Tetracyclines induce changes in accessibility of ribosomal proteins to proteases

It is generally assumed that folding intermediates contain partially formed native-like secondary structures. However, if we consider the fact that the conformational stability of the intermediate state is simpler than that of the native state, it would be expected that the secondary structures in a folding intermediate would not necessarily be similar to those of the native state. beta-Lactoglobulin is a predominantly beta-sheet protein, although it has a markedly high intrinsic preference for alpha-helical structure. We have studied the refolding kinetics of bovine beta-lactoglobulin using stopped-flow circular dichroism and find that a partly alpha-helical intermediate accumulates transiently before formation of the native beta-sheets. The present results suggest that the folding reaction of beta-lactoglobulin follows a non-hierarchical mechanism, in which non-native alpha-helical structures play important roles.     

The orphan opioid receptor and its endogenous ligand--nociceptin/orphanin FQ

Following the elucidation of the amino acid sequences of the mu-, delta- and kappa-opioid receptors, a new 'orphan opioid receptor' was cloned with a high degree of homology to the 'classical' opioid receptors. The endogenous opioid peptides show little or no activity at this new receptor; however, a novel endogenous peptide for the orphan opioid receptor has been isolated and sequenced. Here, Graeme Henderson and Sandy McKnight review recent findings on this new receptor and its endogenous ligand, and address the contentious issue of whether activation of this receptor results in hyperalgesia or analgesia.     

From genes to development: phenogenetic contributions to developmental biology in Soviet Russia from 1917 to 1967

A prospective study of all new cases of chronic renal failure (CRF) including inservice referrals was done at our hospital over a period of 1 year from May 1994 to April 1995. The diagnosis of CRF was based on clinical, laboratory, and radiological features. Kidney biopsies were done when indicated. The patients were subdivided into various etiologic groups of primary renal disease according to standard criteria. There were a total of 835 cases of CRF with a median age of 43 years (range 10 days to 90 years); 67.8% of them were men. Glomerulonephritis (28.6%), diabetic nephropathy (23.2%), and interstitial nephritis (16.5%) were the most common causes of CRF, followed by obstructive nephropathy (6.4%), benign nephrosclerosis (4.1%), and polycystic kidney disease (2%). However, in patients more than 40 years of age, diabetic nephropathy was the most common cause (36.8%). The cause of CRF was unknown in 16.2% of the cases. One hundred twenty-one patients (14.5%) had an acute deterioration of their underlying renal dysfunction at presentation. This was most commonly due to accelerated hypertension (26.1%), infection (22.4%), volume depletion (20.1%), and drugs (14.9%). Anti-inflammatory drugs were the most common drugs responsible for the acute decline in renal function. One year after their initial presentation, of the 512 patients (61.3%) with end stage renal disease, 12.5% had died, 17% had received a kidney allograft, 12.7% were on some form of maintenance dialysis, and 295 patients were lost to follow-up. Of the 323 patients with less severe illness, 7 died, 209 were on outpatient treatment, and 107 patients were lost to follow-up. We conclude that the pattern of CRF in India does not differ greatly from that in the developed countries. However, it carries a poorer prognosis due to late referral and limited availability and affordability of renal replacement therapy in India.     

Enzymatic hydrolysis of anchovy oil: production of glycerides enriched in polyunsaturated fatty acids

In an attempt to produce the polyunsaturated fatty acid (PUFA)-enriched glycerides, commercially available Turkish anchovy oil (PUFA content of 27%), was hydrolyzed with 1,3-specific Rhizomucor miehei lipase. After the hydrolysis, the triglyceride (TG), diglyceride (DG), monoglyceride (MG), and free fatty acid (FFA) composition of the reaction mixture was determined, and fatty acid components of these fractions were analyzed. R. miehei lipase released PUFA extremely slowly, resulting in their accumulation in the TG and DG fractions, especially in TG. The PUFA content in the glyceride mixture (including TG, DG, and MG) increased as hydrolysis progressed. The effects of operational parameters (pH, temperature, time, and enzyme concentration) on the extent of hydrolysis were investigated. Based on these results, optimal reaction conditions were established. At optimal conditions (pH 4.0, 35 degrees C, 3 h, and enzyme concentration of 500 U/g oil), the level of PUFA in the glyceride mixture was raised to 40%. The individual TG and DG fractions contained 45 and 30% PUFA, respectively. Less than 2% of the total PUFA was lost in the FFA fraction.     

Vasectomy and vasovasostomy. I. Timing of histologic changes in immature and mature dog testis after vasectomy

The effects of vasectomy on the development and maintenance of spermatogenesis was studied using immature and mature dog testes. Bilateral vasectomy in immature dogs delayed the development of advanced spermatocytes, spermatids, and spermatozoa for about 3 months postsurgery. Spermatogenesis appeared to be recovered to control levels by 4 months postvasectomy. Spermatogenesis in mature dogs was also altered after bilateral vasectomy. Decreased numbers of advanced spermatocytes as well as maturation arrest was observed by 3 weeks postvasectomy. Seminiferous tubule cell layers quickly decreased to one to three layers as the lumina became occluded with sloughed cells by 3 to 6 weeks postvasectomy. Recovery in terms of the numbers of spermatocytes, spermatids, and spermatozoa was evident by 13 weeks postvasectomy, although occasional dog testes did not recover and appeared to be more sensitive to vasectomy-induced damage. It thus appears that vasectomy temporarily inhibits both the development and maintenance of spermatogenesis in immature as well as mature dog testes. Spermatogenesis does recover but may be maintained at somewhat lower levels after vasectomy. Changes are rapid in onset and take several weeks to be reversed. Some dog testes appear to be more sensitive to the damage and it may be irreversible in these testes.     

Determination of ftorafur and 5-fluorouracil levels in plasma and urine

The clinical diagnosis of meniscus lesions is often difficult. The authors have therefore used arthrograpy of the knee with double contrast medium. The fluoroscopic technique used in fifty cases is described. The results obtained are reported and compared with 105 other cases in which arthrography was carried out with standard radiological technique. The diagnostic accuracy for meniscus lesions is very high.     

Genetic controls of meiotic recombination and somatic DNA metabolism in Drosophila melanogaster

Recombination-defective meiotic mutants and mutagen-sensitive mutants of D. melanogaster have been examined for their effects on meiotic chromosome behavior, sensitivity to killing by mutagens, somatic chromosome integrity, and DNA repair processes. Several loci have been identified that specify functions that are necessary for both meiotic recombination and DNA repair processes, whereas mutants at combination and DNA repair processes, whereas mutants at other loci appear to be defective in only one pathway of DNA processing.     

A cytogenetic survey of 200 unclassifiable mentally retarded children with congenital anomalies and 200 normal controls

A cytogenetic survey was carried out on 200 patients with mental retardation and multiple congenital anomalies, and on 200 normal adult controls. Patients with a known syndrome were excluded from the survey. Chromosome analyses were carried out on 'blind-coded' slides using the ASG banding technique as the routine stain. After the initial analyses (at least 15 cells per person) the slides were decoded, destained and reused for C and Q band polymorphism studies. Five major chromosome abnormalities were detected in the patient group during the survey. They included three patients with de novo, apparently balanced, reciprocal translocations, karyotypes 46,XY,rcp(3;16)(q21;p12); 46,XX,rcp(5;8)(p15;q22); and 46,XX,rcp(5;12)(p11;q24); one with karyotype 47,XX,+mar and one with karyotype 46,XX,der(13),t(13;?)(q34;?). One additional patient whose karyotype in lymphocytes was 46,XX,inv(9)(p11;q13) was found to have a mosaic karyotype 46,XX,inv(9)(p11;q13)/46,XX,inv(9) (p11;q13), der(12),t(12;?)p13;?) in cultured skin fibroblasts. None of the 200 controls had a major chromosome abnormality. From the combined results of this and previous surveys it is now apparent that about 6.2% of the unclassifiable mentally retarded patients with three or more congenital anomalies and about 0.7% of the controls reveal major chromosome abnormalities.     

Effects of cardiovascular disease on driving tasks

Heart disease, even in the elderly individual, need not preclude driving; however, safety for the patient and the public is dependent on close cooperation between the patient and the physician. The patient with ischemic heart disease must be in a stable condition wherein the risk of sudden incapacitation is acceptably low. The physician must take into consideration not only the symptom history, but also the potential impact of concomitant illnesses, devices (e.g., pacemakers), and medications. The patient with congestive heart failure must be assessed for functional ability. Where there is doubt about a subjective report, a practical road test may be advisable. Consideration also should be given to limited driving under preset conditions, such as daytime only, or local roads (excluding highways). Many elderly drivers already limit their driving in such a fashion. Finally, it should be realized that a driving permit is a means to independent mobility. Where heart disease precludes driving and personal transportation is not available, physicians should advise and support their patients to obtain paratransport services where communities offer such services for otherwise immobile citizens.