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Biomedical subjects

H Gardner

Publications and source records attributed to H Gardner.

At least 37 records · Page 2Linked to original sources

Are your minimal pairs too neat? The dangers of phonemicisation in phonology therapy.

Using Conversation Analysis (CA) to look at the interactional dynamics of therapy repair sequences, this paper shows exactly what happens for children when idealised misrepresentations of their phonology are used in therapy. The primary video extract involves a 4-year-old phonologically disordered boy and his therapist. It is not new to warn of the dangers of overlooking any subtle phonetic distinctions that the phonologically disordered child may have but this paper adds something new to the debate. The child's interpretation of the adult's prior turn in the sequence is made explicit and the likelihood of the child producing phonetic revision following an error is seen to be affected by the way the therapist chooses to initiate repair. This is especially true where a 'redoing' of the error is incorporated into such an initiation, when the child's phonetic output is 'tidied up' so that it fits in with the neat minimal pair which forms part of the therapy programme. This is one factor that can be seen to militate against appropriate phonetic repair by the child, especially when used in certain turn structures that are routinely associated with lexical rather than phonetic matters. When the adult 'redoing' more accurately reflects the child's output phonetic revision is more likely to occur. Implications for assessment and therapy are drawn from this evidence, with accurate phonological assessment and continuing interactional error analysis being recommended.

Child, Preschool↗

Zfx mutation results in small animal size and reduced germ cell number in male and female mice.

The zinc-finger proteins ZFX and ZFY, encoded by genes on the mammalian X and Y chromosomes, have been speculated to function in sex differentiation, spermatogenesis, and Turner syndrome. We derived Zfx mutant mice by targeted mutagenesis. Mutant mice (both males and females) were smaller, less viable, and had fewer germ cells than wild-type mice, features also found in human females with an XO karyotype (Turner syndrome). Mutant XY animals were fully masculinized, with testes and male genitalia, and were fertile, but sperm counts were reduced by one half. Homozygous mutant XX animals were fully feminized, with ovaries and female genitalia, but showed a shortage of oocytes resulting in diminished fertility and shortened reproductive lifespan, as in premature ovarian failure in humans. The number of primordial germ cells was reduced in both XX and XY mutant animals at embryonic day 11.5, prior to gonadal sex differentiation. Zfx mutant animals exhibited a growth deficit evident at embryonic day 12.5, which persisted throughout postnatal life and was not complemented by the Zfy genes. These phenotypes provide the first direct evidence for a role of Zfx in growth and reproductive development.

Animals↗

Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis.

THE D-type cyclins (D1, D2 and D3) are critical governors of the cell-cycle clock apparatus during the G1 phase of the mammalian cell cycle. These three D-type cyclins are expressed in overlapping, apparently redundant fashion in the proliferating tissues. To investigate why mammalian cells need three distinct D-type cyclins, we have generated mice bearing a disrupted cyclin D2 gene by using gene targeting in embryonic stem cells. Cyclin D2-deficient females are sterile owing to the inability of ovarian granulosa cells to proliferate normally in response to follicle-stimulating hormone (FSH), whereas mutant males display hypoplastic testes. In ovarian granulosa cells, cyclin D2 is specifically induced by FSH via a cyclic-AMP-dependent pathway, indicating that expression of the various D-type cyclins is under control of distinct intracellular signalling pathways. The hypoplasia seen in cyclin D2(-/-) ovaries and testes prompted us to examine human cancers deriving from corresponding tissues. We find that some human ovarian and testicular tumours contain high levels of cyclin D2 messenger RNA.

Animals↗

Deletion of integrin alpha 1 by homologous recombination permits normal murine development but gives rise to a specific deficit in cell adhesion.

Integrin alpha 1 is a receptor for laminin and collagen which is expressed widely and dynamically in embryogenesis and has been implicated in various developmental processes including establishment of the placenta and formation of the central and peripheral nervous system. In the adult it is the sole collagen receptor in smooth muscle and liver and is thought to be important for the stability of these tissues. We have generated a null allele of the alpha 1 gene in the germline of mice by homologous recombination in embryonic stem cells. Mice homozygous for the mutation are viable and fertile and have no overt phenotype, demonstrating that the molecule is not required for development. Embryonic fibroblasts derived from mutant animals are unable to spread on or migrate into substrata of collagen IV and are deficient in spreading on and migrating into laminin. Further in vitro analysis of cell spreading and migration suggests that alpha 1 beta 1 is not required for binding to collagen I and implicates a third receptor, possibly integrin alpha 3 beta 1, in collagen I binding.

Alleles↗

Cyclin D1 provides a link between development and oncogenesis in the retina and breast.

Mice lacking cyclin D1 have been generated by gene targeting in embryonic stem cells. Cyclin D1-deficient animals develop to term but show reduced body size, reduced viability, and symptoms of neurological impairment. Their retinas display a striking reduction in cell number due to proliferative failure during embryonic development. In situ hybridization studies of normal mouse embryos revealed an extremely high level of cyclin D1 in the retina, suggesting a special dependence of this tissue on cyclin D1. In adult mutant females, the breast epithelial compartment fails to undergo the massive proliferative changes associated with pregnancy despite normal levels of ovarian steroid hormones. Thus, steroid-induced proliferation of mammary epithelium during pregnancy may be driven through cyclin D1.

Animals↗

The effect of testicular nongerm cell tumors on local spermatogenesis.

OBJECTIVE: To assess ipsilateral spermatogenesis in men with malignant and benign nongerm cell tumors of the testis. DESIGN, PATIENTS: Histologic review of radical orchiectomy specimens performed for 20 men with malignant nongerm cell tumors and 15 with benign testicular lesions, including five Leydig cell tumors with benign clinical features. MAIN OUTCOME MEASURES: Degree of spermatogenesis was determined on a 1 to 10 scale, with 10 representing mature sperm within a seminiferous tubule. For each patient "near" and "far" scores were determined by obtaining the mean score of 50 tubules adjacent (< 3 mm) to the tumor and 50 tubules distant (> 3 mm) from the tumor, respectively. RESULTS: Total, near, and far scores were all lower for malignant tumors than for benign lesions. Scores for Leydig cell tumors were similar to benign lesions. Malignant tumors demonstrated a gradient effect, with greatest impairment of spermatogenesis occurring adjacent to tumor. In contrast, a distinction between near and far scores was not observed for benign lesions or Leydig cell tumors. CONCLUSIONS: Malignant nongerm cell tumors of the testis were associated with significant impairment of ipsilateral spermatogenesis, particularly in areas adjacent to tumor. These findings are similar to those observed for testicular germ cell tumors, suggesting a generalized negative influence on ipsilateral spermatogenesis by malignant tumors.

Adult↗

The relationship between early giftedness and later achievement.

Although some prodigies grow up to become creative masters as adults, there is no necessary link between early signs of talent and ultimate achievement. Four possible relations between early and late achievement are explored here. The analysis draws upon two lines of evidence: (1) a new theoretical approach that posits the existence of multiple intelligences and examines the important role of the domains and fields in which individuals work; (2) case studies of seven highly creative individuals who lived at the turn of the century. A strong contrast emerges between the adult creator, who must discover the domain in which he or she can excel and the child prodigy, who must invent a creative personality.

Achievement↗

Story processing in right-hemisphere brain-damaged patients.

The understanding of stories requires sensitivity to structural aspects of narrative, the emotional content conveyed by the narrative, and the interaction between structural and emotional facets of the story. Right-hemisphere-damaged (RHD) and normal control subjects performed a number of different analytic tasks which probed their competence at story comprehension. Results revealed that RHD subjects perform at a level comparable to that of normal controls with stories that follow a canonical form and that they show few difficulties with structural aspects of narrative. Contrary to expectation, they are strongly influenced by the "interest" level of a story and by other factors that tap emotional sensitivity. Findings are discussed in terms of the processing and arousal mechanisms which may give rise to the observed pattern of difficulties in RHD patients.

Aged↗

Sensitivity to conversational deviance in right-hemisphere-damaged patients.

To participate meaningfully in conversation, speakers must be sensitive to statements which advance and those which block the direction of a discourse. The effect of right-hemisphere damage (RHD) on sensitivity to conversational advancers and blockers was investigated by asking subjects to interpret normal conversations and conversations which were blocked by violations of Gricean maxims: specifically, tangential and redundant statements. Results indicate that RHD patients function normally in canonical, directed conversation. However, they have difficulty interpreting and judging the effect of blocking statements, particularly with regard to tangentiality. The results are discussed in terms of a mental model of directed conversation which incorporates both structural and affective components.

Brain↗

Influence of testicular carcinoma on ipsilateral spermatogenesis.

A histological review of radical orchiectomy specimens was performed to assess the impact of testicular cancer on spermatogenesis. Slides from 28 patients with testicular cancer were available for review, consisting of 14 pure seminomas, 12 embryonal carcinomas and 2 mixed tumors. For each specimen tubules adjacent (less than 3 mm.) to the tumor and distant (more than 3 mm.) from the tumor were evaluated. This study indicates that marked impairment of ipsilateral spermatogenesis is associated with testicular carcinoma, particularly in the vicinity of the tumor. The quality of distant spermatogenesis appears to be influenced by tumor type and not by elevation of known serum tumor markers, such as human chorionic gonadotropin and alpha-fetoprotein, nor by the presence of carcinoma in situ.

Adult↗

Mass sociogenic illness in a youth center.

In July, 1989, 63 (42%) of 150 children ages 4-14 years attending an outreach program at a youth center in Florida, but no employees, developed acute and rapidly resolving upper gastrointestinal symptoms 2 to 40 minutes after a prepackaged lunch. All ill children were sent to 3 local hospital emergency departments for evaluation. However, clinical evaluation was normal for all. Of 102 children who ate any prepackaged foods, 48 (47%) became ill compared to 1/19 (5%) for children who did not eat (rate ratio [RR] = 8.9; 95% confidence interval [CI]: 1.3-60.9). No employees ate any of the food items served. Consumption of sandwiches was associated with a moderate increased risk of illness (RR = 1.7, 95% CI: 1.0-2.9). The attack rate did not differ by age, but was greater for girls (39/56, 70%) than for boys (9/46, 20%; [RR = 3.6, 95% CI: 1.9-6.6]). Over 3,000 similar prepackaged meals from the same caterer were served in the same area of Florida that day. An inquiry in the area documented absence of similar symptoms elsewhere. Unopened meal samples tested negative for pesticide residues, heavy metals, staphylococcal toxin, or Bacillus cereus. We diagnosed the outbreak as mass sociogenic illness. Complaints of a bad tasting sandwich by the index case and possible staff anxiety about food poisoning may have contributed to the development of the outbreak.

Child↗

DNA alterations and enzyme activities in Japanese medaka (Oryzias latipes) exposed to diethylnitrosamine.

Several molecular and biochemical markers of genotoxicity were adapted for measurement in the medaka, and were used to describe the effects of treatment of the organism with diethylnitrosamine (DEN). DEN treatment inhibited the activity of a detoxication enzyme activity (ethoxyresorufin-O-deethylase) and increased the activity of glutathione-S-transferase. This pattern of response has been described in preneoplastic rodent cells. No O6-ethyl guanine adducts were detected, and a slight, but statistically significant, increase in DNA strand breaks was observed. These results are consistent with the hypothesis that prolonged exposure to high levels of DEN induced alkyltransferase activity which enzymatically removes any O6-ethyl guanine adducts but does not result in strand breaks or hypomethylation of the DNA such as might be expected from excision repair of chemically modified DNA.

Animals↗

Appreciation of metaphoric alternative word meanings by left and right brain-damaged patients.

Appreciation of metaphoric and nonmetaphoric alternative word meanings was assessed in 19 aphasic, left (LHD) and 15 non-aphasic, right (RHD) hemisphere brain-damaged stroke patients. With the one exception in the aphasic group, all patients were male. In an unspeeded sorting task, subjects responded on the basis of less frequent, alternative meanings of polysemous target words. Targets were either polysemous adjectives (e.g. "warm") having metaphoric alternative meanings (loving) or polysemous nouns (e.g., "pen") having non-metaphoric alternative meanings (writing implement, cage). Both patient groups performed worse overall than a group of nonbrain-damaged control subjects. Relative to the RHD patients, LHD patients showed a spared appreciation of metaphoric alternative meanings. In addition, LHD, but not RHD, patients performed better on metaphoric adjective trials when there was high similarity between a word's dominant and (metaphoric) alternative meaning. The results suggest a pervasive insensitivity of RHD patients to alternative interpretations of linguistic units, and a special role for the intact right hemisphere in lexical-semantic processes related to metaphor comprehension.

Aged↗

The effects of right hemisphere damage on the pragmatic interpretation of conversational remarks.

The ability to interpret conversational utterances was assessed in a group of 12 male patients with unilateral right hemisphere brain damage (RHD) and 12 non-brain-damaged, age-matched male control subjects. Subjects listened to short vignettes which described both the affective tone of the relationship between a speaker and an actor, and the actor's performance on a task. Each vignette concluded with the speaker characterizing the actor's performance. In half of the items, the speaker's utterance was literally true; in the other half, the utterance was literally false and invited a nonliteral interpretation. Results showed no appreciable differences in the performance of control subjects and RHD patients when interpreting literally true utterances. In contrast, the two groups differed reliably when interpreting the pragmatic intent of nonliteral utterances: Control subjects used information about both the actor's performance and the speaker-actor relationship, while RHD patients demonstrated difficulty in using the information about the speaker-actor relationship. Results have implications for patients' understanding of essential elements of conversations, such as characters' internal states and their intentions in employing different forms of literal and nonliteral language.

Affect↗

Beyond scripts: a note on the capacity of right hemisphere-damaged patients to process social and emotional content.

Individuals with right hemisphere damage (RHD) can comprehend simple scripts but have difficulties understanding more complex forms of discourse such as stories and jokes. This study sought to discover the point beyond simple scripts at which such patients begin to experience difficulties. Three-sentence, script-like vignettes which described everyday situations were created along two major dimensions: a social dimension (reflecting presence or absence of interactions between characters); and an emotional dimension (reflecting a positive, negative, or neutral emotion felt by a protagonist in the situation). Right hemisphere-damaged patients were asked to provide emotional characterizations of, and continuations to, these situational vignettes. Results indicated that individuals with right hemisphere damage were more likely than control subjects to attribute a positive emotional state to a character in a neutral situation. In other respects, there were no significant differences between RHD subjects and controls, although the RHD subjects made significantly more factual errors in their continuations than did control subjects.

Adult↗

Appreciation of indirect requests by left- and right-brain-damaged patients: the effects of verbal context and conventionality of wording.

Unilaterally right (RHD)- and left (LHD)-hemisphere-damaged patients were tested on their ability to discern the correct, nonliteral interpretation of indirect requests (e.g., "Can you open the door?") embedded in short vignettes and presented without any pictorial support. Each stimulus vignette incorporated two verbal cues--context and conventionality of form--designed to influence interpretations of a critical utterance located at the end of each vignette. Contexts were biased to encourage either the direct, literal reading of critical utterances as a question, or the indirect meaning of the utterance as a request for action. The critical utterances themselves were either high in conventionality (e.g., "Can you ...?") which encouraged an indirect interpretation, or low in conventionality (e.g., "Is it possible for you to ...?") which encouraged a direct interpretation. Results indicated that RHD patients were significantly impaired, relative to controls, in their ability to make judgments based on contextual information. RHD patients performed comparably to the aphasic, LHD group in the use of both context and conventionality. These results replicate earlier findings of disrupted indirect request comprehension by RHD patients tested in pictorially supported paradigms.

Adult↗