betacell function during insulin or chlorpropamide treatment of maturity-onset diabetes mellitus. Maturity-onset diabetic patients usually have raised overnight-fasting plasma glucose levels associated with "normal" basal plasma insulin levels. The basal hyperglycemia is proportional to the degree of insulin deficiency. Basal insulin or C-peptide levels become subnormal if normal fasting plasma glucose levels are attained with insulin. Basal hyperglycemia is probably a compensatory response to maintain near-normal basal insulin levels. A logical therapy of maturity-onset diabetes is to produce basal normoglycemia by means of a constant basal insulin supplement, which can be provided by ultralente insulin. The reduced insulin response of diabetics to intravenous glucose is slightly increased when basal normoglycemia is established, suggesting that the high plasma glucose levels compromise beta cell function. The insulin response to meals in a mild diabetic is not affected by mild hyperglycemia but can be depleted if gross hyperglycemia occurs. Maintenance of normoglycemia then allows beta cell "recovery". In mild diabetics (c. less than 9 mmol per liter basal plasma glucose), chlorpropamide sufficiently stimulates beta cell secretion so that basal normoglycemia can be produced. The C-peptide response to meals is improved, whereas comparable reduction of the plasma glucose with insulin does not alter the meal response. Thus basal normoglycemia can be produced by "resting" beta cells with a basal insulin supplement or by stimulating them with sulfonylurea therapy.


C. parvum clinical protocols: prototypes and summary results in U. S. trials with Wellcome Coparvax. Clinical investigations utilizing Wellcome C. parvum in cancer therapy number more than one hundred in multiple institutions. Multiple diseases in various stages are being attacked by multi-modality therapy, making the role of immunotherapy very difficult to assess. Fundamental laboratory observations have suggested ways of weaving non-specific with specific immunotherapy, and these with chemotherapy and radiation to yield maximum therapeutic benefit. Current protocols include examples of the critical interactions as well as instructive information on dosing, timing and adjunctive symptomatic therapies. Several protocols will be reviewed, especially where promising clinical results are expected. Important differences between systemic and regional administration are observed.


HLA, islet cell antibodies, and types of diabetes mellitus. Insulin-dependent diabetes mellitus, in contrast to non-insulin-dependent diabetes mellitus, is associated with HLA factors B8, BW15, and B18. Recent studies have shown the association to be even stronger with HLA, DW3, and DW4 and have produced evidence for the existence of two "diabetogenic" genes predisposing to insulin-dependent diabetes in different ways. Evidence to suggest the existence of a gene--associated with DW2--that protects against the disease is accumulating. Islet cell antibodies are a feature of insulin-dependent diabetes mellitus and can be seen, in most cases, at the time of diagnosis.


Clinical immunotherapy experiences in the Southeastern Cancer Study Group. The Southeastern Cancer Study Group has been particularly interested in the use of immunological adjuvants in the treatment of melanoma and acute myelogenous leukemia. A study of chemotherapy versus chemoimmunotherapy in randomly selected patients with metastatic malignant melanoma revealed no significant increase in either complete remissions or overall survival in the group receiving chemoimmunotherapy. Preliminary results in a study involving maintenance of patients with acute myelogenous leukemia (chemotherapy versus chemoimmunotherapy) revealed suggestive but not statistically significant increases in remission duration and survival in the group receiving immunotherapy. Data from these ongoing studies and plans for new group studies are presented in this paper.


Prevalence of residual beta-cell function in insulin-dependent diabetics in relation to age at onset and duration of diabetes. The influence of the age at onset as well as the duration of disease on the prevalence of residual beta-cell function was studied in insulin-dependent diabetic patients. Two hundred and sixty-seven patients presented at an early age (10-19.9 years) and 158 patients had a late onset (30-39.9 years of age). beta-cell function was evaluated by measuring serum C-peptide immunoreactivity. Fifty-six patients (21.0 per cent) in the early-onset group and 64 (40.5 per cent) in the late-onset group had residual beta-cell function. The prevalence of residual beta-cell function was almost 100 per cent during the first two years of disease and was lower thereafter in diabetics with early onset. About 15 per cent of all patients with a duration between 15 and 35 years had residual beta-cell secretory function.


Islet function in diabetics with persistent islet cell antibodies. Seventeen (14 per cent) of 121 long-term insulin-treated diabetics were found to be positive for islet cell antibodies. Their duration of diabetes ranged between five and 45 years. Thirteen of these 17 patients were tested for the persistence of islet cell function by measurement of C-peptide. There was no detectable C-peptide in 12 patients, confirming that islet function had ceased. The significance of the persistence of islet cell antibodies in diabetes is unknown.


Lactic acidosis in biguanide-treated diabetics: a review of 330 cases. The paper presents an analysis of clinical symptoms, signs and laboratory data of 330 diabetic patients who developed lactic acidosis after having been treated with biguanides (phenformin, buformin, metformin). From the review of the literature an attempt is made to find special features that predisposed patients to develop lactic acidosis such as accompanying illnesses and additional medications, to describe the course of illness and also the factors that influenced the prognosis. Of the patients that developed lactic acidosis 50.3% died. These patients were older, they suffered more frequently from cardiovascular shock, their acidosis was more severe, the whole blood lactate concentration was higher, and the degree of renal insufficiency was more advanced. From our observations we conclude the the treatment of diabetes mellitus with biguanides should be reserved for specially selected patients.


Failure of glucagon in the treatment of alcoholic pancreatitis. Glucagon has been claimed to be an effective treatment for pancreatitis, but the studies reporting this were either uncontrolled or did not use concurrent controls, and none were double blind. To evaluate the efficacy of glucagon for alcohol-related pancreatitis, we performed a controlled, randomized, double blind study. Twenty-six patients with pancreatitis associated with alcohol ingestion received either glucagon or placebo in addition to intravenous fluids, nasogastric suction, and meperidine as needed. There were no statistically significant differences between the group which received glucagon and the group which did not in any of 12 parameters which included symptoms, signs, laboratory tests, and requests for analgesia. We conclude that glucagon in addition to conventional therapy is no better for the treatment of alcoholic pancreatitis than conventional therapy alone.


Protective effect of metronidazole in experimental ulcerative colitis. Administration of carrageenan to guinea pigs produces colonic lesions which are similar to those noted in idiopathic ulcerative colitis of human beings. This model was used to determine fecal flora changes and response to antimicrobial probes during the evolution of carrageenan-induced colitis. The results of fecal flora analysis showed that mean coliform concentrations increased from 10(2.7) to 10(7.4) per g during the initial stages of colonic ulceration. Pretreatment of carrageenan recipients with antimicrobials directed against coliforms reduced the concentrations of these organisms, but failed to attenuate the disease process. On the other hand, pretreatment with metronidazole, an antimicrobial primarily active against anaerobic bacteria, prevented carrageenan-induced colitis in a majority of animals. Delayed treatment with metronidazole until after colitis was established showed no salutory benefits. These results suggest that anaerobic bacteria play a role in the initial events of carrageenan-induced colitis in the guinea pig model.


Quantitation of antral gastrin cell populations in the dog. A method for enumerating G cells in dog antral mucosa by a fluorescent antibody technique was shown to be valid with respect to specificity and reproducibility. The state of intracellular gastrin storage does not influence G cell identification by this technique. To obtain values representative of the entire antrum, all G cells in long strips of antral mucosa must be counted. Results are best expressed as G cells per centimeter length of mucosa. Even with large mucosal samples there are considerable variations in G cell density within a single antrum. The "average" dog antrum contains about 35 million G cells. We observed as much as 2-fold range in G cell density from one dog to another. Each animal should, therefore, serve as its own control when influences on G cell populations are to be studied experimentally.


Immunoelectron cytochemical localization of motilin in human duodenal enterochromaffin cells. Two types of enterochromaffin cells can be demonstrated in the human duodenal mucosa by means of the Masson-Fontana reaction for argentaffinity applied to ultrathin sections. The 22-amino acid peptide motilin has now been localized exclusively to the duodenal type of enterochromaffin cell by immunoelectron microscopy. This cell occurs predominantly in the duodenum and upper jejunum. It is concluded that at least two types of enterochromaffin cells exist in the human gut mucosa and that they produce at least one biogenic amine as well as two peptides. Therefore they could provide a useful model for studies of the interrelationship of storage and release of amines and peptides.


Liver disease and nutrition.

Liver disease and nutrition. The liver plays a central role in the digestion, metabolism, and storage of nutrients. A deficiency of nutrients is often associated with liver disease and may be caused by decreased intake, decreased absorption, decreased storage, abnormalities in metabolism, or the increased requirements for nutrients. Alcoholism is a frequent cause of both malnutrition and liver disease, but nutritional deficiencies are also common in liver diseases not associated with alcoholism.


[Problems in paediatric gynaecology (author's transl)]. The present survey deals with the physiological development and pathological disturbances of the female genital organs in childhood. The different phases in development of the female genitals are discussed under sections on the newborn phase, the resting phase and the maturing time. Then follows a description of the most important illnesses met with in practice including various types of vulvovaginitis, tumours, genital bleeding and accidental injuries. This review could not be extended to include a description of congenital malformations and endocrinological disturbances.


Insertion sequence IS2 associated with int-constitutive mutants of bacteriophage lambda. We have examined mutations in bacteriophage lambda called int-c, which confer elevated constitutive expression on the int gene for prophage integration. One class of mutations, which map between the b538 and bio386 endpoints, does not appear to be associated with any major chromosomal modification, whereas the second class has the IS2 insertion sequence in orientation II within the region between gene int and the b538 endpoint, All int-c mutations are within gene xis, with the possible exception of int-c548, which might be located between int and xis. The present data are most consistent with the following notion: (1) the point mutations of class one inactivate the tI terminator signal of the pI-tI leader RNA for gene int and thus render int expression independent of the antiterminating action of the cII and cIII products, and (2) the second class of int-c mutants is constitutive for Int because the IS2 insertion, when strategically located between int and tI, provides a new constitutive promoter for int transciption.


Construction and characterization of new cloning vehicles. I. Ampicillin-resistant derivatives of the plasmid pMB9. In vitro recombination via restriction endonucleases and the in vivo genetic translocation of the Ap resistance (Apr) gene resulted in the construction of a new cloning vehicle, the plasmid pBR313. This vector was derived from a ColE1-like plasmid and, while it does not produce colicon E1, it still retains colicin E1 immunity. The Apr and tetracycline resistance (Tcr) markers carried in pBR313 were derived from the ampicillin transposon (TnA) of pRSF2124 and pSC101 respectively. During the construction of pBR313, the TnA component was altered and the Apr gene in pBR313 can no longer be translocated. This plasmid has a molecular weight of 5.8 Mdalton and has been characterized using thirteen restriction enzymes, six of which (EcoRI, SmaI, HpaI, HindIII, BamHI and SalI) cleave the plasmid at unique restriction sites. This allows the molecular cloning of DNA fragments generated by these six enzymes. The restriction sites for the latter three enzymes, HindIII, BamHI and SalI, are located in the Tcr gene(s). Cloning DNA fragments into these sites alters the expression of the Tcr mechanisms thus providing a selection for cells carrying recombinant plasmid molecules. An enrichment method for AprTcS cells carrying recombinant plasmid molecules is described.


Construction and characterization of new cloning vehicles. II. A multipurpose cloning system. In vitro recombination techniques were used to construct a new cloning vehicle, pBR322. This plasmid, derived from pBR313, is a relaxed replicating plasmid, does not produce and is sensitive to colicin E1, and carries resistance genes to the antibiotics ampicillin (Ap) and tetracycline (Tc). The antibiotic-resistant genes on pBR322 are not transposable. The vector pBR322 was constructed in order to have a plasmid with a single PstI site, located in the ampicillin-resistant gene (Apr), in addition to four unique restriction sites, EcoRI, HindIII, BamHI and SalI. Survival of Escherichia coli strain X1776 containing pBR313 and pBR322 as a function of thymine and diaminopimelic acid (DAP) starvation and sensitivity to bile salts was found to be equivalent to the non-plasmid containing strain. Conjugal transfer of these plasmids in bi- and triparental matings were significantly reduced or undetectable relative to the plasmid ColE1.


Enrichment for the globin coding region in a chromatin fraction from chick reticulocytes by endonuclease digestion. A nuclease-sensitive fraction was obtained from chick reticulocyte chromatin by brief digestion with an endonuclease (DNAase II, deoxyribonucleate 3'-oligonucleotidohydrolase, EC 3.1.4.6). The nuclease-sensitive fraction typically contained less than 1% of the chromatin-DNA but about 50% or more of the nascent chromatin-bound RNA. Hybridization of chick globin complementary DNA to the DNA component of the nuclease-sensitive fraction of reticulocyte chromatin indicated a 3--5 fold enrichment for the globin coding region of the chromatin. The control experiment utilizing DNA from a nuclease-sensitive fraction of chick liver chromatin did not show a comparable enrichment for the globin coding region. This suggests that the endonuclease-effected enrichment for the globin coding region in the nuclease-sensitive fraction of reticulocyte chromatin is to some degree specific for structural genes transcribed in reticulocytes.


ColE1 cloning of a ribosomal RNA promoter region from lambdarifd18 by selection for lambda integration and excision functions. The expression of the ribosomal RNA gene carried by the lambda transducing phage lambdarifd18 is shown to be subject to stringent amino acid control. lambdarifd18 DNA was digested with endonuclease EcoRI and ligated to similarly restricted ColE1 plasmid DNA. Selection for expression of lambda integration and excision gene activity carried by the same DNA fragment results in cloning of the promoter proximal portion of the 16S ribosomal RNA gene. The resulting chemera expresses lambda integration and excision functions as well as encoding the promoter proximal half of a 16S ribosomal RNA gene.


Heteroduplex mapping of small plasmids derived from R-factor R12: in vivo recombination occurs at IS1 insertion sequences. Small, autonomously replicating plasmids derived by in vivo recombination from R-factor R12 (= R100) have been structurally mapped by heteroduplex formation between the plasmids and an R-factor which is structurally closely related to R6-5. Recombination resulting in generation of the small resistance-free plasmids occurs between the (IS1)b insertion sequence and various other sites on the opposite side of an origin of replication. A larger R12-derived plasmid pSM17, carrying streptomycin (Sm), sulfadiazole (Sa), and chloramphenicol (Cm) resistances, has recombined in a similar manner but at the (IS1)a sequence. A new structural coordinate origin for R100 and for partially homologous R-factors is proposed based upon the location of the (IS1)b sequence.


Colicinogenic mutant of ColE1 plasmid that fails to confer immunity to colicin E1. Insertion of the ampicillin transposon (Tn3) into ColE1 DNAs causes various mutations in the plasmids. Escherichia coli K-12 cells carrying one of these mutants showed novel properties; they were sensitive to colicin E1 and were able to produce active colicin E1. The site and the orientation of Tn3 insertion in this mutant ColE1 DNA were determined by heteroduplex analysis and by enzymatic digestion with restriction endonucleases. The potential usefulness of this mutant ColE1 DNA as a cloning vehicle is discussed.


Current status of coliphage lambda EK2 vectors. This article summarizes the rationale behind the design of standardized laboratory tests for certification of bacteriophage lambda EK-2 vector systems. A discussion and description of the six vector systems which have been certified by the U.S. National Institutes of Health are also included. An appendix describes the officially approved laboratory tests in detail.


Isolation and characterization of transducing coliphage fd carrying a kanamycin resistance gene. The DNA segment (Tn903) with a size of 3100 nucleotide pairs which carries a gene specifying kanamycin resistance derived from a chimeric plasmid pML21 (Hershfield et al., 1976) was transposed to various sites on the filamentous phage fd DNA. Wild type fd can be restored by excision of Tn903 from the resulting hybrid DNA molecule. The fd DNA carrying Tn903 when converted to the mature phage particle, was capable of transducing the kanamycin marker, and its replicative form DNA could be maintained in a bacterial cell like a plasmid.


DNA cleavage of lambda and phi 80 transducing phages carrying the argA, argECBH, argF and argI operons of Escherichia coli K-12 with the restriction endonucleases EcoRI, SmaI and HindIII. DNA isolated from each of the seven arginine transducing phages lambdaargA2cI857susS7, phi80ppc argECBH, phi80argF, phi80argF ilambdacI857, lambdaargF2, lambdaargF23 and lambdaargI valScI857susS7 has been specifically cleaved by the restriction endonucleases EcoRI, SmaI and HindIII. The DNA fragments resulting from single, and in some cases, double endonuclease digests were separated by electrophoresis in agarose and also in polyacrylamide gel. The electrophoretic patterns thus obtained were compared with those produced by digestion of DNA isolated from the corresponding lambda and phi80 parental phages. The majority of cleavage sites produced by the action of these restriction enzymes on arginine transducing DNA have been physically mapped.


Escherichia coli antibodies in patients with inflammatory bowel disease. Sera from 30 patients with inflammatory bowel disease (IBD) (16 with Crohn's disease (CD) and 14 with ulcerative colitis (UC) were assayed for the presence of antibodies against 159 Escherichia coli O-antigens and compared with sera from 16 matched control subjects. The majority of patients with IBD had agglutinating antibodies to a higher number of Escherichia coli O-antigens and in higher titres than the control group. The number of positive agglutinins was O-33 mean 13.8 in CD, O-26 mean 7.9 for UC, and O-7 mean 1.5 in controls. Eight patients with IBD and arthropathy had antibodies to fewer O-antigens (O-7 mean 3.2). The antibodies were in the IgG and IgM, in titres corresponding to original values. No specific O-serotypes were associated with IBD. Common serotypes, R-plasmid carrying serotypes, and those associated with shigella-like adult diarrhoea were detected. O14 was detected only in five patients and O119 in none. There was no correlation between the number of Escherichia coli agglutinins and the site and severity of the disease or type of therapy. It is suggested that the presence of the high numbers of Escherichia coli antibodies is secondary to the disease process and is unlikely to be causally involved in the pathogenesis of the disease, but may play a role in the perpetuation of the disease and in the extraintestinal complications.


Effects of bran on serum cholesterol, faecal mass, fat, bile acids and neutral sterols, and biliary lipids in patients with diverticular disease of the colon. Twenty-two patients with symptomatic diverticular disease of the colon were randomly allocated to control and high-fibre groups so that the long-term effect (up to 12 months) of bran on serum, faecal and biliary lipids could be studied. Even in cases of high initial values, faecal mass was increased by bran and the change was positively correlated with the change in dietary fibre. Faecal fat and dry weight were also increased. Faecal bile acids were initially slightly raised and were positively correlated with wet weight both off and on bran. The latter significantly decreased the excretion and concentration of bile acids, in particular the high initial values. The change in bile acids was not correlated with the change in dietary fibre or faecal wet weight. Sterol balance values indicated that the bran-induced decrease in faecal bile acids was associated with a lower cholesterol synthesis. Serum cholesterol decreased significantly in two hypercholesterolaemic individuals only. Correlations between different parameters revealed that the higher the initial level or the greater the drop in cholesterol synthesis, the greater the decrease in serum cholesterol. Bran had no effect on the biliary saturation of cholesterol. The percentage of biliary deoxycholate was negatively correlated with faecal mass (less so with faecal bile acid output) both before and during bran and was significantly decreased by bran. The percentage of cholic acid increased correspondingly and that of chenodeoxycholate remained unchanged. Faecal bile acids also indicated that the synthesis of the two primary bile acids was lowered by bran to the same degree.


Effect of prolonged cimetidine therapy on gastric acid secretion in man. In a double blind trial, 23 patients with endoscopically confirmed duodenal ulceration received cimetidine (300 mg four times daily in six patients, or 400 mg four times daily in 10 patients) or placebo (seven patients) for six weeks. Before entry into the trial, pentagastrin (6 microgram.kg-1.h-1)--stimulated gastric acid secretion after a single oral dose of 300 or 400 mg cimetidine was lowered by 82.1% and 81.0%, respectively, while no significant inhibition was recorded in the patients receiving placebo (8.8%). The same test repeated after six weeks of continuous treatment showed that the effect of the drug was maintained, the percentage inhibition of acid secretion being of the same order as in the first test.


Glucagon therapy in acute pancreatitis. Report of a double-blind trial. The results of a double-blind trial of glucagon in 69 patients with acute pancreatitis are reported. In a subgroup of 59 patients statistical analysis showed no significant differences between the glucagon-treated (n = 29; 2 X 5 mg protamine-zinc glucagon intramuscularly per day) and the placebo-treated (n = 30) subjects for the following data: duration of pain left spontaneously and induced by palpation, amounts of analgesics and antispasmodics required by the patients, duration of hospital stay, amylase activities in serum and 24 hour urine collections. Mortality rates did not differ significantly between the glucagon-treated and the placebo-treated subjects in the total group of 69 patients and in the two subgroups of patients who were treated conservatively (n = 59) and those who underwent laparotomy because of severe peritonitis (n = 10). From the results of this study it is concluded that favourable effects of glucagon upon the course of acute pancreatitis--if they do exist--are not significant.


Serum level of immunoreactive gastrin: influence of kidney function. Serum gastrin levels have been studied in 70 patients with chronically reduced glomerular filtration rate (GFR) as estimated by 51Cr-EDTA clearance, creatinine, and beta2-microglobulin values. A strong dependence upon GFR was found, although the correlation between gastrin levels and GFR was not as high as that between beta2-microglobulin and GFR, indicating the existence of extrarenal factors regulating the levels of circulating gastrin. In a separate group of 31 patients on maintenance dialysis the mean gastrin level was 65.9 pmol/l--that is, a fourfold increase compared to healthy subjects. Three of the uraemic patients had pronounced rises in serum gastrin in the range 800-1800 pmol/l. Finally, the influence of acute alterations of kidney function on serum gastrin was studied in 11 patients undergoing renal transplantation. In addition to a GFR dependence the results indicate the existence of feedback mechanisms in gastrin homeostasis. Although the clinical importance of the increased gastrin levels in renal failure is unknown, hypergastrinaemia occurs with sufficient frequency to be involved in upper gastrointestinal complications of uraemic patients.


Isolation of antilymphocyte antibodies, with a solid water-insoluble not gel-like immunoadsorbent. An immunoadsorbent, consisting of a copolymer from acrylnitrile and methacrylic acid's beta-amino-ethylester as the insoluble, not gel-like carrier, 1.3-difluor-4.6-dinitrobenzene as the binding substance and isolated sheep spleen lymphocytes, is described. It may be especially useful for the preparation of "pure antibodies" to cells and greater or smaller antigenic particles. The immunoadsorbent can easily be prepared in an one-step method, it is stable, and high flow rates can be obtained in column chromatography.


Neural repair for sensory restoration in a groin flap. A preliminary study of the recovery of sensation in groin flaps, after suture of the lateral cutaneous branches of the twelfth thoracic nerve supplying the groin flap with those of the hand, is described. This appears to be a worthwhile procedure.


Eliminating the gap in flexor tendon surgery. A new method of suture. A new method of tendon suture has been designed to eliminate the development of a gap when tension is applied to the repair. It has been demonstrated to resist distraction at relatively high tensions on cadaveric tendon. The possible advantages of the technique are discussed.


[Tendon suture in the tendinous sheath--experimental study]. Tendon sutures were carried out in the flexor digitorum longus tendon 54 rabbits within the osteofibrous canal at the level of the ankle joint. The suture technique of BUNNELL, LENGEMANN and KESSLER were compared. The adhesions and the vascular pattern in the suture are were observed by means of idian ink injection, microdissection and in thin sections cleared with methyl salicylate. Tendon healing with only minimal adhesions seems to be possible provided that the gap between the tendon stumps is rather small. It originates from the vascularised epitenon of the tendon stumps. In tendon sutures after KESSLER the gap averaged only 2,5 mm whereas the average after BUNNELL suture was 6,7 mm, after LENGEMANN suture 9,8 mm. Early mobilisation of the tendons without tension according to the technique of KLEINERT seems to be suitable to minimise adhesions in the suture area.


[Therapeutic possibilities malformations of the metacarpus]. The most common deformities of the metacarpus occur in conjunction with poly- and oligodactyly. The authors first refer to the most important operations in treating these deformities and emphasize that in certain cases solitary resection of surplus fingers is not enough: in addition, outgrown articular process must be removed, bent metacarpals osteotomised and capsular defects closed. The treatment of oligodactylic hands is made difficult by cutaneous and osseous syndactyly. The operating surgeon should have sufficient experience in plastic surgery to be able to take care of severe adduction contractures of the thumb with constriction of thumb commissure. For aplasia and hypoplasia in the thumb ray the already proven index finger pollizisation is thetherapy of choice. Triphalangeal thumbs are operated according to the same principles. On the other hand in brachyphalangeal thumbs commissure increase and correction of the clinodactylia are of prime importance. Phalangisation is very rewarding in certain forms of synbrachydactyly. In some deformities only the thumb is present. In these cases we recommend an opposition post built out of a tubed flap and autogenous bone graft. Some examples of defective hands surgically treated are shown.


Calcium and pancreatic beta-cell function: glucose stimulation uptake of lanthanum-displaceable 45-Ca from low or normal calcium-containing media. The uptake of 45Ca was studied in beta-cell-rich pancreatic islets microdissected from ob/ob-mice. Glucose stimulated 45Ca incorporation in a lanthanum-displaceable pool remaining after correction for the extracellular space occupied by sucrose. It is suggested that the glucose effect on the lanthanum-displaceable calcium is the cause rather than the result of the secretion of insulin since it could be demonstrated also in the presence of only trace amounts of extracellular calcium.


Effect of caerulein upon insulin and glucagon secretion in dogs. In order to investigate the action of caerulein upon insulin and glucagon secretion, experimental studies were carried out using anesthetized dogs, in which graded doses of caerulein were infused into the pancreatic artery, and insulin and glucagon were measured in the blood obtained from the pancreatic vein. When caerulein was administered at a rate of 15 ng/min, neigher changes of blood glucose in the femoral artery nor plasma levels of insulin or glucagon in the pancreatic vein were prominent. Caerulein infusion at a rate of 120, 240 or 480 ng/min caused a prompt rise of plasma insulin and a delayed increase of plasma glucagon in the pancreatin vein. Blood glucose in the femoral artery increased only with caerulein doses of 240 ng/min or more. A significant increase in pancreatic vein blood flow rate was demonstrated after the infusion of caerulein at a rate of 240 ng/min or more. Neither caerulein-induced insulin secretion nor glucagon secretion was influenced by a simultaneous infusion of glucose. In contrast, caerulein-induced glucagon secretion was exaggreated by a simultaneous arginine infusion. It was concluded from the present experiments that caerulein infusion into the pancreatic artery resulted in increased secretion of insulin and glucagon from the pancreas.


Tax and Medicare aspects of hospital malpractice insurance. Part 1. This first part of a two-part article on how tax laws and Medicare regulations affect hospital malpractice insurance discusses self-insurance mechanisms, particularly trust funds. Relationships among tax exemptions, Medicare and other intermediaries' reimbursements, investment income from such funds, and payments to and from the funds are examined.


Voluntary effort was inevitable, head of FAH says. The voluntary effort to contain costs was never intended to fight off a single piece of legislation, says Michael Bromberg, executive director of the Federation of American Hospitals. It will unite the various elements in the health care field so that they can successfully face the threat of federal intervention year after year. In addition to the Federation of American Hospitals, the American Hospital Association and the American Medical Association are partners in the voluntary effort.


The lymphoid system. Its normal architecture and the potential for understanding the system through the study of lymphoproliferative diseases. This article presents a view of lymphoid tissue architecture as defined by the traffic of defined lymphoid cell classes. The compartmentalization of lymphocytes is discussed in reference to specific cell-cell interactions that occur in antigen-driven immune responses. Finally, the distribution of normal and neoplastic lymphocytes in humans is defined and compared with animal model systems.


Recent progress in the study of autoantibodies to nuclear antigens. Autoantibodies to nuclear antigens can now be classified according to their immunologic specificities. They include antibodies that react with DNA, deoxyribonucleoprotein, nuclear histones, and nuclear acidic protein antigens. It has been established that there are several antinuclear antibodies that react with nuclear acidic proteins, and these include antibodies to Sm antigen, nuclear ribonucleoprotein, and SS-A and SS-B antigens. It has also been established that certain systemic rheumatic diseases, such as systemic lupus erythematosus, Sjögren's syndrome, and scleroderma, are characterized by antibodies of some specificities and not of others. Thus, distinct profiles of antibodies to nuclear antigens may be present, and these may be used as diagnostic aids. Further characterization of these specific nuclear antigen-antibody systems may help in unraveling the etiology and pathogenetic mechanims of these diseases.


Hepatitis B. Cytologic localization of virus antigens and the role of the immune response. Antigens of the hepatitis B virus have been localized within liver tissue by various immunologic, histochemical, and electron microscopic methods. The abundance and distribution of these virus antigens are in part determined by the host immune response. This interaction of immune mechanisms with the hepatitis B virus may be related to the pathogenesis and natural history of human hepatitis B virus infection.


The detection of human B lymphocytes by both light and electron microscopy utilizing colloidal gold labeled anti-immunoglobulin. Colloidal gold was used to label rabbit anti-goat IgG for the indirect detection of goat anti-human IgD and IgM. Utilizing this technique, surface immunoglobulin was visualized on human blood B lymphocytes at both the light and electron microscopic levels of resolution. By this technique, percentages of lymphocytes were found to closely correlate with those of the standard immunofluorescent procedure. The ease of the procedure along with the clarity of the marker in both light and electron microscopy suggest wide applicability in clinical and research studies of lymphocyte membrane markers.


Sequential IgM and IgG2 anti-DNP antibody responses against DNP-E. coli and DNP-lipopolysacchardies in guinea-pigs. When 2,4-dinitrophenylated cells (DNP-E. coli) and lipopolysaccharides (DNP-LPS) of Escherichia coli were injected i.p. into guinea-pigs, they were capable of inducing sequential production of IgM and IgG2 anti-DNP antibodies, both of which were substantially thymus-independent, but only a trace of IgG1 anti-DNP antibody was produced. On the other hand, thymus-dependent DNP-bovine serum albumin (DNP-BSA) induced concomitantly both the IgG1 and IgG2 antibody responses in the presence of LPS. Therefore, the preferential IgG2 antibody response against DNP-LPS seems to be elicited with DNP-LPS itself and not by a combination of mitogenic stimulation with LPS and haptenic stimulation with other contaminating substances carrying DNP residues. Furthermore, it may not be related to affinity of the antibodies produced since there was no significant difference in the affinity for DNP residue between the IgG2 and IgG1 anti-DNP antibodies produced with DNP-E. coli and DNP-BSA, respectively.


Preparation of a specific antiserum towards the microfibrillar protein of elastic tissues. The microfibrillar protein (MFP) of bovine foetal ligamentum nuchae was prepared and used to induce an antiserum (I) in rabbit. Antibody (I), reacted with a dispersion of MFP in Ouchterlony plates, produced one major precipitin band (A) and two minor bands (B and C). The major band (A) was used to prepare antiserum (II) in a second rabbit. Antibody (II) was monospecific for precipitin band (A) and was shown to be selectively directed against MFP of bovine and chick elastic fibres by immunofluorescent and immunoperoxidase techniques. Immunoperoxidase-labelling techniques demonstrated the regular organization of microfibrillar protein on the surface of elastic fibres and suggested the ability of MFP to assemble into a framework defining the three dimensional polymerization of elastin monomers during the formation of elastin fibres. It was observed that collagen fibrils, which were in close association with the microfibrillar protein on the surface of elastic fibres, also possessed a protein which was immunologically related to MFP.


Quantitative phagocytosis by human polymorphonuclear leucocytes. Use of radiolabelled emulsions to measure thae rate of phagocytosis. A new micro-method for the quantitative measurement of phagocytosis by neutrophils is described. The material used for phagocytosis consists of a radioactive oil emulsion coated with E. coli lipopolysaccharide. Uptake of radioactive material is a function of cell number, duration of incubation, dilution of serum used for opsonization, content of lipopolysaccharide and concentration of emulsion. This method can be used to quantify rapidly and precisely phagocytosis rates of as few as 5 x 10(4)-10(6) polymorphonuclear leucocytes and the opsonic activity of 10 microliter serum.


Role of mouse IgG and IgE homocytotropic antibodies in passive cutaneous anaphylaxis. The role of the mouse homocytotropic antibodies in passive cutaneous anaphylaxis reaction was investigated. One class of antibody was heat stable, detected at 2 h but not at 48 h after passive transfer, and belonged to a sublcass of mouse IgG. The other was heat labile, detected at 2 h and 48 h after passive transfer, and belonged to the IgE class of mouse immunoglobulins. In the presence of IgG, IgE homocytotropic antibody was not detected early after passive transfer. This was thought to be due to a masking of IgE by IgG antibodies rather than a competition for mast cell surface receptors, since inhibition studies with rat IgE myeloma protein suggested that mouse IgE and IgG1 may have different receptor sites on mast cell surfaces.


The effects of splenectomy, mesenteric lymphadenectomy and portacaval shunt on antibody responses to antigens within the small intestine. The primary and secondary systemic antibody responses to protein antigens introduced into the gut (diphtheria toxoid, lauroylated human serum albumin) were not diminished or enhanced by previous splenectomy, mesenteric lymphadenectomy or portacaval shunt. Immunization with diphtheria toxoid before such operations did not produce significant alterations in the responses. The cells forming antibody were found predominantly in the lamina propria of the small bowel and to a lesser extent in the subcapsular sinuses of the mesenteric lymph nodes when tissues were examined by the fluorescent antibody technique, ten days after the secondary stimulus of intestinal diphtheria toxoid. The experiments show that the responses, stimulated locally by gut absorbed protein are little affected by an altered portal circulation.


Immunity to Mycobacterium leprae infections induced in mice by BCG vaccination at different times before or after challenge. Viable suspensions of BCG, an attenuated strain of Mycobacterium bovis, have been previously shown to immunize mice against infections with M. leprae. Usually, the mice have been vaccinated about 1 month before challenge. Experiments have now been carried out with single intradermal injections of BCG given before or after the M. leprae challenge. Approximately equal immunizing effect was seen in one experiment when the BCG was given at -168, -119, -70, and -28 days relative to challenge. Approximately equal protection was observed in another experiment when the vaccine was given at -28, +28, and +56 days. In the latter experiment, however, vaccine given at +91 days appeared to be somewhat less effective. Enlargement of the lymph nodes regional to the intradermal vaccine site persisted for at least the duration of the experiment, approximately 400 days. Thus, antigenic stimulation appears to have continued throughout the period of observation.


Unsustained multiplication of treponema pallidum (nichols virulent strain) in vitro in the presence of oxygen. Treponema pallidum (Nichols virulent strain) was incubated with or without oxygen using a modified medium supplemented with reduced glutathione and a variety of nutrients (PRNF10-B). Two- to fourfold increases in treponemal numbers were observed in cultures without mammalian cells within 96 h of incubation under 5 to 6% oxygen. Treponemal motility and multiplication were maintained more satisfactorily in cultures that were diluted and transferred daily, using an equal volume of fresh medium. Treponemes incubated without oxygen did not significantly increase in number. Virulent microorganisms were detected for at least 96 h in the cell-free system. In the presence of 3 to 4% oxygen, two- to fivefold increases in treponemal numbers were observed in the supernatant fluids of cultures containing human prepuce cells after 48 to 120 h at 35 degrees C. Without oxygen, treponemal numbers rarely approached a threefold increase. Virulent treponemes were detected by the rabbit skin lesion test after at least 120 h in vitro. Regardless of the system of incubation, increases in treponemal numbers could not be sustained for longer than 120 h, and treponemal virulence decreased as a function of time in vitro.


Effect of zinc chloride on hamster lymphoid cells: mitogenicity and differential enhancement of lipopolysaccharide stimulation of lymphocytes. ZnCl2 over a very narrow concentration range was found to be mitogenic for hamster lymph node cells but not for thymocytes or splenocytes. Maximal leucine, [3H]uridine, and [3H]thymidine incorporation. Addition of 10 micron ZnCl2 was found to greatly enhance the stimulation observed with the B-lymphocyte mitogen lipopolysaccharide but not with dextran sulfate or the T-lymphocyte mitogen lipopolysaccharide but not with dextran sulfate or the T-lymphocyte mitogen concanavalin A. Although not mitogenic for splenocytes, 10 to 25 micron ZnCl2 slightly enhanced lipopolysaccharide stimulation but not concanavalin A or dextran sulfate stimulation. The effect of ZnCl2 on lipopolysaccharide stimulation was also confirmed with outbred Hartley guinea pig splenocytes and lymph node cells. Zinc chloride (50 micron) was mitogenic for both of these tissues; the response to lipopolysaccharide was enhanced by addition of 50 micron ZnCl2, but the concanavalin A response was unaffected. The possibility that the zinc effect is mediated by proteolytic mechanisms is discussed.


Suppression of antibody response by group A streptococcal pyrogenic exotoxin and characterization of the cells involved. The effect of purified streptococcal pyrogenic exotoxins (SPE) on the antibody response to sheep erythrocytes was studied in cultures of mouse spleen cells. Purified SPE types A, B, and C shared the ability to suppress the day 4 direct plaque-forming cell response when added to cultures. SPE A and C were most suppressive at concentrations of 0.1 to 1 ng per culture, while SPE B was active at 1 microgram per culture. Pretreatment of mice with SPE A, 3 h before removal of their spleens for culture, also produced suppression. Cell populations were separated from spleens of normal and toxin-treated mice and recombined in culture to test the cellular site of action of SPE immunosuppression. When nonadherent cells (lymphocytes) and adherent cells (macrophages) from control and SPE-treated mice were separated and recombined, the plaque-forming cell response depended on the source of lymphocytes. Macrophages from toxin-treated mice functioned normally in the presence of control lymphocytes. In a further experiment, toxin pretreatment failed to suppress the plaque-forming cell response of spleen cells that were T-cell depleted and reconstituted with control thymocytes. When the T lymphocytes were removed from toxin-treated spleen cell suspensions, the remaining cells were able to respond normally to antigen if normal helper T cells were provided. The results suggest that the suppressive activity of SPE on antibody production is mediated by altered activity of T lymphocytes.


Chicken embryo model for type III group B beta-hemolytic streptococcal septicemia. A lethal septicemia was induced in 11- and 12-day-old chicken embryos with intravenous inoculation of relatively small numbers of a clinical isolate (GBBHS-III-Bell) or a reference strain (GBBHS-III-D136-C) of group B beta-hemolytic streptococci (GBBHS). GBBHS-III-Bell was more virulent than GBBHS-III-D136-C, and 11-day-old chicken embryos were more susceptible than 12-day-old chicken embryos. Type-specific rabbit antisera protected the embryos from bacterial challenge, and this protective effect was absorbed with homologous but not heterologous GBBHS strains. A heterologous antiserum and normal rabbit sera provided some protection, which could be absorbed with either homologous or heterologous GBBHS strains. The chicken embryo is a suitable animal model for the study of infection and immunity with GBBHS type III.


Experimental murine candidiasis: pathological and immune responses to cutaneous inoculation with Candida albicans. Cutaneous infection of mice with Candida albicans elicited a predominantly acute inflammatory response, stimulated the production of precipitating antibodies, and conferred protection against subsequent intravenous challenge with the same organism. The acute inflammatory skin reaction seen after cutaneous infection suggested a predominantly humoral response to Candida. Animals infected cutaneously a second time with viable C. albicans developed larger skin lesions than animals infected only once, and the twice-infected animals were more resistant to an intravenous challenge as well. The cutaneous inoculation of mice with heat-killed C. albicans was less effective in stimulating antibody production, in eliciting the inflammatory response, and in inducing a protective response demonstrable by intravenous challenge with viable Candida. This model of experimental candidiasis represents a reproducible means of studying a protective immune response to the organism.


Humoral bactericidal systems: antibacterial potential of serum from young animals. The antibacterial potential of fresh serum obtained from young animals during a pre-antibody period of development was assessed against two smooth and two rough strains of gram-negative bacteria. The bactericidal capacity of serum from 3- to 4-week-old guinea pigs and 4- to 5-week-old rabbits was compared with that of serum from adults. Serum from young animals was deficient in natural antibodies, and in conventional dilution assays the bactericidal action was unimpressive, especially against the smooth strains. However, when decimal increments of bacteria were incubated in fresh undiluted serum, killing of both smooth and rough strains proved substantial. This finding may have particular meaning in the very young animal when natural antibodies are at ebb: cellular defense mechanisms may function less efficiently at this time and effect a greater reliance on humoral antibacterial systems.


Humoral bactericidal systems: nonspecific and specific mechanisms. Bactericidal systems in normal serum from month-old rabbits and guinea pigs were characterized in terms of activity against rough- and smooth-phase species of gram-negative bacteria. Killing of the rough strains in the absence of natural antibody required complement and at least one additional nonspecific component exhibiting lability to freezer storage and to heating at 52 degrees C. Bactericidal action against the smooth-phase organisms, on the other hand, appeared to require natural antibody in addition to complement and the labile component. Both nonspecific and specific bactericidal systems were also functional in normal serum from adult animals. In immune systems, the labile nonspecific component was not essential for bactericidal activity. Whereas immune systems were subject to inhibition by homologous endotoxins, the normal serum bactericidal systems were not, indicating that the natural antibodies in normal serum were specific for surface antigens other than the O-somatic polysaccharides. The significance of these observations is discussed in relation to probable complement pathways that mediate killing in each of the systems described.


Comparative efficacy and toxicity of a ribosomal vaccine, acetone-killed cells, lipopolysaccharide, and a live cell vaccine prepared from Salmonella typhhimurium. The protective and toxic properties of a ribosomal vaccine prepared from Salmonella typhimurium W118-2 were systematicaly compared with those of an acetone-killed whole cell vaccine, purified lipopolysaccharide, and living cells in CD-1 mice. Tests of graded immunizing doses of each vaccine against several  challenge doses of live strain W118-2 showed that, although the protection given by ribosomes approached the levels of protection conferred by living organisms, acetone-killed cells administered in appropriate dosages provided levels of protection comparable to that of ribosomes. Lipopolysaccharide was found to be significantly less protective than the other vaccines. On a dry-weight basis, ribosomes were the least toxic with a 50% toxic dose (TD50) of 5,000 microgram; acetone-killed cells had an intermediate TD50 of 1,400 microgram; and lipolysaccharide was the most toxic, with a TD50 of 320 microgram. The dose of each vaccine that protected 50% of the mice against a challenge of 1,00 times the 50% lethal dose was determined and divided by the TD50 to give the therapeutic index. This ratio also indicated that the ribosomes and acetone-killed cells were equally effective, whereas lipopolysaccharide was markedly inferior.


Parasite-specified phagocytosis of Chlamydia psittaci and Chlamydia trachomatis by L and HeLa cells. Phagocytosis of the 6BC strain of Chlamydia psittaci and the lymphogranuloma venereum 440L strain of Chlamydia trachomatis by L cells and HeLa 229 cells occurred at rates and to extents that were 10 to 100 times greater than those observed for the phagocytosis of Escherichia coli and polystyrene latex spheres. Both species of Chlamydia were efficiently taken up by host cells of a type they had not previously encountered. Phagocytosis of chlamydiae was brought about by the interaction of parasite surface ligands with elements of the host cell surface. The chlamydial ligands were readily denatured by heat, were masked by antibody, and were resistant to proteases and detergents. The host cell components were reversibly removed by proteases. Chlamydial phagocytosis was inhibited when host cells were incubated for many hours with cycloheximide. It was suggested that the presence on the chlamydial cell surface of ligands with high affinity for normal, ubiquitously occurring structures on the surface of host cells is an evolutionary adaptation to intracellular existence. The term parasite-specified phagocytosis was used to describe the efficient phagocytosis of chlamydiae by nonprofessional phagocytes and to distinguish it from the host-specified immunological and non-immunological phagocytosis carried out by professional phagocytes.


Contribution of immunoglobulins M and G, complement, and properdin to the intracellular killing of Escherichia coli by polymorphonuclear leukocytes. The effect of immunoglobulins and complement (C) on phagocytosis and intracellular killing of Escherichia coli was studied in vitro. The incubation system consisted of monolayers of human polymorphonuclear leukocytes and C-resistant, [3H]thymidine-labeled E. coli C source was human serum deprived of immunoglobulins and properdin by immunoabsorption. In the absence of C, only immunoglobulin G-coated bacteria were phagocytosed, whereas immunoglobulin M lacked opsonic activity. In the presence of C, phagocytosis was enhanced; however, immunoglobulin M was now more efficient than immunoglobulin G. Intracellular killing was notably augmented when C was activated by immunoglobulin G- or immunoglobulin M-coated bacteria; in contrast, the alternative activation of C by properdin had no effect on phagocytosis or intracellular killing. These results demonstrate the importance of immunoglobulins together with C not only for phagocytosis but also for efficient intracellular killing.


Scanning and transmission electron microscopic study of Escherichia coli O15 (RDEC-1) enteric infection in rabbits. RDEC-1 is a piliated strain of Escherichia coli that was isolated from and produces diarrhea in rabbits without invading the mucosa or synthesizing one of the classical enterotoxins. Previous histological and fluorescent-antibody studies of RDEC-1 diarrhea revealed an acute inflammatory response and large numbers of RDEC-1 associated with (adhering to) the mucosal surface of the ileum, cecum, and colon. The purpose of the present investigation was to further elucidate the histopathology by scanning (SEM) and transmission (TEM) electron microscopy. SEM revealed aggregates of bacteria on the surface of the gut; their distribution was patchy in the ileum and diffuse in the cecum and colon. Bacteria were in contact with each other and appeared to be closely associated with the epithelial surface. TEM showed that the brush border region of the epithelial cells was found to be in varying stages of degeneration, and the bacteria could not be seen adhering to the mucosal cells unless the brush border was absent. Bacteria were in close contact only with epithelial cells that had lost their brush border. The space between the bacteria and the epithelial cells was 11 nm, and it appeared to be filled, in most cases, with densely stained material. This E. coli rarely penetrated epithelial cells, but when it did; it was found in the supranuclear region and never reached the lamina propria. From previous and present studies, it seems probable that RDEC-1 produces diarrhea in rabbits by a mechanism that may be cytotoxic and differs from the classic mechanisms by which E. coli produces diarrhea.


Cell-associated levan of Actinomyces viscosus. Actinomyces viscosus ATCC 15987 was examined for the presence of cell-associated levan by absorption of myeloma proteins with antilevan activity and direct immunofluorescence. Levan was not detectable on the surface of glucose-grown A. viscosus, but after a brief incubation of these cells with 5% sucrose, they were encapsulated with tenaciously adhering levan. The levan layer constituted between 0.02 and 0.03% of the cell dry weight. In contrast, sucrose-grown A. viscosus cells possessed a low level of cell-associated levan, which was only moderately increased by incubation in sucrose and which partially existed as a loose slime rather than a tenacious capsule.


Detection and characterization of colonization factor of enterotoxigenic Escherichia coli isolated from adults with diarrhea. The fimbriate colonization factor antigen (CEA) of Escherichia coli strain H-1047 was isolated and used to prepare anti-CFA antiserum. Enterotoxigenic E. coli (ETEC) isolated from 29 adults with diarrhea acquired in Mexico were examined for CFA by using this serum. Retrospectively, it was found that ETEC possessing the H-10407-type CFA were isolated from 25 (86%) of these diarrhea cases as compared with 2 of 11 (18%) from asymptomatic controls from whom ETEC had been isolated. CFA was found onE. coli of various serotypes, as demonstrated by bacterial agglutination by the anti-CFA serum. Heat treating the cells at 65 degress C for 1 h prevented the agglutination. CFA-positive strains did not react with anti-CFA serum when the cultures were grown at a low incubation temperature (18 degrees C). E. coli isolates identified serologically as CFA positive were shown to adhere to the intestinal villous surfaces of infant rabbits. By the indirect immunofluorescence technique, it was found that adhesion occurred preferentially in the upper 20 cm of the small intestine. Also, the ability or inability of various isolates to adhere to intestinal mucosa in vivo correlated with the presence or absence of fimbriae on the cells when grown in vitro. Agglutinability with anti-CFA serum, fimbriae, and adhesiveness were spontaneously lost by many isolates after laboratory passage in a manner previously described with E. coli H-10407. These observations suggest that the H-10407-type CFA plays a role in the virulence of ETEC possessing this antigen.


Immunity to experimental renal candidiasis in rats. Germfree rats were found to be more susceptible to intravenous challenge with Candida albicans than were conventional rats. The resistance of conventional rats could be overcome by increasing the challenge dose. The resistance of the germfree rat was enhanced by vaccination with Formalin-killed C. albicans in complete Freund adjuvant, complete Freund adjuvant, or incomplete Freund adjuvant. These results, and histological evidence obtained from infected gnotobiotic rats, provided further information on the mechanism of resistance to the disseminated form of candidiasis.


Adult mice as a model for early onset group B streptococcal disease. The intravenous inoculation of adult mice with virulent group B streptococci serotype Ia resulted in fulminating sepsis with extensive colonization of the lungs and kidneys. The time course of the infection lasting 24 to 40 h, extensive pulmonary colonization, and resistance of the type Ia organism to phagocytosis in the absence of specific antibody suggest that mice are an appropriate model for the study of early onset streptococcal infection of human neonates.


Acid precipitation of Clostridium botulinum type C and D toxins from whole culture by addition of ribonucleic acid as a precipitation aid. The ratios of ribonucleic acid to protein contents of Clostridium botulinum type C, D, and E cultures were lower than those of type A, B, and F cultures. Addition of ribonucleic acid at 0.4 mg/ml to culture satisfactorily aided acid precipitation of type C and D toxins, but not that of type E toxin.


Immunomorphology and pathogenesis of echinococcosis. III: Microscopic immunofluorescence studies in experimental alveolar echinococcosis. By application of immunohistological methods in experimental alveolar echinococcosis, detailed information was obtained on the antigenic properties of each component of the echinococcus cyst. It was established that of the various layers, the capsula germinativa of the parasite cyst possesses the strongest antigenicity regardless of localization and maturity of the cysts. The dissemination of echinococcal antigens within the internal organs of the experimental animals was found to follow the general trends of other infections. Substances obtained from the capsula germinativa appear most suitable as reagents for immunodiagnostic purposes due to their strong antigenicity.


Treatment with a single daily dose of gentamicin in urinary tract infection in relation to the site of infection. Twenty-three patients with various types of recurrent urinary tract infection were treated with a single daily dose of 160 mg gentamicin for eight to nine days. The treatment eliminated bacteriuria in 19 patients. Evaluation of the therapeutical results according to the site of infection showed elimination of bacteriuria in all patients with lower urinary tract infection. Thus a single daily dose of gentamicin can be recommended in recurrent lower urinary tract infection, and also in upper urinary tract infection not associated with a major impairment of renal function.


The diagnostic application of specific antiprocollagen sera. II. Analysis of liver biopsies. Frozen, unfixed sections of human liver biopsies from patients with acute, subchronic, and chronic hepatitis or fibrotic liver disease were studied in indirect immunofluorescence with specific antisera to type I and type III procollagen. In early stages of both hepatitis and fibrotic liver disease, intralobular type III collagen synthesis is increased. Maximum values are reached years after the onset of disease. Intralobular procollagen I content is not increased in the acute stage, but rises only later. An increase of procollagen I seems to herald irreversible liver changes. This approach allows for exact localization and semiquantitative analysis of the synthesis of type I and type III collagen, and adds a new parameter to the diagnostic approaches in liver diseases.


Partial purification of human kidney antigens. A chromatographic method using immunoaffinity has been utilized in the search for kidney-specific antigens. After repeated absorptions by liver proteins coupled to a column of Sepharose CN-Br of a rabbit anti-human kidney serum, several antibodies remained. When these antibodies were coupled to a similar column and used for immunoaffinity chromatography, 8 kidney antigens, studied as peptides with molecular weights of 33,000, 80,000, 98,000 and 110,000-125,000 were obtained. They should not be found in similarly treated liver extracts.


Regulating influence of transferred immune spleen cells on the primary response of mice to sheep red blood cells. The regulating influence of transferred immune spleen cells on the primary response of mice to sheep red blood cells (SRBC) was investigated. When splenic memory cells were intravenously inoculated, the greater part of these cells disappeared from the peripheral blood between 30 min and 6 h after injection. Transfer of immune spleen cells 2 days before immunization with 4 X 10(8) SRBC intravenously caused decreased numbers of PFC in the recipient spleen and up to 10 times as many PFC in the bone marrow. Apparently, the regulating influence of immune spleen cells upon antibody formation during the primary response can differ in different organs.


Eosinophil chemotactic factor (ECF). III. Generation in human peripheral leukocytes. Eosinophil chemotactic factor (ECF) can be released from human peripheral leukocytes by an IgE-anti-IgE reaction, by the calcium ionophore A 23187 and during phagocytosis. Supernatants and sonicates of unstimulated cells contain little or no ECF. On stimulation, however, ECF activity increases in the cells and even more so in the supernatants. This holds for purified neutrophils (PMNs) as well as for basophil-containing mononuclear cell preparations. These findings contrast with those in lung homogenates, where ECF-A is present in mast cells in a preformed state. On chromatographic analysis, the ECF present within cells does not differ from that released into the supernatant. For the generation of ECF, calcium and an intact cell are necessary. Inhibition of deoxyribonucleic acid (DNA) and protein synthesis do not affect ECF generation or release. The metabolic inhibitor, 2-deoxyglucose (2-DG), suppresses ECF activity in leukocyte supernatants to a greater extent than in the cell pellets while the reserve is true for colchicine. This further confirms that ECF is not preformed within cells and that its generation and release are two active, distinct metabolic processes.


Eosinophils chemotactic factor (ECF). IV. Inhibitory activity in human peripheral leukocytes. A low molecular weight eosinophil chemotactic factor (ECF) can be released from human peripheral polymorphonuclear leukocytes by phagocytosis, by reverse anaphylaxis or by the calcium ionophore A 23187. During later phases of ECF-release, a leukocyte-derived ECF inhibitor (LDI) is concomitantly released. Inhibitory activity is also present in sonicates of unstimulated cells, suggesting that the factor is preformed. On chromatographic analysis of neutrophil (PMN) sonicates, two peaks of inhibitory activity at greater than 200,000 and at about 80,000 daltons each are eluted. With preparations containing lymphocytes, monocytes and basophils (L/M/B), only peak (greater than 200,000 daltons) is apparent. The LDI is heat stabile (56 degrees C, 1 h), affects only the ECF and not the migrating eosinophils, and does not inactive bacterial factor or deactivate neutrophils. Evidence is presented suggesting that the mode is by binding of ECF rather than by enzymatic destruction.


Production and traffic of B lymphocytes in the extracortical central area of the guinea pig thymus. Lymphocytes in the stroma and lymphatics of the extra-cortical central area (ECCA) of the guinea pig thymus have been studied with light microscopy, quantitative microscopy, colchicin-induced mitotic arrest, EA (IgG) and EA (IgM) C adherence, surface immunoglobulins (Ig total, IgM, IgG), alkaline phosphatase activity and the effect of cyclophosphamide administration. The results suggest, that AP-positive, SIg-positive EAC-negative lymphocytes in the ECCA proliferate and maturate into AP-negative, SIg-positive, EAC-positive lymphocytes. The latter leave the thymus through the lymphatics. Calculations show that daily 8-9 X 10(6) B lymphocytes are produced in the ECCA and leave this area through the lymphatics. As this number is more than 10% of the number of T cells which daily leave the thymus, we conclude that in the ECCA a considerable number of B lymphocytes is produced.


Prognostic indicators of alcoholism treatment outcome. This literature review is a systematic attempt to isolate the personal characteristics of alcoholics generally associated with their prognosis. Forty-five studies which met certain standards for inclusion are summarized here. The description of each study and its corresponding list of characteristics of alcoholics investigated for prognostic value are reported in tables. The tables do not reveal stable predictors across the studies, though some personal characteristics are more generally of predictive value than are others. A number of reasons for the absence of predictor stability are discussed--among them the possibility that certain treatments may work best with certain alcoholic patients.


Acupuncture in the treatment of addiction: a review and analysis. Many claims have been made about the usefulness of acupuncture as an analgesic and in the cure of certain conditions. The background of some of these claims is examined as are alternative hypotheses for some of the observations that have been reported. The studies that have served as the basis of much of what has been said and written about the use of acupuncture in the management of addictions are reviewed and found to fall seriously short of adequate clinical trials. The utility of acupuncture remains unproven, and some directions for future research are suggested.


Outcome research on treatment and on the drug abuser: an exploration. The study of treatment outcome has its own history, and the experience of other service fields in this area may be of considerable interest to researchers concerned with the effectiveness of treatment for drug abusers. Methodological issues that emerged from psychotherapy's efforts at self-evaluation are reviewed and contrasted with work done on treatment outcome in drug programs. An overview is presented of current research on the improvement of drug abusers and on treatment effectiveness.


Alcoholism scales of the MMPI: contributions and future directions. Though MMPI alcoholism scales have been constructed to provide objective information for making alcoholism diagnoses, they have not met with general acceptance. Research has been criticized since alcoholics were not clearly defined and were not subdivided into homogeneous categories. Prealcoholics were not studied and no consistent findings emerged. The present review of alcoholics and prealcoholics indicates that some scales, such as the MacAndrew, are consistent in discriminating alcoholics from controls even when alcoholics were not subdivided into homogeneous categories. These findings suggest that alcoholics have personality characteristics that distinguish them from other groups and provide psychometric justification for alcoholism diagnoses.


Locus of control research on alcoholic populations: a review. I. Development, scales, and treatment. Research literature dealing with the relationships of locus of control to alcoholism and the treatment of alcoholism is reviewed. The review includes a discussion of some of the scales used in this research, the relative locus of control of alcoholics compared with controls, the change in locus of control during treatment of alcoholics, and the relationship of locus of control to treatment success. Much of the research is inconclusive. Research on the control orientation of alcoholics compared to controls has had equivocal results, but the better designed studies tend to find no difference or externality in alcoholics. Most studies find that alcoholics become more internal over treatment, but the relationship of locus of control to treatment success is unclear. Methodological difficulties have included problems with sampling, selecting appropriate controls, assuming homogeneity of alcoholics as a group, and assuming linearity and unidimensionality of the scales. A number of needed studies which would clarify some of the questions are suggested.


Pinta, yaws, and venereal syphilis in Colombia. Three treponemal infections of man have coexisted in Colombia, South America for centuries. In former years, Colombia and Mexico were the world's most highly endemic countries for pinta. Within Colombia, highest rates of infection with pinta occurred among the mestizo and Indian populations in the Andean and Caribbean departments of Huila, Tolima, Antiochia, Magdalena and Cesar. Yaws occurred primarily in rural areas along the Pacific coast among descendants of African slaves. Infectious syphilis is most often reported from the three largest urban areas, and from three other densely populated departments in the Andean region. During the 21-year period from 1954 to 1974, almost four times as many cases of pinta as yaws were reported. The incidence rates of yaws and pinta have declined almost in parallel in Colombia, even though there has been a national campaign against yaws, but not against pinta. The incidence of primary and secondary syphilis increased only slightly during the same period. The total burden of reported treponematoses (excluding tertiary and congenital syphilis) declinded by over 40 per cent, while the ratios of reported yaws, pinta and infectious syphilis rose from 1:3:4 in 1954 to 1:7:975 in 1974.


A study of cellular and humoral immunity in three species of armadillos. Part I. In the present study the membrane receptors of immunocompetent cells and immunoglobulins in three varieties of armadillos were explored for determining, in later studies, the possible differences in inoculated animals developing leprosy. The studies of cellular immunity were performed in five Chaetophroctus villosus (Ch.v), one Dasypus hibridus septecinctus (DHS) and one Zaedus Pichei (ZP), while the humoral immunity was studied with a serum pool of 17 Ch.v and 6 DHS. The results obtained demonstrate that the lymphocytes of the three species studied have receptors for SRBC, C3 and Ig-s, and no receptors for Fc segment of immunoglobulins. With reference to immunoglobulins no definite alteration of the humoral immunity was observed with the exception that DHS presents increased IgG levels and Ch.v increased IgM.


Solid phase synthesis of porcine LH-releasing hormone with hydrogen chloride in formic acid as the deblocking reagent. The decapeptide corresponding to the amino acid sequence of porcine luteinizing hormone-releasing hormone (LH-RH) which involves 1 mol of tryptophan was synthesized via solid phase synthesis with two different deblocking procedures which used hydrogen chloride in formic acid and hydrogen chloride in acetic acid containing 1% 2-mercaptoethanol. After some fundamental studies on the former reagent with respect to deblocking efficiency toward the Boc group, 0.5 M hydrogen chloride (a 10-fold molar excess with respect to the N-terminal Boc group) in formic acid was used in the present synthesis. The two synthetic products exhibited the same chemical and biological properties as an authentic LH-RH. Hydrogen chloride in formic acid has proved effective without a scavenger although loss of peptide from the resin occurred to a somewhat greater extent than that with hydrogen chloride in acetic acid. A derivative of the synthetic LH-RH formylated at the indole nitrogen had a greatly diminished biological activity, indicating that the intact indole side chain is essential for the activity.


Involvement of membrane lipids in radiation damage to potassium ion permeability of Escherichia coli. Radiation damage to K+ permeability of an unsaturated fatty acid auxotroph of E. coli grown with oleate or linolenate was investigated at different temperatures. A remarkable effect of radiation was observed at 0 degrees C with cells that had been grown with linolenate at 42 degrees C. This indicates that, besides protein, membrane lipids at least are involved in the radiation damage. The damage also seems to be affected by the fluidity of membrane lipids.


Effect of ratio of enzymes to substrate on amino acid patterns released from proteins in vitro. Using an in vitro procedure, with both plant (gluten and edestin) and animal proteins (egg white and casein) as ratio of protein substrate to enzymes (pepsin, trypsin, erepsin) was increased in progressive stages, there was a change in the amino acids released; the proportions of some amino acids progressively increased, others progressively decreased while still others remained constant. The pattern of amino acids released was distinct for each protein and as substrate increased relative to enzymes, certain amino acids essential for the human increased with some proteins and decreased with others which suggests nutritional implications. The variations in amino acids released with changes in ratio of substrate to enzymes was not a random effect but an apparent orderly process. The phenomenon is termed "variable ratio effect".


A closed submucous cervical suture for the incompetent cervix. Twenty-five consecutive cases of cervical incompetence were treated by a closed submucous cervical suture that I developed. Twenty patients proceeded to term and delivered live babies. This was statistically significant when compared to their own reproductive performance before operation (P less than 0.001). The suture described is simple, easy, quick, bloodless, anchored to three points in the cervical musculature and is passed deep to the cervical blood vessels.


Studies of superobesity III: Body image changes after jejuno-ileal bypass surgery. Changes in the perceptual-cognitive and affective components of the body image were studied in ten women who had undergone jejuno-ileal bypass surgery. As weight loss occurs, the cognitive body schema adjusts readily to the patients' new reality, whereas the affective component remains essentially unchanged during the first year after surgery. Implications of findings are discussed.


Experience with auto suture surgical stapling instruments. Fate of enterically applied staples. Inverting serosa-to serosa staple applications may lead to intraluminal extrusion of staples. The possible clinical pathological consequences of such a migration are examined. Technical maneuvers designed to prevent errors and expedite safer handling of automatic stapling devices are presented. Automatic stapling instruments, both in the animal model and in the clinical situation, have produced eminently satisfactory results for us.


Antibacterial prophylaxis in patients after prostatectomy. Seventy-five patients with prostatic adenoma and sterile urine cultures were treated prophylactically after operation, with one of four antibacterial drugs (Nitrofurantoin, Mandelamine, Biseptol, Chlorocid). Administration of Nitrofurantoin and Mandelamine in the postoperative period was found to be advantageous. In patients receiving these drugs, incidence of urinary tract infections was reduced by one half compared with a control group of untreated patients.


Malacoplakia of testis.

Malacoplakia of testis. A case of malacoplakia of testis with a typical clinical course, related to urogenital E. coli infection is presented. By means of electron microscopy, we have identified several forms of Michaelis-Gutmann bodies within the lesion. X-ray spectral analysis revealed that these bodies contain large amounts of calcium, phosphate, sulfur, sodium and chloride. The pathogenesis of malacoplakia and the formation of Michaelis-Gutmann bodies is shortly discussed.


Interrelationships among arenaviruses measured by indirect immunofluorescence. An evaluation of reciprocal indirect immunofluorescent antibody titers for at least one representative of each known arenavirus serotype leads to the conclusion that the Old World aranaviruses are more closely related to each other than to other members of the group. These relationships are particularly evident in evaluations of human convalescent sera. New World arenaviruses cross-react strongly with each other in most instances but only weakly with with Old World arenaviruses.


Altered phenotypic expression of ultraviolet-irradiated nuclear polyhedrosis virus. UV (254 nm) irradiation of nuclear polyhedrosis virus results in formation of small plaques. The small-plaque effect is reversed by photoreactivation. Analysis of plaque formation kinetics indicates a slower formation and subsequent enlargement of plaques from UV-irradiated virus in comparison to non-irradiated virus. A delay in viral DNA synthesis is suggested as an explanation for the observed small-plaque effect.


The clinical, pathologic and radiographic spectrum of the intrathoracic lymphomas. The malignant lymphomas have many similarities, both pathologically and radiographically. The several unique or unusual features of these neoplasms should be kept in mind to identify their radiographic patterns of presentation. The radiologist confronted with the responsibility of evaluating a person with a known lymphoma should design his study and bias his opinion based on a thorough knowledge of the type and clinical stage of the tumor, as well as the treatment status of the patient.


Isolation of field rabies virus strains in CER and murine neuroblastoma cell cultures. Infection of CER and murine neuroblastoma (clone N18) cell cultures by inoculation of brain tissue from rabid skunks, dogs, equines, foxes, bats and cows was detected by immunofluorescence 2--5 days after inoculation.


Effect of endotoxemia on contrast media reactions. Since complement activation is sharply temperature-dependent, we have examined the effects of fever produced by a very small dose of endotoxin on contrast media lethality in rabbits. After the injection of 8.2 ml/kg of 52% methylglucamine iodipamide, a group of rabbits exhibiting an average temperature elevation of 1.5 degrees C had a 100% mortality rate. This was contrasted to a 30% mortality in control rabbits receiving contrast alone, and no mortality in rabbits receiving endotoxin alone. The rabbits with fever and increased mortality exhibited increased activation of serum complement. From this preliminary data it appears that caution should be observed in performing a contrast examination in a patient with endotoxemia and/or a fever.


Epiphyseal chondroblastoma (a study of 39 cases). A fully documented series of thirty nine cases of epiphyseal chondroblastoma is described. This is a remarkable series because of the rarity of this tumour. There is a slight predilection for the male sex. The age most affected is ten to twenty years. The tumour progresses slowly and joint involvement and pain are slight. The commonest site is the proximal epiphysis of the humerus, followed by the epiphyses of the knee. The classical appearances are of a clearly defined area of osteolysis, central or eccentric, with foci of calcification, in the epiphyseal or apophyseal regions, and often transgressing the epiphyseal cartilage. We have never observed involvement of the opposite bone in the affected joint. In four of our thirty nine cases the neoplasm invaded the point and/or soft tissues. The differential diagnosis, especially in localisations at the knee, is with giant cell tumour. The tumour is slow growing and the prognosis is always good. We have never seen malignant transformations or so-called "benign" pulmonary metastases. The few recurrences in this series (five out of thirty nine) were all cured by a second operation. Curettage and grafting is the operation of choice.


[Skin changes in art. I. Examples from the Germanistic National Museum in Nürnberg]. At three works of art in possession of the Germanic National Museum, Nürnberg, the attempt was made of diagnosing dermatologic alternations. The three paintings show naevi pigmentosi, basaliomas and varicosis.


Selenalysine as substrate of lysine decarboxylase. Selenalysine, a lysine analog having the C4 methylene group substituted by a selenium atom, may be decarboxylated to selenolanthionamine by bacterial lysine decarboxylase. The kinetic parameters obtained studying comparatively the decarboxylation of lysine, thialysine and selenalysine showed that while the enzyme is more effective on lysine than on its two analogs, there are no great differences between the last two. These results indicate that the substrate specificity of lysine decarboxylase is greatly affected by the substitution of a carbon atom of the substrate molecule, but the presence of either sulfur or selenium as eteroatom is without appreciable effect on the binding of the lysine analogs to the enzyme. In other words either sulfur- or selenium-containing substrate analogs are acted upon in the same way by lysine decarboxylase.


A simplified method for the evaluation of human faecal flora in clinical practice. Qualitative and quantitative evaluation of aerobic and anaerobic faecal flora was determined by a new and easy method. 10 microliter of 12 ten-fold dilutions in saline of samples of faeces were plated on the surface of culture media solidified in wells of sterile virology plexiglass plates (diameter 16 mm; 0.5 ml culture media) and incubated at 37 degrees C for 24 h. The same dilutions and the same plexiglass plates were used under anaerobic conditions for analysis of anaerobic flora (under atmosphere of N2 85%, CO2 10%, H2 5%, negative pressure, at 37 degrees C for 48 h). The analysis was performed on 35 healthy breast-fed newborn infants, 1--6 days old. After birth, the meconium in sterile; already at 25 h of life some bacterial species (Lactobacilli, Bifidobacteria, Bacteroides) show the maximal concentration in faeces and do not grow afterwards; other bacterial species (Coliforms, aerobic and anaerobic Streptococci) increase gradually during the first week of life. This method gives the same results as the conventional techniques (i.e. Petri dishes), but in an easier and quicker way; therefore it seems useful in clinical practice.


Bacterial infections in the newborns.

Bacterial infections in the newborns. In the care of 5178 live newborns from October 1971 to October 1974, 252 (4.7%) cases of bacterial infections were diagnosed. Of this number, 131 were full-term and 121 premature newborns. The three most frequent types of infections were gastroenteritis (103 cases = 40.8%), urinary tract infections (77 cases = 30.5%), and septicaemia (51 cases = 20.2%). The three organisms most frequently found were E. coli, Proteus and Enterobacter. The prevalence of gram-negative over gram-posivite germs was very remarkable. In 38 infected newborns the highest IgM levels were achieved at the acme of the illness, and they decreased when the infection subsided.


Nonketotic hyperglycinemia treated with strychnine, a glycine receptor antagonist. A 6 1/2-month-old boy suffering from nonketotic hyperglycinemia has been treated for at least 12 months with oral strychnine. The drug caused improvement of muscle tone, motoricity, vigilance and social behavior. Glycine is one of the putative neurotransmitters of postsynaptic inhibition, particularly at the spinal and reticular levels, strychnine its antagonist at the postsynaptic membrane. Strychnine improved the patient's motoricity presumably by blocking the excessive glycine-mediated inhibition of motoneurons. The beneficial effect of strychnine on vigilance and social behavior is more difficult to explain but may have been related to its antagonism of glycine inhibition of brainstem reticular neurons.


Sympathetic influence on alveolar surface activity in hyperventilated dog. Hyperventilating IPPB, defined as intermittent positive-pressure breathing with a frequency of 32 beats/min and inspiratory pressure of 30 cmH2O, was administered for 14 h to open-chested anesthetized dogs in which nerves to one bronchus were operatively blocked. In the nerve-intact lungs, the lung stability index calculated from the pressure-volume relationship decreased with the duration of the hyperventilating IPPB (correlation coefficient r = -0.66, P less than 0.001), and atelectasis and hemorrhage appeared. In the nerve-blocked lungs, the index did not decrease during the 14 h of hyperventilating IPPB, and the appearance was almost normal. After pharmacologic sympathetic block with phenoxybenzamine, the lung stability index of both the operatively nerve-blocked lung and the nerve-intact lung was not decreased by hyperventilating IPPB. From these findings, we conclude that sympathetic block can protect pulmonary surface activity from the adverse effects of hyperventilating IPPB.


Spatial distribution of pulmonary blood flow in dogs in increased force environments. Spatial distribution of pulmonary blood flow (SDPBF) during 2- to 3-min exposures to 6-8 Gy acceleration was studied, using radioactive microspheres in dogs, and compared to previously reported 1 Gy control distributions. Isotope distributions were measured by scintiscanning individual 1-cm-thick cross sections of excised, fixed lungs. Results indicate: 1) the fraction of cardiac output traversing left and right lungs did not change systematically with the duration and magnitude of acceleration; but 2) the fraction is strongly affected by the occurrence or absence of fast deep breaths, which cause an increase or decrease, respectively, in blood flow through the dependent lung; and 3) Gy acceleration caused a significant increase in relative pulmonary vascular resistance (PVR) in nondependent and dependent regions of the lung concurrent with a decrease in PVR in the midsagittal region of the thorax. Result 3 may be mediated primarily by changes in regional alveolar volume and geometry in the nondependent hemithorax conbined with hydrostatic effects of extravascular fluid and active hypoxic response in the dependent region and is superimposed on, and may override, hydrostatic effects of perfusion pressures on SDPBF during acceleration.


Pretreatment with colistin and Proteus sensitivity to other agents. The effects of pretreatment with colistin (polymyxin E) on the sensitivity of Proteus mirabilis, P. vulgaris and P. morganii strains to tris and sodium deoxycholate (DOC) have been studied. Pretreatment of two P. mirabilis strains (NCTC 60 and 4199) with low concentrations (0.25 approximately 1 microgram/ml) of colistin rendered them sensitive to lysis by tris (0.05M) or DOC (250 approximately 1,000 microgram/ml) although DOC induced lysis of control (non-colistin-treated) suspensions also. In contrast, the other P. mirabilis strains, as well as the P. vulgaris and P. morganii strains were little affected by tris (0.2M) or DOC (10,000 microgram/ml) even after exposure of the cells to high colistin concentrations (up to 500 microgram/ml). Colistin-pretreated or control cells of P. mirabilis NCTC 60 rapidly lost viability when suspended in water but not when held in 0.16M sodium chloride solution. Ethylenediamine tetraacetate-pretreated cells of strains 60 and 4199 were fairly sensitive to tris, although the extent of the lysis was less than when colistin was used as pretreating agent. One strain of P. vulgaris (NCTC 4175) became sensitive to tris and to DOC following exposure of the cells to ampicillin.


The comparative synergistic activity of amikacin, gentamicin, netilmicin and azlocillin, mezlocillin, carbenicillin and ticarcillin against Serratia marcescens. The synergistic activities of netilmicin, gentamicin and amikacin combined with carbenicillin, ticarcillin, azlocillin and mezlocillin were investigated against 32 Serratia marcescens isolates. Synergy could be demonstrated by killing curve technique, isobologram plots as susceptibility data with any of the aminoglycosides and penicillins combinations. No antagonism was shown with any of the combinations. The majority of the isolates were resistant to the aminoglycosides and penicillins. Combination of either ureido-penicillin or carbenicillin with gentamicin or netilmicin did not reduce the MIC values to levels achievable in serum but did reduce the MIC levels of both agents to those achievable in urine. The combination of ureido-penicillins or carbenicillin and ticarcillin with amikacin reduced the inhibitory levels of all isolates to levels achievable in both serum and urine.


The hyperkinetic child syndrome and brain monoamines: pharmacology and therapeutic implications. Decreased catecholaminergic activity within the central nervous system has been associated with altered arousal, attention, learning, and kinetic function in animals and humans. The hyperkinetic child syndrome (HCS) involves dysfunction in all these spheres and may thus reflect diminished catecholamine activity, particularly as related to brain dopamine. Accordingly, the efficacy of catecholaminergic agents in treating the HCS is a predictable rather than a paradoxical effect of these agents. Sufficient evidence is now available to strongly implicate catecholamine hypoactivity in the pathopharmacology of the HCS.


Doxepin or diazepam for anxious and anxious-depressed outpatients? A six-week double blind comparison of doxepin and diazepam in the treatment of 61 anxious outpatients showed few drug differences. Diazepam treated patients improved significantly more early in the trial, according to a few measures. They also had significantly fewer complaints of drowsiness. By six weeks, the medicines appeared roughly equal in efficacy. Practically no support was found for the position that doxepin may be more beneficial for anxious-depressive syndromes. In all patients, and also within the anxious-depressive subgroup, there were small mean differences on many criteria favoring doxepin at six weeks, but none reached significance. The doxepin group gained significantly more weight. Possible biasing influences were present requiring that the results be interpreted with particular caution.


Evaluation of loxapine hydrochloride oral concentrate (loxitane C) in acute schizophrenia. In an open study of 4-weeks duration, both an oral liquid concentrate formulation of loxapine hydrochloride (LOXITANE C) and capsules of loxapine succinate (LOXITANE) were administered to 11 acutely disturbed schizophrenic patients. Optimal dosage levels achieved with the concentrate proved satisfactory with the capsules. Efficacy evaluation with the Brief Psychiatric Rating Scale (BPRS), Systematic Nurses' Observation of Psychopathology (SNOOP), and Clinical Global Impressions (CGI) indicated rapid improvement with concentrate administration and continued improvement with capsule administration. All but two side effects were extrapyramidal or sedative, all but one were mild or moderate in severity, and the frequency was similar with the two formulations. Cardiovascular and clinical laboratory findings remained essentially unchanged with both formulations.


Prediction of lithium response in affective disorders. Lithium carbonate has established itself as an effective therapeutic agent in primary affective disorders. As not all the patients with primary affective disorders respond to lithium therapy, it is necessary to identify responders prior to treatment. The important indicators of favourable lithium response include a definitive diagnosis of primary affective disorder, occurrence of less than four episodes of mania and depression within one year, psychotic features during both manic as well as depressive episodes, "grandiose-elated" picture during manic episodes; a family history of bipolar illness and response of affected family members to lithium treatment. While those with more than four episodes are not likely to respond to lithium therapy, those with episodes less frequent than once a year or two may not need prophylactic lithium. Among the depressed, hypersomnic depressed patients respond to lithium combined with a monoamine oxidase inhibitor. In addition to clinical predictors of response to lithium treatment, there are a number of pharmacokinetic, neurophysiological and biochemical indices which have been employed as supplementary predictors of response to lithium therapy.


Stereotaxic treatment of seizure disorder. Individuals with intractable epilepsy have a murky existence, fraught with medical helplessness, social rejection and personal despair. Drugs control many, but unfortunately not all, cases of epilepsy. An attempt to elucidate on the indications, selections and rationale for the stereotaxic interruption is made. Three cases of intractable epilepsy treated by stereotaxic Fields of Forel Interruptions are reported with special emphasis on pre and postoperative evaluations. Based on the data so far available, it appears that a significant number of patients with medically intractable epilepsy who are not candidates for "standard" neurosurgical interventions, can be helped further by stereotaxic interruptions with minimal morbidity.


Legal aspects of electrotherapy in a catatonic renal transplant patient. The treatment of a case of catatonic schizophrenia in a renal transplanted patient is presented and demonstrates that electrotherapy can be life-saving and that there are already adequate legal controls which guarantee the patient's rights. Yet zealots are attempting to have legislators pass laws preventing the use of electrotherapy even in voluntary patients. To help prevent these resolutions from being passed, psychiatrists must become more active in the legislative process.


Some characteristics of beta-naphthyl triphosphate as a substrate of heavy meromyosin. F-actin-inactivated hydrolysis showing initial burst. The initial burst of Pi liberation was found in the hydrolysis of beta-naphthyl triphosphate (beta-NapP3) by heavy meromyosin (HMM) in the presence of Mg ions as well as in the hydrolysis of ATP. However, unlike that of ATP, the steady-state hydrolysis of beta-NapP3 by HMM was inhibited by the addition of F-actin to the reaction solution. Although the possession of an initial burst-like property during interaction of a substrate and myosin is believed by many investigators to be a key factor in F-actin activation of substrate hydrolysis in vitro and in the molecular mechanism of muscle contraction, the above results suggest that this is not generally true. beta-NaP3 did not induce superprecipitation of actomyosin solution and suppressed ATP-induced superprecipitation.


Coordination of levels of elongation factors Tu, Ts, and G, and ribosomal protein SI in Escherichia coli. The amounts of the polypeptide chain elongation factors Tu, Ts, and G, and ribosomal protein SI were assessed under various growth conditions using three independent procedures: (a) Immunoprecipitation and gel electrophoresis, (b) radioimmune assay, and (c) activity measurements. It was demonstrated that, during balanced growth of E. coli, the intracellular levels of these proteins increased in proportion to the growth rate, and the ratio of EF-Tu:EF-Ts:EF-G:protein SI was 4-5:1:1:1, at all growth rates. The effects of isoleucine starvation on the rates of synthesis of these proteins were examined using a pair of isogenic stringent and relaxed strains. The syntheses of all these proteins were found to be under the influence of stringent control. These results indicate that in E. coli the syntheses of the above four proteins are regulated in a coordinated manner and are subject to stringent control.


Purification and properties of a pig heart thiolase with broad chain length specificity and comparison of thiolases from pig heart and Escherichia coli. A thiolase (acetyl CoA acyltransferase, EC 2.3-1.16) which acts on substrates of various chain lengths (thiolase I) has been purified from pig heart muscle 366-fold to near homogeneity as judged by gel electrophoresis. Its molecular weight was estimated to be 200,000 in the absence and 46,000 in the presence of sodium dodecyl sulfate. Kinetic measurements with acetoacetyl coenzyme A, 3-ketohexanoyl-CoA, 3-ketooctanoyl-CoA, and 3-ketodecanoyl-CoA yielded apparent Km values of 16, 8.3, 2.4, and 1.8 micron, respectively, whereas apparent Vmax values of 65 to 69 mumol/min/mg were obtained with all substrates except for acetoacetyl-CoA, with which a value of 26.5 mumol/min/mg was observed. Antibodies prepared against this thiolase were used to demonstrate that thiolase I and acetoacetyl-CoA thilase (thiolase II) from pig heart mitochondria are immunologically unrelated. The antibodies cross-reacted, however, with thiolase I from beef heart. Kinetic constants (Km, Vmax) were also determined for thiolases I and II from Escherichia coli, as were the native and subunit molecular weights of E. coli thiolase II. Although the E. coli thiolases were found to be immunologically distinct from the pig heart enzymes, their physical and kinetic properties are strikingly similar to those of the heart thiolases. In view of this finding and in view of the known physiological functions of the E. coli thiolases, it is proposed that thiolase I from pig heart is only involved in fatty acid metabolism, whereas thiolase II functions solely in ketone body degradation.