Influence of piecemeal necrosis on the compensatory increase of mitochondrial respiratory enzymes of the tumour-bearing liver: Clinical study of 53 surgical cases

The relationships between histological findings, adaptively increased cytochrome a(+a3) levels in chronic liver disease and complications after hepatectomy were studied in order to clarify the mechanism of mitochondrial derangement. The liver specimens of 53 hepatectomized patients were randomly evaluated by three independent hepatopathologists and were compared with cytochrome a(+a3) levels in the biopsied liver, the extent of operation and postoperative complications. The cytochrome a(+a3) concentrations did not show any significant difference between cases of chronic hepatitis and liver cirrhosis nor groups classified by regeneration. Severity of piecemeal necrosis was categorized into three groups: group A--minimal (n = 20); group B--moderate (n = 19); and group C--severe (n = 14). There were significant differences (P less than 0.01) in cytochrome a(+a3) concentrations between the groups (A: 99 +/- 9; B: 135 +/- 6; C: 155 +/- 10 pmol/mg of mitochondrial protein). Extensive hepatectomy, involving segmentectomy or more, was frequently complicated (four of nine, 44.4%) in group C, whereas there were few complications (two of 16, 12.5%) in group A cases in which extensive hepatectomy was performed. Evidence will be presented which will show that deranged liver function, as indicated by cytochrome a(+a3) levels, is closely correlated with piecemeal necrosis. This may be attributed to the damage of periportal hepatocytes which are the main sites of oxidative phosphorylation.     

Synthesis of human angiotensinogen (1-17) containing one of the putative glycosylation binding sites and its hydrolysis by human renin and porcine pepsin

The N-terminal heptadecapeptide of human angiotensinogen (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Asn-Glu-Ser-Thr-NH₂), with the C-terminal carboxyl group amidated, was synthesized in order to study the role of Asn-Glu-Ser, a putative carbohydrate binding site, on the hydrolysis by human renin. The synthesis was performed by fragment condensation using the Honzl and Rudinger azide procedure. In our conditions for azide segment condensation, histidine racemization was demonstrated to be negligible for most of the condensation reactions. Human renin liberates angiotensin I from h-angiotensinogen (1-17)-NH₂ with a K_m value of 3.4 × 10^?5m , at pH 7.3 and 37° being similar to h-angiotensinogen (1-13), an analog without the carbohydrate binding site. However, the V_max value of 4.1 × 10^?9mol/G.U. min is one order of magnitude higher. Porcine pepsin was demonstrated to cleave preferentially Leu¹⁰-Val¹¹ bond and, surprisingly, His⁹-Leu¹⁰ as well.     

Oral Tolerance Induced by Enterobacteria Altered the Process of Lymphocyte Recruitment to Intestinal Microvessels: Roles of Endothelial Cell Adhesion Molecules,TGF‐beta and Negative Regulators of TLR Signaling

Objective: Although enterobacteria are implicated in intestinal immune response, there has been no report on how intraluminal pathogens affect lymphocyte recruitment. The aim of this study was to determine how the presence of intestinal flora affects lymphocyte migration to intestine under physiological and lipopolysaccharide (LPS)‐induced inflammatory conditions. Methods: Interaction of T‐cells with ileal microvessels was monitored by using an intravital microscope in mice under germ‐free (GF) and specific pathogen‐free (SPF) conditions. LPS was administered into either the peritoneal cavity or duodenum before lymphocyte injection. Results: Adherence of T‐cells was greater in SPF than in GF mice, indicating that the presence of enterobacteria upregulated migration under physiological conditions. Intraperitoneally administered LPS significantly increased the adherence of T‐cells in both GF and SPF mice accompanied by the expression of adhesion molecules and proinflammatory cytokines. However, intraluminally administered LPS did not enhance the adherence of T‐cells in SPF mice. A significant induction of increase in mRNA expression of IRAK‐M, a negative regulator of TLR4 signaling, and transforming growth factor beta (TGF‐beta), a regulatory cytokine, was observed in SPF mice after luminal LPS treatment. Conclusions: Tolerance to intraluminally administered LPS in the lymphocyte recruitment process was induced by enterobacteria, possibly via the induction of IRAK‐M and TGF‐beta.     

Metastasizing atrial myxoma: a case with multiple subcutaneous tumours

We report a case with rapidly growing subcutaneous and intra-muscular tumours that were identical histopathologically to a pre-existing left atrial myxoma. No invasion of visceral organs or skeleton was found. This is a very rare case of metastasizing myxoma with wide dissemination and rapid metastastic growth, despite the benign appearance of the original tumour.     

Randomized Trial Comparing Chemotherapy Alone and Chemotherapy Plus Chest Irradiation in Limited Stage Small Cell Lung Cancer: A Preliminary Report

In order to assess the effectiveness of chest irradiation inaddition to intensive chemotherapy in limited stage small celllung cancer, 50 patients were randomized to receive either chemotherapyalone or chemotherapy plus chest irradiation, between April1981 and October 1985. The chemotherapy regimen consisted ofa four-drug combination of cyclophosphamide, vincristine, methotrexate,and procarbazine, and a three-drug combination of etoposide,adriamycin, and nimustine, given alternately every 8 weeks.One group of 26 patients received the chemotherapy alone, andanother group of 24 patients received chest irradiation with40 Gy between cycles 1 and 2 of the chemotherapy. Complete responserates were quite similar in the two groups; 50% for those receivingchemotherapy alone, and 59% for those receiving chemotherapyplus chest irradiation. There were no significant differencesin median survival (15 months versus 12 months) and in long-termsurvival rates between the two groups with a median follow-upperiod of 26 months. The combined modality treat ment was moretoxic than chemotherapy aIone two patients receiving such treatmentdied of radiation pneumonitis. It is concluded that chest irradiationcombined with chemotherapy does not affect the response rate,survival, or pattern of recurrence in patients with limitedstage small cell lung cancer.     

Experimental and Clinical Studies of Biodegradable Polymeric Stents

The metallic stent has become the most common device to reduce acute occlusion and late restenosis after balloon angioplasty, but the long-term effects of metallic stents in human coronary arteries are still unknown. To overcome several problems of conventional stenting, there have been many attempts to manufacture stents made of biodegradable materials. Although some studies have noted various degrees of inflammatory responses after biodegradable stent implantation, stents made of poly-1-lactic acid (PLLA) showed high biocompatibility with minimal inflammatory response and neointimal formation in porcine coronary arteries. A clinical study of PLLA self-expanding stent implantation is underway in Japan. The initial and 6-month results are favorable and suggest the feasibility, safety, and efficacy of the PLLA biodegradable stent in humans. However, long-term follow-up with larger numbers of patients will be required to validate the long-term efficacy of PLLA stents.     

Stage–specific antigens of Hymenolepis microstoma recognized in BALB/c mice

Antigenicity of eggs (oncospheres), cysticercoids and adults (with immature segments only) of the bile duct tapeworm Hymenolepsis microstoma was analysed using immunoblotting techniques and indirect immunofluorescent antibody (IFA) techniques with immune sera of BALB/c mice (i) infected with different doses of cysticercoids, (ii) during patent or prepatent infection with the lumen phase of the parasite or (iii) sensitized with live or dead eggs. Antibody responses detected by IFA test and immunoblotting showed that antigenicity of eggs (oncospheres) differed from that of cysticercoids and adults. Single worm infections were sufficient to stimulate antibody responses. Mice which had patent infection showed strong antibody responses to all three (egg (oncosphere), cysticercoid, adult) antigens, while mice given two prepatent infections showed some antibody responses to cysticercoid and adult antigens only. Although the normal intermediate hosts of this parasite are arthropods, antibodies to some major egg (oncosphere) antigens were produced in mice given eggs of this parasite orally, either through inoculation of eggs or ingestion of faeces contaminated with eggs. Antibodies were not produced in mice dosed with non-viable eggs. The results are consistent with the hypothesis that cestode parasites express phase- (or stage-) specific antigens.     

Fast-Slow Type of Atrioventricular Nodal Reentrant Tachycardia: Horizontal Dissociation of the AV Node During Tachycardia

Two patients with recurrent supraventricular tachycardia are presented. The tachycardia was initiated and terminated by atrial extrastimulation beyond the atrial relative refractory period and the atrial activation sequence during the tachycardia was low to high. The induction of tachycardia was dependent on a critical AH interval. In patient 1 who had ventriculoatrial conduction, the tachycardia was initiated by the premature ventricular stimulation followed by double atrial response. In patient 2 the ventriculoatrial conduction was not observed. In both patients, the unchanged atrial cycle length during the tachycardia with antegrade Wenckebach AH block was observed. When AH block occurred during tachycardia the first AH interval was shorter than the subsequent HA interval. In patient 2 verapamil (5 mg) prolonged the atrial cycle length during tachycardia and rapid intravenous injection of adenosine triphosphate (10 mg) terminated the tachycardia. Oral diltiazem (280 mg/day) suppressed the tachycardia in patient 1. These findings suggest that the mechanism of tachycardia may be fast-slow type of AV nodal reentry in the upper portion of the AV node and this type of arrhythmia has tendency to show incessant form.     

Time- Versus Frequency-Domain Analysis in Predicting Cycle Length of Inducible Ventricular Tachycardia After Myocardial Infarction

To determine whether time- and frequency-domain analyses differ in their ability to predict sustained ventricular tachycardia (VT) induced by programmed ventricular stimulation, 60 consecutive patients with myocardial infarction and 30 healthy control subjects were evaluated. Programmed ventricular stimulation using three extrastimuli and signal-averaged ECG recordings were performed in patients with myocardial infarction. Of the 60 patients, sustained monomorphic VT (SMVT) with cycle length (CL) ± 250 ms (slow SMVT) was inducible in 9, and SMVT with CL < 250 ms (fast SMVT) was inducible in 9. The durations of the filtered QRS (f-QRS) at each high-pass filter (25, 40, and 80 Hz) and the low amplitude signal (LAS) at 25-Hz high-pass filtering were significantly longer in the slow SMVT group than in the fast SMVT, no VT, or normal control group. The root-mean- square voltages at 25-Hz and 8Q-Hz high-pass filters in the slow SMVT group were significantly lower than in the fast SMVT, no VT, or normal control group. There was no significant difference in time- domain variables among fast SMVT, no VT, and normal control groups. The CL of the induced sustained VT was significantly correlated with the durations of f-QRS and LAS, Concerning frequency-domain variables (area ratio and factor of normality), there was no significant difference between slow and fast SMVT groups. Both the slow and fast SMVT groups had a significantly higher area ratio and a significantly lower factor of normality than the group with no VT or the normal control subjects. In conclusion, there were significant correlations between time-domain variables and CL of SMVT, while there was no correlation when using frequency-domain parameters.