Intra-operative administration of neocarzinostatin into the duodenal subserosa and levels found in the regional lymph nodes in pancreato-duodenal cancer

As an intraoperative chemotherapy treatment for the regional lymph nodes in resectable cases of pancreatoduodenal cancer, Neocarzinostatin (NCS) was administered in the duodenal subserosa and the NCS concentration was measured in the resected lymph nodes. Experiments: NCS 4,000 units (n = 4), or 10,000 units (n = 4) was administered into the duodenal subserosa of mongrel dogs, and 2 hours after administration, the lymph nodes of the mesentery root were resected. The NCS concentration in the lymph nodes was 0.21 U/g in the 4,000-U group and 1.39 U/g in the 10,000-U group. Clinical findings: NCS 10,000 U was administered into the duodenal subserosa in 6 cases of pancreatoduodenal cancer. The total number of resected lymph nodes was 49 and the mean NCS concentration was 5.65 U/g. According to site, the highest concentration was measured in lymph nodes from the anterior and posterior region of the pancreas head, which were near to the administration site. Also, NCS was well distributed in the lymph nodes in the hepatoduodenal ligament and mesentery root which lay in the direction of lymph flow. NCS concentration was high in lymph nodes resected 1 hour after administration. According to experimental reports of in vitro studies, an NCS concentration of more than 0.5 U/g is required to obtain an anticancer effect. This method is therefore considered to be useful as a form of intraoperative chemotherapy for the regional lymph nodes in pancreatoduodenal cancer.     

HISTOPATHOLOGIGAL STUDY OF HYPERTROPHIC CARDIOMYOPATHY WITH PROGRESSION TO LEFT VENTRICULAR DILATATION

The heart of seven cases of fatal congestive heart failure with dilated left ventricle, developing in 5 patients with symptomatic hypertrophic cardiomyopathy (HCM) and 2 patients with histologically widespread disarray of both ventricles, was morphologically investigated. These 7 cases showed myocardial widespread disarray and massive fibrosis, the mean percent area of fibrosis was 40.6% and 59.4% at upper and lower levels of left ventricles, respectively. Fibrosis was most extentsive in the lateral wall, and followed by anterior, posterior and interventricular walls. The severity of cell infiltration in left ventricle was completely matched to that of fibrosis and was most extensive in subepicardial area followed by middle and subendocardial areas of left ventricle. The intima and medial thickness of intramural small arteries in the fibrotic areas was significantly larger (p<0.05) than that of nonfibrotic areas, which suggested that the effect of intramural small artery was not essential for pathogenesis of massive fibrosis. ACTA PATHOL. JPN. 37: 1041 -1052, 1987.     

Urinary dysfunction and autonomic control in amyloid neuropathy

Abstract Uro-neurological assessment was performed in four patients with small-fiber neuropathy due to amyloidosis (2 transthyretin-type/2 immunoglobulin light-chain-type). Voiding difficulties were due to detrusor weakness and impaired bladder sensation. In two patients cholinesterase inhibition treatment caused urge incontinence, indicating detrusor denervation supersensitivity. The underlying mechanisms of urinary dysfunction seem to involve postganglionic cholinergic and afferent somatic nerves.     

Effect of verapamil on ventilatory and circulatory responses to hypoxia and hypercapnia in normal subjects.

Recent investigations have shown that the calcium channel blocker verapamil attenuated the hypoxic ventilatory chemosensitivity of carotid body in animals. To determine whether this is also the case in humans, transient physiological chemodenervation by O2 breaths (withdrawal test) during sustained hypoxia (N = 7), and ventilatory and circulatory responses to progressive hypoxia and hypercapnia (N = 8) were examined after oral administration of verapamil. During sustained hypoxia after verpamil, there was a significant reduction of withdrawal response from 5th to 25th min value (p < 0.01), but not after placebo. On the other hand, no significant difference in ventilatory responses to progressive hypoxia and hypercapnia was observed after verapamil. Verapamil run reveals similar features with placebo run in circulatory parameters except blood pressure response, which tended to be suppressed by verapamil. We conclude that verapamil attenuates peripheral chemoreceptor activity with time during sustained mild hypoxia in normal adult humans and this may be explained by delayed depletion in intracellular Ca2+ for chemotransduction of the peripheral chemoreceptors.     

The determination of thymidylate synthetase inhibition for testing fluoropyrimidines--pharmacokinetics and metabolism of carmofur (HCFU) in patients with gynecologic malignancies--Tokai HCFU Study Group for Gynecologic Malignancies

The pharmacokinetics and metabolism of carmofur (HCFU) were studied. Sixty-six patients were administered 100 mg of HCFU orally, and the plasma levels of the HCFU fraction (HCFUf) and 5-fluorouracil (5-FUra) were determined at 0, 1, 2, 4 and 6 hours. The average half-life of HCFUf and 5-FUra were 1.05 and 1.31 hours, and the average areas under the curves (AUC) of the plasma concentration were 6.51 hr X mcg/ml and 0.46 hr X mcg/ml, respectively. Surgical specimens of the tumors were obtained about three hours after the administration and assayed for HCFUf. 5-FUra fluorodeoxyuridine-monophosphate (FdUMP), deoxyuridine-monophosphate (dUMP), total thymidylate synthetase (TS total), and non-FdUMP-bound free enzyme (TS free). The TS inhibition rate (IR) was calculated by the follow method: IR = (TS total-TS free)/TS total X 100 levels of the TS total varied from not-detected (less than 0.10 pmol/g) to 20.5 pmol/g. The average FdUMP: dUMP ratio was 3.44 X 10(3), However, more than 80% inhibitions of TS were observed in nine cases (21.4%). The correlation indicates between TS IR and tissue FdUMP level or FdUMP: dUMP ratio were 0.57 and 0.62 in ovarian malignancies respectively. No significant correlations were observed between TS inhibition and levels of tissue 5-FUra or AUC of 5-FUra.     

Pseudotype hepatitis C virus enters immature myeloid dendritic cells through the interaction with lectin

Dendritic cells (DC) are the most potent antigen-presenting cells that regulate immune responses. One of the mechanisms for hepatitis C virus (HCV) persistence is the ability of HCV to suppress DC function. Direct HCV infection to blood DC has been implicated for DC dysfunction. To clarify the susceptibility of each DC subset to HCV, we used pseudotype vesicular stomatitis virus (VSV) coated with chimeric HCV envelope glycoproteins (E1 and E2). We demonstrate that pseudotype VSV enters myeloid DC (MDC) but not plasmacytoid DC (PDC). The highest efficiency of pseudotype VSV entry to MDC was observed when MDC were cultured with GM-CSF. Such efficiency decreased when MDC are matured with the treatment of IL-4, CpG oligodeoxynucleotide, or CD40 ligand. Mannan inhibited pseudotype VSV entry to MDC, but Ca(2+) chelators failed to do so. These results show that pseudotype VSV possessing HCV-E1 and E2 enters immature MDC through the interaction with lectins in a Ca(2+)-independent manner.