Piribedil inhibition of prolactin release induced by mechanical breast emptying in puerperal women. The effects of a 5 day course of Piribedil, a dopaminergic agonist, on prolactin release evoked by mechanical breast emptying in puerperal women, was investigated. A daily dose of 75 mg. caused a significant decrease in the prolactin response to mechanical breast stimulation. Piribedil also proved clinically useful in inhibiting lactation. The role of dopaminergic mechanisms in the regulation of prolactin release induced by mechanical breast emptying are discussed.


Complement fixation in acute serum sickness: assembly of glomerular-bound C3-convertase. Complement (C) fixing properties of glomerular immune deposits were studied in vitro in two groups of rabbits with acute serum sickness (ASS). Deposits were studied early in decomplemented (cobra venom factor-treated) rabbits (Group I) and during the evolution of the nephritis in non-decomplemented rabbits (Group II). Following perfusion of kidneys of animals from Group I (which contained no autologous C3) with rabbit serum deficient in factor B (classical pathway) or serum pre-treated with Mg++EGTA (alternative pathway), fixation of C3 was observed in both systems. No C3 deposition was found when EDTA-rabbit serum was used. When kidney sections obtained from serial biopsies and autopsy material from Group II (which contained rabbit C3-C3rb) were incubated with purified factors B and D, followed by either purified human C3 (C3hu) or EDTA-guinea-pig serum (C3gp), fixation of C3hu or C3gp to early C3 deposits was observed. When sections were pre-incubated with heat-inactivated rabbit serum (source of C3b-inactivator), C3 fixation was substantially reduced. Little or no C3 fixation was found after incubation of sections with human or guinea-pig serum depleted of factor D (classical pathway). Thus, in ASS, glomerular complement deposition appears to be predominantly dependent on the activation of the alternative pathway (C3b-feedback) which is progressively lost during the evolution of the nephritis.


A study of the aetiology of gastritis following gastric surgery. I. Immunofluorescent studies of the gastric mucosa. The gastritis which follows surgical trauma is probably not of autoimmune origin. Although identical with the gastritis of pernicious anaemia (PA) upon routine histological examination, immunofluorescent examination of post-operative gastritis differs in that IgA-containing plasma cells alone are found, in contrast to the predominantly IgG-containing plasma cells in PA.


Studies on guinea-pig macrophage migration inhibitory factor (MIF). II. Purification of MIF after treatment with reducing and denaturing agents. Treatment of guinea-pig macrophage migration inhibitory factor (MIF) containing culture supernatants with the denaturing agents guanidine hydrochloride (Gu HCl) or urea, in the presence or absence of the reducing agent 2-mercaptoethanol (2-ME), or with sodium dodecyl sulphate (SDS), does not destroy biological activity. Alkylation of reduced MIF preparations results in a considerable decrease or total loss of MIF activity. Treatment of supernatants with the combinations, Gu HCl and 2-ME or urea and 2-ME results in the recovery of MIF activity in association with molecules less than 30,000 in molecular weight (mol. wt). After removal of the agents by dialysis, MIF activity is found associated with molecules larger than 30,000. The reduction in mol. wt is dependent on the presence of 2-ME. When MIF-containing supernatants are treated with urea and SDS and fractionated by preparative polyacrylamide gel electrophoresis (PAGE) in the presence of the same agents, MIF activity is recovered in the mol. wt range of 42,000--80,000. When supernatants are treated with 2-me, in addition to urea and SDS, and preparative PAGE is performed in their presence, MIF activity is found associated with material having a mol. wt of 15,000--18,000. Analytical SDS-PAGE of this fraction reveals two or three closely grouped bands corresponding to the above mol. wt range.


Participation of a histamine-Sepharose-adherent subpopulation of human mononuclear cells in the production of leucocyte migration inhibition factor (LIF) in healthy children. The separation of mouse splenic T lymphocytes into distinct subpopulations by fractionation on histamine-rabbit serum albumin Sepharose (H-RSAS) columns has been described. The H-RSAS-adherent T cells have been attributed regulatory functions associated with B cell activity, T cell-mediated cytotoxicity and the secretion of mediators such as immuno-interferon. The possibility that H-RSAS-adherent T cells exert a similar regulatory effect on an in vitro parameter of T cell-mediated immunity was investigated by assaying the production of leucocyte migration inhibition factor (LIF) in human blood samples, using the agarose droplet method. Phytohaemagglutinin (PHA) and BCG-purified protein derivative (PPD) were used as stimulants of LIF secretion which was measured as a percentage of inhibition of linear leucocytic migration. In normal individuals a highly significant (P less than 0.001) decrease was demonstrated in the production of LIF by peripheral blood leucocytes depleted of H-RSAS-adherent cells. Migration inhibition dropped from 36 +/- 11.7% to 21.2 +/- 12.9% in eighteen cases tested with PHA and from 29.3 +/- 11.7% to 17.2 +/- 9.8% in twelve cases tested with PPD. These results suggest the existence of a lymphocytic subpopulation involved in LIF production which expresses histamine receptors.


The role of hepatitis B surface antigen in the pathogenesis of glomerulopathies. The frequency of hepatitis B surface antigen (HBsAg) has been studied in the sera and renal biopsies of 276 patients with various forms of glomerulonephritis (GN), the nephrotic syndrome and other nephropathies. Using a modified Hepanosticon method, HBs antigenemia was detected in 32 of 196 patients (16.3%) with immune complex (IC) GN and the nephrotic syndrome. Indirect immunofluorescence revealed HBsAg in 33 renal biopsy tissue specimens (16.8%). HBsAg was found in the sera of four of the 80 remaining patients with other renal diseases (5%), and in the renal biopsy tissues of another four (5%). Antibody against HBsAg could only be demonstrated in the serum of one glomerulonephritic patient. The sera of 18,799 normal blood donors were used as controls; of these 186 (0.99%) had positive tests for HBsAg. It is concluded that, in some patients with GN and the nephrotic syndrome, HBsAg-containing IC may be implicated in the development and/or progression of the disease.


Bleeding in renal failure: a possible role of vascular prostacyclin (PGI2). Specimens of venous tissues from a group of 25 patients with chronic uremia and 7 patients with acute renal failure generated significantly higher PGI2-like (platelet aggregation inhibiting) activity than venous tissues from 30 normal subjects. After repeated washings, when this activity could barely be detected in the controls, pronounced inhibitory activity was still evident in samples containing venous tissues from uremic patients. Both prolonged bleeding times and increased PGI2-like activity returned to normal in 4 acute uremic patients on restoration of their renal function. These findings may be relevant to the pathogenesis of bleeding in renal failure.


Hereditary C2 deficiency associated with non-systemic glomerulonephritis. A patient with non-systemic idiopathic glomerulonephritis was found to have a complete deficiency of C2, the second component of complement. The clinical course, histological findings and serological abnormalities are reported in detail. The renal disease was a mild glomerulonephritis with mesangial and subendothelial immune deposits comprising IgG, IgM and C3, increased mesangial matrix without significant cell proliferation. An immunogenetic analysis of the patient's family was carried out. It was demonstrated that the homozygous C2 deficiency was associated with heterozygotism for HLA-A, B and D. Only one of the C2 deficient genes was associated with the expected HLA-A10, B18 haplotype and the propositus was HLA-D2 negative. This report confirms the fact that non-systemic glomerulonephritis should be included in the variety of immunological disorders associated with a complement deficient state. However, C2 deficiency does not seem to be related specifically to a given histological variety of glomerulonephritis.


Membranous nephritis in infantile systemic lupus erythematosus associated with chromosomal abnormalities. A white female infant who developed a sudden onset of gross hematuria and proteinuria at 3 months of age was referred for evaluation of nephrotic syndrome at 6 months. Laboratory investigations revealed severe Coomb's negative hemolytic anemia, leukopenia, thrombocytopenia, hypocomplementemia and elevated anti-nuclear antibody titer and DNA antibodies. Renal biopsy showed a membranous type of morphology. She was also found to have chromosome abnormalities. She had an eventual favorable response to steroid therapy. Systemic lupus erythematosus (SLE) is rarely seen in young infants and the renal expression of the disease found in our case has never been reported.


Serial quantitative imaging with 99Tcm-DTPA in pediatric renal transplantation. Three hundred and fifty-eight renal imaging studies with quantitation of renal perfusion were performed following injection of 99Tcm-DTPA in 22 children aged 6--15 years with renal transplants. In 58 of 62 scans performed at the onset of a rejection episode, renal perfusion was decreased. This was the only feature of rejection in 6 episodes, in 5 of which the patient was oliguric due to post-operative acute tubular necrosis. In 4 episodes perfusion fell, but antirejection treatment was not given as a repeat scan was normal. On 18 occasions the plasma creatinine concentration (Pc) rose, but the scan was unchanged; no treatment was given and repeat Pc was normal. Three patients had a ureteric obstruction and 2 patients a lymphocoele detected from the images. There was no morbidity. Sequential renal scintigraphy was valuable in the early diagnosis of rejection and in the avoidance of unnecessary therapy.


Hemodialysis and renal transplantation in progressive systemic sclerosis: report of 2 cases. Renal failure is a common cause of death in patients with progressive systemic sclerosis (PSS). The present paper describes two patients with chronic renal failure secondary to PSS whom we have treated by a combination of chronic hemodialysis and renal transplantation. Also reviewed are reports of six additional patients who have undergone renal transplantation. We conclude that chronic hemodialysis and renal transplantation are successful life-sustaining treatment modalities in some patients with end-stage renal disease due to PSS.


Rapid recurrence of membranous nephropathy in a related allograft. A patient with membranous nephropathy (MN) received a renal allograft from his brother. The allograft functioned immediately but nephrotic range proteinuria developed seven days after transplantation in the absence of any signs of rejection. Renal function deteriorated five weeks after transplantation due to ureteric obstruction. Nephrostomy drainage resulted in the return of renal function to normal and demonstrated that the allograft was the source of the nephrotic range proteinuria. An open renal biopsy of the allograft performed at the same time revealed the presence of recurrent MN. The recipient was investigated in an attempt to identify possible humoral immune mechanisms that may explain this very rapid recurrence of MN.


Postpartum hemolytic uremic syndrome: a study of three cases with a review of the literature. Three cases of postpartum hemolytic uremic syndrome (HUS) are presented. Symptoms of acute renal failure, hypertension and microangiopathic hemolytic anemia with thrombocytopenia occurred 10, 17 and 24 days after delivery. Despite early heparin therapy in all cases, one patient went into terminal renal failure needing chronic hemodialysis, with persistent hypertension which became uncontrollable requiring bilateral nephrectomy 6 months later. The second patient had diuresis one month after starting hemodialysis, but 3 months later developed malignant hypertension. Slight improvement in renal function with  persistent hypertension occurred after hemodialysis for 20 months. The third patient showed complete clinical recovery after 2 months. Pathological examination of renal tissue showed the typical lesions of thrombotic microangiopathy (TMA). However, striking differences were observed in the lesion seen in early and late specimens. Early lesions could be differenciated from infancy TMA because the medium-dize arteries were more severely involved. Late lesions were variable, ranging from minor changes in glomeruli and blood vessels, via ischemic and sclerotic lesions in glomeruli with arteriolosclerosis, to the vascular and glomerular lesions seen in malignant nephrosclerosis. There was a good correlation between the renal pathology and the clinical outcome of the patients. HUS with renal TMA as a cuase of postpartum renal failure has been reported in 49 patients with a fatal outcome in 61%. The pathogenesis of the syndrome probably involves a primary endothelial damage. This causes local renal intravascular coagulation in the presence of the usual postpartum hypercoagulable  state. This is shown by the presence of fibrin-fibrinogen in glomeruli and vessels, increased plasma fibrin degradation products, thrombocytopenia and lowered levels of coagulation factors. There is little hematological or pathological evidence fo disseminated intravascular coagulation or an immune-complex disease. Hypocomplementemia seen frequently is probably due to local C3 activation via the alternative pathway.


Myocardial imaging with extractable cations and inert tracers: the effects of flow and metabolism. The physical and biological properties of 201thallium (Tl) have been investigated and are discussed in this review. A new technique using the ultra-short lived 81mkrypton (81mKr) as a continuous infusion into the aortic root in dogs and man is described. This provides a dynamic assessment of changes in regional myocardial perfusion. Experiments using 201Tl and 81mKr in dogs have shown that regional decreases in myocardial perfusion alone cannot be detected in images of the heart using 201Tl. The effects of perfusion and a variety of factors on the energy dependent cellular uptake of 201Tl are discussed as being of primary importance in changing the regional myocardial distribution of this tracer. The constant infusion of 81mKr in patients with anginal chest pain provides continuous measurement of regional myocardial perfusion in high spatial resolution images. This dynamic method provides a physiological assessment of stenosed coronary arteries at rest and during stress.


A double-blind trial of disopyramide, procaineamide and digoxin in paroxysmal suptraventricular tachycardia. A double-blind cross-over study has been performed in 10 patients with an established diagnosis of paroxysmal suptraventricular tachycardia to compare the effectiveness of three active agents with placebo. The drugs were administered in random sequence for two-week periods with three-day washout intervals and in standard dose regimes as recommended for prophylaxis by authoritative works on the subject. The results suggest that digoxin is ineffective at the recommended dosage. Procaineamide was effective in controlling some arrhythmias, but disopyramide was the most effective agent studied. All these patients showed a mixture of arrhythmias, and also had a lot of ectopic activity. Arrhythmic activity is erratic and unpredictable, and a larger number of patients would need to be studied for long periods of time to obtain enough data for valid statistical assessment.


Antianginal efficiency of nifedipine with and without a beta-blocker, studied with exercise test. A double-blind, randomized subacute study. Twenty-one patients, mean age 60.3 years, with stable angina pectoris earlier treated with beta-blockers, were investigated with standardized exercise tests to evaluate the action of nifedipine alone and in combination with a beta-blocker. The first exercise test was performed 3 weeks after treatment with the patient's usual beta-blocker. Following this, the patients were tested twice after a double-blind cross-over 3-week trial with nifedipine and placebo. The patients were subsequently treated for 3 weeks with nifedipine 10 mg 3 times daily or placebo and then performed an exercise test. During the 4th period of 3 weeks the patients took a combination of nifedipine, 10 mg 3 times daily, and their usual beta-blocker and then performed the final exercise test. Nifedipine alone raised the heart rate by 5 beats/min at rest and diminished the systolic blood pressure at rest by 17 mm Hg. During exercise at comparable load the heart rate did not change significantly, but the systolic blood pressure decreased with 22 mm Hg. The exercise tolerance expressed as total work increased on a average by 20%, range-14 - + 194%. Nifedipine in combination with a beta-blocker gave a further decrease in the systolic blood pressure, totally 37 mm Hg at comparable load. The exercise tolerance increased more, totally by an average of 41%. There was a significant correlation between basal values for systolic blood pressure registered during the placebo period at rest and the percentage change in total work. The atrioventricular conduction time did not change significantly compared to placebo during treatment with nifedipine or the combination nifedipine + beta-blocker. No serious side-effects were observed during the study.


A new look at the epidemiology of ankylosing spondylitis and related syndromes. Among the rheumatic diseases, non so clearly illustrates the relations between host and environmental factors as the seronegative spondyloarthropathy group of disorders. The strongest association is with the histocompatibility antigen HLA-B27, which accounts for a striking susceptibility to these diseases and is present in over 90% of individuals with idiopathic ankylosing spondylitis. Next in importance appears to be a difference in sex penetrance with males predominating in all categories. The most dramatic sex relationship is with postvenereal Reiter's syndrome which has a male-to-female ratio of nearly 50:1. Another potent host factor is age, with increased predisposition to onset at puberty and young adulthood in HLA-B27-positive patients. Environmental or possibly infectious agent influence are most apparent in Reiter's syndrome, where the antecedent circumstances of venereal contact and bacillary dysentery are frequent precipitating events. Secondary forms of peripheral arthritis, radiographic sacroiliitis, and ankylosing spondylitis frequently occur in psoriasis and inflammatory bowel disease; in the case of peripheral arthritis, there is no or a significantly reduced association with HLA-B27 compared to AS or RS. Secondary factor seem to be contributing to spondyloarthropathy in these disorders. These iterrelations emphasize the powerful effects of host characteristics on the type of rheumatic disease syndrome acquired and provide superb opportunities for more precise understanding of disease pathogenesis and ultimate control through the integration of epidemiologic, clinical, and laboratory research.


Treatment of osteoporoses by manipulation of coherent bone cell populations. Up to and including the year 1979, no agent, combination of agents or other treatment has been found which, when given continuously to the intact incoherent adult human skeleton, can store in it clinically useful amounts of bone in a way which can continue with continued treatment. BMU theory suggests that failure derives from a depression by such treatments of both resorptive and formative activity, partly by depressing the naturally coupled activities of already existing 'clast and 'blast populations, and partly by reducing BMU activation. However BMU theory also suggests that selected agents given in special sequences can create a positive bone balance in repeatable increments. One such proposal, called the ADFR sequence, involves generating a pulse of increased BMU activations. The resorptive and formative activities created by that pulse will occur at predictably different periods of time, that is, they will prove coherent. By depressing the coherent resorption with a suitable agent during its lifetime, and then freeing the skeleton of treatment during the following coherent osteoblastic activity one stores an increment of new bone, because the ADF sequence causes remodeling BMU to deposit normal amounts of new bone in smaller than normal holes. The sequence is repeated as often as needed to add further increments. Other manipulations of coherent bone cell populations could remove bone or simply alter its turnover speed, as desired. Thus special sequences of simple pharmacologic actions, which have no useful ultimate effects upon global bone balance when delivered continuously and alone to the incoherent skeleton, create a simple new kind of therapy which should (and did) exert dramatic (and probably repeatably incrementable) effects in the coherent skeleton. The concept of manipulating deliberately induced coherent skeletal states for therapeutic purposes would not appear to depend for its success upon any one or 2 or even 3 special drugs.


The control of bone induction in soft tissues. The induction of bone at the boundary of parenchymal organs has been studied using acid demineralized rib implants in rabbits. The induction of bone is usually confined to that portion of an implant protruding from such an organ though both scant cartilage induction and the induction of bone within the territory of parenchymal organs were seen on a few occasions. Neonatal splenectomy does not influence the inductive properties of bone matrix in muscle or other soft tissues. The inclusion of composite autografts of liver and acid demineralized bone in muscle results in a reduction in the induction rate. It is postulated that the parenchymal organs exclude osteoprogenitor cells and possibly blood-bone bone-marrow-derived osteoinductor releasing cells by some mechanism that is diffusable, thus preventing the initial inductive event. Composite grafts of matrix and muscle produce bone in these tissue, demonstrating that once bone cell differentiation by induction is initiated bone tissue develops even in spleen, liver and kidney parenchyma.


The anterior cruciate ligament: a technique of repair and reconstruction. Both primary repair and late substitution of anterior cruciate ligaments can be accomplished by intra-articular methods. This principle is to provide temporary struts that are initially avascular but can later undergo revascularization and metaplasia to form a new ligament. The graft does afford initial support, however. An understanding of anatomic principles, suture placement, freedom of graft from impingement, avoidance of acute angular deviation of the graft, solid static stability, anatomic attachment points, and blood supply, is absolutely essential for success in this field of surgery.


Biliary excretion of drugs in man.

Biliary excretion of drugs in man. Biliary excretion is an important route for the elimination of some drugs and drug metabolites in man. The factors which determine elimination via the biliary tract include characteristics of the drug such as chemical structure, polarity and molecular size as well as characteristics of the liver such as specific active transport sites within the liver cell membranes. A drug excreted in bile may be reabsorbed from the gastrointestinal tract or a drug conjugate may be hydrolysed by gut bacteria, liberating original drug which can be returned to the general circulation. Enterohepatic circulation may prolong the pharmacological effect of certain drugs and drug metabolites, but the quantitative importance of this in man appears to be less than in animals. Biliary elimination may play a role in the interindividual differences in drug response observed in healthy subjects and in patients with certain diseases. Cholestatic disease states, in which normal bile flow is reduced, will influence drug elimination by this route resulting in increased risk of drug toxicity. Bile may serve as an alternate route of elimination in renal failure, but this has not been determined in man. Lack of reliable information regarding the biliary excretion of drugs in man is partly due to the relative inaccessibility of the human biliary tract. Most studies of drug excretion in human bile have been performed in post-surgical patients with T-tube drainage. This method of bile collection is not ideal because bile flow and composition are often severely altered during the period of study, not all bile is collected and enterohepatic circulation is partially interrupted. Recent advances in the methods of collection of bile may improve future studies of drug excretion in human bile.


Steroid absorption and enterohepatic recycling. A short review on steroid absorption and enterohepatic recycling in man with special emphasis on contraceptive and related steroids is presented. Some new experimental data on the intestinal metabolism of steroids is described and includes further observations on the effect of antimicrobial agents on steroid hormone metabolism. Evidence is presented that plasma levels of steroids may be influenced if the intestinal microflora is altered. Some formation of biologically active steroids, like estradiol, may occur in the intestinal tract and this may have both biological and pathological consequences and may be influenced by such factors as diet and sex. It is concluded that our knowledge of the intestinal and especially, the mucosal metabolism of steroids is scanty and further studies are needed to clarify the role of the intestine and enterohepatic circulation in determining the bioavailability of natural and synthetic steroids.


Contraception via topical application? - A review. The skin, generally speaking, is not an absorption organ but one of its major functions is the protection of the body against the entrance of foreign material. Under certain circumstances, however, drugs can be introduced into the skin and thereby into the body as can be seen in the topical treatment of skin diseases. Though percutaneous pharmacokinetics of steroids seem appropriate for contraception, the variability of the absorption process appears to be too high for this purpose.


The anatomy of transcarboxylase and the role of its subunits. Biotin enzymes in general catalyze the fixation of CO2 and in a few instances decarboxylations yielding CO2. Transcarboxylase is an exception; it catalyzes the transfer of a carboxyl group from one compound to another and CO2 is not involved. This enzyme plays an essential role in the formation of propionic acid by propionibacteria and its structure and catalytic mechanism have been extensively investigated including studies of the quaternary structure by electron microscopy. The structure is complex, consisting of three types of subunits: (1) a central hexameric subunit, (2) six dimeric outside subunits, and (3) twelve biotinyl subunits which bind the outside subunits to the central subunit. There are 12 substrate sites on the central subunit (2 per polypeptide) and 2 substrate sites on each of the dimeric outside subunits. The carboxyl is transferred between these sites via the biotin of the biotinyl subunit. The biotinyl subunit (approximately 123 residues) has been completely sequenced and it has been shown that the first 42 residues serve in binding the outside subunits to the central subunit and the remainder of the sequence is involved in placing the biotin between the subunits so that it may serve as the carboxyl carrier between the substrate sites on the central and outside subunits. It is proposed that the dual sites on the polypeptides of the central subunit have arisen as a consequence of gene duplication and fusion. An intriguing question is why such a complicated structure is required for catalysis of a rather simple reaction.


Noninvasive three-dimensional viewing of the motion and anatomical structure of the heart, lungs, and circulatory system by high speed computerized X-ray tomography. A new generation X-ray computerized tomography system now under construction, the Dynamic Spatial Reconstructor (DSR), will record 1680 multiple view X-ray video images of the chest or other segments of the body per second. This allows com0utation of stop-action and 60-per-second instant replay motion pictures of the dynamic three-dimensional changes in shape and dimensions of the full anatomic extents of the internal and external surfaces of the heart chambers or the vascular anatomy and circulatory dynamics in any region of the body. Current commercially available scanners require one or more seconds per cross-sectional scan and lack the synchronous volumetric scanning capabilities of the DSR. These capabilities allow nondestructive mathematical selection and removal of any subvolume of interest from a reconstructed volume. The associated abilities to "zoom in" and "section" this subvolume so as to examine its structure and physiologic function in detail allow direct visualization of the internal anatomy and function of organ systems within the body. These capabilities of "noninvasive numerical biopsy" and "vivisection" have heretofore been the preserve of pathologists at autopsy or surgeons at the operating table. Possible future availability of these techniques to the practicing internist carries promise of revolutionary improvements in clinical diagnosis and treatment of the myriad of disease processes, including cancer, which may affect the heart, lungs, vascular anatomy or circulatory dynamics in any region of the body.


Plasma protein patterns in health and disease. The complex nature of protein metabolism has made interpretation of serum protein data a difficult task. Interpretive efforts can be facilitated by use of protein profiles which consist of quantitative immunochemical data combined with qualitative electrophoretic patterns. These profiles can be designed to clarify physiological relationships and emphasize pathological conditions through pattern recognition. This review will present protein profiles observed in acute, subacute, and chronic inflammation: liver diseases, protein losing disorders, plasma cell dyscrasias, humoral immune deficiencies, autoimmune diseases, genetic deficiency states, and other disorders. The value of consultative interaction and the use of combined profiles in the assessment of a patient's protein status will be covered. A discussion of protein patterns in normal individuals will include data on day-to-day, age- and sex-related variation. A section on management of protein data will present various approaches to profile reporting. Graphical report formats which minimize the time required for information transfer and simplify assimilation of results will be emphasized.


Lipoprotein-X.

Lipoprotein-X. Lipoprotein-X is an abnormal lipoprotein that appears in the sera of patients with obstructive jaundice, and thus is a sensitive indicator of cholestasis. In patients with familial plasma lecithin, Cholesterol acyltransferase (LCAT) deficiency, there is an inverse relationship between plasma Lp-X levels and LCAT activity. Ultracentrifugation procedures utilized for isolation of Lp-X have shown that it is associated with the low density lipoprotein fraction. Lp-X can be visualized by electrophoresis on either Agar or Agarose. The purity of Lp-X preparations has been documented by immunochemical procedures. The availability of highly purified antisera to Lp-X has served as a basis of one of the assay procedures for this lipoprotein. It's chemical composition has been established. Phospholipids and unesterified cholesterol constitute the bulk of the Lp-X molecule. Electron microscopic studies have demonstrated that Lp-X is a spherical particle which has strong aggregating properties. Membrane bound enzymes have been shown to aggregate with Lp-X. The fact that bile lipoprotein can be converted to Lp-X by the addition of albumin and that Lp-X can be converted to bile lipoprotein by the addition of bile salts offers a possible explanation for the origins of Lp-X. Phospholipases of plasma might play a role in the catabolism of Lp-X. The value and limitations of Lp-X determinations will also be addressed in this review.


Actinomycosis of the head and neck.

Actinomycosis of the head and neck. Actinomycosis has been known to involve virtually every anatomic site in the body; those infections involving the head and neck will be reviewed. Actinomycosis of the head and neck has many presentations; it may disguise itself as a tumor or present as a draining abscess which has failed to reveal an infectious agent as its etiology. With more recent attention directed toward the detection of anaerobic organisms especially in the cervicofacial region, this diagnosis is being made more frequently. In this review, a discussion of the bacteriology of Actinomyces, including a review of its taxonomy, morphology, growth requirements, and biochemistry, will be presented. Recommendations are made to clinicians and laboratory personnel who handle such specimens in order that they might obtain maximum information. In addition, infections which mimic or accompany actinomycosis will be reviewed. The diagnosis and management of this infection, including the physical exam, X-ray and laboratory tests, and collection and handling of specimens, as well as the surgical and antibiotic therapy will be discussed in depth. The variety of clinical presentations with their differential diagnosis is used to illustrate the complexity of this disease.


Screening tests for cell-mediated immunodeficiency diseases. As our knowledge of immunology has become more sophisticated we have had to alter our ideas of the etiology of many immune deficiency diseases. Indeed, current concepts now prevalent have led to reclassification of a number of disease entities. In order to keep our diagnostic efforts abreast of the information being generated by the extensive immunology research programs now in progress, the clinical laboratory has been required to offer a new array of sophisticated tests on a relatively routine basis. This article is intended to serve as a brief review of immunobiology and immunodeficiency diseases with an indepth coverage of specialized tests generally available at the large centers. With an understanding of the principles, procedures, and pitfalls of the tests carried out the laboratory scientist is in a better position to assist the clinician in reaching the correct diagnosis. The detailed review is concerned with methods available to separate, classify, and subclassify lymphocytes and thereby allow a categorization of immune deficiency diseases. Toward that end there is a discussion of surface markers, rosetting, mitogenic and antigenic responsiveness as well as lymphokine production. With a view to present day research tests that might eventually find their way into the armamentarium of the clinical laboratory in the future, there is brief discussion of the methods presently used to classify T-cells as helper, suppressor, or effector cells, assays of some of the lymphokines, and measurement of antibody synthesis in cell culture.


Pulmonary interstitial gas: first sign of barotrauma due to PEEP therapy. Radiographic identification of pulmonary interstitial gas is a prime indicator of possible further complications in patients treated with PEEP therapy for severe respiratory failure. Records and chest radiographs of 89 adult patients treated with PEEP in a 40-month period were reviewed. Data of 7 were incomplete, 82 cases were analyzed. Of 17 patients who developed interstitial gas, 9 progressed to further barotrauma complications of pneumomediastinum, pneumothorax, and extrathoracic dissection. Interstitial gas is manifested radiographically by vesicular rarefactions (cystic changes), linear streaks along the bronchi and vessels, halos of gas around vessels, and subpleural gas.


Pneumothorax and pneumomediastinum during pediatric mechanical ventilation. The incidence of pulmonary barotrauma during mechanical ventilation in children beyond the neonatal age group was studied in two groups of patients. In the first group, 179 cases of pediatric mechanical ventilation for over 12 hours were retrospectively analyzed for the occurrence of pneumothorax and pneumomediastrinum. Eleven percent (6 of 57) of young infants (0--6 months) without hyaline membrane disease and 3% (4 of 122) of older infants and children (over 6 months) developed these complications. Pulmonary barotrauma in young infants occurred only after cardiothoracic surgery and involved the same site as the intraoperative repair in all cases. Pulmonary barotrauma in older infants and children occurred in patients with severe respiratory disease requiring high peak airway pressures, PEEP, and respiratory rates. In the second group, the incidence of pulmonary barotrauma during ventilation with PEEP greater than or equal to 15 cm H2O was analyzed in 14 patients including 4 patients from the previous group. Overall, 64% (9 of 14) of this group developed pulmonary barotrauma and 43% (6 of 14) developed pneumothorax. Of 9 patients receiving PEEP greater than or equal to 15 cm H2O for longer than 24 hours, 6 developed pulmonary barotrauma after the first 24 hours. The incidence of pneumothorax and pneumomediastinum in ventilated infants without hyaline membrane disease and children is comparable to adult series.


Use of positive airway pressure without endotracheal intubation. Continuous positive airway pressure (CPAP) and expiratory positive airway pressure (E-PAP) may be used safely without endotracheal intubation in patients with acute respiratory failure when strict selection criteria are adhered to. The therapy should be titrated to reduce intrapulmonary shunting, improve PaO2, and reduce FIO2. Other considerations include balancing oxygen consumption against cardiac output and oxygen transport. Absolute or relative indications for abandoning the technique and using endotracheal intubation with mechanical ventilatory support include unrelenting hypoxia, patient exhaustion, rising PaCO2, development of metabolic acidosis, presence of ventricular arrhythmias, and inability to protect the airway.


Radiologic demonstration of anomalous pulmonary venous connection and its clinical significance. 1. As surgical techniques continue to improve, early diagnosis and early surgical intervention of APVCs become increasingly important. 2. For a thorough understanding of APVCs, normal development of the pulmonary veins and the embryological basis of these anomalies are briefly reviewed. 3. Radiologic signs and clinical implications of varying types of APVCs are illustrated. 4. TAPVCs are less frequent, but clinically more significant, than PAPVCs. 5. The symptomatology of TAPVC is directly related to (1) the degree of pulmonary venous obstruction, (2) the severity of CHF secondary to volume overload, and (3) the magnitude of pulmonary hypertension. Patients with PAPVC become symptomatic only when the left to right shunt is greater than 50%9 6. TAPVC to the LVV produces a pretracheal density on the lateral view prior to the appearance of snowman configuration on the postero-anterior view. TAPVC to the PV shows a combination of severe pulmonary edema and a normal-sized heart. 7. PAPVC may be diagnosed by visualization of the anomalous vein(s) in addition to the usual signs of an ASD (increased pulmonary blood flow plus right-sided cardiomegaly). 8. PAPVC is usually associated with an ASD. Scimitar syndrome is an exception to the rule. 9. The surgical repair of TAPV without obstruction is generally relatively simple because of the strong tendency for all of the pulmonary veins to converage into a common chamger. Emergency operation is the only hope for patients with TAPVC with obstruction. 10. The surgical treatment of PAPVC consists of reconstruction of the atrial septum; thus, the anomalous veins can be diverted into the left atrium. 11. Surgical correction of PAPVC prevents detrimental resection of the lung with normal pulmonary venous connection.


Angiographic diagnosis and control of postoperative bleeding. The use of diagnostic and therapeutic angiography for postoperative bleeding which began with its application for bleeding following GI surgery can be ezpanded to almost all other areas of the body. Severe postoperative hemorrhage that previously required a second operation can now be successfully managed by the use of intraarterial or intravenous vasoconstrictors or transcatheter occlusion, thus significantly reducing patient morbidity and mortality. In those patients where a reexploration becomes necessary, diagnostic angiogarphy is a useful guide and helps to tailor the operative procedures.


Determination of vitamin D in foods: a review. Determining vitamin D content in foods is difficult because in natural foods of highest vitamin D activity, and even in vitamin D-fortified foods, only small quantities are present, and many other compounds are extracted along with vitamin D that cause difficulties in purifying the extract or in the spectrophotometry or colorimetry that follows. Several physicochemical methods--such as spectrophotometric, colorimetric, thin-layer chromatographic, adsorption, partition, gas-liquid, and high-performance column chromatographic--have been tried for assay foods for vitamin D, but none of them have been accepted for official or routine use; they are time consuming and expensive, or lack the required sensitivity, precision, or accuracy. Curative biological assays, based on degree of healing of a leg bone of rats previously made rachitic, is the generally accepted method to determine vitamin D content of foods. However, that method also requires too much time and is expensive. The recently developed high-performance liquid chromatographic method may offer the most for establishing a satisfactory physicochemical method for determining vitamin D in foods. Many of the difficulties and problems in assaying foods for vitamin D are discussed.


Flavor composition of wines: a review.

Flavor composition of wines: a review. The formation of flavor in fermented beverages is due to various biosynthetic mechanisms. In wine, flavors arise as the result of compounds: 1. Originating from the native fruit (grap) 2. Which are formed or altered during the various processes employed in production 3. Which are developed or transformed by yeast during fermentation 4. Arise during the aging process In this review the results of investigations on the development of flavors in grape and wine will be discussed. Special attention will be devoted to the effects of specific processes in winemaking on the development of flavor.


The effects of malnutrition on secretory and cellular immune processes. About 15 million children under 5 years of age die each year due to suppressed immunity and the resulting increased infection. In severely malnourished children and animals some immune systems such as T-cell function, secretory IgA and complement are significantly suppressed. Other systems, such as the serum IgG or IgA, are normal or even elevated. Some of these changes are apparently caused by nutritional stress while others may be due to stimulation by increased incidence of infection and antigen load. On the other hand, marginal malnutrition stimulates increased phagocytosis and T-cell function with increased immunity to cancer but decreased resistance to certain microbial agents. The mechanisms of immune suppression by malnutrition, persistence of these effects after renutrition, and the effect of maternal malnutrition on newborn immunity are critically reviewed. Possible non-nutritional means of rapid immunological restoration of malnourished children are described.


Mutagenic factors in cooked foods.

Mutagenic factors in cooked foods. The charred surface of fish and beef showed strong mutagenic activity in Salmonella typhimurium test strains when activated by S-9 mix of rat liver. The pyrolysis products of proteins and amino acids were also highly mutagenic. Among the pyrolysis products of amino acids, those of tryptophan, serine, and glutamic acid were most active. The new gamma-carboline derivatives, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole and 3-amino-1-methyl-5H-pyrido[4,3-b]indole, were purified from the pyrolysis products of tryptophan. These new compounds were stronger mutagens than aflatoxin B1 towards S. typhimurium TA98, a frameshift type mutant, and they also transformed cryopreserved Syrian hamster embryo cells in vitro. Tryptophan pyrolysate also contained the beta-carboline derivatives, norharman and harman, which are not mutagenic alone, but act as comutagens. A mixture of norharman or harman and nonmutagenic aniline or o-toluidine was strongly mutagenic. The mutagenicities of charred products of other foods, such as seaweed and garlic, are reviewed in this article. Flavonoids, such as kaempferol and quercetin, and glycosides of these flavonoles were mutagenic. The mutagenicity of cooked vegetables depends partly on these flavonoid derivatives. The already-known existence of benzol[a]pyrene and nitroso compounds in cooked food is also reviewed.


Macrophage polykarya.

Macrophage polykarya. Multinucleated giant cells are commonly found in a wide variety of inflammatory reactions. They are formed at sites of tissue injury by fusion of freshly exuded monocytes, the rate of fusion being dependent on a range of extracellular and intracellular factors. Electron miscroscopy shows that the pooled components of the fused monocytes are not randomly dispersed in the syncytium, but are highly reorganized into a functioning unit. In addition, histochemical and biochemical profiles of cell populations containing these polykarya display a range of metabolic activities, including DNA synthesis, which, on occasions, is followed by successful mitotic division and the formation of polyploid daughter cells. Fusion results in the loss of some surface receptors which in turn interferes with the phagocytic performance of polykarya, which is generally less pronounced than their mononuclear precurses. In addition, polykarya are not as actively motile as macrophages although phenomena of contact inhibition are less obvious. On the other hand, the multinucleate giant cells display prominent exocytosis which may aid in the degradation of extracellular material. The properties of macrophage polykarya contrast with macrophage homokarya produced in vitro. The latter are actively phagocytic, do not synthesize DNA, and have a longer half-life than the syncytia produced in chronic inflammatory reactions. It may well be that the polykarya in such reactions are not true homokarya.


Behavioral, neurological, and toxic effects of methyl chloride: a review of the literature. A large number of reports have been devoted to the physiologic and toxic effects of methyl chloride, many of which are based on case histories involving occupational exposure. The detrimental actions of methyl chloride on the central and peripheral nervous systems are well established effects. It is a moderately severe narcotic and potentially severe nerve poison. Chronic intoxication is associated with damage to the central nervous system (CNS), kidneys, liver, bone marrow, cardiovascular system, respiratory system, and intestinal tract. The signs and symptoms range from the more severe medical dysfunctions such as cardiac irregularities, respiratory paralysis, nerve degeneration, and severe convulsions to the more subtle clinical observations such as CNS depression, nervousness and emotional instability, insomnia and anorexia, ataxia, blurred vision, light-headedness, nausea, dizziness, narcosis, and disorientation. The behavioral correlates of these and other neurotoxic effects of methyl chloride suggest that a gradual behavioral degradation occurs. Pharmacodynamic studies have shown the compound to be rapidly absorbed by the blood with most authors attributing the toxicity to an enzyme-catalyzed methylation reaction in the body. Despite the fact that several investigators have attempted to correlate such biological responses of methyl chloride with its toxicity, the present knowledge of the problem still lacks a detailed mechanism of action. Until such mechanisms are verified, adequate methods to assess subclinical neurological and behavioral changes must be effectively developed.


Ultrastructural localization and in situ analysis of iron, bismuth, and gold inclusions. The purpose of this article is to review ultrastructural and electron probe X-ray analytical studies on metallic deposits in cells. The metals that will be dealt with are iron, bismuth, and gold, mainly because they have been extensively studied in recent years. The nature and chemical composition of endogenously (e.g., from breakdown of autologous blood) and exogenously (e.g., after a transfusion or injection of iron compounds) produced hemosiderin (i.e., iron deposits) has been the subject of time-hallowed controversies. Quite a few of these have now been resolved by ultrastructural studies and the atomic composition of such deposits has been determined by electron probe X-ray analysis. The interest in bismuth centers around the fact that this is one of the two metals (the other being lead) that produces quite large intranuclear inclusions. Here again much has been learned by ultrastructural and X-ray analytical studies. The interest in gold stems from the fact that soluble salts of this metal are used for the treatment of rheumatoid arthritis and current studies with the above-mentioned techniques indicates how gold produces its beneficial and toxic effects.


Hypervitaminosis A induced teratogenesis. In the past decade, the toxicology of reproduction has become increasingly important. This branch of toxicology focuses on mutagenic and embryotoxic effects. The study of embryotoxicity requires an extensive knowledge of the interaction of drugs and embryonic tissues, normal and abnormal developmental processes, and the susceptible stages during prenatal development. Hypervitaminosis A is one of the most extensively studied teratogens. It produces defects in almost all organ systems. Therefore, this article will first of all review the vitamin A-induced malformations in several organ systems. Moreover, it will discuss their morphogenesis and the susceptible developmental stages. Thus, the first ten chapters will cover the following subjects: malformations of the nervous system, ocular malformations, malformations of the ear, craniofacial malformations, cleft palate, defects of the circulatory system, defects of the respiratory systems, defects of the digestive tract, urogenital defects, skeletal malformations, and abnormal postnatal development. Since in general little is known about the mechanisms involved in the induction of congenital defects, we think it is of great value to review the knowledge and experience that have been gathered by the experimental work with hypervitaminosis A. Therefore, the next chapters will discuss the following subjects: teratogenic effects in different species, minimum effective dose, interaction with other agents, influence of chemical form, solvent, and route of administration, pathophysiology of vitamin A embryotoxicity, and hypervitaminosis A and human pregnancy.


The detection and diagnosis of early occult and minimal breast cancer. This article has attempted to describe the present status of efforts toward routine detection of breast cancer at a stage when it is readily curable and to point out, not only the potentials of screening programs, but also the problems and difficulties that beset them. We believe that efficient, safe screening and accurate early diagnosis are achievable and that trial directed toward this end should not only continue but expand. We see no other avenue that offers as bright a prospect for a meaningful reduction in breast cancer mortality and the monstrous toll--medical, emotional, sociologic and monetary--it exacts.


Creatine kinase MB isoenzyme in the evaluation of myocardial infarction. The measurement of serum CK-MB isoenzyme is a very sensitive and specific indication of myocardial injury since only myocardium has substantial amounts of CK-MB. Serum CK-MB levels are most helpful clinically when the total creatine kinase is nonspecifically elevated, as with intramuscular injections, cardiac catheterization, stroke, noncardiac surgery and electric cardioversion. Elevations of serum CK-MB occurring in Duchenne's muscular dystrophy and other neuromuscular disorders may be due to the presence of abnormal regenerative skeletal muscle fibers, which are known to contain large amounts of CK-MB isoenzyme. These examples emphasize that under normal, nonregenerative conditions, elevations of serum CK-MB are rare in the absence of myocardial injury.


Malignant group B streptococcal endocarditis associated with saline-induced abortion. A 20-year-old woman developed acute group B streptococcal endocarditis following saline-induced abortion. In the pre-antibiotic era, most cases of group B streptococcal endocarditis occurred in parturient or postabortal women. Currently, this disease is rarely described in obstetrical patients, and no previous cases following saline-induced abortion have been reported. Purulent pericarditis and a perivalvular abscess were present in our patient and represent only the second instance in which these findings have been documented in this disease.


Invasive aspergillosis presenting as pericarditis and cardiac tamponade. A 38-year-old leukemic patient developed pericarditis and cardiac tamponade due to Aspergillus niger one month after undergoing bone marrow transplantation. She failed to improve even though amphotericin B and rifampin therapy had been initiated before infection was evident. Her unique case illustrates both the unusual presentations of invasive aspergillosis and the difficulty of diagnosing and treating this increasingly common disease.


[Clinical use and comparative study of Ulmer drainage and of the usual Redon tissue drainage]. After discussing the shortcomings of the usual Redon drainages and the description of our own technique of vacuum-tissue suction drainage, there follows a report about a comparative examination between Redon drainages and the new 'Ulmer drainage'. Up to now the superiority of the Ulmer drainage was proven only by calculation and experiment, now this fact can be fully confirmed by a succession of clinical examinations. By inserting both types of drainages in one surgical wound, the Ulmer drainage delivered on the first day 1.5 times; on the second and third day, almost 2.5 times the amount of secretion compared with the usual Redon drainage.


Biochemical studies of transient intermediates in relation to chemical carcinogenesis. Many chemical carcinogens must be metabolized to chemically reactive transient species before they can exert their full toxic action on mammalian cells. In general, this metabolic activation is performed by NADPH-dependent enzymes in the endoplasmic reticulum; the NADPH-cytochrome P-450 electron-transport chain is very important in this respect. Biochemical studies on the chemical reactivities of such transient intermediates require the application of various fast-reaction and free-radical techniques: the use of such techniques is illustrated by reference to the metabolism of carbon tetrachloride. CCl4 is metabolized by liver endoplasmic reticulum in the presence of NADPH to a highly reactive product, probably CCl3; this activation of CCl4 results in covalent binding of CCl3 and lipid peroxidation. The steady-state concentration of CCl3 is too low to be measured directly by e.s.r. spectroscopy but radical species can be accumulated with spin-trap techniques. The CCl3 radical can be generated by pulse radiolysis and the ensuing reactions with biologically important neighbouring species can be followed in the microsecond range by kinetic spectroscopy. The results point to the high reactivity of CCl3 and its restriction to a microenvironment within the endoplasmic reticulum. Highly reactive electrophilic radicals (e.g. CCl3) can initiate lipid peroxidation in biomembranes and this is associated with changes in polyunsaturated fatty acids and in membrane fluidity. The results are discussed in relation to carcinogen activation, to free-radical-mediated reactions in biomembranes, and to the general thesis that the production of reactive aldehydes by lipid peroxidation may act as a 'coarse control' of cell division.


G-cell population in antral mucosa of the dog. The gastrin-cell (G-cell) population in the pyloric antrum of 8 dogs was studied quantitatively by immunofluorescence. The G-cell population was dense in the pyloric antrum and very few cells were seen in the antrocorporal junction. The estimated total number of G cells was (1.66 +/- 0.12) X 10(7) in the pyloric antrum and the greatest number of G cells per unit mucosal surface area was along the greater curvature of the pyloric antrum. Except along the greater curvature, G cells per unit musocal volume were significantly greater in number (P less than 0.05) in the proximal antrum adjacent to the antrocorporal junction that in any other regions distal to it. Differences in mucosal thickness were considered as a causative factor for these differences.


Gastrointestinal manifestations of diabetes mellitus. This review briefly outlines the gastrointestinal manifestations of diabetes mellitus. Usually, gastrointestinal abnormalities are asymptomatic. Severe gastrointestinal dysfunction may be quite debilitating, however. Gastrointestinal symptoms that are a consequence of diabetes may be confused with other primary gastrointestinal disorders. We attempt to provide a clinical approach to differentiating the basis of symptoms and outline the therapeutic plan that we generally employ. Much additional research is necessary to clarify our understanding of the pathophysiology of the gastrointestinal complications of diabetes and to develop improved therapeutic strategies.


[A case of legionnaire's disease in Germany (author's transl)]. Severe bronchopneumonia in a 66-year-old patient failed to respond to sensitivity-tested antibiotics, with only erythromycin providing improvement. The indirect immunofluorescence test for legionnaire's disease gave a highly significant titre rise (eightfold). Legionnaire's disease should be considered in the differential diagnosis of treatment-resistant bronchopneumonia.


[Immune-haematological diagnosis of neonatal immunothrombocytopenia (author's transl)]. The diagnosis of immunologically caused platelet deficiencies in newborn infants requires use of methods permitting demonstration of platelet auto- and allo-zntibodies, complete and incomplete antibodies. Taking the well known differentiation of neonatal immunothrombocytopenias into auto- and allo-immune diseases as a basis, the immune-haematological findings in eight cases are reported. For the first time two cases are reported in which both idiopathic thrombocytopenic purpura of the mother was known and allo-immunisation against paternal HLA antigens of the child could be demonstrated.


Glipizide: a review of its pharmacological properties and therapeutic use. Glipizide is a 'second generation' oral hypoglycaemic agent similar in potency to glibenclamide. It is completely absorbed after oral administration and has a rapid onset of action, but the duration of its hypoglycaemic effect is shorter than that of glibenclamide. It is rapidly metabolised to inactive metabolites which are excreted in the urine. Therapeutic trials have shown the efficacy of glipizide in maturity onset diabetes mellitus to be comparable with that of glibenclamide and chlorpropamide in newly diagnosed patients unresponsive to diet as well as in patients previously treated with oral hypoglycaemic drugs. Glipizide is well tolerated, but careful adjustment of dosage and attention to diet may be needed to avoid hypoglycaemic symptoms a few hours after a single daily dose.


Drug-induced renal disease.

Drug-induced renal disease. The clinical manifestations of drug-induced renal disease may include all the manifestations attributed to natural or spontaneous renal diseases such as acute renal failure, chronic renal failure, acute nephritic syndrome, renal colic, haematuria, selective tubular defects, obstructive nephropathy, etc. It is therefore vital in any patient with renal disease whatever the clinical manifestations might be, to obtain a meticulous drug and toxin inventory. Withdrawal of the offending drug may result in amelioration or cure of the renal disorder although in the case of severe renal failure it may be necessary to utilise haemodialysis or peritoneal dialysis to tide the patient over the period of acute renal failure. Analgesic nephropathy is an important cause of terminal chronic renal failure and it is therefore vital to make the diagnosis as early as possible. The pathogenesis of some drug-induced renal disorders appears to be immunologically mediated. There are many other pathogenetic mechanisms involved in drug-induced renal disorders and some drugs may under appropriate circumstances be responsible for a variety of different nephrotoxic effects. For example, the sulphonamides have been incriminated in examples of crystalluria, acute interstitial nephritis, acute tubular necrosis, generalised hypersensitivity reactions, polyarteritis nodosa and drug-induced lupus erythematosus.


[Temperature and reaction heat of elastomer casting materials]. Cross linking of the elastomer cast material is an exothermic process. The heat of reaction may produce temperature increases of several degrees centigrade in the thermically insolated samples. The heat of reaction per volume was measured; polysulfide and polyether values are approximately 10 times higher than those for silicone.


[Change of the pier distance in saw models dependent on the setting expansion of the base cast]. Saw models of Duroc were constructed from a cast made over a Siccoform model. Various base casts were used. Compared with the original cast, the pier interval was reduced in all models. The dies were slightly tilted toward each other; the degree of tilting increased in direct proportion to the setting expansion of the base cast.


[Prosthetic aspects in the planning of progenia operations]. Operative planning for progenia is carried out using prosthetic principles. Correction of a malpositioned mandible, modelling of incongruent dental arches, functional distribution of piers, and a favorable interalveolar connecting line form the basis for stable occlusion and articulation. The fitting of a prosthesis later is simplified by such intensive interdisciplinary cooperation.


The fate of fertilized ova in rats receiving luteinizing hormone-releasing hormone (LRH). The development and eventual fate of unimplanted fertilized ova in rats receiving pregnancy-inhibiting doses of luteinizing hormone-releasing hormone (LRH) were studied during the first 14 days of gestation. The results suggest that LRH accelerates passage of ova through the oviducts. Also, the zona pellucida of treated animals is retained by the majority of ova until day 7; zona-encased ova were observed as late as day 10. Elimination of the ova appears to occur by expulsion with uterine fluids through the vagina upon the animals' return to estrus.


Regulation of epididymal function and sperm maturation--endocrine approach to fertility control in male. The structural and functional integrity of the epididymis, the acquisition of fertilizing ability by spermatozoa and their viability within the epididymis are androgen dependent phenomena. Although the precise mechanism by which sperm maturation and viability in the epididymis are brought about by androgen are not clearly understood, it is generally held that specific epididymal secretions produced under the influence of androgen affect these events. Though the spermatozoa appear to remain viable in a low androgen environment, sperm maturation requires a relatively high androgen environment. Against this background the potentiality of antiandrogens as extragonadal antifertility agents has been discussed. Studies with steroidal and nonsteroidal antiandrogens have revealed that in adult animals the secretory activity of the epididymis, as evidenced by the level of glycerylphosphorylcholine, either remains unaffected or is stimulated under their influence. These studies have further indicated that the extragonadal antifertility action of antiandrogens will depend upon their ability to (1) lower the testicular androgen synthesis and/or androgen binding protein, which possibly serves as a carrier of androgen from the testis to epididymis; (2) to lower local androgen synthesis as a result of reduced levels of circulating androgen, and (3) to inhibit 5 alpha-reduction of testosterone to dihydrotestosterone and/or to inhibit androgen binding to receptors. Success in the rational development of new antifertility agents for male which will act by controlling epididymal function will depend upon a clear understanding of the factors that regulate epididymal secretion and the role of epididymal secretions in sperm maturation and survival.


Studies on (pro)insulin biosynthesis and secretion of pancreatic islets of sand rats (Psammomys obesus) after different feeding conditions. It was possible to induce different metabolic states in sand rats of our breeding colony or in newly caught Egyptian sand rats, respectively, by feeding a pellet diet or vegetable diet (green cabbage). Newly captured sand rats fed only on native food were used as reference group (group C). Plasma IRI-level and glucose in vivo and [3H]-leucine incorporation into proinsulin and insulin, insulin secretion and insulin content in vitro were investigated. Sand rats fed on pellet chow and ad libitum (group B) developed a hyperinsulinism and showed higher sensitivity of [3H]-leucine incorporation into proinsulin and insulin to glucose (maximal stimulation at 3 mM) and increased incorporation rates in vitro. Restriction of pellet food to 35-40 kcal/animal/day (group A) lead to changes of all parameters, which were investigated in the same direction as in group B, but to a much smaller extent. Newly captured sand rats, which were fed green cabbage for 4 to 6 weeks divided into two groups: One group (group D1) was comparable to the normal group (C) in IRI levels, glucose levels, glucose sensitivity and amount of [3H]-leucine incorporation. The other group (group D2) tended to group A. Marked changes in insulin content and insulin secretion of isolated pancreatic islets could not be found in any group.


Consequences of the AF-2 incident in Japan. The discovery of the potent mutagenicity of AF-2, which was once used in Japan as a food preservative, has exerted a great influence not only on screening procedures for carcinogenic compounds but also on legislative approaches to mutagenic substances. It promoted the synthesis of exceedingly sensitive and reliable tester strains in Salmonella and supported the hypothesis of a common mechanism between mutagenicity and carcinogenicity. Thus preliminary screening for carcinogenic substances has become feasible using mutagenicity as an index. It also contributed greatly to the formulation of legislative measures for chemical substances which for the first time gave due attention to mutagenicity. Furthermore, the exposure of a large population to such a potent mutagen raised a question as to what extent the genetic constitution of the Japanese population might have been damaged. This suggested that urgent need for a system to monitor the total genetic damage to a human genome.


Arrangement of proteins O-8 and O-9 in outer membrane of Escherichia coli K-12. Existence of homotrimers and heterotrimers. 1. The molecular arrangement of major outer membrane proteins O-8 and O-9 that exist as trimers has been studied by means of cross-linking with dimethylsuberimidate. 2. The cross-linked samples were examined on a urea/sodium dodecyl sulfate/polyacrylamide gel which was developed to separate cross-linked trimer and dimer of O-8 from those of O-9. 3. Cells simultaneously synthesizing both O-8 and O-9 formed heterotrimers (trimers containing both proteins) as well as homotrimers. 4. Quantitative analyses revealed that there was no discrimination between O-8 and O-9 in the assembly process to form trimers. 5. When cells were grown sequentially under two different sets of conditions so that the cells synthesized either one of the two proteins in the first stage and the other in the second stage of growth, no heterotrimers were formed. This result indicates that subunit exchange did not take place between trimers which had been incorporated into the outer membrane.


The complete nucleotide sequence of the ribosomal 16-S RNA from Excherichia coli. Experimental details and cistron heterogeneities. The complete nucleotide sequence of the 16-S RNA from Escherichia coli has been determined using rapid RNA-sequencing gel methods. The experimental data are fully described in this paper. The specificities of the ribonucleases, especially the ribonuclease PhyI are discussed and the consequences of the persistence of stable secondary structure are considered. The proposed sequence contains 1541 nucleotides and agrees completely with the DNA sequence of the rrnB cistron deduced by Brosius, J., Palmer, M.L., Kennedy, P.J., and Noller, H.F. [Proc. Natl. Acad. Sci. U.S.A. (1978) 75, 4801-4805]. But there are several cistron heterogeneities of which we described 16 single-base heterogeneities, 7 of the deletion/insertion type and 9 of the transition or transversion type. Our observations suggest the existence, among the 7 ribosome RNA cistrons, of one or two mutated ones. The respective advantages and disadvantages of both RNA and DNA sequencing methods are discussed.


Purification and some properties of deoxyribonuclease whose synthesis is controlled by gene 49 of bacteriophage T4. An enzyme which specifically cleaves very-fast-sedimenting DNA of bacteriophage T4 is synthesized after infection of T4, and its synthesis is controlled by gene 49 [1,2]. This enzyme has been proved to be a DNase [2]. We have purified this DNase 3000-fold from extracts of E. coli infected with T4. The purified preparation was practically free from other DNases, and the DNase activity was not detectable in cells infected with a mutant defective in gene 49. The enzyme activity from cells infected with a temperature-sensitive mutant of gene 49 was also temperature-sensitive, suggesting strongly that gene 49 is a structural gene of the DNase. The molecular weight of the wild-type enzyme was estimated to be 50 x 10(3) by gel filtration chromatography. The purified DNase did not cleave native and denatured DNAs of T3 and T4, but cleaved renatured T3 DNA with enzymatically fragmented T3 DNA, indicating that gaps in the DNA duplex are structures susceptible to the DNase. Cleavage of the hybridized T3 DNA occurred when the fragmented DNA was phosphorylated at either the 3' or 5'-strand termini.


Procollagen synthesis and processing in periodontal ligament in vivo and in vitro. A comparative study using slab-gel fluorography. A combination of dodecylsulphate/polyacrylamide gel electrophoresis and fluorography has been used to quantify the synthesis of type I and type III collagens by periodontal ligament in situ and periodontal-ligament fibroblasts in vitro. The separation of 14C-labelled collagen alpha chains was achieved by introducing an interrupted reduction step, and the total radioactivity in the alpha-chain bands related to the fluorographic response by a series of standard curves. From these curves an accurate assessment of the relative amounts of type I and III collagen synthesized could be made. The same system also allowed the synthesis and processing of the respective procollagens to be analyzed. For the study in vivo, 200-g male rats were injected with 2 mCi [14C]glycine and killed 0.5-6 h later. Periodontal ligament was dissected from the mandibular molars and the newly-synthesized collagens extracted with 0.45 M sodium chloride. In the study in vitro, confluent monkey periodontal-ligament fibroblasts were cultured in the presence of [14C]proline and [14C]glycine. Analysis of labelled collagens showed a rapid conversion of type I procollagen to collagen but type III collagen was recovered as a procollagen intermediate both in vitro and in vivo. Analysis of duplicate samples after pepsin digestion showed type III collagen synthesis to comprise 15% of the total collagen synthesized in vivo and 20% in early subcultures in vitro. However, the proportion of type III synthesized by the fibroblasts decreased on subculturing. The data demonstrate that fibroblasts in vitro retain the basic characteristics of collagen synthesis and procollagen processing found in vivo, but the overall phenotypic expression of the cells is not stable in culture.


F-Actin-depolymerizing activity of human serum. Non-heated human and animal sera contain a factor which exhibited an inhibiting activity on the staining of actin-containing structures by anti-actin antibodies in indirect immunofluorescence experiments. The presence of this factor lowered the viscosity of F-actin preparations and caused, as studied by electron-microscopy, a depolymerization of F-actin filaments as well as inhibition of filament formation of G-actin. The factor was, after its reaction with F-actin, liberated seemingly unaffected, indicating an enzymatic activity. The factor tentatively termed 'F-actin depolymerizing factor' was heat-sensitive and trypsin sensitive but resisted reduction. It was Ca2+ dependent and the staining inhibiting reaction was faster at 30 degrees C and 37 degrees C than at lower temperatures. Gel filtration experiments on Sephadex G-200 suggested a molecular size of the actin depolymerizing factor slightly higher than that of albumin. The electrophoretic mobility was that of gamma 2 globulin. The physiological role of the factor might be to prevent the presence of F-actin filaments within the circulation.


Translation by Escherichia coli ribosomes of alfalfa mosaic virus RNA 4 can be initiated at two sites on the monocistronic message. Substantial evidence is provided to corroborate our previous finding that Escherichia coli ribosomes recognize two binding sites on the 5' end of alfalfa mosaic virus (AMV) RNA 4 [for a preliminary report see Castel, A., Kraal, B., Kerklaan, P. R. M., Klok, J., and Bosch, L. (1977) Proc. Natl Acad. Sci. U.S.A. 74, 5509--5513]. Translation can start at either site using AcPhe-tRNA or fMet-RNA as initiator and takes place in the same reading frame along the monocistronic mRNA. The size and composition of the isolated extra NH2-terminal fragment of the acetylphenylalanyl product were found to be in agreement with the 5' non-coding region of the messenger. Removal of the 5'-terminal cap structure of AMV RNA 4 did not influence significantly both initiation reactions. Ribosomal protein S1 was essential for binding as well as incorporation of both fMet-tRNA and AcPhe-tRNA. A similar interaction on the ribosome was found for AcPhe-tRNA directed by AMV RNA 4 as for fMet-tRNA directed by either AMV RNA 4 or MS2 RNA with respect to the influence of initiation factors. It is concluded that the heterologous plant viral messenger is reliably translated in the E. coli system and that E. coli ribosomes recognize with high specificity an extra initiation site close to the 5' extremity of the messenger. The relationship of this site to a hypothetical entry site involved in the early recognition in the initiation mechanism between ribosome and messenger is discussed.


Mössbauer spectroscopic studies of iron in Proteus mirabilis. Mössbauer measurements of Proteus mirabilis cells grown in 57Fe-enriched media show that considerable quantities of iron are incorporated, particularly in the stationary phase of growth. A major part of the iron is in a form which shows magnetically split spectra at low temperatures. Fractionation of cells reveals that iron is present in both the soluble and particulate fractions, with the larger proportion being found in the soluble fraction. The iron in the particulate fraction is predominantly found in the outer membrane.


Pancreatic endocrine response to the first feed in term newborn infants. Blood glucose, insulin, C-peptide and glucagon were evaluated in 36 newborn term infants at birth, and before and 60 min after the first feed during the first day of life. Under basal conditions glycaemia diminished during the first day of life and glucagon increased, while insulin and C-peptide did not show any variation. The C-peptide: insulin molar ratio was higher in the newborn than in adults because of the longer half-life of C-peptide, probably due to reduced renal function in the neonatal period. The subjects were divided into two groups: 18 newborn infants were given a feed of commercially available milk powder reconstituted in water at 10% (5 ml/kg); the other 18 were given a feed of 5 ml/kg 10% glucose solution. In each group 6 were given the first feed after a fast of 6 h, 6 after a fast of 12 h and 6 after a fast of 24 h from birth. After the first feed with milk, the average increase of glycaemia was 19.83 mg%, of insulin 6.06 muU/ml, and of C-peptide 1.88 ng/ml. After the first feed with glucose the average increase of glycaemia was 13.59 mg%, of insulin 2.46 muU/ml, and of C-peptide 0.59 ng/ml. Glucagon did not show significant changes after the first feed.


Study of the protective effect of methylprednisolone, furosemide, and mannitol on ischemically damaged kidneys. Canine kidneys subjected to 90 min of warm ischemia (37 degrees C) were protected by the administration of methylprednisolone but not by furosemide or mannitol. There was no protective effect observed through the vasodilating or diuretic effect of furosemide in the ischemic canine kidney. Mannitol-induced diuresis before warm ischemia also did not prove to be beneficial for severely ischemic kidneys. Methylprednisolone (30 mg/kg) given 2 h prior to warm ischemia prevented irreversible kidney damage observed in the control and experimental groups. By day 8 the serum creatinine and creatinine clearance returned to normal levels.


Echocardiographic studies of children operated on for congenital heart disease; evaluation in the immediate postoperative period. In the immediate postoperative period, echocardiography was used to study left ventricular function in 69 children after correction of various congenital cardiac malformations. Left ventricular contractility indices and systolic time intervals measured from aortic cusp echoes were repeatedly obtained during the fist postoperative week. The degree of impairment of left ventricular function was assessed for different diagnostic groups and are tabulated. Decrease in left ventricular function was strongly correlated to operating time, cardiac bypass time, and aortic clamping time, the most important factor being cardiac bypass time. Left ventricular ejection time (LVET) was the most useful parameter of cardiac function in the immediate postoperative period and was of prognostic value in 5 patients who died early in that period. Abnormal septal movement was seen in most patients, but usually normalized within 2 wk. After extensive operations, changes in the movement pattern of the aortic leaflets were also seen. Although pericardial effusion was commonly found during the postoperative period, it did not indicate postcardiotomy syndrome and disappeared spontaneous within 2 mth.


Dissociation between drug-induced increases in nerve terminal and non-nerve terminal pools of GABA in vivo. To examine whether increased GABA levels produced by n-dipropylacetate (DPA) and amino-oxyacetic acid (AOAA) are associated with nerve terminals, we compared the effect of these drugs on the GABA content of substantia nigra (SN) in rats in which the GABAergic afferent projections to SN had been unilaterally destroyed. In the SN largely devoid of GABAergic nerve terminals, AOAA (30 mg/kg) produced a 2-fold increase in GABA, whereas DPA (300 mg/kg) was without effect. Since DPA and AOAA both increased GABA to a similar extent in the intact SN, it appears that the GABA increase produced by DPA is associated with GABAergic nerve terminals, while AOAA primarily elevates GABA in non-nerve terminal components (neural perikarya and glial cells) which are not destroyed by our lesions.


Effects of cervical dislocation on colony-forming cells in murine marrow cultures. Bone marrow obtained in a conventional manner after killing mice by cervical dislocation demonstrates increased absolute numbers of GM-CFC when compared to that from living anesthetized mice. The anesthetic agent does not account for the observed difference. Interpretation of all studies of murine marrow culture must take this observation into account, and extrapolation of the results of such studies to living human marrow should be made with care. Further studies of the mechanisms by which cervical dislocation increases the numbers of GM-CFC may help to elucidate certain mechanisms of commitment of the pluripotential hemopoietic stem cell.


Engraftment of bone marrow transplants in W anemic mice measured by electronic determination of the red blood cell size profile. Defective stem cells of WBB6F1-W/Wv mice produce macrocytic red blood cells (RBCs); stem cells of WBB6F1-+/+ mice produce normocytic RBCs. Utilization of the Coulter counter channelyzer permitted good dissociation between the size distribution of populations of +/+ and W/Wv RBCs. Peaks (mean cell volumes) for +/+ and W/Wv RBCs have been determined to be between the 30th and 40th channel and 50th and 60th channel, respectively. Variability of profiles for individual mice of both genotypes did not exceed the variability of separate determinations of the same cell suspension from a single mouse. Admixture (approximately 15%) of either type of erythrocytes could be quantitatively detected by this method. One week after transplant of 10(7) +/+ marrow cells into W/Wv recipients, 25% of donor type erythrocytes were detected. Eighteen days post-graft, concentration of +/- normocytes exceeded the concentration of macrocytes in the W/Wv recipients' circulation. Approximately 45 days post-transplant, the proportion of macrocytes decreased below the 10% detectable level. Calculation of the daily RBC production rate during repopulation and estimation of the number of RBCs produced by a single hematopoietic colony were determined. The RBC size profile was found to be a convenient method for studying the effect of implantation of W/Wv marrow into lethally irradiated +/+ mice. This method proved suitable for repetitive determination of the size population in individual transplanted mice.


Adverse effects of nutritional deprivation on transplanted hematopoietic cells. We studied the effect of food deprivation on hematopoietic reconstitution of B6D2F1 mice given 900 rad total body irradiation followed by 2 x 10(5) syngeneic bone marrow cells. Animals deprived of food from the day of cell transfer to the day of sacrifice were compared to control animals allowed ad libitum laboratory chow. The body weight of food deprived mice decreased by 36% on day 7 as compared to a 9% decrease in fed controls. The mean number of nucleated cells/femur on day 7 was only 22% of that found in fed controls. The spleen weight in the experimental animals was only 48% of that in the controls. Food deprived animals showed complete suppression of macroscopic hematopoietic spleen colony formation. Both marrow and spleen from the primary recipients, when studied for content of CFU-s in secondary ad libitum fed recipients, showed that food deprived animals had less than 25% of the number seen in controls. A third group of animals receiving vitamin supplements and small amounts of dextrose, but no protein, showed hematopoietic suppression similar to that seen in the totally food deprived mice.


Age variation in the increase of hypothalamic and brain stem contents of phenylethanolamine m-octopamine and p-octopamine in spontaneously hypertensive rats (SH Kyoto). Phenylethanolamine, m-octopamine and p-octopamine contents were determined as a function of age in the hypothalamus and brain stem of spontaneously hypertensive rats and controls Wistar Kyoto. In hypothalamus, the content of the 3 amines was 2--4-fold greater for the SH rats. In the brain stem, the phenylethanolamine and p-octopamine contents were 2--3-fold greater in SH rats but 5--6-fold higher in the case of m-octopamine. The difference appears at 3 weeks and correlates the blood pressure with the increase of age. The significance of these findings is discussed.


Population dynamics of soil inhabiting mites in cucumber treated with granular insect growth regulators (IGRs). In small field trials, certain granular insect growth regulators (IGRs) induced significant reduction in soil inhabiting mites of cucumber plantation at a rate as low as 0.25 kg a.i./acre. However, suborders specificity relationship could easily be detected.


The effect of BCG-vaccination on vaccinia virus infections in mice. Pretreatment with BCG yielded a high degree of protection against experimental vaccinia virus infections in mice. Corynebacterium parvum and Aristolochia acid were less protective; other immunostimulants were ineffective.


Dietary immunostimulation: interaction with BCG and LPS. The action of BCG and LPS mR595 used in conjunction with a formula-defined diet is dependent on the administration timing and resembles that of interacting adjuvants affecting different elements of the immune system.


Immunocytochemical localization of hyperglycemic hormone (HGH) in the neurosecretory system of the eyestalk of the crayfish Astacus leptodactylus. Hyperglycemic hormone (HGH) from Astacus leptodactylus can be visualized by an immunocytochemical procedure using a specific antiserum against HGH and the peroxidase-anti-peroxidase (PAP) method. HGH containing cells are localized in the most distal portion of the x-organ in the medulla terminalis. Their cell diameter is about 47 +/- 7 micrometer; the nucleus measures about 22 +/- 2 micrometer. They form a subgroup of neurosecretory cell type 1, already described for the crayfish. A large amount of this HGH material is homogeneously stored in the sinus gland. A group of fibres in the x-organ - sinus gland - tractus can be followed, due to their positive reaction with the PAP-reagent.


A reanalysis of the structure-activity relationships of sulfonamide derivatives. A reanalysis of correspondence between electronic distribution of sulfonamides and their antibacterial activity is proposed. Correlation equations show that the rate limiting steps for sulfonamide action on E. coli cell-free system and whole cell system have similar dependence on the negative logarithm of the ionization constant. The existence of a "bilinear relationship" demonstrates that the whole class of compounds has a single mechanism of action and that permeability factors are unimportant in both biological processes.


The bromination of 6-methyl-4-methoxy-2H-thiopyran-2-one. The bromination of 6-methyl-4-methoxy-2H-thiopyran-2-one was studied under ionic and radical conditions. The 6-bromomethyl, respectively 6-dibromomethyl derivatives were hydrolyzed to the corresponding 6-hydroxymethyl and 6-formyl derivatives. The antibacterial and antimycotic activities of the new compounds were tested.


Current status of hysteroscopy in gynecologic practice. During the past century hysteroscopy has developed into a highly sophisticated and effective technique with increasing applicability. Hysteroscopic instruments have been refined with fiberoptics, allowing light to be introduced into the uterine cavity with high intensity but without danger of thermal injury. Safe methods for uterine distention provide an undistorted panoramic view of the uterine cavity. As a diagnostic technique, hysteroscopy affords accuracy in detecting intrauterine conditions which may not be revealed by traditional methods of exploration. As an operative technique, hysteroscopy increases the precision of surgery and minimizes trauma to the endometrial lining, and may, on some occasions, preclude major surgical intervention. In addition, hysterscopy is potentially useful for female sterilization and offers promise as an investigative tool for studies of the intratubal milieu.


Luteolytic effect of intranasal administration of [D-Ser(TBU)6,DES-Gly-NH2(10)]-luteinizing hormone-releasing hormone ethylamide in normal women. Intranasal administration of two doses of potent agonist of luteinizing hormone (LH)-releasing hormone (LHRH), [D-Ser(TBU)6,des-Gly-NH2(10)]LHRH ethylamide (500 micrograms), a 8 A.M. and 5 P.M. on 1 day between day 4 and 9 following the LH peak in six normal women during two consecutive menstrual cycles shortened the luteal phase from 13.6 +/- 0.3 days to 10.9 +/- 0.3 days (mean shortening, 2.7 days; range, 0.5 to 4.5 days) and reduced plasma progesterone levels to 61.3% +/- 9.2% of control. Hormone changes were followed by daily measurements of plasma LH, follicle-stimulating hormone, 17 beta-estradiol, and progesterone during two pretreatment cycles, two treatment cycles, and two post-treatment cycles. No side effect was observed, and apparently normal cycles occurred immediately after treatment. The present data indicate that the intranasal administration of a potent LHRH agonistic analog can induce luteolysis and control time of occurrence of menses in normal women. This finding opens the possibility of a new and physiologic approach to fertility control.


Reanastomosis of the previously ligated fallopian tube. Tubal sterilization procedures are being performed on young women in increasing numbers. For a variety of reasons a small but significant number of women are requesting reversal of the tubal interruption. This report presents a series of 20 consecutive patients on whom tuabl reanastomoses of previously noncoagulated, surgically ligated fallopian tubes were performed. An intraluminal tubal suture technique is described. Low magnification (X2 to X4) was used. The comparative results of the patients operated upon revealed a tubal pregnancy rate of 80%, a total pregnancy rate of 70%, a viable pregnancy rate of 55%, three abortions, and one ectopic pregnancy.


Prospective studies of the gonadotropin responses to graded injections of gonadotopin-releasing factor in women using a low-estrogen type oral contraceptive for three months. A prospective study of pituitary gonadotropin response to gonadotropin-releasing factor (GnRF) was made in women before and after 3 months of use of a low-estrogen type oral contraceptive containing 0.035 mg of ethinylestradiol and 0.4 mg of norethindrone. A series of three intravenous GnRF injections (0.5, 5.0, and 50.0 micrograms) was given in each test and 10 blood samples were obtained and analyzed for their luteinizing hormone (LH) and follicle-stimulating hormone (FSH) content by radioimmunoassay. The results show that there was no significant effect of the contraceptive steroids on either basal or stimulatable FSH or LH levels. These data are different from those for higher-estrogen types of oral contraceptives, and the possible clinical importance of these findings is discussed.


The role of acrosin in sperm penetration through human cervical mucus. Enzymes have been implicated in facilitating cervical mucus penetration by spermatozoa. One of these enzymes in the neutral proteinase acrosin, which is associated with the sperm acrosome. To determine the validity of this hypothesis, human spermatozoa were incubated with the following acrosin inhibitors: p-aminobenzamidine (AB), N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK), and p-nitropheyl-p'-guanidino benzoate (NPGB). An in vitro slide test system was developed which allowed inhibitor-treated and control spermatozoa to be evaluated against the same human cervical mucus sample. At inhibitor concentrations far exceeding those necessary for the inhibition of human acrosin, there was no effect on spermatozoal penetration into or through the mucus. These findings indicate that, in man, acrosin activity is neither necessary nor facilitory to sperm penetration of cervical mucus. Evidence is also presented that demonstrates the superiority of the newly developed double-interface slide test, especially for comparative purposes, over the tests currently in use.


[Compositional integration of nervous processes in mechanisms of adaptive autoregulation of functions and detection of ecologically significant stimuli]. The latest data on regulatory mechanisms based on synchronization principle elucidate the selective responses of cellular systems to ecologically adequate stimuli, and the mechanisms of formation of the stable neurodynamic changes in separate cerebral structures. The elementary mechanism consists in facilitation of excitatory and inhibitory processes, which respectively increases or suppresses the current level of the brain functional activity. A more complex mechanism of the adaptive plasticity relies on associations involving motivational structures into the biorhythm control. The functional interaction among the cortex and subcortical structures increases at that, the cyclic pattern and the spatial-temporal composition of intracentral interrelationships alters, as well as the correlation between the central and the peripheral functions.


Quantitative aspects of marriage, fertility and family limitation in nineteenth century America: another application of the Coale specifications. This paper deals with three aspects of the decline in the fertility of white women in the United States from 1800 to 1920. The first concerns the portion of the secular decline in the total fertility rate which was due to changes in marriage rates and the portion due to decreases in marital fertility rates. The second concerns the fraction of couples in the nineteenth century who acted effectively to reduce their fertility and the third deals with the importance of abortion as a family-limiting practice among white couples in the nineteenth century.


Factors from fibroblasts promote pancreatic islet B cell survival in tissue culture. A possible role for fibroblasts in promoting the survival and function of islet B cells in tissue culture was examined by the addition of fibroblasts from a mouse embryo cell line (3T3-L2) to islet cell monolayer cultures prepared from newborn rat pancreases. Co-culture of islet cells with fibroblasts significantly increased the recovery of insulin in medium and cells after 7 days of culture in medium supplemented with 10% serum, and prevented the deterioration of islet cells cultured in serum-free medium. Similarly- serum-free medium, conditioned by cultures of either 3T3-L2 fibroblasts or fibroblasts freshly isolated from newborn rat pancreases, maintained the release and content of insulin in islet cell monolayer cultures at levels four- to eightfold higher than in control serum-free medium. Serum-free, fibroblast-conditioned medium also enhanced the survival of intact islets maintained in free-floating culture for 28 days. The active factor(s) in fibroblast-conditioned medium has a high molecular weight and is heat-stable. We conclude that fibroblastic cells produce a macromolecular factor(s) capable of enhancing the survival of functional islet B cells in tissue culture.


Adolescents and young people with spina bifida. This study investigated how young people with myelomeningocele see their situation, and defines some of their problems. 35 adolescents and young people with this condition were interviewed. The evidence suggests that the over-all problems of these young people are common to many with congenital physical disabilities, but neurogenic bowel and bladder are additional complications not often experienced by others with orthopaedic disabilities. Those with ileal conduits frequently reported both social embarrassment and management difficulties, but bowel incontinence was rarely a dominant problem. The findings indicate that the young person's ability to cope with physical and emotional situations is ultimately not determined by the severity of the disability, but is a product of all the environmental support systems that have been available to him since birth.


Pathogenetic and preventive aspects of non-progressive ataxic syndromes. The article reviews the collected knowledge concerning the non-progressive syndromes of ataxic cerebral palsy. Three syndromes are described: (1) simple ataxia (signs of dyssynergia); (2) ataxic diplegia (ataxia with added diplegic spasticity); and (3) dysequilibrium syndrome (defective postural control and equilibrium). The probable aetiological factors in each syndrome are discussed. In simple ataxia prenatal factors dominate; a high proportion of cases have an untraceable aetiology. Genetic factors play a large rôle, and birthweight is usually normal. With ataxic diplegia the aetiology is again most commonly prenatal, but the proportion of cases with an untraceable aetiology is low. Fetal deprivation of supply and perinatal factors, either isolated or in combination, are important. Low birthweight is frequently found. Genetic aetiological factors are the rule in the dysequilibrium syndrome. Possible preventive measures are discussed on the basis of the aetiological pattern. It is concluded that the possibilities of prevention are greatest in ataxic diplegia.


Islet cell antibodies and diabetes mellitus in Pima Indians. Pancreatic islet cell antibodies and 12 other autoantibodies were measured at the time of diabetes diagnosis in 46 Pima Indians, aged 17--47 years, and in 46 age-sex matched non-diabetic controls. Islet cell antibodies were found in only two diabetics, aged 20 and 25, compared with none of 46 controls. Neither of the subjects with islet cell antibodies had other autoantibodies. At least one type of autoantibody was found in 14 (30%) of the diabetics and in 14 controls, but none was significantly associated with diabetes. This study indicates that diabetes in the Pima Indians, even those with an onset below 25 years of age, is almost entirely of type II, in that the disease is not associated with islet cell antibodies, ketoacidosis, or insulin dependence.