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Biomedical subjects

J Lahti

Publications and source records attributed to J Lahti.

17 recordsLinked to original sources

Small body size at birth and behavioural symptoms of ADHD in children aged five to six years.

BACKGROUND: Behavioural disorders with a neurodevelopmental background, such as attention deficit hyperactivity disorder (ADHD), have been associated with a non-optimal foetal environment, reflected in small body size at birth. However, the evidence stems from highly selected groups with birth outcomes biased towards the extreme low end of the distribution in birth weight. Whether a similar association exists among the normal range of term birth is unclear. METHODS: The ADHD Rating Scale was filled in by the biological mothers and fathers of children aged five to six years who were born healthy at term. Information on weight (kg), height (cm), head circumference (cm), and gestational age at birth were obtained from hospital records, and the ponderal index (kg/m3), a commonly used measure of thinness, and head circumference-to-length ratio were calculated. RESULTS: Behavioural symptoms of ADHD were predicted by a lower ponderal index, a smaller head circumference, and a smaller head circumference-to-length ratio (beta's: -.12 to -.14, p's < .05). Adjustments for length of gestation, mother's age, tobacco and alcohol use during pregnancy, pre-pregnancy body mass index (BMI), or parity, the monthly gross income of the family, child's BMI at the age of five to six years or gender did not change the associations. CONCLUSION: These results suggest that physiological adaptation in utero, indicated by small body size at birth, within term gestational range may increase the susceptibility to behavioural symptoms of ADHD.

Attention Deficit Disorder with Hyperactivity↗

Mdr1b facilitates p53-mediated cell death and p53 is required for Mdr1b upregulation in vivo.

The mdr1b gene is thought to be a "stress-responsive" gene, however it is unknown if this gene is regulated by p53 in the whole animal. Moreover, it is unknown if overexpression of mdr1b affects cell survival. The dependence of mdr1b upon p53 for upregulation was evaluated in p53 knockout mice. Wild-type (wt) or p53-/- mice were treated singly or in combination with gamma irradiation (IR) and/or the potent DNA damaging agent, diethylnitrosoamine (DEN). Both IR and DEN induced mdr1b in wild-type animals, but not in the p53-/- mice. IR also upregulated endogenous mdr1b in the H35 liver cell line, and the mdr1b promoter was activated by IR and activation correlated with p53 levels; moreover activation required an intact p53 binding site. Colony survival studies revealed that co-transfection of both mdr1b and p53 dramatically reduced colony numbers compared to cells transfected with either p53 or mdr1b alone and cells microinjected with both mdr1b and p53 had a more dramatic loss in viability compared to cells injected with either expression vector alone. Further studies using acridine orange and ethidium bromide to measure apoptosis revealed that mdr1b caused apoptosis and this was enhanced by p53, however the increased apoptosis required a functional p53 transactivation domain. These studies indicate that mdr1b is a downstream target of p53 in the whole animal and expression of mdr1b facilitates p53-mediated cell death.

ATP Binding Cassette Transporter, Subfamily B↗

Sneddon's syndrome: a case report.

We report a case of Sneddon's syndrome with the triad of livedo reticularis, hypertension, and neurologic symptoms. The procedures for diagnosis and the tests to delineate clotting abnormalities are examined.

Adult↗

G1-phase regulators, cyclin D1, cyclin D2, and cyclin D3: up-regulation at gastrulation and dynamic expression during neurulation.

Gastrulation in rodents is associated with an increase in the rate of growth and with the start of differentiation within the embryo proper. In an effort to understand the role played by the cell cycle control in these processes, expression of cyclin D1, D2, and D3--three major positive regulators of the G1/S transition--has been investigated by in situ hybrization and RT-PCR. Cyclin D1 and D2 transcripts are first detected in the epiblast at gastrulation, when a proliferative burst occurs, and subsequently in its differentiated derivatives within the embryo proper, indicating that activation of their expression takes place prior to the differentiation of epiblast progenitors. In contrast, cyclin D3 transcript is undetectable in the epiblast itself and its expression is activated exclusively in extraembryonic tissues of both epiblast and trophoblast origin. During neurulation, expression of each cyclin D RNA is dynamically regulated along the anterior-posterior axis. In the hindbrain, cyclin D1 and D2 show distinct segment-specific restricted expression and this pattern is conserved between mouse and chick. These results strongly suggest that D-type cyclins act as developmental regulators.

Animals↗

Effect of obesity on the response to insulin therapy in noninsulin-dependent diabetes mellitus.

An initial improvement in glycemic control is often followed by gradual deterioration of glycemia during insulin treatment of patients with noninsulin-dependent diabetes mellitus (NIDDM). We examined the causes of such worsening in a 12-month follow-up analysis of 100 insulin-treated NIDDM patients in the Finnish Multicenter Insulin Therapy Study who were treated with either combination therapy with insulin or insulin alone. In the entire study group, glycemic control averaged 9.7 +/- 0.2% at 0 months and 8.0 +/- 0.1%, 8.0 +/- 0.1%, 8.2 +/- 0.1%, and 8.5 +/- 0.2% at 3, 6, 9, and 12 months (P < 0.001 for each time point vs. 0 months). Glycemic control at 12 months was significantly worse than that at 3 (P < 0.001), 6 (P < 0.001), and 9 months (P < 0.02). Baseline body mass index was the most significant predictor of deterioration in glycemic control. During 1 yr, hemoglobin A1c decreased almost 3-fold more (by 1.7 +/- 0.2%; P < 0.001 vs. 0 months) in patients whose baseline weight was below the mean baseline body mass index of 28.1 kg/m2 (nonobese patients) than in those whose weight exceeded 28.1 kg/m2 (obese patients; 0.5 +/- 0.2%; P = NS vs. 0 months; P < 0.01 vs. obese patients). Glycemic control improved similarly over 1 yr in the nonobese subjects and deteriorated similarly in the obese patients regardless of their treatment regimen. Insulin doses, per body weight, were similar in the nonobese and obese patients. The nonobese patients consistently gained less weight during 12 months of combination therapy with insulin (3.5 +/- 0.6 kg at 12 months) than during insulin therapy alone (5.1 +/- 0.6 kg; P < 0.05). The treatment regimen did not influence weight gain in the obese group, who gained 4.4 +/- 1.0 kg during combination therapy with insulin and 4.5 +/- 1.1 kg during insulin therapy alone. We reached the following conclusions: 1) after an initial good response, glycemic control deteriorates more in obese than in nonobese patients with NIDDM; 2) in obese patients, weight gain per se cannot explain the poor glycemic response to combination or insulin therapy, but it may induce a disproportionately large increase in insulin requirements because of greater insulin resistance in the obese than in the nonobese; 3) in nonobese patients, glycemic control improves equally during 1 yr with combination therapy with insulin and insulin alone, but combination therapy with insulin is associated with less weight gain than treatment with insulin alone; 4) weight gain appears harmful, as it is associated with increases in blood pressure and low density lipoprotein cholesterol.

Adult↗

Partner violence: a systematic approach to identification and intervention in outpatient health care.

Although partner violence is a common source of injury for women, physicians and female patients rarely discuss this problem. We outline a systematic approach to clinical practice that includes screening, case finding, intervention, and changes in the office environment. The clinician can begin to address partner violence by artfully applying these techniques. Future health outcomes research will provide additional guidance to clinical practice. We conclude with a quote from a third year medical student at the Medical College of Wisconsin who has a clear and challenging vision of the future: "I look forward to helping victims of domestic violence and eradicating domestic violence from the face of the earth just as smallpox has been eliminated."

Adolescent↗

Identification of T-cell receptor alpha-chain genes in the chicken.

T-cell receptor (TCR) alpha-chain (TCR alpha) and beta-chain (TCR beta) genes are well characterized in mammals, while only TCR beta genes have been identified in other vertebrates. To identify avian TCR alpha genes, we used monoclonal anti-CD3 antibodies to isolate chicken TCR alpha for peptide sequence analysis. Degenerate oligonucleotide probes were then used to isolate a candidate TCR alpha cDNA clone that hybridized with a 1.7-kb mRNA species present only in alpha beta T cells and in tissues populated by these cells. Southern blot analysis revealed gene rearrangement in thymocytes and alpha beta T-cell lines. The TCR alpha cDNA candidate encoded an open reading frame of 275 amino acids, the predicted variable (V)-, joining (J)-, and constant (C)-region amino acid sequences of which shared approximately 40%, 60%, and 25% homology with corresponding mammalian sequences. A single C alpha gene and approximately 25 V alpha genes were identified by using region-specific probes. The V alpha cDNA probe isolated from a V beta 1+ cell line reacted with transcripts from one of five V beta 2+ cell lines, suggesting shared use of V alpha genes by V beta 1+ and V beta 2+ T cells and the existence of other V alpha gene families. A genomic V alpha sequence was flanked by classical recombination signal sequences but, unlike previously defined V genes, the leader and V alpha region were encoded by a single exon. The data indicate evolutionary conservation of the basic TCR alpha gene structure in birds and mammals.

Amino Acid Sequence↗

Comparison of insulin regimens in patients with non-insulin-dependent diabetes mellitus.

BACKGROUND: Insulin is widely used to improve metabolic control in patients with non-insulin-dependent diabetes mellitus (NIDDM), but there is no consensus about the optimal regimen of insulin treatment. METHODS: We treated 153 patients with NIDDM for three months with five regimens: (1) oral hypoglycemic drug therapy plus NPH insulin given at 7 a.m. (the morning-NPH group), (2) oral hypoglycemic drug therapy plus NPH insulin given at 9 p.m. (the evening-NPH group), (3) NPH and regular insulin (ratio, 70 units to 30 units) given before breakfast and dinner (the two-insulin-injection group), (4) NPH insulin at 9 p.m. and regular insulin before meals (the multiple-insulin-injection group), and (5) continued oral hypoglycemic drug therapy (the control group). RESULTS: The mean (+/- SE) value for glycosylated hemoglobin decreased similarly in all four insulin-treatment groups (1.7 +/- 0.3, 1.9 +/- 0.2, 1.8 +/- 0.3, and 1.6 +/- 0.3 percent, respectively). The decrease was significantly greater in these four groups than in the control group (0.5 +/- 0.2 percent; P < 0.001 vs. all insulin-treated groups). Weight gain was significantly less (1.2 +/- 0.5 kg) in the evening-NPH group than in the other insulin-treatment groups (2.2 +/- 0.5 kg in the morning-NPH group, 1.8 +/- 0.5 kg in the two-insulin-injection group, and 2.9 +/- 0.5 kg in the multiple-injection group; P < 0.05). In addition, the increment in the mean diurnal serum free insulin concentration was 50 to 65 percent smaller in the evening-NPH group than in the other insulin-treatment groups. Subjective well-being improved significantly more in the insulin-treatment groups than in the control group (P < 0.001). CONCLUSIONS: In patients with NIDDM who are receiving oral hypoglycemic drug therapy, the addition of NPH insulin in the evening improves glycemic control in a manner similar to combination therapy with NPH insulin in the morning, a two-insulin-injection regimen, or a multiple-insulin-injection regimen, but induces less weight gain and hyperinsulinemia. The data thus suggest that patients with NIDDM do not benefit from multiple insulin injections and that nocturnal insulin administration appears preferable to daytime administration.

Administration, Oral↗

Homozygous deletions within human chromosome band 9p21 in melanoma.

Genetic studies have implicated the early involvement of a gene on chromosome arm 9p in the development of cutaneous melanoma. We have performed loss-of-heterozygosity studies to confirm these original findings and identify the most frequently rearranged or deleted region of 9p. Eight markers were analyzed, including (from 9pter to proximal 9q) D9S33, the beta-interferon (IFNB1) locus, the alpha-interferon (IFNA) gene cluster, D9S126, D9S3, D9S19, the glycoprotein 4 beta-galactosyltransferase (GGTB2) gene, and the argininosuccinate synthetase pseudogene 3 (ASSP3). Two or more of these loci were found to be hemizygously reduced in 12 of 14 (86%) informative metastatic melanoma tumor and cell line DNAs, and homozygous deletions of the marker D9S126 were observed in 2 of 20 (10%) melanoma cell lines. These findings have resulted in the identification of a small critical region of 2-3 megabases on 9p21 in which a putative melanoma tumor-suppressor gene appears likely to reside. Several 9p candidate genes, including IFNB1, the IFNA gene cluster, GGTB2, and the tyrosinase-related protein (TYRP) locus, have all been eliminated as potential targets because they are located outside of the homozygously deleted regions.

Base Sequence↗

Morning or bed-time insulin with or without glibenclamide in elderly type 2 diabetic patients unresponsive to oral antidiabetic agents.

We studied in a group of elderly (mean age 77 yr) non-obese Type 2 diabetic patients (n = 9) in a randomised, placebo-controlled prospective cross-over study of 8 months duration, the effects of substituting maximal sulfonylurea medication with a single injection of human zinc insulin taken either at bedtime (BTI) or morning (MI). All patients were poorly controlled with oral antidiabetic agents. After a 2-month regimen with either BTI or MI, a glibenclamide (GL, 3.5 mg/day) was given for an additional 2 months. Both insulin regimens decreased mean diurnal blood glucose and glycosylated HbA1c values to a similar extent (2.6-2.7%; p < 0.01-0.05), but with a lower daily insulin dose with BTI (0.30 +/- 0.03 IU/kg) as compared with MI (0.39 +/- 0.05 IU/kg; p < 0.01). A further improvement in metabolic control was observed in both groups after the introduction of GL; the mean reduction in glycosylated HbA1c was 1.4% for BTI and 0.7% for MI (p < 0.01 and 0.05, respectively), In conclusion, a subgroup of poorly controlled elderly Type 2 diabetic patients showed an improvement in metabolic control after a single injection of insulin despite discontinuation of maximal doses of oral antidiabetic agents. After 2 months of insulin treatment, a further improvement was achieved by a low dose of sulfonylurea in these patients who were formerly considered unresponsive to oral antidiabetic agents.

Aged↗

Signs and symptoms of TMJ dysfunction in patients with mandibular condyle fractures.

Signs and symptoms of TMJ dysfunction in a total of 52 mandibular fracture patients comprising 15 with condylar fractures (Group I), 22 with combined condylar and mandibular body fractures (Group II), and 15 with mandibular body fractures (Group III) were examined an average of 44 months after injury. In terms of the Helkimo dysfunction index, it was shown that more severe subjective and objective dysfunctions were observed in the Group II, in which condylar fracture patients were treated with long-term intermaxillary fixation (IMF) and in which the patients' injuries were caused by more energetic impacts. There was, nevertheless, a tendency for the dysfunction to be graded as milder as the time elapsing since the injury increased.

Adolescent↗

Evolutionary conservation of antigen recognition: the chicken T-cell receptor beta chain.

T cells play important regulatory roles in the immune responses of vertebrates. Antigen-specific T-cell activation involves T-cell receptor (TCR) recognition of a peptide antigen presented by a major histocompatibility complex molecule, and much has been learned about this antigen-recognition process through structural and genetic studies of mammalian TCRs. Although previous studies have demonstrated that avian T cells express cell-surface molecules analogous to the mammalian TCR heterodimers, TCR genes have not been identified in nonmammalian species. We now report the cloning of a cDNA that encodes the beta chain of the chicken TCR. Southern blot analysis using this TCR beta cDNA probe demonstrated that the chicken TCR beta locus was clonally rear-ranged in chicken T-cell lines. TCR beta mRNA was expressed in cells isolated from the thymus but not in cells from the bursa of Fabricius where B cells are generated. Sequence analysis of six additional TCR beta cDNAs suggested the existence of at least two variable (V) region families, three joining (J) elements, and single diversity (D) and constant (C) elements. As in mammals, considerable nucleotide diversity was observed at the junctions of the variable, diversity, and joining elements in chicken TCR beta cDNAs. Genomic V beta and J beta elements were also cloned and sequenced. Both elements are flanked by classical heptamer/nonamer recombination signal sequences. Although the chicken and mammalian TCR beta chains displayed only 31% overall amino acid sequence identity, a number of conserved structural features were observed. These data indicate that (i) the chicken TCR beta repertoire is generated by combinatorial and junctional diversity and (ii) despite divergent evolution at the level of nucleotide sequence, important structural features of the TCR beta polypeptide are conserved between avian and mammalian species.

Amino Acid Sequence↗

Prognosis of permanent teeth in the line of mandibular fractures.

A total of 45 mandibular fracture patients with 54 teeth in the fracture line were evaluated retrospectively. One tooth in the fracture line was lost in the accident, 6 were extracted later and 47 could be saved (87%). At the follow-up examination 38% of the teeth were diagnosed to have pulp necrosis, which was found more frequently in the older patients and in cases in which the time elapsing between the injury and the follow-up was longer. Pulp necrosis was also more frequent in cases in which the fracture line ran through the apex or dislocation of the fracture parts existed after the injury.

Adolescent↗