Mental aging and its medico-psycho-social background in the very old Japanese.

By clinical observations of 115 centenarians and 742 nonagenarians, the actual state of mental aging of the very old Japanese and some factors relating to it are shown in this paper. A great difference in psychophysical functions was found between the centenarians and the nonagenarians. Most centenarians manifested a distinct decline in these functions, while a decline was less prominent in the 90-year-olds. There was a significant relationship between mental and physical functions. Those manifesting a prominent decline in intellectual ability showed more frequent reduction in physical ability as well, and vice versa. The degree of their intellectual ability was also related to the following factors: their sex, academic and occupational careers, some types of personality traits and personality changes. The mental decline was less prominent in males, in the educated and in those with a syntonic personality than in others.


Environment and face-hand test performance in the institutionalized elderly.

Long term institutionalized elderly people were tested over nine months on the Face Hand (FH) test. Orinally other neuropsychological tests also were to be given, but most patients could only respond to FH at first. Experimental subjects were transferred either to an enriched stimulation environment or a token economy program while control subjects remained in custodial care settings. Analysis of variance interaction between experimental condition and time of testing indicated significant improvement in performance in the enriched environment compared to the token economy and control groups. In supplementary analyses on a subsample capable of other tests at the end of nine months, FH correlated significantly with some neuropsychological measures and not with social skills.


Attitude change in older age: an experimental study.

The role of age in the attitude change process was experimentally studied by exposing older (Mean age: 77.5 years) and younger (Mean age: 19.7 years) women to persuasive information presented at different speeds. In general, the higher speed levels which were employed to decrease information reception resulted in less attitude change, but no overall age differences in the amount of attitude change were observed. In fact, the older women changed their attitudes somewhat more than the younger ones in the normal speed condition. Two mediating processes--positive evaluation and information reception--seemed to counteract each other in producing attitude change in the two age groups: the older women reacted more positively toward the presentation than the younger women, but they understood less of the presented information.


Age differences in the effects of perceptual noise.

Elderly (60 to 82 years) and young (18 to 25 years) subjects were tested on a visual task in which noise items were present but did not require processing to test the hypotheses that elderly persons have more difficulty ignoring irrelevent stimuli and suppressing response competition than do younger persons. Tachistoscopically presented displays contained a precued central target letter either alone or flanked by noise items that required (1) a response the same as, or (2) opposite to that required by the target letter, or (3) did not require a response in this task. No evidence was found to support differentially greater response slowing by the elderly due to the presence of irrelevant stimuli. Elderly persons showed significantly less effects of response competition, suggesting that the two groups processed the task information differently. The results suggest that age differences in effects of perceptual noise and response competition are not general phenomena, but depend upon the demand characteristics of the specific task.


Attribution for success and failure as a function of perceived age.

Based on an attributional model of achievement-related behavior, it was predicted that success on the part of a young person and failure on the part of an old person, being expected outcomes, would be attributed to stable causes, whereas success on the part of an old person and failure on the part of a young person, being unexpected outcomes, would be attributed to unstable causes. Using a between-subjects experimental design, subjects were asked to estimate the probability that a young vs an old stimulus person would succeed in college and to judge the causes for his success or failure. Although there occurred no differences as a function of age in expectancy of success or attributions for success, failure on the part of the old stimulus person was attributed more to the stable causes of lack of ability and task difficulty, while failure on the part of the young stimulus person was attributed more to the unstable cause of lack of effort. The results were discussed in terms of those conditions under which negative stereotypes concerning the competency of the elderly will be considered appropriate and thereby exert an influence on evaluations.


Psychic and somatic symptoms of depression among young adults, institutionalized aged and noninstitutionalized aged.

Beck Depression Inventory scores were obtained from 48 elderly who had been residing in homes for the aged for more than one year, 31 elderly residing in the community and waiting to enter an old-age home, and 424 young adults enrolled in a fist-year psychology course. The residents of old-age homes reported no more symptoms of depression than the waiting-list controls, a finding that provides no support for the hypothesis that the institional nature of old-age homes increases depression in the elderly. Both the institutionalized and noninstitutionalized aged reported more somatic symptoms of depression than the young adults, but no greater cognitive or affective symptoms of depression. These results were interpreted as providing no support for the widely belief that the aged are more depressed than any other age group. Finally, it was argued that somatic complaints can be valid indicators of depression in the elderly if normative differences between young and old are taken into account.


Factors related to attitude towards retirement among French preretired managers and top executives.

This study aimed to investigate the determinants of a favorable attitude towards retirement among 175 male executives aged 63 or 64 and still professionally active. Findings were based on a questionnaire for attitude as well as a variety of other examinations designed to reveal the determinants involved. Multiple regression analysis indicated that four possible determinants are significantly related to a favorable attitude toward retirement: a good cardiovascular status, a poor state of vision, a high degree of life satisfaction and an important amount of time devoted to leisure activities. The relationship between commitment to work and attitude towards retirement was not found to be significant.


Wage determination and discrimination among older workers.

In this study, the determinants of the wage rates of a large sample of individuals aged 58 to 63 are first analyzed. Second, an explanation for the large discrepancies existing between the average wage rates earned by whites and nonwhites and by men and women is attempted. Human capital and geographic variables were found to be important wage determinants. Education, vocational training, years of job tenure, health, region of residence and local cost of living were significant explanators, especially for whites. Differences in these variables, however, cannot completely explain the wage differentials that exist by race and sex. There is a large unexplained component (especially in the male-female comparison) offering evidence of race and sex discrimination among older workers. In the case of sex discrimination, much of the problem appears to be occupational segregation--the crowding of women into low paying industries and occupations.


Going home: aged return migration in the United States 1965-1970.

Two related issues concerning aged return migration are explored in this paper. They are: (1) the common features of states that strongly attract their migration-prone native sons and daughters, and (2) what might account for the differences, if any, in the demographic and socioeconomic characteristics of return and non-return migrants. Individual characteristics of persons, age 60 and over, from the 1970 1-in-100 Public Use Sample of Basic Records were analyzed. A cluster of Sunbelt states, and Utah, strongly attract return migrants; otherwise they tend to be attracted by states which are popular destinations for aged migration in general. Using discriminant function analysis and tests for mean differences of migrant characteristics, it was found that return migrants tend to be negatively selected on socioeconomic characteristics relative to other interstate migrants. Comparisons of migrant characteristics in streams from New York and Ohio to Florida with counterstreams from Florida to New York and Ohio were consistent with a model of secondary post-retirement moves to state of birth when service and social support needs increase.


Relative deprivation and perception of financial adequacy among the aged.

This paper presents a conceptual framework that incorporates the notion of relative deprivation to explain the perceived financial adequacy among the elderly. The model not only provides a more heuristic interpretation of older people's financial satisfaction but also further clarifies the role of actual income. The relative deprivation model was evaluated by using data from the General Social Survey conducted by the National Opinion Research Ctr. from 1972 through 1977. The findings support the predictions derived from the model and were replicated with high consistency across these six data sets. According to the findings, financial satisfaction is directly related to relative deprivation while income only indirectly affects one's sense of financial well-being. Social status, income, and labor force participation have been demonstrated to be either directly or indirectly related to feelings of deprivation.


[A histological and hormonal study of 399 women near the menopause or with confirmed menopause (author's transl)].

This work is concerned with 399 women who were either near the menopause or had had the menopause and on whom 476 hormone levels and 169 examinations of the endometrium had been carried out. It is possible to put the women into three groups. 13 p. 100 showed a diphasic cycle, with more or less normal ovarian function. Among the group of women whose cycle was not diphasic an appreciable number had normal oestrogenic activity, or were indeed hyperoestrogenic. The others were hypo-oestrogenic. Several facts can be derived from this study. Raised levels of E.2 can be found even when there is no cyclical activity and even in women who have raised levels of FSH. Normal ovarian function may be resumed several months after the menopause, although when the levels of FSH are raised the occurrence of the postmenopausal state would seem to be confirmed. The presence of hot flushes does not seem to correspond to a particular hormonal state. Marked differences seem to exist between the levels of the plasma hormones and the endometrial biopsy results. It is possible to have an atrophic endometrium with a raised level of oestradiol-17 beta, or on the other hand a polypoidal endometrium in women who are hypo-oestrogenic. The presence of levels of progesterone such as are found in a normal luteal phase does not indicate that the endometrium will necessarily be secretory. These contradictions cannot be resolved by studying the intra-cellular concentrations of the hormone receptors. The approach of the menopause is not always characterized by a progressive and continuous state of oestrogen deficiency or by hypophysial overactivity. This classical picture can be heavily shaded. All kinds of hormone profiles and responses by the receptor organs may be met and the clinician should be aware of these facts when he chooses therapy.


[Myocardial necrosis due to tocolysis with fenoterol (author's transl)].

95 women had undergone treatment with beta-adrenergic Fenoterol for periods lasting as long as 9 weeks in order to try to avoid premature labour. Electrocardiographic studies and regular controls of the kinase isoenzymes of creatin which is specific for cardiac muscle were carried out in order to avoid myocardial damage, as was MB creatinkinase. In no case was a pathological rise in the activity of the enzyme shown even after full doses of the substance had been given for a long time.


[Early repeated abortions and karyotypes. A cytogenic study of 80 consecutive couples (author's transl)].

The authors report the results of a cystogenic study of 80 couples (160 individuals) who had early repeated abortions. A significant karyotype abnormality was found in 5 per cent of the partners. Where a translocation of 2 heterological chromosomes is found in a partner, the recommendations is to attempt an antenatal diagnostic. Once a couple have had 2 abortions karyotype investigation is absolutely indicated.


Congenital hypoplasia of the thumb with absence of the extrinsic extensors, abductor pollicis longus, and thenar muscles.

An unusual congenital anomaly of the thumb has been seen in 10 hands of eight patients. It consists of skeletal hypoplasia, instability of the metacarpophalangeal joint, absence of the extrinsic extensors and abductor, and adduction contracture of the first web space. Surgical reconstruction consisted of transfer of the extensor indicis proprius, the palmaris longus, and the abductor digiti minimi, as well as ankylosis of the metacarpophalangeal joint and release of the web space contracture. Useful grasp and pinch were provided for all patients. The patients were followed from 2 to 5 years.


[Contact embryoscopy (author's transl)].

Prenatal diagnosis based on anatomic definition of the fetus in utero is an difficult task, in the first trimester of pregnancy. The authors have recently introduced a new method : contact embryoscopy which consist in applying the optic piece of a contact hysteroscope (diameter of six millemeters) to the intact and translucent ovular membranes by the cervix. They have performed fifty embryoscopy prior to termination of pregnancy at 8 to 12 weeks. In 41 cases, they have seen the hands of fetus with the fingers. If this technic fails, it is possible, later, to use Echography and fetoscopy. The side-effects are discussed. Contact embryoscopy would be particularly useful in the detection of malformations of the extremities, for instance : chondro-ectodermal dysplasia (Ellis Van Creveld Syndrome) or ectrodactily.


[Teratospermia consisting of the absence of the head of the spermatozoa because of a fault in the joint between the head and the neck of the sperm in man (author's transl)].

An ultrastructural sperm study was conducted in a sterile man whose sperm count showed 100 percent headless spermatozoa. Testicular biopsy showed abnormal spermatogenesis : within the spermatid, the sperm head developed separately from the flagellum, which alone was ejected during spermiation.


Congenital radial head dislocation.

Fifty patients with 77 congenitally dislocated radial heads were reviewed to assess the diagnostic features, functional limitations, symptomatology, and results of treatment. Twenty-three patients had associated anomalies of the affected upper extremity, and 35 had anomalies in other parts of the body. In six patients no other anomaly was found, all six had bilateral involvement. No patient had congenital radial head dislocation as a unilateral isolated anomaly, and therefore we doubt its existence. Functional limitation with congenital radial head dislocation is minimal and pain is uncommon. Radial head excision relieves pain and improves appearance: however, it does not increase motion.


Vascular anatomy of flexor tendons. I. Vincular system and blood supply of the profundus tendon in the digital sheath.

The detailed blood supply of the flexor tendons in the digital canal was studied in 35 fresh human hands by means of an India ink-latex vascular injection technique. The specimens were examined by first exposing the pulley system, followed by examination of the intact tendon which had been rendered transparent by immersion in a solution of tributyl and tricresyl phosphate. Five annular and three cruciform pulleys were shown. There were five types of long vincula to the profundus (VLP) and three types of long vincula to the superficialis (VLS). The vincular systems of index and little fingers were symmetrical. Occasionally, neither the VLP nor the VLS was found in either the long or the ring fingers. The vincula received blood supply from four transverse branches of the digital arteries. A volar avascular area of the profundus tendon was seen in the cleared cross-sections, and the cross-over zone of its intrinsic vessels was found to be at the midproximal phalanx.


[Lack of the central pair of axial filaments in a case of short-tailed spermatozoa human teratospermia (author's transl)].

A case of short-tailed human spermatozoa is presented in a patient with severe teratospermia. The middle piece was generally short, showing abundant cytoplasmic droplets, disruption of the mitochondrial sheath and absence of some coarsed fibers. The majority of spermatozoa showed enlargement of the principal piece, reduplication of proliferation of the fibrous sheath, and disorganization as well of the axial filament complex as of the coarsed fibers. An abnormal great number of microtubules and coarsed fibers were frequently randomly scattered throughout the cytoplasmic droplet. A further abnormality, consisting in the lack of the central pair of axial filaments was relevant in a 70 p. 100 of spermatozoa. This latter abnormality could be or not associated with the former alterations.


Determination of muscle-tendon unit properties during tendon transfer.

Data on passive lengthening and active shortening from electrical stimulation to give a total functional excursion are presented. Length-tension characteristics of certain muscles used for transfer are given. Electrical stimulation of the newly transferred tendon gives useful information that is reproducible. This new knowledge obtained at operation is an important adjunct to the traditional techniques and provides helpful information in performing better procedures.


[The value of cis-diamminedichloroplatinum (cis-platinum) CDDP in the treatment of stage III and IV cancers of the ovary (author's transl)].

Cis-diamminedichloroplatinum is remarkably useful in stage III and IV cancers of the ovary. It should therefore be added to the armamentarium of chemotherapeutic substances used up till now. This effectiveness adds extra indication to the use of chemotherapy as a first treatment for stage III cancers of the ovary after the lesions have been reduced as far as possible by surgery.


[Comparative action of an impeded estrogen, zeranol, and estradiol on some receptors in the female rat (author's transl)].

We have studied the estrogenic action of zeranol and have compared it to the action of estradiol on the uterus--the vagina, the mammary gland and the pituitary gland of the pre-pubescent, castrated female before the opening of the vagina. The weakest dose at which estradiol is active is 0.1 microgram injected for a period of three days : it is capable of opening the vagina on the fourth or fifth day and of developping the uterine glands to the maximum : injected over a period of ten days it provokes a hypertrophy of the pituitary gland : only the mammary gland reacts exclusively to doses other than physiological ones. The estrogenic action of zeranol is weak : 1 mg administered orally for three days is necessary in order to reproduce the same effects of 0,1 microgram of estradiol on the opening and the keratinisation of the vagina and on the stimulation of the uterine epithelium ; its efficacy is greater on the uterine glands (250 micrograms is equivalent to 0.1 microgram) and on the pituitary gland (500 microgram reproduce the hypertrophy provoked by 0,1 microgram). The doses administered are by 100 g of body weight. The uterine glands are more sensitive to stimulation by the estrogens employed (estradiol, zeranol) than is the uterine epithelium. The study of the relation between the estrogenic dose and the response of the uterine weight shows that the gradient of the curve is weaker with zeranol than with estradiol. This observation shows that zeranol behaves as an impeded estrogen.


The mechanism of dorsal fracture dislocation of the fifth carpometacarpal joint.

Fracture dislocation at the base of the fifth metacarpal is a rare injury. Fewer than 25 cases have been published in the English-language literature. A force acting along the longitudinal axis of the fifth metacarpal causes a fracture dislocation at the base of the bone in a dorsal-ulnar direction, because of the anatomy of the joint and the mechanical properties of the bone and the intermetacarpal ligament. The mechanism of other types of injury to this joint, namely dorsal-radial or palmar-radial dislocation of the base of the fifth metacarpal is different. A case is presented which demonstrates the mechanism of the fracture dislocation.


[Tobacco and pregnancy (author's transl)].

The evil effects of tobacco on the health of those who smoke it have been emphasized broadly in the past few years, both in the public and in the medical press. The possible damage that can be done to those who are "passive" smokers has also been pointed out. Now the fetus is in the front row of these. That is why it is important to point out this fact. After a brief statement about the physio-pathology of the condition the authors review the literature and extract the following points which can be ascribed to the use of tobacco: -- lowering of the birth weight; -- considerable increase in risk of premature separation of the placenta; -- a negative correlation with the frequency of pre-eclamptic toxaemia. The authors point out the additional feature that the effect of tobacco can potentiate the effects of an associated pathological condition. Finally, they emphasize the methodological difficulties which account for the numerous discrepancies and uncertainties that still exist about the action of tobacco on pregnancy.


Rupture of the radial collateral ligament of a metacarpophalangeal joint to one of the ulnar three fingers.

In six patients rupture of the radial collateral ligament of the metacarpophalangeal joint of one of the three ulnar fingers, surgical reconstruction was successful using local tissues in five and a tendon graft in one. Operative treatment of this injury is indicated only when significant instability is present.


Mechanical analysis of Kirschner wire fixation in a phalangeal model.

Transverse divisions of the mid-shaft of freshly frozen pig metacarpals were fixed with Kirschner wires of two sizes and using four different configurations. Compared to the usual cross-pin fixation using wires of 0.889 mm. four wires (0.712 mm) eccentrically placed and with their ends hooked provided a 300% improvement in bending rigidity and 170% in bending movement.


External fixator use in comminuted gunshot fractures of the proximal phalanx.

Comminuted low velocity gunshot fractures of the proximal phalanx were stabilized with an external fixator in 15 patients. This device was found to be useful. It allowed healing of the fracture in good alignment in 13 patients. And motion of the metacarpophalangeal joint was preserved.


Epitheloid sarcoma: a case report.

Epitheloid sarcoma of the pulp of the thumb followed repeated penetrating injuries to the digit. It was treated aggressively and successfully to date, nearly 5 years later. In some respects this case report parallels those animal experiments in which foreign body tumorigenesis has been demonstrated, and one might entertain a correlation.


Heparin-induced thromboembolism: a case report.

A case of heparin-induced thrombosis of the brachial artery with thrombocytopenia is described. With discontinuation of the heparin, the circulating platelet volumes returned to normal. The role of pre-existing arterial disease and sepsis in patients exhibiting this phenomenon is unresolved.


Cataract--webbed Peromyscus. I. Genetics of cataract in P. maniculatus.

Cataract--webbed (cw) in the deer mouse (Peromyscus maniculatus) is a recessive mutant that is manifested by syndactyly (involving soft tissues) and eye defects including cataract. Within cw/cw mice, the age at which cataract first appears is genetically controlled. Evidence for the activity of genetic modifiers is the early appearance of cataracts in the offspring of parents that developed cataracts at early ages.


Allozyme variability and relatedness in six crayfish species.

A total of twenty-six allozyme loci were assayed in six crayfish species. Estimated mean heterozygosity was low (5.5 percent) for all species in comparison with the invertebrate average. The specific values, however, ranged from 2.9 percent to 8.3 percent. These crayfish estimates are consistent with estimates for other decapods where low heterozygosity is the rule. The consistency of low heterozygosity estimates in the order Decapoda suggests that its explanation may include both order specific differences such as low mutation or intracistronic recombination rates and species specific differences. A dendrogram, constructed using Nei's D, is in agreement with the morphological clustering.


Green shanks and adult mortality in chickens.

A mutation of recent origin in Cornell randombred Leghorn chickens causes the shanks to be colored green due to melanin-like deposition in the dermis, in contrast to normal yellow. Some pigment is often present in the mandibles and the mature feathers display an ashen cast. This mutant is determined by an allele, idc, on the sex chromosome. Excessive adult mortality with a high incidence of tumors, mainly hemangiomas, is associated with this gene--at least extending over a two-generation observation interval. Pullets receiving this mutant allele (idc) from their sire die at 2 to 3 times the rate of sisters, with yellow shanks, that carry the Id allele.


Esterase variation at three loci in meat ants.

The meat ant (Iridomyrmex purpureus) occurs in a number of color forms, with uncertain taxonomic status. Gel electrophresis of meat ant extracts, followed by nonspecific esterase staining, reveals several zones of activity. Allelic variation at three loci is proposed to account for variation in some of these zones. Two of the loci (Es-1, Es-2) appear to have recessive null alleles, whose frequencies have been estimated by the method of maximum likelihood. Geographic variation in allele frequency is attributed to behavioral and geographic subdivision of the population. Apparent disturbances in segregation ratios and deviations from Hardy-Weinberg equilibrium can be accounted for if it is argued that some nests contain more than one queen. Differences in gene frequency between sympatric populations of the red and blue forms of I. purpureus are observed, confirming their reproductive is isolation and sibling species status.


Identification of a 16--17-day lethal factor in a chondrodystrophic stock of turkeys.

Chondrodystrophy in turkeys is a lethal condition produced by an autosomal allele, ch. Mutants are characterized by very short and thick legs, shortened wings, globular head with parrot beak, and a protruding abdomen. Classification of ch/ch embryos may be accurately made at 12 days incubation, prior to which limited appendicular development precludes distinction from normal or heterozygous birds. Death caused by the mutant allele occurs between 24 and 28 days; some embryos are alive but unpipped at time of hatch. Analysis of the pattern of embryonic mortality for the stock carrying the ch allele revealed at 16--17-day lethal factor that appears to be independent of chondrodystrophy. Of 52 females mated to Ch/ch males, 41 were determined to be Ch/ch; 32 of these heterozygous females exhibited normal embryonic mortality patterns. Nine hens, in addition to being Ch/ch, displayed a significant increase in embryo death between 15 and 18 days, peaking sharply at 17 days. Of the 11 females determined to be Ch/Ch, five showed the same 15 to 18 day pattern of mortality observed for the nine Ch/ch females.


Intracellular labeling with ferritin conjugates. A specificity problem due to the affinity of unconjugated ferritin for selected intracellular sites.

Nonspecific binding of ferritin to chromatin and the cytoplasmic aspect of the nuclear envelope was observed when nonantigenic, serum-washed hepatocyte nuclei were incubated in ferritin-antibody conjugates. This labeling was duplicated when nuclei from a wide range of species and cell types were exposed to unconjugated ferritin. Unconjugated ferritin binding to nuclei did not depend on a subpopulation of denatured molecules or on the ferritin purification procedure. Binding occurred equally on unfixed and formaldehyde-fixed nuclei, but no ferritin bound to glutaraldehyde-fixed nuclei. Inconjugated ferritin also bound to the cytoplasmic aspects of the rough endoplasmic reticulum and the plasma membrane. The tracer did not bind to lysosomes, mitochondria, Golgi vesicles, the extracellular surface of plasma membranes, or the intracisternal surfaces of ruptured nuclear envelopes. The addition of 0.4 M KCl or 0.7 M NaCl to ferritin solutions and washing media at neutral pH reduced the binding of conjugated and unconjugated ferritin to nuclei to about 3% of that seen in 0.10 M phosphate buffer alone. The added salts caused little extraction of nuclear contents from formaldehyde-fixed nuclei. The use of one of these salts in ferritin conjugates should considerably improve the specificity of intracellular labeling.


Desired family size and sex of children in Botucatu, Brazil.

During 1977--78, 715 unmarried college students at the Universidade Estadual Paulista, Botucatu, Brazil, were surveyed for their preferences for family sizes and combinations and permutations of sexes of children. The most preferred family size by both male and female respondents was two children. A slightly lower proportion of respondents preferred a family size of three children. Average size of the desired families was approximately 2.76 children. The most preferred combinations of sexes were one male, one female; one female, two males; and two females, two males, respectively, in families of two, three, and four children. Preferred permutations of sexes were those in which the first child was male and subsequent children resulted in an alternation of sexes.


A technique for assessing nutritional 'at-risk' factors in residential homes for the elderly.

A technique for assessing the degree of nutritional risk to residents in old people's homes is outlined. Administrative, psychological and social factors are considered as well as food. Twenty-six risk factors are identified. In one short visit, using questionnaires to the matron, cook and the residents and a check-list of general observations, the degree of risk, high, moderate or low, can be assessed. The technique has been used in a pilot study for comparisons between homes, and for advice to individual homes.


Assignment of the H-Y antigen gene to the short arm of chromosome Y.

We have presented two cases strongly suporting a Y chromosome short-arm location for the H-Y antigen gene. The first case was HY antigen-positive with an isochromosome for the short arm of the Y with no long arm of the Y being present. The other case was H-Y antigen-negative in fibroblasts from an individual with a 46,X,i(Yq) karyotype with no short arm of the Y present. The two cases presented also confirmed previous reports that the testicular forming gene is also located on the short arm of chromosome Y.


Portion sizes, preparation and cooking yields, and plate waste in school meals.

Available portion sizes for a wide range of menu items were measured in seven junior schools and three senior schools in one local authority area. Serving waste was also measured and used as a criterion of acceptability. Portion sizes for entrees, desserts and potatoes were generally acceptable except for a few unpopular items. Custard was the most acceptable milky sauce. A small range of vegetables was acceptable in small quantities, but excess was rejected while others were almost totally rejected. Peeling, trimming and cooking yields for vegatables, trimming and cooking yields for meat, and plate waste were measured over one year in 180 schools in eight local authority areas. Results for vegetables compared favourably with previously published data  except for new potatoes where the yield after machine peeling was lower. Cooking yields for pork, beef and lamb were slightly lower than previously published values. Trimming waste from meat for stewing was substantially greater than the 5 per cent visible fat which is the catering specification for ordering. The mean plate waste was 33 g per child meal (excluding bones).


Food preferences of some United Kingdom residents.

A food preference questionnaire was completed by 1304 people. There were considerable differences in food preferences related to age, sex, and area of residence of the respondents. In spite of these differences, five distinct clusters of foods showing similar preference patterns were indentified. These clusters were of sweet fruits, meats, vegetables, alcoholic beverages, and some high carbohydrate foods. The cause of the clustering was uncertain.


Fertile dominant spotting in the house mouse.

Recognition of a new allele (Wf) at the W locus of the mouse is based on genetic analysis and demonstration of defective hair pigmentation, macrocytic anemia, and defects in pluripotent hemopoietic stem cells. Unlike other alleles of the W series, this one does not result in sterility.


An interview model for use in dietetic training.

Student dietitians commonly encounter difficulties with interviewing patients. These difficulties may arise through ignorance of either the function of the interview or the interview technique. Some major problems are described and an interview model is proposed as one method of helping the student to cope.


A national nutrition policy: can we devise one?

The reasons for the success of the British food and nutritional policy of the second world war are discussed. Subsequent trends in Britain and elsewhere towards the affluent pattern of diet are described and the current views about diet and heart disease and diet and cancer are summarised. Conclusions are drawn about the need for public education on the modification of diet towards amore prudent pattern. The terms food policy and nutritional policy are distinguished.


The impact of OSHA inspections on manufacturing injury rates.

This paper estimates the effects of OSHA inspections on injury rates at the plant level. The methodology involves comparing injury rates of plants inspected 'early'in a given year with those inspected "late" in the year, after controlling for prior injury rates and other factors. The results suggest that OSHA inspections in 1973 reduced injury rates by about 16 percent, but that 1974 inspections had no statistically significant impact.


The ability of the murine placenta to absorb monoclonal anti-fetal H-2K antibody from the maternal circulation.

In previous work we have found that partially purified 125I-labeled anti H-2 antibody is localized in the placenta when injected i.v. into females pregnant by males bearing the target haplotype. This led to the concept that the placenta is an H-2 antigen-bearing immunoabsorbent barrier between mother and fetus. In this report we have used an anti-H-2Kk monoclonal antibody of the IgG2a subclass, also labeled with 125I, to verify this concept, as well as to improve the genetic definition of the immunoabsorbent antigen. In addition we have prepared F(ab')2 fragments of this antibody, and these also show the immunoabsorbent effect. This indicates that transport into fetally derived tissues via Fc binding is not a prerequisite for reaction of the antibody with paternal strain H-2 K antigens.


Binding constants of NZB myeloma antidextrans for dextrans and isomaltose oligosaccharides determined by affinity electrophoresis.

Association constants of dextrans (Ka) and oligosaccharides (Kia) from NZB myeloma antidextrans (PC3858 and PC3936) were studied by affinity electrophoresis. With linear dextrans or with those with a low degree of branching, Ka ranged from 2.7 X 10(3) to 5.4 X 10(4) ml/g for PC3858 and from 1.3 X 10(4) to 2.6 X 10(5) ml/g for PC3936. Completely linear alpha-(1 leads to 6)-linked dextrans, LD7 and D3, showed relatively high affinities for the two NZB antidextrans. With oligosaccharides, the Kia value increased as the number oa alpha-(1 leads to 6)-linked glycosyl residues increased. Isomaltoheptaose (IM7) showed the highest Kia (1.9 X 10(4) M-1 for PC3858 and 1.63 X 10(4) M-1 for PC3936), whereas isomaltose (IM2) had the lowest Kia (2.36 X 10(2)M-1 for PC3858 and 1.32 X 10(2)M-1 for PC3936). Pullulan and glycogen showed very weak affinity for PC3936, but they did not react at all with PC3858. These findings indicate that NZB myeloma antidextrans, PC3858 and PC3936, are specific for internal chains of alpha-(1 leads to 6)-linked dextrans. Data on the precision with which Ka and Kia can be determined are presented.


The release of a platelet-activating factor by stimulated rabbit neutrophils.

Normal rabbit peripheral blood neutrophils released a platelet-activating factor upon stimulation by opsonized zymosan. The liberation was Ca++ dependent and the time course of release was closely associated with phagocytosis. The material extracted into chloroform and exhibited an identical mobility by thin layer chromatography to basophil-derived, IgE-stimulated, platelet-activating factor (PAFb). It was similar to PAFb in its effect on platelets in both aggregation and release but was distinguished from ADP, thrombin, arachidonic acid, and thromboxanes. This factor appears to be responsible for some previously reported neutrophil-platelet interactions.


Suppression of cell-mediated tumor cell lysis and complement-induced cytotoxicity by trypan blue.

Different forms of cell-mediated cytotoxicity were suppressed in the presence of trypan blue. The systems affected included lysis of antibody-coated tumor cells by normal and C. parvum-stimulated mouse peritoneal cells and lysis of allogeneic targets by immune effector cells. The inhibition, measured in a 4-hr 51Cr release assay, was reversible and did not occur in the presence of 30% fetal calf serum or albumin. Binding between effector and target cells through Fc receptors was not affected, and lysis of allogeneic cells was inhibited at the lytic step rather than at the binding step. In contrast, lysis of sensitized erythrocytes was not inhibited by trypan blue, suggesting that lysis of these targets may not involve the steps required in tumor cell lysis. Trypan blue blocked the function of antibody before binding to target cells and also suppressed complement-induced cytolysis. Most individual complement components were susceptible to the inhibitory action of trypan blue. These results reveal an affinity of trypan blue for proteins in general that may be responsible for many of its biologic actions.


Potentiation of antiboty-dependent cell-mediated cytotoxicity by target cell-bound C3b.

Antibody-dependent cytolytic effector lymphocytes are known to possess, in part, receptors for activated C3. Employing a model system consisting of 51Cr-labeled chicken erythrocytes and purified human peripheral lymphocytes, we investigated the effect of target cell bound C3b on antibody-dependent cellular cytotoxicity (ADCC). At concentrations of anti-target cell antibody too low to cause effective ADCC, target cell bound C3b cooperated with antibody to produce marked target cell lysis. In the presence of a 1/6.25 X 10(6) dilution of anti-chicken erythrocyte rabbit IgG, cell lysis increased from 20% to 65% by the attachment of 18,000 C3b molecules per cell. C3b-dependent enhancement of ADCC was dose dependent. It was augmented by attachment of activated properdin (P) to the C3b-bearing target cells.


Cyclophosphamide and cortisone acetate inhibit complement biosynthesis by guinea pig bronchoalveolar macrophages.

To explore mechanisms of drug-induced alterations in local host defenses in the lung, the capacity of guinea pig alveolar macrophages to synthesize the second (C2) and fourth (C4) components of complement was studied following treatment with cyclophosphamide and cortisone acetate. Administration of either drug significantly inhibited biosynthesis of C2 and C4 within 1 day. After 1 week of treatment, local complement synthesis was inhibited approximately 80%, although serum levels of the corresponding proteins were normal.


Passive enhancement of mouse tumor allografts by alloantibodies is Fc-dependent.

Enhancement of growth of a B10.D2 fibrosarcoma in B6AF1 recipients could be induced by administration of B6AF1 anti-B10.D2 lymphocyte serum. The role of the Fc part in this phenomenon was studied by treatment of the B6AF1 recipients with F(ab')2 fragments of enhancing alloantibodies. A highly purified F(ab')2 preparation was used to exclude any effects of undigested IgG. Administration of F(ab')2 did not lead to enhancement of the tumor allografts, not even when given in a dose that was 22 times the molar amount of the lowest enhancing dose of undigested IgG. We therefore conclude that passive enhancement of mouse tumor allografts by alloantibodies is Fc dependent.


The enzymatic nature of human c1r: a subcomponent of the first component of complement.

The esterase activity of the C1r subcomponent of the first component of complement has been investigated. C1r was found to hydrolyze two amino acid methyl esters; N-acetyl-L-arginine methyl ester and N-acetyl-glycyl-L-lysine methyl ester, and two amino acid p-nitrophenyl esters, N-carbobenzyloxy-L-tyrosine-p-nitrophenyl ester and N alpha-carbobenzyloxy-L-lysine-p-nitrophenyl ester. A detailed kinetic analysis of the hydrolysis of N-Z-L-Tyr-ONp by C1r revealed that the enzymatic activity per microgram of protein decreased as the C1r concentration was increased. The loss of activity suggested that above 0.5 micron C1r was undergoing aggregation with a loss of active sites. Similarly, when C1r was titrated with the active site titrant p-nitrophenyl-P'-guanidinobenzoate the number of titratable sites per milligram of protein decreased with increasing protein concentration. The hydrolysis of N-Z-L-Tyr-ONp by C1r was inhibited by several synthetic inhibitors including phenylmethanesulfonylfluoride, p-amidinophenylmethanesulfonylfluoride, diisopropylfluorophosphate, and p-tosyl-L-lysine-chloromethyl ketone. However, the peptide esterase inhibitors Trasylol, hirudin, leupeptin, and C1 esterase inhibitor had no effect on the esterase activity of C1r.


A semi-automatic method of measuring leucocyte movement.

A semi-automatic system has been developed for measuring the migration of leucocytes within a micropore filter. The distance in micrometers is displayed digitally or analysed on-line by a digital computer. These improvements have resulted in considerable saving in time, permitting the full potential of the micropore method to be utilised. To illustrate this technique we report results from experiments to measure dose-response relationships of leucocytes to casein and the variation in response to Staphylococcus aureus and casein of cells from normal human subjects.


A capillary diffusion method for determining hemolytic complement activity in undiluted serum .

A method is presented for measuring the hemolytic activity of undiluted guinea pig serum. Undiluted serum is placed in contact with a column of sensitized sheep red blood cells in an agar matrix in a capillary tube. After incubation, the length of the zone of lysis is measured. Comparison with a standard curve prepared from dilutions of a pool of normal serum allows relative quantitation. Because the serum is not diluted, this method allows detection of reversible inhibitors of the complement system.


The effect of label affinity on the sensitivity and specificity of a hapten radioimmunoassay: a comparison of three [125I]diphenylhydantoin radioligands with the 14C-labelled drug.

The effect on the sensitivity and specificity of a radioimmunoassay for diphenylhydantoin (DPH)has been investigated using three 125I-labelled tyrosine ester derivatives of DPH having different bridge lengths between the tyrosine moiety and the DPH moiety and 14C-labelled DPH. The results demonstrate that for a hapten which does not completely fill the antibody-binding sites, greatest sensitivity is achieved when the bridge of the iodine label is most dissimilar to that present in the original immunogen, when the hapten and label affinities are nearly equivalent. Greatest specificity is achieved with the label which most resembles the original immunogen. These results illustrate the difficulty of designing satisfactory labels for assays of both high specificity and sensitivity since minimal changes in label structure may produce greatly amplified changes in the subsequent affinity of the label for the antiserum.


Purification of rodent eosinophils on discontinuous metrizamide gradients.

Methods are described for the purification of rat and mouse eosinophils. Peritoneal exudate cells obtained from Schistosoma mansoni- or Trichinella spiralis-infected mice were plated on plastic dishes, and the nonadherent cells were centrifuged over discontinuous hypertonic metrizamide gradients. Approximately 41% of those eosinophils present in the original preparations were recovered from the interfaces between 20% and 22% metrizamide at an average of 88% purity. Peritoneal cells obtained from either uninfected or S. mansoni-infected rats  were placed directly onto metrizamide gradients. After centrifugation, essentially all eosinophils present in the original preparations were recovered at the interface between 18.5% and 22.5% metrizamide, with an average of 80% purity. These methods for eosinophil purification have proven to be reproducible and to yield cells which are morphologically preserved and functional, as demonstrated by their ability to respond to a chemotactic stimulus.


Receptors for IgM on human lymphocytes. I. Detection of receptors on freshly drawn lymphocytes and at physiological temperature.

Receptors for the Fc portion of IgM (RFcmu) have previously been found to be primarily associated with the T lymphocyte subpopulation in humans, and their detection has frequently required overnight incubation of the cells before assay. In the present study, using highly sensitized indicator cells (EAmu), lymphocytes with receptor for IgM (EAmu-RFC) were detected immediately after isolation from human peripheral blood. Identification of EAmu-RFC on freshly isolated lymphocytes was greatly facilitated by assay at room temperature (RT) or 37 degrees C, implying that analogous interactions between IgM-antigen complexes and lymphocytes with receptor for IgM normally occur in vivo. These results seem to indicate that some RFcmu on lymphocytes may be occupied by IgM and/or IgM-antigen complexes in vivo and that immediately after isolation many RFcmu are still occupied and unavailable for interaction with EAmu. It is suggested that the successful competition of IgM-antigen complexes for RFcmu on T lymphocytes is the signal for and/or mechanism of expression of help by the lymphocyte. The sensitivity of the assay for EAmu-RFC also permitted the identification of a small subpopulation of RFcmu+ lymphocytes in the non-T cell fraction of the peripheral blood of some individuals.


Activity of mouse macrophages purified by adherence to, and removal from, a plastic surface.

Mouse peritoneal exudate macrophages were allowed to adhere to plastic Petri dishes and, after washing, were removed by means of EDTA. Cells with the morphology of macrophages were recovered in a fair degree of purity (90-98%) but in low yield (31-34%). The macrophages recovered were fully active in the following ways: re-adherence to glass; pinocytosis of colloidal gold; phagocytosis of opsonized sheep erythrocytes; binding cytophilic antibody; production of lymphocyte activating factor; cytotoxic and cytostatic effects on tumour cells.


Particle counting immunoassay (PACIA). III. Automated determination of circulating immune complexes by inhibition of an agglutinating factor of mouse serum.

A factor capable of agglutinating human IgG coated particles (latex) has been found in mouse serum. This factor (MAG) was used in an unpurified form to detect circulating immune complexes in the particle counting immunoassay (PACIA) system, which allows measurement of agglutination with great precision. MAG did not react with monomeric IgG, nor with reduced and alkylated aggregated IgG. It was inhibited by immune complexes in small antigen excess. Among the various subclasses of IgG, IgA and IgM, only IgG1 and IgM when coupled to Sepharose beads displayed an inhibitory activity towards MAG. That the inhibitory factors detected in serum were immune complexes or aggregated Ig was suggested by the correlation obtained with the amounts of 'heavy' IgG found in the serum samples by Ultrogel chromatography and by the polydisperse distribution of the inhibitory factors in the heavy fraction of gradient ultracentrifugation.


The occurrence and treatment of false positive reactions in enzyme-linked immunosorbent assays (ELISA) for the presence of fungal antigens in clinical samples.

Non-specific positive reactions have been revealed in enzyme-linked immunosorbent assays (ELISA) of sera for the presence of fungal antigen. These false positives were recognized by their occurrence in tests for both Candida albicans and Aspergillus fumigatus antigens and by their response to dithiothreitol, combined with their reaction with non-immune rabbit globulin. A scheme is proposed which differentiates between true and false positive reactions. Use of fractionated anti-fungal globulin in conjugates reduced the incidence of false positive results in sera from hospitalized patients and eliminated them from sera of healthy subjects. The test scheme was applied to two panels of sera containing samples from patients with (a) invasive candidosis and (b) invasive aspergillosis. The relevance of ELISA tests for the detection of fungal antigen in human serum is discussed.


A single-step immunization by sustained antigen release.

An inert polymer pellet less than 1 mm in diameter, implanted subcutaneously in mice, releases free antigen continuously and enhances antibody formation for over 6 months. The immune response stimulated by sustained antigen delivery is comparable to the secondary response induced by the same total dose of antigen emulsified in complete Freund's adjuvant. The sustained release polymer implants, using antigens over a wide molecular weight range, proved effective in eliciting prolonged antibody formation. The antigens tested included bovine serum albumin, gamma-globulin, and ribonuclease. Superior biocompatibility and release characteristics make the ethylene-vinyl acetate copolymer a promising method for the single-step induction of immunity.


Particle counting immunoassay. IV. The use of F(ab')2 fragments and N epsilon-chloroacetyl lysine N-carboxyanhydride for their coupling to polystyrene latex particles.

Improved performance with the latex agglutination immunoassay, PACIA, is possible when the F(ab')2 fragments of antibody are chemically coupled at their hinge region to a protein-coated latex using a new coupling reagent, N epsilon-chloroacetyl lysine N-carboxyanhydride. This reagent, whether by orientating the complete antibody molecule or its F(ab')2 fragment or by preventing antibody denaturation, increased the sensitivity of the PACIA method. The use of F(ab')2 fragments eliminated most serum interference with the test.


A new method for measuring antibody using radiolabeled protein A1 in a solid-phase radioimmunoassay.

A micro solid-phase radioimmunoassay was developed which utilizes radiolabeled staphylococcal Protein A ([125I]Protein A) in place of radiolabeled anti-immunoglobulin ([125I]anti-IgG) for the measurement of antibody. For the assay, antigen is adsorbed to the wells of a microtiter plate followed by dilutions of serum and [125I]-Protein A in subsequent steps. We found that this assay can be used to measure antibody (Ab) against a variety of antigens in human and rabbit but not goat immune serum. Binding of [125I]Protein A and [125I]anti-IgG to human and rabbit IgG was comparable. It was possible to quantify this amount of Ab in human serum by reference to immune rabbit serum. The sensitivity of this assay for rabbit antibody was 1 ng/ml.


Determination of phenobarbital by radioimmunoassay.

A radioimmunoassay for phenobarbital has been studied. Antiphenobarbital antisera were obtained by repeated immunization of rabbits with p-succinamidophenobarbital conjugated to bovine serum albumin. Less than 0.2 pmol of phenobarbital could be measured by this procedure. The specificity of the antibodies was directed to substituents on the nitrogen atoms of the barbituric ring as well as to substituents at the carbon 5-position of the ring.


Radioimmunoassay of glycosphingolipids: application for the detection of forssman glycolipid in tissue extracts and cell membranes.

Development of a radioimmunoassay for detecting glycosphingolipids has been difficult, primarily because of transfer of radiolabeled glycolipid antigen to the unlabeled antigen pool. This difficulty has been overcome by the use of a radiolabeled glycolipid-polymer. Thus, an assay system has been developed for measuring picomolar quantities of Forssman hapten glycolipid. This assay is based on competition for rabbit anti-Forssman antibodies between Forssman glycolipid and a radiolabeled Forssman polyacrylic hydrazide polymer. Antigen-antibody complexes are removed quickly and efficiently by binding to formalin-fixed Staphylococcus aureus and subsequent centrifugation. One nanogram of Forssman glycolipid can be readily detected both in plasma membrane preparations and in purified glycolipid fractions. The isoantigenic expression of Forssman glycolipid in human gastrointestinal tissues has been reported previously (Hakomori et al., 1977). Using the radioimmunoassay, the Forssman status of several additional cases has been determined quantitatively.


Dithiothreitol separation of newborn rodent dermis and epidermis.

Incubation of newborn mouse skin in media containing 0.01 M dithiothreitol at 4 degrees C for 2 hr reduces dermal-epidermal cohesion, and the 2 layers may be separated readily. Unlike other methods of separation, this technique does not require heating, nonphysiologic pH or ionic strength, or addition of proteolytic enzymes. The split occurs beneath the basal lamina. The separated epidermal sheet retains the periodic acid Schiff-positive "basement membrane," and the basal cells can incorporate 3H-thymidine.


Repair of ultraviolet light damage to the DNA of cultured human epidermal keratinocytes and fibroblasts.

Pure cultures of dermal fibroblasts and epidermal keratinocytes have been obtained from a single biopsy of newborn foreskin. The cells were labeled, exposed to several doses of UV light, and allowed to repair in the dark for 16 hr. The number of pyrimidine dimers before and after repair was assessed by measuring the numbers of sites in the DNA sensitive to a specific UV endonuclease. At all doses used, the extent of repair was similar in the cultured keratinocytes and cultured fibroblasts.


Comparison of lymphocyte function after isolation by ficoll-hypaque flotation or elutriation.

Mononuclear leukocytes were separated from whole blood by ficoll-hypaque flotation and by elutriation (counterflow centrifugation). Lymphocytes isolated from 6 control subjects by elutriation showed a 30% greater response to stimulation with phytohemagglutinin and 130% greater response to streptokinase-streptodornase stimulation than did autologous lymphocytes obtained by ficoll-hypaque separation. Cell yields of major mononuclear cell subpopulations and cell viability were comparable after separation of leukocytes by both techniques. These results indicate that ficoll-hypaque flotation may diminish lymphocyte responses, and that elutriation offers a useful alternative to ficoll-hypaque separation. In addition, elutriation may be the preferable method for evaluation of lymphocytes from patients with suspected immunologic dysfunction and may be valuable in the isolation of mononuclear cells from infiltrated skin lesions.


Interstrand crosslinks in DNA of phage lambda after exposure to 8-methoxypsoralen and trimethylpsoralen in the presence of light.

Two medically useful photosensitizing furocoumarins, 8-methoxypsoralen (8-MOP) and 4,5'8-trimethylpsoralen (TMP) were compared with respect to their abilities to produce interstrand crosslinks in DNA. DNA from bacteriophage lambda, labeled with 32P, was subjected to sedimentation in alkaline sucrose gradients following exposure to several concentrations of 1 of the 2 psoralens and irradiation (UV-A, 360 nm) for various times. In alkaline sucrose gradients, crosslinked DNA molecules sediment about 1.4 times faster than undamaged DNA strands and the proportion of molecules carrying crosslinks can be estimated with reasonable accuracy. At equimolar psoralen concentrations (2 x 10(-7)M, or 4 x 10(-5)M) and with increasing irradiation times, the rate of production of crosslinked DNA was 4 to 30 times greater for TMP than for 8-MOP. Differences in the therqpeutic efficacy of 8-MOP and TMP in various clinical situations may be accounted for by the types of photoadducts formed by each drug as well as by their solubilities, rates of absorption and rates of metabolic degradation.


Cholinesterases isoenzymes: a comparative study in the skin and plasma.

Acetylcholinesterase (Ache) and pseudocholinesterase (BUche) activities were studied quantitatively in healthy skin by spectrophotometric methods and qualitatively by polyacrylamide gel electrophoresis. The results were compared to those obtained in plasma. The substrates used to reveal enzyme activities were acetylthiocholine (ATC) iodide and butyrylthiocholine (BTC) iodide, respectively. A linear relationship exists between the values of BUche and Ache activities in plasma and those in skin. Six isoenzymes of different electrophoretic mobility were observed in the skin. One of them, which is never found in plasma extracts, appears to be specific to the skin. On gradient gel electrophoresis, with both substrates (ATC and BTC), a single band of enzyme activity, corresponding to a molecular weight of 600,000 was observed. These results suggest that in the skin there is only one enzyme, most probably butyryl cholinesterase, which cleaves BTC somewhat faster than ATC. This methodology, when applied to the study of dermatoses in which abnormalities of cutaneous nerve terminals are suspected, should furnish precise functional pathophysiological details.


Dermatological and ocular examinations in rabbits chronically photosensitized with methoxsalen.

Four groups of female Dutch-belted rabbits (Oryctulagus cuniculus) were given methoxsalen (12 mg/kg) or placebo by oral intubation and 1 hr later were exposed to UVA for either 2 or 8 hr. This procedure was repeated 5 days each week for 18 mo. A fifth group received no drug and no UVA exposure. The skin of the animals given methoxsalen and UVA showed signs of acute and chronic phototoxicity. Multiple peripheral blood parameters of hepatic, renal and hematologic function were normal and were not different between groups. Complete ophthalmoscopic examinations were performed periodically. No cataracts were seen in any of the animals. This data provides the perspective that in one species the daily dose of methoxsalen and UVA required to induce chronic cutaneous photosensitization is lower than the daily dose required to induce cataracts. It is inadvisable to interpret this data as suggesting that no risk exists for patients being treated with oral methoxsalen photochemotherapy. The experimental evidence supporting photosensitization as a cause of cataracts and implicating a role of lens DNA in this cataractogenesis is reviewed. Because methoxsalen-UVA alterations of lens DNA or protein could lead to delayed onset of cataracts, and because of the serious nature and potential preventability of phototoxic lens opacification, appropriate protective eye wear is recommended for all patients receiving oral psoralen photochemotherapy.


The influence of longwave ultraviolet radiation on sunburn cell production by UVB.

The potentiation of sunburn by longwave ultraviolet radiation (photoaugmentation) has been examined with regard to the influence of these waves on sunburn cell production in human skin. It was found that UVA did not enhance sunburn cell production. Photoaugmentation is limited to the erythemal component of the sunburn reaction.


Antibody method for measurement of dihydrotestosterone receptors in cultured human skin fibroblasts.

We have adapted the method of Castañeda and Liao to the assay of DHT receptors in cultured fibroblasts arising from human skin. An antitestosterone antibody (100% crossreactivity for DHT) was coupled to CNBr-activated Sepharose. Confluent monolayers of fibroblasts were incubated with 3H-DHT (2 nM) at 37 degrees C for 30 min. Fibroblasts were then collected, sonicated, and centrifuged at 1200 x g for 15 min. The receptor assay was carried out on the supernatant; the antibody-sepharose was used to remove both unbound and nonspecifically bound DHT. Experience showed that the antibody did not entirely remove the nonspecifically bound and free DHT. A blank (sample heated at 60 degrees C for 3 min) was therefore subtracted to obtain an accurate value of specifically bound DHT. In spite of this, the antibody method, when compared to the gel filtration method, was more rapid and more convenient. Its reproducibility was similar to that of the gel filtration method, and its sensitivity was somewhat greater in patients with low levels of DHT-receptor complex. Improved sensitivity could be particularly useful when dealing with partial AIS.


In vitro effects of single alkylating agents on normal peripheral blood lymphocytes.

The separate in vitro effects of HN2 and L-PAM on resting and stimulated peripheral blood lymphocytes were evaluated with biochemical and morphologic experimental endpoints. Both alkylating agents caused dose-dependent reduction of protein, RNA, and DNA synthesis, but the patterns of diminution differed. The number of cells staining with Erythrosin B, as a toxicity indicator, also rose with higher drug concentrations, but a large proportion of lymphocytes remained unstained even at the maximum drug dose. Stimulation with PHA partially nullified the suppression caused by HN2 but did not influence the effects of L-PAM. Exposure to PWM rendered the in vitro HN2 innocuous but L-PAM remained cytotoxic. Simultaneous lectin-induced blastogenesis proceeded unaltered. Finally, comparisons between 72 and 4 hr drug exposures imply that interference with intracellular synthesis occurs promptly, continues after drug removal, and is related quantitatively to drug concentration rather than to duration of contact.


The measurement of erythrocyte deformability using micropore membranes. A sensitive technique with clinical applications.

This article describes a positive-pressure filtration technique using low pore-density, 3 microns pore-diameter polycarbonate membranes employed to evaluate erythrocyte deformability in a clinically oriented hematology laboratory. Mean erythrocyte resistance to filtration was expressed by a numerical index which takes into account both the initial resistance of dilute red cell suspensions to passage across the membrane and the relative pressure rise observed after filtration of 30 ml of the same suspension (3 . 10(8) cells). The resistance index of 99 blood samples obtained from 88 healthy adult volunteers ranged between 1.4 and 2.9, with normal Gaussian distribution and mean of 2.04. Values obtained on similarly prepared samples from 20 patients with various hemolytic anemias always fell outside this range, indicating a reduced deformability in every case. The existence of a strong positive correlation was found between the resistance index and the degree of reticulocytosis in these patients. This method appears more sensitive than previously described filtration techniques in detecting the presence of small numbers of poorly deformable erythrocytes in vivo, while being more practical and statistically more significant than the micropipette elastimetry technique. Our results, however, raise a new question concerning the role of reticulocytes in the evaluation of red cell deformability on blood samples from patients with hemolytic anemia.


Alterations of intestinal and renal functions in rats after intraperitoneal injections of lead acetate.

When lead acetate was administered intraperitoneally to young rats at a dose of 20 mg/kg (five times a week for 6 weeks), their growth rate was retarded when compared with controls injected with sodium acetate. Only a small amount of the heavy metal reached the circulation and exerted limited effects on typical target organs. However, large, electron-dense inclusion bodies were found in the abdominal cavity. The in vivo intestinal absorption of glucose was reduced. When perfused at 40 mM concentration, the experimental animals had a mean absorption rate of 152.1 nmol/min . cm vs. 230.6 in the controls (p less than 0.01). Also, sodium and potassium transport was reduced. No effects were observed on amino acid transport and (Na+-K+)-ATPase. Mg++-ATPase, glucose-6-phosphatase, fructose-1, 6-diphosphatase, pyruvate kinase, succinic dehydrogenase, and tryptophan hydroxylase in the small intestinal mucosa and the kidney were unaltered. Renal alkaline phosphatase was decreased. These studies confirm the greater susceptibility of some active transport mechanisms of the small intestinal mucosa to lead toxicity, compared to those of the kidney.


Reversal of skeletal resistance to parathyroid hormone in uremia by vitamin D metabolites: evidence for the requirement of 1,25(OH)2D3 and 24,25(OH)2D3.

This study evaluates the role of vitamin D metabolites in the genesis of the skeletal resistance to the calcemic action of PTH in uremia. The changes in serum calcium after infusion of 2 U of PTE per kilogram per hour for 8 hr were evaluated in thyroparathyroidectomized dogs before and after 1 and 3 days of acute uremia produced by bilateral nephrectomy. The animals received vitamin D metabolites during the 3 days of uremia. Supplementation of 0.68 microgram/day 1,25(OH)2D3 and 24R,25(OH)2D3 restored the calcemic response to PTE to normal. This is in contrast to only partial correction of the response to PTE by 1,25(OH)2D3 alone. Administration of 1.36 microgram/day 24R,25(OH)2D3 did not improve the calcemic response to PTE. The results indicate that (1) both 1,25(OH)2D3 and 24R,25(OH)2D3 are necessary for the complete reversal of the impaired calcemic response to PTE, (2) this effect is not due to the increase in the amount of the dihydroxylated compounds of vitamin D, since equivalent amounts of these compounds in the form of 24R,25(OH)2D3 alone had no effect, and (3) the better effect of the combination of 1,25(OH)2D3 and 24R,25(OH)2D3 is most probably due to an interaction between these two metabolites of vitamin D permitting an intact calcemic action of PTH.


Phenolsulphotransferase: enzyme activity and endogenous inhibitors in the human erythrocyte.

PST (E.C. 2.8.2.1) plays an important role in the metabolism of many drugs, catecholamine metabolites, and catecholamines. PST activity was detected in each of 178 human RBC lysates. When MHPG was used as a substrate, the activity ranged from 28 to 1385 U/ml of RBC, with an average value of 217.7 +/- 13.1 (mean +/- S.E.M.). However, there was not a direct relationship between quantity of RBC lysate and enzyme activity, an observation that raised the possibility of endogenous enzyme inhibitors. Therefore human RBC PST was partially purified (415-fold) to use in the study of tissue enzyme inhibitors. The pH optimum of the partially purified enzyme was 7.5, with an apparent Km value for [35S]PAPS of 0.46 microM and an apparent Km value for MHPG of 260 microM. When the partially purified enzyme was added to each of 20 human RBC lysates, its activity was inhibited an average of 91% +/- 0.6 (mean +/- S.E.M.). Endogenous inhibitors were also present in homogenates of human renal cortex and in homogenates of a variety of rat tissues. RBC lysates contained at least two PST inhibitors: a low-molecular-weight inhibitor (less than 2000) that was heat-, acid-, and base-stable, dialyzable, and resistant to digestion by chymotrypsin; and a high-molecular-weight inhibitor (greater than 65,000) that was heat-labile and nondialyzable. Whether the RBC enzyme activity may serve as an indicator of PST activity in less accessible tissues remains to be determined. However, the first step toward testing this hypothesis will require the accurate measurement of PST activity in tissue preparations by a procedure that removes or inactivates enzyme inhibitors.


A direct radioimmunoassay of rat urinary kallikrein and comparison with other measures of urinary kallikrein activity.

A highly sensitive radioimmunoassay for rat urinary kallikrein (minimal detectable amount, 40 pg/tube) has been developed. The assay uses a sheep antibody (Keq = 3.25 X 10(10)M-1) against purified Sprague-Dawley rat urinary kallikrein in a final dilution of 1 : 1,200,000. The assay incorporates a convenient and inexpensive PEG technique for separation of free from bound antigen. Parallel standard curves with rat urine or kidney homogenates were obtained. No cross-reactivity with human or dog urine samples or purified human urinary kallikrein was seen. Correlations among this assay, an esterolytic method, and a kininogenase radioimmunoassay for kallikrein were highly significant, with only the esterolytic assay demonstrating any significant nonspecificity. The radioimmunoassay can detect changes in urinary kallikrein levels produced by a maneuver known to alter urinary kallikrein excretion.


Postfeeding radioimmunoassay artefact in heparinized pig plasma: studies with intestinal calcium-binding protein.

Samples of pig blood were taken in relation to feeding and assayed for intestinal CaBP by radioimmunoassay. When heparinized plasma was assayed by a double-antibody technique, significant postprandial increases of plasma immunoreactivity between twofold and 10-fold were noted. These apparent feeding responses were seen only with heparinized plasma and not with EDTA plasma, ACD plasma, or serum. Nor were such responses seen when heparinized plasma was assayed with talc or charcoal methods for phase seperation. The height of the artefactual response in immunoreactivity following feeding was related to the amount of carrier serum added during the incubation with second antibody and with the duration of this incubation. The artefact was seen in the presence of 0.01M EDTA. These results demonstrate a striking postfeeding radioimmunoassay artefact localized to the second-antibody precipitation step. The artefact can easily be avoided by several methodological changes. Such an artefact could conceivably affect other double-antibody radioimmunoassays of hormones or other substances. Caution is advised when double-antibody radioimmunoassays are used to assay samples taken in relation to feeding.


Abnormalities of hepatic mitochondrial urea-cycle enzyme activities and hepatic ultrastructure in acute fatty liver of pregnancy.

Two patients presenting with acute fatty liver of pregnancy were studied. Because of similarities between acute fatty liver of pregnancy and Reye's syndrome, we investigated hepatic ultrastructure, urea-cycle enzyme activities, and plasma amino acids. Initial liver biopsies obtained 12 and 21 days after the onset of illness demonstrated microvesicular fat deposition and mitochondrial ultrastructural changes, including pleomorphism and abundant crystalline inclusions. In both biopsies, activity of the mitochondrial urea-cycle enzyme OTC was markedly below normal limits. Activity of the other mitochondrial urea-cycle enzyme, CPS, was low in one patient. Abnormalities of these enzymes persisted in second biopsies obtained at 9 and 28 weeks, respectively. By 44 weeks all urea-cycle enzyme activities had returned to normal in one patient. However, in the other patient OTC activity was still reduced at 52 weeks, although it had doubled in comparison to previous biopsies. Morphological changes of the mitochondria generally improved in parallel with the urea-cycle enzymes. Plasma amino acids, obtained at the time of the initial biopsies, demonstrated a generalized hypoaminoacidemia with the exception of glutamate. Serial observations in patients with this rare disease indicate that there are similarities with Reye's syndrome, in particular, reduced activity of the mitochondrial urea-cycle enzymes. But there are important differences. (1) Enzymatic and ultrastructural abnormalities of mitochondria persist for a longer period of time than in Reye's syndrome. (2) Mitochondrial ultrastructure is different. (3) Plasma amino acid profiles are different.


Metabolic fate of exogenous delta-aminolevulinic acid in Dubin-Johnson syndrome.

The underlying mechanism of abnormal urinary distribution of CP isomers in DJS is unknown. We administered ALA to DJS patients and carriers as well as to normal controls, and urinary and biliary porphyrins and plasma bilirubin were studied. In sharp contrast to the remarkable increase in urinary CP-III excretion in normal controls (2234 nmol/gm creatinine during the first 2 hr) after ALA, very small increase was observed in DJS patients (19 nmol). In DJS carriers the increase took intermediate values (1122 nmol). The increments in urinary CP-I were smallest in DJS patients, and the peak of its increase was delayed. These data are compatible with the hypothesis that a carrier-mediated mechanism in transporting CP-gen isomers I and III from the liver cells to the plasma may be anomalous in DJS hepatocytes and that the increased urinary CP-I characteristic of DJS may be the result of a disturbance in the uptake process of CP-gen I, derived mainly from the erythropoietic tissues, by DJS liver cells. Although the biliary percent of CP-I in controls decreased after ALA, it remained unchanged in DJS, suggesting the existence of a bile canalicular barrier against CP-gen-III in DJS. The elevated biliary porphyrins and plasma bilirubin after ALA in DJS patients favor an idea that there may be no major enzymatic derangements in the metabolic sequences from ALA to bilirubin. The increased excretion of PP in DJS bile after ALA remained to be explained.


Vascular compartmentalization of plasma norepinephrine in normal man: the relationships between venous and arterial norepinephrine concentration and the urinary excretion of norepinephrine.

To examine whether the concentration of NE in human plasma is dependent on the vascular source of the sample and to examine the contribution of the kidney to urinary NE, 14 normal men were studied. Plasma samples were obtained from a superficial forearm vein, and radial artery and urine samples were obtained during 1 hr of recumbency and 1 hr of upright posture. The Vne was greater than Ane during both recumbency and upright posture in black males. Such differences were not seen in age-matched white subjects. Stimulation of the sympathetic nervous system by upright posture increased both Vne and Ane in all subjects. NE concentrations in simultaneously obtained arterial and venous samples were different during the time of cardiovascular adjustments to upright posture. The urinary Xne increased after standing. Endogenous CCr decreased, whereas apparent NE clearance, calculated from the Ane, increased after standing, suggesting that a major portion of the augmented urinary Xne induced by upright posture was from an intrarenal source. We conclude that the concentration of NE in human blood is related to the specific vascular bed from which the sample is obtained, and that urinary NE is not solely derived from plasma by glomerular filtration but also arises from an unidentified renal source.


Specific and quantitative method for estimation of platelet adhesion to fibrillar collagen.

A quantitative method (Sepharose test) was devised to measure the adhesion of blood platelets to fibrillar collagen. [14C]5HT-labeled platelets were isolated from plasma, resuspended in EDTA buffer, and incubated with buffer (control) or with fibrillar collagen for 150 sec at 33 degrees C. The mixtures were then filtered through Sepharose 2B columns. In controls the platelets were rapidly eluted, and this was confirmed after 51Cr labeling. [C]5HT was recovered in two stages: 60% with the platelets and 40% retarded, as free 5HT. After incubation with fibrillar collagen (50 micrograms), platelets were retained with the fibrils on the top of the column, and only free [14C]5HT (released from the platelets) was eluted. The percentage of adhesion depended on the number of platelets, the amount of collagen, its degree of polymerization, and the time of incubation at 33 degrees C. [14C]5HT release was markedly diminished when both incubation and filtration were performed at low temperature. ASA, used either in vitro or in vivo in rabbits, did not change the percentage of adhesion but significantly diminished the total amount of [14C]5HT eluted. This method offers a quantitative and reproducible system for the differentiation of adhesion and release, independent of platelet aggregation.


Class- and subclass-specific antibody response to hemocyanin in nonmalignant paraproteinemia.

IgM, IgG, and IgA class-specific, as well as IgG subclass-specific antibody titers against the primary immunogen HPH were measured with ELISA in 19 patients with nonmalignant paraproteinemia (eight with IgG1, two with IgG2, two with IgG4, four with IgM, and three with IgA) and in a simultaneously studied age- and sex-matched control group. After primary immunization only IgM and IgA anti-HPH titers were significantly lower in the patient group. Four patients with relatively high IgG or IgA serum paraprotein levels did not produce antibodies in some Ig classes or IgG subclasses, whereas all other patients and all controls developed antibody titers in all classes and IgG subclasses. Low or absent antibody titers did not occur preferentially in the Ig (sub)classes to which the paraproteins belonged. After secondary immunization the patients could not increase or maintain their antibody titers as well as the controls, and this was most clear in the IgM and IgA antibody class. A direct correlation between polyclonal serum IgM levels and IgM anti-HPH titers was present in the patients. Such a correlation was absent for IgA in the patients and for all classes in the controls. It is concluded that humoral immunosuppression as measured with a newly encountered antigen in patients with nonmalignant paraproteinemia is most clearly expressed in the IgM and IgA antibody class and that the paraprotein (sub)class is not preferentially involved.


The antithrombotic effects of warfarin and heparin following infusions of tissue thromboplastin in rabbits: clinical implications.

An animal model for the production of stasis thrombi was employed to obtain the data reported in this study. Rabbits treated with warfarin (1.5 mg/kg/day) exhibited a maximal increase in prothrombin time and decreases in factor VII, factor X, and prothrombin within 48 hr with no additional changes occurring after 10 days of drug administration. In contrast, Xa inhibitory activity was unchanged after 48 hr of warfarin treatment but was significantly increased by the tenth day. When thrombosis was induced by infusions of 60 micrograms of tissue thromboplastin, the warfarin regimen produced an antithrombotic effect by the sixth hour, which increased to significance by day 2 and was further significantly increased by day 10. These three stages correspond to the initial depletion of the vitamin K-dependent clotting factors, the maximal depletion of these proteins, and the maximal increase in Xa inhibitory activity, respectively. Thus these experiments separate the antithrombotic potential of warfarin into two components: an early effect related to the decrease in factor VII and a delayed augmentation of Xa inhibitory acticity. Intravenous heparin alone (5 U/kg) did not protect against infusions of 60 micrograms of tissue thromboplastin but did provide an antithrombotic effect against 45 micrograms of the same infusate. Higher doses of heparin, however, did protect against infusion of 60 micrograms of tissue thromboplastin. After 48 hr of warfarin treatment, 5 U/kg heparin increased protection against 60 micrograms of tissue thromboplastin to a degree equivalent to that provided after 10 days of warfarin therapy alone.


Effects of cigarette smoke on elastase secretion by murine macrophages.

Mice were chronically exposed to cigarette smoke for various time periods up to 4 weeks. As a consequence of the exposure, there was an increase in the number of alveolar macrophages obtained from the lungs of these mice. Light microscopic examination of cultured cells revealed increased numbers of highly pleomorphic cells filled with pigmented residues of cigarette smoke. These cells were more mitotically active, with a five fold increase in the number of alveolar colony-forming cells compared to the controls. When macrophages derived from mice exposed to cigarette smoke were cultured at high density in the absence of serum, they secreted significantly greater amounts of elastase than did the same number of control macrophages. At concentrations as low as 0.50 micrograms/ml, cycloheximide reversibly inhibited elastase secretion from both the control and experimental cultures. The effects of cigarette smoke inhalation on elastase secretion by alveolar macrophages do not appear to be a direct effect of cigarette smoke on these cells. Exposure of normal mouse macrophages in vitro to pulses of aqueous extracts of cigarette smoke, while significantly increasing secretion of elastase by peritoneal exudative macrophages, did not augment that of resident or exudative alveolar macrophages. These results suggest that the increased elastase secretion observed with the use of cultured macrophages derived from mice exposed to cigarette smoke is the result of either indirect activation of resident macrophages or the recruitment of a highly activated exudative population into the lungs of the exposed animals.


Relationship between packed cell volume, platelets, and platelet survival in red blood cell-hypertransfused mice.

In this study we have measured platelet and megakaryocyte concentration, blood volume, and platelet survival of mice after RBC hypertransfusion to PCVs of 62% to 90%. The platelet concentration of mice with PCVs up to 75% was decreased by up to one half. At higher PCVs a more severe thrombocytopenia developed, with platelet concentrations decreased to less than 10% of baseline in approximately one half of the mice. Blood volumes of the hypertransfused mice were increased up to twofold. Megakaryocyte concentrations were normal or increased. Platelet survival in mice with PCVs less than 75% was normal but was sharply decreased for mice with higher PCVs. The decrease in platelet concentration at moderately elevated PCVs may be explained by hemodilution in the larger blood volume. However, hemodilution alone cannot explain the severe thrombocytopenia at higher PCVs. The presence of decreased platelet survival with normal or increased megakaryocyte concentrations in this latter group suggests that the severe thrombocytopenia is the result of more rapid platelet destruction. In summary, elevation of the PCV by RBC hypertransfusion produces thrombocytopenia. The severity of the thrombocytopenia and the mechanisms involved in producing it change abruptly when the PCV exceeds 75%. These findings should be considered in interpretations of the influence of RBC hypertransfusion on hematopoiesis and in clinical and experimental studies of thrombopoiesis in polycythemic subjects.


Metabolic investigations in Menière's disease. Preliminary findings.

The aetiology of Menière's disease is unknown but in recent years many theories have been advanced to explain the observed pathological changes. These include abnormal metabolic states, allergy and personality type. In an attempt to throw more light on this and to confirm or refute the earlier work we studied twenty-seven (fifteen male:twelve female) patients with Menière's disease who conformed to the criteria set out by the Committee of Hearing and Equilibration of the American Academy of Ophthalmology and Otolaryngology (Alford, 1972). In this series the incidence of abnormal metabolic states was no higher than that of a comparable group in the general population. There was no significant difference in response to pin prick skin tests compared with a control group. Klockhoff and Lindblom's (1966) glycerol dehydration test was applied to twenty-one patients. The response to this test was measured by changes in the osmolality of the serum, the pure tone threshold of hearing and the maximum speech discrimination score. Continuous transtympanic electrocochleographic recordings during glycerol dehydration were carried out and in 10 patients there was a definite decrease in the negative summating potential. An electrophysiological explanation for this has been put forward and the possible use of this measurement in the diagnosis and management of Menière's disease has been discussed. The intercorrelation between these measures and their predictive value will become apparent in the future.


Obliterative otitis media.

The clinical history, pathology and results of tympanoplasty in 12 patients with obliterative otitis are described. The condition is characterized by an intact, not retracted, thick drum and a middle ear totally filled with fibrous tissue and small cholesterol granulomas. The tube is anatomically obstructed in most cases. The results are poor and it is concluded that tympanoplasty is not indicated in this disease.


Amniotic graft in the management of severe epistaxis due to hereditary haemorrhagic telangiectasia.

In selected cases of Hereditary Haemorrhagic Telangiectesia with severe, life-threatening epistaxis, a new surgical procedure has been performed. It consists of a thorough, near total excision of the diseased nasal mucosa and its replacement by an amniotic memebrane graft. The surgical details dealing with preparation of the amniotic graft are described. Surgery has been performed by this technique in six cases. During 9 to 30 min months of follow-up, no nasal bleeding has occurred and the haemoglobin level has remained normal. The aminiotic membrane has served as an adequate grafting material for the lining of the nasal chambers.


Changes in the lower respiratory epithelia induced by oestrogen intake. An experimental histopathological study.

Fifty-eight male and non-pregnant female guinea pigs with an average weight of 400 gm were used in this work, ten animals as a control group, the remaineder receiving oestrogen in the form of ethanyl oestradiol in a dose of 10 microgram/animal/day. Histopathological studies were carried out after periods of one, two, three, four and eight weeks, and three, six and twelve months respectively. The respiratory mucosa, at the different levels mentioned, showed definite changes. The surface epithelium showed metaplastic changes with mitotic figures, until complete and definite stratifications were reached. The cilia decreased and then disappeared completely, while the mucus-secreting goblet cells showed an initial augmentation in number and increased activity, followed by a gradual decrease in their number, until total disappearance occurred at the stage of stratification in the surface epithelium.


Pituitary calcospherites: an aid to highly selective hypophysectomy.

A case of a prolactin-secreting pituitary adenoma containing calcospherites is reported. The difficulties in achieving a highly selective microdissection of large pituitary tumours are discussed and the value of calcification within a prolactinoma emphasized.


Cervical ranula.

Ranulas are mucous extravasation cysts, and usually originate from the sublingual salivary gland. They may occasionally infiltrate the tissue planes of the neck and present as a cervical tumour. The literature is reviewed, and four personal cases of cervical ranula presented. Successful treatment may be achieved in the vast majority of cases by removal of the sublingual salivary gland.


Bone mineral content in osteogenesis imperfecta tarda and in otosclerosis.

In 22 patients with osteogenesis imperfecta and in 63 patients with otosclerosis the bone mineral content in peripheral bones was determined by photon absorptiometry. The bone mineral content proved significantly reduced in patients with osteogenesis imperfecta as compared with normals and with patients with otosclerosis. In the latter patients the bone mineral content was normal. These findings support the assumption that stapedial fixation in otosclerosis and in osteogenesis imperfecta is of different aetiology.


Histopathological changes in experimental free thyroid transplants.

Free thyroid autotransplants into new receptor sites have been tried in 28 dogs, by two different techniques. Good but irregular histopathological survival of thyroid acini has been found after free autotransplantation of bisected and everted thyroid lobes into the external genitalia of dogs. The results have been very encouraging and the functional assessment of these implants is essential; such work is already in progress in our laboratory. Our findings and their significance have been discussed.


Malignant oncocytoma of the nasal cavity.

Malignant oncocytoma of the major salivary glands is uncommon. Those of the endocrine, minor salivary and mucous glands are certainly rare. A case of a slowly-growing, low-grade malignant oncocytoma of the nasal cavity in a 50-year-old male, with no lymph node or distant metastases or local invasion of vital adjacent structures, and treated with combined radiotherapy and radical surgery, has been presented. The literature has been briefly reviewed, and the histological types; the electro-microscopic, histochemical and clinical pictures; and the outlines of treatment of oncocytomas have been discussed.


Parotid gland calculus. Report of a case.

A patient, was admitted with multiple calculi in the left parotid gland. Plain radiography and sialography confirmed the diagnosis. A partial parotidectomy was done and the calculi were removed.


A rare 'parotid tumour'.

A ganglion of the temporo-mandibular joint presenting as a tumour of the deep lobe of the parotid gland is described. This appears to be the first description of such a case in the literature. Simple excision of the lesion after mobilization of the superficial lobe was performed. This form of management gives a very good cosmetic result for the occasional simple cyst of the deep parotid lobe. The ganglion reported in this paper presented as a parotid tumour. It was managed by mobilization of the superficial part of the gland from the facial nerve until the nature of the lesion was determined. The fact that the superficial lobe of the gland was not excised has caused no ill effect to the patient but has given a better cosmetic result by preventing the usual pre-tragal depression. Conservative surgery has previously been suggested in similar cases (Brennan et al., 1970).


Stochastic models for X chromosome inactivation.

A multivariate Gaussian model for mammalian development is presented with the associated biological and mathematical assumptions. Many biological investigations use the female mammal X chromosome to test hypotheses and to estimate parameters of the developmental system. In particular, Lyon's (1961) hypotheses are used as a basis of the mathematical model. Experimental mouse data and three sets of human experimental data are analyzed using the hypothesized Gaussian model. The estimated biological parameters are consistent with some current biological theories.


Spatial patterns for an interaction-diffusion equation in morphogenesis.

A certain interaction-diffusion equation occurring in morphogenesis is considered. This equation is proposed by Gierer and Meinhardt, which is introduced by Child's gradient theory and Turing's idea about diffusion driven instability. It is shown that slightly asymmetric gradients in the tissue produce stable striking patterns depending on its asymmetry, starting from uniform distribution of morphogens. The tool is the perturbed bifurcation theory. Moreover, from a mathematical point of view, the global existence of steady state solutions with respect to some parameters is discussed.


A simple model for phase locking of biological oscillators.

A mathematical model is presented for phase locking of a biological oscillator to a sinusoidal stimulus. Analytical, numerical and topological considerations are used to discuss the patterns of phase locking as a function of amplitude of the sinusoidal stimulus and the relative frequencies of the osillator and the sinusoidal stimulus. The sorts of experimental data which are needed to make comparisons between theory and experiment are discussed.


Representation of Nonepistatic selection models and analysis of multilocus Hardy-Weinberg Equilibrium configurations.

The paper develops conditions for the existence and the stability of central equilibria emanating from selection recombination interaction with generalized nonepistatic selection forms operating in multilocus multiallele systems. The selection structure admits a natural representation as simple sums of Kronecker products based on a common set of marginal selection components. A flexible parametrization of the recombination process is introduced leading to a canonical derivation of the transformation equations connecting gamete frequency states over successive generations. Conditions for the existence and stability of multilocus Hardy-Weinberg (H.W.) type equilibria are elaborated for the classical nonepistatic models (multiplicative and additive viability effects across loci) as well as for generalized nonepistatic selection expressions. It is established that the range of recombination distributions maintaining a stable H.W. polymorphic equilibrium is confined to loose linkage in the pure multiplicative case, but is not restricted in the additive model. In the bisexual case we ascertain for the generalized nonepistatic model the stability conditions of a common H.W polymorphism.


Some analytical results about a simple reaction-diffusion system for morphogenesis.

The reaction-diffusion system considered involves only one nonlinear term and is a gradient system. In a bifurcation analysis for the equilibrium states, the global existence of infinitely many solution branches can be shown by the method of Ljusternik-Schnirelmann. Their stability is studied. Using a Ljapunov functional it can be shown that the solutions of the time-dependent system converge to the equilibrium states.


A simple model of delay, block and one way conduction in Purkinje fibers.

A simple qualitative model of the cardiac Purkinje fiber is introduced for the purpose of numerical simulation of experiments on conduction of the cardiac impulse. Well known approximation techniques are used to illustrate the behavior of the model membrane in the cases of space clamp and propagation of traveling pulses in a uniform infinite fiber. The results of the numerical simulations are then presented, and shown to be comparable to experiment.


A new mathematical approach for solving carrier-facilitated steady-state diffusion problems.

A new mathematical treatment is presented which simplifies the solution of carrier-diffusion problems. The method is generally applicable and is illustrated and tested for a specific, commonly occurring situation: facilitated diffusion of a single substrate through flat layers. Results predicted for total substrate flux are in excellent agreement with control computer calculations. The method also can be used to obtain concentration profiles for each species; here the results are good only if conditions at the boundaries are predicted correctly.


On the kinetics of lead in the human body.

A compartment model is derived for the kinetics of lead in the human body. The parameters are estimated from field data. Numerical solutions of the equations are obtained. They are used to discuss recent theories on lead intake, in particular from the atmosphere.


Limitations of exercise testing in critical left coronary artery disease.

Exercise testing was evaluated in 51 patients with critical left coronary artery disease (LCA) documented by coronary arteriography within two weeks of their bicycle ergometer (26 patients) or treadmill (25 patients) electrocardiographic study. Adequate tests, as defined by the patient having reached 85% of predicted maximum heart rate, were achieved in only 16 patients on the ergometer (62%) and in 21 (84%) on the treadmill. Nevertheless mean maximum double product (220 vs 232) and mean exercise time (4.6 min vs 5.0 min.) were similar (p:NS). The sensitivity for ergometry and treadmill testing was 75 and 62% respectively. If however we include those negative studies in which for various reasons patients were unable to achieve 85% of their predicted maximal heart rate (i.e., inadequate studies), sensitivity was only 46 and 52% respectively. Thus a sizable group of patients with critical LCA disease cannot adequately perform exercise tests especially on the ergometer; and over half of all such patients studied will be found for one reason or another to respond negatively, regardless of exercise protocol.