Preparing chronic patients for community placement: a four-stage treatment program.

Norristown (Pa.) State Hospital has a four-stage treatment program that prepares chronic patients for returning to the community. the program, which began in 1970, includes three token economy wards that are segregated by sex, and a coed activities ward, socialization ward, and exit ward. Over the past five years, 258 chronic patients have been discharged to the community after completing the treatment program. During the three months to five years since their discharge, 227 patients, or 88 per cent, have made a successful adjustment to the community. The unit's 12-per-cent recidivism rate is well below the national average for such programs.


Massachusetts: The transfer of state hospital resources to community programs.

Gardner (Mass). State Hospital began transferring its resources to two community programs two years ago. During the transfer administrative problems increased and become more difficult to resolve, hospital staff and community members became fearful that the hospital would be phased out, and the possibility of a budget cut was a constant threat. When the hospital census was reduced to 225 patients who could not enter community programs, the commissioner of mental health appointed a commission to make recommendations about the hospital's future role. Five options open to the commission, and its recommendations, are discussed.


Illinois: Community mental health: a noble failure?

Two studies were made in the northwestern region of Illinois to determine if the community approach helped restore the social competence and reduce the build-up of chronically ill patients. In the first study there was no indication that community care was superior to that of a traditional state hospital. Seventy-four per cent of the patients in the sample, however, had a history of repeated hospitalizations. The second study evaluated only first-admission patients and found that community-oriented programs were more effective. Both the center and the hospital had some patients for whom neither system of care was more effective in preventing chronicity. The center has established several pilot projects for managing those chronic patients.


California: Orange County's alternative to state hospital treatment.

In the early 1970s Orange County, thtough the Orange County Department of Mental Health, began building a local network of regionalized and centralized services, the goal of which is to provide all needed mental health services locally. Despite budgeting setbacks and temporary program freezes, many of the services are now operating. The author describes those services, their estimated costs and staffing requirements, and the organizational structure established to administer them with a minimum of overlap.


Kansas: a survey of state hospital admissions from an area served by a mental health center.

The authors made a survey of all admissions to Topeka (Kans.) State Hospital from a three-county catchment area over an 11-year period during which a private psychiatric clinic in the area assumed the functions of a comprehensive community mental health center. The center's activities brought a significant decrease in the number of direct admissions to the hospital from the catchment area. However, the center consistently referred more patients with psychotic disorders to the state hospital than would be expected on the basis of over-all state hospital admissions. Similarly, a high proportion of patients with organic brain syndromes were admitted directly to the hospital from the three-county area. The authors say the findings suggest that the public mental hospital still has an important role to play on the delivery of mental health services.


Adopting new models for continuity of care: what are the needs?

There are glaring, almost universal deficiencies in the organization of community resources for treating and rehabilitating the mentally ill, particularly psychotic patients, the author says. The deficiencies could be partly remedied by reorganizing psychiatric hospitals to play a key role in outpatient service delivery, and by paying more attention to the principles of continuity of care for psychotic patients. One way of doing both is through the model of a mini-mental-health-center adopted at a Veterans Administration hospital: the same terms provide active, continual care for patients regardless of whether they are in or out of the hospital. The program developed on one ward is described further in the next paper, written by ward staff members and others.


The NLRB decisions on appropriate bargaining units.

It appears that the NLRB's lack of familiarity with the health care industry and particularly with the day-to-day functioning of a hospital led it to search for touchstones such as the status of an RN or the certification of technicians that would enable it to make easy but illogical distinctions. As the cases are reviewed in the judicial system, the separate units for RNs, technical employes, and business office clerical employes will be closely scrutinized. Finally, the bargaining units as outlined and the placement of particular groups of employes based on their formal status will necessarily have an impact on the functional integration of hospital activities.


Invasive and metastasizing carcinoma in a small adenomatous polyp of the colon: report of a case with demonstration of a tumor associated antigen.

An unusual case of metastasis to two lymph nodes from an adenocarcinoma arising in an adenomatous polyp of the sigmoid colon is presented. Invasion of the stalk could not be detected, but penetration of the muscularis mucosae was observed. Immunoperoxidase staining was used to detect an antigen in the invasive and metastatic components of the tumor that reacted with an antiserum to a tumor associated antigen. A focus of intraepithelial carcinoma was also detected by this method. The relevance of these findings to the adenoma-carcinoma sequence is discussed.


Practical use of electron microscopy for the diagnosis of glomerular disease.

In the past few years many clinically significant new glomerular lesions have been reported from observations made on renal biopsy specimens by electron microscopy. The clinical applicability of electron microscopy is illustrated by examples of specific ultrastructural patterns of glomerular reaction making possible a more accurate diagnosis, prognosis, and prediction of the response to treatment.


The usefulness of electron microscopy in the diagnosis of human tumors.

Ultrastructural features of neoplastic cells can provide clues for correct diagnosis when light microscopy fails. Secretory granules are characteristic in the following tumors: mucin granules in poorly differentiated adenocarcinomas, zymogen granules in acinic cell carcinomas, lysosomal granules in prostatic carcinomas, melanin granules in malignant melanoma, carcinoid, islet cell tumors, pheochromocytoma, and neuroblastoma granules in the corresponding neoplasms. Among cytoplasmic organelles, rough surfaced endoplasmic reticulum characterizes adrenocortical, ovarian, and hepatocellular carcinomas and plasmacytomas. Tonofibrils are characteristic of squamous cell carcinomas. Glycogen deposits distinguish Ewing's sarcoma from lymphoreticular neoplasms. Intercellular relationships and membrane specialization are important features in the differential diagnosis of various undifferentiated tumors. The frequent resolution of difficult diagnostic problems by electron microscopy outweighs the disadvantages of this technique, such as the expense and time required.


Diabetic capillaropathy.

Diabetic capillaropathy is defined and reviewed. A number of physiological and pathological variables, such as aging, venous stasis, and environment, may affect the thickness of the capillary basal lamina. Since these effects have not been adequately measured, it is impossible to know precisely what increment diabetes mellitus adds to the basal lamina. Because of these variables and technical difficulties, the detection of early diabetes is impossible at this time. However, the ultrastructure of the peripheral capillaries in the late stages of diabetes provides a means of detecting the presence of widespread capillaropathy when clinical evidence is difficult to obtain or uncertain.


Significance of the Reed-Sternberg cell.

Our concept of the Reed-Sternberg cell has evolved considerably since the turn of the century. At the present, it is generally accepted that this cell is a polyploid lymphoreticular cell incapable of mitotic division. The two nuclei of the classic Reed-Sternberg cell probably represent the two lobes of a markedly convoluted or segmented nucleus. The Reed-Sternberg cell may be regarded as the end stage of a transformed lymphocyte that has undergone in vitro blastogenesis. It is not definitely known whether it is of the T or B cell variety. There seems to be no valid histochemical or ultrastructural evidence that it is a histiocyte. The Reed-Sternberg cell, although not 'pathognomonic,' continues to be an essential landmark for the diagnosis of Hodgkin's disease. The actively dividing cells in the neoplasm are considered to be the small lymphocytes as well as the mononucleated reticulum cells, although the triggering mechanism for cell division remains unknown.


Problems in the development of a clinically oriented program in electron microscopy.

The educational, organizational, and fiscal aspects of electron microscopy are discussed.. with emphais on the desirability of making electron microscopy an integral part of the formal training of residents in pathology and of the overall educational program of the medical staff. The rapidity of feedback of information from the pathologist to the clinician is stressed. The number of specimens processed and the variety of tissues submitted for electron microscopy can be regulated by the pathologist but should reflect the particular strength of the hospital or its department of pathology. The organization of the electron microscopy facility, its funding, and sharing of the electron microscopy program in the local community of clinical scientists are discussed


The application of electron microscopy and cellular biochemistry to the autopsy. Observations on cellular changes in human shock.

A method based on the utilization of electron microscopy, morphometric analysis, tissue culture, and biochemical analysis in the study of human autopsies is described. In this method rapid sampling immediately following somatic death is conducted in order to make meaningful the application of such techniques. In addition to describing the procedure, we present some new findings relating to cellular changes associated with shock. As in cellular pathobiology, it is of utmost importance that ultrastructural changes be correlated with alterations in chemistry and function.


Excretion of urinary testosterone in Klinefelter's syndrome.

The urinary testosterone excretion in 55 patients with Klinefelter's syndrome was determined by gas-chromatographic methods. The mean testosterone level in the group of Klinefelter patients was significantly decreased (15.7 mug/24 hrs) compared with the excretion by 30 normal men (44.1 mug/24 hrs). An age dependency of excretion levles was not obvious in chromatin-positive men when compared to healthy subjects. A correlation between testosterone excretion and configuration types seemed to be probable by reason of observations and statistical values. Average testosterone excretion increased with increasing normalization of body proportions. Gynecomastia was noticed in 56% of those examined. With increasing severity of gynecomastia the mean testosterone levels decreased. A correlation between beard and body hair, which was decreased in almost all subjects, and testosterone excreiton was not visible. With diminishing mean testosterone excretion an increase of osteoporosis seemed to be probable. A statistically significant difference was found when comparing patients who never had ejaculations with those who had regular libido and ejaculations. Klinefelter patients who had not succeeded in completing school or an occupational education showed a significantly decreased testosterone level as compared with others who had a profession.


G-6-PD polymorphism and racial admixture in the Cuban population.

The frequencies of the Gd-A, Gd-A- and Gd-B alleles have been estimated in a random sample of 455 female and 405 male high school students from Habana. The estimates of the Negro and Caucasian relative contributions to the present genetic make-up of the Habana population, based on these gene frequencies, are 0.20 and 0.80 respectively.


Nephrogenic diabetes insipidus in an Australian aboriginal kindred.

Four Australian aboriginal children were found to have nephrogenic diabetes insipidus. They are the sons of 3 sisters who were shown to have a urinary concentrating defect uncorrected by vasopressin. An extensive genealogy did not reveal any caucasian genetic influence suggesting that a new genetic mutation was responsible.


Chromosome studies in patients with congenital malformations and mental retardation.

16 (41%) out of 39 individuals referred by physicians because of sexual anomalies showed abnormal karyotypes; the corresponding figure for those investigated due to suspected autosomal aberrations was 37 out of 104 (36%). A special survey was also conducted among 51 mentally defective children with at least 3 malformations; 5 individuals (10%) were observed with chromosome abnormalities plus 3(6%) with rare variants. These results were compared with those presented in 26 other surveys reported in the literature.


[Chromosomal instability in homo- and heterocygocity for microcephalia vera )author's transl)].

In a family with microcephalia vera, not only the 3 microcephalic probands, but also their healthy mother showed a significantly increased rate of spontaneous structural chromosomal aberrations in cultures of lymphocytes of the peripheral blood. Thus an increased aberration rate in the lymphocytes of asymptomatic family members could serve as a sign of heterocygocity. The qualitative analysis revealed aberrations of the chromatid and chromosomal type; exchanges that are frequently found in Fanconi's and Bloom's syndrome could not be detected. Therefore it can be assumed that the chromosomal instability of microcephalia vera is caused by a specific mechanism.


Del (10)p autosomal deletion syndrome: clinical, cytogenetic and gene marker studies.

A 46,XX,del(10)p13 karyotype (Paris Conference, 1971) was identified in a 5-year-old Negro girl with mental and growth retardation, brachy- and trigonocephaly, downward slanting palpebral fissures, hypotelorism, epicanthal folds, ptosis, strabismus, dysplastic nose, high-arched palate, microdontia, small low-set posteriorly rotated ears, asymmetrical thorax, wide-spaced nipples, and minor abnormalities of hands and feet. Both parents and a brother had normal karyotypes. Expression of more than 50 polymorphic gene loci determining blood groups, serum proteins and red cell enzymes was studied. The results did not permit localization of a gene locus on the deleted segment of chromosome 10. The proposita was heterozygous for the Rh and MN blood groups and for the red cell enzymes adenosine deaminase, glutamate pyruvate transaminase and esterase D. These gene loci are thereby excluded from region 10p13 yields 10pter.


Cytological and cytogenetical studies on brain tumors. V. Preferential loss of sex chromosomes in human meningiomas.

Twelve out of 88 cytogenetically examined meningiomas of female patients showed, in addition to the typical loss of a chromosome 22, a loss of 1 or more chromosomes of group C. Among them 8 tumors had less than 8% cells with Barr-body-like particles, whereas in one tumor 12% and in 3 others over 20% Barr bodies were found, which, based on control studies, were classified as sex-chromatin negative, partly positive, and positive, respectively. In one case the loss of an X chromosome was verified by Giemsa banding. In 6 out of 24 meningiomas of male origin, the chromosomal morphology and association pattern strongly indicated that besides the loss of a chromosome 22, the Y chromosome was also missing. Moreover, the loss of the male sex chromosome could be ascertained in 4 tumors by the conspicuous absence of Y fluorescence in interphase nuclei and in metaphase plates after fluorescence staining. The findings are discussed in connection with the gonosomal loss in other human tumors and in old age.


Immunoglobulin allotypes in portugal.

The frequency of several immunoglobulin allotypes has been evaluated in a sample of 419 Portuguese subjects. It was found that the percentage of Gm (1) and of Gm (2) are among the highest in Europe, although Portugal is situated in the extreme southwest of Europe. A few cases of dissociation of Gm (1) and Gm (2) were noted and attributed to the probable presence of African admixture.


Polymorphism of red cell glyoxalase I (EI: 4.4.1.5); a new genetic marker in man. Investigation of 169 mother-child combinations.

The polymorphism of glyoxalase I was investigated in 169 mother-child combinations from southwestern Germany. Glyoxalase I (GLO) has 3 common phenotypes: GLO 1, GLO 2-1, and GLO 2. The results are in good agreement with the formal hypothesis: Two alleles GLO1 and GLO2 at an autosomal locus. The GLO1 gene frequency was estimated to be 0.39. From the electrophoretic pattern the GLO-molecule appears to consist of two subunits.


Probable loose linkage between the ABO locus and Waardenburg syndrome type I.

The possibility of linkage was tested in 3 large kindreds with Waardenburg syndrome type I against the ABO locus. Loose linkage is probably present; the recombination fraction in males, females, and both sexes combined seems to be approximately theta' equals 0.175, theta equals 0.255, and theta', theta equals 0.20, respectively. There are still more informative matings to be studied in those pedigrees, as well as the inminent possibility of determining the phase status in several of them, for the ABO locus and a few other loci.


[45,X/46,SYq dic-Sexchromosome mosaic].

This is the report on an obese girl with small stature and sexual infantilism. A 45,X/46,XYq dic mosaic was found in blood and fibroblast cultures. A summary is given of the cases so far reported in the literature. The clinical picture does not differ significantly from that of 45,X/46,XY cases. The relationship of phenotype and structural abnormalities of the Y chromosome is discussed.


Exclusion gene mapping utilizing patients with chromosome imbalance: the HL-A system as a prototype.

17 chromosomally unbalanced patients, their siblings and parents were tested for HL-A types and for up to 25 other polymorphic systems to determine whether there was gain or loss of an allele concurrent with the gain or loss of chromosome material. 5 patients had trisomy of part or all of a chromosome; 2 had trisomy of a segment and also deletion of chromosome material. All 7 were due to a familial translocation. The remaining patients had small deletions; 5 had ring chromosomes, 4 had rod deletions and 1 had missing chromosome material due to a heritable translocation. All cases were informative at the HL-A loci because of the high degree of polymorphism of the system whereas only some of the other systems were informative. None of the 17 patients showed unusual inheritance of HL-A or any other of the polymorphic systems examined. These results provide evidence excluding the HL-A and other loci from a number of possible locations in the human genome.


[Centronuclear myopathy with autosomal dominant inheritance(author's transl)].

For the first time in Germany cases of a "centronuclear myopathy" are described in a 14-year-old boy and his 18-year-old sister.  First symptoms in both patients appeared at 4 to 5 years of age with a "sleepy facial expression", clumsy gait and rapid fatigue.  Within few years the disease progressed to generalized muscle weakness and atrophy, ptosis, ophthalmoplegia externa and areflexia.  Weakness and atrophy were most pronounced in the distal muscles of the lower extremities.  Both patients were free of epilepsy and the EEG recordings were normal.  Motor and sensory nerve conduction velocities were normal.  Repetitive stimulation of nerves revealed a normal transmission from nerve to muscle.  Muscle biopsy showed a type I muscle fiber hypotrophy and a type II muscle fibre hypertrophy in addition to a predominance of type I fibres.  Both fibre types showed central nuclei, sometimes appearing as chains in longitudinal sections.  In most cells with central nuclei there persists a very small pericentral zone free of myofibrils but with increased activity of oxidative enzymes and phosphorylase.  2--3% of muscle fibres in cross sections showed a decreased of absent enzyme activity in the most peripheral fibre zone.  Electron microscopy showed evidence of a centrally distinct myofibrillar disintegration.  The father of both children had a ptosis at least from the 20th year of age.  5 years later generalized progressive muscle atrophy was recorded.  Aged 51 years he died of pneumonia.  Though not proved most probably the father suffered from the same disease as the children, pointing to an autosomal dominant inheritance in this family.  The disease, according to the literature, seems to be genetically heterogeneous.  The clinical picture seems to be independent of the mode of inheritance.  Our patients showed a relatively rapid progression of symptoms.  Pathogenetically the "centronuclear myopathy" may result from a disturbance of correlated nerve-muscle structures starting during early fetal life.


Three cases of minor chromosomal aberrations discovered by prenatal chromosome determination.

A case of pronounced secondary constriction of a chromosome belonging to pair N0. 9, a case of deletion of the short arms of one of the chromosomes in pair No. 13, and a case of partial trisomy of the distal portion of a chromosome in pair No. 14 were discovered by prenatal chromosome determination.  Analysis of the parents' karyotypes enabled the clinical importance of the three different chromosomal aberrations to be elucidated.


Hereditary defect of the sacrum.

A family in which both the mother and two of her daughters had partial agenesis of the sacrum and coccygeal bones is presented.  Further studies demonstrate a neurogenic bladder and a presacral mass in the 4-year-old girl who had severe urinary incontinence.  The mode of inheritance in this entity may be x-linked dominant as has been suggested.  Previously by Cohn and Bay-Nielsen (1969).  The gene may act as a lethal factors in hemizygous males.  A brief review of the literature showed a remarkable paucity of reports on the hereditary aspects of sacrococcygeal defects in man.  It is concluded that this may be misleading, since the true incidence of hereditary sacroccygeal deformities can not possibly be established until family members  of the probands are also examined radiologically.


Red blood cell acid phosphatase: ambiguity in phenotype and activity estimations in the proof of the "single allele" states.

A population sample of sick children was analyzed for the phenotypes and enzymatic activity of the erythrocyte acid phosphatase.  These data were statistically examined for the reliability with which the enzymatic activity of a given phenotype, supposed to be derived from a single allele in the phosphatase gene locus, may be used as a decisive criterion in distinguishing such an event from the normal states with the fully functioning pair of alleles.  Due to the overlapping of the statistical distribution curves of the normal and defective kins os isozymes, dependent on the relation of x and s, ranges of activity are shown where the measured enzymic activity is not conclusive for the judgement on the number of acting alleles, on the chosen probability level.  On the same basis a time saving screening system is proposed for the inteded search for the single-allele states of the phosphatase isozymes; some consequences for the paternity tests with the RBC phosphatase are also mentioned.


G-6PD "ankara".  a new G-6PD variant with deficiency found in a Turkish family.

A new G-6PD varient with enzyme deficiency is described in a 7-month-old Turkish boy without any hemolytic manifestation, except neonatal hyperbilirubinemia. The main characteristics of this variant were the following: Severe enzyme deficiency in erythrocytes (8% of normal), fast starch-gel-electrophoretic mobility (110% of normal), increased Ki NADPH with respect to NADP+, slightly biphasic pH curve, enzyme instability, in vivo and in vitro, decreased molecular specific activity (58% of normal).


Dicentric Yp chromosome in a patient with the gonadal dysgenesis and gonadoblastoma.

A patient with a short stature, gonadal dysgenesis, and bilateral gonadoblastoma had 3 cell lines in the blood and in the skin: 46,X,dic (Y) (pter vector q 1 2 : : 1 2 vector pter) as a major cell line 46,X,del(Y) (q 1 2), and 45,X. The intensively flourescent distal part of the Yq was deleted in both the Y-dicentric and Yq--chromosome. Both parents had normal karyotypes.


Deletion of long arms of chromosome 13.

The case is presented of a girl with the banded karyotype 46,XX,del(13)(q22) and a phenotype of severe mental and growth deficiency, mongoloid slant of palpebral fissures, ptosis, hypertelorism, microcephaly, microstomia, micrognathia, nystagmus, gothic palate, uvula fissa, low-set malformed ears, short fingers, pedes excavati, dislocation of hips and diabetes insipidis.  Both parents have a normal phenotype and karyotype.


[A case of atypical galactosemia(author's transl)].

The case of a male infant suffering from clinical manifest galactosemia in connexion with a disease of only about 70% in uridyltransferase activity is characterized as atypical galactosemia.  As compared with the described "Indiana variant" of a galactosemic female infant showing an unstable uridyltransferase activity this case demonstrates an unchanged enzyme activity still after 72 hrs.  The metabolic disease of this patient clearly demonstrated that the lack of a typical pronounced reduction of enzyme activity maybe not the leading criterion for excluding the clinical diagnosis of galactosemia.  In the present case only the consistent galactose-free diet lead to the decisive improvement of the clinical picture.  The investigation of the family revealed the typical pattern of an autosomal recessive mode of heredity.


Heterozygote tests and genetic counseling in maple syrup urine disease: an application of Baye's theorem.

The discriminatory power of a quantitative heterozygote test for Maple Syrup Urine Disease (MSUD) which we have been using is analyzed on the presumption that a single rare mutant allele is involved in MSUD.  Bayes theorem then predicts that only a small portion of persons from the general population with activities in the heterozygous range really are heterozygotes.  In addition, overlap of heterozygous and normal homozygous activity distributions requires rather high activities in first-cousin matings of a patient's sib in order to obviate the necessity for prenatal diagnosis.  Thus, the principle emerges that quantitative heterozygote tests for rare autosomal recessive diseases cannot fulfill the task they were designed for.


Rapid determination of hypoxanthine-guanine-phosphoribosyl transferase in human fibroblasts and amniotic cells.

A micromodification of the method of HGPRT and APRT assay is described, which measures the incorporation of 14C hypoxanthine and 14C adenine into cultured skin fibroblasts and amniotic cells grown on microtiter plates.  Only about 10000 cells are needed per assay.  By this method HGPRT deficient cells can be easily distinguished from normal cells.  Investigations with respect to the effect of substrate concentrations and time of incubation have been carried out on some normal fibroblast cell lines, amniotic cell lines and 3 Lesch-Nyhan cell lines.  Another modified method is described for quantitative determination of HGPRT activity by means of radio thin-layer chromatography.


ABO blood groups and chicken pox.

In 974 patients with chicken pox (varicellae) from four large children's hospitals in Germany, a weak association with blood groups A (and probably AB) was found.


Non-random appearance of Y-chromatin-like fluorescence in the nuclei of thyroid and brain and its chromosomal background.

Non-random distribution of fluorescing chromatin bodies resembling Y chromatin was observed among the cell populations of various organs obtained by autopsy of 52 adults.  This type of Y-chromatin-like fluorescence is more frequent in thyroid and brain than in other organs.  The Y-chromatin-like bodies of thyroid nuclei are not closely correlated with the brilliantly fluorescing autosomal blocks of lymphocyte mitoses of the same persons, as it was demonstrated in surgical cases.


Esterase-D polymorphism in Assam by cellulose acetate electrophoresis.

With the help of a simplified and quick method, cellulose acetate electrophoresis, the phenotypes of esterase D were determined in an Assamese population.  The gene frequencies of Es D(1) were 0.7263 and 0.2737 for Es D(2).


Haemoglobin norfolk in nepali gorkhas.

Three instances of fast moving haemoglobins in heterozygous form have been found in Indian soldiers of Nepali Gorkha, during a routine screening for abnormal haemoglobins.  The affected individuals were not related and seemed clinically well.


A 46,XX,10Q+ chromosome constitution in a girl. Partial long arm duplication or insertional translocation?

A girl with slight psychomotor retardation, microphthalmia, and colobomata of the left eye, a hypotrophy of the right arm and a surnumerary digit on the right hand is described. The routine chromosome analysis and a G-banding analysis revealed an elongated long arm of chromosome 10. An extra light and dark band was present proximally. Both parents had normal chromosomes. While the visual comparison of the abnormal with the normal chromosome 10, did not enable the extra bands of the normal bands q21 and q22 to be distinguished. However, measurements of length, surface area, and relative reflection of the different light and dark bands of the long arm on tracings or directly on the normal and abnormal chromosomes, enabled us to precisely locate the extra bands and to determine that the abnormal chromosome was a result of an insertional translocation. The value of such measurements is discussed.


The diagnosis of the early infantile form of hypophosphatasia tarda.

The diagnostic characteristics of the early infantile form of hypophosphatasia tarda are demonstrated in a case of a first child of healthy, probably consanguineous, unmarried parents. The diagnosis of the disease is based on the clinical and radiographic findings. The absence of alkaline phosphatase activity in the blood serum and leukocytes, and the excretion of phosphorylethanolamine in urine confirm the diagnosis. The inheritance appears to be autosomal recessive.


Fluorometrical detection of thymine base differences in complementary strands of satellite DNA in human metaphase chromosomes.

Using the fluorochrome "Hoechst 33258", intensity of fluorescence was found to differ distinctly between the sister chromatids in the paracentric regions of chromosomes 1, 16, and 19, after one round of replication in medium containing BUdR. Thus the effect of fluorescence asymmetry is not limited to the part of the Y chromosomes that fluoresces intensely with quinacrine; it can also be determined in the weakly Q-fluorescent pericentric regions of chromosomes, which are known to be the sites where highly reiterated sequences of satellite DNA are located. However, an exception is the paracentric region of chromosome 9 which does not show the effect of lateral asymmetry. The difference of fluorescence intensity in the heterochromatic regions of the sister chromatids of human chromosome 1 is measured by densitometric tracement along the long axes of chromosomes; this is obtained from two individuals with an "uncoiler" heterchomatic block (type III) having a relative intensity of 1:1.93 in an average of the total measured blocks. This corresponds to the uneven distribution of thymine base of 22.8 and 43.2 in the two strands of the DNA double hexlix. A chromatid exchange rate of 9 in 100 metaphases per cell cycle was found within the uncoiler region of chromosome 1.


Pyruvate kinase isozyme patterns of human neoplastic, fetal and adult tissues.

A method of starch gel electrophoresis is described which enables detection of 6 isozymes of human pyruvate kinase (PK, E.C.2.7.1.40). Comparing the PK-isozyme patterns of 53 diverse human tumors with those of normal adult and fetal organ tissues, it was found that the isozyme PK I is predominant in all malignant tumors as well as in almost all fetal organs.


Esterase D polymorphism: high-voltage agarose-gel electrophoresis and distribution of phenotypes in different European populations.

Esterase D phenotypes were determined in 1082 non-related individuals from the western region of Germany by agarose-gel electrophoresis. Gene frequencies were compared with previous data and all European populations studied so fare agreed with the Hardy-Weinberg equilibrium. Mean gene frequencies for Europeans are: EsD1 0.8888, EsD2 0.1112.


Galactosaemia: estimated live birth incidence in New Zealand.

194 cord blood samples were studied in both a fluorimetric assay and an electrophoresis method for Gal-1-PUT. From this the expected live birth incidence was 1:37000. The New Zealand neonatal screening programme has detected 5 cases in 223326 live births--an apparent incidence of 1:44600. The Beutler testing of dried blood spots collected on filter paper cards is a satisfactory method of detecting galactosaemia in the neonate.


Derivative chromosomal structures from a ring chromsome 4.

This report describes the results from cultured lymphocytes studied at metaphase, anaphase, and interphase from an individual with a ring chromosome 4. A ring was present in 90.1% of metaphases. Special attention was directed towards the occurrence of derivative chromosomal structures, such as partially duplicated and triplicated rings, tricentric rings, chains of 3 interlocked rings, rod-shaped chromosomes, "pulverized" rings, and others. The clinical features of the individual (small stature and impaired mental development, hypoplastic thumbs, ptosis palpebrae hypoplastic external male genitalia, abnormal dermatoglphic pattern) did not conform to a specific phenotype.


[Phenotypic variation in partial trisomy 4q (author's transl)].

The clinical and cytogenetic data of 3 non-related patients who have a partial trisomy 4q in common are reported. The chromosome aberration originated from a parental balanced translocation in 2 cases (t(3p+;4q--)and t(4q--;18q+)); in the 3rd case an inverted insertion of 4q22 yields q34 into 4q34 occured spontaneously. A comparison of the symptoms exhibited by these probands and 7 cases from the literature gives no indication of an uniform phaenotype of this aberration.


[Pericentric inversion of chromosome 2 (p11 q13) in unrelated families (author's transl)].

A pericentric inversion of chromosome 2 has been detected in 4 unrelated families. The break points are identical in band 2p11 and band 2q13. Reproductive history of these couples is analyzed. The pathology of these particular regions of chromosome 2 is discussed.


Serum haptoglobin type and liver cirrhosis.

Haptoglobin phenotypes were studied by a polyacrylamide gel electrophoresis on 200 blood donors and 105 patients with liver cirrhosis, of which 79% belonged to non-alcoholic etiology. Though no difference of haptoglobin types could be found between blood donors with positive and negative hepatitis B antigen, the cirrhois patients had an excess haptoglobin gene 1. The patients with haptoglobin gene 1 were associated with severe liver dysfunction. Since the family pedigrees of the patients with type 1--1 excluded individuals with type 2--2, the phenotypes seemed to be stable in the cirrhotic process. The possibility that the haptoglobin 2 gene offered resistence to the non-alcoholic cirrhosis was discussed.


Serum and tissure proteins in tuberous sclerosis. II. Immunoglobulin levels.

Serum levels of the four main immunoglobulins, IgA, IgM, IgG and IgD were estimated in a sample of 54 subjects with tuberous sclerosis and the data compared with similar findings in a sample of 100 mentally retarded subjects chosen at random. Normal levels of IgA and IgD were found in the T.S. group, but elevated levels of IgM significant at P equals 0.001 was found in 49 of the 54 cases. A reduction in IgG levels (significant at P equals 0.001) was a much less constant feature being found in 29 of the 54 subjects. The significance of these results in the light of the observation that one of the principal causes of death in T.S. is from recurrent infection is discussed.


A mechanism of x chromosome aneuploidy in lymphocytes of aging women.

One and sometimes both X chromosomes in cultured lyphocytes of women donors showed division of the centromere when the centromeres of other chromosomes were entire. This premature centromere division (PCD) was associated with evidence of non-disjunction of the X chromosome. On average, 2% of metaphases from 32 women donors showed PCD, but the incidence was 4 times greater in women over 59 years of age than in women under 40 years. Increased X chromosome aneuploidy was associated with the higher frequency of PCD in cultured lymphocytes from older women. PCD of the X chromosome is considered to be the mechanism of non-disjunction causing the previously described aneuploidy in cultured lymphocytes of aging women.


Premature chromosome condensation in a case of Fanconi's anemia.

Evidence is presented for the occurrence of premature chromosome condensation (PCC) from micronuclei even in the first in vitro mitoses in a case of Fanconi's anemia.


G-6-PD Poznań, variant with severe enzyme deficiency.

A new variant of G-6-PD with severe enzyme dificiency without chronic hemolysis is characterized. The biochemical properties of the variant closely resemble those of the G-6-PD Ramat-Gan described in a case of chronic non-spherocytic hemolytic anemia. As the family data on linking of chronic hemolysis with Ramat-Gan variant are lacking, the differentiation of the variants on the basis of clinical manifestations is not well-founded.


Confirmation of the linkage HL-A/PGM3.

In a series of 42 families with 101 children the linkage between HL-A and PGM3 could be confirmed (most likely recombination fraction for male equals 0.15).


Population genetics of red cell glyoxalase I (E.C.:4.4.1.5): Gene frequencies in southwestern Germany.

The polymorphism of Glyoxalase I was investigated in a population sample from Southweatern Germany. The frequency of the GLO-2 allele was determined to be 0.427.


De novo (11;13) translocation.

A male infant is described with unusual facial appearance, clubfeet, and moderate hydrocephalus internus without obvious deficiency in mental and physical development. Cytogenetic studies revealed a karyotype of 45,XY,--C,--D,+t(C;D). A chromosome 11 and a 13 are involved in the formation of the translocation chromosome. The long arm of chromosome 13 is linearly attached to the end of the long arm of chromosome 11 (tandem translocation). Chromosome material of the distal part of the long arm of chromosome 11, as well as the short arm plus the centromere of chromosome 13 seem to have been lost.


Partial monosomy 13 as the result of a balanced translocation 3/13 pat.

In a 4 1/3-year old girl we found the karyotype 45, XX, del13(pter yields q12). The father showed a balanced translocation 3/13 (karyotype: 46,XY,t(3;13) (p27;q12). Psychological investigation of the patient revealed almost normal intelligence (DQ91). Clinical symptoms were: low birth weight, growth retardation, dolichocephalus, microgenia, antimongoloid slant of the eyes, edema on hands and feet, strabismus convergens, clubfoot (left), slight decrease in IgA and IgM.


Premature chromosome condensation in the bone marrow of chinese hamsters after whole body irradiation with Co-60 gamma rays in vivo.

In the Chinese hamster bone marrow chromosomal aberrations were induced after whole body irradiation with Co-60 gamma rays in vivo. Aberrant mitoses give rise to lagging chromatin that forms micronuclei. Eventually the micronuclei are slowed down in their cell cycles in comparison to the main nuclei. The mitotic chromatin of the main nuclei induces premature chromosome condensation (PCC) in the micronuclei that are still in the interphase state of their cell cycles.


Gm(1) and Gm(2) immunoglobulin allotypes in patients with malignant melanoma.

Gm allotype markers were determined in sera from 71 melanoma patients and 400 control persons. There was no significant difference between both groups in Gm distribution. The results were compared to a recent report. Furthermore, in 25 malanoma patients the capacity of serum to interfere with cell-mediated cytotoxicity (CMC) of autologous lymphocytes was determined and related to the Gm allotype.


Implications of somatic recombination and sister chromatid exchange in Bloom's syndrome and cells treated with mitomycin C.

It is suggested that the somatic recombination observed in Bloom's syndrome and cells treated with mitomycin C may be the result of selection for recombination events that can occur only between homologous segments of DNA, rather than a result of somatic pairing in the nucleus.


[Does there exist a correlation between the number of whorls of the finger tips and birth order of sibs? (author's transl)].

It was stated by Birdsong and Rashad (1972) that the child of birth order number six of Korean families has significantly more true whorls on the finger tips than older brothers and sisters. To verify this assertion we studied a sample of all members of 43 normal German families with 5 or more legitimate children. The findings of the epidermal finger pattern types and those of the toe patterns were analysed. Results indicate a different conclusion regarding the number of digital whorls which were not increased statistically with increasing number of sibs. The number of whorls were randomly distributed within the heritable range of variability of the particular family. It appears of importance that, due to our analyses, the value of information of the characteristic "number of whorls" is not reduced and does not require a specific consideration regarding birth order. Furthermore, it can be stated preliminarly that there is no hint pointing to an influence of the maternal age on the number of whorls in their offspring.


Demonstration of a factor in the serum of homozygotes and heterozygotes for cystic fibrosis by a non-biological technique.

A factor has been isolated from serum of homozygotes and obligate heterozgotes for cystic fibrosis using isoelectric focusing and disc electrophoresis as analytical methods. The factor is focused within an IgG-fraction with an isoelectric point of pH 8 to 9 but differs from IgG in its lower molecular weight. It is thus similar to, if not identical with, the ciliary dyskinesia factor.


[Familial neuroblastoma: cytogenetic investigation of the peripheral blood (author's transl)].

A cytogenetic investigation was performed in a family which included 2 individuals with congenital neuroblastomas of the suprarenal gland confirmed by autopsy and one with a ganglioneuroblastoma of the thoracic wall as well as 3 other individuals with tumors which probably were also neuroblastomas. The lymphocytes of the peripheral blood of 5 healthy relatives as well as of the child with the treated ganglioneuroblastoma failed to show a constant alteration of chromosomes. In this family, therefore, the suggestion could not be proofed that the very rare familial aggregation of neuroblastomas is caused by a hereditary chromosomal aberration.


Lactate dehydrogenase: inhibition of subunit A by the sulfhydryl reagent AgNO3.

Lactate dehydrogenase isoenzymes including the subunit A--LDH 5 (A4), LDH 4 (A3B), LDH 3 (A2B2), and LDH 2 (AB3)--are inhibitable by the sulfhydryl reagent AgNO3, while the isoenzyme LDH 1 (B4) is not.


Red cell glyoxalase i (E.C.: 4.4.1.5): formal genetics and linkage relations.

The segregation of GLO-phenotypes was analysed in 119 families with 266 children. The results are in agreement with the formal two-allele-model. Close linkage was ruled out for a number of informative markers.


Multiple forms of enolase (E.C. 4.2.1.11): their distribution in human tissues.

By means of starch gel electrophoresis, the enzyme enolase was found to be a family of at least 3 isozymes in human tissues. Enolase III shows a strong band in extracts of human brain and in some malignant tumors.


Toxicity of antibiotics on cultured human skin fibroblasts.

Human diploid fibroblasts cultured in Dulbecco's Modified Eagle's medium (DME) were exposed to different concentrations of 15 antibiotics to determine the limiting toxic concentration. The number of cells surviving after antibiotic treatment was given as the index of toxicity. No visible chromosomal damage could be detected when half the maximal toxic concentration was applied. The maximum limiting concentration was found to be the same for both the preconfluent and postconfluent phases.


Ring 17 chromosome detected by amniocentesis.

A fetus with a 46,XX,r(17) karyotype identified initially by amniocentesis and confirmed by banding studies is described. No significant phenotypic abnormalities were identified despite isolation of the ring chromosome from multiple fetal tissues. This paucity of abnormal features of gross development is consistent with findings in 3 previously reported patients with ring 17 chromosomes.


Haemoglobins J in Canada.

A search has been conducted in Canada on 222,000 blood samples, for haemoglobin variants detectable electrophoretically. A pattern of Hbs A h was found in 41, and of these, 23 have been identified as J Baltimore (in 18), J Toronto (in 1), J. Broussais (in 3) and St. Claude (in 1). 12 instances of J Baltimore and one of J Toronto came from English Canadians, while the remainder came from French Canadians. Of those not identified, five were considered to be J-alpha and 13 J-beta variants. The known distribution and incidence of J Baltimore, and of the Hbs J that have been found in the indigenous populations of the United Kingdom and of France, are reviewed.


Haemoglobin A-2-NYU in a London population.

Electrophoresis of haemolysates from a population in London resulted in the detection of a variant of haemoglobin-A-2. Purification and characterisation of the variant globin revealed that this was a further example of haemoglobin A-2-NYU.


A note on the distribution of haptoglobin types in Turkey.

The investigation of serum samples of 200 unrelated adult Turks revealed the following gene frequencies: Hp-1 = 0.265; Hp-2 = 0.735. The frequencies are in the range of most of the Asiatic population.


Distribution of GPT types in Norway.

GPT phenotype determinations were performed in 4,148 unrelated Norwegians. The frequencies of the two common alleles were Gpt1 = 0.537 and Gpt2 = 0.461. A total of 13 individuals showed the phenotypic expression of 3 rare GPT alleles, Gpt3, Gpt6, and Gpt7. No heterogeneity in phenotype distribution was found, neither in the two sexes nor regionally in Norway. 97 foreigners involved in paternity cases in Norway showed a phenotype distribution not differing from that of Norwegians. In two small additional samples of Ethiopians and Easter Islanders, Gpt1 frequencies were 0.737 and 0.531, respectively. There were significant differences in phenotype distribution between NOrwegians and all African populations tested, some of the Asiatic population, Lapps and a few other populations.


Possible dominant inheritance of the idiopathic hypercalcemic syndrome.

A girl, aged 16 months, with idiopathic hypercalcemia (failure to thrive, characteristic face, supravalvular aortic stenosis) was observed. Her serum calcium level was between 14 and 20 mg/100 ml. Both her father and brother were mentally retarded and had calcium deposits in their corneae. Their serum calcium values were 11.9 and 13.0 mg/100 ml, respectively, with increased urinary output of calcium. The family history is suggestive of autosomal dominant inheritance of the disease.


Retinoblastoma.  A model of hereditary fragile chromosomal regions.

Direct karyotyping of tumour cells from three familial and two sporadic cases of retinoblastoma revealed the existence of a Dq- marker chromosome. The hypothesis is launched that a specific region on the long arm of one of the D chromosomes is the site of a locus which is essential for the sustained differentiation of specialized retinal tissue and may be the site of other loci essential for the maturation of other embryonic tissues. Fragility of this region and its potentiality for breakage under the influence of various environmental insults could be the basic cytological event leading to the development of sporadic retinoblastoma. Mutants at these loci, including those of sustained differentiation, could be a less common operational event whereby some variants could enhance the fragility of their respective chromosomal region and thereby explain the genetic transmission of retinoblastoma in certain families. It is common for the critical functional disruption of the locus to precede the deletion which may then be considered the terminal event in the fragile region.


Haemoglobinopathy survey in an Eti-Turk village.

Blood specimens were obtained from 281 inhabitants of an Eti-Turk village with a population of about 500. Starch gel (pH 8.6) and agar gel (pH 6.45) electrophoresis were performed in 279 of the specimens. Hb S was present in 105 partially interrelated persons (37.36%), three of whom had sickle-cell anaemia. Hb E was detected in 5 persons (1.79%), one of whom was a double heterozygote for Hb S and Hb E. One Hb S+alpha-thalassaemia and 7 Hb S with elevated Hb A'2 combinations were found. The beta-thalassaemia gene prevalence was 0.0377. Hb A2 was found in 4 persons (1.42%), and Hb F was slightly increased in 37 (22.3%) persons with a normal haemoglobin picture. Erythrocyte G-6-PD deficiency was 10% among males.


Haemoglobin G-Szuhu, beta80 Asn-Lys, in the homozygous state in a patient with abetalipoproteinaemia.

An 11-year-old Jewish girl of Turkish extraction with abetalipoproteinaemia was found to be homozygous for haemoglobin Szuhu (beta80 Asn leads to Lys). Except for the abnormal haemoglobin, no other haematological or biochemical abnormalities were found in her consanguineous parents and one sister. In the propositus, erythrocyte morphology showed the acanthocytosis known to be in association with abetalipoproteinaemia. Increased autohaemolysis was also found, which reverted to normal after treatment with vitamin E. This case represents the first reported association of abetalipoproteinaemia with an abnormal haemoglobin, and the first homozygous Hb G-Szuhu.


Erythrocyte adenosine deaminase in Malaysians.

944 adenosine deaminase phenotypings of Malay, Chinese, and Indian blood donors and newborns at Kuala Lumpur, Malaysia, yielded ADA1 gene frequency estimates of 0.885 for the Malays, 0.939 for the Chinese, and 0.853 for the Indians.


Information processing immunogenetic analysis. IV. Information amount and predictive power of different immunogenetic models.

Principles of information theory are imposed on immunogenetic information processing, whereby the 'information amount', simplicity, 'redundancy' and 'predicatability' of different encodings, models, theories or mappings can be objectively compared. As an example, the experimental observables emanating from the Rh system at its 10 reagent-8 haplotype level is shown to obtain an information amount of 140,120 and 78 bits when interpreted (encoded according to a simple-complex, complex-simple and complex-complex theory, model or program, respectively. The 'predictive' or 'accomodating' power of the simple-complex and complex-simple theories is shown to be 134, respectively 366 bits for a given set of experimental observables emanating from a S3 universe.


Distribution of sibship size in families manifesting a genetically determined disorder.

The effect on sibship size distribution of the birth of a child with a genetical defect is considered for several different conditions. Family size continues to be over-dispersed in such cases, rather than showing any sign of reduced variation, though theoretical expectations about the correlation between numbers of normal and affected children are not well-supported by the data.


Gm and Inv allotypes in a Gypsy sample.

Serum samples from 226 Gypsies were tested for Gm(1,2,4,5,8,10,11,14,17,21,23,25) and for Inv(1,2). The Gm phenotypes found are very numerous and the more frequent among this population are: Gm(4,5, 8,10,11,14,17,23,25) and Gm(1,2,4,5,8,10,11,14,17,21,23,25). All the phenotypes except three can be explained by nine haplotypes: Gm4,5,8,10,11,14,23,25, Gm1,4,5,8,10,11,14,23,25, Gm4,5,8,10,11,14,25, Gm1,17,21, Gm1,10,11,17,25, Gm1,2,17,21, Gm1,8,17,21, Gm1,8,17,21,23 and Gm1,5,10,11,14,17. The haplotypes Gm1,17,21, Gm1,2,17,21, Gm4,5,8,10,11,14,25 (with or without Gm[  3]) are all three common among Caucasoids, Gm1,4,5,10,11,14,23,25 (common among Mongoloids) and Gm1,5,10,11,14,17 (common to Negroids). For the Inv system, this population possesses a very low frequency of Inv(1) and Inv(2).


Esterase D: some population and formal genetical data.

562 healthy blood donors and 65 families with 149 offspring were types for esterase D (EsD). The observed allele frequencies are in good agreement with those determined in other Caucasian populations. The rare variant EsD3 was found in a blood donor who transmitted it to his daughter. The observed segregation ratios in our family material showed no deviation from expectation.


Distribution of haptoglobin subtypes in French Basques.

THE Hl1f, Hp1s and Hp2 gene frequencies were studied in two French population samples: one from the Toulouse area and one from a Basque district. The hp alpha1F and alpha1S polypeptide chains were determined by a simple technique. The observations were in accordance with previous findings in Caucasoid populations. The frequency of the Hp1S gene was slightly higher in the Basque sample than in the group from Toulouse.


Proportion with low birth weight infants in an Indian population and its relationship with maternal age and parity.

The overall proportion of low birth weight infants is found to be relatively higher in the Indian population. Data collected from two hospitals in Calcutta, India indicate that although the proportion of infants weighing less than 2,001 g is approximately 10%, the dependence of this proportion on maternal age and parity is similar to the studies conducted elsewhere, suggesting a definite biological significance of the phenomenon. The proportion of low birth weight infants is found to be the greatest for the first and late pregnancies, the minimum being at the third birth rank. Young mothers showed a tendency to have an increasing proportion of low birth weight infants with increasing birth order; whereas for older mothers a general U-shaped dependence of the proportion on parity is suggest from the analysis.


Erythrocyte glucose-6-phosphate dehydrogenase in the Niokolonko (Malinke of the Niokolo) of Eastern Senegal. Identification of a slow variant with normal activity (Tacoma-like).

In a survey of blood genetic markers in the Niokolonko of Eastern Senegal, three types of G6PD variants were discovered: (1) fast variants, common Negro G6PD A +; the frequency of the Gd A + gene was 0.183; (2) deficient G6PD A--, occurring with a fairly low frequency: 0.079, and (3) some individuals were carriers of a slow moving electrophoretic variant with normal activity. After purification, the analysis of kinetic parameters showed that this enzyme was closely similar to G6PD Tacoma. We proposed to label it 'G6PD Tacoma-like'. The incidence of this mutation in the whole group studied was 0.020. G6PD Tacoma-like may be common in some African tribes.


Gm and Inv allotypes in French Guiana Indians.

Data from 302 individuals belonging to three populations of French Guiana Indians are reported. All the phenotypes except two can be explained by three haplotypes: Gm1,21, Gm1,2,21 and Gm1,10,11,25. The gene frequencies found in the present study are generally in accordance with those previously described among other South American Indians. For the Inv1,2 gene a high value has been found for the Wayanas and the Oyampis, but a difference appears for the Emerillons who possess a low frequency.


Extensions to pedigree analysis  I. Likehood calculations for simple and complex pedigrees.

A graph theoretic definition of pedigrees is given and a distinction drawn between simple and complex pedigrees. Algorithms are presented to calculate the likeihood of any kind of pedigree, assuming only segregation at a finite set of loci, nonassortative mating and no environmental correlations; multiple births and consanguineous marriages are explicity allowed for. The formulation given can lead to more powerful genetic counselling, segregation analysis and linkage analysis.


Brown adipose tissue and immunity.  Effect of neonatal adipectomy on humoral and cellular immune reactions in the rat.

This work concerns the involvement of brown adipose tissue in the immune system ofthe rat.  Wistar rats were thymectomized, adipectomized (surgical extirpation of the interscapular brown adipose tissue), thymectomized and adipectomized, and sham-operatedat birth, only 8-week-old females being employed in the experiment.  The production of antibody to bovine werum albumin (BSA) and sheep red blood cells (SRBC), delayed skin reactions to BSA, rejection of thyroid allograft implanted under the kidney capsule, and development of experimental allergic encephalomyelitis were investigated.  Neonatal adipectomy did not affect the production of anti-BSA and anti-SRBC antibodies.  On the other hand, delayed skin reactions to BSA, rejection of thyroid allograft, and incidence and severity of allergic encephalomyelitis were much more pronounced in adipectomized animals.  It has been postulated that the immune function of brown adipose tissue is an expression of the secretory activity of the tissue.  Since the immunosuppressive effect of neonatal thymectomy on demyelinating disease was neutralized by neonatal adipectomy, and vice versa, and since thymectomy rendered ineffective the immunopotentiating influence of adipectomy on this disease, as demonstrated in thymo-adipectomized rats, it was concluded that the brown adipose tissue is a naturalantagonist of the thymus in cell-mediated immunity.  This paper also describes the extra thymuses which were situated in the vicinity of the thyroid and parathyroid lobes of23.2 per cent of rats.


An analysis of those components of Toxoplasma gondii responsible for delayed hypersensitivity reactions in mice.

Testing of extracts of Toxoplasma gondii (RH strain) indicated that delayed hypersensitivity as manifested by delayed skin reactions and inhibition of macrophage migration was induced only by those fractions containing RNA.


The haemopoietic and immunogenic capacities of living hybrid bone marrow cells tested in tumour allograft rejection.

In irradiated mice the capacity to reject allogenic tumours can be reconstituted with syngeneic lymphoid cells if the transferred cells are primed with the allogenicantigen.  Living semi-allogeneic cells proved to be 30-100-times more acitve as priming antigen than cell membrane fractions.  The tumour-suppressive activity of primed lymphoid cells increased in the following order: bone marrow less than Peyer's patches less than thymus less than spleen less than lymph node cells.  Even bone marrowcells showed a considerable suppressing activity after priming with live antigen.  It was a great advantage that 2 times 10-6 semi-allogeneic bone marrow cells could be used both for the restoration of the haemopoietic system after irradiation and for stimulation of the transferred parental lymphocytes.  Priming with large numbers of semi-allogeneic spleen cells abolished the tumour-suppressive activity of the transferred lymphoid cells.  This tolerogenic effect disappeared when the priming cells were pretreated with mitomycin.  Tolerance could be induced when the cell donors were treated with cyclophosphamide in combination with the living cells.  Cell membranes were not effective.


Catabolism of human IgG in mice sensitized to various IgG fragments. Similarities to the catabolism of rheumatoid IgG in mice.

Whole body elimination studies of human serum IgG have showm that C57Bl miceare tolerant to this protein at low concentrations.  The present study demonstrates that tolerance to this protein may be broken by presensitization of the mouse with the pepsin-derived fragments of human IgG (F(ab)2 and pFc), in marked contrast to the papain-derived fragments (Fab and Fc).  Sensitization with F(ab)2 fragments induced a distinctive elimination pattern of the intact protein which was analogousto that observed in non-sensitized mice injected with serum IgG isolated from patients with rheumatoid arthritis.  Since, by circular dichroism studies, we have previouslyimplicated a structural anomaly at or near the hinge region of the 'rheumatoid' IgGmolecule, our observations are discussed in relationship to a possible immune aetiologyfor rheumatoid arthritis.


Physiological and biochemical effects of the mycotoxin patulin on Chang liver cell cultures.

Patulin exhibits both cytotoxic and cytopathic effects on cultured Chang liver cells. The LD50 found was 1.85 mug per ml of patulin. Effects on growth were observed with as little as 0.1 mug per ml of patulin; a 50% reduction in growth was observed at 0.38 mug per ml of patulin. Using a challenge dose of 2.5 mug per ml of patulin, the cytotoxic effect was reversible after an exposure of 10 min, but was not reversible after 20 min. Protein synthesis was depressed after 60 min and RNA synthesis after 20 min of contact with patulin. Neither protein nor RNA synthesis was completely inhibited after 260 min.


Ascorbate and phagocyte function.

Scorbutic guinea pig neutrophils (PMN) were found to produce H2O2 and kill Staphylococcus aureus as well as control PMN, suggesting that ascorbate does not contribute significantly to phagocyte H2O2 production or bacterial killing. Total and reduced ascorbate contents of human PMN was observed to fall upon phagocytosis, whereas dehydroascorbate increased to a lesser extent. These observations are consistent with the view that ascorbate constitutes a functional part of the PMN's redox-active components and may thus function to protect cell constituents from denaturation by the oxidants produced during phagocytosis.


Changes in buoyant density relationships of two cell types of Coxiella burneti phase I.

Coxiella burneti phase I, purified from a formalin-inactivated yolk-sac vaccine, was separated into two bands of morphologically distinct cell types when subjected to sucrose gradient centrifugation. Recycling of the less dense, rod-shaped cells in unbuffered sucrose gradients (pH 5.5 to 6.0) resulted in the formation of bands having the location and appearance of the original two bands. Recycling of the denser band of larger ovoid-shaped cells yielded a single band, suggesting that the larger cell type arose from the smaller cell. In contrast to vaccine-derived rickettsiae, live, cell culture-propagated phase I organisms formed a single band in unbuffered sucrose gradients, at the same density as the upper band of the vaccine preparation. Centrifugation of cell culture-derived rickettsiae for 26 to 48 h in sucrose gradients of pH 5.5 resulted in the formation of a second band, at the same density as the lower band of the vaccine preparation. This did not occur in gradients of pH 7.0. Treatment of cell culture-propagated rickettsiae with formalin or germicidal ultraviolet radiation induced a total shift of the less dense cell population to a zone of higher density when centrifuged isopycnically in CsC1 gradients. This density change did not occur in sucrose gradients, suggesting a difference in the effect of these treatments on the permeability of the cell membrane to sucrose and CsC1.


Anaphylactoid-inflammation-promoting factor. An insulin-induced factor derived from non-sensitized lymphocytes increases anaphylactoid inflammation in rats.

The experiments reported here indicate that, when exposed to insulin, viable lymphocytes rapidly released into the incubation medium a factor capable of increasing the dextran-induced anaphylactoid reaction, but having no effect  on the inflammatory response evoked by 5-HT. This pro-inflammatory factor was shown to be elaborated by cell suspensions derived from lymph nodes of rats, rabbits, pigs or calves as well as from human tonsils. Thymus cells showed no such activity. The pro-inflammatory factor was termed as anaphylactoid-inflammation-promoting factor (AIPF). Its production depended upon the dose of insulin, and the time of exposure. AIPF was found to have an elution pattern in Sephadex G-100 gels similar to that of BSA (67,000 daltons). The activity was abolished by heat or incubation with DNase or a-chymotrypsin, but was not influenced by RNase. AIPF by itself did not induce increased vascular permeability, and proved to be distinct from the permeability factors present in the lysate of lymph node cells.


Arterial and muscle oxygen tension in experimental models of asthma. Experimental models of asthma.

The immediate-type airway response in anesthetized dogs and rhesus monkeys to two antigens (ascaris and keyhole limpet hemocyanin) and pharmacologic agents (histamine, methacholine and prostaglandin F2alpha) were studied. The pulmonary function abnormalities demonstrated by changes in breathing frequency, peak expiratory flow rate, pulmonary resistance, expiratory-inspiratory time ratio, tidal volume, and dynamic compliance were compared with simultaneous determinations of arterial pO2, muscle pO2 or both, using indwelling electrodes. The results demonstrate that the O2 determinations provide an additional parameter of study of these experimental models of asthma, and that it may be one of the more sensitive indicators of an induced airway response of the immediate-type. The hypoxia parallels the degree of severity of the respiratory response and demonstrates a further similarity of this model to human asthma.


Adjustment to loss of job at retirement.

This paper presents an approach to adjustment to the loss of job at retirement which attempts to integrate earlier approaches by focusing on the impact of retirement on the individual's hierarchy of personal goals. If the job is high in that hierarchy and yet unachieved, then the individual can be expected to seek another job or job substitute. If this is unsuccessful, then the hierarchy of personal goals must be reorganized. If the individual is broadly engaged, the hierarchy can be consolidated. If he or she is narrowly engaged, then alternate roles must be sought. If the search is successful, a new hierarchy emerges. If not, the individual must withdraw. If the job is not high in the hierarchy to begin with, then no serious change in personal goals accompanies retirement.


Being single in old age.

The routine, everyday life of single elders differs from that of other old people. On the basis of interview date both about themselves and some aspects of the quality of their everyday lives, it is proposed that single elders constitute a distinct type of social personality in old age. Interviews provide subjective and methodological evidence to support this. The "normal", taken-for-granted social world of single elders is: relatively isolated; but not perceived in terms of loneliness, at present or anticipated; and considered an ordinary extension of their past. Death is conceived as "just another" event of their ongoing experiences.


The perception of the common cold, and other ailments and discomforts, as related to age.

Perception of the common cold and other discomforts was studied as a function fo age among 456 normals ranging in age from 18 to 82. Respondents completed a questionnaire which deal with the frequency and duration of their colds, their symptoms and treatments-and, finally, with the perceived severity of various discomforts. Though older Rs were found to suffer more than younger with body aches, the former had less difficulty with a variety of other physical and psychological symptoms-and also contracted relatively few colds. Older Rs treated their colds less often with Contac and Dristan, but more often by staying home and/or calling their doctor. As compared with younger Rs, older respondents perceived intestinal flu to be relatively less serious-but earache, sprained toe, indigestion, having a tooth filled, stiff neck, and hangover to be relatively more serious.


Who cares if I say good morning: an unobtrusive study of the elderly.

Senior Citizens from three high rise apartment buildings were studied to find if the elderly present special needs. The investigation consisted of a number of shopping trips by chartered bus to a supermarket. A tally was kept recording responses to a greeting on a cue day and responses on a non-cue day when no greeting was given. Four null hypotheses were tested resulting in evidence that the elderly respond more often when a verbal stimulus is present, than when not. It was found that the elderly do present unique needs and society must communicate more with them and with those who are dealing with the elderly on a regular basis.


The pooling of logitudinal studies of aging.

This report describes the pooling of 5 longitudinal studies conducted during the last 20 years in West Germany. The pooling provides the following improvements: By increasing the number of participants the reliability and precision of the results are improved. The sample becomes representative of the whole area of the FRG. Both cohort and age comparisons are improved by extending their ranges. The time-of-testing range is increased from 5 to 17 years. Since the significance of this factor has been recognized often but since few empirical explorations have been made in the past, the extension of the time-of-testing range represents the most important contribution of the present work. The pooling of different studies is possible only if they share a common set of methods. This requirement is met under the present conditions. Moreover, each study adds unique methods to the pool, thus, supplementing the common explorations in a constructive manner.


The functions of progressionals in gerontology in policy making: a case history from Massachusetts.

This paper describes and assess the functions which a Professional Task Force Committee has performed as an advisory body to the State Unit on Aging in Massachusetts, the Executive Office of Elder Affairs, and how this committee has aided in its development in the past 2 years. As such it illustrates the kind of contributions which professionals in gerontology can make in policy-making for the elderly. This experience in Massachusetts has demonstrated that a body of professionals linked together through an appropriate structure, can shape and effect policies that a State Unit on Aging eventually promulgates. The expert can and should make his expertise available in policy anlysis, policy development, and in policy implementation. But, at the same time, the expert must recognize that, like everybody else, he needs a corrective; otherwise expert power will be guiding too much the direction of a State Unit on Aging  (or any other government department) and this may not always be in the interest of those who are going to receive services and to be the beneficiaries of social programs.


Retirement to the porch in rural Appalachia.

Successful retirement in old age depends on the existence of a set of social arrangements in which a person has accumulated a considerable longtime social standing that justifies his claims for support from the community. In a small, rural Appalachian settlement, the pattern of retirement to the porch illustrates how claims by old men for social attention and care are anchored in the interests of others and are vested with significance for the entire community. While the use of the porch to facilitate the assertion of such claims on others may be more evident in small settlements, it is suggested that comparable strategies to afford successful retirement can occur in urbanized areas. These may be more difficult to develop and maintain, since collective sanctions to enforce the performances of relevant juniors are weakened or are transferred to formal facilities that render common services, not personal recognition, to old people.


Public Interest Report No. 15, is there an ideal form of care of the old?

Some characteristics of an "ideal" nursing home are proposed. It is possible to develop facilities for the aged in which rehabilitation-opportunities are maximized, and the sense of hope and self-esteem are nurtured.


Computation of exact confidence intervals for the odds ratio.

A time-sharing program written in BASIC language has been developed to compute exact confidence limits for the odds ratio parameter in a 2 x 2 table. The program offers the user a choice between the classical exact limits and limits based upon a recent redefinition of the exact p-value aimed at avoidance of conservatism in the classical procedure. The user selects the degree of confidence desired during a run of the program, which then computes the exact limits and p-value.?23Athor


A method for prediciting localised areas of cerebral ischemia from visual evoked responses.

Responses to light flashes recorded from several scalp electrodes of a normal subject at rest and during alternate compression of the carotid arteries in the neck are analysed. The diffences found in response characteristics between the subject at rest and during carotid compression may serve as indicators of localised areas of cerebral ischemia. The results indicate a strong evidence that information about localised areas of cerebral ischemia is contained in the cepstra of the averaged visual evoked responses. The probability with which such areas can be localised using cepstral values as samples and linear multiple regression techniques for classification purposes has been estimated for our procedure and our sample size as being: Pa equals 79 plus or minus 17 per cent for left-right localisation, and Pb equals 61 plus or minus 16 per cent for left-none-right localisation.


Immunological studies of women with primary breast carcinoma.

Lymphocytes from disease-free women and women with primary breast carcinoma were comparable vis-a-vis their capacity to inactivate breast tumor cells in vitro. Sera from comparable numbers of women in each of these two groups either blocked, potentiated or left unaffected the anti-tumor-cell cytotoxicity of their lymphoctes. As such, the results cast doubt on the validity of the hypothesis that there is a positive correlation between the presence of humoral blocking factors and in vivo tumor progression.


Lectin agglutinability of non-neoplastic and neoplastic human lymphoid cells in vitro.

Agglutination by two lectins, Concanavalin A (Con A) and Ricinus communis agglutinin (RCA), has been investigated in a human lymphoid cell system. The main conclusions of this study are: (1) no systematic correlation exists between the neoplastic state and sensitivity to Con A or RCA; (2) cells of neoplastic lines vary unsystematically in their surface properties as evaluated by Con A agglutination, with the possible exception that presence of Epstein-Barr virus (EBV) is associated with a high degree of agglutination and (3) cells of diploid lymphoblastoid lines and phytohemagglutinin (PHA)-stimulated lymphoctes agglutinate similarly and significantly better than unstimulated T- or B-lymphocytes. The relatively simple Con A agglutination assay can be used as an adjunct in classification of human lymphoid cell lines.


Tumour inhibition mediated by BCG in immunosuppressed rats.

Two rat sarcomas (CC5 and P7) which grow progressively on transplantation into normal syngeneic hosts failed to develop when injected in admixture with the Glaxo strain of Bacillus Calmette-Guérin (BCG). Under comparable conditions, the local development of a third neoplasm (P8) was temporarily inhibited and the number of pulmonary metastases significantly reduced. Experiments were undertaken to determine the extent to which the anti-tumor action of BCG required an immunocompetent host. Rats were immunosuppressed by sub-lethal whole-body irradiation (450 R), with or without prior thymectomy and challenged with inocula of mixed BCG and tumour cells when their capacity to respond to bacterial, tumour and unrelated antigens was maximally depressed. In non-sensitized immunosuppressed rats, the ability of BCG to limit tumour outgrowth was abrogated only in the case of sarcoma CC5. For this neoplasm, immunogenic in syngeneic hosts by conventional criteria, there was a statistically significant difference in the number of tumours in immunosuppressed rats (51%) compared with non-sensitized immunocompetent controls (6%). Presensitization to either bacterial or tumour antigens, prior to thymectomy and/or irradiation, fully restored the tumour-inhibitory capacity of BCG. By contrast, sarcoma P7 was not significantly less susceptible to BCG-induced regression in non-sensitized immunosuppressed rats than in nonsensitized normal rats; and sarcoma P8 similarly failed to reveal any significant differences in susceptibility to BCG affecting primary or secondary tumour development. It is concluded that tumours may vary widely in their sensitivity to host reactions aroused by BCG. Certain neoplasms, exemplified by sarcoma CC5, require participation of an immune reaction of delayed hypersensitivity type for optimal destruction at BCG sites, while for others (e.g. sarcoma P7) an immunoreactive component of this type is not essential. By contrast, a third category of tumour (e.g. sarcoma P8) is relatively resistant to host reactions induced by the mycobacteria. An important component of BCG-mediated tumour inhibition is not dependent on an immunologically intact host.


Origin and partial characterization of Fc receptor-bearing cells found within experimental carcinomas and sarcomas.

A variety of murine connective and epithelial tissue tumors, including the SAD/2 and FS9 fibrosarcomas, the TA3/Ha and CAD/2 mammary carcinomas and a primary methylcholanthrene-induced sarcoma, were found to contain a high proportion of cells with receptors for the Fc portion of immunoglobulin G ("Fc receptors"). Experiments were undertaken to assess whether these cells were neoplastic, or whether they represented the infiltration into the tumor of non-malignant host cells such as macrophages or lymphocytes. It was found that long-term established in vitro cell lines of the TA3/Ha SAD/2 and CAD/2 tumors were entirely negative for the Fc receptor, whereas injection of these cells led to the formation of tumors containing a high proportion of Fc receptor-bearing cells. Many of these cells were actively phagocytic as assessed by ingestion of iron filings or antibody-coated erythrocytes. Injection of Fc receptor-negative cultured tumor cells into F1 hybrids, in which host cells could be distinguished from the tumor cells by anti-H2 sera, revealed that many or all of the Fc receptor-bearing cells in the resultant tumor were of host origin. In contrast to its effect on normal spleen cells, anti-theta serum treatment also partially inhibited Fc rosettes, suggesting a T-lymphocyte origin for some of the Fc receptor-bearing cells. Since almost all cells with potential anti-tumor activity bear Fc receptors, it is suggested that an index of host cell infiltration of carcinomas and sarcomas can quickly and easily be ascertained by enumeration of Fc receptor-bearing cells.


Genetic variation of in vitro cytolytic activity and in vivo rejection potential of non-immunized semi-syngeneic mice against a mouse lymphoma line.

Spleens of normal young mice of certain genotypes contain lymphocytes that can kill strain A-derived YAC-1 and some other in vitro-grown Moloney lymphoma lines in a 51Cr-release cytotoxic test. We have previously shown that mouse strains can be classified as high or low reactors in this test. F(1) hybrids between low- and high-reactive strains are high-reactive. In the present study, strain-A mice and eight different A F(1) hybrids were tested in parallel for their spleen-cell-mediated killing effect in vitro and their ability to reject graded numbers of YAC ascites or in vitro cultivated cells in vivo. There was a clear correlation between in vitro cytotoxicity and in vivo rejection in all tested genotypes. In segregating (A times C57Bl) times A backcross mice, in vivo rejection of YAC cells was H-2 linked. This is in line with the earlier backcross analysis of the in vitro cytotoxicity, suggesting a polygenic control with at least one H-2 linked factor.


Risk indicators in childhood malignancies.

A series of 972 childhood malignancies was compared with a control series of healthy children matched for date and place of birth. Several variables were tested for possible aetiological significance. The information was obtained from the Finnish Cancer Registry and from the antenatal records of the mothers. No significant associations were found between the various types of malignancies and the variables studied. In the group consisting of all malignancies, a risk ratio of 2.0 could be significantly excluded for most variables. In the leukaemia group, both pelvic X-ray and polio vaccination were associated with slightly elevated risk ratios, but the differences between this group and the match controls were not statistically significant. BCG vaccination was performed during the perinatal period in 90% of the children, but the proportion was the same in the study and control groups, and hence the hypothesis that this vaccination confers protection was not supported. The information is considered prospective and relatively reliable, and the authors suggest that these data may be useful when more extensive series are compiled from various sources.


Lung cancer and smoking in Danish women.

In most developed countries, including Denmark, cancer of the lung is the most frequent malignant disease among men, whereas the problem is less among women. Examination of Danish mortality data for the period 1931 to 1972 reveals a 5-fold increase in female rates as opposed to a 16-fold increase in male rates. Since about 1960 female rates have, however, increased faster than male rates with a consequent decline in the male-famale ratio. It is demonstrated that more recent female birth-cohorts have higher mortality rates than the older ones. The increasing mortality from lung cancer among more recent female cohorts is shown to parallel increasing proportions of smokers in these cohorts. Further data are presented to indicate that not only is smoking more widespread among young than among old women, but the proportion of cigarette smokers among all smokers falls from 98% in the youngest to 33% in the oldest agegroup. No causal relationship between smoking and lung cancer can be claimed from the evidence presented. The present findings are, however, what would be expected if cigarette-smoking were an aetiological factor in female lung cancer.


Inhibition of syngeneic fibrosarcoma growth by lymphocytes sensitized on tumor-cell monolayers in the presence of the thymic humoral factor.

The present experiments were performed to investigate the possibility of inhibiting tumor growth in vivo with syngeneic lymphocytes sensitized in vitro on monolayers of the tumor under test, and to study the effect of a thymic humoral factor (THF) in this sensitization process. Monolayers of fibrosarcoma cells were used to sensitize spleen cells from syngeneic donors against the tumor. Such sensitized lymphocytes manifested cytotoxic activity against cells fo the fibrosarcoma in a microassay measuring tumor-cell detachment. However, when the sensitized lymphocytes were mixed with the fibrosarcoma cells and injected into syngeneic mice, enhanced tumor growth was observed in vivo. Addition of thymic humoral factor to the cultures during sensitization resulted in increased cytotoxic activity by the lymphocytes in vitro and a reduction in the tumor enhancement caused by these cells when injected in vivo. Enhanced tumor growth occured when activated lymphocytes of allogeneic as well as syngeneic origin were injected together with the fibrosarcoma cells. Enhancement, which was already apparent when the spleen cells had been sensitized for 24 h, could be circumvented by separate administration of lymphocytes and tumor cells. Syngeneic lymphocytes injected systemically after sensitization for 5 days exerted anti-tumor reactivity against the fibrosarcoma grafted in the foot-pad of syngeneic mice. Tumor growth was further inhibited by systemic injection of lymphocytes which had been sensitized in the presence of the thymic humoral factor.


Lack of correlation between growth characteristics, agglutinability by plant lectins and the malignant phenotype.

Wheat germ agglutinin and Concanavalin A were found to agglutinate a variety of normal hamster cells as well as a number of lines of transformed or tumor cells. The normal cells included preparations from embryos and neonatal organs, and the spontaneous line, BHK-21 C13. In order to explore more fully the situation in regard to the BHK cells, three sublines were isolated and studied. A "flat revertant" selected by FUdR treatment grew to diminished saturation density and failed to produce colonies in soft agar in contrast to the parent line, which did. Yet, it was only minimally less tumorigenic and less agglutinable than the parent line. Lines derived from one and four consecutive in vivo tumor passages showed increased tumorigenicity and growth in soft agar when compared to the parent line. Although the first passage line showed increased saturation density, the saturation density of the fourth passage line was similar to or less than that of the parent cells. Agglutinability of these lines was not significantly increased. These results indicate that, in contrast to widely accepted beliefs, tumorigenicity may correlate poorly with growth characteristics and agglutination by plant lectins.


The relationship between nasopharyngeal carcinoma and the HL-A system among Tunisians.

Previous reports have demonstrated an association between the HL-A system and risk for nasopharyngeal carcinoma among the Chinese in Singapore. The present paper describes an investigation of HL-A profiles among NPC cases and non-NPC controls from Tunisia, to determine whether a similar association occurs in a different ethnic group. A total of 109 NPC cases and 84 controls were typed. At the second HL-A locus the results were similar to those found in Singapore, but the effect was less marked and did not reach high statistical significance. At the first HL-A locus, no association between A2 and NPC was found, in contrast to the Singapore results.


Comparative in vitro sensitivity of twom methylcholanthrene-induced murine sarcoma lines to humoral and cellular immune cytotoxicity.

MC57M and G are the tissue-culture derivatives of two methylcholanthrene-induced murine C57Bl sarcomas. Their sensitivity to immune cytoxic3, cytostatic or cytolytic spleen cells and sera was compared in parallel in vitro assays. The level of cross-reactivity displayed by the two lines was found to depend on the nature of the immune effector rather than on the assay which was used. It was high with immune spleen lymphocytes, alone or in the presence of decomplemented antisera, and low with antisera in the presence of rabbit complement. MC57G cells were more sensitive than MC57M cells to both effectors. Both cell lines were insensitive to antibody-dependent cell-mediated cytotoxicity. Preliminary evidence is presented, suggesting a probable involvement of embryonic and Moloney leukemia virus-induced cell surface antigens in the vitro sensitization of the two tumor lines to immune sera.


DNA repair synthesis of cultured human cells as a rapid bioassay for chemical carcinogens.

The feasibility of detection of carcinogenic chemicals using DNA repair synthesis of cultured human fibroblasts as measured by an unscheduled 3HTdR incorporation has been explored. Of 64 chemicals tested, 29 were proximate or ultimate carcinogens, 15 were precarcinogens that required metabolic activation, 16 were non-oncogenic compounds and 4 were of unknown carcinogenicity. All directly acting carcinogens triggered a DNA repair synthesis, whereas no unscheduled 3HTdR incorporation was observed following the application of the 16 non-oncogenic compounds. As a rule, the precarcinogens (without metabolic activation) do not elicit DNA repair synthesis. However, longer exposures and higher concentrations of the precarcinogens 2-AAF, aflatoxin B1 and sterigmatocystin gave unscheduled 3HTdR uptake. The results suggest the suitability of using repair synthesis as endpoint, and cultured human cells as subjects in a prescreening programme for chemical carcinogens.


Specific anti-tumor responses by cultured immune spleen cells. II. Culture supernatants induce specific anti-tumor cytotoxicity by non-immune lymphoid cells in vitro.

Sera from tumor-bearing mice induce specific cytotoxicity to tumor cells by non-immune lymphoid cells (antiserum-dependent cytotoxicity or ADC). When spleen cells from BALB/c mice bearing autochthonous or syngeneic sarcomas were cultured in vitro, culture supernatants were obtained which specifically sensitized sarcoma cells to injury in vitro by normal lymph-node cells (LNC). Culture supernatants of spleen cells from mice whose transplanted sarcomas had been excised also induced ADC. The ADC activity resided in the mouse immunoglobulin fraction of the culture supernatants and its synthesis did not depend on the presence of theta-positive cells. Following a brief in vivo exposure to culture supernatant with known ADC activity, LNC from non-immune mice specifically destroyed tumor cells in an in vitro assay.


Carcinogenicity of methylated nitrosopiperidines.

The carcinogenicity of nitrosopiperidine and five methylated derivatives was compared by feeding them to rats at equimolar concentrations in drinking water, at the rate of 20 ml per day, 5 days a week. The maximum treatment time was 50 weeks. Nitrosopiperidine, 2-methyl-, 3-methyl- and 4-methyl-nitrosopiperidine induced tumors of the nasal turbinates or upper gastrointestinal tract in almost 100% of the animals. There was a significantly longer time to death from these tumors in the group treated with 2-methylnitrosopiperidine and a number of hepatocellular carcinomas appeared in this longer lived group. Very few tumors of these sites were seen in rats treated with 2,6-dimethyl- or 2,2,6,6-tetramethyl-nitrosopiperidine. It was concluded that blockage by methyl groups of one or more carbon atoms alpha to the nitroso function in nitrosopiperidine significantly reduces carcinogenic activity of the molecule.


Evidence for two factors in sera of tumor-immunized mice which induce specific lymphoid cell-dependent cytotoxicity: IgG2 and a rapidly appearing factor not associated with IgG or IgM.

As previously shown, sera from tumor-bearing mice can induce specific antiserum-dependent lymphoid cell-mediated cytotoxicity (ADC) to syngeneic tumor cells in vitro. The ADC activity in such sera is now shown to be removed by adsorption of the sera to Sepharose-linked rabbit anti-mouse immunoglobulin or to goat anti-mouse IgG2. Immunoglobulins recovered by elution from the affinity columns mediated ADC to the specific tumor cells. In addition, the eluted immunoglobulin passively "armed" normal lymph-node cells in vivo so they were specifically cytotoxic when tested in vitro. Sera taken 48 h after inoculation of tumor or syngeneic tumor cells (before the appearance of palpable tumor) were also shown previously to induce lymphoid cell-mediated cytotoxicity in vitro. This cytotoxic activity was not removed by adsorption of the sera to either anti-IgG or anti-IgM-linked Sepharose. Thus both IgG and an early-appearing serum component which is apparently neither IgG nor IgM can induce specific cell-mediated cytotoxicity by non-immune lymphoid cells in vitro.


Gentamicin pharmacokinetics in rats with reduced renal parenchyma.

Pharmacokinetics of intramuscular gentamicin was observed in healty rats, in rats with renal parenchyma reduced to 1/5 of normal and in rats after bilateral nephrectomy. The results obtained support the assumption that in rats gentamicin is excreted only through the kidneys. Reduction of the renal parenchyma to 1/5 of normal is associated with extention of biological half-life only to double the control value. The results support the hypothesis that in the given experimental conditions gentamicin excretion in residual nephrons increases.


Effect of alphamethyldopa and of phenobarbitone on angiotensin responsiveness and renin activity in man.

Changes of angiotensin sensitivity and renin activity were studied in 25 subjects after one week's administration of alphamethyldopa, phenobarbitone and both compounds. The increase of angiotensin sensitivity produced by alphamethyldopa is abolished by the simultaneous administration of phenobarbitone, moreover angiotensin sensitivity rather decreases. Peripheral renin activity does not change in either of the cases. Phenobarbitone per se does not affect either angiotensin sensitivity or plasma renin activity. Possible mechanisms of the phenomenon are outlined. It is also concluded that angiotensin sensitivity may change considerably without detectable alteration of plasma renin sensitivity.


Dopamine-beta-hydroxylase after treatment with beta-blockers in hypertension.

Dopamine-beta-hydroxylase (DBH) the enzyme responsible for the biosynthesis of noradrenaline from dopamine, was assayed in the blood plasma of 19 cases with hypertension before and during beta-receptor blockade. Propranolol was given to 15 patients and I.C.I. 66,082 (a new cardioselective beta-adrenergic blocker without intrinsic sympathomimetic properties) to 4 patients. - There was no effect by the drugs on the level of plasma DBH activity in spite of a good reduction of the blood pressure.


Effect of guanethidine and of reserpine on angiotensin responsiveness in man.

The respective effects of guanethidine and reserpine on angiotensin responsiveness in man have been investigated. Oral administration of 0.5 mg guanethidine per kg for a week has been found to reduce angiotensin responsiveness considerably, while plasma renin activity remained unaffected. Daily 1 mg reserpine for a week did not influence either angiotensin responsiveness or renin activity. Comparison of the results obtained with the enhancing effect of alphamethyldopa on angiotensin responsiveness has led to the conclusion that there is no relationship between the hypotensive activity of the two drugs in question and their respective effects on angiotensin responsiveness.


Studies on the therapeutic use of Mercurascar. Part III. Influence of Mercurascan on some metabolic changes in experimental myocardial ischaemia in dogs. Section I: Energetic and ionic metabolism.

In experimental studies on dogs, the authors investigated the effect of small does of mercurascan (MSC) on metabolism of the heart muscle damaged by ischaemia. MSC is selectively accumulated and fixed in tissue damaged by ischaemia. MSC was demostrated to inhibit severe disturbances of metabolism in the ischaemic focus. It improves energy metabolism in the damaged tissue by maintaining the concentrations of nucleotides, creatinephosphate and total creatine at a higher level, thereby increasing the energy potential level of the adenylate system. Further, MSC decreases lactate concentration in tissue and reestablishes the disturbed ionic balance. By an hitherto unknown mechanism MSC regulates concentrations of potassium and sodium ions in the ischaemic focus and prevents increased hydration of tissue. Improved metabolic relations in the ischaemic tissue contribute towards normalisation of the heart action.


Anitdiuretic effect of carbamazepine in diabetes insipidus.

A study was made of the effect of the antiepileptic carbamazepine on the water metabolism in 13 vasopressin-sensitive and 4 ADH-resistant diabetes insipidus patients. It was found that in 12 ADH-sensitive diabetes insipidus cases the drug decreased the urinary output and the free water clearance, and increased the urinary osmolarity. The diuresis did not change in ADH-resistant diabetes insipidus patients. The investigations suggest that carbamazepine exerts an ADH-like effect, and can be applied with good results in the treatment of ADH-sensitive diabetes insipidus.


The interaction between alpha-methyl-dopa and tricyclic antidepressants.

The central hypotensive action of alpha-methyl-DOPA is antagonized by tricyclic antidepressants like desipramine and imipramine. This antagonism has been demostrated in chloralose-anaesthetized cats. The drugs to be tested were infused into the left vertebral artery. The antagonism pProbably takes place in the pons-medulla region of the CNS. Probably, the alpha-adrenolytic properties of the tricyclic antidepressants bring about the blockade of central alpha-adrenergic receptors that are stimulated by alpha-methyl-noradrenaline, the biotransformation product of alpha-methyl-DOPA.


Calculation of drug dosage regimens in patients with renal disease: a new nomographic method.

A simple nomograph is described which allows to estimate graphically the individual elimination rate constants of 43 drugs in patients with renal disease based on the endogenous creatinine clearance or the serum creatinine concentration. It is shown how modified dosage regimens are calculated from the estimated elimination rate constants.