Quality assurance for community mental health centers: impact of P.L. 94-63. The Community Mental Health Centers Amendments of 1975 (Public Law 94-63) contained three requirements relating to quality assurance in community mental health centers: the development of national standards for the centers, the development of quality assurance programs, and the collection of data to be used in program evaluation. The authors describe the CMHC standards developed by the National Institute of Mental Health in compliance with the law. They discuss quality assurance programs in the centers in relation to the developing network of professional standards review organizations. They also describe the kinds of activities centers must conduct to meet the program evaluation requirements and some of the materials that have been developed to assist the centers.


Developing and implementing a personnel budget report. Few issues are as vital to the health care industry as those surrounding the notion of cost containment and cost control. If hospital executives are to gain a handle by which to institute programs of cost containment, however, they must have access to pertinent and timely information on hospital operations. Because labor costs represent such a large percentage of total hospital costs, a personnel budgeting report can be a useful first step in gaining valuable management information.


Costly materials retrieved from laundry chutes. About +47,000 in replacement costs have been saved since the hospital instituted a plan to retrieve materials that are inadvertantly deposited in laundry chutes with soiled linens. Scissors, hot-water bottles, and rubber pillows, as well as a variety of expensive surgical instruments and clamps, are now placed in boxes at sorting sites at the hospital's laundry.


'Natural death' laws cause hospitals few problems. Laws covering a patient's "right to die" have been passed in eight states. With the exception of a very few minor problems, hospitals in these states report no difficulties and few changes in their procedures as a result of the new laws. Most hospital association activities have centered on education of member institutions about the content of the legislation.


Shared project studies, revises hospital record retention policies. Through their shared service organization, six hospitals conducted a study that showed that they had similar practical needs and legal requirements for medical record retention but widely varying retention policies. Written policies that were developed for and jointly adopted by the hospitals have ensured consistent, cost-effective retention practices.


Deaf patients' access to care depends on staff communication. To ensure equal access to care for deaf patients, hospitals must make certain that their staff members can communicate effectively with these patients. To do so, common misconceptions about deaf people and about how they communicate must be corrected, and resources and techniques for staff members to use in communicating with deaf patients must be identified and learned.


Commission report addresses future of public-general hospitals. The Commission on Public-General Hospitals, which was established two years ago to assess current problems in the public hospital sector and to point to possible future solutions, recently released its final report. The basic findings and recommendations of that report and the future of public-general hospitals as seen through the eyes of the commission's chairman and director are presented herein.


Tax and Medicare aspects of hospital malpractice insurance (Part 2). Any discussion of tax exemption for malpractice insurance associations must begin by recognizing that, although the tax-exempt status of certain forms of malpractice associations eventually should be recognized by the courts or Congress, resistance will presently be met from the Internal Revenue Service (IRS). For this reason, the authors focus first on the various possibilities for exemption under the Internal Revenue Code, second on the IRS position with respect to these different modes of exemption, and third on the type of arguments that can and should be made to support a claim to exemption.


Complex medicolegal issues surround modern nursing practice. Increasingly, nurses are being involved in malpractice suits and are being called upon to appear as expert witnesses or as friends of the court. The legal responsibilities of nurses today as well as the complex current and emerging medicolegal issues that are affecting their practice were the subject of a recent conference. The findings and recommendations resulting from that conference are described herein.


Medical waste disposal: to burn or to landfill? Conflicting regulations and varying definitions with regard to medical wastes and their disposal have long been a source of confusion for health care institutions attempting to resolve this problem. Presented for the interest of other concerned agencies are guidelines recently drafted by the task force on medical waste disposal of the Maryland Department of Health and Mental Hygiene for the handling and disposal of medical wastes.


Guidelines to assist hospitals in the use of ethylene oxide. A survey undertaken by the American Society of Hospital Central Service Personnel and a study by the National Institute of Occupational Safety and Health formed the background for issuance of these guidelines. A listing of the guidelines is presented herein, including explanatory material.


Hospitals enter antitrust era.

Hospitals enter antitrust era. In the past, the courts tended to rule on antitrust cases in the health care field largely on the basis of motions. Increasingly, however, they are now viewing these cases on their merits. What is more, the Federal Trade Commission has shown an interest in looking more closely at the health care field in terms of antitrust activities.


Curbing the nation's appetite: the case for controlling demand. For too long, controls have been placed on the costs of services, the construction of health care facilities, the numbers and kinds of providers, and the health insurance industry with no concomitant limits being set on the rising demand for capital-intensive and specialized services. If we are to avoid having a debilitated health care system that will be unable to respond to community needs, the author says, a more balanced approach in controlling supply and demand will have to be sought. He discusses some of the conceptual, technical, and operational problems that must be addressed immediately if these actions are to be successful.


Aggressive utilization review shortens stays, lowers costs. Reducing the number of overextended hospital stays no longer presents a problem at Framingham (MA) Union Hospital. Through the use of aggressive techniques designed by its utilization review committee, the hospital consistently has a better average length of stay by diagnosis than its peers in its geographic area. The hospital also has been able to avoid having an adversary relationship with its medical staff and has been successful in increasing patient awareness of the impact of federal regulations and cost constraints on hospitalization.


Flexibility planning keys cost-effective construction. When planning capital improvements, it is imperative that all involved recognize the importance of flexibility of design. Long-term cost savings can be realized if hospital buildings are designed with change in mind.


Construction manager can reduce costs, frustrations. Working as a team, the architect, the owner, and the construction manager can provide substantial savings in the design and construction process. Key to the success of such an effort is a well-conceived selection process for the architect and the construction manager and a firm contract with each. Close coordination at each step of the design/construction process also is important.


Updating disaster plans: a tale of three hospitals. Three hospitals that were struck by disaster in 1977 have undertaken major revision of their disaster plans as a result of unexpected problems that occurred during the crises. Lee Hospital, Johnstown, PA, is installing a tough "floodproofing" system; Jewish Hospital and Medical Center, Brooklyn, NY, and Bellevue Hospital Center, New York City, are revamping their emergency electrical systems.


Controlled drug release from polymers.

Controlled drug release from polymers. Unlike conventional routes of drug administration, controlled-release systems that use implanted, inserted, or surface-applied noninflammatory polymeric vehicles can deliver a steady quantity of drug to a target area over long periods of time. This is now true for drugs of both high and low molecular weight. Some of the devices are described, and existing as well as potential clinical applications are discussed.


Management of variant angina and coronary spasm. When a patient's coronary arteries are anatomically normal, variant angina probably results from transient spasm that narrows and occludes a coronary artery; medical treatment is usually advised. But this distinctive type of pain can also occur in conjunction with atherosclerotic disease, in which case bypass surgery may prove highly effective in relieving symptoms and averting the risk of myocardial infarction.


Current status of fallopian tube transplantation. Experience in both animals and humans has shown that it is technically feasible to transplant the vascularized oviduct alone, without the ethically complicating ovary, using a procedure compatible with a concurrent standard hysterectomy in the donor. But although the operation is well within the capability of many gynecologic surgeons, immunologic barriers still stand in the way of its widespread clinical utilization.


The changing scene in graduate medical education: implications for pathology. During the past several years a number of unrelated events have occurred that will have a marked impact upon residency training in pathology in the United States. These factors include: (1) a twofold increase in the annual number of graduates from American medical schools, (2) Public Law 94-484, which will reduce the number of foreign medical graduates eligible for postgraduate training in this country by 70 to 80 per cent, and (3) increased emphasis on permitting Americans studying abroad to transfer to United States medical schools. Barring unforeseen changes, the culmination of these events is expected circa 1984 when the number of applicants for first year house office positions will equal or exceed the pool of available slots. Therefore, a significant proportion of graduates either will not be matched at all or will not be matched with the specialty(ies) of their choice. The implications of these trends with respect to residency training in pathology, with particular reference to the motives and motivation of persons seeking a first year slot, are discussed and alternative strategies for maximizing benefits discussed.


The fine structure of large cell undifferentiated carcinoma of the lung. Evidence for its relation to squamous cell carcinomas and adenocarcinomas. The light microscopic diagnosis of large cell undifferentiated carcinoma of the lung is known to be highly subjective and shows poor interobserver reproducibility; the very existence of this tumor as a separate entity has been challenged. The ultrastructure of seven large cell undifferentiated carcinomas was examined in an attempt to determine whether they were merely poorly differentiated adenocarcinomas and squamous cell carcinomas, or actually represented an entirely separate class of tumors. Four large cell undifferentiated carcinomas demonstrated intra- and intercellular lumina and were designated adenocarcinomas. In three cases there were well formed desmosomes with numerous tonofilaments and intercellular bridges. These tumors were classified as squamous cell carcinomas. An eighth tumor metastatic to the abdominal wall also showed the features of squamous carcinoma. In addition, all tumors contained a variable population of primitive cells without identifying features. The large cell undifferentiated carcinomas were compared ultrastructurally with eight cases of poorly differentiated adenocarcinomas and squamous cell carcinomas classified by light microscopy. These tumors were morphologically similar, but contained fewer primitive cells and greater numbers of differentiated cells. Cells with a clear cytoplasm as seen by light microscopy were present in both the large cell undifferentiated and poorly differentiated groups; these cells contained variable amounts of glycogen but were otherwise similar to the nonclear cells. It is suggested that most of the subcategories of large cell undifferentiated carcinoma represent very poorly differentiated adenocarcinomas and squamous carcinomas.


Amyloid deposition in immunoblastic lymphadenopathy. Two cases of immunoblastic lymphadenopathy are reported that in addition to having the usual histologic and electron microscopic appearance previously described exhibit perivascular and intersitial green polarization when stained with Congo red, indicating amyloid deposition. Electron microscopic examination confirmed the light microscopic findings. This finding may have significance in regard to etiology, progression, and treatment of this disease entity.


Infective endocarditis associated with cell wall-deficient bacteria. Electron microscopic findings in four cases. Although cell wall-deficient bacteria have been isolated in vitro from cases of endocarditis, no pathogenic role has been established for these forms in human disease. One criterion difficult to satisfy is the demonstration of these variants in human tissue, and electron microscopic documentation has not been reported. Cardiac valvular vegetations from four cases of endocarditis were examined by electron microscopy because of unusual histologic features of minimal inflammation and organization and small organisms that stained poorly by Gram stain. Although cell wall-complete bacteria were identified in the specimens, each showed the presence of cell wall-deficient forms within the vegetations; these variants predominated in three cases. Since manifestations of infective endocarditis were present in three cases and conventional cultures were negative, the evidence indirectly suggests a pathogenic role for these aberrant bacteria in human disease.


A comparative study of 14 cases of familial and nonfamilial pheochromocytomas. A comparison is made between epidemiological features found in a group of 14 patients with familial and nonfamilial pheochromocytomas at M. D. Anderson Hospital and Tumor Institute. The Sipple syndrome (familial) group comprised eitht patients from three different families, and the nonfamilial group consisted of six nonrelated patients. The main differences were noted in the age of onset, sex ratio, bilaterality, malignant behavior, and occurrence of a second nonendocrine primary tumor. An attempt was made by light microscopy to define features that would indicate malignant behavior. No such features could be delineated. Survival time was unrelated to the presence of pheochromocytoma except in operative and investigative procedures.


Intranuclear filaments in a soft tissue sarcoma. Intranuclear filaments aggregating into rodlike structures were found in cells of an undifferentiated soft tissue sarcoma in a child. Similar structures have been uncommonly described in human neoplasms, and uncertainties exist concerning the nature of the inclusion bearing cells in previous reports. The filaments were found to be resistant to mild trypsin digestion. Review of the pertinent literature indicates that these structures may represent the structural manifestation of a highly specialized functional state, rather than a degenerative phenomenon or an artifact. A certain selectivity of occurrence has also been noted. It is therefore plausible to speculate that intranuclear filaments may eventually constitute a morphologic criterion of interest for new tumor classifications.


A mixed hamartoma of the liver: light and electron microscopy. The gross, microscopic, and ultrastructural features of a mixed liver hamartoma occurring in a three month old infant are reported. The differentiation from two solid liver masses, focal nodular hyperplasia and liver cell adenoma is emphasized. Mesenchymal hamartomas, though usually cystic rather than solid masses, share the histologic feature of fibroductular tissue with mixed liver hamartomas and focal nodular hyperplasia. Only the mixed liver hamartoma has extremely broad fields of ductules and an embryonic type of hepatocyte at the ultrastructural level. These and other hepatic lesions show morphologic evidence of transformation of liver cells into biliary epithelial cells in association with vascular connective tissue.


Brunnian adenoma (inverted papilloma) of the urinary bladder: report of a case. An additional case of a benign polypoid tumor of the urinary bladder is reported, the first one observed at autopsy and the first in which photographic documentation of the gross appearance is presented. The lesion was first described as an adenomatoid polyp in 1927. We consider the subsequent (1963) designation of inverted papilloma misleading. Because its histologic morphology bears a striking resemblance to Brunn's nests and because the term papilloma of the urinary bladder connotes potential malignant change, we propose the designation brunnian adenoma. All cases previously reported have been benign.


Extraovarian teratoma with peritoneal gliomatosis. A 25 year old woman underwent removal of a large, incidentally discovered cul de sac teratoma. It was solid but histologically mature and had given rise to multiple peritoneal implants of mature glial tissue. She was alive without evidence of disease 57 months later. This tumor appears to represent the extraovarian counterpart of previously reported ovarian teratomas with peritoneal gliomatosis.


Hepatolienal fusion: case report of an unusual lesion. A unique fusion of liver and spleen was observed at autopsy between a tongue of hepatic parenchyma and the superolateral aspect of the spleen in an adult Caucasian male. No instance of hepatolineal fusion was found in the literature, prompting this report. An embryologic explanation is offered.


Minor chromosome variations and selected heteromorphisms in 200 unclassifiable mentally retarded patients and 200 normal controls. Lymphocyte chromosome preparations from 200 mentally retarded children and 200 normal adult controls were analyzed by G-, Q-, and C-banding techniques for minor chromosome variations (G and Q) and selected heteromorphisms (G and C). Minor variations scored included inv(9), prominent or decreased short arms and/or satellites on acrocentric chromosomes, and 17 ph. C heteromorphisms analyzed included those involving 1qh, 9zh, and 16zh regions. Length variations of Yq were scored on G-banded karyo types. No significant differences in frequencies of scored minor variations or heteromorphisms were noted between the retarded and control populations.


The fate of DNA satellites I, II, III and ribosomal DNA in a familial dicentric chromosome 13:14. In a family with a stable dicentric 13:14 translocation chromosome, the distribution of DNA sequences complementary to satellite DNAs I, II and III and ribosomal RNA were studied. The translocation chromosome showed a loss of sequences complementary to all three satellite DNAs, located in the short arms of the acrocentric chromosomes, but slightly more of the sequences complementary to satellite I were retained than of the other two satellite DNAs. The fact that material was lost from all three satellites indicates that they are not present as single discrete blocks in these chromosomes, when we would expect to find the distal sequences lost and the proximal ones retained, but consist of interspersed blocks with each sequence represented by more than one, and probably several blocks. There was a total loss of ribosomal DNA from the nucleolar organiser regions of the chromosomes involved in the 13:14 translocation, but an interesting finding was the presence of extra ribosomal DNA and satellite DNAs I, II and III in one chromosome 22 which was found in seven out of nine individuals of the family with the 13:14 translocation, and in only one of five individuals without the translocation. There may be a compensatory mechanism present when certain sequences are elminated during chromosomal rearrangements. The relationship of such mechanisms to reproductive fitness is discussed.


Lack of association between psoriasis vulgaris and red cell acid phosphatase polymorphism. Polymorphism of red cell acid phosphatase (ACP-1; E.C. 3.1.3.2.) has been studied using the Cellogel technique of Martin et al. (1975) in 102 patients with psoriasis and 102 healthy controls. In contrast to two previous reports, no anomalies in distribution of phenotypes were found in patients or in controls.


Common and uncommon immunoglobulin haplotypes among Lebanese communities. Allotypes of IgG1, IgG2, IgG3, and IgA2 subclasses were investigated in seven Lebanese communities (three Moslem and four Christian). The Gm-Am haplotypes found were mainly those prevalent in Caucasians with a low frequency of haplotypes usually observed in Africans and Orientals. The difference between highlanders and lowlanders as expressed by G2m(23) was highly significant and suggested a possible adaptation to selective pressure related to the gamma2 genes, possibly due to endemic malaria in the past. Exceptional Gm-Am haplotypes were unambiguously determined by family studies. Some were characterized either by a deletion or a repression or, in contrast, by a partial or total duplication of gamma genes. Two others had uncommon combinations of allotypes: Gm17;23;5,10,11,13,14 A2m1, where G1m (17) was present without G1m (1); and Gm3;23;5,14 A2m1, where the CH3 allotypes G3m (10,11,13) were lacking.


[Length of Y chromosome, intelligence and behaviour in a mental penal population (author's transl)]. The Y/F ratio was established in 128 mentally disordered offenders in a maximum security hospital. The 50 Y/F greater than 0.90 subjects were compared with the 78 Y/F less than 0.90 subjects as regards intelligence and behaviour. With the exception of the highest frequency of intelligence quotients lower than 70 in the criminal patients Y/F greater than or equal to 0.90, no statistical correlation exists to support the theory of a relation between a long Y chromosome and the type of psychiatric (psychopathy, psychosis) or criminality diagnosis.


De novo trisomy 4pter leads to q21.

De novo trisomy 4pter leads to q21. Clinical and cytogenetic findings in an infant girl with multiple congenital anomalies, principally anophthalmia, are presented. The patient's karyotype was 47,XX,+del(4)(pter leads to q21), the largest partial trisomy of chromosome 4 reported. The possible mechanism of the origin of this abnormality is discussed.


45,X/47,XYY mosaicism in a patient with Turner's syndrome. A patient with classical Turner's syndrome and a 45,X/47,XYY mosaicism is described. Each cell line was present in approximately equal amounts in the peripheral blood lymphocytes, while in fibroblasts derived from skin and both gonads only the 45,X karyotype was present. It is suggested that the latter fact is responsible for the patient not having the mixed gonadal dysgenesis syndrome or tumor formation in both streak gonads.


Partial trisomy 10p in two generations.

Partial trisomy 10p in two generations. Two cases of partial 10p trisomy due to a t(10;20)(p12;p12) in two generations of a family are presented. Analysis of 20 known cases of such aberrations confirmed the opinion of Schleiermacher et al. (1974) that partial trisomy 10p is a distinct clinically recognizable entity. The most important diagnostic features of this syndrome are dolichocephaly, prominent forehead, wide open sutures and fontanelles, broad root of the nose, cleft lip and palate, clubfoot, and cystic changes in kidneys.


A possible role for polymorphonuclear leucocytes in the defence against recrudescent herpes simplex virus infection in man. We have used a 51Cr release assay to demonstrate that human polymorphonuclear leucocytes (PMNL) can damage herpes simplex infected target cells sensitized with antiviral antibody. Effective sensitizing antibodies were found in both serum and saliva of all those persons tested who were subject to recurrent cold sores. PMNL were much less effective as killer cells than peripheral blood mononuclear cells, but as they are the predominant inflammatory cell with the HSV1 lesion they may be, quantitatively, more important. The cytotoxic effects of both PMNL and mononuclear cells were significantly reduced by prostaglandin E1 as well as by several drugs that were tested. It is suggested that antibody dependent PMNL-mediated cytotoxicity may play a role in the human host defences against recrudescent herpes simplex infection.


Secretory antibody responses in axenic mice to perorally administered Staphylococcus aureus. Topical oral immunization of axenic mice with non-replicating Staphylococcus aureus resulted in the production of both serum and salivary agglutinins. A latent period of approximately 5 days was noted before salivary antibodies were detected against both a carbohydrate (ChoA) and a protein (PrA) antigen isolated from this micro-organism. The local response to ChoA exhibited a linear increase until day 9 when the reciprocal titres reached a plateau [32 (16--64)]. Salivary antibodies to PrA peaked by day 13 at a mean reciprocal titre of 60 (32--128). The agglutinin response in saliva was found to be initially IgG; however, by day 9 of a 14-day-immunization regimen, IgA became the predominant class of exocrine anti-S. aureus antibodies. The serum agglutinin response followed that found in saliva by approximately 2--4 days. By day 14, all sera (6/6) contained PrA agglutinins, while 4/6 sera agglutinated sheep erythrocytes coated with ChoA. Serum antibodies to ChoA were exclusively IgM, in contrast to IgM and IgA agglutinins elicited by PrA. Absorption studies provided evidence of a specific local and systemic immune response to both ChoA and PrA antigens of perorally administered S. aureus.


The reaction between the complement subcomponent C1q, IgG complexes and polyionic molecules. The strength of the bond between 125I-labelled C1q and immune complexes, Fc piece, dextran sulphate, polyglutamic acid and polylysine has been investigated. The binding of C1q to Fc piece, small molecular weight (less than 10,000) dextran sulphate, polyglutamic acid and polylysine have value; for the functional affinity constant (Ko) in the range of 0.2-1.5 X 10(4) M-1. In contrast the binding of C1q to immune complexes and large molecular weight polyions (greater than 100,000 is much greater and lies in the range 3 X 10(7)--4 X 10(8) M-1. The differences in the binding constants between the two groups can be explained if the Fc piece and small molecular weight compounds bind to only 1 head of the C1q molecule but the immune complexes and large molecules bind to 2 heads. There are probably 6 binding sites on the C1q molecule for dextran sulphate. The enhancement of the binding affinity of C1q by reduction in ionic strength and the reaction with polyions, indicate that ionic groups are present near or within the binding sites.


The respiratory response in sensitized rats to aerosol challenge. Hooded Lister rats were sensitized to DNP-ovalbumin. These rats showed a significant alteration in respiratory pattern when challenged with DNP-ovalbumin aerosol. The respiratory response was not produced by challenging sensitized rats with intragastric DNP-ovalbumin. The magnitude of the respiratory response did not correlate with the specific IgE concentration in the serum. A similar pattern of respiratory response was inducible in unsensitized rats by intravenous administration of IgE-rich sera.


Comparative studies on antibody and antibody production to poly(ADP-ribose) in mice. Antibodies to poly(ADP-ribose) were produced in C3H/He mice by injection of poly(ADP-ribose) in Freund's incomplete adjuvant or its complexes with methylated bovine serum albumin in Freund's incomplete adjuvant. Titres of the antibody obtained from the latter were about 50-fold higher than those from the former. Thus, the effect of methylated bovine serum albumin on the antibody production to poly(ADP-ribose) resembled the case of poly(I).poly(C) and was different from the case of single stranded DNA. The class of the antibodies obtained from these two different procedures mainly consists of 7S antibodies, and the specificity of these antibodies was independent of their titres. It was also found that antibodies to poly(ADP-ribose) were most reactive to poly(ADP-ribose) with 20 repeating ADP-ribose units. The reactivity of the antibody was dependent on the chain length of the polymer. Neither the complex in Freund's incomplete adjuvant nor poly(ADP-ribose) alone in Freund's imcomplete adjuvant could induce an immune response to poly(ADP-ribose) in athymic nude mice. Therefore, the immune response to poly(ADP-ribose) may occur through a thymus function.


The distribution of antigen in flare up reaction in contact sensitivity to DNCB. The distribution of DNP groups in various tissues of guinea-pigs following intravenous injection of DNBSO3Na was investigated by an immunofluorescent method using FITC-labelled anti-DNP antibody. DNP groups were detected either in the cytoplasms of epidermal cells or on/in lymphoid tissue cells. The epidermal distribution of DNP groups was shown in the skin obtained from 5 min to 3 days after injection. There was no fundamental difference in the epidermal localization of DNP groups between at the previously tested site and at virgin site in DNCB sensitized animals. Unreacted DNBSO3Na was demonstrated in the blood plasma of DNBSO3Na injected animals. The injection of either DNP-lysine or 2,4-dinitrophenol was found incapable of inducing flare up reaction and no epidermal localization of DNP groups in the sensitized animals was observed. A possibility that intravenously injected DNBSO3Na forms a complete antigen by conjugation with epidermal proteins and sensitized cells, which have been indicated by Polak, Turk & Frey (1973) to remain at the site of old contact reaction, react with the antigen resulting in flare up reaction, is suggested.


Isolation of glycopeptides with skin test activity from dermatophytes. By using ethylene glycol extraction of whole submerged cultures followed by Sephadex G-200 and diethylaminoethyl-Sephadex chromatography, we isolated four distinct glycopeptides from Trichophyton mentagrophytes, T. rubrum, and Microsporum canis. Chemical analyses revealed that these glycopeptides contained mostly carbohydrate (42.5 to 81.6%) and protein (4.3 to 11.3%), with lesser amounts of phosphorus (0.4 to 6.0%) and hexosamines (0.3 to 0.6%). Based upon total carbohydrate and monosaccharide content, these dermatophyte glycopeptides could be divided into two chemical groups: glucopeptides (DSI1) and mannopeptides (DSI2, DSII1, and DSII2). The mannopeptides and glucopeptides of each species of dermatophyte were not significantly different chemically from those derived from the other two dermatophyte species studied. Skin testing of DSI1-glycopeptides or DSI2-mannopeptides in immunized guinea pigs indicated that only the DSI2-mannopeptides elicited a delayed hypersensitivity reaction. Skin testing T. mentagrophytes 62-infected guinea pigs with the four purified DS-glycopeptides, as well as earlier fractions from the purification scheme, derived from T. mentagrophytes, T. rubrum, and M. canis, again indicated that only the DSI2-mannopeptides of the two Trichophyton species elicited a delayed hypersensitivity reaction. The number of infections or duration of infection had no effect on the size of the skin test response. DSI2-mannopeptides were non-cross-reactive between genera when tested in Trichophyton-immunized or -infected guinea pigs and Microsporum-immunized guinea pigs.


Toxic activity of Bacillus sphaericus SSII-1 for mosquito larvae. Using larvae of the mosquito Culex pipiens var. quinquefasciatus as a bioassay system, we have verified an earlier proposal that pathogenicity of Bacillus sphaericus SSII-1 is a toxin-mediated rather than an infectious process. Chloroform or ultraviolet-light treatments that decreased the viable count of SSII-1 cells by 4 or 5 logs did not significantly alter the ability of the bacterial cells to kill larvae. Three lines of evidence indicated that toxic activity was not related to sporulation: (i) cells grown in either a complex or a defined medium were toxic at all ages; (ii) when supplemental Mn2+ was excluded from a complex medium, the culture yielded few spores but was of equal toxicity to a culture containing many spores; and (iii) several early blocked oligosporogenous mutants were isolated that had toxic activities comparable to that of the parent. The toxin was shown to be relatively unstable because activity was destroyed by heat and decreased by refrigeration, a freeze-thaw cycle, or two methods of cell breakage. Thin sections of SSII-1 cells did not reveal the presence of any inclusion body that might be related to toxicity.


Adherence of Bacteroides fragilis in vivo. The ability of the encapsulated species Bacteroides fragilis to adhere to rat peritoneal mesothelium was compared to the adherence of unecapsulated strains of Bacteroides (B. distasonis, B. vulgatus, B. thetaiotaomicron, B. ovatus, and B. "other"). Adherence was assayed by attaching plexiglas plates containing 8-mm holes to the peritoneal mesothelium of anesthetized rats. Cell suspension (0.25 ml) was incubated in each well, after which the suspension was aspirated, and a 4-mm punch biopsy was removed. Viable organisms adhering to the biopsy specimen were enumerated by plate count following washing of the biopsy tissue. It was found that B. fragilis adhered significantly better to mesothelial tissue (10(3.00) colony-forming units per biopsy) than unencapsulated species of Bacteroides (10(1.07) colony-forming units per biopsy). This effect was not due to differential oxygen sensitivity of the various inocula. Immunization of rats with capsular polysaccharide did not demonstrate decrease in the adherence of B. fragilis; however, preincubation of the mesothelium with purified capsular polysaccharide resulted in a substantial reduction in adherence. These results indicate that B. fragilis adheres to rat peritoneal mesothelium better than unencapsulated species and suggests that the capsular polysaccharide of B. fragilis plays some role in this increased adherence.


Encapsulation of Bacteroides species.

Encapsulation of Bacteroides species. Capsules were detected by the India ink method in cultures of Bacteroides fragilis, B. vulgatus, B. thetaiotaomicron, and B. ovatus. No capsules were found in the five strains of B. distasonis examined.


Potentiation of endotoxicity by carrageenan. Carrageenan can potentiate the lethal effects of endotoxin by 100- to more than 3,000-fold.


Inhibition of hemolysis by zinc and its reversal by L-histidine. Hemolysis induced by staphylococcal alpha-toxin, staphylococcal beta-toxin, streptolysin O, and streptolysin S was inhibited by zinc ions by virtue of inhibition of an early step in the events leading to lysis, presumably by preventing the lysins from attaching to the plasma membrane. In contrast, in hemolysis induced by Clostridium perfringens alpha-toxin and by perfringolysin O, a later step was inhibited by zinc. In hemolysis caused by saponin, lysolecithin, and Triton X-100, hemoglobin was precipitated by zinc ions as it was released from the erythrocyte. Inhibition by zinc was abolished by several amino acids of which L-histidine was the most effective.


Venezuelan encephalitis virus: in vivo induction of a chromosomal abnormality in hamster bone marrow cells. This study reports the induction in vivo of aneuploidy in bone marrow cells of the Syrian hamster after short-term infection with Venezuelan encephalitis virus.


Heterogeneity of the rhamnomannans from one strain of the human pathogen Sporothrix schenckii determined by 13C nuclear magnetic resonance spectroscopy. The synthesis of different rhamnomannans in a strain of Sporothrix schenckii (1099.12) was shown by use of 13C nuclear magnetic resonance spectroscopy. Fractionation of a polysaccharide preparation from cells grown at 25 degrees C provided a neutral monorhamnosyl rhamnomannan and an acidic rhamnomannan containing 4-O-substituted glucuronic acid units and also (1 leads to 2)-linked dirhamnosyl side chains.


Immunity to vaginal reinfection in female guinea pigs infected sexually with Chlamydia of guinea pig inclusion conjunctivitis. Guinea pig boars were inoculated intraurethrally with the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC). At the heights of their urethral infections, they were caged with sows in estrus. Whereas some of the sows had not been previously exposed to GPIC agent, others had received an intravaginal inoculation 5 to 8 weeks earlier. Those sows for which infected boars provided the first exposure were challenged by intravaginal inoculation 5 to 8 weeks later. Vaginal and conjunctival scrapings were taken regularly and stained for chlamydial inclusions. Titers of serum anti-GPIC antibodies and of vaginal secretory IgA anti-GPIC antibodies were determined by immunofluorescence. Our results show for the first time that a sexually acquired vaginal GPIC infection induces immunity to manual reinfection of the vagina. Because of the high incidence of secondary conjunctival infections among the vaginally infected sows, we could not provide a sound statistical basis for our tentative conclusion that manual infection of the vagina induces immunity to sexual reinfection. The results of our antibody titrations confirm previous work showing that vaginal GPIC infection induces formation of both serum antibody and vaginal secretory immunoglobulin A antibody.


Loss of inorganic ions from host cells infected with Chlamydia psittaci. Mouse fibroblasts (L cells) infected with the 6BC strain of Chlamydia psittaci released potassium ion (K(+)) into the extracellular milieu in a way that depended on size of inoculum and time after infection. When the multiplicity of infection was 500 to 1,000 50% infectious units (ID(50)) per L cell, loss of intracellular K(+) was first apparent 4 to 10 h after infection and was nearly complete at 6 to 20 h. Magnesium ion and inorganic phosphate (P(i)) were also released. Similar multiplicities of ultraviolet-inactivated C. psittaci also caused release of K(+). Leakage of inorganic ions probably resulted from immediate damage to the host-cell plasma membrane during ingestion of large numbers of chlamydiae. With multiplicities of 1 to 50 ID(50) per L cell, ingestion of C. psittaci was not by itself enough to cause release of K(+) and P(i) from infected L cells. There was a delay of 36 to 72 h between infection and massive leakage of intracellular ions during which time the chlamydiae multiplied extensively. Fifty ID(50) of ultraviolet-inactivated C. psittaci per L cell did not bring about significant leakage of K(+), even after 72 h. The mechanism whereby these multiplicities of infection destroy the ability of host cells to retain intracellular molecules is not known. HeLa 229 cells also released K(+) and P(i) after infection, but these losses occurred more slowly than in comparably infected L cells, possibly because C. psittaci did not multiply as extensively in HeLa cells as it did in L cells. The significance of the inability of chlamydiae-infected cells to regulate the flow of molecules through their plasma membranes is discussed.


Effect of chemoattractants on chemiluminescence. Upon ingestion of particulate matter, polymorphonuclear leukocytes produce a chemiluminescence that can be measured in a liquid scintillation counter. In the experiments reported here, the influence of three chemoattractants and three chemotactic modulators upon the chemiluminescence induced by opsonized zymosan was studied. The chemoattractants investigated (including bacterial factor derived from Escherichia coli, the simple peptide formylmethionylalanine, and activated human complement), which initiate directed movement when presented to cells in a concentration gradient, significantly enhanced zymosan-induced chemiluminescence. In the absence of opsonized zymosan, however, they had no effect on the chemiluminescence response. In contrast, the chemotactic modulators studied (including carbamylcholine, phenylephrine, and cyclic guanosine 5'-monophosphate, which are not chemotactic by themselves but can enhance or depress the movement of polymorphonuclear leukocytes initiated by chemoattractants) produced no enhancement of chemiluminescence. Other experiments were carried out in which neutrophils were pretreated with cytochalasin D, a compound that inhibits phagocytosis by interacting with microfilaments. Under these conditions, the chemiluminescence induced by opsonized zymosan was markedly reduced, but the response resulting from the addition of a chemoattractant to the leukocyte/zymosan mixture was not. This indicates that the chemiluminescence in response to chemoattractants is not dependent on phagocytosis per se. Neutrophils were also pretreated with dinitrofluorobenzene, a compound that binds amino groups and can be expected to react with proteins on the cell membrane. In these experiments, the chemiluminescence induced by opsonized zymosan and the pronounced spike of activity produced by the addition of a chemoattractant were completely abolished. These results suggest that the polymorphonuclear leukocyte chemiluminescence response to chemoattractants is mediated by cell surface proteins. Thus, chemoattractants may have a dual role in the acute inflammatory response: (i) the initiation and maintenance of directed cell movement, and (ii) enhancement of metabolic steps mediated at the cell membrane, resulting in microbicidal activity.


Comparative estimates of bacterial affinities and adsorption sites on hydroxyapatite surfaces. The adsorption of strains of prominent oral bacteria to hydroxyapatite (HA) surfaces was studied by use of an adsorption model based on the Langmuir adsorption isotherm; this permitted comparative estimates of the number of adsorption sites and the strength of the adsorption bonds on untreated and salivatreated HA surfaces for strain of Streptococcus mutans, S. salivarius, S. sanguis, S. mitis, Actinomyces viscosus, and A. naeslundii. The experimental data closely followed the adsorption model as judged by the high correlation coefficients obtained for all strains studied. Adsorption to untreated HA was similar for strains of the six species studied, suggesting that a common adsorption mechanism, possibly Ca(2+) bridging, may exist for attachment to HA. More complex interactions appeared to be involved in bacterial adsorption to saliva-treated HA since adsorption of the strains tested at unsaturating cell concentrations varied more than 30-fold. This indicates that adsorbed salivary components on HA surfaces impart a higher order of specificity for subsequent bacterial adsorption. Fewer cells of strains of S. mutans, S. salivarius, and A. naeslundii adsorbed to saliva-treated HA than to untreated HA because adsorbed salivary components presented fewer adsorption sites. Substantially higher numbers of cells of strains of S. sanguis, S. mitis, and A. viscosus adsorbed to saliva-treated HA because the film of adsorbed salivary components increased the number of adsorption sites for these strains. The affinity constants for all but one strain studied were lower on saliva-treated HA than on untreated HA. The number of bacterial cells which adsorbed to saliva-treated HA more closely related to the number of available binding sites than to the strength of their adsorption bonds when tested at an initial concentration of 2 x 10(7) organisms/ml. Although some differences were observed in the adsorption of strains of S. mutans representative of five serological groups, the numbers which attached to saliva-treated HA did not vary widely; this suggests that factors other than their ability to attach to a pellicle-covered HA surface may be responsible for their varying geographic distribution in human populations.


Lymphocyte blastogenic responses to influenza virus antigens after influenza infection and vaccination in humans. Virus-specific in vitro cell-mediated immune responses were investigated in 20 normal volunteers who were challenged with liver influenza A/VIC/3/75 (H3N2) virus and in 13 volunteers who were vaccinated with inactivated vaccine containing A/VIC and A/NJ/8/76 (HswN1) antigens. Lymphocyte cultures were established from peripheral blood samples obtained prior to and at various times after infection or vaccination. Blastogenesis was determined by [3H]thymidine incorporation after stimulation of cultures with purified, inactivated, whole influenza viruses. Six days after infection, significantly elevated levels of blastogenesis were observed after in vitro stimulation with A viruses of hemagglutinin and neuraminidase subtypes that were the same as (H3N2) or antigenically distinct from (Heq1Neq1 or HswN1) those of the challenge virus, although maximum stimulation was noted with virus of the same hemagglutinin subtype (H3) as the challenge virus. Similar although more prolonged blastogenic responses were noted in lymphocyte cultures from vaccinees who had serum antibody rises after vaccination. The kinetics of these responses suggest that cell-mediated immunity may play a role in early events after infection and vaccination with influenza virus.


Interaction of lipopolysaccharides and lipid A with complement in rats and its relation to endotoxicity. Uniform salt forms of endotoxic lipopolysaccharides (LPS) and free lipid A showing distinct differences in their anticomplementary activity, as well as a nontoxic LPS, are used in a new approach of studying the role of complement in endotoxin shock. The use of these defined LPS forms led to the identification of two timely, distinct depressions in complement hemolytic activity after administration of endotoxin in rats. An early depression occurred within 10 min after injection, and a late one developed more gradually, with lowest values at 6 to 9 h. The early depression represents a direct interaction of LPS with complement. It was obtained by toxic and nontoxic preparations that exhibit a high molecular weight and anticomplementary activity in vitro. The early depression was not related to the toxic properties of the LPS. The late depression was obtained only with endotoxically active LPS in lethal and 100-fold-lower concentrations, regardless of their molecular weight and of their in vitro anticomplementary activity.


Phagocytosis by sheep alveolar macrophages: relationship between opsonin concentration and light emission in the presence of luminol. The observations reported may be applied to determining the effects of various compounds, e.g., environmental pollutants and agricultural chemicals, upon the phagocytic activity of alveolar macrophages, and the method described will aid in detecting compounds which alter Fc receptor activity. A direct linear relationship existed between the concentration of antibody used to opsonize bacterial particles and the quantity of luminol-dependent light emitted by a population of sheep alveolar macrophages exposed to the opsonized particles. The relationship can be illustrated with a Lineweaver-Burk-style double-reciprocal plot. An analogy is suggested between the kinetics of enzyme substrate reactions and the interaction of antibody-coated particles with Fc receptors on cell membranes.


Monocyte function in human neonates.

Monocyte function in human neonates. Monocytes of healthy, full-term newborns were isolated from cord blood, and functional and biochemical activities were quantitated. The yield of monocytes per milliliter of cord blood was 60% greater than that from the peripheral blood of healthy adults. Placental monocytes were initially less well spread than cells from adults, but no other morphological differences were noted. During 4 days of in vitro cultivation, placental monocytes secreted lysozyme at a constant rate, lost peroxidase activity, and increased 5'-nucleotidase activity 15- to 25-fold. Similar findings were obtained with monocytes from adults. Placental monocytes also displayed Fc and complement receptor activity. Ingestion and intracellular multiplication of Toxoplasma gondii were identical in normal placental and adult monocytes. Furthermore, toxoplasma multiplication was significantly inhibited by cells from both sources when the monocytes were preincubated with supernatants prepared from sensitized lymphocytes and toxoplasma antigen. Monocytes from newborns were competent cells in terms of the specific functions and activities we examined.


Production of enterotoxin by Yersinia enterocolitica. Forty-three strains of Yersinia enterocolitica isolated from children with gastroenteritis and 18 laboratory strains were examined for enterotoxin production by using the infant mouse, Y1 adrenal cell, and rabbit ileal loop assay systems. All clinical isolates and seven laboratory strains were found enterotoxigenic in the infant mouse model, but none of the strains produced toxin in the Y1 adrenal cell system. One enterotoxin-producing strain was also tested by the rabbit ileal loop assay, confirming the results of the infant mouse assay. The enterotoxin was heat-stable and as active in the 6-h rabbit ileal loop as in the 18-h assay, suggesting a similarity to the heat-stable enterotoxin of Escherichia coli.


Influence of encapsulation on staphylococcal opsonization and phagocytosis by human polymorphonuclear leukocytes. In previous studies, encapsulated Staphylococcus aureus strains have been shown to resist phagocytosis. In this investigation, the nature of the interference with phagocytosis by human polymorphonuclear leukocytes was examined by studying the opsonization of two pairs of unencapsulated (Smith compact and M variant) and encapsulated (Smith diffuse and M) S. aureus strains. The uptake of [3H]glycine-labeled bacteria by normal leukocytes was quantitatively measured after incubation of bacteria in pooled serum, C2-deficient serum, immunoglobulin-deficient serum, and serum from a rabbit immunized with S. aureus M. The presence of a capsule was found to interfere with opsonization by both the classical and alternative pathways of complement as well as by heat-stable opsonic factors in nonimmune human serum. This interference was significantly greater in the case of the S. aureus M strain than in the case of the Smith diffuse strain. The only effective opsonic source for S. aureus M was immune rabbit serum. It is proposed that encapsulation of S. aureus strains interferes with phagocytosis by preventing effective bacterial opsonization.


Reversion of dextran sulfate-induced loss of antibacterial resistance by Bordetella pertussis. Parenteral injection of dextran sulfate 500 (DS 500; 50 mg/kg of body weight) into mice caused a complete loss of resistance to a sublethal (2 X 10(3) to 5 X 10(3)) infection with Listeria monocytogenes. Such loss could be prevented by pretreatment of animals with 3 X 10(9) heat-killed Bordetella pertussis organisms (PO) 5 to 30 days before the administration of DS 500. The increased phagocytic capcity induced by PO was only exhausted when a fourfold dose of DS 500, effecting complete loss of antibacterial resistance (50 mg/kg ob body weight), was administered. Listeriosis in mice treated with DS 500 is characterized by rapid-progressive necro-purulent inflammation of liver and spleen, lack of mononuclear phagocyte response, and 100% lethality within 72 h after infection. In contrast, the time course, extent, and morphological characteristics of listeriosis in animals pretreated with PO before the DS 500 application were not significantly different from those of nonpretreated controls. Evidence is presented that the protective effect of PO is due to activation of the mononuclear phagocyte system, which without such treatment is blocked by the DS 500 administration. The data presented indicate that the protective effect of PO is due only in part to the endotoxic moiety of these bacteria. Differences in the course and morphology of listeriosis in animals with dysfunction of the mononuclear phagocyte system and in animals with deficiency of the cellular immune system are discussed.


Ultrastructural and immunological aspects of the phagocytosis of Trypanosoma brucei by mouse peritoneal macrophages. Trypanosome-activated mouse peritoneal macrophages phagocytized and digested Trypanosoma brucei in vitro and in vivo, but in the absence of specific antiserum and complement the degree of phagocytosis was minimal. Ultrastructurally, the parasites attached to the macrophage by their flagella, and ingestion proceeded flagellum first. Once ingested, T. brucei was degraded, presumably due to fusion of the parasite-containing phagosome with lysosomes. Contrariwise, normal mouse peritoneal macrophages displayed negligible ability to ingest T. brucei, even in the presence of specific antiserum and complement. During trypanosomiasis in deer mice (Peromyscus maniculatus), the development of hypergammaglobulinemia correlated with enhanced phagocytosis of T. brucei by macrophages, but only at early post-inoculation days (PID 5 to 15). Complement lysis of trypanosomes was not identified in these experiments. Between PID 20 to 30, antiserum and complement either had no phagocytosis-promoting ability or depressed the phagocytosis of T. brucei by macrophages. These results indicate that both specific antibody and complement contribute to the ingestion of T. brucei by activated macrophages, but that parasite antigenic variation effectively abrogates the phagocytic defense mechanism.


Mediation of immunity to intracellular infection (Toxoplasma and Besnoitia) within somatic cells. Antigen-treated lymphocytes from immune hamsters specifically protected not only macrophages, but also cultured fibroblasts and kidney cells infected with Toxoplasma gondii or Besnoitia jellisoni. Macrophages were not necessary for the protection of fibroblasts and kidney cells. A mediator that inhibited the intracellular proliferation of these microbes was obtained from immune lymphocytes in contact with specific antigen. Again, macrophages were not necessary for the elaboration of this mediator or its activity in kidney cells or fibroblasts. The mediator was microbe and host specific, had a molecular weight between 4,000 and 5,000, was resistant to heating at 56 degrees C for 30 min, and was sensitive to chymotrypsin, but resistant to ribonuclease and deoxyribonuclease. A single injection of Besnoitia mediator afforded better protection to hamsters infected with Besnoitia than did antibody. Whereas antibody lysed extracellular organisms, the microbe-specific mediators conferred immunity not only on macrophages, but also on other cells of the body, apparently the first such demonstration.


Cell-mediated immunity in the lungs of rabbits using conjugated proteins. A study using direct macrophage migration inhibition of cells from the lower respiratory tract of rabbits immunized with conjugated proteins, incorporated into a killed BCG-oil emulsion, revealed that the reaction was largely carrier specific. The only exception was when bronchoalveolar cells (BAC) from animals immunized with dinitrophenol coupled to ovalbumin (DNP-OA) were significantly immobilized with DNP coupled to bovine gamma-globulin (BGG) in which the ratio of DNP/BGG was high [DNP-BGG(H)]. This result could not be explained by a toxic effect or by a high net negative charge on DNP-BGG(H). In addition, inhibition of BAC from DNP-OA-immunized rabbits was not observed when the ratio of DNP to BGG was reduced approximately 5-fold.


Demonstration of antibodies to chlorophenothiazine derivatives. Antibody to 2-chloro-10-(2-carboxyethyl)-phenothiazine (CECP) was produced in rabbits by immunization with the hapten-BSA conjugate. The titer of antibody was determined by passive hemagglutination (PHA) using erythrocytes coupled with the CECP-protein carrier. Results from inhibition tests using structurally related (CECP, CPZ, PCPZ, CMP) and almost unrelated haptens (DDA, RF) strongly suggested that both the side chain and the nucleus of the haptens are important in determining the specificicity of immunological reactions. 18 sera from psychiatric patients administered phenothiazine derivatives for a long time as well as 20 control sera from healthy individuals were then tested for their reactivity to CECP. Of patients' sera, 12 had detecable hemagglutination titers (1:8 or greater), while all of the normal human sera were negative. The PHA activity was contained in euglobulin fraction and was specific in the inhibition tests. From these results, the activity to CECP in patients' sera was supposed to be specific antibody.


Thymoindependent antigentic stimulation in nude mice: response to polyvinylpyrrolidone and adjuvant effects of Corynebacterium parvum and LH1. The humoral thymoindependent response to polyvinylpyrrolidone (PVP) measured by the Farr test, was not different in athymic nude and phenotypically normal mice. In athymic and normal mice, this response was significantly increased by Cornebacterium parvum administered at the time of immunization. A recently synthetized compound, LH1 (3alpha-N-[2 aminoethanol]-amino 5-alpha-pregnane-20-one) was, however, a better immunostimulant of the anti-PVP response in athymic mice.


An effect of actin on cell migration.

An effect of actin on cell migration. A specific inhibitory effect on mononuclear cell migration by smooth muscle actin and skeletal muscle actin is reported. Actin aged at 4 degrees C or heated at 56 degrees C for 10 min had little or no effect, but papain-denatured actin had a strong inhibitory action. Actin and/or its breakdown product(s) may interfere with mononuclear cell movement in vivo in pathological conditions where release of actin from damaged or dead cells occurs.


Relationships between IgE antibody production and other immune responses. II. Effect of thymectomy at various times after birth. Mice were subjected to thymectomy at various times after birth and immunized with ovalbumin in aluminum hydroxide gel at 4 or 8 weeks of age. The capacities to produce IgE, IgM and IgG antibodies were abolished by thymectomy carried out within 48 h after birth. The capacity to produce IgE antibody was not affected by thymectomy at 7 days or later, whereas the capacities to produce IgM and IgG antibodies were reduced by thymectomy carried out at 4 weeks of age.


Studies on the role of histamine and 5-hydroxytryptamine in immunity against the nematode Trichostrongylus colubriformis. V. Changes in amine levels in the intestine following infection of guinea pigs of different immune status. A temporal relationship was established between the onset of expulsion of the parasitic nematode Trichostrongylus colubriformis from the intestine of both vaccinated and adoptively immunized guinea pigs with a sudden increase in small intestinal mucosal histamine to two or three times pre-infection levels. However, in guinea pigs whose capacity to expel T. colubriformis was inhibited by treatment with anti-lymphocyte serum, mucosal histamine remained at pre-infection levels. The results support previous findings which suggest an important role for histamine in the effector mechanism of the immune response of guinea pigs against T. colubriformis.


Changes in host resistance caused by Nocardia brasiliensis in mice: cross-protection against Listeria monocytogenes. Listeria monocytogenes was used to study the rate of development, magnitude, and persistence of the antimicrobial resistance engendered by Nocardia brasiliensis infection in mice. The growth of Listeria in the liver and spleen was more effectively restricted in Nocardia-infected mice than in noninfected animals. The development of delayed-type hypersensitivity to the Nocardia antigen was closely correlated to the increased resistance to Listeria, suggesting that both properties are the consequence of a single immunological event. The antibacterial resistance was also demonstrated in vitro. The results of the foregoing studies indicate that the microbicidal ability of macrophages, very likely activated by cell-mediated immunity, in enhanced in mice infected with Nocardia.


Different suppressive effects of combined cyclophosphamide-antigen treatment compared with exclusive cyclophosphamide treatment on primary and secondary humoral immune reactivity. The immunosuppressive effect of a combined treatment with antigen (C3H erythrocytes - ME) and cyclophosphamide (CY - dosage 65% LD50) has been studied in inbred CAP rats showing different degrees of immunological reactivity. When primary reactivity existed before treatment, this reactivity was not abolished but diminished. When weak secondary reactivity (after one antigen injection) existed before treatment this reactivity was abolished and again diminished primary reactivity was found. When strong secondary reactivity (after 4 antigen injections) existed before treatment selective unresponsiveness was found during the 4 weeks following treatment. 12 weeks after treatment  diminished primary reactivity was found again. When the same dose of CY was given without antigen no immunosuppressive effect could be seen - irrespective of whether primary, weak or strong secondary reactivity existed. The results indicate that in this model it is easier to induce selective unresponsiveness in sensitized than in nonsensitized rats and suggest that primed lymphocytes are more susceptible to a combined antigen-CY treatment than unprimed cells.


Early rheumatoid-like lesions in rabbits injected with foreign serum: relationship to localization of immune complexes in the lining tissues of joints and cellular content of synovial fluid. Immune complex localization in joint tissues and white cell effusion into the joint space as well as synovial lesions are shown to occur in rabbits injected intravenously with bovine serum. Synovial lesions of one knee were found to be associated with immune complexes in joint tissues of the contralateral knee (because of the experimental design very few rabbits had both immunofluorescence and histology performed on the same joint). There was also a week correlation between moderate and gross synovial lesions and cellular effusions of the same joint. Cartilage proteoglycan depletion was seen in some injected animals and this was related to lining cell hyperplasia. Rabbits from different breeding colonies displayed different incidences of lesions suggesting an environmental or genetic influence on the development of rheumatoid-like lesions.


Modification of prostaglandin and thromboxane release by immunological sensitisation and successive immunological challenges from guinea-pig lumg. The release of prostaglandins (PGs) and thromboxanes (Txs) from perfused guinea pig lungs was investigated during different immunological states. The major product released from normal lungs perfused with exogenous arachidonic acid was 6-oxo-PGF1a. The procedure of sensitisation to specific antigen resulted in an increase in the release of 15-oxo-13,14-dihydro-TxB2 and a decrease in the release of 6-oxo-PGF1a- and 6,15-dioxo-13,14-dihydro-PGF1a from lungs perfused with arachidonic acid. The relative amount of 15-oxo-13,14-dihydro-TxB2 released progressively increased with the number of immunological challenges with both exogenous and endogenously derived substrate, arachidonic acid. This change in response to successive immunological challenges may represent a protective mechanism to prevent parent Txs and PGs entering the systemic circulation.


Neutrophil chemotaxis: the kinetics of cellular locomotion in vitro. The Boyden chamber system has been used to study the motile response of rabbit peritoneal neutrophils to partially purified casein cytotaxin. The results of these in vitro experiments indicate that neutrophils respond in two distinct ways to cytotaxin. Firstly, they increase their innate random mobility. Secondly, they respond to the information contained in a cytotaxin concentration gradient by exhibiting directional movement with a velocity vector directed towards the higher cytotaxin concentration. Since the two responses are kinetically distinct, one may infer that they are mechanistically distinct.


Selective killing of mitogen-induced transformed cells by quinine sulfate in vitro. Increase in incorporation of 3H-thymidine ([3H-]-Tdr) in blast-transformed cells was induced in vitro by either lipopolysaccharide or concanavalin A (Con A) in spleen cells of Balb/c mice and by Con A in rabbit peripheral lymphocytes. Small lymphocytes were not affected by the addition of quinine to the medium. This was shown by a dye exclusion test and by mitogen stimulation after exposure and removal of quinine from the medium. On the other hand, immunoblasts were not formed in lymphocyte cultures containing both quinine and the cell mitogen. The degree of [3H]-Tdr incorporation after mitogenic stimulation was also markedly reduced by subsequent addition of quinine. An incubation period of at least 5 h was required for the expression of quinine effect. It is concluded that quinine acts as a cytotoxic agent for immunoblasts in vitro.


Demonstration of distinct allergens by means of immunological methods. Comparison of crossed radioimmunoelectrophoresis, radioallergosorbent test and in vivo passive transfer test. An immunosorbent column was prepared containing a purified major allergen fraction from codfish (DS 22) covalently coupled to agarose. Sera from patients allergic to codfish were run through the column at pH 7.2. After extensive washing, the IgE retarded in the column was eluted with a buffer at pH2.5. The original sera and fractions from the chromatography experiments were examined by means of crossed immunoelectrophoresis (CIE), crossed radioimmunoelectrophoresis (CRIE), radioallergosorbent test (RAST) and in vivo passive transfer (PK) tests using the DS 22 from codfish and a crude codfish extract. The experiments demonstrated that the crude extract contained a minor codfish allergen (antigen-17-cod) which was distinct from DS 22. RAST was the most convenient technique for the identification of fractions containing allergenic activity. The PK tests served to prove the biological activity in vivo. CIE/CRIE were superior to RAST and PK tests regarding their ability to identify distinct allergens. Full agreement was found between results using different techniques including the immunosorbent experiments. Some of the radiostaining in CRIE, however, was misleading due to coprecipitation of DS 22 in several precipitates in the CIE preparations of the crude codfish extract.


Social and psychological characteristics of alcoholics: a male--female comparison. Male and female alcoholics from a public health clinic were compared on social and psychological characteristics. Although sex was not found to be associated with the number of close friends reported by subjects, it was found to be significantly associated with designations of the alcoholic's "significant others", incidence of marital difficulty and with scores on the Definition of Alcohol Scale and the Neuroticism Index. There was a statistically significant relationship between sex and the number of social complications resulting from alcohol abuse; however, male and female alcoholics conceptualized their drinking as a problem in strikingly similar ways.


The assessment and training of assertive skills with drug addicts: a preliminary study. The effects of a short-term behaviorally-oriented assertion training program were evaluated with a sample of drug-abuse patients concurrently involved in an ongoing inpatient program. Assertion questionnaire and verbal performance data were obtained from both a treatment and a no-treatment group prior to and following 3 weeks of assertion training. The results indicated consistent and significant group differences on the verbal behavior variables, but not on the questionnaire data. The results also suggested that the assessment of assertion by situationally defined problem areas may be more accurate and sensitive to change than a more general definition and assessment of assertive behavior.


Illicit opiat use during methadone maintenance. The core hypothesis deduced from the Dole-Nyswander blockade formulation is that methadone is a sufficient but not necessary condition for abstinence from heroin. It is argued that this hypothesis has not been tested with scientifically adequate research. A research design is suggested. Since the Dole-Nyswander focus is at the physiological and metabolic level, it is argued that the blockade theory, pending, its scientific validation, should be supplemented by sociological, organizational, and economic theory.


Cigarette smoking in social interaction. Studied behavior patterns by smokers and others in social interaction correlated with various behaviors comprising cigarette smoking. Field observation methods were used in observing 91 smokers in 117 social interaction settings. Settings were chosen to vary in degree of intimacy between participants in social interaction, and in degree of physical activity. Reliability of observations was established using independent field observers and raters of a videotape of one interaction. Findings generally were that smoking behaviors occur at points in the interaction when the smoker is relatively uninvolved and passive in the context of the social interaction. It is speculated that smoking is a form of self-involvement which is incompatible, on a momentary basis, with active social involvement.


Prevalence survey of inhalant abuse.

Prevalence survey of inhalant abuse. Although there is a paucity of hard epidemiologic data on the prevalence of inhalant abuse, there is considerable anecdotal evidence that such abuse is continuing. Recently, we received repeated reports that one particularly public housing project in Atlanta had high rates of inhalant abuse, and to assess the prevalence of such abuse in children 4 to 20 years old, we conducted a random household survey in 400 of the project's 1,140 units. In an attempt to get complete and reliable data, wer chose and trained 10 residents as interviewers. Fifty youngsters were identified as ever having used inhalants, representing a sample prevalence of approximately 4%. The typical sniffer was a male, age 15, in the 9th grade or currently out of school. Some sniffers, though, continued to use inhalants into the 20s. Not unexpectedly, sniffers were found to use alcohol and other drugs at greater rates than other children. Although the parents of sniffers often said that they recognized drug-related problems in their children, the seldom sought help. Nevertheless, most residents felt that a drug-counseling program should be established in the project to provide alternative recreational activities.


Methadone dose and human sexual behavior. Among 31 male and 17 female former addicts in methadone maintenance or drug-free treatment, the frequency of sexual behaviors was determined by questionnaires administered at least weekly over several weeks. Daily methadone dose (mg/kg) correlated significantly with frequency of genital contacts (r = -.54) and organs (-.43) among females, and with frequency of ejaculation (-.31) among males. Although open and nonblind, the study suggests that higher doses of methadone may suppress human sexual behavior.


Thought-stopping as a treatment for reducing cigarette smoking. Three treatments, thought-stopping, group discussion, and the wearing of a badge saying "I don't smoke", each combined with self-monitoring, were compared to one another and to self-monitoring alone for their ability to modify the smoking behavior of 60 volunteers. All procedures led to an important reduction of the smoking rate at the beginning of treatment, the reduction being significantly greater with thought-stopping. The latter remained the most successful treatment during the 6-month follow-up, although it did not differ significantly from self-monitoring alone.


Drug use, attitudes, and behaviors of youth in an urban free clinic. A questionnaire regarding drug use, attitudes, and behaviors was completed by youths attending a free clinic on randomly selected evenings. Compared to a sample of suburban high school youths, the clinic youths were heavier drug users and were more antiestablishment in their attitudes and behaviors. The clinic youth as a whole tended to have antiestablishment attitudes but within the sample drug use was, with specific exceptions, not related to such attitudes. Youths whose first drug was not marijuana tended to be relatively heavy users, as compared to youths who started with marijuana. Data regarding reasons for use are reported. A brief discussion focuses on society's influence on the implications with the phenomena of drug use and free clinics.


Methaqualone abuse among U.S. army troops stationed in Europe. Methaqualone (primarily Mandrax) abuse among United States troops stationed in Europe increased significantly from 1972 onward as seen by morbidity reports related to medical treatment and mortality studies related to autopsy toxicology reports. Rarely was methaqualone used alone. It was generally combined with alcohol and hashish, the combination of which resulted in an extremely dangerous situation for both the individual and society.


The crisis of the western system of medicine in contemporary capitalism. This article makes a critique of current interpretations of the crises of the western system of medicine and presents alternative explanations for those crises. It indicates that the crises of medicine--reflected in its ubiquitous problems of costs and ineffectiveness--are due to and reflect the crises of legitimation and capital accumulation of contemporary capitalism. The article is divided into six parts: the first two define the characteristics of the crises of western contemporary capitalism and of its system of medicine, with a critique of current theories which try to explain them. Parts three and four contrapose to these theories a Marxist interpretation of the crises, tracing their causes to the needs created by the process of capital accumulation and to the demands expressed by the working population. The needs and demands generated by Capital and Labor are intrinsically in conflict, and are realized in the daily practice of class struggle. The characteristics and consequences of that struggle for health and for the organization, content, and ideology of medicine are analyzed in the fifth part. This class struggle takes place within a political context in which Capital and its social expression, the bouregeoisie or corporate class, have the dominant influence on the organs of the State. The sixth part of the article shows how that dominance determines the nature of the State responses to the crises of medicine. A primary thesis of this paper is that social class, class struggle, capitalism, and imperialism are not passé categories, as most ideologists of capitalism postulate, but rather they are the most important paradigms for understanding the crises of the western system of power and its medicine.


Health and labor-power: a theoretical investigation. In this historical materialist analysis of health and medical care, health is defined as a component of labor-power (capacity to work). Investment in health, including provision of medical services, represents part of the cost of maintaining the labor force. The primary determined of the level of health and medical care under capitalism is the tendency toward maximization of the rate of exploitation. The absolute level of health and medical care tends to decline as unemployment rises and individual workers become more "replaceable." Health differentials by socioeconomic status are similarly explained by the easier replacement of lesser-skilled workers. Medical care services in the context of the capitalist system constitute a drain on surplus-value. In periods of economic decline, attempts are made to conserve surplus-value through reductions in medical services ("social wages"). Institutional and ideological racism yields additional surplus-value savings and weakness public resistance to medical care retrenchment. The profits of health-related industries are shown to be merely partially recouped surplus-value losses. The social epidemiology of capitalism has been characterized as social murder. "Public health" measures appropriate to this systemic pathology are suggested.


Laws of motion in the for-profit health industry: a theory and three examples. The dynamics generated in the for-profit health industry by the drive for accumulation combine with the life cycle of a product to produce, within a given political framework, tendencies toward certain types of industry structure. The evolution of this structure is characterized by increased concentration of economic activity in diversified multinational corporations which combine health and non-health products. Three industries representing different stages of product and market development are analyzed in this article. The pharmacological industry is a mature industry dominated by large diversified multinational corporations which grow mainly through expansion abroad and diversification. The medical and dental instruments and supplies industry is newer, smaller, and faster growing. Its growth potential is attracting many companies an; increasing competition. The newest industry, investor-owned hospitals and hospital chains, is characterized by rapidly growing but still relatively small companies. The appendix, included to illustrate certain social, economic, and political issues, focuses on Medtronics, a highly scientific, fast-growing firm which produces electronic pacemakers.


Drought and dependence in the Sahel.

Drought and dependence in the Sahel. The relationship between human activity and environmental degradation has been documented in numerous studies. With regard to West Africa, E.P. Stebbing was already warning of ecological degradation due to overcultivation and overgrazing in the 1930s. Less well documented are the reasons why people who understand many of the requirements of ecologically sound farming and herding nonetheless mismanage natural resources to the point of disaster. An examination of the 1968-1973 drought in the Sahel zone of West Africa (formerly French West Africa) suggests that the lack of economic autonomy for Sahelian countries is a major cause not only of their economic stagnation and underdevelopment but equally of the degradation of their ecosystems. Specific policies, initiated during the colonial period and continued by independent governments, can be identified as reducing the ability of West African famers and herders to exploit their environment with an adequate safety margin. Largely as a result of the 1968-1973 drought, there has been asn upsurge of interest in the Sahel on the part of international and national aid agencies. However, it is very possible that the programs devised by these groups will promote neither economic autonomy nor ecological stability for the countries in that region. A development strategy based largely on self-reliance, on the other hand, could the more successful in protecting both the populations and the ecology of the Sahel.


The political economy of controlling transnationals: the pharmaceutical industry in Sri Lanka, 1972-1976. This paper describes the experience of Sri Lanka in reforming the structure of production, importation, and distribution of pharmaceuticals in the period 1972-1976. It highlights the actions and reactions of transnational pharmaceutical corporations to these reforms, and traces the achievements and problems of the State Pharmaceuticals Corporation which was set up to implement the reforms. The roles of political leadership in regulating the power of drug transnationals, and of the medical profession in resisting reform, seem to be of crucial significance. Developing countries wishing to lower the present high cost of drug delivery must proceed with great care and immense caution, since complex problems of quality control, bioequivalence, medical acceptance, and consumer reeducation are involved.


Education and income effects in the use of ambulatory services in the United States: an analysis of the 1970 National Health Interview Survey data. The roles of education and income as determinants for utilization of ambulatory services in the U.S. are investigated by the application of path analysis to a subsample of the 1970 National Health Interview Survey. The methodology permits the identification of both the direct and indirect effects of each independent variable on utilization within a model that views need as the major determinant of care. Previous findings that income has no direct effect on utilization, while education does, are reaffirmed. Contrary to previous analyses, however, it is shown that income does have a strong indirect effect on utilization via its impact on need arising from chronic conditions, measured as limitation of activity. Individuals in the highest income category have a mean annual visit rate of 4.13, while the rate for those in the lowest is 5.43. Most of the differential, 1.3, is attributable to the lower prevalence of chronic conditions in the highest income bracket. The total effect of education, on the other hand, is only 60% of its direct effect since higher educational attainment is associated with lower levels of chronicity. Disaggregation of direct and indirect effects through the need variables shows that income has a greater effect on utilization than does education.


Synthesis and beta-conformation of copolypeptides with alternating hydrophilic and hydrophobic residues. Copolypeptides with alternating hydrophilic and hydrophobic residues were prepared, and their ability to form beta-structures in aqueous solutions was investigated by circular dichroism. Optically pure samples of poly (Lys-Leu-Lys-Leu) and poly (Leu-Glu-Leu-Glu), obtained via the 2-hydroxyphenyl esters, undergo a coil-to-beta transition in presence of salt. The beta-structures obtained under identical conditions with partially racemized samples of poly (Leu-Lys)Np and poly (Leu-Glu)Np, prepared by polycondensation of the corresponding dipeptide p-nitrophenyl esters, appear to be less regular. Non-alternating poly (Gly-Lys-Leu-Lys-Leu) does not form beta-structures in presence of NaCl as does alternating poly (Lys-Leu-Lys-Leu) indicating that the amino acid sequence can dramatically change the tendency to form beta-structures.


An AB initio investigation of molecules with a disulfide bond: (HS)2, (CH3S)2 and cystine. ab initio Calculations at the Gaussian-70 STO-3G and 4-31G basis levels have been carried out for (HS)2 and (CH3S)2. Cystine was investigated at the STO-3G level. The STO-3G energy minimized geometry agrees well with experiments for (HS)2 and (CH3S)2. The barriers to internal rotation are predicted to be (at the 4.31G level): (HS)2, cis 8.5 kcal, trans 3.03 kcal; (CH3S)2, cis 18.47 kcal, trans 6.04 kcal.


beta-endorphin: synthesis and biological activity of shortened peptide chains. Three analogs of beta-endorphin have been synthesized by the solid-phase method: betac-endorphin-(1--5)-(28--31), betac-endorphin-(6--31) and betah-endorphin-(1--5)-(16--31). The analgesic activities of these synthetic peptides relative to that of the parent molecule are reported. All three peptides at high doses exhibit either no or much weaker analgesic activity than beta-endorphin. These data suggest that the entire beta-endorphin molecule is necessary for full in vivo analgesic activity.


Size and shape of two intestinal dipeptidases. Physicochemical parameters were determined on glycyl-L-leucine hydrolase (glycy-leucine dipeptidase, EC 3.4.13.2) and aminoacyl-L-proline hydrolase (proline dipeptidase, EC 3.4.13.9), purified from pig small intestine. The native molecular weights were found to be 115,000 and 113,000, respectively, as determined by a sedimentation equilibrium technique. Under denaturing conditions the molecular weights were found to be 51,000 and 63,200, respectively, using the same technique. It is concluded that each dipeptidase is composed of two subunits of equal molecular weight. The two dipeptidases have the same Stokes radius, 4.2 nm, analysed by gel chromatography. The sedimentation coefficients were found to be 5.8. S and 6.5 S and the intrinsic viscosities 5.4 ml/g and 5.8 ml/g, respectively. For both dipeptidases the measured physicochemical parameters are in accordance with the model of a prolate ellipsoid of revolution, having an axial ratio of about 5.


Coacervation of sequential polypeptide models of tropoelastin. Synthesis of H-(Val-Ala-Pro-Gly)n-Val-OMe and H-(Val-Pro-Gly-Gly)n-Val-OMe. Syntheses of two sequential polytetrapeptide models, H-(Val-Ala-Pro-Gly)n-Val-OMe and H-(Val-Pro-Gly-Gly)n-Val-OMe via the p-nitrophenyl ester method are described. The p-nitrophenyl ester method gave high yields (85%--100%) of large molecular weight polymers. H-(Val-Pro-Gly-Gly)n-Val-OMe exhibited the interesting property of coacervation on raising the temperature of aqueous solutions while H-(Val-Ala-Pro-Gly)n-Val-OMe precipitates irreversibly under similar conditions. Whereas non-dialyzed lower molecular weight polymers of H-(Val-Pro-Gly-Gly)n-Val-OMe with n = 8 to 40 did not coacervate, but did show a transition to increased intramolecular order on raising the temperature of aqueous solutions above 50 degrees C, the dialyzed higher molecular weight polymer, n greater than 40, does coacervate beginning at about 50 degrees C. This demonstrates the molecular weight dependence of coacervation and also suggests the importance to coacervation of side chain interactions in the Val-Pro sequence. The increase in intramolecular order, seen as the formation of a 14-atom hydrogen-bonded ring, occurs simultaneously with the Val-Pro hydrophobic side chain association.


Training of voluntary torsion.

Training of voluntary torsion. By means of a visual feedback technique, human subjects were trained to make large conjugate cyclorotary eye movements at will. The range of movement increased with training at a rate of approximately 0.8 degrees per hour of practice, reaching 30 degrees at the end of training. Photographs recorded the ability to make voluntary cyclofixations at any amplitude within the subject's range. Cyclotorsional pursuit was also trained, with ability increasing with greater amounts of fisual feedback. In addition, torsional saccadic tracking was trained, showing a magnitude vs. peak velocity relationship similar to that seen for normal saccades. Control experiments indicate that all of these movements were voluntary, with no significant visual induction. With extended practice, large torsional movements could be made without any visual stimulation. The emergence of voluntary torsion through training demonstrates that the oculomotor system has more plasticity than has generally been assumed, reopening the issue as to whether other movements could also be trained to alleviate the symptoms of strabismus.


Ocular absorption and metabolism of topically applied epinephrine and a dipivalyl ester of epinephrine. An analogue of epinephrine (EPI), dipivalyl epinephrine (DPE), has been found to reduce intraocular pressure (IOP) significantly at lower concentrations than EPI itself. In order to understand the reason for this increased activity, the ocular penetration, distribution, and metabolism of these two compounds were compared. About 10 times as much DPE as EPI was absorbed by rabbit eyes, with the cornea as the major repository for the increased amount of drug absorbed. Comparison of the partition coefficients of the two compounds showed DPE to be from 100 to 600 times as lipophilic as EPI. The radioactive materials found in the aqueous humor after treatment with either compound had the same mobility in a thin-layer chromatographic system. The data indicate that following the increased penetration of the lipophilic prodrug, DPE is hydrolyzed to EPI in the eye.


Histopathology of delayed hypersensitivity reacitons in the guinea pig uveal tract. Two distinct patterns of delayed-onset, cell-mediated hypersensitivity have been induced in the guinea pig eye with the same soluble protein antigen and two different methods of immunization. The predominant histologic feature of these reactions was the large number of eosinophils which infiltrated the uveal tract and the limbus. Skin test reactions in the same animals contained very few eosinophils and were typical of cutaneous basophil hypersensitivity or classic delayed hypersensitivity of the tuberculin type. It is suggested that local factors play a role in determining the character of immune expression in different tissues.


Stereopsis and unilateral brain disease. Performance on a random-letter stereoscopic task has been reported to be affected by right but not left cerebral disease. Subsequent studies employing a conventional stereoacuity test have challenged these results and proposed that dementia may be the primary determinant of impaired stereopsis in the patients with brain disease. The latter investigators have failed to distinguish between local and global stereopsis. The present study confirms the original findings, rules out dementia as a potential artifact, and attempts to reconcile the conflicting series of reports.


Experimental, ultrasonically induced lesions in the retina, choroid, and sclera. Lesions of the retina, choroid, and sclera were created in the proptosed eye of the rabbit with the use of focused ultrasound at 9.8 MHz. Exposure levels greatly exceeding those encountered in diagnostic systems were required. Histological examination of selected tissue samples, analysis of lesion-producing exposures, and lesion size variations suggest that thermal mechanisms are the principal cause of permanent tissue alterations. Subthreshold lesions, which consist of transitory effects, were observed. 'Threshold" lesions first manifested tansitory effects followed by permanent alterations which appeared within 24 hr. Suprathreshold lesions were evidenced by the immediate appearance of a highly blanched area with an overlying edema and occasional hemorrhage, appearing within 24 hr. The edema in these cases was resorbed within a few days, leaving behind a permanently blanched region. The threshold curve developed from these data is similar in shape to the threshold curve for light-induced lesions created with a commensurate focal spot.


Acuity and contrast sensitivity in 1-, 2-, and 3-month-old human infants. The importance of assessing infant visual function is indicated by recent demonstrations that early visual experience in part determines the eventual state of adult visual function. It is argued that the contrast sensitivity function (CSF) could be a valuable index in the assessment of infant vision because it provides information concerning several aspects of vision. CSF's were measured in 1-, 2-, and 3-month-old infants. The "cut-off" spatial frequencies, which are estimates of visual acuity, were 2.4 cy/deg for 1-month-olds, 2.8 cy/deg for 2-month-olds, and 4.0 cy/deg for 3-month-olds. Sensitivity to contrast was shown to increase between 1 and 3 months of age. The CSF's measured also provide evidence for the presence of a low-frequency fall-off at 2 and 3 months.


A new, albino-beige mouse: giant granules in retinal pigment epithelium. Albino-beige mice were produced in order to combine two experimentally useful characteristics, albinism and lysosomal dysfunction, in the same animal. The retinal pigment epithelium of albino-beige mice formed giant intracellular granules. Exposure of albino-beige mice to white light of 150 foot-candles for 3 to 10 hr induced marked phagocytosis of rod outer segment fragments by the retinal pigment epithelium, resulting in intracellular accumulations of undigested disk membranes within the giant granules. Additional, incompletely processed membranes accumulated as the mice aged or were exposed to 150 foot-candle light for longer periods. Such accumulations of ingested membranes were not observed in the pigment epithelium of exposed or aging albino mice heterozygous for the beige gene. Because of its altered processing of ingested outer segment membranes, this new albino mouse should be useful for studying the possible roles of the retinal pigment epithelium in the maintenance of  photoreceptor cells and in their recovery from light damage and other insults.


The canine eye: in vitro studies of the intraocular pressure and facility of aqueous outflow. Possible interdependence of facility of aqueous outflow and intraocular pressure was examined by quantitative aqueous perfusion at four levels of intraocular pressure in 69 canine eyes, freshly excised post-mortem. Statistically similar, time-dependent increases in facility of outflow occurred over steps of increasing and decreasing, and at constant intraocular pressue. Pretreatment with intracameral hyaluronidase diminished the rate of facility increase, reducing it to 20% or less in one third of the eyes so perfused. Observed increases in canine facility of outflow with changing intraocular pressure appeared to result primarily from "washout" of the hyaluronidase-sensitive component of the barriers to aqueous outflow and not from direct effects of the intraocular pressure.


Identification of heavy-molecular-weight soluble protein in aqueous humor in human phacolytic glaucoma. Aqueous humor was obtained by paracentesis at the time of cataract surgery from six patients with phacolytic glaucoma, diagnosed on the basis of acute unilateral open-angle glaucoma associated with an apparently leaking hypermature or mature cataract, and from six control patients with immature cataracts. Three of the latter had primary open-angle glaucoma. Quantities of heavy-molecular-weight (HMW) protein (MW greater than 150 X 10(6)) sufficient to obstruct aqueous outflow were identified in all six phacolytic aqueous humor specimens but in none of the controls. Three of the hypermature cataractous lenses from the cases of phacolytic glaucoma were also examined and were found to have 14-fold greater quantities of HMW protein in their liquefying cortex than were present in the cortex of immature cataractous lenses. These findings, correlated with experimental HMW protein perfusion studies in excised human eyes that we have already reported, strongly suggest that direct obstruction of the aqueous outflow channels by liberated HMW soluble lens protein may be a significant and previously unappreciated factor in the pathogenesis of phacolytic glaucoma.


Molecular sieving in suprachoroidal fluid formation in man. Suproachoroidal fluid (SCF) obtained at the time of the surgical evacuation of a clinically significant choroidal detachment (CD) was analyzed for its chemical and cellular components in four distinct subgroups: (1) CD following cataract surgery, (2) CD (nonhemorrhagic) following glaucoma surgery, (3) CD (hemorrhagic) following glaucoma surgery, and (4) intraoperative CD during glaucoma surgery in patients with elevated episcleral venous pressure. The fluid obtained in groups 1, 2, and 4 was clear and slightly xanthochromic and contained low-molecular-weight substances in concentrations essentially equal to serum. Proteins and other high-molecular-weight substances were present in lesser amounts than in serum. Albumin, alpha1-antitrypsin, and transferrin were present in amounts approximately equal to those in serum, whereas alpha2-macroglobulin, IgM and IgG were decreased. beta-Lipoprotein and beta-complement were absent. It is postulated that this distribution of serum proteins is a manifestation of molecular sieving and is consistent with the existence of an isoporous membrane between the intravascular and suprachoroidal space with a pore diameter of 144 A. In the intraoperative choroidal effusions, there was evidence for exclusion of more of the lower, as well as all of the higher, molecular weight proteins. This suggested that the degree of molecular sieving increased with increasing filtration rate. In the hemorrhagic SCF, the distinctive character of the fluid and the protein concentrations indicated that the integrity of the capillary membrane was mardkedly disrupted, thereby allowing higher-molecular-weight proteins and cellular elements to enter the space.


Vision through cataracts.

Vision through cataracts. Contrast thresholds for a range of different spatial frequencies were compared with "acuity" tests for 10 subjects with uniocular senile cataract. The results indicate that the magnitude and extent of the intra-resolution limit abnormality vary dramatically in cataract subjects and that, for some subjects, vision is abnormal for objects of all sizes. This finding indicates that the present acuity evaluation of vision with cataracts is inadequate because, in some cases, it grossly overestimates the nature of the visual world of the cataract patient.


A phase-specific adaptation effect of the square-wave grating. The existence of wide-band, phase-specific channels in the human visual system has been suggested in recent investigations. We used a number of adapting gratings to test for phase-specific adaptation effects. Observers were asked to discriminate between a simple 3 cpd sine-wave grating, (3), and a complex grating composed of this (3) plus a 9 cpd grating combined in one of two phases: peaks-subtract, (3,9:0), or peaks-add, (3,9:pi). The results show a significant phase-specific adaptation effect. That is, following adaptation to a square-wave grating, discrimination performance for (3,9:0) vs. (3) deteriorated significantly more than for (3,9:pi) vs. (3). Adaptation to the first two harmonics of the square-wave, (3,9:0), or a 3 cpd triangle-wave grating failed to produce phase-specific adaptation effects that reached significance.