromuscular stripping method, a new technique to create a nipple valve, was applied to 17 patients with bladder cancer in the construction of a continent urinary reservoir by the ileocolonic pouch (Mainz pouch). Metal staples were not used. The results were satisfactory except for 2 patients who became incontinent because of prolapse of the nipple in one and insufficient valve function due to ischemic change of the nipple valve in the other. Histology of the nipple valve from an autopsy case showed a good double layer nipple valve that functioned well to preserve continence.     

Development of a new perfusion system for pharmacological study on rabbit basilar arteries

We developed a constant-flow perfusion system to measure vascular responses to vasoactive agents applied intraluminally or extraluminally. The intraluminal and extraluminal sides of a cylindrical section of rabbit basilar artery were isolated completely. By loading with 0.75 g of tension, the resting condition of each preparation was made constant. The intraluminal side was perfused at a constant flow of 8 ml/min and under an intraluminal pressure of 8 mm Hg. When 30 mM KCl was administered intraluminally the preparation showed marked contraction, whereas only slight contraction was observed with extraluminal administration. When 2 x 10(-7) M 5-hydroxytryptamine was administered, no significant differences in contraction could be detected between the intraluminal and extraluminal routes. Application of 10(-6) to 10(-4) M acetylcholine after precontraction with 30 mM KCl resulted in much stronger dilatation upon intraluminal application. Thus, it was demonstrated that under certain conditions significant differences exist in the responses of rabbit basilar arteries to vasoactive agents applied intraluminally or extraluminally. This system can detect the effects of vasoactive agents administered intraluminally and extraluminally at a high level of sensitivity and shows good reproducibility as a means of analyzing vascular functions and characteristics.     

Modeling the dependence of hexose distribution volumes in brain on plasma glucose concentration: implications for estimation of the local 2-deoxyglucose lumped constant

The steady-state distribution volumes of glucose, 3-O-methylglucose, and 2-deoxyglucose (2DG) are known to change as the concentration of glucose in plasma ranges from hypo- to hyperglycemic values. Model estimates of the three distribution volumes were compared with distribution volume values experimentally measured in the brains of conscious rats as the concentration of glucose in plasma was varied from 2 to 28 mM. The dependence on plasma glucose concentration of the 2DG lumped constant, the factor that relates the phosphorylation rate of 2DG to the net rate of glucose utilization at unit specific radioactivity in the plasma, had been determined previously in separate series of experiments. The model was extended to incorporate this dependence of the lumped constant. In the model both the transport and the phosphorylation barriers were assumed to be single and saturable. The values of their respective half-saturation concentrations and the ratio of the two maximum velocities for glucose were assumed to be invariant over the entire range of plasma glucose concentration. Good agreement between measured and estimated values for the distribution volumes and the lumped constant was attained over the full range of plasma glucose concentration. The model estimates reflected the progressive transport limitation of the brain glucose content as plasma glucose levels were reduced to hypoglycemic values. The results also indicated that these changes should be evident in the time course of 2DG in brain following administration by bolus or continuous infusion, and thus that indexes of local lumped constant change could be derived from the time course data.