Ethnic differences in GRHPR mutations in patients with primary hyperoxaluria type 2.

The objective of this study was to investigate ethnic differences in the glyoxylate reductase/hydroxypyruvate reductase (GRHPR) gene in patients with primary hyperoxaluria type 2 (PH2). GRHPR was genotyped in Japanese patients with PH2 and all GRHPR mutations described to date were reviewed in terms of geographic and ethnic association. We identified a novel mutation, a two-nucleotide deletion (c.248_249delTG) in exon 3 creating a premature 'stop' at codon 91. Also, we found that the c.864_865delTG mutation was associated with the rs35891798 single-nucleotide polymorphism. The allelic frequencies of the c.103delG, c.494G>A, c.403_404+2 delAAGT, and c.864_865delTG mutations in PH2 patients were 37.8%, 15.6%, 10.0%, and 10.0%, respectively. All patients with the c.103delG mutation were Caucasian. Patients with the c.494G>A mutation and 78% (7/9) of those with the c.403_404+2 delAAGT mutation were from the Indian subcontinent, whereas those with the c.864_865delTG mutation were Chinese or Japanese. Molecular analysis of GRHPR of four Japanese PH2 patients identified a novel mutation (c.248_249delTG in exon 3). Caucasians with PH2 should be screened for the c.103delG mutation; patients from the Indian subcontinent for c.494G>A; and patients of East Asian origin (particularly) for c.864_865delTG. The prevalence of the latter mutation in PH2 patients from East Asia was 75.0%.

Noble-gas-rich chondrules in an enstatite meteorite.

Chondrules are silicate spherules that are found in abundance in the most primitive class of meteorites, the chondrites. Chondrules are believed to have formed by rapid cooling of silicate melt early in the history of the Solar System, and their properties should reflect the composition of (and physical conditions in) the solar nebula at the time when the Sun and planets were forming. It is usually believed that chondrules lost all their noble gases at the time of melting. Here we report the discovery of significant amounts of trapped noble gases in chondrules in the enstatite chondrite Yamato-791790, which consists of highly reduced minerals. The elemental ratios 36Ar/132Xe and 84Kr/132Xe are similar to those of 'subsolar' gas, which has the highest 36Ar/132Xe ratio after that of solar-type noble gases. The most plausible explanation for the high noble-gas concentration and the characteristic elemental ratios is that solar gases were implanted into the chondrule precursor material, followed by incomplete loss of the implanted gases through diffusion over time.

A novel missense mutation in human lactate dehydrogenase B-subunit gene.

Reduced activity of serum lactate dehydrogenase (LDH; EC 1.1.1.27) was found in a male medical student during practical examinations of his own blood. Serum LDH isoenzyme pattern showed reductions in activities of the isoenzymes with lower subunit A/B ratios such as LDH1 and LDH2. These findings were indicative of a partial LDH-B subunit deficiency, which was confirmed in erythrocyte hemolysates by Western blotting. Polymerase chain reaction (PCR)-based DNA sequence analysis of the LDH-B subunit gene revealed a heterozygous nucleotide change: a guanine to adenine substitution in codon 69 (GGG --> GAG) at the third exon of the LDH-B subunit gene that resulted in a glycine to glutamic acid substitution (G69E). The mutation was confirmed by PCR-restriction fragment length polymorphism (RFLP) analysis using a mismatched primer to introduce a new NcoI restriction site. The same heterozygous mutation was found in his mother but not in other family members. This mutation involves a residue belonging to alphaC helix in LDH-B subunit protein molecule that functions as an interface for other subunits.

Promoter analysis of the membrane protein gp64 gene of the cellular slime mold Polysphondylium pallidum.

We cloned a genomic fragment of the membrane protein gp64 gene of the cellular slime mold Polysphondylium pallidum by inverse PCR. Primer extension analysis identified a major transcription start site 65 bp upstream of the translation start codon. The promoter region of the gp64 gene contains sequences homologous to a TATA box at position -47 to -37 and to an initiator (Inr, PyPyCAPyPyPyPy) at position -3 to +5 from the transcription start site. Successively truncated segments of the promoter were tested for their ability to drive expression of the beta-galactosidase reporter gene in transformed cells; also the difference in activity between growth conditions was compared. The results indicated that there are two positive vegetative regulatory elements extending between -187 and -62 bp from the transcription start site of the gp64 promoter; also their activity was two to three times higher in the cells grown with bacteria in shaken suspension than in the cells grown in an axenic medium.

[Deaths caused by venomous snakes in the State of São Paulo: evaluation of 43 cases from 1988 to 1993]. / Obitos por serpentes peçonhentas no Estado de São Paulo: avaliação de 43 casos, 1988/93.

UNLABELLED: The prognostic factors and the causes for obit occurrence in ophidian envenoming are yet not completely clear. PURPOSE: To determine the prognostic factors and the most probable causes for obit occurrence in ophidian envenoming. METHODS: In the State of São Paulo were notified 12,639 cases of accidents by venomous snakes from 1988 to 1993. There were 43 deaths (0.34%). The variables from the accident notification reports were compared with the promptuary notes and/or with the death records (in lethal cases). RESULTS: The snake genus was classified in 11,297 accidents and in 41 from the lethal ones. Bothrops was responsible for 9,828 (87%) accidents and 28 (68.3%) deaths, Crotalus for 1,359 (12.0%) accidents and 13 deaths (31.7%) and Micrurus for 110 (1%) accidents and no death (p < 0.05). The information regarding to sex and age of the patients was available, respectively, in 12,620 and 12,527 accidents and in all lethal ones. There were 9,783 (77.5%) male patients in the accidents and 35 (81.4%) in the lethal cases (p > 0.05). Regarding to age, 15.9% of the patients and 41.8% of the ones who died were 50 years-old or more (p < 0.05). The most frequently bitten anatomic regions were: foot (42.2%), hand (20.6%), leg (17.6%), and ankle (13.1%) in the accidents, and foot (35.7%) and leg (35.7%) in the lethal cases (p < 0.05). Coagulation disorders occurred in 34 (91.9%) from 37 patients who died (those where this datum was available). The information above was not available in non lethal cases. The most common manifestations and complications implicated as possible death causes were: acute renal failure (34-79.1%), acute respiratory failure (28-65.1%), shock (18-41.9%), and sepsis (18-41.9%). Among all lethal cases but one without information, 29.4% of the patients died within the first two days after bite and 67.6% within the first 5 days. Acute respiratory failure was most common among the patients who died owing to crotalic envenoming, and sepsis was only seen in bothropic envenoming. CONCLUSION: Most of the accidents and obits are caused by Bothrops; Crotalus envenoming, leg bites, and accidents in 50 year-old patients (or more) are frequently lethal; the most common complication in lethal cases is acute renal failure.

Obitos por serpentes peçonhentas no Estado de Säo Paulo: avaliaçäo de 43 casos, 1988/93 / Obits by venomous snakes in the State of Säo Paulo: evaluation of 43 cases from 1988 to 1993

Sao ainda mal estabelecidos os fatores prognósticos para a ocorrência de óbito nos envenenamentos por serpentes e as causas que o determinam. Objetivo. Determinar, no envenenamento ofídico, os fatores prognósticos e as causas mais prováveis do óbito. Métodos. No período de 1988 a 1993 foram notificados 12.639 casos de acidentes por serpentes peçonhentas no Estado de Sao Paulo, com 43 óbitos (0,34 por cento). Foram comparadas as variáveis obtidas das fichas de notificaçao dos acidentes com aquelas dos prontuários e/ou dos relatórios médicos dos casos de óbito. Resultados. O diagnóstico quanto ao gênero da serpente foi realizado em 11.297 acidentes, sendo 9.828 (87 por cento) por Bothrops, 1.359 (12 por cento) por Crotalus e 110 (1 por cento) por Micrurus, e em 41 casos de óbito, sendo 28 (68,3 por cento) por Bothrops e 13 (31,7 por cento) por Crotalus (p<0,05). Informaçao quanto a sexo e idade dos pacientes foi fornecida em, respectivamente, 12.620 e 12.527 acidentes. Pertenciam ao sexo masculino 9.783 (77,5 por cento) pacientes picados e 35 (81,4 por cento) que faleceram (p>0,05). Tinham 50 anos ou mais 15,9 por cento dos pacientes picados e 41,8 por cento daqueles que faleceram (p<0,05). As regioes anatômicas mais freqüentemente picadas foram: pé (42,2 por cento), maos (20,6 por cento), perna (17,6 por cento) e tornozelo (13,1 por cento), nos acidentes, e pé (35,7 por cento) e perna (35,7 por cento), nos casos de óbito (p<0,05). A alteraçao da coagulaçao ocorreu em 34 (91,9 por cento) de 37 pacientes que evoluíram para o óbito. As manifestaçoes e complicaçoes mais referidas como possíveis causas de óbito foram: insuficiência renal (34-79,1 por cento), insuficiência respiratória (28- 65,1 por cento), choque (18- 41,9 por cento) e septicemia (18- 41,9 por cento). Dentre os pacientes que evoluíram para óbito, excluindo-se um caso sem informaçao, 29,4 por cento faleceram dentro dos primeiros dois dias após a picada. A insuficiência respiratória foi mais comum entre os que faleceram devido ao envenenamento crotálico e a septicemia só foi referida para o envenenamento botrópico. Conclusao. A maioria dos acidentes e dos óbitos é causada por Bothrops; sao mais freqüentemente letais os envenenamentos por Crotalus, as picadas na perna e em pessoas com mais de 50 anos; a complicaçao mais comum nos casos fatais é a insuficiência renal.

Vigilância epidemiológica ambiental / Environmental epidemiological surveillance

Aborda a Agenda 21 do Município de Säo Paulo, em relaçäo ao binômio saúde-ambiente, que contempla, dentre outros objetivos, a eliminaçäo, diminuiçäo e prevençäo de riscos e agravos à saúde do indivíduo e da coletividade, por meio de açöes de saneamento ambiental, com fiscalizaçäo e controle sobre o meio ambiente, e os fatores que interferem na sua qualidade, propondo para isso, promover vigilância dos pontos de poluiçäo do ar, água e solo

Vigilância epidemiológica ambiental / Environmental epidemiological surveillance

Aborda a Agenda 21 do Município de São Paulo, em relação ao binômio saúde-ambiente, que contempla, dentre outros objetivos, a eliminação, diminuição e prevenção de riscos e agravos à saúde do indivíduo e da coletividade, por meio de ações de saneamento ambiental, com fiscalização e controle sobre o meio ambiente, e os fatores que interferem na sua qualidade, propondo para isso, promover vigilância dos pontos de poluição do ar, água e solo (AU)

[Clinical significance of valvular regurgitation during long-term antihypertensive therapy in patients with mild to moderate essential hypertension].

Changes in valvular function and blood pressure level during long-term pharmacological anti-hypertensive therapy were investigated in patients with mild to moderate essential hypertension. Sixty-seven patients with hypertension (mean [+/-SD] 60 +/- 10 years) were followed up for 5.4 +/- 1.6 years with antihypertensive medication. During the follow-up period, valvular dysfunction was assessed by color Doppler echocardiography. Increased mitral valve regurgitation > or = grade II and/or aortic valve regurgitation > or = grade II were aggravated in 17 patients, whereas the other 50 patients did not reveal any significant changes in valvular functions. Systolic blood pressure and end-systolic wall stress at the end of the follow-up period were higher in the aggravated group (156 +/- 30 mmHg and 79 +/- 23 dyne/cm2) than in the unchanged group (143 +/- 17 mmHg and 63 +/- 18 dyne/cm2). Dimensions of the left atrium and left ventricle at both systole and diastole were enlarged in the aggravated group (37 +/- 4 to 40 +/- 4, 31 +/- 4 to 33 +/- 4 and 48 +/- 3 to 51 +/- 3 mm, respectively), but not in the unchanged group. Nine patients in the aggravated group received additional treatment with imidapril hydrochloride over 6 months in an attempt to further reduce blood pressure levels, resulting in significant improvements in systolic blood pressure (151 +/- 12 to 129 +/- 7 mmHg), diastolic blood pressure (91 +/- 4 to 79 +/- 8 mmHg), left atrial dimension (41 +/- 3 to 39 +/- 3 mm) and left ventricular end-diastolic dimension (49 +/- 4 to 48 +/- 3 mm). Adequate pharmacological intervention can ameliorate valvular dysfunction, left ventricular enlargement and increased ventricular wall stress.

[A case of Wilson-Mikity syndrome with marked and monoclonal elevation of IgM in blood].

Wilson-Mikity syndrome, a chronic respiratory insufficiency occurring in premature newborn infants, is known to show an elevation of serum IgM, but its etiology is obscure. We studied the immunological properties of IgM in a female infant of this syndrome, whose IgM in cord blood was very high level at 639.1 mg/dl with monoclonal elevation. The IgM bound to protein(s) in human umbilical venous endothelial cells and in human lung tissue. However, IgMs from this patient after recovery, from patient's mother and from another normal newborn did not bind to the proteins. Tissue-binding activity of the patient's IgM may be associated with tissue damages in this syndrome.

Relations among heart rate, immediate memory, and time estimation under two different instructions.

The present study was done to elucidate the relations among heart rate, digit memory, and time estimation under two different instructions, standard and evaluative. 60 women heard and recalled 8 digits. Subjects reproduced 4-, 8-, and 16-sec. durations of a buzzer and also estimated the durations. Data were discussed in terms of the hypothesis of an inverted U-shaped relationship between arousal and performance. These data suggest relations among the three variables which were influenced by two different instructions.

Pyruvic acid production by an F1-ATPase-defective mutant of Escherichia coli W1485lip2.

An F1-ATPase-defective mutant, TBLA-1, was constructed by the transduction of a defective gene for the alpha subunit of F1-ATPase, atpA401, into Escherichia coli W1485lip2, a lipoic acid-requiring pyruvic acid producer. The pyruvic acid production of the strain TBLA-1 was found to be improved markedly compared with that of strain W1485lip2. In cultures using a jar fermentor, the strain W1485lip2 consumed 50 g/liter of glucose and produced 25 g/liter of pyruvic acid after culture for 32h, while strain TBLA-1 consumed the same amount of glucose, and produced more than 30 g/liter of pyruvic acid in a 24-h culture. A revertant, No. 63-1, derived from the strain TBLA-1, had a normal level of F1-ATPase activity, and showed a similar pattern of pyruvic acid production to that of strain W1485lip2.

[Respiratory changes in the blood flow pattern of the superior vena cava in patients with chronic obstructive pulmonary diseases].

Blood flow patterns in the superior vena cava (SVC) obtained from 20 elderly cases of COPD (aged 60-81) were compared with those from 24 elderly normal subjects (aged 61-80). The peak flow velocity and duration of two major antegrade flows during systole and diastole (S & D wave) were both qualitatively and quantitatively assessed with pulsed Doppler echocardiography. While peak flow velocity and duration of the S and D waves increased during inspiration and decreased during expiration in normal subjects, respiratory variations of these antegrade waves were extremely greater in patients with COPD with augmented and/or fused antegrade waves during inspiration, and there decrease was associated with an upward shift above the zero level during expiration. The duration of the D wave was significantly longer in COPD patients than in normal subjects and also revealed a significantly positive correlation with FEV1.0%. These findings suggest that SVC flow pattern is useful for the assessment of early right ventricular dysfunction in patients with COPD, but further clinical studies are required to confirm this thesis.

Acidente ofídico no Estado de Säo Paulo / Snakebites in Säo Paulo, Brazil

Foram notificados à Secretaria de Saúde, no quadriênio 1986-1989, 8.721 acidentes por serpentes peçonhentas no Estado de Säo Paulo (média anual de 2.180 casos), com coeficiente de incidência variando entre 6,8 e 7,4/100.000 habitantes. Dentre 6.834 casos em que houve referência ao gênero da serpente, 85,6% foram Bothrops, 13,3% Crotalus e 1,1% Micrurus. Os meses de novembro a abril apresentaram maior incidência (5.807) casos. Houve predominância de pacientes do sexo masculino (77,0%) e com idades entre 10 e 49 anos (74,4%). As regiöes anatômicas mais freqüentemente picadas foram pés/tornozelos (52,8%), mäos (20,5%) e pernas (17,2%). O atendimento na unidade de saúde que notificou o acidente ocorreu dentro de uma, duas, tres e seis horas após em, respectivamente, 16,9%, 46,1%, 67,5% e 88,1% dos casos. Os envenenamentos foram classificados, de acordo com a gravidade, em leves (53,5%), moderados (38,3%) ou graves (8,2%). Foram utilizadas 60.954 ampolas de antivenenos (média de 7,0 ampolas por caso). A letalidade foi de 0,4%, sendo maior no acidente por Crotalus (1,1%)do que naquele por Bothrops (0,3%). Acidentes por serpentes peçonhentas representam problema de saúde pública no Estado de Säo Paulo, acometem principalmente a populaçäo jovem do sexo masculino e têm sido causa de óbito

[Snake bites in the state of São Paulo, Brazil]. / Acidente ofídico no Estado de São Paulo.

From 1986 to 1989, 8,721 accidents caused by poisonous snakes have been notified to the Government of the State of São Paulo (Brazil), Health Department, which represented the average annual incidence rate of 6.8 to 7.4/100,000 persons. The classification of the snake genus had been possible in 6,834 cases and the distribution was: Bothrops (85.6%), Crotalus (13.3%) and Micrurus (1.1%). The vast majority of cases (5,807) occurred from November to April. The age distribution shows that 74.4% of the accidents had been suffered by people from 10 to 49 year old people with great predominance in males (77.0%). The anatomical areas more frequently bitten were feet and ankles (52.8%), hands (20.5%) and legs (17.2%). At the health center 67.5% of the patients had been treated within the first, second and third sixth hour after the accident. The distribution according to the severity of poisoning was: light (53.5%), moderate (38.3%) and severe (8.2%). The case fatality rate was 0.4%, 60,954 vials of various anti-venoms were used (an average of 7.0 vials per patient). Accidents owing to poisonous snakes are frequent in the State of São Paulo; the most important genus is Bothrops; the young male population is more often attacked; they are an important cause of death.