Breast parenchymal activity on scintimammography: Comparison between bone-seeking agents and99mTc-sestamibi

The aim of this study was to evaluate breast parenchymal activity on scintimammography with bone-seeking agents and 99mTc-MIBI. Scintimammography was performed with bone-seeking agents in 61 patients and with 99mTc-MIBI in 33 patients. Activity in the breast parenchyma contralateral to the suspected lesion was visually assessed by two independent observers. Increased breast parenchymal activity was shown in 19 of 61 patients examined with bone-seeking agents, while it was demonstrated in only two of 33 patients examined with 99mTc-MIBI. Breast parenchymal activity of bone-seeking agents was higher in patients aged 50 years or younger than in those older than 50. Increased parenchymal activity of bone-seeking agents may disturb visualization of primary breast cancer especially in relatively young patients. Low parenchymal activity is suggested to be a favorable characteristic of 99mTc-MIBI as a scintimammographic agent.     

Intra-arterial chemotherapy via reservoir system for advanced bladder cancer and prostate cancer

A clinical study was performed on the efficacy of intra-arterial chemotherapy using a reservoir system for advanced urological malignancies. The reservoir system was indwelted in the femoral subcutaneous layer by Seldinger's method. Fifteen cases of inoperable complicated advanced bladder cancer and 10 cases of postoperative local recurrent bladder cancer were administered intra-arterial chemotherapy using a reservoir system. Then, 23 cases of local relapsed prostate cancer and two cases of endpocrine-resistant prostate cancer were administered the chemotherapy. The administered anti-cancerous agents were methotraxate, cis-platinum and adriamycin, then 5-FU or carboplatin was administered as maintenance therapy. The mean number of courses of chemotherapy was six for bladder cancer and four for prostate cancer. During stabilization of the local lesion, no distant deterioration was recognized. The overall clinical efficacy was a positive response (PR) and no change (NC): for 18 and 7 cases of bladder cancer, and 11 and 14 cases of prostate cancer, respectively. The median duration of stabilization was 23 months for bladder cancer and 12 months for prostate cancer. The adverse effects were fever than those with systemic chemotherapy.     

Structure-activity relationships of quaternary protoberberine alkaloids having an antimalarial activity

Seventeen quaternary protoberberine alkaloids related to berberine 1 were tested for antimalarial activity in vitro against Plasmodium falciparum and structure-activity relationships are proposed. The activity of the protoberberine alkaloids was influenced by the type of the oxygen substituents on rings A, C and D and the position of the oxygen functions on ring D. The position of the oxygen functions on ring D and the type of the oxygen substituents at the C-13 position (ring C) strongly influenced the activity. Shifting the oxygen functions at C-9 and C-10 to C-10 and C-11 on ring D resulted in a significant increase in the activity. Compounds bearing a methylenedioxy function at C-2 and C-3 (ring A) or C-9 and C-10 (ring D) showed higher activity than those which have methoxy groups at the same positions. Introduction of a methoxy group into the C-1 position (ring A) decreased the activity. Replacement of a hydroxy group at C-2 or C-3 (ring A) by a methoxy group led to a reduction in the activity. Displacement of a hydroxy function at C-13 (ring C) by the oxygen substituents such as OMe, OEt, OCOOEt, and OCON(Me)₂ reduced the activity. In the same replacement at C-9 (ring D), the activity depended upon the type of the oxygen function. Six protoberberines displayed more potent activity than berberine 1. The activity decreased in the order: 10, 11, 17 and 18 > 7 and 8 > 1.     

Neurovascular developmental interaction: a specific form of vascular maldevelopment in the malformed brain

The process of the development of the intracranial vessels was studied by means of immunohistochemical analysis of factor VIII in normal and exencephalic chick fetuses. The results revealed that the development of blood vessels in exencephalic brain was far advanced beyond the norm, with intense immunoreactivity to factor VIII on postincubation day 16 exceeding that on day 21 in normal controls. Compared with results regarding the direction of the overgrowth in the neuronal maturation process in the previous study using the chick exencephaly model, the findings of overmatured blood vessels were compatible with NSE- and somatostatin-positive elements that appeared especially in the overgrowth foci. The results of the present study suggested the pathogenic development of the area cerebrovasculosa in the neural placode as a phenomenon consequent upon hypervascularization in response to neuronal overgrowth, as seen in human cases of exencephaly or anencephaly. We emphasize the significance of this specific phenomenon in the development of the fetal central nervous system, namely neurovascular developmental interaction.     

Circulatory effects of verapamil during normovolemic hemodilution in anesthetized rats

Patients who have undergone perioperative normovolemic hemodilution may require calcium channel blockers for the treatment of myocardial ischemia and/or supraventricular tachyarrhythmias. The purpose of this rodent study was to examine the effect of intravenous verapamil on the hyperdynamic circulatory response to acute normovolemic hemodilution (hematocrit 20%). Anesthetized animals were randomly divided into four groups equal in number: (1) controls (no hemodilution, no drug); (2) hemodilution only; (3) verapamil only; and (4) hemodilution followed by verapamil. Cardiac output was recorded using an electromagnetic flow probe. Pre- and afterload tests were performed, the former consisting of rapid infusion of blood adjusted for hematocrit, the latter consisting of an aortic clamp technique. Animals in group 2 had significantly (P less than 0.05) greater percent increases in cardiac index, stroke volume index, and dP/dt, and greater percent decreases in mean arterial pressure, systemic vascular resistance, and oxygen delivery than did control animals (group 1). Infusion of verapamil after hemodilution (group 4) did not interfere with the compensatory increases in cardiac index and stroke volume index seen in group 2, nor did it reduce the peak stroke volume index in response to preload stress, although it did reduce resting dP/dt, mean arterial pressure and systemic vascular resistance, and peak cardiac index and "left ventricular developed pressure" after preload and afterload stress, respectively. We conclude that reduced ventricular function after verapamil administration does not interfere with the compensatory increase in stroke volume index after normovolemic hemodilution.     

Immunological comparison between prostate-specific antigen and γ-seminoprotein

Summary Prostate-specific antigen (PA) and -seminoprotein (-Sm) were compared by immunocytochemical, immunodiffusion and immunoblotting methods using rabbit anti-PA antibody and rabbit anti--Sm antibody. Enzyme immunoassys (EIAs) were developed for measurements of PA and -Sm to determine a correlation between serum PA and -Sm levels in patients with prostate cancer. The patterns of localization and distribution of PA and -Sm were identical in prostate tissue sections, including benign and cancerous human prostacs. The immunodiffusion study showed that the antigens with which anti-PA antibody and anti--Sm antibody reacted in seminal plasma and prostate tissue homogenates were identical to each other. In the immunoblotting study, anti-PA antibody and anti--Sm antibody recognized a single antigen corresponding to a molecular weight of approximately 33,000 both in seminal plasma and prostate tissue homogenates. The EIAs developed in this study were sensitive, specific, and reproducible, and the correlation between serum PA and -Sm values determined by these EIAs was highly significant (r=0.99, P(0.001). These results indicated that PA and -Sm were immunologically identical and that serum PA and -Sm determined by immunoassays using anti-PA antibody and anti--Sm antibody should be evaluated as identical tumor markers for serodiagnosis of prostate cancer.     

Cell biological basis for combination radiotherapy using heavy-ion beams and high-energy X-rays.

We investigated the biological effect of combining carbon-beam and X-ray in vitro. The results showed that when we employed Gray equivalent as the indication of therapeutic dose, the effects could be explained with simple additive way in the treatment plan. This fact provides important information about the combined therapy of carbon-beam and X-ray.     

Primary pleomorphic adenoma in posterior cranial fossa

A 35-year-old woman had an intradural tumor in the posterior fossa adjacent to the posterior wall of the left pyramidal bone, which was totally removed and histologically diagnosed as a pleomorphic adenoma. Follow-up examination for 2 years showed no recurrence of the tumor. There was no primary lesion in any other gland of the body, and therefore there is no alternative but to conclude a “migration” of some gland cells. The pathogenesis of this tumor remains unclassified.     

Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence.

PURPOSE: To evaluate the relationship between mutations of the epidermal growth factor receptor (EGFR) gene and the effectiveness of gefitinib treatment in patients with recurrent lung cancer after pulmonary resection. PATIENTS AND METHODS: We sequenced exons 18-21 of the EGFR gene using total RNA extracted from 59 patients with lung cancer who were treated with gefitinib for recurrent lung cancer. Gefitinib effectiveness was evaluated by both imaging studies and change in serum carcinoembryonic antigen (CEA) levels. RESULTS: EGFR mutations were found in 33 patients (56%). Of these mutations, 17 were deletions around codons 746-750 and 15 were point mutations (12 at codon 858, three at other codons), and one was an insertion. EGFR mutations were significantly more prevalent in females, adenocarcinoma, and never-smokers. Gefitinib treatment resulted in tumor shrinkage and/or CEA decrease to less than half of the baseline level in 26 patients, tumor growth and/or CEA elevation in 24 patients, and gefitinib effect was not assessable in nine patients. Female, never-smoking patients with adenocarcinoma tended to respond better to gefitinib treatment. Gefitinib was effective in 24 of 29 patients with EGFR mutations, compared with two of 21 patients without mutations (P < .0001). Of note, del746-750 might be superior to L858R mutations for prediction of gefitinib response. Patients with EGFR mutations survived for a longer period than those without the mutations after initiation of gefitinib treatment (P = .0053). CONCLUSION: EGFR mutations were a good predictor of clinical benefit of gefitinib in this setting.