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D I Smith

Publications and source records attributed to D I Smith.

At least 19 recordsLinked to original sources
PubMed1992

Localization of three novel hybrid breakpoints and refinement of 18 marker assignments in the human 3cen-p21.1 region.

Using the human/hamster cell line UCTP2A-3, we have generated and isolated three hybrids, each containing a novel human chromosome 3p break. All chromosome 3 materials distal to the breaks were lost. Two of the breakpoints were produced using aphidicolin induction; the third breakpoint occurred spontaneously. The aphidicolin-induced breaks were localized to 3p21.1 in hybrid AR1 and to p14.1 in hybrid AR2. The spontaneous break was localized to 3p11 in hybrid 2A-3-1. These hybrids were used to sublocalize 18 chromosome 3 probes further to five regions within 3cen-p21.1. The new hybrids and sublocalized markers will be useful in the study and characterization of the 3p11, 3p14.1, and 3p21.1 segments of chromosome 3.

Animals↗
PubMed1992

The human loci DNF15S2 and D3S94 have a high degree of sequence similarity to acyl-peptide hydrolase and are located at 3p21.3.

The short arm of chromosome 3 undergoes genetic loss in most small-cell lung cancers and renal cell carcinomas. The most frequently deleted region includes the DNF15S2 locus (mapped to 3p21), suggesting that a putative recessive tumor-suppressor gene might be located nearby. A cosmid clone, cA476, contains the D3S94 locus and two HTF islands and detects a PstI RFLP. We have isolated cDNAs homologous to conserved fragments within cA476; and these cDNAs have 96% sequence similarity to a cDNA derived from the DNF15S2 locus. Sequence information from cDNAs derived from both the rat and pig acyl-peptide hydrolase (E.C.3.4.19.1) gene show that they have a high degree of sequence similarity to cDNAs derived from D3S94 and DNF15S2, suggesting that they are all the same locus. Cosmid cA476 (DNF15S2) has been mapped, by fluorescent in situ hybridization, to chromosome 3p21.3. D3S94 and DNF15S2 are quite distinct from aminoacylase 1 (ACY1), which has been physically linked to D3S2, D3S92, and D3S93, all localized within 3p21.1.

Animals↗
PubMed1991

Genetic flanking markers refine diagnostic criteria and provide insights into the genetics of Von Hippel Lindau disease.

Von Hippel Lindau disease (VHL) is a hereditary syndrome, associated with tumors and cysts in multiple organ systems, whose expression and age of onset are highly variable. The availability of a genetic test for the early and reliable detection of individuals carrying the defective gene would be beneficial for VHL patients and their relatives, since many of the manifestations of VHL can be successfully treated if detected in their early stages, while the complications of undetected disease can be devastating. We have previously shown that the VHL gene maps to chromosome 3p. To provide genetic markers for the development of a reliable diagnostic test, and to further narrow and eventually clone the VHL defect, we have generated DNA markers for chromosome 3p. With these markers, we have performed a multipoint genetic linkage analysis in 28 VHL pedigrees, comprising 470 individuals, 164 of whom were affected with VHL. Here we report the identification of tightly linked markers, including flanking markers that bracket the VHL gene to a small region on chromosome 3p25-p26. This finding has several major implications. While visceral cysts of the kidney, pancreas, and epididymis are commonly found in VHL and are considered diagnostic criteria for this disorder, they also occur in the general population. The presence of cysts, unaccompanied by other more typical lesions such as retinal and cerebellar hemangioblastoma, may therefore represent a major diagnostic problem, leading to errors in the assessment of disease status. The application of flanking markers for the VHL gene for presymptomatic diagnostic testing confirms that epididymal cysts are indeed not suitable as a diagnostic criterion in this disorder. Pheochromocytomas occur nonuniformly in VHL families and may also be associated with other hereditary tumor syndromes; our genetic studies imply that the phenotype in VHL families with and without pheochromocytomas is caused by defects within the same gene. The absence or presence of this tumor type is therefore due to the pleiotropic expression of a single gene rather than to the existence of several different genes for VHL. The region on chromosome 3p13-p14 known to contain several chromosomal translocation breakpoints in families with "pure familial renal cell carcinoma" is quite proximal to the VHL locus in 3p25-p26 we have identified. Chromosome 3p may therefore contain two loci for renal cell carcinoma: one gene (or genes) in 3p13-p14 and the VHL gene in 3p25-p26, whose aberration is also associated with other typical manifestations of VHL. Since renal cell carcinoma, pheochromocytoma, and visceral cysts can occur sporadically even in young people and may also be associated with other tumor syndromes, the availability of flanking markers for the VHL gene will be useful in identifying VHL gene carriers, particularly among those individuals at risk in whom these are the only manifestations of disease. The isolation and characterization of the VHL gene, based on the identification of flanking markers, will have important implications for diagnosis and treatment of patients with VHL, as well as for a much larger number of individuals having the sporadic counterparts of VHL-associated tumor types.

Cell Line↗
PubMed1991

The human kininogen gene (KNG) mapped to chromosome 3q26-qter by analysis of somatic cell hybrids using the polymerase chain reaction.

Kinins, peptide products of kininogens, may be involved in hypertensive and diabetic diseases, and inflammatory disorders. The human kininogen gene (KNG) has been mapped to chromosome 3, using a panel of human-hamster somatic cell hybrids by polymerase chain reaction of hybrid DNA with gene-specific primers. KNG was further assigned to 3q26-3qter, using DNA from a second panel of chromosome 3 deletion mapping cell hybrids.

Animals↗
PubMed1991

Relationship between alcohol consumption and attempted suicide morbidity rates in Perth, Western Australia, 1968-1984.

Per adult (greater than or equal to 15 years) consumption of beer, wine, spirits, and absolute alcohol for a 17-year period (1968-1984) was related to the attempted suicide morbidity rates in the Perth urban area of Western Australia. For both males and females aged 15-39 years, Mann-Whitney U tests showed that during the years of highest spirits consumption, the highest rates for attempted suicide occurred. A similar finding also applied to 15-39-year-old males for wine. The effect of a rapidly rising blood alcohol level, together with a preselection factor as to the personal characteristics of persons who consumed the higher alcohol content drinks, may explain the results, which need to be confirmed by clinical studies of the type of alcoholic beverage consumed by persons prior to attempting suicide.

Adolescent↗
PubMed1991

Low-frequency component of the gerbil brainstem response: response characteristics and anesthesia effects.

The auditory brainstem response (ABR) was recorded with epidural electrodes in awake and anesthetized gerbils. Low- and high-frequency components of the ABR were separated by analog filters and compared as functions of stimulus intensity, frequency, repetition rate, and effects of anesthesia. In response to 0.5 kHz tone bursts, thresholds of the low-frequency component (LF-ABR) were significantly lower than that of the most prominent peak of the high-frequency components (wave P4). At both 2 and 4 kHz, thresholds of the LF-ABR and wave P4 were not significantly different. Changes in stimulus intensity over a 70 dB range produced similar changes in peak amplitudes and latencies for the LF-ABR and P4. However, while the amplitude of the LF-ABR was inversely related to stimulus frequency, the amplitude of P4 was reduced at 0.5 kHz, as compared to 2 and 4 kHz. Increases in stimulus rate from 7 to 100 bursts/s produced little change in the amplitude of the LF-ABR. At rates of 80 and 100 bursts/s, the LF-ABR was sinusoidal in appearance due to the proximity of successively generated potentials. In contrast, the amplitude of P4 varied inversely with stimulus rate between 20 and 100 bursts/s. Administration of ketamine and xylazine produced minor changes in the amplitudes and latencies of both the LF-ABR and wave P4. The response characteristics of the gerbil LF-ABR are similar to those of the low-frequency component of the ABR in humans and cats. The LF-ABR provides an estimate of hearing threshold at low frequencies (0.5 kHz) as well as higher frequencies (2-4 kHz). A major advantage to the LF-ABR is that it can be recorded at high stimulation rates in awake and anesthetized animals, thus providing an efficient measure of auditory function.

Acoustic Stimulation↗
PubMed1991

A 2.5-Mb physical map within 3p21.1 spans the breakpoint associated with Greig cephalopolysyndactyly syndrome.

Numerous investigations suggest that one or more genes residing in the p14 to p21 region of human chromosome 3 are critical to the development of neoplastic diseases such as renal cell carcinoma and small-cell lung cancer (SCLC). This region is additionally involved in several interchromosomal translocations, one of which is associated with the developmental disorder Greig cephalopolysyndactyly syndrome. A series of five loci that map in close proximity to the Greig syndrome breakpoint [t(3;7)(p21.1;p13)] at 3p21.1 have been physically linked by pulsed-field gel analysis over a 2.5-Mb region. The probes include ACY1, cA84 (D3S92), cA199 (D3S93), pHF12-32 (D3S2), and MW-Not153 (D3S332). The Greig 3;7 translocation breakpoint was discovered between clones cA199 and MW-Not153, separated by 825 kb. Further analysis revealed comigration of a rearranged fragment detected by MW-Not153 and a chromosome 7 probe previously shown to be in close proximity to the breakpoint (CRI-R944). This latter probe also detects a rearrangement in a second Greig-associated translocation, (6;7)(q27;p13). The physical map resulting from this analysis orders the markers along the chromosome and identifies several locations for CpG islands, likely associated with genes. Although probe pEFD145.1 (D3S32) has been genetically linked to D3S2 (2 cM), physical linkage to the other five loci could not be demonstrated. One of the linked loci, D3S2, has been widely utilized in the analysis of chromosome 3p loss in several malignant diseases. Since expression of ACY1, a housekeeping gene, is specifically reduced in many cases of SCLC, knowledge of its precise chromosomal position and identification of neighboring putative gene loci should facilitate investigation into the mechanism of this reduction.

Cell Line↗
PubMed1991

Localization of 616 human chromosome 3-specific cosmids using a somatic cell hybrid deletion mapping panel.

A total of 5700 human chromosome 3-specific cosmid clones was isolated from a series of cosmid libraries constructed from somatic cell hybrids whose only human component was an entire chromosome 3 or a chromosome 3 containing an interstitial deletion removing 50% of long arm sequences. Several unique sequence chromosome 3-specific hybridization probes were isolated from each of 616 of these cosmids. These probes were then used to localize the cosmids by hybridization to a somatic cell hybrid deletion mapping panel capable of resolving chromosome 3 into nine distinct subregions. All 616 of the cosmids were localized to either the long or short arm of chromosome 3 and 63% of the short arm cosmids were more precisely localized. We have identified a total of 87 cosmids that contain fragments that are evolutionarily conserved. Fragments from these cosmids should prove useful in the identification of new chromosome 3-specific genes as well as in comparative mapping studies. The localized cosmids should provide excellent saturation of human chromosome 3 and facilitate the construction of physical and genetic linkage maps to identify various disease loci including Von Hippel Lindau disease and renal and small cell lung carcinoma.

Animals↗
PubMed1991

Mapping of the gene for human cysteine proteinase inhibitor stefin A, STF1, to chromosome 3cen-q21.

The gene for the human cysteine proteinase inhibitor stefin A (STF1), alias cystatin A, has been mapped to chromosome 3, using the polymerase chain reaction to specifically amplify the human stefin A sequence in human-hamster hybrid DNA. STF1 is further sublocalized to regions between centromere and 3q21 using a deletion mapping panel for this chromosome. This assignment shows that stefin A is not syntenic with cystatin C which has been localized to chromosome 20.

Animals↗
PubMed1991

Isolation of large numbers of chromosome 3-specific cosmids containing clusters of rare restriction-endonuclease sites.

We tested 519 chromosome 3-specific cosmids for the presence of rare restriction-endonuclease sites in a search for cosmids containing HTF islands. We have identified 49 cosmids (9% of those tested) that contain multiple rare restriction-endonuclease sites. The cosmids were digested with several common cutting restriction endonucleases to liberate small fragments which were tested as unique-sequence chromosome 3-specific hybridization probes and for evolutionary sequence conservation. Unique-sequence hybridization probes isolated from the cosmids were hybridized to a somatic cell hybrid deletion mapping panel to subchromosomally localize the cosmids. Fragments from many of these cosmids demonstrated conservation of sequence through evolution, and these fragments hybridize to distinct transcripts. These cosmids should therefore prove a useful resource for the identification of many chromosome 3-specific genes, in addition to having potential use as linking clones for pulsed-field gel mapping studies.

Biological Evolution↗
PubMed1990

Frequency selectivity of the middle latency response.

A forward masking paradigm was used to assess the frequency selectivity of the middle latency response (MLR). Tuning curves of the MLR were obtained in unanesthetized gerbils. Changes in the amplitudes of MLR waves A, B, and C with latency values of 10 to 13 ms, 14 to 17 ms, and 20 to 25 ms, respectively, were analyzed as a function of masker frequency and intensity. Tuning curves of the MLR were also compared to tuning curves of the auditory brainstem response (ABR), which was recorded simultaneously with the MLR. The MLR and ABR differed in their response to forward masking. The MLR was reduced in amplitude or eliminated by masker stimuli that had minimal or no effect on the ABR. Forward masking often caused variable and non-monotonic changes in the amplitude of the MLR. Tuning curves of the MLR indicate that the MLR is less frequency selective than the ABR. The MLR is an electrophysiological measure of auditory function central to the auditory brainstem. Therefore, it may provide information concerning central components of normal and pathological auditory function. However, because of the variability of MLR amplitudes with forward masking, tuning curves of the MLR are difficult to obtain and are not efficient for routine measurements of frequency selectivity.

Acoustic Stimulation↗
PubMed1990

Relationship between male pancreatitis morbidity and alcohol consumption in Western Australia, 1971-84.

Acute pancreatitis morbidity rates for Western Australian men aged 20 to 39 years, and over 40 years, were related to per adult (greater than or equal to 15 years) alcohol consumption, using the Mann-Whitney U test. A significant result was obtained for the young men. The male 20 years and over chronic pancreatitis morbidity rate was also significantly related to alcohol consumption. Various reasons for the results are discussed, and in particular from the view point that changes in the level of alcohol consumption appear to affect subsequent pancreatitis morbidity rates.

Acute Disease↗
PubMed1990

Relationship between morbidity and mortality due to alcoholic cardiomyopathy and alcohol consumption in Australia.

The study was undertaken to determine whether morbidity and mortality rates for alcoholic cardiomyopathy vary with community alcohol consumption levels. The cardiomyopathy mortality comparisons for Australia from 1968 to 1978 showed a positive relationship for both males and females aged 30 to 59 years, and 60 years and over. From 1979 to 1986 a decrease in consumption was associated with a decrease in alcoholic cardiomyopathy mortality for females, and to a lesser extent males, aged 30 to 59 years. The morbidity comparisons for Western Australia from 1971 to 1984 gave similar results to the Australian mortality findings for the males aged 30 to 59 years. It appears that the prevention of alcoholic cardiomyopathy will be facilitated by lowering the overall level of alcohol consumption in the community.

Adult↗