Histo-clinical classification and follow-up study of gastric polyp. Gastric polyp was found in 1,616 cases or 0.23% of 711,455 persons through the gastric mass-survey. They were classified into 3 groups: hyperplastic polyp in 61%, gastric polyposa in 34%, and polyp composed of metaplastic epithelium with marked atypism (ATP) in 5%. Gastritis polyposa was subclassified into 5 groups according to its histo-clinical features. Malignant degeneration was suspected in 5 or 2.1% of 236 hyperplastic polyps operated, while no polyp which had changed into cancer was experienced among 974 polyps followed-up by biopsy during the time course of 6 months to 11 years at the longest. On the other hand, coexistence of gastric cancer was found in 13% of cases with ATP. In polyps composed of metaplastic epithelium, there are two kinds of polyp: metaplastic polyp in hyperplastic proliferation and neoplastic polyp. In the follow-up study of 1,104 polyps, the growth of polyp was seen in only 14, and 12 of which were hyperplastic polyp. No change from gastritis polyposa to hyperplastic polyp was observed. The increase in size in 14 polyps was seen mostly 3 to 4 years after they were found and was always transient. From these results, it is considered that most of gastric polyps clinically detected have already completed their growth.


Fasting therapy for psychosomatic diseases with special reference to its indication and therapeutic mechanism. It has been well known that the fasting therapy which was invented in Medical School of Tohoku University reveals an excellent effect upon various kinds of psychosomatic diseases, but its therapeutic mechanism and suitable indication are not yet explained completely. In order to corroborate these problems, this study was undertaken on 262 cases of psychosomatic diseases in the field of internal medicine. It is a complete fasting for 10 days with nothing by mouth except for drinking water, and 500 ml of parenteral fluid containing vitamins are administered intravenously every day. Absolute bed rest and self meditation are required in a closed individual room, and patients are not allowed to meet anyone but physicians and nurse in charge. The return to normal ordinary diet follows the order of fluid diet, soft diet and semiordinary diet during 5 days. In the period of the therapy, various clinical and laboratory examinations were carried out. Significance of these examinations consists in prediction of possible danger during the fasting period and elucidation of its therapeutic mechanism. Consequently, an outstanding efficacy rate of 87% with excellent prognosis was attained, and the following diseases were determined as suitable indication of this therapy; irritable colon, dysorexia nervosa, borderline hypertension, neurocirculatory asthenia, bronchial asthma, mild diabetes mellitus, obesity, lumbago without organic findings, conversion hysteria, various neurosis with somatic symptoms and masked depression. Possible mechanism of action of the therapy is that fasting acts as an extreme stress on the function of the autonomic nervous and endocrine systems, then it regulates the function of whole body including the brain, also it acts as one of the behaviour therapy for abnormal conditioning.


Role of the kidney in gastrin metabolism. Fasting blood gastrin level among various clinical entities was measured by means of radioimmunoassay. Hypergastrinemia of various degrees was found in some cases of chronic renal failure. During angiography arteriovenous difference of gastrin level was investigated in the kidney in 22 patients without renal diseases. The high rate of gastrin removal from the blood circulation by the kidney was also confirmed in the synthetic human gastrin 1-17 (SHG 1-17) infusion experiment in dogs. In this study, hypergastrinemia seen in renal diseases was thought to be caused partly by impaired gastrin metabolism in the kidney.


Endoscopical polypectomy of the gastric polyp with electro-coagulation wire loop. A forward-viewing fiberscope equipped with two channels was designed for safer and easier gastric polypectomy under endoscopic control using electro-surgical technique. No electrical accident, bleeding, perforation or significant complications were noticed. Mucosal ulcerations at the polypectomy site healed within a month leaving minor scars behind. In 30 cases, U1 II gastric ulcers developed after polypectomy, which healed leaving convergence of mucosal folds behind. Fiberscopic excision of gastric polyps was also useful for establishing a reliable diagnosis of gastric polyp cancer which is sometimes overlooked by routine biopsy procedure. It may be the "perfect biopsy". The patient with gastric polyp who is aware of his own illness and feels uneasy can be released from his anxiety and regain both physical and mental health at the cost of minimal risks of endoscopic polypectomy.


Evaluation of mass screening program for stomach cancer. Particular method and program of mass survey examination of gastric cancer were introduced into Miyagi Prefecture and the results accumulated during the past 14 years are presented. During this period, 1,427 cases of gastric cancer (0.18%), as well as many cases of other diseases of the stomach and duodenum, were found by the mass survey. 450 cases were those of early cancer in which invasion of carcinoma was limited to the mucosa and submucosa. The ratio of surgically confirmed early cancer cases to all the stomach cancer cases was 36.4%. Almost in all cases of early stomach cancer there were neither complaints nor clinical symptoms; that is, they were the cases of so-called preclinical cancer of the stomach. The prognosis after surgery of early stomach cancer was remarkably favorable with a five-year survival rate over 90% and the death rate due to stomach cancer was actually decreased in the surveyed population.


Extraventricular lesions demonstrated by gastric photofluorographic study. In a mass survey for diseases of the stomach with photofluography, lesions other than those of the stomach were studied in 85,040 subjects. Gastric lesions were detected in 2.17%, while other lesions were found in 1.97%, giving an approximately similar ratio. Duodenal lesions were found most frequently and in 1.47%, followed by intraabdominal calcification in 0.44%. Among duodenal lesions, duodenal ulcer was seen in 0.14%, and duodenal diverticulum in 0.34%. Among diseases with abdominal calcifications, calcification of lymph nodes was found most frequently and in 0.24%, followed by cholelithiasis in 0.085% and urolithiasis in 0.004%. Lower esophageal lesions were found in 0.05%, in which esophageal diverticulum was the most frequent and found in 0.034%.


Relationship between disturbances of micellar formation and steatorrhea. In order to clarify the correlation between decrease in micellar formation and degree of steatorrhea, upper intestinal content was analyzed after administering a test meal of Borgström et al. Fecal fat was also measured. It was demonstrated that micellar phase was composed chiefly of fatty acid and monoglyceride, with low concentrations of diglyceride and triglyceride. The fat composition of micellar phase was nearly constant in normal subjects and in cases of malabsorption syndrome. The correlation between the ratio of micellar fat to the whole ingested fat in the intestinal content and daily excretion of fecal fat was very marked.


Abnormal micelle formation in various malabsorption syndromes. In order to clarify the abnormal micelle formation in various malabsorption syndromes, the analysis of upper intestinal contents after administering a test meal of Borgström et al. was performed. It was demonstrated that the percentage of micellar fat to total fat and lipase concentrations decreased markedly from the normal controls despite of normal concentrations of bile salts and pH in cases of pancreatitis and pancreatectomy. In contrast, it was shown that the percentage of micellar fat was markedly low and the concentrations of conjugated bile salts were reduced in cases of ileal diseases. Unconjugated bile salts were detected although the concentrations of total bile salts were normal in blind-loop syndrome. The correlation between the percentage of micellar fat and lipase concentrations or bile salts concentrations in normal controls and various malabsorption syndromes was also reported.


Cytological diagnoses of early gastric cancer. To evaluate the clinical value of gastric cytology in the detection of stomach cancer, the results of cytological examinations in 417 cases of early cancer of the stomach in which cancer cell infiltration was limited to the mucosa or submucosa were analyzed. The cytological examination revealed positive for cancer cells in 93% of these cases, and therefore it is concluded that this method is not only useful but indispensable for the diagnosis of early cancer of the stomach. The gastric cytology proved to be more reliable than the endoscopic and X-ray examinations in terms of detection rate of the early gastric cancer. Among various cell collection methods for gastric cytology, which include the washing, abrasive and fibergastroscopic methods, the washing method under direct vision by the use of fiberscope showed the highest value of positivity (92.8%) in the cases of early cancer of the stomach. With the help of endoscopic guidance and biopsy techniques, the cytological examination further increased its reliability and ability in the detection of early gastric cancer. Cancer lesions even smaller than 1 cm can now be correctly diagnosed by the gastric cytology.


Crohn's disease, non-specific ulcers of the small intestine, and idiopathic proctocolitis in a Japanese university hospital from 1954 to 1974. Most of the cases of Crohn's disease reported in Japan were originally treated surgically as acute appendicitis and, after appendectomy, they were diagnosed as acute terminal ileitis or acute Crohn's disease, which should belong to a category different from typical Crohn's disease, according to the international nomenclature by the Council for International Organization of Medical Sciences in 1973. Reviewing our university hospital records from 1954 to 1974, the incidence of typical Crohn's disease and idiopathic proctocolitis has been increasing, while the patients with intestinal tuberculosis have been decreasing. Clinical and histopathological features of operated three groups of our patients with Crohn's disease of the small intestine, non-specific ulcers of the small intestine and prestomal ileitis were comparatively studied. Furthermore, 9 cases of operated Crohn's disease of the colon and 23 cases of operated idiopathic proctocolitis were similarly evaluated. The importance of diagnosing Crohn's disease as a whole from both clinical and histopathological stand points of view was emphasized, and main differential diagnostic criteria between Crohn's disease and idiopathic proctocolitis were discussed.


[Effectiveness of antibiotic premedication in colonic surgery]. The value of preoperative bowel preparation with antibiotics in colon surgery was studied in a prospective randomized trial: 58 patients received only mechanical and dietary preparation and 50 patients were treated additionally with a combination of neomycin and bacitracin 4 days preoperatively. Bacteriologic studies of stools from the day before beginning of preparation and from the day before surgery which were done quantitatively per 1 gram stool revealed that the fecal flora of 90% of the patients with colonic disease is abnormal. After antibiotic treatment a significant reduction of Escherichia coli, Bacteroides, Bifidus, Clostridium, and Proteus was obtained in more than 70% of the patients. The effect on Klebsiella was poor. Candida were increased in 86% of the cases without resulting in a systemic candida infection. In the stool samples of 16 patients no bacteria were found after antibiotic treatment. If there was a high bacterial count in the preoperative stool infectious complications followed postoperatively. The rate of infectious complications was 28 (48.7%) in the control group and 7 (14%) in the antibiotic group. This significant lower rate of complications speaks in favor of preoperative bowel preparation with neomycin and bacitracin, especially in the absence of adverse side-effects.


[2 years of experience with balanced oral feeding in abdominal surgery]. Together with the progress of surgical technique there is the continued development of pre- and postoperative care of patients. There are two fields for the use of BSD (balanced synthetic diet): I. Preoperative: a) Full caloric nutrition b) Intestines free from waste matter and lowering of bacterial content. II. Postoperative: Interruption of the vicious circle of diminished offer of nutrition, postoperative katabolism, which increases the need for amino-acids and so interferes with the process of wound-healing and the protection against infection.


[Physical flow studies of new surgical aspiration drains]. Mathematical and experimental results demonstrate that the customary Redon drain as well as the improved Neo-Redovac drain develop suction only over a short initial distance. The above mentioned innovation of three additional oval holes does not increase efficiency. The disadvantage of rapidly diminished suction is overcome in the "Ulmer Drain", in which equidistant openings of continually increasing aperture are aligned towards the drain end.


[The so-called spontaneous nodular panniculitis (Weber-Christian lipodystrophy)]. Enlarged lymph nodes and a tumor, the size of a man's fist, were found in the abdomen of a female patient of 63. Histologic diagnosis determined a non-suppurative panniculitis with typical proliferation of foam cells and reactive inflammatory infiltration attaining the stage of granulomatosis. The disease is seen as granulomatous histiocytosis; a sure explanation of its pathogenesis is not yet possible.


[The programmed medical report in surgery]. Our experience in programs for semi-automatic medical reports developed and used in the course of the last 4 years was as follows: 9 programs for inpatients and 3 for outpatients have been developed. Programs for semi-automatic medical reports have proved especially advantageous in frequent diseases (as for example appendicitis, cholelithiasis) and in managing large special consulting hours for outpatients with predominantly similar diseases. Due to rational and cheap work the use of semi-automatic medical reports in a certain range shows an alternative to the conventional ways of writing from dictation.


[X-ray archivation with microfilm].

[X-ray archivation with microfilm]. The LogEtronics X-Ray Microfilms system, which is used in our clinic as well as in two other Berufsgenossenschaftliche Unfallkliniken for archiving of x-ray films, has enabled us to microfilm all x-rays of 4 years within 14 months. The conception of the microfilm system has also stood the test from the point of view of fulfilling all legal requirements.


[Esophagopericardial fistula with tension pneumopericardium]. Reported on is a 72 year old man in whom a diverticulum of the lower esophagus had perforated into the pericardium causing pyopneumopericardium and cardiac tamponade during esophagoscopy. After resuscitation and drainage of the pericardial cavity the patient ameliorated and three weeks later the fistula between the esophagus and the pericardial sac had closed at least functionally as judged by a gastrografin-swallow. Planned definitive surgical closure of the fistula could not be performed because the patient's condition deteriorated following tracheobronchial aspiration. He succumbed due to bilateral pleuro-bronchopneumonia, progressive renal failure and central circulatory dysregulation. Reviewing 24 reported cases the clinical signs, etiology, differential diagnosis, therapeutic management and prognosis of this rare condition are discussed.


[Blunt renal trauma: diagnosis, therapy and possible complications]. 223 cases of blunt renal injuries, which were observed over a period of 19 years at the department of Surgery, University of Graz, are presented in this study. The value of several diagnostic procedures and the therapy are discussed in respect of early and late complications and the literature reviewed.


[Solitary bone cysts in the foot].

[Solitary bone cysts in the foot]. The localisations of bone cysts known under the title of "intraosseous ganglion, synovial cyst of bone and solitary unicameral cyst" are summarised from the literature. Two of the authors' patients are added to the few cases of talar cysts recorded up to the present. In addition, a patient with a calcaneal cyst is described. The cysts can be traumatic or non-traumatic in origin. The various theories concerning their etiology are discussed. The clinical findings, differential diagnosis and therapy of subchondral bone cysts particularly in the region of the foot are considered.


[Cultivation possibility for obligatory anaerobic bacteria from contaminated cotton carriers after storage. Comparative testing of simple swabs and swabs in transport medium using Stuart's method]. 26 strains of obligate anaerobic bacteria, which had been isolated from clinical specimens, were tested for their survival on artificially contaminated cotton swabs after storage. All strains could hardly if at all be cultivated, if the cotton swabs had been stored in empty test tubes at 4 degrees C for 48 hrs. In contrast to that it was possible to cultivate all strains without significant reduction of their number from swabs, which were stored at 4 degrees C for 48 hrs in test tubes containing Stuart's transport medium. The necessity of an improvement of techniques and transport-methods to isolate anaerobic bacteria is discussed. The use of a special transport medium is recommended as an important aid to the early recognition of anaerobic infection.


[Wound infection following arterial surgery in the pelvis-leg region]. In a series of 581 reconstructions of the aorta to the leg arteries, 28 cases (4.8%) developed wound infection with positive microbiological identification. There were 24 monoinfections with significant prevalence of Staphylococcus aureus and S. epidermis. Thirteen patients with prosthetic implants and one patient with autologous saphenous vein bypass showed graft infection, which occurred in 13 patients as a complication of reoperation for bleeding or graft occlusion in the early postoperative period. The incidence of vascular infection in patients without reoperation was 0.4%. The risk of wound infection could not be lowered by the use of prophylactic broad spectrum antibiotics. Five (33%) patients with graft infection died because of sepsis and/or rupture of anastomosis. In the group of 9 survivors there were 3 patients with excision of the graft and limb preservation without reconstruction, and 3 patients with partial or total excision of the graft and successful simultaneous axillofemoral or obturator bypass. From this study it is assumed that improvement of indication and operative technique in reconstructive procedures is more promising in preventing wound infection than the extended administration of prophylactic antibiotic drugs. In case of vascular infection the excision of the graft is very urgent and consequent "extraanatomic" reconstruction can prevent loss of limb and life.


[Spontaneous splenic rupture].

[Spontaneous splenic rupture]. Discussion of rupture of the spleen apparently without cause; the patient suffered no trauma nor did he have a disease of the spleen. The conclusion is that the rupture occurred spontaneously.


[Ischemic necroses of the colon and rectum following alloplastic vessel substitution of the abdominal aorta]. Arterial insufficiency to the colon and rectum followed by ischemic necrosis of this bowel portion is considered to be a rare complication after resection of abdominal aortic aneurysms and alloplastic replacement of the abdominal aorta in arterial occlusive disease. The main symptom is diarrhea and mucus or blood in stool. Sigmoidoscopic examination is of diagnostic value; the treatment of choice has to be colostomy and resection. A causative factor for the development of large bowel necrosis is diminution of collateral blood supply, which is discussed in detail.


[Lymph flow disorders following arterial surgery of the leg]. In a series of 342 arterial reconstructions of the iliacolic to popliteal arteries 24 patients with lymph vessel damage were observed. The diagnosis of lymphedema was established in 18 patients by clinical findings and in 2 of them the diagnosis was confirmed by lymphography with followup of 1 year. Three patients developed an internal lymphogenic cyst, 3 showed an external lymph fistula, and 1 patient developed an infection of a dacron bifurcation graft. The infection occurred when an additional occlusion of the left femoral artery was bypassed with an autologous saphenous vein graft and a lymph cyst in the groin, which was excised several times, became infected. The patient was treated successfully by excising the graft and performing an axillofemoral bypass. Although cases of surgical damage to lymph vessels following arterial reconstructions are rare in the literature, it is assumed that this complication occurs more often than reported, because of lack of lymphographic information.


[Leiomyoma of the portal vein].

[Leiomyoma of the portal vein]. A case report of a 34-year-old female with leiomyoma of the portal vein is presented. The tumor was found accidentally, when laparatomy with diagnosis of cholelithiasis was performed. Total excision of the leiomyoma including a part of the anterior wall of the portal vein was necessary and could be carried out. The continuity of the portal vein could be preserved using continuous vascular suture. Microscopical examination of the tumor showed an increased proliferation rate in the leiomyoma; therefore the tumor was classified "semimalignant". A review of the literature concerning leiomyoma and leiomyosarcoma of the central and the peripheral veins showed 91 published cases and no other report of portal vein leiomyoma. The tumors of the vena cava inferior, which have been observed mostly, are listed in particular.


[Liver resection under occlusion of hepato-duodenal ligaments. Renunciation of a textbook opinion]. The belief that the hepatoduodenal ligament should only be clamped for 5-10 min, then the clamp released for a shorter or longer period, can no longer be upheld. The author's clinical investigations have shown that continous clamping up to 20 min can be tolerated by the liver without adverse effect. The authors consider a clamping time of 30-40 min tolerable particularly if the liver is cooled by pouring cold Ringer's solution over it. In one case, splenic capsule rupture was a complication of clamping the hepatoduodenal ligament.


[Unusual indication for 2/3 gastroduodenopancreatectomy in ulcer of the papilla, acute pancreatitis and massive ascites]. A 32-year-old worker, an alcoholic with a history of duodenal ulcer for 2 years, was admitted because of weight loss, severe pain in the upper abdomen, and ascites. Serum lipase was 1200 mU. X-ray showed a possible postbulbar ulcer. Laparotomy was performed, and 10 1 ascitic fluid were evacuated, the latter caused by a peripancreatic callosity compressing the portal vein. multiple necrotic areas in the pancreas; sequestrum cavity in the head of the pancreas connected with a callous ulcer at the duodenal papilla (histology: no malignancy). Two-thirds gastric resection, subtotal duodenopancreatectomy, extirpation of the gallbladder and common bile duct, splenectomy, gastroenteroanastomosis, and antecolic hepatojejunostomy were performed. After a transitory cerebrovascular incident, the patient was discharged on the 34th postoperative day. The patient has gained 11 kg, and works in the construction business. The pathogene development, frequency of complications, and therapy of postbulbar ulcer are described.


[Modification of postoperative intestinal atony using caerulein. Comparative studies in the rat and man]. The effect of caerulein upon postoperative enteral paralysis was investigated in animals and men. The increase in motility effected by cerulein in rats was proved by the increase in passage demonstrated after administration of radioactive test food (51CrO4Na2 solution). A clinical survey comprising 20 patients in the postoperative period following cholecystectomy, compared to an untreated control group, confirmed our findings.


[Proximal rupture in the triceps surae a typical, but often unrecognized injury]. An account is given of 12 high ruptures of the triceps surae, a traumatic lesion of the medial belly of the gastrocnemius, caused by sudden overstreching of the muscle by concomitant ankle dorsiflexion and full knee extension. In all cases the authors found characteristic clinical features. Surgical exploration in 5 of 12 cases verified the ruptures of the musculotendinous junction of the medial gastrocnemius belly. A follow-up study of 2 years showed that the surgical treatment seems to be better, especially in younger and athletic patients.


[Studies on the antibacterial efficacy of Cu-compounds in combination with acridine orange as additive to a polymethylacrylate]. Copper acetate of suitable specific surface (Kupferacetat Fargua) and copper acetate plus acridin orange intermixed with Palacos powder have bactericidal efficacy against gram-negative and gram-positive bacterias depending on bacterial species. The Palacos osseous cement releases the intermixed substances over long periods of time. There exists a mutual influence on the bactericidal increase of both substances.


Single copy DNA and structural gene sequence relationships among four sea urchin species. Measurements of the divergence of single copy DNA sequences among four sea urichin species are presented. At a standard criterion for reassociation (0.12 M phosphate buffer, 60 degrees C, hydroxyapatite binding) we observe the following extents of reaction and reductions in thermal stability for single copy DNA reassociation between Strongylocentrotus purpuratus tracer and heterologous driver DNA: S. dröbachiensis 68% and 2.5 degrees C; S. franciscanus 51% and 3.5 degrees C; Lytechinus pictus 12% and 7.5 degrees C. The implied extents of sequence relatedness are consistent with the phylogenetic relationships of these species. The rate of single copy sequence divergence in the evolutionary lines leading to the Strongylocentrotus species is estimated to be 0.06-0.35% per million years. The rate of divergence of total single copy sequence has been compared to that of structural gene sequences represented in S. purpuratus gastrula polysomal messenger RNA. When closely related species, S. purpuratus and S. franciscanus, are compared, these polysomal sequences are found to diverge at a lower rate than does the total single copy sequence. For two very distantly related species, S. purpuratus and L. pictus, a small fraction of the single copy DNA sequence is probably conserved. These conserved sequences are not enriched in their content of structural gene sequences.


Haploid genome reactivation and recovery by cell hybridization. Induction of DNA synthesis in spermatid nuclei. DNA replication in haploid spermatid nuclei has been induced by hybridization of mouse early spermatids to proliferating HeLa cells. Use of polyethylene glycol rather than inactivated Sendai virus as the cell fusion agent was found to be essential to the production of large numbers of heterokaryons containing spermatid nuclei. DNA replication was detected in the heterokaryons by autoradiography. Density of silver grains over spermatid nucleic closely approximated the grain density over labelled HeLa nuclei in the same heterokaryons. Mouse centromeric heterochromatin appeared to be labelled last during the spermatid DNA synthetic period. On the average, HeLa nuclei in heterokaryons began DNA synthesis before spermatid nuclei. Results indicated, however, that DNA synthesis by HeLa nuclei might not be a prerequisite for spermatid DNA synthesis. These experiments demonstrate induction of DNA synthesis in spermatid nuclei, the first major step toward reactivation and recovery of their haploid genome by cell hybridization.


Chromosome constitution of in vitro segregated haploid and diploid cells of the mouse. The composition in segregated haploid sets of paternal and maternal chromosomes has been studied in order to verify whether their composition is uniparental of mixed, fixed or variable. Primary cultures where prepared using kidneys from hybrids of strains of Mus musculus in which the parental chromosomes are distinguishable; the maternal set consists of 20 teleocentric chromosomes, the paternal set of 9 metacentric chromosomes, derived by Robertsonian fusion and 2 telocentrics. Applying Seabright's banding technique, an analysis of segregated haploid and diploid cells, which have originated spontaneously through polyploidisation-segregation processes was carried out. It was concluded that the haploid sets have a variable composition of paternal and maternal chromosomes.


Analysis of the frequency of sister chromatid exchange in different regions of chromosomes of the kangaroo rat (Dipodomys ordii). The frequency of sister chromatid exchanges (SCEs) has been determined for C band and non-C band regions of chromosomes of the kangaroo rat after staining with the fluorescence plus giemsa (FPG) technique. After one complete round of DNA synthesis in the presence of bromodeoxyuridine (BrdU) staining of the C band regions revealed simple or complex asymmetries between chromatids. After two complete rounds of DNA synthesis in the presence of BrdU "harlequin" chromosomes were observed. Analysis of the distribution of SCE in chromosomes at their 1st and 2nd mitosis showed that relatively few exchanges occur within C band regions, although the frequency of SCEs is high at the junction between C band and non-C band chromosome regions.


Fistula-in-Ano: perineal fistula of intra-abdominal or intrapelvic origin simulating fistula-in-ano--report of seven cases. Fistulas manifesting in the perianal region but originating in the abdomen often have their true origin not recognized for extended periods. Examples of seven such complex cases are presented and discussed. Removal of the abdominal abnormality is mandatory before any cure can be effected; the perianal portion usually heals without any special local treatment.


Fistula-in-ano: a ten-year follow-up study of horseshoe-abscess fistula-in-ano. A preliminary report in 1965 described a conservative surgical procedure for the management of acute and chronic horseshoe anal fistulas. The operation has been used exclusively at the Ochsner Clinic for this problem since 1963. Forty-one patients were treated from 1963 to 1973. The paper reviews the pathology of acute and chronic horseshoe anal fistulas and describes the surgical procedure for both acute and chronic horseshoe abscess anal fistulas with accompanying illustrations. The excellent results with minimal deformity of the anus and anal canal are attributed to avoidance of severing the superficial external sphincter between its coccygeal origin and the anus. Of the 41 patients treated in the period from 1963 to 1973, healing was good, and there has been no recurrence.


Volvulus of the sigmoid colon: a ten-year study. A ten-year study of volvulus of the sigmoid colon is presented. Although the results of treatment of volvulus of the sigmoid colon are generally improving, the challenge for further improvement remains.


Malignant duodenocolic fistula: report of two cases, each with one or more other synchronous gastointestinal cancers. Two patients had duodenocolic fistulas, each following a carcinoma of the colon in the area of the hepatic flexure that had perforated into the duodenum. The first patient was treated by a radical pancreatoduodenectomy with right colectomy; the second by subtotal colectomy with excision of the duodenal wall and suture. Both patients are alive and without evidence of recurrent disease. In addition, the first patient had two other primary carcinomas, in the cecum and in the stomach, and the second patient had another primary in the sigmoid. The definitive procedure had to be adjusted to encompass all lesions. The radical operation in one stage seems to be the preferred procedure and certainly is most satisfactory as a cancer operation. Our patient treated by this procedure has survived more than 11 years. An intestinal fistula related to colonic carcinoma, evan though rare, should not be considered as a separate entity. Treatment of the cancer with an en-bloc resection of the communicating organs should be employed if possible.


Adenocarcinoma arising in a sigmoid diverticulum: report of a case. A case of adenocarcinoma arising in a sigmoid diverticulum is presented. A patient who had colonic diverticulosis was found to have one diverticular lumen distended by tumor mass. Microscopically, this was seen to be adenocarcinoma arising from the diverticular mucosa. Apparently, this is the first reported case of adenocarcinoma arising in an intact diverticulum of the colon.


Gangrene and spontaneous perforation of the cecum as a complication of pseudo-obstruction of the colon: report of three cases and speculation as to etiology. "Pseudo-obstruction of the colon" refers to a condition in which physical and radiologic findings identical to those associated with mechanical obstruction of the large bowel are found, but in which no organic cause of colonic distention can be identified. These cases may involve progressive proximal large-intestinal dilation to the point of cecal perforation or necrosis. Two cases of spontaneous perforation of the cecum and one case of gangrene of the cecum secondary to proximal distention of the right colon that followed pseudo-obstruction of the colon are presented. Various etiologic factors reported in the medical literature are discussed and analyzed, and an anatomicophysiologic explanation of a possible mechanism, based on sympathetic-parasympathetic neurostimulatory imbalance, is offered.


[Ultrasonic diagnosis of space-occupying lesions of the kidney (author's transl)]. In 140 patients who were suspected of having space-occupying lesions of the kidney the ultrasound findings were analysed. There were no false negative results. Out of 4 false positives two could be explained by nontumourous focal renal disease. In a further 10 cases a space-occupying lesion could not be excluded with certainty on the grounds of the ultrasound investigation alone. Out of a total of 96 space-occupying lesions (48 solid tumours, 48 cystic processes) 83 were correctly diagnosed sonographically.


[Dose-activity relationships of the BCG vaccine for newborn infants (author's transl)]. BCG vaccine with the Kopenhagen strain was injected intracutaneously in 217 newborn infants in four different concentrations (22.000, 50.000, 110.000, and 160.000 organisms per dose). 171 children could be followed up and tested. The results showed a good activity (tuberculin conversion) with a low risk (no ulcers, no severe regional lymph node swelling). There were no complications. As would be expected the conversion rate was highest (95%) with the vaccine with the highest concentration (160.000 U per dose). This concentration is thus recommended for the general BCG vaccination of newborn infants. In contrast to previous experience tuberculin conversion could be demonstrated in 22 babies without a local reaction at the vaccination site. In 13 children the opposite was true.


[Out-patient treatment of periproctitic abscesses (author's transl)]. A total of 237 patients were treated over a period of five years for anorectal abscesses. Wide circular opening with removal of all purulent foci and necroses from outside had been preferred, because almost only "late forms" of anorectal inflammatory processes (perianal and ischiorectal abscesses) were seen. Sphincterotomy was possible in only a few patients. Postoperative fistulae occurred in 14% of the patients.


[Elimination of toxic peptides from amanita phalloides by charcoal perfusion in vitro (author's transl)]. Charcoal perfusion in vitro resulted in virtually complete detoxication of an extract from 170 g of Amanita phalloides in aqueous or plasma protein solution. After 4 min of perfusion the amanitin content was reduced to 1-2% after 15 min it was less than 1% of the starting material. Under the same conditions toadstool toxin was eliminated from plasma protein solution too: after 4 min of perfusion a dose of remaining material, corresponding to the LD70 of the starting material, was nontoxic in mice.


[Coarctation of the aorta on the plain chest x-ray (author's transl)]. Chest X-rays were analysed in 22 male and 16 female patients (mean age 30.7 years) with coarctation of the aorta. The results were correlated with angiography, haemodynamic pressures and operative findings. The left subclavian artery was prominent in 33 cases, signs indicating a collateral circulation (rib notching, internal mammary artery) were present in 26 cases. In addition there were changes of cardiac and aortic configuration. The least reliable sign was constriction of the aorta due to the stenosis itself. Frequent combinations of X-ray signs were dilatation of the left subclavian artery and a collateral circulation, in addition to signs of increased pressure (n = 25). Less frequently (n = 8) only a dilated subclavian artery and signs of increased pressure were found. The prominence of the subclavian artery was particularly marked in systolic pressure gradients through the stenosis of greater than 40 mm Hg, and the formation of a collateral circulation when average aortic pressure differences above and below the stenosis were less than 40 mm Hg. Collaterals were to be found most frequently with a correlation of 2:1 of the systolic gradient to the mean pressure gradient delta Ps/delta Pm. A very good correlation existed comparing X-ray signs with findings at operation. The diagnosis of coarctation of the aorta can thus be made with sufficient certainty from the plain chest X-ray.


[ECG changes in dextran intolerance (author's transl)]. In a 46-year-old patient following infusion of 5-10 ml of dextran ECG changes resembling those of infarction occurred together with severe left-sided chest pain, tachycardia, and an immeasurably low blood pressure. Rapid recovery occurred and normalisation of the ECG within an hour without signs of an intermediate phase. On these grounds it can be assumed that these previously unrecognised changes are probably the expression of a short-term coronary perfusion disturbance as part of an anaphylactoid reaction of the intima.


Comparative in vitro biological activity of 1-34 N-terminal synthetic fragments of human parathyroid hormone on bovine and porcine kidney membranes. 1-34 N-terminal fragments of human parathyroid hormone with sequences according to Brewer et al (hPTHB) and to Niall et al (hPTHN) were synthesized and compared for their ability to activate bovine and porcine kidney cortex membrane adenylate cyclase. Results show that these two hormone sequences are able to activate these membranes but at least in this in vitro assay, hPTHN is about 10 times more active than hPTHB on bovine as well as on porcine membranes. These "apparent potencies" with respect to the potency of bPTH 1-34 in bovine and porcine membrane assay systems are respectively 4% and 11% for hPTHB and 39% and 156% for hPTHN. These relative potencies may be interpreted as corresponding to species specificity of the hormone receptor structural relationships.


Induction of uterine ornithine decarboxylase (ODC) by antiestrogens. Inhibition of estradiol-mediated induction of ODC: a possible mechanism of action of antiestrogens. The ability of antiestrogens (tamoxifen and nafoxidine) to affect uterine ornithine decarboxylase (ODC) in the ovariectomized rat was determined. Tamoxifen citrate (1 mg or 10 mg/kg) and nafoxidine (0.5 mg/kg) markedly elevated ODC levels. Tamoxifen (1 mg/kg) given for 4 days totally inhibited the E2 (0.5 mug/kg)-mediated induction of ODC. Similarly nafoxidine (0.5 mug/kg) given once a day for 2 days inhibited the E2-mediated induction of ODC. The relation of the inhibition of ODC induction by antiestrogens to their mechanism of action as antiestrogens is discussed.


Uterine tubulin production during early pregnancy in the rabbit. Rabbit uterine tubulin levels rise rapidly in the preimplantation period to peak values of about 10-fold in the endometrium and about 4-5 fold in the myometrium on days 3-5 of pregnancy. Endometrial tubulin falls to non-pregnancy levels by mid-pregnancy while myometrial tubulin declines much more slowly. The rise in tubulin exceeds the early rate of increase in total uterine protein and DNA. Following implantation, tubulin content of the decidual basal plate area increases rapidly to peak about day 12 then declines. Production of uterine tubulin appears capable of a major, short term response to gonadal hormone stimulation.


The half-life of luteinizing hormone in intact and castrated quail during photoperiodic stimulation. In the Japanese quail (Coturnix coturnix japonica) the plasma concentration of luteinizing hormone (LH) depends on the physiological state of the animal. Low levels are found in sexually immature birds on short days (0.8 +/- 0.1 (n = 20) ng/ml) while after exposure to long days, sexually mature birds have a significantly higher LH level (4.4 +/- 0.4 (n = 20) ng/ml). Castration of long day males results in an even higher rise in LH concentration to 16.8 +/- 1.8 (n = 16) ng/ml. When the half-life (t1/2) of circulating LH was determined it was found to have two components: a fast t 1/2 of about 6 min and a slower component of either 20 min (determined by a radioisotope method), or 40 min (following hypophysectomy). No significant difference was observed in either of these components between birds in the three physiological states (short days, long days, castration plus long days). It would appear, therefore, that since the half-life of plasma LH remains constant, the difference in circulating LH observed under the various physiological conditions results solely from a change in the rate of LH secretion.


Continuous measurement and rapid kinetics of ATP synthesis in rat liver mitochondria, mitoplasts and inner membrane vesicles determined by firefly-luciferase luminescence. Oxidative phosphorylation in rat liver mitochondria, the mitoplast or inner membrane-matrix fraction, and inverted inner membrane vesicles was studied with firefly luciferase luminescence. All preparations showed relatively high ATP/O ratios under initial reaction conditions in the presence of Mg2+, but only intact mitochondria demonstrated significant respiratory control. Mitochondria and mitoplasts, but not vesicles, catalyzed nearly complete conversion of ADP to ATP. Vesicles converted between 50% and 70% of added ADP to ATP establishing a phosphate potential of 9.8 to 10.5 kcal/mol (43.9 kJ/mol). In "loosely coupled" submitochondrial systems which do not display respiratory control, the phosphate potential appears to be a useful parameter of the integrity of the phosphorylating membrane, while ATP/O ratios may be dependent on the relative concentrations of ADP and ATP in the reaction medium. The rapid kinetics of oxidative synthesis of ATP by inverted inner membrane vesicles was investigated in stopped-flow rapid-mixing experiments. After an oxygen pulse to reduced vesicles, ATP synthesis commenced within 20 ms. In antimycin-inhibited vesicles, ATP synthesis resulting from the rapid oxidation of the terminal portion of the respiratory chain commenced within 20ms and took approximately 100 ms for half completion. Since half oxidation of the terminal portion of the respiratory chain occurs within a few milliseconds, ATP synthesis resulting from such redox reactions must occur over a significantly longer time course than the redox reactions themselves.


The structure of pentasaccharides and hexasaccharides from blood group substance H. Six individual reduced pentasaccharides and hexasaccharides were isolated after sodium borohydride degradation of blood group substance H from pig stomach linings. Their structure was determined by means of periodate oxidation, methylation analysis, mass spectrometry, partial acid and enzymic hydrolysis and chromic anhydride oxidation. It has been found that all the oligosaccharides investigated contain the common tetrasaccharide core to which terminal alpha-L-fucose and N-acetyl-alpha-D-glucosamine residues are attached. Some problems of carbohydrate chain heterogeneity in blood group substances are discussed.


Human-polymorphonuclear-leucocyte neutral protease and its inhibitor. Studies with fluorescein-labelled polymeric collagen fibrils as a substrate. Human polymorphonuclear leucocytes were obtained from the synovial fluids of patients with inflamed knee joints suffering either from Reiter's syndrome or from rheumatoid arthritis. The polymorphonuclear leucocytes were collected by gentle centrifugation followed by disruption and their subcellular fractionation by centrifugation in 0.34 M sucrose to provide a granule fraction and a post-granule supernatant fraction. 0.5 M KCl extraction of the granule fraction yielded neutral protease activity, similar to trypsin, when assayed against fluorescein-labelled polymeric collagen fibrils. The post-granule supernatant fraction contained an inhibitor towards the neutral protease and trypsin. The inhibition of the neutral protease was found to be time-dependent, this inhibition being released after 1.5-2 h. In contrast, the inhibition of trypsin was irreversible and this property was used to devise an assay procedure for the inhibitor.


Synthesis of the brain-specific S-100 protein in a cell-free system from wheat embryo programmed with poly(A)-containing RNA from rabbit brain. Polyadenylated polysomal RNA was prepared from rabbit cerebral hemispheres using phenol extraction and chromatography on oligo(dT)-cellulose. This RNA directed the synthesis of the brain-specific S-100 protein in cell-free extracts from wheat embryo. S-100 protein was absent from the products of endogenous incorporation and from a reaction programmed with kidney mRNA. These results suggest that S-100 protein mRNA contains a poly(adenylic acid) sequence and rule out the necessity of a brain-specific factor for translation of -S100 protein mRNA.


Structural determination of three glycoasparagines isolated from the urine of a patient with aspartylglycosaminuria. Three different glycoasparagines have been isolated from the urine of a patient with aspartylglycosaminuria and their structures determined using sugar, amino acid and methylation analysis, enzymic degradation and measurements of the optical rotations. The structures were 2-acetamido-1-N-(4'-L-aspartyl)-2-deoxy-beta-D-glucopyranosylamine (yield 135 mg/l) beta-D-galactopyranosyl-(1 leads to 4)-2-acetamido-1-N-(4'-L-aspartyl)-2-deoxy-beta-D-glucopyranosylamine (yield 35 mg/l), and alpha-D-mannopyranosyl-(1 leads to 6)-beta-D-mannopyranosyl-(1 leads to 4)-2-acetamido-2-deoxy-beta-D-glucopyranosyl-(1 leads to 4)-2-acetamido-1-N-(4'-L-aspartyl)-2-deoxy-beta-D-glucopyranosylamine (yield 30 mg/l). The first two compounds have previously been described, whereas the third compound is different from any of the glycoasparagines isolated before.


Structure and function of rat-liver ribosomes. Modification by 2-methoxy-5-nitrotropone treatment. Rat liver ribosomes and 60-S ribosome subunits were treated with the primary-amino-group-specific reagent 2-methoxy-5-nitrotropone. Important differences in the sensitivity of several ribosomal activities to inactivation by the reagent were observed. While elongation-factor-dependent activities are totally abolished in the treated particles, peptidyl transferase activity is either unaffected in 60-S ribosomal subunits or even strongly stimulated in 80-S ribosomes. Analysis of the ribosomal proteins modified by nitrotropone made it possible to draw some conclusions on their accessibility in the ribosomal structure and to relate some proteins with their involvement in the ribosome active centers. Thus, proteins L3, L13, L15 and L23 seem to be in a rather well protected position while proteins L10, L35, L37, X1 and X2 are totally exposed to the reagent. The protein accessibility also depends on the ribosome conformation, proteins L14 and L17, for instance, being sensitive in 80-S ribosomes and protected in 60-S subunits. In relation to the implication of proteins in functional centers, the data presented here together with other data obtained from protein-deficient core particles seem to indicate a possible role of proteins L21 and/or L26 in the peptidyl transferase center.


A novel pathway for the synthesis of solanidine in the isolated chloroplast from greening potatoes. Synthesis of chlorophyll always preceded the synthesis of solanine in cold-stored potatoes in the presence of dim light (30--40 lux). Isolated chloroplasts from green peelings were able to fix CO2. The evidence obtained showed a direct reduction of CO2 to formate, which was the primary product of fixation. Apart from this the chloroplasts were capable of incorporating NaH14CO3, [14C]formate, [2-14/C]glycine, [2-14C]pyruvate, [2-14C]acetate, [2-14C]mevalonate and [U-14C]serine into the solanidine moiety of the alkaloid. The intermediates in the pathway between CO2 and acetate have been identified as formate, glycine, serine and pyruvate. The localization of the enzymes involved in the reaction sequence viz. serine hydroxymethyl-transferase, and pyruvic dehydrogenase complex, in the isolated chloroplast has been established.


The keratin chains of avian scale tissue. Sequence heterogeneity and the number of scale keratin genes. The three major proteins of chick scale keratin were isolated as their S-carboxymethylated derivatives and shown to be similar or identical in molecular weight by gel filtration but to be distinct by amino acid analysis and gel electrophoresis. The major amino-terminal sequence of scale keratin chains was determined and shown to be highly homologous to the corresponding region of feather keratin chains. The carboxyl-terminal peptides of the three scale keratin fractions differed in sequence but were all homologous to the carboxyl-terminal segment of feather keratin chains. The pronounced concentration of cysteine residues at the amino-terminal and carboxyl-terminal segments suggested a similar role for these regions in both scale and feather keratin chains, namely to provide a disulphide-linked matrix to maintain the organisation of fibrils which arise from the internal hydrophobic segments of both types of chain. Analysis of a large hydrophobic segment from each of the three isolated protein fractions revealed that each was composed largely of repeating tripeptide units of the type Gly-Gly-X (where X = Phe, Leu or Tyr). At a few positions in each hydrophobic peptide, microheterogeneity was apparent in the sequences indicating that each isolated protein fraction was composed of at least three different chains each encoded by a different gene. A minimum of nine keratin genes are therefore expressed in scale tissue.


Pyridoxal 5'-phosphate and the regulation of ornithine decarboxylase activity and stability. There are two forms of ornithine decarboxylase with respect to pyridoxal 5'-phosphate (pyridoxal-P) affinity in exponentially-growing Swiss 3T3 mouse fibroblasts: form I (Km approximately 10 muM) accounts for 30% of the total activity, and form II (Km approximately 0.4 muM) the remainder. Each form of the enzyme is in rapid equilibrium with ornithine and pyridoxal-P; neither form recognizes the Schiff base between ornithine and pyridoxal-P as a substrate. Total pyridoxal-P concentrations indicate that both forms may normally be at least partially active in vivo. Upon stimulation of 3T3 cells by pituitary growth factors, form I becomes undetectable within 4 h. As total activity increases over 10-fold during this time and continues to increase thereafter, a possible conversion of form I to form II could account for this increase only if the Km change reflects other changes in preexisting enzyme. The rates of cofactor dissociation are apparently the same for each form and neither rate changes with the growth state. Since rapid equilibrium kinetics apply, the forms apparently differ in their rate of cofactor association. The half-lives of the two forms in vivo are the same in unstimulated cells when measured concurrently. Also, the half-life of total activity decreases markedly upon stimulation as form II becomes dominant. These and other observations are not consistent with pyridoxal-P serving a major protective function for the enzyme in vivo.


A comparison of some kinetic properties of soluble and bound lactate dehydrogenase isoenzymes at different temperatures. A comparison was made of some kinetic properties of three chicken lactate dehydrogenase isoenzymes (1, 3 and 5) at 4, 16, 23 and 40 degrees C. Assays were performed with an enzyme concentration of 0.01 muM at pH 6.0. Under the conditions of assay, lactate dehydrogenase 3 and 5 bound to the particulate fraction of homogenized skeletal muscle and were evaluated in the soluble and particulate state. Binding of isoenzymes 3 and5 to the cellular particulate fraction decreased V. This decrease was much greater for lactate dehydrogenase 5 and 3. Values of V for lactate dehydrogenase isoenzymes 1 and 3 did not follow a simple Arrhenius relationship; there was a rapid change in activity between 16 and 23 degrees C. The apparent Km (pyruvate) values of all isoenzymes (bound or soluble) increased with increasing temperature, changing 4--10-fold. The apparent Km for lactate dehydrogenase 5 was greater than that for lactate dehydrogenase 3, which in turn was greater than that for lactate dehydrogenase 1.


Structure-activity relationships in acetylcholinesterase reactions. Hydrolysis of non-ionic acetic esters. The Michaelis-Menten parameters kcat, Ks(app) and the second-order rate constants kII = k2/Ks of acetylcholinesterase-catalyzed hydrolysis of 25 acetic esters with non-ionic leaving groups have been determined at 25 degree C and pH 7.5 in 0.15 M KCL. A linear relationship between the substrate noncovalent binding capacity and the leaving group hydrophobicity, and a multiparameter correlation of the acetylation reaction rate constant logarithm with the leaving group inductive effect, hydrophobicity, and steric effect, have been established. The acetyl-enzyme deacetylation rate constant has been calculated. Taken together, a fairly complete understanding of acetylcholinesterase specificity is possible. The data are consistent with a model of the acetylcholinesterase active site, in which the catalytically active groups are located at the bottom of a jaws-like slit with a limited range of hydrophobic walls that provide the sorption of the substrate leaving groups not longer than that in n-butyl acetate.


Synthesis of a class of DNA-binding proteins in synchronized untransformed and virus-transformed cells. The synthesis of a classs of proteins with affinity for denatured DNA has been studied in synchronized cultures of the established hamster fibroblast line HIL-1 and its virus-transformed derivative NIL-1-hamster sarcoma virus. It has been found that the synthesis of a DNA-binding protein (P6, molecular weight 50 000) in synchronized untransformed NIL-1 cells follows a pattern different from that observed in the transformed cells. The protein is low in stationary cultures of NIL-1 and NIL-1-hamster sarcoma virus but increases after the cells are stimulated to grow, although the time of maximal P6 synthesis relative to cellular DNA synthesis is different in NIL-1 and NIL-1-hamster sarcoma virus. In contrast, the pattern of synthesis of two other DNA-proteins (P7 and P8') in essentially identical in synchronized untransformed and transformed cells. P7 is very low in resting cultures of both types of cells, but greatly increases early after the cells are stimulated to divide, while P8'is hish in stationary cultures and decreases slightly after the initiation of cellular DNA synthesis has occurred.


Non-equivalence of human hemoglobin chains in the oxidation-reduction and heme-transfer reactions. A 13C nuclear-Magnetic-resonance study. 12C nuclear magnetic resonance (NMR) spectroscopy has been applied to the investigation of chain non-equivalence for two reactions of human hemoglobin: oxidation-reduction and hemetransfer. The method is based on previous observations that in the carbonyl region, Hb13CO gives two well-resolved resonances which arise from 13C of carbonyls bound respectively to the alpha and beta chains; moreover, integration of spectra allows on e to estimate their relative abundance. A mixture of ferrous and ferric hemoglobins in dye-mediated oxidation-reduction equilibrium can be formally considered to be equivalent to two redox couples in equilibrium, namely alphaIII/alphaII and betaIII/betaII; from a knowledge of these ratios, one can conclude whether the chains are equivalent or not in their oxidation-reduction properties. In this work, these ratios were evaluated by reacting the redox systems with 13CO and integrating the 13C NMR spectra. The results show differences in the intrinsic oxidation-reduction potentials of the chains in hemoglobin tetramer, E1/2(beta)being higher than E1/2(alpha)in neutral solution but not at pH9 and above. The binding of inositol hexakisphosphate does not modify the difference between beta and alpha though substantially increasing the overall potential The results are discussed in the light of current hypotheses to account for the change of Hill coefficient with pH for the reaction studied. The non-equivalence of chains is shown also for heme transfer from methemoglobin. For the phosphate-free protein, the beta chains lose heme more rapidly than that alpha chains; the addition of inositol hexakisphosphate results in the decrease of overall heme transfer as well as of chain heterogeneity.


Structural studies of chicken erythrocyte histone H5. Spectroscopic studies (nuclear magnetic resonance, circular dichroism and infrared) have been carried out on chicken erythrocyte histone H5 and on  three peptides cleaved therefrom: 1-31, 32-197 and 58-197. It is shown that at ionic strengths above o.1M part of the H5 molecule takes up a globular conformation containing 14% alpha helix but no beta sheet structure. Several details of the circular dichroism and nuclear magnetic resonace spectra indicate that the globular region is located in the N-terminal half of the molecule and this proposal is supported by the observation that the peptide 32-197 is largely incapable of folding and the peptide 59-197 is completely incapable of folding. Structural similarities and differences between histone H5 and histone H1 are discussed.


Calcium regulation in heart cells. The interaction of mitochondrial and sarcoplasmic reticulum with troponin-bound calcium. A study has been carried out of the interaction of dog heart mitochondria and sarcoplasmic reticulum with Ca2+ bound to troponin or to its Ca2+-binding component (troponin-C). Both organelles are able to release more than 80% of the Ca2+ bound to the two proteins. However, sarcoplasmic reticulum is only able to do so in the presence of oxalate, whereas mitochondria are active also in the absence of permeant Ca-complexing anions. On the other hand, calcium uptake in heart mitochondria is severely inhibited by Mg2+. The results are discussed with reference to the problem of the control of Ca2+ in heart sarcoplasm.


The structure of Artemia salina haemoglobins. A comparative characterisation of four naupliar and adult heamoglobins. Haemoglobins of Artemia salina were investigated during development and the results obtained are summarised as follows. a)A new haemoglobin (haemoglobin N) was induced de novo in the hatching nauplius, but not in the prenauplius nor in the embryo. b)Haemoglobin N seemed not to be synthesised in the adult. c)The adult contained three distinct haemoglobins (haemoglobins I, II and III) in a quantitative ratio of 1:6:3, respectively, and these haemoglobins were not detected in nauplius. d)Isoelectric points determined were 5.7,5.6,5.7, and 5.9 for haemoglobin N, I, II and III, respectively. e)All four haemoglobins contained one large polypeptide (Mr= 1.1-1.3 X 10(5)) and possibly two minir polypeptides (Mr = 8-9.5 X 10(4) and Mr = 5.4 X qo(4), respectively).


Acetyl-CoA hydrolase; activity, regulation and physiological significance of the enzyme in brown adipose tissue from hamster. 1. Acetate production in hamster brown adipose tissue is a consequence of the existence of an acetyl-CoA hydrolase. The enzyme is soluble and is localised to the mitochondrial matrix. 2. Acetyl-CoA hydrolase has an apparent Km for acetyl-CoA of 51 muM and a specific activity at 30 degrees C of 870 nmol of acetate formed/min per mg 100 000 X g supernatant protein. 3. The enzyme is noncompetitively activated by ADP and inhibited by NADH and the effect of these nucleotides may well serve to regulate the enzyme activity in vivo. 4. A strong product inhibition by CoA is observed. The inhibition is of S-linear-I-hyperbolic noncompetitive nature. 5. The hydrolase has a q10 of 2.0, which represents a 7.3% change in the rat of acetate production per degrees C. The energy of activation is 12,200 cal/mol (53905 J/mol). 6. The regulatory role of acetyl-CoA hydrolase for fatty acid oxidation in brown adipose tissue of the hamster (a hibernator) at low as well as at normal body temperature is discussed.


Solubilization of the chromatin-bound estrogen receptor from chicken liver and fractionation on hydroxylapatite. 1. High-affinity estrogen-binding sites can be solubilized from the liver chromatin of estrogenized chickens by treatment of the chromatin with 2 M KCL/5 M urea and fractionation on hydroxylapatite. Two estrogen-binding proteins are eluted from hydroxylapatite columns by 20mM phosphate (binding protein I) and 200mMphosphate (binding protein II), respectively. 2. The binding protein I is part of a non-histone protein fraction containing acid-soluble and insoluble proteins, whereas the binding protein II elutes together with high molecular weight nonhistone proteins containing acid insoluble proteins only. Both binding proteins exhibit the smae affinity for estradiol (Kd approximately 10(-9) M). 3. From chromatin of untreated chickens very small amounts of binding protein I (0.1 pmol/mg protein compared to 1.9 pmol/mg protein from estrogenized chickens) with the smae affinity for estradiol as that from estrogenized animals can be solubilized. Binding protein II is not detectable. 4. The "soluble nuclear estrogen receptor" extracted from crude liver nucleir of estrogenized chickens by 0.5 M KCL behaves on hydroxylapatite very similarly to salt/urea-dissociated chromatin with respect to the binding protein I. No binding protein II, however, can be demonstrated. 5. Chromatography of various preparations on Bio-Gel A-1.5 m indicates that the binding protein II is a residual chromatin fragment containing an unseparated binding protein-DNA complex, whereas the binding protein I represents the solubilized nucleic-acid-free chromosomal estrogen receptor. The "soluble nuclear receptor" and the binding protein I, however, are not identical with respect to their chromatographic behaviour on Bio-Gel A-1.5m, even though their estrogen binding entity remaining after trypsin treatment seems to be very similar.


Functional identity of the monomeric and multiple forms of elongation-factor 1 from Krebs-II mouse ascites-tumor cells. Highly purified 3H-labelled elongation factor 1 (EF-1) from Krebs II mouse ascites tumour cells was separated into biologically active monomeric and aggregate forms of the enzyme by either gradient centrifugation or gel filtration. When corrected for their content of inactive enzyme both forms of the factor were found to be equally active whether tested in the binding or synthesis reaction. The only form of the enzyme found bound to ribosomes was the monomer; it was therefore concluded that the aggregate form of the enzyme must first dissociate before it reacts with the ribosome. The stoichiometry of the aminoacyl-tRNA binding reaction to ribosomes in the presence of guanosine nucleotides was also studied. It was found that one molecule of aminoacyl-tRNA and of Guo-5'-P2-CH2-P is bound per molecule of EF-1 bound to the ribosome. Following interaction with a release from, the ribosomes, EF-1 was found to be predominantly monomeric.


The kinetics in vivo of the synthesis of albumin-like protein and albumin in rats. The incorporation of radioactivity into total protein, albumin-like protein and albumin in liver and into total protein and albumin in blood plasma, was studied for a time period of 2 h after intraportal injection of L-[1-14C]leucine. 1. In the liver, radioactivity began to increase in albumin-like protein before 2.5 min and in albumin at about 10 min after injection. In the plasma, radioactive albumin appeared at about 15 min. No albumin-like protein could be detected in the plasma. 2. Maximum radioactivity was reached first in albumin-like protein, then in hepatic albumin and finally in albumin in the blood-stream. The maximum specific radioactivity of albumin-like protein was 15 times higher than that of extravascular hepatic albumin which, in turn, was 6 times higher than that of plasma albumin. 3. The increase of radioactivity in albumin in the blood corresponded almost quantitatively to the decrease of radioactivity in albumin-like protein. 4. It is concluded that the albumin-like protein is the precursor of albumin in vivo. It is converted into albumin 5-6 min before the appearance of newly synthesized albumin in the blood-stream.


The amino-acid sequence of the alpha-crystallin A chains of red kangaroo and Virginia opossum. The amino acid sequence of the A chain of the eye lens protein alpha-crystallin from the red kangaroo (Macropus rufus) was completely determined by manual Edman degradation of tryptic, thermolytic and cyanogen bromide peptides. The sequence of the alpha-crystallin A chain from the Virginia opossum (Didelphis marsupialis) was deduced from amino acid analyses and partial Edman degradation of peptides. The 173-residue A chains of kangaroo and opossum differ in six positions, whereas comparison with the bovine alpha-crystallin A chain reveals 17 and 22 substitutions, respectively. Most substitutions occur in the COOH-terminal part of the chain.


Hamster brown-adipose-tissue mitochondria. The role of fatty acids in the control of the proton conductance of the inner membrane. The specific ability of fatty acids to increase the proton conductance of the inner membrane of mitochondria from the liver and brown adipose tissue of cold-adapted hamsters was compared. The liver and brown-adipose-tissue mitochondria had their effective proton conductances increased by respectively 0.028 and 0.94 nmol H+- min-1. (mV of proton electrochemical gradient)-1 for each nmol of palmitate bound. No difference could be detected between the abilities of liver and brown-adipose-tissue mitochondria to bind fatty acids. Purine nucleotides did not displace farry acids from the brown-adipase-tissue mitochondria. The endogenous fatty acid content of hamster brown-adipose-tissue mitochondria prepared in the absence of album was found to be equivalent to 17 +/-  7 nmol of palmitate/mg protein. The fatty acid content was reduced to 1 nmol/mg after preincubation of the mitochondria with CoA, ATP and carnitine. No inert pool of fatty acids could be detected. The endogenous fatty acids of hamster liver mitochondria were less than 4 nmol of palmitate equivalent/mg protein. Some of the fatty acid associated with the brown-adipose-tissue mitochondria originates during preparation of the mitochondria. In the light of these results, the physiological role of the fatty acids in controlling the proton conductance of the brown-adipose-tissue mitochondrial inner membrane, and hence- non-shivering thermogenesis, is re-evaluated.


Messenger RNA translation in the presence of homologous and heterologous tRNA. The effect of tRNA distribution in the cell on the rate of specific protein synthesis has been investigated. A tRNA-dependent cell-free protein-synthesizing system derived from Krebs-II ascites cells has been worked out. In this system it is possible to synthesize specific proteins (egg-white proteins or globin) by the translation of oviduct or reticulocyte messenger RNA in the presence of tRNA from homologous or heterologous tissues. The rate of translation of a give messenger RNA is optimal in the presence of tRNA from the homologous tissue. The lower level of protein synthesis obtained with an excess of heterologous tRNA can be overcome by adding the homologous tRNA. Nevertheless homologous isoaccepting species partly purified by a reversed-phase chromatography or a benzoylated DEAE-cellulose column cannot fully restore the optimal synthesis, eliminating the hypothesis according to which a particular tRNA species is involved in this phenomenon. The correct distribution of tRNA is necessary for optimal translation of a messenger RNA.


Isolation and chracterization of rat-lens messenger RNAs. Comparison of lens proteins, synthesized in lens culture and in homologous and heterologous cell-free systems. Messenger RNA has been isolated from rat lens tissue. The mRNA species which codes for the A2 chain of alpha-crystallin, revealed the same extremely high sedimentation value (14S) as the corresponding messenger from calf lens. However, it has been shown that in rat lens the 14-S messenger preparation directs the synthesis of an additional alpha-crystallin chain, designated as alpha-X with an approximate molecular weight of 24000. For comparative purpose crystallin synthesis has also been studied as well in cultured rat lens cells as in the rat lens cell-free system.


Identification of a membrane protein involved in mitochondrial phosphate transport. A specific labeling by radioactive N-ethylmaleimide of a protein involved in phosphate transport was obtained by protecting one of the two-SH-groups of the transport system with low concentrations of mersalyl. Subsequently, the other free-SH groups were blocked with excess N-ethylmaleimide. Removal of mersalyl by cysteine and subsequent inbucation with labeled N-ethylmaleimide results in a "specific" binding of N-ethylmaleimide to one-SH group functionally involved in phosphate transport. The isolated inner membrane fraction of the labeled mitochondria was subjected to dodecylsulfate gel electrophoresis. The followin results were obtained. 1. The difference of the radioactivity pattern on the dodecylsulfate-polyacrylamide gel of inner membrane proteins, labeled with N-[14C]ethylmaleimide in the absence and with N-[3H-A1-ethylmaleimide in the presence of mersalyl during preincubation of mitochondria, shows only one main labeled peak. The same labeled peak is obtained from the difference of labeling after preincubation with a constant low concentration of mersalyl at 32 degrees C and at 0 degrees C. 2. The position of the labeled peak on the dodecylsulfate-polyacrylamide gel corresponds to a protein of molecular weight of 26500 +/- 800. 3. The amount of one of the two-SH groups, involved in phosphate transport, was estimated to be 30 nmol per g of mitochondrial protein.


Light-induced increase in the activity of maize plastid DNA-dependent RNA polymerase. Illumination of dark-grown maize plants induces a rapid rise in DNA-DEPENDENT RNA polymerase activity in plastids. Within 16 h illumination the enzyme activity is isolated plastids increases 3-4 fold as compared to other dark-grown plants illuminated for only 2 h. This change in activity is unaccompanied by either a quantitative rise in the amount of chloroplast RNA polymerase or qualitative changes in the purified enzyme. It is suggested that other factors may be present which interact either with the enzyme or the DNA template and that these factors are responsible for the light-induced enhancement of the RNA polymerase activity inplastids.


Isopycnic centrifugation of thyroid iodoproteins: selectivity of endocytosis. Isopycnic centrifugation in RbCl was shown to be an effective method both for evaluating the iodine content of thyroglobulin labelled in vivo and for the fractionation of thyroglobulin molecules as a function of their iodine content. Iodination and degradation of thyroid iodoproteins were studied by this method and by zonal centrifugation in sucrose density gradients. Based on these methods it was shown that iodination in vivo is a selective process, 19-S and poorly iodinated thyroglobulin having a higher reactivity toward iodine than 27-S and iodine-rich thyroglobulin. The disappearance of iodoproteins from the thyroid was evaluated by equilibrium, labelling the iodoproteins, blocking iodine incorporation with thiourea derivatives and observing (by sucrose gradient and by RbCl isopycnic centrifugation) at different times the properties of the remaining molecules. Among molecules of different size (19-S and 27-S) and among molecules of the same size (19 S) but different iodine content it was shown that reabsorption from the thyroid gland occurred at the same rate. It was concluded, therefore, that the degradative pathway is essentially a random, non-selective process. Newly iodinated (pulse-labelled) iodoproteins were degraded faster than preexisting molecules. Among the pool of those newly iodinated thyroid proteins, 27-S molecules were reabsorbed faster than 19-S molecules and iodine-rich thyroglobulin molecules were reabsorbed faster than the iodine-poor ones. Since iodination in vivo occurs as repeated pulses of iodine incorporation, it is suggested that this latter phenomenon is a regulatory mechanism which minimizes degradation of molecules which are iodine-poor and have a lower hormonal content.


Structure and synthesis of a lipid-containing bacteriophage. Purification, chemical composition, and partial sequences of the structural proteins. The four structural proteins of the lipid-containing bacteriophage PM2 have been purified by dissociation of the virus in the presence of acetic acid followed by a combination of gel filtration and ion-exchange chromatography in the presence of sodium dodecylsulfate and guanidine hydrochloride. Amino acid analyses of each of the proteins were performed and correlated with the properties and functions of the proteins. Protein I has the highest polarity and is the only water-soluble protein. Protein II has a rather high polarity and hydrophobicity index and probably interacts electrostatically and hydrophobically with the bilayer. Proteins III and IV have low polarities and possess the solubility properties of proteolipids. At least protein III and perhaps also protein IV may interact with the bilayer. No fatty acids are covalently linked to these proteins. Tryptic fingerprints showed that proteins I and II contain a high proportion of hydrophobic peptides, but especially protein I also contains a large number of hydrophilic peptides. Proteins III and IV have relatively few hydrophobic peptides despite their relatively high hydrophobicity. Protein IV has two distinct regions, as shown by partial sequence studies. Basic amino acids at the N-terminus would serve for interaction with the viral DNA, the following hydrophobic sequence might interact with protein III or with the bilayer.


Matrix-bound phosphoglucose isomerase. Formation and properties of monomers and hybrids. Dimeric phosphoglucose isomerase from rabbit muscle was immobilized by reaction with cyanogen-bromide-activated Sephrose 4B. The catalytic parameters and stability properties of the free and matrix-bound isomerases were essentially identical. Total monomerisation of the matrix-bound enzyme was achieved with 8 M urea as determined by a study in which one subunit was labelled with iodo[14C]acetate and the other with the 3H-labelled reagent. Although matrix-bound monomers were devoid of isomerase activity, they were still capable of binding the substrate. Matrix-bound monomers exhibited the ability to redimerize with soluble isomerase subunits from either rabbit or human yielding catalytically active dimers. Yeast isomerase monomers, in contrast, did not yield active hybrids with the rabbit monomers. Furthermore, soluble subunits, which had been inactivated with pyridoxal 5'-phosphate were also capable of hybridizing with and inducing catalytic activity in the matrix-bound monomers. These studies indicate the prerequisite of dimer formation for catalytic activity but the independent action of the catalytic centers of the dimer.


Effects of prolactin and progesterone on expression of casein genes. Titration of casein mRNA by hybridization with complementary DNA. Prolactin injected into pseudopregnant rabbits induced lactogenesis. Progesterone injected simultaneously considerably reduced this effect. The content of mRNA for casein in total cellular RNA and in total polysomal RNA was estimated during these two hormonal actions using a hybridization technique. The synthesis of DNA complementary to casein mRNA was carried out with mRNA obtained from polysomes immunoprecipitated with anti-casein antibody. The content of casein mRNA was determined by hybridization of this cDNA with the RNA fractions. This technique revealed that prolactin induced the synthesis of mRNA for casein whereas progresterone greatly limited this effect of prolactin. These variations of casein mRNA content are in good agreement with values previously determined by translation and with the ability of mammary gland to synthesize casein.


Formation of extracellular protein A by Staphylococcus aureus. Staphylococcus aureus contains cell wall protein A as well as extracellular protein A. The two types of protein A have very similar amino acid compositions, electrophoretic mobilities and sizes. The release of extracellular protein A from exponentially growing bacteria is dependent on protein synthesis de novo and protein A is released directly after being synthesized on the ribosomes. Bacteria in the stationary phase, however, release protein A as a result of cell lysis. Protoplasts have been isolated which produce protein A as extensively as the intact bacteria but because of the absence of of the formation of extracellular protein A is observed from cells also producing cell wall protein A.


Analysis of proteins synthesized in mitochondria of cultured mammalian cells. An assessment of current approaches and problems in interpretation. 1. The conditions which enable highly efficient utilization of [35S]methionine by cultured mammalian cells and the resolution of selectively labelled mitochondrial products are described. 2. Analysis of mitochondria purified from cells labelled in the presence or absence of inhibitors of cytoplasmic (or mitochondrial) protein synthesis indicated that about 5% of the [35S]methionine incorporated into mitochondrial proteins results from synthesis on mitoribosomes. 3. The electrophoretic profile of the detergent-solubilized proteins of mitochondrial isolated from cells which were labelled in the presence of 50 mug/ml emetine was similar to those obtained with extracts prepared by direct solbuilization of the intact cells after incorporation of label. 4. Pulse-labelling studies suggested that the components resolved by electrophoresis and autoradiography under the conditions described, apparently represent discrete and stable end products radiography under the conditions described, apparently represent discrete and stable end products of mitochondrial protein synthesis. No post-synthetic modification or degradation of these products was detected. 5. Erythromycin was found to suppress the synthesis of additional labelled products which were detected in extracts of one cell line, when analysed by procedures which normally detected only mitochondrially synthesized proteins. These additional bands were attributed to the synthetic activity of Mycoplasma.


Kinetic studies of the reactivity of the sulfhydryl groups of glyceraldehyde-3-phosphate dehydrogenase. The reaction of sulfhydryl groups of glyceraldehyde-3-phosphate dehydrogenase from rabbit and pig muscles with a large molar excess of 5,5'-dithiobis(2-nitrobenzoate) (Nbs2) shows three-phasic pseudo-first-order kinetics. Since the fastest reaction between active cysteine-149 and Nbs2 is apparently biphasic, half-of-the-sites reactivity towards Nbs2 is suggested. Further sulfhydryl groups become reactive as an effect of conformational changes in the protein molecule after formation of a mixed disulfide on cysteine-149. In the presence of 40 mM borate the reaction is biphasic only, and two sulfhydryl groups per subunit react very quickly. The bound NAD+ is only partially released even after a long reaction with Nbs2. It was demonstrated that the two NAD+ binding sites with the highest dissociation constants have no significant effect on the reaction between cysteine-149 and Nbs2.


Diffusion of dextran in concentrated solutions. A free-diffusion method has been developed for the determination of the intradiffusion coefficient ('self-diffusion coefficient') of a polymer in highly concentrated solutions. A fraction of the polymer is labelled with a small amount of light-absorbing substituent. The diffusion of this labelled species, present in low concentration, is followed in the presence of a high concentration of unlabelled material with the aid of absorption optics in the analytical ultracentrifuge. The diffusion proceeds over a boundary at which the difference in concentration of unlabelled material is varied. The average concentration of total polymer and the concentration of the labelled material are, however, constant. From theoretical considerations it is shown that by extrapolation of the diffusion coefficient so obtained to zero concentration difference of total material, the intradiffusion coefficient of the polymer at that concentration is obtained. The procedure also permits the ordinary translational diffusion coefficient to be estimated. The method has been applied to two dextran fractions with weight-average molecular weights of 19000 and 150000, which were labelled with fluorescein groups. As expected, the intradiffusion coefficient decreases with increasing polymer concentration, the decrease being more pronounced for the high-molecular-weight material. This decrease in the diffusion rate of dextran is, however, less than the corresponding decrease in the sedimentation rate which proteins with similar hydrodynamic parameters experience in dextran solutions. This agrees with the hypothesis that flexible linear polymers move through a network as chains rather than as hydrodynamic spheres. By combining measurements of the ordinary diffusion coefficient and the intradiffusion coefficient, it is possible to calculate the thermodynamic properties (as expressed by the virial expansion) of the system. This method is of particular importance in studies on concentrated solutions of high-molecular-weight polymers.


Respiratory failure and cardiac disturbances in myotonic dystrophy. Cardiopulmonary abnormalities are frequently encountered in myotonic dystrophy. We present five patients with myotonic dystrophy who entered the intensive care unit in acute respiratory failure. The possible etiologic factors of pulmonary complications are reviewed. The most important is probably aspiration pneumonia. The difficulties in the treatment of the respiratory failure are emphasezed. Myotonia of the chest muscles and diaphragm make artificial ventilation difficult. Recovery is delayed chiefly by swallowing disturbances. General anaesthesia is hazardous. Four patients presented cardiac arrhythmias and/or conduction abnormalities which were transient.


A nomogram to obtain pulmonary shuntflow (Qs/Qt). A nomogram to simplify the determination of pulmonary shunt is presented. It is based on Leigh's et al. shunt-equation (1969). The nomogram aggregates the factors which contribute most to the pulmonary shunt in acute respiratory failure. Arterial and venous oxygen saturation, Hb content, arterial oxygen tension and barometric pressure do influence strongly the result of calculated shuntflow. For the factors with little importance in the calculation (vapor pressure, mixed venous oxygen tension, alveolar-CO2 tension), international mean values are used. The shunt determined with the nomogram deviates less than 1% from the calculated values, if the range of PCO2 is between 32 and 52 mm Hg and the error does not exceed 1,5% with a PCO2 up to 82 mm Hg unless it is combined with a very low Hb and a high mixed venous saturation. By the nomogram the effect of the different parameters on the shunt can be very well illustrated. Especially mistakes in determination of the mixed venous saturation and of arterial O2 tension result in errors. Too high saturation values in mixed venous blood occur in distally located catheters due to pulmonary capillary admixtures. This contamination can be easily detected if the relationship between PVO2 and PACO2 is examined. The other source of error lies in the technical problems of PO2 determination in high ranges and is caused by escape of O2 into the PO2-electrode and O2-consumption of the blood. The end effect which the factors of O2 escape have on the accuracy of PO2 determination in high ranges is demonstrated with blood samples which have been equilibrated with different gas mixtures at different temperatures and had their PO2 measured at regular intervals. The error in PaO2 measurement can be reduced if blood-gas analyses are performed immediately or on cooled samples.


Side effects of doxapram infusion.

Side effects of doxapram infusion. Four cases are reported where patients reacted with severe restlessness, violence or hallucinations at low doses of doxapram infusion. A possible association with hepatic dysfunction is discussed. These reactions persisted long after the cessation of doxapram infusion and the various treatments used are described.


The use of tombramycin in the management of severe infections. Clinical and pharmacological data. Tobramycin was used in the treatment of 35 severe infections. Its clinical effectiveness was confirmed in broncho-pulmonary infections without septicemia and in septicemia without lung involvement. Poor results were obtained in septicemia where the initial site 9 infection was in the lungs. This antibiotic appeared as a very good antistaphylococcal agent. In vitro superiority over gentamicin against Pseudomonas was not be confirmed clinically. Tobramycin deserves to be administered initially in serious infections because of the possibility that the causative organism might be a gentamicin-resistant, tobramycin susceptible strain. Three such cases were observed in our 35 patients. This susceptibility dissociation in favor of tobramycin was demonstrated in two strains of Klebsiella and one strain of Enterobacter. A dosage regimen in patients with impaired renal function is proposed. It requires confirmation.


Retrograde atrial preexcitation following premature ventricular beats during reciprocating tachycardia in the Wolff-Parkinson-White syndrome. In 34 successive patients with Wolff-Parkinson-White syndrome premature beats were induced from the right ventricular apex during reciprocating tachycardia (RT) at progressively shorter coupling intervals. The presence of an accessory pathway was confirmed by a reduction in the atrial cycle length (A-A interval) during which the premature ventricular beat was introduced. This retrograde preexcitation occurred at a time when the His-AV node pathway was refractory; i.e. there was premature activation of the atria over a pathway other than the His-AV node. 3 patients were excluded because of unsatisfactory or unstable H-H intervals. In the remaining 31 patients with constant preceding H-H intervals, the A-A interval shortened; (a) 35-65 msec in 4 patients with right-sided pathways and normal conduction during RT and by 110 msec in a 5th patient with a right-sided pathway, in whom bundle branch block aberration persisted during RT, (b) 45 msec in the single patient with both a right-sided and a septal accessory pathway, (c) 35-65 msec in 5 patients with septal pathways, and (d) 15-35 msec in only 4/20 patients with left-sided pathways and normal conduction during RT. Left-sided ventricular premature beats were introduced in 5 patients with left-sided pathways and normal conduction in RT. In 4/5, left-sided premature beats shortened the A-A interval 40-75 msec whereas right-sided premature beats at the same coupling interval failed to do so. In the fifth case, the left-sided premature resulted in a 65 msec abbreviation of the A-A interval compared to 30 msec from the right ventricular outflow tract and 15 msec from the right ventricular apex. In 5 patients with left-sided pathways, right ventricular premature beats were introduced during RT with left bundle branch block aberration, and shortened the A-A interval 30-50 msec in all of these, whereas right-sided premature beats in 4 of the 5 during normal conduction failed to do so. This technique is useful to confirm the participation of accessory pathways in reciprocating tachycardias associated with the preexcitation syndromes, and emphasizes the importance of the site of stimulation used relative to the location of the accessory pathway. Because of the possibility of multiple accessory pathways, stimulation of the left ventricle should be performed in patients undergoing surgery for preexcitation unless the left ventricle is already inplicated by right-sided studies.


The retrograde His bundle deflection: its recognition and value in the analysis of tachyarrhythmias induced by stimulation on the T wave. Interpretation of deflections presumably retrograde His bundle in origin has to be performed in context considering the coexisting changes in simultaneously recorded intracardiac and surface leads. His bundle electrocardiography thus conceived is helpful in the analysis of the runs of ectopic beats elicited by premature ventricular stimulation during the antecedent T wave in patients without coronary artery or primary myocardial disease. Identification of AV nodal echoes within the paroxysms as well as the subsequent runs of reciprocating tachycardias, was possible in patients with and without preexcitation, although a thorough study of these cases also requires recording of coronary sinus and low lateral right atrial electrograms. The behavior of the retrograde H deflection in respect to the first extra beat following the premature QRS complex helped in excluding bundle branch reentry. The latter is improbable in patients with 'complete' bundle branch block pattern, if extra beats show a contralateral bundle branch morphology. However, in absence of bundle branch block, retrograde H deflections were not helpful in elucidating the mechanisms of pacemaker-induced intraventricular (bundle branch, fasicular or vulnerability-related) reentry.


A study of the acute electrophysiological and cardiovascular action of disopyramide in man. The acute electrophysiological and hemodynamic effects of intravenous disopyramide (1.5 mg/kg body weight) were studied in 12 patients with suspected coronary artery disease. Plasma levels of disopyramide were monitored. Disopyramide delayed conduction within the His-Purkinje system and increased the effective refractory period of the atrium. Conduction within the AV node and its refractory period, however, was not significantly altered by the drug. The corrected Q-T interval was significantly increased. Disopyramide increased systemic arterial pressure and slightly raised the left ventricular end diastolic pressure. Heart rate, cardiac and stroke index were unaltered. Peak mean levels of disopyramide were reached 5 minutes after the injection of the drug.


A new approach to simultaneous multiple unipolar and bipolar esophageal electrocardiograms, and the findings in normal sinus rhythm. A multielectrode catheter for esophageal electrocardiography, using the cardia as point of fixation and reference, was tested in 10 normal adults. The ECG configurations derived from simultaneous multiple unipolar and bipolar leads in normal sinus rhythm are delineated. The bipolar recordings are particularly informative as they demonstrate the separate depolarization of each atrium, the distribution of atrial potentials in the sagittal plane with an obligatory shift in polarity at the midatrial level, and the pattern of left atrial depolarization. No previous report seems to have compiled these distinctive features.


Prinzmetal's variant angina: clinical, angiographic and pathologic correlations in two typical cases. ECG and cinecoronary angiography of two patients with Prinzmetal's variant angina are reported. A pathologic study was performed on both. In one case, a transient luminal obstruction of the left circumflex coronary artery became apparent during selective coronary arteriography. Histologic examination of the corresponding coronary segment revealed a severe concentric atherosclerotic process with a normal-sized muscular layer, so that the angiographic transient occlusion might be attributed to an arterial spasm. In the second case no angiographic narrowings were demonstrated by cinecoronary angiography. Nevertheless, histologic examination revealed significant obstructive atherosclerotic narrowing in some coronary segments. It is suggested that atherosclerotic disease may be present also in cases with variant angina who have apparently normal coronary angiograms.


The grip test: a simple method for the assessment of left ventricular performance. 37 patients with mixed cardiac pathologies were subjected to isometric exercise (hand grip) during routine cardiac catheterization. On the basis of a simple and safe grip test it was possible to distinguish three groups of patients according to the left ventricular pressure at rest and its response to this test. Group 1 consisted of 14 patients with left ventricular end diastolic pressures remaining below 12 mm Hg both at rest and on exercise. These patients were considered to have normal left ventricular function some, even in the presence of organic heart disease. No deaths occurred in this group during the follow-up period which averaged 33.8 months. At the other extreme (Group 3) there were 12 obviously disabled patients with resting left ventricular filling pressures above 12 mm Hg rising further under isometric stress. Six of these patients (50%) died during the period of the study. (Average follow-up 21.4 months). By the application of the hand grip test, an intermediate population (Group 2) of 11 patients was discernible. These patients were able to maintain a normal cardiac reserve at rest (LVEDP less than 12 mm Hg) but not during isometric effort (LVEDP greater than 12 mm Hg). Two of these patients (18%) died during the follow up period (average 22.1 months). Assuming a pathological progression with time from groups 1-3 and in view of the different prognoses observed in the course of the long-term follow-up it would appear that the Group 2 patients should be considered more critically and offered more active management.


Familial prevalence of asymmetric septal hypertrophy. Echocardiography was used to detect the familial prevalence of asymmetric septal hypertrophy in relatives of patients with proven idiopathic hypertrophic subaortic stenosis. Idiopathic hypertrophic subaortic stenosis is only one clinical expression of a cardiomyopathic disease spectrum, including asymptomatic patients having asymmetric septal hypertrophy as a characteristic anatomic marker which can be detected by echo. The validity of previous proposed criteria to detect this marker was checked in our population. Therefore we examined normal subjects, patients with fixed left ventricular outflow obstruction (valvular aortic stenosis), and those with idiopathic hypertrophic subaortic stenosis who served as index cases. A septal thickness exceeding that of the free left ventricular posterior wall by 30% separates patients with a cardiomyopathy from those without this disease. 27 of 73 examined relatives of 14 index cases were found to have asymmetric septal hypertrophy. In those instances where information was available from the parents of the index cases, one parent was found to be affected. When the examined group is considered from a parent-child relationship (including the index case when appropriate), it included 78 children of affected single parents of which 20 males and 19 females had asymmetric septal hypertrophy. The history, clinical examination and electrocardiogram were not useful to detect the disease. The results suggest an autosomal dominant mode of inheritance of asymmetric septal hypertrophy with a high penetrance.


Effect of transducer placement on echocardiographic mitral valve systolic motion. The influence of transducer position and angulation upon the mitral systolic echo was studied in 100 presumably healthy females. Echocardiographic studies were performed from the second, third, fourth and fifth intercostal spaces (ICS). The role of the sound beam's path relative to cardiac motion was assessed by analyzing the recorded mitral valve pattern as a function of transducer orientation, independent of the absolute ICS used. With the transducer directed caudally when both mitral leaflets and left atrium were recorded, holosystolic or midsystolic posterior motion of the mitral valve leaflet echo was seen in 59% of the subjects. These patterns, recorded this way, were not related to phonocardiographic signs suggesting mitral valve prolapse. Best correlation with phonocardiographic findings was obtained when the echocardiographic examination was performed with the transducer either perpendicular to the chest in the sagittal plane, or pointing slightly cephalad ('perpendicular' position). With the transducer in 'perpendicular' position, both holosystolic and midsystolic posterior motion of the mitral systolic echo, deviating more than 2 mm from a line joining the C and D points, were highly related statistically to phonocardiographic findings suggesting mitral valve prolapse. This study demonstrates that transducer position and angulation on the chest wall are important determinants of echocardiographic appearance of mitral valve during systole. Only the 'perpendicular' transducer position should be used when analyzing echocardiograms for the presence of mitral valve prolapse.