Phase I trial of bruceantin.

Bruceantin was administered to 33 patients with advanced solid tumors or hematologic neoplasms. The schedule consisted of four weekly iv injections at one dose level followed by a 2-week "no-treatment" period; this program was repeated every 6 weeks. A total of 156 weekly injections were given over a dose range of 0.8-8.5 mg/m2. Systolic and diastolic hypotension was dose-related and dose-limiting at doses of greater than or equal to 6.0 mg/m2. Transient febrile reactions were dose-related. Gastrointestinal toxicity was commonly observed but was not dose-limiting. There was no hematologic or renal toxicity; hepatic toxicity was subclinical and reversible. Of 18 patients evaluable for antitumor response one patient with adenocarcinoma of the cervix experienced a less than 50% disease regression lasting 10 months and one patient with pleural mesothelioma experienced disease stabilization lasting 4 months. A phase II study of bruceantin is recommended at a starting dose of 5.5 mg/m2 weekly for 4 weeks as a 4-hour iv infusion repeated at 6-week intervals.


Treatment of mouse tumors with 7-con-O-methylnogarol and other analogs of the anthracycline antibiotic, nogalamycin.

The chemotherapeutic activity of analogs of the anthracycline antibiotic, nogalamycin, was investigated in the P388 and L1210 leukemias and the B16 melanoma in mice. Among the compounds tested, 7-con-O-methylnogarol was found to have superior activity. Depending on the route and schedule of administration, increases in lifespan (ILS) in excess of 100% were observed in all three tumor systems. Additional testing of 7-con-O-methylnogarol demonstrated significant activity in the murine colon 26 and colon 38 tumors and the CD8F1 mammary tumor. 7-Con-O-methylnogarol was not significantly effective against murine Lewis lung carcinoma, although ILSs of 38% and 29% were achieved in two experiments. Activity was observed against ip inoculated P388 leukemia after ip, sc, oral, and iv drug administration. 7-Con-O-methylnogarol was also highly active (ILS greater than or equal to 120%) after ip drug administration to mice with iv inoculated P388 leukemia. Significant ILS values resulted from a variety of schedules of administration against ip inoculated P388 leukemia and B16 melanoma. Experiments in which the time of single-dose administration was varied prior to the time of ip P388 leukemia inoculation showed that residual drug or bioactive drug-related materials remained in mice for 8 hours after 50 mg/kg administered ip and for 48 hours after 200 mg/kg administered sc.


Phase I study of anguidine administered weekly.

Anguidine was administered on a weekly schedule to 20 patients. Gastrointestinal and neurologic toxic effects were dose-limiting for both 4- and 8-hour infusions of anguidine. Myelosuppression was infrequent and not dose-related. Recommended starting doses for weekly anguidine are 6.0 mg/m2 for patients with normal hepatic function and 3.5 mg/m2 for patients with liver dysfunction.


Phase I study of hycanthone.

Hycanthone, an antischistosomal drug possessing activity against experimental murine tumors, was administered by 20-minute infusion daily x 5 days to 12 patients with advanced cancer to determine dose-limiting toxicity and to look for therapeutic effect. No objective responses were seen. The dose-limiting toxic effect was acute hepatitis occurring in two of four patients treated at 100 mg/m2/day x 5. Moderate nausea and vomiting occurring on treatment days was the only other toxic effect. Hycanthone was not myelosuppressive. Assay of plasma concentrations of hycanthone revealed a plasma half-life of 3-5 hours and no accumulation of drug over the 5 days of treatment.


A carcinoembryonic antigen standardization experiment for the conduct of multi-institutional clinical trials. Gastrointestinal Tumor Study Group.

The Gastrointestinal Tumor Study Group conducted a carcinoembryonic antigen standardization experiment to address the issue of reproducibility of assays performed at participating institutions and a central laboratory. Samples were drawn in quadruplicate from 37 patients, representing five participating institutions. Systematic biases were observed in four of the five institutions: two series were consistently higher and another two series were consistently lower than the corresponding central laboratory determinations. Significantly higher variations were found in three of the five series, comparing the sample variances associated with the matching assay series. Overall, the standard deviation associated with the central laboratory was one third that of the participating institutions. These results point toward the limitation of pooling multi-institutional carcinoembryonic antigen data. The use of multivariate models with parameters for institution comparison is proposed as a solution to this problem.


Phase I evaluation of a weekly schedule of anguidine. Southeastern Cancer Study Group Committee on Gastrointestinal Malignancies.

A phase I evaluation of a weekly schedule of anguidine was undertaken as an alternative to the present continuous daily schedules. The dose ranged from 1.5 to 7.5 mg/m2 given as an infusion over 3 hours. No myelosuppression was noted at any dose level. The toxic effects included nausea and vomiting, hypotension, CNS symptoms (confusion, hallucinations, and psychomotor seizures), chills, fever, and diarrhea. A dose of 5 mg/m2 of anguidine produced acceptable toxicity.


Alterations of lactate dehydrogenase isoenzymes with subacute adriamycin toxicity.

Single doses of Adriamycin (ADR) and isoproterenol in CDF rats produce significant increases in total serum lactate dehydrogenase (LDH) activity, LDH isoenzymes, and LDH-1/LDH-2 ratio. Isoproterenol produced significant increases in LDH-1, LDH-2, and LDH-3 and the LDH-1/LDH-2 ratio; ADR produced significant increases in all isoenzymes, reflecting widespread toxicity, with peak levels of total LDH, LDH isoenzymes, and LDH-1/LDH-2 ratio at 48 hours after injection. While the increased LDH-1/LDH-2 ratio may suggest myocardial leakage with ADR administration, the results are too nonspecific to conclude that the heart is the primary source of serum LDH-1 and LDH-2.


Vindesine in the treatment of esophageal carcinoma: a phase II study.

Vindesine, a new vinca alkaloid, has shown therapeutic activity in several human malignancies. A phase II study in 26 patients with squamous cell carcinoma of the esophagus was performed. Sixty percent of these patients had received prior chemotherapy. The starting dose was 3.0 mg/m2, which was escalated by 0.5 mg/m2 to a maximum of 4.5 mg/m2. Treatment was given once weekly for 7 weeks and every other week thereafter. Twenty-three patients were evaluable for response and toxicity. One complete remission (3 months), three partial remissions (5, 4, and 2+ months), and two minor responses (1.5 and 1 month) were seen. The major toxic effects were peripheral neuropathy, leukopenia, fever and myalgias, and alopecia. There was one drug-related death from leukopenia and sepsis. Vindesine has demonstrated therapeutic activity in esophageal carcinoma. Further studies with this agent are indicated.


Pulmonary hyaline membrane disease occurring in the course of VM-26 therapy.

During treatment with VM-26 a 20-year-old patient with metastatic medulloblastoma developed an acute, fulminating pulmonary illness. Open lung biopsy revealed advanced alveolar hyaline membrane formation with interstitial round cell infiltrate. This is the first reported case of podophyllotoxin-related pulmonary disease.


On the specificity and mode of action of a xylanase from Trametes hirsuta (Wulf.) Pilát.

The mode of action of the extracellular endo-(1 leads to 4)-beta-D-xylanase produced by Trametes hirsuta on a (4-0-methyl-D-glucurono)-D-xylan and a modified, essentially neutral D-xylan from white willow (Salix alba L.) has been studied. Xylotetraose and xylohexaose, together with aldotetraouronic and aldohexaouronic acids, were the main products. The acidic oligosaccharides had a 4-O-methyl-D-glucopyranosyluronic acid group attached to the non-reducing D-xylosyl end-group. The action pattern of the xylanase corresponds to that of a typical endo-enzyme that acts more readily in the middle of chain, and the specific region of its action appears to involve five D-xylosyl residues. The products of the enzymic treatment of the D-xylan have revealed a regular distribution of the 4-O-methyl-D-glucopyranosyluronic acid groups attached to the D-xylan backbone.


Conformational investigation on the bacterial polysaccharide xanthan.

The conformation of xanthan has been investigated as a function of temperature, ionic strength, and polymer concentration. A reversible transition induced by temperature is demonstrated; the melting temperature (TM) is directly correlated to the total ionic-strength and is independent of the polymer concentration. Measurements of circular dichroism show that the polysaccharide exists in a combination of only two characteristic conformations (random and ordered), regardless of the temperature and the concentrations of salt and polymer. Hydrodynamic measurements show that the hydrodynamic volume of both conformations is almost constant over the range of temperature investigated. The mechanism proposed by Morris for melting is confirmed, and a multichain process is excluded. The birefringence stability of the concentrated solutions is discussed.


Phase II study of alternating cytoreductive and cycle-active combination chemotherapy for metastatic breast cancer.

Nineteen females with metastatic breast cancer (73% with visceral disease) treated with cyclophosphamide, Adriamycin, and 5-fluorouracil (CAF) cytoreduction followed by, and then alternated with, an intensive "cycle-active" regimen were evaluable. Sixteen of the 19 (84%) patients responded to CAF prior to initiation of the cycle-active regimen, and median remission duration for CAF responders was 50 weeks. The regimen was tolerable and the remission rates and durations were at least as good as those seen with CAF alone. This regimen is now being compared with CAF in a randomized trial of the Southeastern Cancer Study Group.


Phase II evaluation of dianhydrogalactitol in advanced head and neck carcinomas.

Twenty-eight patients with advanced squamous cell carcinomas and adenocarcinomas of the head and neck were treated with dianhydrogalactitol at a dose of 25 mg/m2 iv on each of 5 consecutive days monthly. All patients except one had received previous surgical and/or radiotherapeutic treatments and 12 had received previous chemotherapy. Disease progression (or symptomatic deterioration) occurred in nine patients after the initial course and in eight others after two courses. In 11 patients, the disease remained stable during at least three courses; however, no instances of objective regression of disease were observed during treatment with dianhydrogalactitol despite significant toxic effects in most patients.


Partial purification and properties of a bacterial isoamylase.

Isoamylase has been prepared by affinity chromatography of a commercial enzyme-preparation from a strain of Cytophaga (also known as a Flavobacterium or Polyangium). The enzyme was not very stable, but the stability could be improved by calcium ions. The enzyme had a very low but significant activity on pullulan and on alpha-dextrins having maltosyl side-chains. This observation, which is contrary to previous reports, has been related to the specificity of isoamylase and other bacterial debranching-enzymes.


Structure of Klebsiella type 61 capsular polysaccharide.

An aldotriouronic acid was isolated from the acid hydrolyzate of the polysaccharide from Klebsiella Type 61 (K-61), and its structure was established. Degradation of the permethylated polysaccharide with base established the identity of the sugar unit preceding the glucosyluronic acid residue. The modes of linkage and the sequence of different sugar residues were further confirmed by Smith degradation of K-61. The anomeric configurations of the different sugar residues were determined by oxidation of peracetylated native, and carboxyl-reduced, polysaccharides with chromium trioxide. The anomeric configuration of nonreducing D-galactosyl side-chains was further confirmed by enzymic degradation of K-61. Finally, gentiobiose was identified in the partial, acid hydrolyzate of K-61. Based on these results, the structure assigned the repeating unit of K-61 was as follows.


Arterialization of the portal vein in cirrhosis: the findings at celiac arteriography.

An angiographic study of a new operation for portal hypertension involving arterialization of the portal vein in combination with an end-to-side portacaval shunt is described. The angiographic appearances differ from those of end-to-side shunts alone. With the new operation there is, in particular, no significant change in the wedge pressure or in the hepatic artery size from preoperative to postoperative studies, and in the majority of patients, the liver size is also unchanged. The incidence of porto-systemic shunting from the portal vein to the low pressure caval system (66%) is lower than for end-to-side shunts alone. Changes are seen in the distal portal bed in the majority of cases.


Radiologic investigation of splenic trauma.

The radiologic findings in blunt and penetrating splenic injuries are discussed with emphasis on the angiographic demonstration of these injuries. The angiographic findings are correlated with the time interval between trauma and radiologic investigation.


Percutaneous transluminal angioplasty (PTA) with the Grüntzig balloon catheter: technical problems encountered in the first forty patients.

Forty patients have undergone percutaneous transluminal angioplasty (PTA) of the iliac or femoral-popliteal system with the Grüntzig balloon catheter. Technical problems ahve included experience with difficult antegrade puncture, production of intimal flaps, and loss of collateral vessels, as well as the need to develop an approach for recanalization of obstructions and for use of the balloon. Since problems in these areas may jeopardize the success of the procedure, they have been elucidated with some discussion of prevention. Preliminary results on the success of the procedure are included.


Autotransfusion in surgical practice.

The authors have used autotransfusion of intraoperatively collected blood in 58 vascular surgery cases over a period of more than two years. The clinical results confirm the experimental and laboratory studies on the quality of the autotransfused blood. A more liberal use of intraoperative autotransfusion is advocated. Intraoperative autotransfusion is a simple, safe, inexpensive and cost-effective technique. It saves homologous banked blood and provides a readily available, compatible, normothermic transfusate with superior hematologic qualities.


Indications and use of abdominal angiography in trauma.

A series of 148 angiographic examinations in patients with blunt abdominal trauma have been reviewed. The major indications for arteriography were: (1) manifestations of shock in conjunction with clinical signs of abdominal injury; (2) the necessity for differentiation of multiple abdominal injuries; and (3) clinical signs of delayed rupture. Few false positive or false negative results were noted. The typical angiographic findings are discussed.


Anomalous venous connections involving the portal system.

Five cases representing four different venous anomalies involving the portal system are described. The clinical importance of these anomalies, especially in patients with portal hypertension, is stressed.


The place of angiography in the evaluation of traumatic injuries to the heart and coronary arteries.

The mechanisms leading to traumatic injuries of the heart and coronary arteries and the typical lesions found are analyzed in light of experience with a total of 21 cases from several centers. The indications for angiography are discussed. Early angiography may be used for the emergency verification of a valvular, coronary, or myocardial rupture after intensive treatment has stabilized the patient's condition; in such situations the relative indications for angiography versus immediate surgery must be determined. Delayed angiography may be used in the more usual situations in which clear, persistent anomalies of a clinical, electric, or radiologic nature are observed.


Right-sided cervical aortic arch associated with tetralogy of Fallot and peculiar tortuosity of the descending aorta.

A right-sided cervical aortic arch, tetralogy of Fallot, and a peculiar tortuosity of the descending aorta in which the aorta formed triple loops were diagnosed by angiocardiography in a 12-year-old girl. Histologic examination of the biopsied wall of the left subclavian artery, taken at the time of a Blalock-Taussig anastomosis, revealed no elastic-tissue defect.


Value of arteriography in the evaluation of a sonolucent pancreatic mass.

A pseudoaneurysm of the pancreaticoduodenal artery secondary to chronic pancreatitis was erroneously diagnosed as a pancreatic pseudocyst by abdominal plain films, barium gastrointestinal studies, and abdominal ultrasound. Because of the operative findings, it was necessary to interrupt surgery undertaken to drain the presumed pseudocyst. Angiography is strongly recommended as a preoperative study in patients with sonolucent pancreatic masses to distinguish pseudoaneurysms of pancreatic vessels from pseudocyts.


Thrombosis after phlebography: a comparison of two contrast media.

In two studies 267 consecutive patients with suspected leg vein thrombosis were examined by an 125I-fibrinogen uptake test (125I-FUT) and by phlebography. The ionic meglumine calcium metrizoate (Isopaque Cerebral) was used as the phlebographic contrast medium in 161 patients, and the non-ionic metrizamide (Amipaque) was used in 106. In these two groups 47 and 41 patients, respectively, had normal phlebograms as well as an initially normal 125I-FUT. After phlebography 29 (62%) of the patients who had received meglumine metrizoate had a significant rise in fibrinogen uptake, while such a rise was not found in patients examined with metrizamide. Repeat phlebography showed fresh deep-vein thrombosis in seven of the nine patients with increased uptake, indicating a complication rate of 48%. Consequently, we now use metrizamide in leg phlebogrphy; because of its expense a radioisotope test is employed as a screening procedure.


Effect of superior cervical ganglionectomy on monoamine content in the epithalamic area of the Mongolian gerbil (Meriones unguiculatus): a fluorescence histochemical study.

Extirpation of the superior cervical ganglion was performed in a series of Mongolian gerbils. One or two weeks after the ganglionectomy the animals were injected with a monoamine oxidase inhibitor. Subsequently perfusion fixation was performed using the glyoxylic acid-paraformaldehydr-magnesium method (Lorén et al., 1976) for fluorescence histochemical investigation of the monoamines of the pineal complex. In the ganglionectomized animals all of the blue-fluorescent sympathetic fibers in the pineal complex (superficial pineal gland, deep pineal gland and the pineal stalk) completely disappeared. The yellow indolamine fluorescence of the cells in the superficial pineal and the deep pineal, as well as in the pineal stalk, was markedly reduced after ganglionectomy. No change in the morphology or number of sympathetic fibers in the medial habenular nucleus was observed. These results indicate that the presence of sympathetic nerve fibers with perikarya in the superior cervical ganglion is necessary for maintaining a high indolamine content in all three parts of the pineal complex. In addition, the results also indicate that the deep pineal gland is a functional part of the pineal complex. The presence of a functionally active deep pineal, bordering the pineal recess, suggests that part of the pineal hormones might be secreted into the cerebrospinal fluid.


Association of centrioles with clusters of apical vesicles in mitotic thyroid epithelial cells. Are centrioles involved in directing secretion?

The ultrastructure of thyroid epithelial cells in mitosis has been investigated. A spatial association is described between clusters of apical vesicles (believed to contain thyroglobulin destined for secretion into the follicular lumen) and centrioles, in late prophase and late telophase cells. Quantitative techniques demonstrate the statistical significance of this association and suggest that it is not related to proximity of the Golgi apparatus or to the location of the centriole in the cell, which changes considerably during these phases of mitosis. The physical basis for this association remains uncertain, but microtubules emanating from the pericentriolar area may be involved. In interphase cells, centrioles are located very close to the follicular lumen, where the majority of apical vesicles are also found. The association of centrioles with clusters of apical vesicles also in mitotic cells suggests that in interphase cells the apically located centrioles may serve as a focus for apical vesicles, helping to direct these secretory vesicles toward the follicular lumen and to maintain cellular polarization. Previous studies demonstrating that centrioles can act as microtubule organizing centers in interphase cells and studies linking microtubules and secretion also tend to support this hypothesis.


Scanning electron microscopic study of the freeze-fractured pineal body of the rat.

The three-dimensional ultrastructure of the pineal body of the rat is described on the basis of freeze-fractured preparations. The pineal capsule consists of irregular cells with very flat and perforated processes. Through these openings, extremely branched canaliculi, extending to almost every pineal cell, communicate with the tissue compartment outside the organ. The pericapillary spaces contain, in juxtaposition with capillaries of the fenestrated type, nerve fibers as well as a flocculent granular and filamentous material of unknown origin and chemical nature.


Granular pneumocytes and altitude: a stereological evaluation.

Stereological analysis demonstrates that the granular pneumocytes of mice native to high altitude (4660 m) are significantly larger than those of the same species (Phyllotis darwini) living at sea level. Such cells have larger nuclei and a significantly greater volume of mitochondria. There are both more and larger lamellar bodies in high altitude granular pneumocytes, resulting in about four times more surfactant per cell at high altitude.


Maturation of secretory granules in the endosalpinx one to four days post coitum in sheep.

The ultrastructure of granules in the secretory cells of the endosalpinx of 20 Merino ewes was examined on days 1, 2, 3, and 4 post coitum. Based on the different frequency of granules of different size and structure on days one to four post coitum, one can assume that the ovoid, membrane-bounded secretory granules mature in five successive stages. In stage I small, electron-lucent vesicles with a finely granulated and filamentous content become apparent, initially in the neighbourhood of the Golgi complex. In stage II the granules become larger and progressively more electron-dense by an increase of the granulated material. In stage III, the primarily granulated content forms membranes, that lie in characteristic stacks at different angles to one another, separated by electron-dense areas. This structure fragments when the granule comes to lie beneath the surface of the cell (stage IV) and opens into the lumen of the oviduct, where its content is discharged in membrane fragments or vesicles (stage V). This discharge is mainly observed shortly before the egg is transported into the uterus.


A new morphological aspect of the brush cells of the mouse gallbladder epithelium.

The brush cells of the gallbladder epithelium of the mouse have microvilli not only at their luminal border but also on their lateral surface, from the level of the nucleus to the junctional complex. The lateral microvilli radiate from the brush cell in all directions, contain a core of filaments, and penetrate up to 3 mum into the adjacent cells. The microvilli in these locations display small desmosomes at their base.


Structure of the testis in neonate and adult harp seals, Pagophilus groenlandicus.

The structure of the seminiferous tubules in neonate harp seals, Pagophilus groenlandicus, was essentially similar in one-, five- and ten-day old animals. The tubules were small in diameter, devoid of lumina and contained predominantly supportive cells. The interstitial cells in the neonates were large, numerous and highly vacuolated. They became smaller and appeared less active in the ten-day old animals compared with the one-day old seals, although they were still considerably more numerous and vacuolated than in testes taken from adult harp seals.


Long bone growth during prolonged intermittent corticosteroid treatment and subsequent rehabilitation.

Immature A/J mice were treated for up to 7 weeks intermittent doses of triamcinolone hexacetonide and were thereafter allowed to recover for 7 weeks. Qualitative and quantitative morphological measurements were performed on the epiphyseal cartilage plate and diaphyseal bone of the humerus. By the third injection significant structural changes were noted in the cartilaginous tissue followed by a complete cessation of bone growth. The hormonal inhibitory effect on long bone growth lasted throughout the experimental period. However, at the end of the recovery period the length of the humerus was 96% of the normal. In contrast, the humeral width at midshaft and the width of its medullary cavity revealed slower recovery, achieving only 80% of the control values. Following rehabilitation, the growth of experimental epiphyseal plates exceeded that of nontreated animals as their width and the number of hypertrophic chondrocytes were 131% and 125% of their controls respectively. Thus, in A/J mice (a highly susceptible inbred strain of mice) intermittent (every four days) administration of a long-acting corticosteroid hormone arrested endochondral and periosteal bone formation; the former, however, underwent full recovery following the termination of the hormonal treatment.


Hypertrophic smooth muscle. I. Size and shape of cells, occurrence of mitoses.

An extensive hypertrophy of the muscle coat develops in the small intestine of the guinea pig oral to an experimental stenosis. The profiles of smooth muscle cells become larger and irregular in shape. From the analysis of serial sections the arrangement of the muscle cells is less orderly than in control muscles. Many muscle cells are split into two or more branches over part of their length. The average cell volume is 3--4 times that of control muscle cells; the cell surface increases less dramatically and, in spite of the appearance of deep invaginations of the cell membrane, the surface-to-volume ratio falls from 1.4 to 0.8. The average cell length is only slightly increased compared with controls. Smooth muscle cells in mitosis are observed in all the hypertrophic muscles examined, in both muscle layers; in the circular musculature they occur mainly found in the middle part of the layer.


Hypertrophic smooth muscle. II. Sarcoplasmic reticulum, caveolae and mitochondria.

The cytological features of hypertrophic smooth muscle cells are investigated in the small intestine of the guinea pig in which a hypertrophy is induced by an experimental stenosis. By freeze-fracture the cell membrane appears richer in intramembrane particles than that of control muscle cells, whereas the number of caveolae per unit surface of cell membrane shows little or no change (16--19 caveolae micron-2). In the sarcoplasm there is a conspicuous increase of both smooth and rough sarcoplasmic reticulum; extent was measured by surface and by volume. Unusual forms of reticulum also appear. Mitochondria are reduced (in percentage volume) to about half the control value.


The pineal gland of the gerbil, Meriones unguiculatus. III. Morphometric analysis and fluorescence histochemistry in the intact and sympathetically denervated pineal gland.

Morphometric analytical procedures were employed to study the pineal gland of the Mongolian gerbil following superior cervical ganglionectomy (SCGX). The purpose of this study was to define the effects of sympathetic denervation on the morphology of the gland at two time periods, 0500 and 1900 h (one hour before lights-on and lights-off, respectively). Fluorescence histochemistry was employed to determine catecholamine and indoleamine content in intact and denervated pineal glands. After SCGX, the pinealocytes decrease in size, concretions are prevented from forming, and the yellow fluorescence in the gland is lost. Following denervation a depression in the volume of most of the pinealocyte organelles, i.e., SER, RER/ribosomes, free cytoplasm, mitochondria and presumptive secretory vesicles, was also observed. However, synaptic ribbons increased in volume in the gerbils that had been killed at 1900 h. It appears that the sympathetic innervation to the pineal gland is a requirement for the presumptive secretory activity of the pinealocytes.


Scanning electron microscopy of peripheral blood leukocytes of the chickens.

Polymorphonuclear leukocytes, e.g., neutrophilic granulocytes, were enriched from heparinized blood by a Ficoll-step-gradient centrifugation procedure. Scanning electron microscopy (SEM) revealed a surface morphology of narrow ridge-like profiles and small ruffles with occasional microprocesses. Mononuclear leukocytes were isolated by centrifugation over a Ficoll-Metrizoat gradient. The lymphocytes showed varying numbers of microvilli of different length, size and shape. B lymphocytes, characterized by their capability of "sheep red blood cell (SRBC)-rosette formation", displayed a similar surface morphology. Completely smooth lymphocytes, described in the literature as T lymphocytes, could not be detected, although many lymphocytes with few microprocesses were observed. Thus, SEM is not a useful tool for distinguishing between B and T lymphocytes in the peripheral blood of chickens. Monocytes were characterized by prominent membrane-like ruffles, but in some cases they closely resembled granulocytes. An influence of the various separation media on the surface morphology of the isolated cells could not be detected when compared with cells isolated by the buffy-coat method.


Synaptic connections of the nervus connectivus in the frontal ganglion of Periplaneta americana L. (Insecta). An electron microscopic and iontophoretic study.

The course of the Nervus connectivus (N.c.), its branches, and synaptic connections within the frontal ganglion (FG) were investigated electron microscopically after cobalt iontophoresis of the N.c. The subsequent treatment of ultrathin sections with Timm's method was found to be very suitable for identifying the smallest branches. In the neuropil, fibers of the N.c. form Gray-I-type synapses, but also dyads are abundant, whereby the N.c. fibers occur exclusively in postsynaptic position with neurosecretory fibers. The possible role of these relationships is discussed.


Functional organization of some auditory nuclei in the guinea fowl demonstrated by the 2-deoxyglucose technique.

The auditory pathway of the Guinea Fowl was labeled with [C14]2-deoxy-D-glucose after stimulation with pure tones, harmonic tones and species-specific calls. In addition to other auditory nuclei, which showed more or less uniform labeling with the present technique, the n. mesencephalicus lateralis dorsalis (MLD) of the midbrain, as well as field L and parts of the hyperstriatum ventrale in the telencephalon, showed a stripe-pattern of labeling after stimulation with a pure tone. The position and orientation of the tone-activated striped areas in field L, observed after stimulation with different tones, correspond to isofrequency contours obtained with microelectrode recordings. The labeling of the three congruent tonotopically organized layers of field L (L1, L2, and L3) was not uniform along the anterior-posterior axis of the field. Harmonic tones produced multiple reactive stripes each of which corresponded to the stripe characteristic of a particular harmonic presented as a pure tone. The species-specific Iambus-call labeled the tonotopic area of field L that corresponds to the frequency band with the highest energy of the call. The hyperstriatum ventrale generally showed a weaker pattern of labeling that, however, resembled the labeling in field L.


Ultrastructural and biochemical studies of the swelling of developing chick telencephalic slices.

An ultrastructural and biochemical study of the importance and localization of tissue swelling was performed on telencephalic slices of 1- and 30-day-old chicks incubated in an oxygenated or a non-oxygenated physiological medium. The swelling of slices is greater for 30-day-old chick material than for that from 1-day-old chicks. It also reaches higher values in the non-oxygenated than in the oxygenated medium. When the 30-day-old chick telencephalic slices are incubated in an oxygenated medium, swelling mainly affects astrocytes, and especially the astrocytic endfeet. When they are incubated in a non-oxygenated medium, the astrocytes and astrocytic endfeet are very swollen and in addition the swelling also affects the neurons and their organelles. Extracellular space is increased. When 1-day-old chick telencephalic slices are incubated in a non-oxygenated medium, the tissue structures are well preserved. Swelling predominantly affects astrocytes and astrocytic endfeet. Neurons are not affected and the extracellular space is reduced. However, when they are incubated in an oxygenated medium, tissue structures are greatly affected showing a high degree of disorganization. Extracellular space is greatly increased. This study thus indicates that the best incubation conditions are an oxygenated medium for 30-day-old chick telencephalic slices which are characterized by an aerobic metabolism, and a non-oxygenated medium for 1-day-old chick telencephalic slices which have a predominantly anaerobic metabolism.


Bone formation in cartilage produced by transplanted epiphyseal chondrocytes.

Chondrocytes were isolated from rat epiphyseal cartilage, cultured in vitro, and exposed to exogenous tracers which accumulated in their lysosomes. The cells were then injected into the posterior tibial muscle of animals from the same outbred strain, where they reconstructed calcifying hyaline cartilage. The mineralization of the tissue was followed by ingrowth of blood capillaries from the host bed. Macrophage-like cells surrounding the vessels phagocytized degenerated chondrocytes and unmineralized matrix, whereas multinucleated chondroclasts removed some of the mineralized cartilage matrix. Mesenchyme-like cells accompanying the invading vessels attached to the remaining septa of calcified cartilage matrix and developed into osteoblasts depositing bone matrix on the surface of these septa. The apparent lack of inherent tracer labeling of the lysosomes in the different bone cells indicate that they were derived from the host. No signs of transformation of chondrocytes into bone cells were observed. When isolated rat epiphyseal chondrocytes were injected into the wall of the hamster cheek pouch, calcifying cartilage was reconstructed without signs of subsequent ossification. Transplantation of cartilage reconstructed in the hamster into the dorsal muscles of rats was, however, followed by formation of bone by a sequence analogous to that described above. Such an osteogenetic response was also obtained when the cartilage had been devitalized before transplantation. These experiments show that calcified cartilage, developing in or grafted into an intramuscular site, is able to induce and serve as a substrate for endochondral bone formation, similar to that occurring during normal development. They further indicate that bone induction by calcified cartilage does not require the presence of living chondrocytes.


The pineal gland of the gerbil, Meriones unguiculatus. II. Morphometric analysis over a 24-hour period.

By means of morphometric analytical procedures, a diurnal rhythm in the cellular volume of gerbil pinealocytes was determined. This rhythm has been attributed primarily to a change in the cytoplasmic volume of the pinealocytes which is low during the daylight hours and increases to reach a peak during the middle of the dark period. At the ultrastructural level, six cytoplasmic components of the pinealocytes were found to exhibit a rhythm: free cytoplasm, smooth endoplasmic reticulum (SER), rough endoplasmic reticulum (RER) and ribosomes, secretory vesicles, microtubules, and mitochondria. The presumptive secretory vesicles and the microtubules reached a peak in volume one hour before lights-off. It is suggested that lights-on and lights-off both signal a decrease in size and/or number of the secretory vesicles. The SER and RER/ribosomes reached their peak volume one hour after lights-off which is interpreted as indicating a peak in indoleamine synthesis and protein synthesis, respectively. The volume of free cytoplasm exhibits two peaks; one occurs one hour before lights-off while the second peak occurs in the middle of the dark phase. It is suggested that, although part of the secretory product of the pinealocyte may be present in dense-cored vesicles, other locations could include the free cytoplasm and clear secretory vesicles.


A 3-dimensional reconstruction of the hypothalamo-neurohypophysial system of the rat. The neurons projecting to the neuro/intermediate lobe and those containing vasopressin and somatostatin.

A three-dimensional reconstruction of the rat's hypothalamo-neurohypophysial system, depicting the neurons that project to the neuro-intermediate lobe of the pituitary, has been made by using retrograde transport of horseradish peroxidase injected into the neuro-intermediate lobe and by using immunocytochemistry with antisera to vasopressin and somatostatin. The overall picture illustrates the neurons situated in the walls of a pair of ill-defined cone-shaped tunnels, the apices pointing anteriorly. Among the neuronal aggregates in the tunnel wall two, the paraventricular and forniceal nuclei, appear similar in shape but clearly separated by a gap of at least 150 micrometers. Many of the vasopressin-positive neurons lie in the same nuclear aggregates with two notable exceptions: the suprachiasmatic nucleus contains many vasopressin-positive cells but does not project to the pituitary, and the forniceal aggregate, which does project to the pituitary, contains no vasopressin-positive cells. Somatostatin-positive cells are situated close to the third ventricle and their size is intermediate between parvocellular and magnocellular. Cell counts show only half the cells in the system lying in the supraoptic and paraventricular nuclei, the rest being in "accessory nuclei".


Immuno-electron microscopical demonstration of vasopressin and oxytocin synapses in the limbic system of the rat.

The extensive distribution of exohypothalamic vasopressin or oxytocin containing nerve fibres is thought to be the anatomical basis for the involvement of these neuropeptides in central processes. Following light microscopic observations suggesting that these fibres terminate on other neurons, the present study was undertaken to demonstrate the existence of such endings in the limbic system, which is one of the main target areas for these peptides. For immunoelectron microscopy glutaraldehyde-paraformaldehyde perfused brains of male Wistar rats and Brattleboro rats, homozygous for diabetes insipidus, with and without postfixation in OsO4, were used. Post-embedding staining revealed false positive reaction product on all dense core vesicles, e.g., in the lateral septum. With pre-embedding staining, however, intense and specific reactions were observed for both vasopressin and oxytocin at their sites of production, as well as the neurohypophysis and in the extrahypothalamic limbic brain regions. In the lateral septum and habenular nucleus only vasopressin-containing synapses could be demonstrated, while in the medial nucleus of the amygdala synapses containing either vasopressin or oxytocin were observed. These peptide containing synapses do not seem to differ in any fundamental way from the classical transmitter-containing synapses in the brain.


Pigment architecture of the human telencephalic cortex. IV. Regio retrosplenialis.

Cortical lamination and parcellation of the retrosplenial region in the human brain is evaluated with the aid of frontal serial sections stained for nerve cells (15 micrometers), myelin sheaths (100 micrometers), and lipofuscin granules (800 micrometers). For the most part, the retrosplenial region is buried in the depth of the sulcus corporis callosi covering the posterior parts of the cingulate gyrus. It lies between the supracallosal derivatives of the allocortex (fascia dentata, cornu ammonis, subiculum) and the mature parietal isocortex. The region can be subdivided into five areas. The transitory periallocortical area ectosplenialis is followed by a richly differentiated proisocortical core displaying extremely externopyramidal, externoteniate, and astriate to unitostriate characteristics. The parvocellular core is averagely poor in pigment (typus clarus) and rich in myelinated fibres (typus dives). Minor structural differences allow for its subdivision into a lateral, an intermediate and a medial retrosplenial field. The accompanying area parasplenialis is adjacent to the equoteniate parietal isocortex. It is only weakly externopyramidal, externoteniate, and propebistriate. The already homotypical field shows an average pigmentation and myelin content. These structural features permit its classification as a belt area of the retrosplenial core.


Pigment architecture of the human telencephalic cortex. V. Regio anterogenualis.

Cortical lamination and parcellation of the anterogenual region in the human brain is studied in sections successively stained for nerve cells (15 micrometers), myelin sheaths (100 micrometers), and lipofuscin granules (800 micrometers). The anterogenual region covers a crescent-shaped territory in front of the genu corporis callosi. It abuts on the allocortex, i.e., the supracallosal derivatives of the cornu ammonis and subiculum on the one side, and the mature frontal isocortex on the other side. The region is divisible into four areas. The transitory unitoteniate area ectogenualis is followed by anterogenual core fields, which show an outstandingly internopyramidal and internoteniate character. Furthermore, the core is of the infraradiate type and shows only the lower band of Baillarger. It is magnocellular, generally poor in myelinated fibres (typus pauper) and rich in pigment (typus obscurus). Minor structural differences permit the distinction of the area anterogenualis simplex from the area anterogenualis magnoganglionaris. Especially in the magnoganglionic field, layer Vb is richly endowed with a large, particularly slender and pigment-laden type of pyramidal cell. Within the proisocortex this special constituent occurs only in the anterogenual region. Structural features indicate its relationship to the Betz-pyramids of the cingulate and precentral ganglionic core fields. The transitory area paragenualis can be considered a belt-area accompanying the anterogenual core. It is weakly internopyramidal and internoteniate, thereby mediating to the surrounding frontal isocortex.


An ultrastructural study of the neurosecretory canopy cell of the pond snail Lymnaea stagnalis (L.), with the use of the horseradish peroxidase tracer technique.

The paired, electrotonically coupled neurosecretory Canopy Cells (CC) of the pond snail Lymnaea stagnalis were microiontophoretically injected with horseradish peroxidase (HRP). Whole mount preparations and ultrathin sections of injected CC were studied to describe in detail the morphology of the CC, their axon tracts and neurohaemal areas. The CC release their secretory product at three different sites, viz. from the soma and from axon terminals in the intercerebral commissure and in the median lip nerve. Neural control over the CC occurs by few synapses found exclusively on the CC axon, not on the cell body. One type of "en passant" synapse was identified. Two morphologically distinct types of synapselike structures (SLS) are numerous. The site of electrotonic coupling between the two CC is most probably located in the cerebral commissure. Serial sectioning showed that the axons contact each other over more than 130 micrometers. The contact is very intimate and the axon membranes interdigitate in a complex manner. Gap junctions, which are often described as the sites of electrotonic coupling, were not found.


The retina of the phalangid, Opilio ravennae, with particular reference to arhabdomeric cells.

The retina of the phalangid, Opilio ravennae, consists of retinula cells with distal rhabdomeres, arhabdomeric cells, and sheath cells. The receptive segment of retinula cells shows a clear separation into a proximal rhabdom, organized into distinct rhabdom units formed by three or four retinula cells, and a distal rhabdom, consisting of an uninterrupted layer of contiguous rhabdomeres. One of the cells comprising a retinula unit, the so-called distal retinula cell (DRC), has two or three branches that pass laterally alongside the rhabdom, thereby separating the two or three principal retinula cells of a unit. The two morphologically distinct layers of the receptive segment differ with respect to the cellular origin of rhabdomeral microvilli: DRC-branches contribute very few microvilli to the proximal rhabdom and develop extremely large rhabdomeres in the distal rhabdom only, causing the rhabdom units to fuse. Principal retinula cells, on the other hand, comprise the majority of microvilli of the proximal rhabdom, but their rhabdomeres diminish in the distal rhabdom. It is argued that proximal and distal rhabdoms serve different functions in relation to the intensity of incident light. In animals fixed 4 h after sunset, pigment granules retreat from the distal two thirds of the receptive segment. A comparison of retinae of day- and night-adapted animals shows that there is a slight (approximately 15%) increase in the cross-sectional area of rhabdomeral microvilli in dark-adapted animals, which in volume corresponds to the loss of pigment granules from the receptive segment. The length of the receptive segment as well as the pattern and shape of rhabdom units, however, remain unchanged. Each retinula unit is associated with one arhabdomeric cell. Their cell bodies are located close to those of retinula cells, but are much smaller and do not contain pigment granules. The most remarkable feature is a long, slender distal dendrite that extends up to the base of the fused rhabdom where it increases in diameter and develops a number of lateral processes interdigitating with microvilli of the rhabdom. The most distal dendrite portion extends through the center of the fused rhabdom and has again a smooth outline. All dendrites end in the distal third of the proximal rhabdom and are never present in the layer of the contiguous distal rhabdom. Arhabdomeric cells are of essentially the same morphology in day- and night-adapted animals. They are interpreted as photoinsensitive secondary neurons involved in visual information-processing that channel current collected from retinula cells of the proximal rhabdom along the optic nerve. A comparison is made with morphological equivalents of these cells in other chelicerate species.


The effect of adenosine triphosphate, magnesium chloride and phospholipids on crystal formation in the demineralized shell-repair membrane of the snail, Helix pomatia L. An in vitro study.

The effect of adenosine triphosphate (ATP), magnesium chloride (MgCl2) and phospholipids on the calcium-binding activity and crystal formation within the decalcified shell-repair membrane of the snail, Helix pomatia, was studied in vitro. The application of ATP produced a characteristic dual effect on calcification: (1) It strongly inhibited the formation of inorganic calcium carbonate (CaCO3) crystals. (2) It stimulated the development of organic crystalline bodies and induced deposition of amorphous calcium carbonate. The demineralized shell-repair membranes became white and rigid after incubation for 7 days in the medium containing 1.0 mM ATP. The inhibitory effect of Mg2+ on CaCO3 crystal formation was diminished by reduction of the concentration of MgCl2 in the incubation solution. Thus, after incubation for only 24h, 1.0 mM MgCl2 promoted the formation of birefringent CaCO3 crystals within the repair membranes. The principal effect of phospholipids on the demineralized shell-repair membrane was stimulatory, but after application of phospholipids to the medium, the formation of crystals proceeded slowly. The very large, composite crystals that were formed within the repair membranes showed strong birefringence. In all cases the development of the crystals and the organic crystalline bodies occurred in close vicinity to the amoebocytes. The role of ATP, MgCl2 and phospholipids in the recalcification of shell-repair membrane is discussed.


Lipid yolk synthesis in a marine teleost, Blennius pholis L.

The site of lipid yolk synthesis in the marine teleost Blennius pholis L. is examined. The relative distributions of cellular organelles and inclusions in the developing oocytes are analysed by morphometric analysis, which indicates that synthesis is probably endogenous occurring in the perinuclear cytoplasm. The role of lipid yolk in this species is discussed.


Phagocytic inability of Kurloff cells in the lung and spleen of the guinea pig.

Adult female guinea pigs received subcutaneous implants of diethylstilbestrol-cholestrol pellets which produced splenomegaly and increased numbers of splenic Kurloff cells. Latex spheres subsequently injected intravenously were not phagocytized by Kurloff cells within the lungs and spleen as examined with the electron microscope. This is considered as evidence that Kurloff cells are probably not phagocytic. The origin of these cells is discussed.


Profiles of radionuclide left ventricular ejection fraction changes induced by supine bicycle exercise in normals and patients with coronary heart disease.

This paper presents the profiles of left ventricular ejection fraction (EF) during and following supine bicycle exercise in normal subjects and in patients with coronary heart disease, as well as the relationship of the described patterns to clinical parameters. Twenty normal men and 40 patients with coronary artery disease were studied using gated equilibrium radionuclide angiography (EQ-EF). In the normals, during exercise, EF increased by a mean of 25% of the resting value, with an increase of no less than 11%. The exercise-limiting symptom in patients with coronary artery disease was angina pectoris in 20 and fatique in the other 20 patients. In the angina patients, there was a mean decrease in EF of 20%, and in the other coronary artery disease patients ejection fraction change little. Only two patients with coronary artery disease increased from a normal resting value to peak exercise by more than 11%, and they had isolated right coronary lesions. An "overshoot" elevation of ejection fraction above resting levels was demonstrated following termination of exercise in most patients. The patients with a significant fall in exercise ejection fraction more frequently had abnormal exercise-induced ECG changes as well as abnormal left ventriculograms and more severe coronary artery disease at cardiac catheterization than the patients with little change in ejection fraction. We conclude that 1) normals could be separated from most patients with significant coronary artery disease in this study population; 2) ejection fraction must be measured at maximal exercise for it to have diagnostic value, since there could be normal rise before and after peak exercise and an abnormal response missed; and 3) the ejection fraction response to exercise reflects the severity of the underlying coronary artery disease. The described patterns of exercise-induced changes in left ventricular ejection fraction are important to consider when using this new technique to diagnose and evaluate patients with coronary artery disease.


Distribution and severity of coronary artery disease in 500 patients with angina pectoris.

The distribution and severity of coronary disease in 500 patients with angina pectoris and at least one area of 50% or greater reduction of luminal diameter in a major coronary artery were compared with respect to patients' age and coronary arterial pattern. The coronary arterial patterns were separated into right (360 patients), mixed (89 patients), and left (51 patients) systems, depending upon the blood supply to the inferior surface of the left ventricle. The following relationships were noted: 1) In patients with angina pectoris, the distribution and severity of coronary artery disease is similar from the third to eighth decade. 2) Coronary arterial stenoses of 50-70% of greater reduction of luminal diameter involve most frequently the proximal portion of the major vessels. Coronary artery disease is multivessel in nature in 80% of cases. In single vessel disease the left anterior descending artery is involved most frequently. 3) The left main coronary artery is moderately to severely obstructed less frequently in individuals with left (2%) as compared to right (8%) and mixed (10%) systems. Otherwise, the distribution of coronary artery disease is similar in right, mixed, and left systems. 4) Coronary artery disease is a diffuse rather than a focal process. As demonstrated by coronary arteriography, patients with coronary artery disease have smaller vessels throughout the arterial tree as compared with individuals free of evident coronary atherosclerosis.


Comparison of digital boundary detection and semi-automated analysis of left ventricular cine angiograms.

A technique has been developed to analyze automatically 35 mm left ventricular cine angiograms with an image dissector and digital computer. The analysis procedure detected the ventricular boundary and aortic valve position, then calculated the projected left ventricular area and estimated volume, and performed a polar wall motion analysis as a function of time. The automated method was compared to a semi-automated method using a technician-operated electronic cursor linked to a mini-computer. The two methods were used to analyze a set of idealized ventricular models as well as normal and abnormal angiographic data. The volumetric and wall motion data for the idealized models calculated by the two methods were equivalent (r greater than 0.99). Volumetric analysis of the patients' ventriculograms produced correlation coefficients of 0.88-0.99. Corresponding wall motion data produced correlation coefficients of 0.72-0.94. The time necessary to analyze 30 frames of cine ventriculogram was approximately 30 minutes for each method.


Low-cost comprehensive data system for cardiac patients.

Functional systems to collect, store and retrieve clinical, hemodynamic, and angiographic information are needed to serve clinical research and quality control in the cardiac laboratory. Computers are ideally suited for this application, but high investment and maintenance costs are a barrier for their wider use. A low-cost data processing and procedure reporting system was developed using a programmable calculator, a floppy disk drive, and a printer. Files have been started on 750 consecutive adult patients undergoing cardiac catheterization and angiography. Each file contains a clinical profile (CP), angiographic interpretation (Al), and hemodynamic data. CP and Al are coded according to a data base definition appropriate for patient care (procedure report) and research analysis. Data input is simplified by the use of multiple choice forms and prompts appearing on the calculator alphanumeric display. One floppy disk may hold 400 patient files. Immediate access to stored information for cross reference, computations, and statistical work is possible in all patients, a patient category, or an individual case. Stored items may be retrieved in coded form for analysis or translated into sentences to generate a multiple-copy procedure report. Follow-up information may be subsequently added to the patient file. Operation requires minimal training and little expertise in computer technology.


Fistulous communication between the left coronary artery and main pulmonary artery: a thirteen-year follow-up.

A patient with a fistula producing a 2:1 left-to-right shunt between the coronary arteries and pulmonary artery followed for 13 years is described. The patient remained asymptomatic and without significant electrocardiographic, hemodynamic, or angiographic changes. Large collateral vessels were demonstrated on initial and repeat angiographic studies. This case illustrates the natural history of coronary artery to pulmonary artery shunts and suggests that surgery may not be necessary, even in the presence of a very large communication.


Demonstration of an inadvertently created aorto-coronary venous anastomosis: evidence against the clinical effectiveness of retrograde coronary venous perfusion.

Arterilization of the coronary venous system has been suggested as a means of myocardial perfusion. We recently studied a patient with a saphenous vein aorto=coronary venous bypass graft created inadvertently during surgery intended to bypass the anterior descending artery. We selectively injected onctrast into this graft during balloon occlusion of the coronary sinus both before and after sublingual nitroglycerin. No arterial visualization was demonstrated from the vein and no evidence to suggest perfusion of the myocardium was found.


Anomalous origin of the right coronary artery from the pulmonary artery with large left-to-right shunt (anomalous right coronary artery).

A coronary arteriovenous fistula was diagnosed in a 20-year-old white male because of a continuous murmur atypically located along the left sternal border. Cardiac catheterization revealed a large left-to-right shunt, and selective coronary arteriography established the precise anatomic diagnosis. The patient was treated successfully by surgical reimplantation of the anomalous coronary artery into the aorta and ligation of its origin at the pulmonary artery. The embryological and clinical features of this anomaly are discussed, and mechanisms for its production are suggested. Attention is called to our observation of an apparent male sex predilection of this anomaly from review of the literature, in addition to the present patient. This is apparently the fourth patient with this anomaly whose condition was diagnosed antemortem by selective coronary arteriography and the fourth to have been treated by aortocoronary anastomosis providing an additive supply for both the present and the future. This is also the second case in the literature to have the transplanted right anomalous coronary artery demonstrated by selective coronary arteriography. It is likely that, with increasing use of selective coronary arteriography inthe diagnostic work-up of cardiac patients, more cases will be discovered and treated surgically.


Cardiac rhabdomyoma simulating pulmonic stenosis.

The angiographic and echocardiographic findings of a right ventricular pedunculated rhabdomyoma prolapsing through the pulmonic valve which mimicked the hypoxic spells of tetralogy of Fallot are presented. A dense mass of echoes was seen within the pulmonic valve during systole. The presence of right ventricular tumor was confirmed by angiography and surgery. The abnormal echoes were no longer seen following surgical excision of the tumor.


Catheter tip entrapment with avulsion of tip: a potential complication of percutaneous transfemoral catheterization through aortofemoral bypass grafts.

A search of the literature revealed only one report [4] of catheter tip entrapment during percutaneous transfemoral catheterization in a patient with an aortofemoral bypass graft. We present another case.


Percutaneous left heart catheterization and coronary arteriography using a femoral artery sheath.

Percutaneous left heart catheterization and coronary arteriography with a standard angiographic catheter introduced through a femoral artery sheath has been performed in over 200 patients during the past 12 months. The use of the sheath for catheter introduction and manipulation offers several advantages, including the capability of monitoring two arterial pressures with only one arterial puncture, the minimization of time in which the guidewire is intravascular, the capability of using all types of catheters from a femoral artery percutaneous approach, and, most importantly, the complete elimination of patient discomfort during catheter changes. The disadvantages of the sheath technique are relatively minor. Thus, percutaneous left heart catheterization and coronary arteriography through a femoral artery sheath can be performed safely and with relatively little trauma to the femoral artery.


Left heart catheterization and angiography via the percutaneous femoral approach using an arterial sheath.

An arterial sheath with a proximal hemostasis valve and a side-arm extension tube was used in 562 consecutive patients undergoing cardiac catheterization and angiography via the femoral approach. Serious complications were rare. There was one death, one peripheral embolism, and one episode of delayed groin hemorrhage. The incidence of minor complications, including hematoma formation, in this series compares favorably with our own and the reported experience of others using the conventional percutaneous femoral approach. The sheath technique facilitated catheter exchanges and reduced patient discomfort. In addition, femoral artery pressure could be monitored via the side arm of the sheath during the catheterization. This proved helpful during retrograde catheterization of patients with aortic stenosis, as well as in detection of damping of coronary artery catheter tip pressure during coronary arteriography and hypotension following left ventriculography. Based upon this experience, use of an arterial sheath has become our standard practice when left heart catheterization is performed via the femoral approach, and the use of several different catheters is anticipated.


Transseptal and retrograde left ventricular catheterization in patients with the stent-mounted porcine xenograft valve prosthesis in the aortic position.

Cardiac catheterization techniques for measuring the systolic pressure gradient across the stent-mounted porcine xenograft in the aortic position and accomplishing left ventriculography are described. The transseptal technique is a rapid and predictable means of entering the left ventricle but requires a highly skilled operator. Retrograde left ventricular catheterization via the femoral artery is a technique familiar to all invasive cardiologists. Usually a pitfall catheter is used. In patients with the stent-mounted procine xenograft in the aortic position, we have found the A2 Multipurpose catheter to be the fastest and most predictable means of entering the left ventricle from the groin. Potential complications of retrograde left ventricular catheterization in patients with aortic valve prostheses are discussed.


[Autochthonous amebiasis in the region of Nantes].

A retrospective study on amoebiasis observed in the central hospital in Nantes since twenty years, shows that, at least, 16 % of the intestinal cases and 1/6, 5 of 30 cases of hepatic amoebiasis are autochthonous.


[Persistence of visceral leishmaniasis in the southeast of France and recorded frequency of the disease in adults. Apropos of recent cases].

The authors report on 9 cases of mediterranean visceral leishmaniasis (Kala-Azar) collected in the south-eastern part of France in 1978. They emphasize the more frequent occurrence of this disease in adults than children. Out of the 40 cases detected in this region between January 1975 and December 1978, 22 affected adults (55 percent) moreover, Kala-Azar appears to occur particularly in adults with decreased general resistance and diagnosis may be difficult because classical clinical features are no complete.


[Hepatic involvement in Trypanosoma rhodesiense trypanosomiasis].

The authors report a clinical and biological study of 40 cases of T. rhodesiense trypanosomiasis. In 40% of cases there was a hepatomegaly, in 3 cases an ascitis, and biological abnormalities in 25% of cases. After having compared these results with other authors works (including T. rhodesiense and T. gambiense), they reached the conclusion that hepatic involvement in T. rhodesiense trypanosomiasis in frequent, leading sometimes to transient acute hepatic failure.


[Verification of a focus of urinary bilharziasis in Khemis El Khechna (ex-Fondouk)].

At focus of urinary bilharziasis of Khemis El Khechna, non inspected since 1966, the urines of 1000 children were investigated. Eggs of Schistosoma haematobium, alive for the most part, were found in 78 samples (7.8%). The authors point out the dangers of the persistence and the possible spreading of this focus.


[Efficacy of UK 4271 (oxamniquine, Pfizer) in Schistosoma mansoni bilharziasis in western Africa (parasitological and serological study of 252 children)].

This study was conducted on 252 childrens afflicted with Schistosomiasis (S. mansoni and S. haematobium) living in endemic area and treated with doses of 15 mg/kg to 60 mg/kg of Oxamniquine. During eight months, parasitologic and serologic (Indirect fluorescent antibody test) controls were continued. A single per os dose of 15 mg/kg appears best and 87% cure rates were obtained with only 12% reinfestation. Antibody studies indicate, at this dosage, an antigenic stimulation that lasts at least 8 months, thus conferring a "vaccinating" action possible to be used with large population groups. Further studies show acceptable tolerance clinically of Oxamniquine and its ineffectiveness against S. haematobium. As mentioned by others, it appears that Oxamniquine has usefulness in treatment of schistosomiasis due to S. mansoni.


[Spontaneous stercoral fistula due to oxyurids: apropos of 1 case].

A spontaneous stercoral fistula containing pinworms was observed in a patient, 35 years after an appendicectomy. The various surgical complications of oxyuriasis are reviewed, in particular, the possibilities for the parasite to traverse the intestinal wall. In the case reported here, it appears that infiltration occurred in the external wall of the caecum.


[Toxic effects of plant extracts on mosquito larvae].

Vegetable extracts prepared with 530 species belonging to 120 botanical families are biologically screened with fourth stage larvae of Aedes aegypti. About twenty species are selected. Eight species of Convolvulaceae are specially toxic.


Synthesis and preliminary antitumor evaluation of 4-(SR)-sulfido-cyclophosphamides.

Crystalline 4-(SR)-sulfidocyclophosphamides, sulfido derivatives of activated cyclophosphamide (4-hydroxycyclophosphamide), were synthesized by ozonation of cyclophosphamide and reaction of the intermediate 4-hydroxycyclophosphamide with various thiols (HSR). The products were characterized by elemental analysis, 1H NMR and IR spectroscopy, and mass spectrometry. 1H NMR and polarimetric analysis demonstrated that they consist of racemic cis-isomers that are stable in the crystalline state at room temperature. In aqueous solution these derivatives are hydrolyzed to 4-hydroxycyclophosphamide and the corresponding thiol, with half-lives ranging between 4 and 17 min at 37 degrees C and pH 7. The cytotoxicity of 4-(S-ethyl)- and 4-(S-ethanol)-sulfidocyclophosphamide against Yoshida sarcoma ascites cells and the toxicity in rats were found to be practically identical with those of activated cyclophosphamide. A preliminary evaluation of the curative effect after a single IV injection of 4-(S-ethane)- and 4-(S-ethanol)-sulfidocyclophosphamide in rats bearing Yoshida ascites sarcoma or of 4-(S-ethanol)-sulfidocyclophosphamide in nu/nu mice bearing human breast carcinoma xenografts suggested that these sulfido derivatives possess the same oncostatic efficacy as activated cyclophosphamide itself.


High-dose methotrexate: preliminary evaluation of a pharmacokinetic approach.

Clinical pharmacologic studies have been carried out in patients with head and neck tumors following 36-h continuous infusions of high-dose MTX (1.5 g/m2). The results indicated considerable variation in the amount of MTX in the blood of individual patients. To control these variations, a modified protocol was set up to try to attain the same MTX blood level in all subjects. The protocol has a pharmacokinetic basis and involves determination of the MTX kinetics in each patient. The information thus obtained allows us to compute a 36-h infusion dose so that the MTX plasma levels never exceed a threshold beyond which there is a risk of toxicity to the host. The computation is validated by taking a blood sample 6 h after the beginning of the infusion. If the MTX concentration is higher than its expected value, the infusion rate can then be immediately reduced. Analytical methods that will allow such a computation, the results of the clinical application of this pharmacokinetic approach, and some implications of such a method are discussed.


A study of visual function in the premature infant.

Within the first week of life visual tracking and pattern differentiation were tested in 34 out of 47 premature infants born between 28--34 weeks of gestation. Positive results were achieved from 30 weeks onwards. Pattern differentiation was tested as soon as infants could be taken out of the incubator. Preference could be observed from 31 weeks post-conceptional age. Both functions showed comparable maturation to full-term controls by 34 weeks gestation.


Physiological basis of visual acuity and its development in kittens.

To answer the questions, (1) Which cells in the visual system are responsible for high visual acuity and (2) Does the function of the cells which provide high visual acuity develop postnatally; single cell studies have been made in the retina, lateral geniculate nucleus (LGN) and visual cortex of cats of different ages. Sustained-X retinal ganglion cells in the area centralis (the equivalent retinal position to the human fovea) set the upper limit of visual acuity. The cellular acuity develops postnatally until it reaches the adult level at 3--4 months-of-age. The improvement of acuity is associated with an increase in the strength of the inhibitory surround mechanism of the receptive field of sustained cells in the area centralis. The maturation of cellular acuity coincides with maturation of retinal and LGN synaptic organisation and of optic nerve myelination.


Determination of 3-mercaptolactate, mercaptoacetate and N-acetylcysteine in urine by gas chromatography.

A method is described for the determination of 3-mercaptolactate, mercaptoacetate (thioglycolate) and N-acetylcysteine in urine. As these compounds are mainly excreted as their mixed disulfides with cysteine, they are first reduced to the free thiols by an insoluble polymer containing thiol groups. After purification by chromatography on an organomercurial adsorbent, the compounds are converted to benzyl derivatives by extractive alkylation and determined by gas chromatography. The identity of the compounds analyzed was verified by mass spectrometry. It was demonstrated that mercaptolactate and mercaptoacetate are almost entirely excreted as their mixed disulfides with cysteine, whereas appreciable amounts of N-acetylcyteine are present as the symmetrical disulfide and the free thiol. The urinary excretion of the compounds from healthy human beings was also studied.


Urine proteins after burn injury.

Two-dimensional immunoelectrophoresis was used to examine the proteins present in urine during the first week following burn injury. Of the "serum" proteins present in the urine some glycoproteins were found to be in different relative proportions from those observed in serum. In patients sustaining severe burns the amount of protein excreted was increased compared to patients with mild burns and to controls. alpha 1-Antichymotrypsin detected in the urine of patients with severe burns was at times seen as a twin peak. This altered peak was of slower electrophoretic mobility and may represent a polymer of the protein or a complex of the protein with some other, possibly tissue-derived, protein.


Increased catecholamine excretion after labetalol therapy: a spurious effect of drug metabolites.

Patients with essential hypertension were treated for four weeks with the alpha- and beta-adreno-receptor blocking agent labetalol. Urinary excretion of total catecholamines, metanephrine plus normetanephrine and vanillylmandelic acid was measured with various methods before and during treatment. An unidentified substance interfering with the fluorimetric method for catecholamines and the photometric assay for metanephrines caused falsely high values of those substances. Using appropriate methodology no changes of total catecholamines, metanephrine plus normetanephrine and vanillylmandelic acid excretion were found after labetalol therapy. Our findings are important in preventing errors in the diagnosis of pheochromocytoma as well as in the evaluation of the effects of labetalol on the sympathetic nervous system in man.


Changes in the visual evoked response during and after occlusion therapy for amblyopia.

The VER was studied in normal children aged 4--11 years and in 71 amblyopic children at Moorfields Eye Hospital. Changes in the VER in amblyopia are best observed with 20% contrast and small square sizes. The better eye of untreated amblyopia has a normal time-to-peak for P1 of the cortical response, while that of the amblyopic eye is delayed, the more so with poor binocular vision in partial agreement with our previous findings. We found with a high degree of significance that occlusion therapy renders the VER from the amblyopic eye more 'normal' but causes considerable delay in the VER from the covered eye, even though its visual acuity does not change. At the end of occlusion, these changes are usually reversible although not always completely in patients who have had prolonged occlusion.


Evaluation of three clinical chemical routine methods for the determination of serum uric acid, by mass fragmentography.

A mass fragmentographic method for assay of serum uric acid was developed and used as a reference method to evaluate the accuracy of different routine methods used in clinical chemistry. [1,3-15N2]Uric acid was added to the serum sample and the mixture was subjected to ion-exchange chromatography. After conversion to the tetra-trimethylsilyl derivative the purified mixture was analyzed by combined gas chromatography-mass spectrometry using a multiple ion detector. Within-series imprecision of the reference method as calculated by means of relative standard deviation was 0.6%. The small difference between calculated and found value obtained in different recovery experiments could be explained by this degree of imprecision. In a comparison between results obtained with the reference method and different routine methods, a significant difference was observed only when using an uricase-oxygen consumption method.


Binocular reflexes in the first 6 months of life: preliminary results of a study of normal infants.

The development of the binocular reflexes during the first 6 months of life was studied in 38 normal infants. Preliminary results indicate that the following reflex is well established by 2 months, convergence by 3 months and the corrective fusion reflex by the age of 5 months.


The significance of disturbances of the motor system of the eye in low vision children.

Defects of the neuromotor system of the eye found to occur in 80% of 70 visually impaired children. The influence of such defects on the developing visual acuity is discussed. Early and intensified treatment is suggested to minimize negative effects and promote visual development.


Refractive error in Yugoslav urban children aged between 3 and 7 years.

A sample of 583 Yugoslav urban children aged between 3 and 7 years, was tested for refraction. It was found that hypermetropia decreased between the ages of 3 and 6, but increased in the seventh year confirming other studies in this area.


Hypomagnesaemia in diabetes.

The plasma magnesium (Mg) concentrations of 582 unselected diabetic outpatients and 140 control subjects were measured by atomic absorption spectrophotometry. Mean plasma Mg (+/-S.D.) was significantly lower in the diabetic patients (0.737 +/- 0.071 mmol/l) than in the control subjects (0.810 +/- 0.057 mmol/l), and 146 (25%) diabetics had values below those of all control subjects except one. Plasma Mg correlated best with clinic blood glucose concentration (r = -0.32, p less than 0.001) and other significant associations were observed with glycosuria, age, sex, insulin therapy and biguanide therapy. Although its significance is unclear, hypomagnesaemia could conceivably predispose to ischaemic heart disease in diabetes.


Glucose-oxidase electrode. Measurements of glucose in samples exhibiting high variability in oxygen content.

Measurements of glucose in samples exhibiting high variability in oxygen content present an important problem to solve for pO2 detection methods. Different solutions exist, all based on the stabilization of the pO2 sample before or during the measurement. The electrode described in this paper itself contains enough O2 to compensate for the variability of the sample oxygen content. The enzyme is cross-linked with gelatin using the bifunctional agent, glutaraldehyde. Amperometric enzyme electrodes have been constructed using these membranes. Measurements have been done by collecting the derivative in time of the signal given by the electrode for blood or plasma samples.


Visual development in successfully treated cases of congenital glaucoma.

The authors assessed visual functions in 10 children after operations for congenital glaucoma. All the children had had one or more operations previously and it was found that the visual development of the child was affected.


A quality control program to evaluate accuracy and precision of clinical chemistry determinations.

An external quality control program is described which, apart from documenting the routine performance of clinical chemistry laboratories with respect to accuracy and precision, also indicates the control efficiency of intra-laboratory quality control procedures. Participants are supplied with a large lot of stable control serum to be used in their intra-laboratory quality control program during a prolonged period of time. The statistical analysis of the submitted data consists of an analysis of variance scheme in order to separate systematic from random errors. The systematic laboratory errors are thereafter graded according to a scoring system independent of the standard deviation. The control efficiency of intra-laboratory quality control procedures is derived from a modified version of the measurability and controllability rules of Van der Grinten (1968) Stat. Neerl. 22, 43--63). Application of these rules in clinical chemistry laboratories is a first step towards a dynamic system of process deviation control. Merits of such an approach are discussed. Principles of the analysis of variance technique are dealt with. A graphical procedure to display its results is shown. Testing procedures to justify application of the analysis of variance technique are discussed and several features are illustrated.


Development of gel filtration and specific analyses of urinary carbohydrate and protein material.

Hitherto investigations into urinary carbohydrate and proteinaceous macromolecular material has largely been restricted to non-dialysable fractions. We found that this limits the investigation to less than 1% of the total material present and we present a method for direct analysis of urine without prior concentration or extraction. This method extends existing techniques allowing deeper investigation into necessary and important chemical aspects of health and disease. The method is based on gel filtration using Bio-Gel P2. Means included to overcome the observed adsorption by the gel matrix of relevant material depend on use of high ionic concentration buffers for column elution. The problems of bacterial contamination of the gel matrix are discussed and the use of presterilised urine samples is proposed to prevent contamination. The coupling of the gel filtration column to three specific automated analyses allows simultaneous determination of uronic acid, neutral sugar and proteinaceous material.


Use of immobilized enzymes in automated clinical analysis: determination of uric acid and glucose using immobilized enzymes in column form.

We studied the use of immobilized enzymes, covalently bound to alkylaminosilane derivative of porous glass, to automated clinical analysis on uric acid and glucose in blood, serum and urine. A microcolumn with an immobilized enzyme was prepared and used in an AutoAnalyzer I continuous flow system. Uricase (EC 1.7.3.3) from Candida utilis and glucose oxidase (EC 1.1.3.4) from Aspergillus niger were immobilized for the determination of uric acid and glucose, respectively. Hydrogen peroxide produced by these oxidases was colorimetrically determined using horse-radish peroxidase (EC 1.11.1.7) and a hydrogen acceptor in solution. Sensitivity and wash charactertistics of a column with immobilized enzyme, 1.5 mm of inner diameter and up to 40 mm in length, were satisfactory at an assay speed of 50 samples per hour. The results correlated well with those obtained by other well established methods utilizing the AutoAnalyzer system. The immobilized enzymes were sufficiently stable for at least two months of 2000 tests when used repeatedly. Clinical trials proved that this method is capable of replacing the soluble enzyme method, giving reliable and reproducible results at lower cost.


The frequency of patulous Eustachian tubes in pregnancy.

Two-hundred and seventy pregnant women (540 ears) were examined for patulous Eustachian tubes. The diagnosis was established by means of a Madsen Zo 70 electroacoustic impedance bridge. Nineteen of the patients were found to have patulous Eustachian tubes in 1 or both ears as evidenced by impedance variations synchronous with the respiration. Only 5 of these women had any subjective symptoms. Nine other women had symptoms, but their Eustachian tubes were closed at the time of examination. The results were related to the duration of the gestation, to oestrogen production and weight gain during pregnancy. A significant correlation was found was found between patulous Eustachian tube and elevated serum oestriol values.


Influence of lingual muscular strength on articulatory proficiency.

The purpose of this study was to examine the relationship between lingual muscular strength (LMS) and articulatory proficiency in 45 normal and 45 lisping speakers utilizing a Lingual Force Scale designed specifically for this investigation. Results revealed that lispers exhibited significantly reduced LMS as compared to their matched controls. No significant differences in LMS between males and females with lisped speech, or between normal speaking males and females were found to exist at 5 age levels. Significant positive correlations were noted between age and LMS in both groups of subjects. In light of these findings, it might be suggested that lisping should not be viewed always as a purely functional disorder of the speech musculature.


Some tuning fork tests revisited.

The Weber, Rinne and Bing tests were examined in normally hearing and hearing impaired subjects, using different techniques. The Weber test was found to be most sensitive and reliable with the tuning fork stem placed on the upper incisors. The Rinne tests showed a transition point from Rinne positive to negative at 19 dB when performed using the normal loudness comparison technique and at 24 dB with a threshold comparison technique. The Bing test with the tuning fork placed either on the mastoid or the vertex showed a transition point from Bing positive to negative at approximately 9 dB air-bone gap.


Chromosome variants and abnormalities detected in 51 married couples with repeated spontaneous abortions.

Chromosome analysis of 51 married couples with repeated spontaneous abortions revealed a normal female karyotype in all wives, whereas 39 (76.5%) husbands showed a normal Y chromosome, 10 (19.6%) a Yq+, one (1.9%) a Yqs and one (1.9%) two Y chromosomes. The high incidence of Yq+ found in this investigation correlates with previous reports and indicates that the risk of spontaneous abortions is increased when the male partner has a large Y chromosome.


Complete and partial trisomy of different segments of chromosome 8: case reports and review.

This report describes some of the clinical, chromosomal and radiological findings in three unrelated patients with trisomy 8 mosaicism syndrome (T8ms), two first cousins with trisomy 8q and a patient with trisomy 8p. On the basis of the phenotypic and cytogenetic findings seen in our six patients and those noted in previous reports, we concur with Riccardi & Crandall (1978) that most physical malformations seen in T8ms are associated with trisomy for the long arm of chromosome 8.


Frontometaphyseal dysplasia with congenital urinary tract malformations.

A 12-year-old by with unusual face and hearing loss was diagnosed as having frontometaphyseal dysplasia. He also had congenital urinary tract malformations and chronic urinary tract infection. The cranial and facial bones of the patient were studied by roentgen cephalometric analysis.


The dermatoglyphic pattern of the trisomy 9p syndrome.

This paper shows that the study of dermatoglyphics is an objective aid in the clinical diagnosis of chromosomal dysmorphic syndromes. The dermatologlyphic patterns of four patients with trisomy 9p were analyzed and compared with dermatoglyphic data from 63 published case reports on the condition. We consider that the following traits constitute the combination of dermatoglyphic patterns that is specific to trisomy 9p: an excess of arches on the fingertips and toes, a low total finger ridge count, the absence of digital triradii b and c, and the presence of zygodactylous triradii z, z' and z'', a simian crease, a single crease on the 5th finger, a hypothenar crease, a distally placed axial triradius t', a proximal or tibial arch or both on the hallux, and increased intensity of the plantar patterns. A "phantom picture" is constructed, which can be used for dermatoglyphic diagnosis of the trisomy 9p syndrome.


Positive H-Y antigen testing in a case of XY gonadal absence syndrome.

H-Y antigen testing was positive in a case of pseudohermaphroditism due to XY gonadal absence syyndrome. In conclusion, H-Y antigen may be present even in the absence of testes. Also, the syndrome could not have originated from a defect in the H-Y antigen system.


Roberts' syndrome. I. Cytological evidence for a disturbance in chromatid pairing.

In the rare developmental disorder Roberts' syndrome, prophase and metaphase chromosomes display premature sister-chromatid separation, most prominently at certain regions in which the chromatin is composed of highly reiterated base sequences. In addition, interphase nuclei present a striking distortion in their contours. The observed abnormalities are interpreted as evidence for the presence of a genetically determined disturbance affecting the normal mechanisms for pairing and disjoining of sister chromatids.


The effect of culture temperature on the kinetics of human lymphocyte stimulation by phytohaemagglutinin.

The effect of varying the culture temperature on the growth kinetics of human lymphocytes stimulated by phytohaemagglutinin (PHA) has been studied by a new method using a Coulter Channelyzer. Each of three subjects had a distinctive percentage of responding cells (P less than 0.01), greater after 22 hr culture than after 15 hr (P less than 0.05) due to continued recruitment, but these values were unmodified by variation of the culture temperature in the range 35 degrees C--39 degrees C. The incremental growth rate is the major descriptor of cellular growth and, not unexpectedly, each subject has a distinctive value (P less than 0.01) which is greater after culture for 22 hr than after 15 hr (P less than 0.05). We attribute the increase to the effect of recruitment in modifying the mean value of this parameter. These growth rates were similar at 35 degrees C and 37 degrees C (P less than 0.01), but higher at 39 degrees C (P less than 0.01). Lymphocytes cultured at 41 degrees C failed to grow satisfactorily in either the control or PHA-stimulated wells and it was obvious that cells were damaged at this temperature. Our results establish that PHA-stimulated lymphocytes grow more quickly at 39 degrees C than at 37 degrees C in the early stages of the first cell cycle, but that there is no increase in the number of responding cells at the higher temperature. The results suggest that moderate fever might have a beneficial effect on lymphocyte responses to infection.


Circulating immune complexes in IgA deficiency.

Circulating immune complexes (IC) were demonstrated in patients with serum IgA deficiency. Sixteen of thirty-one IgA deficient patients had serum IC detected by solid phase C1q radioimmunoassay for IgG class complexes. The presence of cryoglobulins (thirteen out of thirty-one patients) and increased polyethylene glycol precipitation (ten out of thirty patients) provided additional evidence for the presence of IC. Fourteen patients were asymptomatic but seven had clinical evidence of disease which could have been IC mediated: two with glomerulonephritis, three with polyarthritis, one with vasculitis and one with thyroiditis. Serum IC remained detectable in multiple samples over several months but this correlated poorly with the presence or absence of disease. Serum antibody to IgA was detected in fifteen out of thirty-one patients. There was no direct relationship between the presence of IC and the level of serum anti-IgA antibody; however, this antibody was shown to be present in the IC isolate in eight patients. It is proposed that a considerable portion of the IC load in IgA deficiency results from defective antigen exclusion at the level of the mucosa.


Suppression of immunological responses in mice by treatment with amphotericin B.

The polyene antibiotic amphotericin B (AmB) caused a marked suppression of the cell-mediated immune response in mice. Similar treatment did not effect the humoral antibody response. The immunosuppressive property of the drug was related to its ability to inhibit the manifestation rather than the induction phase of the delayed-type hypersensitivity response. In vitro AmB suppressed mitogen-induced lymphocyte proliferation. The drug seemed to act at the proliferative phase of the response. Results presented show that the T cell response was much more sensitive to the action of AmB than was the B cell response. During AmB chemotherapy consideration must be given to the immunosuppressive properties of this drug.


Circulating immune complexes in carcinoma of uterine cervix.

Circulating immune complexes were determined in the sera of forty-eight patients wital status by inhibition of rheumatoid factor (RF) maediated agglutination of IgG coated latex particles. The inhibitory activity was present in 63% of the sera from cervical cancer patients but only 13% of sera from control women contained this activity. Similarly, anticomplementary activity suggestive of the presence of immune complexes was present in 71% of sera from cancer patients and 13% of sera from control women. The incidence as well as the levels of immune complexes (IC) were higher in sera of patients with advanced stages of cancer as compared to those with Stage I cervical cancer. In addition, 95% of sera from cervical cancer patients had cryoblobulins, whereas only 20.8% sera from matched controls were positive for cryoprecipitates. All the cryoglobulins contained IgG type of immunoglobulin except one which had IgA immunoglobulins also. The complexes have not been characterized with regard to the nature of the antigen(s) present.


Immune response to syngeneic or autologous testicular cells in mice. I. Augmented delayed footpad reaction in cyclophosphamide-treated mice.

A delayed footpad reaction against syngeneic or autologous testicular cells was detected in mice of inbred C57BL/6, AKR and C3H/He strains. The reaction was only provoked to a measurable level if the immunization was preceded by treatment with cyclophosphamide (CY). Footpad reaction was strongest on day 6 after immunization and was detected in both male and female mice. It was found that the reaction was elicited not only with the immunizing antigen, but also with allogeneic or xenogeneic testicular antigen in mice immunized with syngeneic testicular cells.


Lymphocyte transformation test with rabbit liver specific lipoprotein (RLSP) in chronic active hepatitis.

Cellular sensitization to rabbit liver specific lipoprotein (RLSP) has been investigated using a lymphocyte transformation test in patients with chronic active hepatitis (CAH). A stimulation index greater than 2 was recorded in twenty out of twenty-five cases (eight of ten HBsAg positive and twelve of fiteen HBsAg negative) while values were lower than 2 in all the normal subjects. These results confirm the finding of sensitization to LSP in chronic active hepatitis irrespective of HBsAg status and show that rabbit LSP can be used as an alternative to the human antigen in the lymphocyte transformation test, and is further evidence that this liver membrane lipoprotein has antigenic determinants which have species-cross-reactivity.


Specificity of antibodies to heterologous glomerular and tubular basement membranes in BALB/c mice.

Balb/c mice were immunized with dog insoluble glomerular basement membrane (GBM) or tubular basement membrane (TBM). The titre of circulating antibodies was sequentially determined and their specificity was analysed using various soluble membrane fractions. Glomerular and tubular deposits were studied on serial biopsies by direct immunofluorescence. After elution, from whole kidneys, IgG fixation on normal mouse kidney sections was analysed by indirect immunofluorescence. The conclusions are the following: (a) after immunization with insoluble GBM, the antibodies are mainly directed against collagenous antigenic determinants shared by GBM and TBM; (b) after immunization with insoluble TBM, the antibodies are mainly directed against noncollagenous TBM-specific antigenic determinants.


Extrarenal immune complex type deposits induced by mercuric chloride in the Brown Norway rat.

It has been reported previously that HgCl2 chronically injected in the BN rat induced a biphasic renal disease. During the first stage, anti-glomerular basement membrane antibodies appeared and during the second stage, an immune-complex type glomerulonephritis was observed. In the present study, a systemic immune disease is described. During the first stage, antibasement membrane antibodies were observed in various extrarenal structures. Their localization has been found to depend mainly on the characteristics of the endothelium. During the second stage, immune-complex type deposits containing IgG and C3 were found in most vascular structures. Their localization did not apparently depend on the endothelial characteristics. Among the organs tested the lung was most often spared. The occurrence of immune complex deposits was found to depend on the dose of HgCl2 injected: deposits were absent in some high dose HgCl2-injected rats but they were very numerous in low dose HgCl2-injected rats. These deposits probably have a pthogenic role although no major histological lesion could be found. This model may help to explain immune complex type deposits in systemic diseases.


Leucoattractants enhance complement receptors on human phagocytic cells.

The N-formyl-methionyl peptides, F-Met-Leu-Phe, F-Met-Met-Phe and F-Met-Phe, when tested at differing concentrations, proportionally increased both in vitro cell locomotion and the expression of surface receptors for C3b on human peripheral blood neutrophils and monocytes. In contrast, the unformylated peptides, Met-Leu-Phe and Me-Met-Phe, had no chemotactic or complement receptor-enhancing activity at comparable concentrations. Casein and supernatants from human lymphocytes (cultured either in the presence or absence of phytohaemagglutinin), also recognized as chemotactic agents for human neutrophils and monocytes, enhanced C3b receptors on these cells in a similar dose-dependent fashion. These data, taken together with our previous findings with the eosinophil, suggest that in addition to promoting cell locomotion a further biological function of leucoattractants may be their capacity to render complement receptors more freely available thereby increasing the magnitude of adhesion of phagocytic cells to opsonized particles.


Maturation-linked expression of the Fc (IgG) receptor on developing human bone marrow and peripheral blood granulocytes.

Expression of Fc(IgG) receptors, as demonstrated by IgG-coated ox cells and heat-aggregated IgG, was assessed on normal human peripheral blood and bone marrow neutrophils and their precursors. The results indicate that Fc receptor development is confined to post-mitotic granulocytes, being primarily associated with neutrophil segmentation. Fc receptors were not detected on myeloblasts or promyelocytes. A mean value of 79% and 99% Fc positive segmented neutrophils were found in bone marrow and peripheral blood respectively. This highly significant difference (P less than 0.001) appears to represent a morphologically indistinguishable terminal maturation stage. Inhibition studies with IgG show that the neutrophil Fc receptor is inhibited by aggregated but not, in contrast to the corresponding monocyte receptor, by monomeric (7S) IgG. Applications of these findings to the in vivo function of the neutrophil in health and pathology are discussed.