ABSTRACT
A series of 4'-thio-D-arabinofuranosylpurine nucleosides was prepared and evaluated as potential anticancer agents. The details of a convenient and high-yielding synthesis of the carbohydrate precursor 1-O-acetyl-2,3,5-tri-O-benzyl-4-thio-D-arabinofuranose (6) are presented. Proof of structure and configuration at all chiral centers of the nucleosides was obtained through an X-ray crystal structure of 9alpha as well as through NOE experiments on 9beta and 9alpha. All six target compounds were evaluated in a series of human cancer cell lines in culture. Two target compounds, beta anomers with diaminopurine (12) and guanine (16) as the bases, had significant cytotoxicity. One of these compounds (12) was selected for animal studies but was found to have no selectivity at the maximum tolerated dose in the murine colon 36 tumor model.
Subject(s)
Antineoplastic Agents , Purine Nucleosides , Adenosine/analogs & derivatives , Adenosine/chemical synthesis , Adenosine/chemistry , Adenosine/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Cell Division/drug effects , Crystallography, X-Ray , Drug Screening Assays, Antitumor , Humans , Magnetic Resonance Spectroscopy , Molecular Conformation , Purine Nucleosides/chemical synthesis , Purine Nucleosides/chemistry , Purine Nucleosides/pharmacology , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
This investigation attempted to clarify the relationship between stuttering in young children and the language factors of length and grammatical complexity. Sentences containing stutterings within the first few words, as produced by 12 stutterers (4-6 years old) in spontaneous conversational dyads, were analyzed for length and grammatical complexity. Results indicated that sentences in which an episode of stuttering occurred within the first three words were significantly longer and more complex than sentences that were free of perceptible stuttering and all other forms of fluency failure. Implications of these findings for the clinician are presented and discussed.
Subject(s)
Language , Stuttering , Child , Child, Preschool , Humans , Retrospective StudiesABSTRACT
Standard counseling practices with the families of young stutterers include recommendations that listeners' negative verbal behaviors be modified in order to reduce the likelihood of stuttering. This study tested the hypothesis that stuttering and normal disfluencies in preschool stutterers are related to selected verbal behaviors in conversational partners. Twelve 2- to 6-year-old stutterers were video recorded while playing with their mother, father, and a familiar peer. The resulting videotapes were transcribed and two types of social communicative analyses (total number of words and utterances, verbal intent of the speaker) were undertaken. Results suggested that fathers used more words and utterances than mothers and peers. Parents provided more positive interactions with their stutterer offspring than did peers. Parents also asked significantly more negative and routine questions when talking to their stuttering child. Peer playmates were significantly more negative and generally commented more frequently when interacting with stutterers than did the parents. Stutterers were involved in significantly more positive interactions with their fathers. The frequency of fluency failures did not differ significantly when stutterers communicated with their mother, father, or peer partners. Implications regarding verbal styles of partners in relationship to the stuttering of preschool children are discussed.
Subject(s)
Parent-Child Relations , Peer Group , Stuttering/psychology , Verbal Behavior , Adult , Child , Child, Preschool , Father-Child Relations , Female , Humans , Interpersonal Relations , Male , Mother-Child Relations , SpeechABSTRACT
The spontaneous conversational speech of 20 children with unilateral left hemisphere lesions and 13 with right lesions was compared to normally developing peers matched by age, sex, race, and social class for instances of stuttering type nonfluencies, normal nonfluencies, and rate of speech. Both left and right lesioned children provided quantitatively more and qualitatively different patterns of nonfluencies than their neurologically normal peers. Left and right lesioned children produced more stuttering types of nonfluencies than their controls, but neither lesioned group produced a greater number of normal nonfluencies than controls. Left lesioned children also had a slower rate of speech as measured by number of syllables per second during either stuttered or fluent speech. Considerable variability was observed among lesioned children. Implications for neurogenic theories of developmental fluency disorders are discussed.
Subject(s)
Brain Damage, Chronic/physiopathology , Dominance, Cerebral/physiology , Language Development Disorders/physiopathology , Stuttering/physiopathology , Verbal Behavior/physiology , Aphasia, Broca/physiopathology , Cerebral Cortex/physiopathology , Child , Female , Follow-Up Studies , Humans , Male , Semantics , Speech Production MeasurementABSTRACT
The purpose of this study was to investigate the hypothesis that stuttering is related to a dysfunction in auditory temporal processing. The performance of 20 adult male stutterers and 20 matched nonstutterers was studied using two auditory processing tasks. The subjects listened to stimuli with differential onset asynchronies during temporal order judgment (TOJ) and dichotic listening tasks. Stutterers and nonstutterers were not significantly different at judging which ear received the stimulation first (TOJ task) at varying stimulus onset asynchronies (SOAs). During the dichotic listening task, stutterers made significantly fewer double-correct responses (correct report for both stimuli in a dichotic pair) than nonstutterers. The stuttering subjects correctly classified one of the syllables in a pair (single-correct response) more frequently than normal controls on the dichotic listening task. These findings suggest that SOAs as a temporal parameter do not differentiate the performance of the two groups. The more difficult auditory processing task (dichotic identification) showed a significant difference in the performance of the stutterers versus nonstutterers.
Subject(s)
Auditory Cortex/physiopathology , Speech Perception , Stuttering/physiopathology , Adolescent , Adult , Humans , Male , Middle Aged , Reaction Time , Time FactorsABSTRACT
Nonfluencies produced by 12 stutterers (2-6 years old) interacting in three dyadic sessions were analyzed. A stutterer played with his own mother, own father, and a familiar peer for 10 min. Results indicated that the total frequencies and types of nonfluency observed were very similar in each of the play situations. Although stutterers exhibited more part-word repetitions and prolongations than any other type of nonfluency, they did not differ in the amount and type of nonfluency when talking to their three conversational partners. Because children have more breakdowns in fluency than adults, it was not surprising that peers were more nonfluent when talking to the stutterer than were the parents. Peers used significantly more part- and whole-word repetitions, tense pauses, and interjections than the parents did. The nonfluency levels of the parent partners were quite similar when talking to the stutterers.
Subject(s)
Speech , Stuttering/psychology , Child, Preschool , Humans , Social Environment , Stuttering/physiopathologyABSTRACT
Parental verbal behavior is often cited as a major precipitating and maintaining factor in the onset and development of stuttering. Parents are frequently counseled to avoid interrupting their stuttering child. The purpose of the present study was to determine (a) whether mothers of preschool stutterers interrupt children's speech more frequently than mothers of nonstutterers, (b) whether stutterers interrupt the speech of mothers more frequently than nonstutterers, and (c) whether there is relationship between interruptive behavior and the occurrence of children's disfluencies. Twenty-four preschool boys (12 stutterers and 12 nonstutterers) and their mothers participated in the study. Ten-min, conversational speech samples of mothers interacting with their own children, unfamiliar stutterers, and unfamiliar nonstutterers were analyzed. Results indicated that mothers of nonstutterers interrupted the disfluent speech of stutterers significantly more often than did mothers of stutterers. Most importantly, all mothers interrupted children's disfluent speech significantly more than they interrupted children's fluent speech. Further, all children demonstrated a tendency to be disfluent when they interrupted a mother.
Subject(s)
Mother-Child Relations , Stuttering/psychology , Child, Preschool , Female , Humans , Interpersonal Relations , Male , SpeechABSTRACT
Three questions were addressed in this study: (a) Do mothers of stuttering children talk faster than mothers of nonstuttering children, (b) do stuttering children talk faster than nonstuttering children, and (c) is there a relationship between child's rate of speech and mother's rate of speech in dyadic conversation? Twelve nonstuttering preschool boys and their mothers were matched with 12 stutterers and their mothers. Ten min of free-play interaction between alternated mother-child dyads were video recorded. Speech rates, defined as syllables per second in fluent utterances, were calculated. Results demonstrated that mothers of stutterers talked significantly faster to all children. Stutterers spoke slower than nonstutterers, and severe stutterers spoke slower than moderate stutterers. A correlational analysis revealed that the more the child stuttered, the slower he talked during fluent speech. Further, the slower the child talked during fluent speech, the faster the mother interacting with him talked. The results reveal an interactive and complex relationship between mother and child speech rates. The interpretation of results relating to child speech rates was complicated by post hoc analyses revealing a significant relationship between speech rates and utterance length.
