The mating‐type region of fission yeast consists of three components, mat1, mat2‐P and mat3‐M, each separated by 15 kb. Cell‐type is determined by the alternate allele present at mat1, either P in an h+ or M in an h‐ cell. mat2‐P and mat3‐M serve as donors of information that is transposed to mat1 during a switch of mating type. We have determined the nucleotide sequence of each component of mat. The P and M specific regions are 1104 and 1128 bp, respectively, and bounded by sequences common to each mating‐type cassette (H1; 59 bp and H2; 135 bp). A third sequence is present at mat2‐P and mat3‐M but absent at mat1 (H3; 57 bp), and may be involved in transcriptional repression of these cassettes. mat1‐P and mat1‐M each encode two genes (Pc; 118 amino acids, Pi; 159 amino acids, Mc; 181 amino acids and Mi; 42 amino acids). Introduction of opal or frame‐shift mutations into the open‐reading‐frame of each gene revealed that Pc and Mc are necessary and sufficient for mating and confer an h+ or h‐ mating type respectively. All four genes are required for meiotic competence in an h+/h‐ diploid. The transcription of each mat gene is strongly influenced by nutritional conditions and full induction was observed only in nitrogen‐free medium. The predicted product of the Pi gene contains a region of homology with the homeobox sequence, suggesting that this gene encodes a DNA binding protein that directly regulates the expression of other genes.

OBJECTIVE -Postprandial hyperglycemia is often inadequately assessed in diabetes management. Serum 1,5-anhydroglucitol (1,5-AG) drops as serum glucose rises above the renal threshold for glucose and has been proposed as a marker for postprandial hyperglycemia. The objective of this study is to demonstrate the relationship between 1,5-AG and postprandial hyperglycemia, as assessed by the continuous glucose monitoring system (CGMS) in suboptimally controlled patients with diabetes.RESEARCH DESIGN AND METHODS -Patients with type 1 or type 2 diabetes and an HbA 1c (A1C) between 6.5 and 8% with stable glycemic control were recruited from two sites. A CGMS monitor was worn for two consecutive 72-h periods. Mean glucose, mean postmeal maximum glucose (MPMG), and area under the curve for glucose above 180 mg/dl (AUC-180), were compared with 1,5-AG, fructosamine (FA), and A1C at baseline, day 4, and day 7.RESULTS -1,5-AG varied considerably between patients (6.5 Ϯ 3.2 g/ml [means Ϯ SD]) despite similar A1C (7.3 Ϯ 0.5%). Mean 1,5-AG (r ϭ Ϫ0.45, P ϭ 0.006) correlated with AUC-180 more robustly than A1C (r ϭ 0.33, P ϭ 0.057) or FA (r ϭ 0.38, P ϭ 0.88). MPMG correlated more strongly with 1,5-AG (r ϭ Ϫ0.54, P ϭ 0.004) than with A1C (r ϭ 0.40, P ϭ 0.03) or FA (r ϭ 0.32, P ϭ 0.07).CONCLUSIONS -1,5-AG reflects glycemic excursions, often in the postprandial state, more robustly than A1C or FA. 1,5-AG may be useful as a complementary marker to A1C to assess glycemic control in moderately controlled patients with diabetes. Diabetes Care 29:1214 -1219, 2006T he importance of tight glycemic control in preventing the complications of diabetes has been well documented (1-3). More recently, studies indicate that postprandial glucose may be an independent risk factor for the development of macrovascular complications (4 -6). Many patients who are otherwise well controlled by HbA 1c (A1C), the current standard indicator of overall glycemia, also have significant postprandial hyperglycemia (7). Currently, available markers for measuring glycemic control, including A1C and fructosamine (FA), only reflect average glucose, potentially missing important hyperglycemic excursions that may be balanced out by hypoglycemia. Therefore, an alternative marker that robustly reflects postprandial glucose excursions could be useful in the management of patients with diabetes.Plasma 1,5-anhydroglucitol (1,5-AG) is a naturally occurring dietary polyol that has been proposed as a marker for postprandial hyperglycemia. An automated assay (Glycomark) has recently been approved in the U.S. as a short-term marker for glycemic control (8), and a similar assay has been in use in Japan for over a decade (9). During normoglycemia, 1,5-AG is maintained at constant steadystate levels due to a large body pool compared with the amount of intake (10) and due to a lack of metabolism (10,11). Normally, in the kidneys, 1,5-AG is filtered and completely reabsorbed (12). However, with elevated serum glucose concentrations (generally Ͼ180 mol/l, the average renal threshold fo...

We completed a systematic genome-wide search for evidence of loci linked to schizophrenia using a collection of 70 pedigrees containing multiple affected individuals according to three phenotype classifications: schizophrenia only (48 pedigrees; 70 sib-pairs); schizophrenia plus schizoaffective disorder (70 pedigrees; 101 sib-pairs); and a broad category consisting of schizophrenia, schizoaffective disorder, paranoid or schizotypal personality disorder, psychosis not otherwise specified (NOS), delusional disorder, and brief reactive psychosis (70 pedigrees; 111 sib-pairs). All 70 families contained at least one individual affected with chronic schizophrenia according to DSM-III-R criteria. Three hundred and thirty-eight markers spanning the genome were typed in all pedigrees for an average resolution of 10.5 cM (range, 0-31 cM) and an average heterozygosity of 74.3% per marker. The data were analyzed using multipoint nonparametric allele-sharing and traditional two-point lod score analyses using dominant and recessive, affecteds-only models. Twelve chromosomes (1, 2, 4, 5, 8, 10, 11, 12, 13, 14, 16, and 22) had at least one region with a nominal P value <0.05, and two of these chromosomes had a nominal P value <0.01 (chromosomes 13 and 16), using allele-sharing tests in GENEHUNTER. Five chromosomes (1, 2, 4, 11, and 13) had at least one marker with a lod score >2.0, allowing for heterogeneity. These regions will be saturated with additional markers and investigated in a new, larger set of families to test for replication.

The effects of acute severe illness on pituitary-gonadal function were determined in 35 men and 19 women, including 12 who were postmenopausal. Seventeen men and 5 women had traumatic brain injury which resulted in coma. Twelve postmenopausal and 2 premenopausal women had intracranial vascular accidents. Eleven men had myocardial infarctions, while 7 men underwent elective surgery. Serial plasma samples were examined for testosterone (men), percentage of ultrafiltrable testosterone (men), estradiol (women), sex hormone-binding globulin, LH, and FSH. In men, mean testosterone levels fell by 271 +/- 72 (+/- SE), 202 +/- 63 and 195 +/- 75 ng/dl within 24 h of brain injury, myocardial infarction, or elective surgery, representing decreases of 55%, 43%, and 58%. Further declines occurred in the first and third groups to mean nadirs of 93 +/- 16 and 117 +/- 5 ng/dl, respectively. During recovery of neurological function there was no correlation between the testosterone level and the degree of neurological impairment; testosterone levels eventually returned to normal (627 +/- 77 ng/ml). The percentage of ultrafiltrable testosterone and sex hormone-binding globulin did not change in any group. Although significant decreases in mean immunoreactive LH and FSH levels were found after head trauma, and decreases in FSH were found in the men after surgery, these changes occurred after the decline in testosterone. Despite the fall in basal gonadotropin levels in the head trauma group, there were no significant differences in the gonadotropin responses to GnRH (100 micrograms) in 4 patients during their acute illness or recovery. LH, FSH, and estradiol levels in the premenopausal women were significantly lower on the second day of brain injury (LH, 10.3 +/- 4.7 vs. 3.5 +/- 0.6 mIU/ml; FSH, 3.8 +/- 1.9 vs. 1.4 +/- 0.8 mIU/ml, estradiol, 200 +/- 41 vs. 102 +/- 16 pg/ml) and remained suppressed for 7 days. Gonadotropin levels also fell in the postmenopausal women within 24 h; reductions in LH of 74% and in FSH of 62% were present by day 7 of study. We conclude that both men and women who are critically ill uniformly develop temporary hypogonadotropic gonadal insufficiency regardless of their illness. In men, it is manifested by low testosterone levels, while a comparable decrease in estradiol is present in women. The low testosterone concentrations are not due to reduced sex hormone-binding capacity. Based upon our data in postmenopausal women, hypogonadotropism also occurs in the presence of nonfunctioning gonads. Although our studies do not completely establish the pathophysiology of this disorder, they suggest a suprapituitary origin.

Activation of the sympathetic nervous system attends traumatic brain injury, but the association of the severity of neurological impairment and recovery with the extent of sympathetic nervous system stimulation is poorly defined. In this study, plasma norepinephrine (NE), epinephrine (E), and dopamine (DA) levels were measured serially in 33 patients with traumatic brain injury and compared with the Glasgow Coma Score (GCS), which was obtained concurrently. A catecholamine gradient that reflected the extent of brain injury was demonstrated within 48 hours of the injury. In patients with a GCS of 3 to 4, NE and E levels increased four- to fivefold and the DA level increased threefold above normal (NE, 1686 +/- 416 pg/ml; E, 430 +/- 172 pg/ml; DA, 236 +/- 110 pg/ml), while patients with mild brain injury (GCS, greater than 11) had slightly elevated or normal levels. Patients with marked (GCS, 5 to 7) and moderate (GCS, 8 to 10) traumatic brain injuries had intermediate levels. The prognostic value of determining admission levels of NE was shown in patients with an admission GCS of 3 to 4 1 week after injury. Patients with severe and unchanging neurological impairment 1 week after injury had markedly elevated initial NE levels (2,176 +/- 531 pg/ml), whereas initial NE levels (544 +/- 89 pg/ml) were only mildly elevated in patients who improved to a GCS of greater than 11. These data indicate that markedly elevated NE levels predict outcome in patients with comparable neurological deficits. Thus levels of circulating catecholamines are excellent endogenous and readily quantifiable markers that appear to reflect the extent of brain injury and that may predict the likelihood of recovery.

Our data support the hypothesis that measures of heart rate power spectra are inversely related and negatively correlated to severity of illness and outcome in critically ill and injured children. The phenomenon of decomplexification of physiologic dynamics may have important clinical implications in critical illness and injury.

We isolated DNA clones of MCF 247, a leukemogenic, recombinant type C virus obtained from the thymus of an AKR mouse. We determined the nucleotide sequence of the viral long terminal repeat (LTR) and the 3' end of env, and we compared the sequences to corresponding sequences of the genome of Akv virus, the putative ecotropic parent of MCF 247. By analogy with Moloney leukemia virus, we identified the amino terminus of Prp15E, the C-terminal proteolytic cleavage product of env and precursor to mature virion p15E. In MCF 247 the presumptive Prp15E is encoded by a 603-nucleotide open reading frame. The majority of this sequence is identical to that of Akv. However, a recombination event near the 3' end of the Prp15E-coding region introduces nonecotropic sequences into MCF 247, and these extend to the 3' end through the U3 portion of the LTR. The U3 regions of Akv and MCF 247 are about 83% homologous. The R and U5 regions of the LTR of MCF 247 and Akv are identical. Large RNase T1-resistant oligonucleotides analyzed previously in numerous ecotropic and MCF viral genomes were located within the Akv and MCF 247 DNA sequences. The resulting precise T1 oligonucleotide maps of the 3' ends of MCF viral genomes reveal that the biologically defined, leukemogenic class I MCFs isolated from thymic neoplasms of inbred mice all share the sequence pattern seen in MCF 247, a representative of this group; they possess recombinant Prp15E genes and derive U3 from their nonecotropic parents.

This article presents the results of two studies designed to investigate the measurement of childhood depression through self-report and reports from others. The preliminary study employed emotionally disturbed children and found that self-report of depression on the Children's Depression Inventory (CDI) was related to self-report of depression on two of three other measures but was not related to any of the measures of depression obtained from other sources. The second study investigated the convergent and discriminant validity of several measures of depression and anger in a multimethod-multitrait matrix (Campbell & Fiske, 1959) with normal children. Measures of depression and anger were obtained from self-report (CDI), peers, and teachers. The results of this second study indicated a method effect twice as large as the trait effect. Results were discussed in terms of the need to consider self-report in the discussion of depression with its covert components, in terms of the need for improved measurement instruments, and in terms of the need for additional research into the nature of depression in children.