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Plasma GH profiles and IGF-I concentrations were determined in Large White intact male (LW-M), female (LW-F) and castrated male (LW-C) and in Meishan intact male (MS-M) pigs between 10 and 140 d of age. Mean GH levels slightly increased between 10 and 45 d of age in LW pigs, in connection with an alteration in the temporal distribution of GH peaks, whereas neither interpulse GH level nor maximum GH level were affected. Mean GH levels decreased after 45 d of age, in connection with a decline in maximum and interpulse GH levels. IGF-I concentrations were low between 10 and 45 d of age and increased thereafter. GH secretory profiles did not differ significantly between LW-M and LW-F at either age. Castration had no effect at 45 d of age whereas LW-C exhibited lower mean, maximum and interpulse GH levels and smaller sum of GH pulse areas and widths than LW-M or LW-F at 140 d of age. IGF-I was lower in LW-C or LW-F than in LW-M at 140 d of age. The pattern of age-related changes in GH and IGF-I was similar in MS and LW pigs. However, interpulse GH level was higher and sum of GH pulse widths was smaller in MS-M than in LW-M, whatever the age. The results indicate that: i), GH and IGF-I secretions were similar in Meishan, and Large White pigs; ii), in both breeds, GH secretion declined after 45 d of age, due to decreased maximum and interpulse GH levels; iii), sex and/or castration effects on GH and IGF-I secretion were observed after 45 d of age only.

Tissue specimens from 15 patients with endobronchial papillary squamous tumours were probed for the presence of human papillomavirus DNA using the technique of in situ hybridization with probes to human papillomavirus genotypes 4, 5, 6b, 8, 11, 16 and 18. Despite the histological similarity of these lesions to known human papillomavirus-associated tumours no evidence of hybridization was detected in any of the cases analysed. It is thus unlikely that human papillomavirus has a significant role in the genesis of these tumours.

This paper reports the first British study to assess the construct validity of Beck's Hopelessness Scale (HS) and the Beck Depression Inventory (BDI). On the basis of interviews with 50 economically active parasuicide patients, it was confirmed that hopelessness accounts for the relationship between depression and suicidal intent. Moreover, it was shown that social desirability neither confounds the relationship between hopelessness and suicidal intent, nor has any predictive power in explaining variation in suicidal intent. On the other hand, the interval ('elapsed time') between the commencement of the parasuicidal act and of the research interview was significantly and positively correlated with suicidal intent, and elapsed time was a significant predictor of the total score on Beck's Suicidal Intent Scale. Two explanations for this finding are proposed: the first is based on the possibility that elapsed time is an indirect or proxy measure of medical seriousness; the second derives from the likely impact of prolonged hospital stay on the patient's interpretation or understanding of his/her behaviour. Researchers are advised to take into account the moderating effect of elapsed time when designing studies which examine psychological processes in parasuicide.

What should one do, and why? Anyone asking such questions--and everyone does so hundreds of time each day--is concerned with ethics. Product development and testing raise many ethical questions. Particularly since the rise of 'green consumerism', these are of increasing concern to people outside the cosmetics industry, and so should be of interest to those inside it. The major problem seems to be that of reaching agreement on moral and ethical issues. Overcoming this problem involves investigating what is meant by 'ethics', and how decisions depend not on facts but on 'facts-as-perceived'. These in turn depend on many factors, with one's philosophy being the most fundamental. The range of philosophical options is reviewed and it is proposed that wider discussion is the only just way to achieve agreement. Yet some things are not negotiable. There are certain key moral concepts in terms of which discussion must take place for it to be relevant. In ethics of human testing, 'respect for others', that is, avoiding exploitation, is the principal one. Some synthesis of the key moral concepts like that of Immanuel Kant is therefore recommended as the soundest and most widely acceptable basis for the necessary discussion. Defining the responsible use of human subjects covers a range of issues, moral, historical, legal and professional. For example, there may be ethical difficulties in deliberate damage induction as in SPF and irritancy testing. But above all, to avoid exploitation, there is a moral and also a legal requirement that subjects are truly volunteers. This is the basis of the concept of 'informed consent', required but not generally explained in current professional codes of practice. It is unjustified to exploit those who may be under duress, such as 'in-house volunteers' and those with low incomes. Hence in conclusion, criteria for obtaining valid informed consent are briefly reviewed. By considering issues such as these, we can help ensure that cosmetic scientists are true professionals, that is, those who recognise and are concerned with the ethical basis of their work.

The influence on protein accretion and whole-body protein turnover of changing dietary protein quality while maintaining constant energy intake was studied by varying the degree of lysine supplementation of a lysine-deficient barley-based diet given to growing pigs. Measurements of nitrogen metabolism and whole-body protein turnover, using both classical and 15N end-product methods following a single dose of [15N]glycine, were made in 49-kg male pigs given diets containing 109 g lysine-deficient protein/kg supplemented to make them (1) 'deficient', (2) 'adequate' and (3) 'in excess' with respect to lysine. The 15N dose and protein intake values used to calculate amino N flux from the cumulative urinary excretion of 15N in urea and ammonia were corrected respectively for apparent digestibilities of [15N]glycine and total N determined in a separate experiment in pigs fitted with simple ileal cannulas. N retention and biological value were significantly increased by lysine supplementation of the deficient diet to the 'adequate' level, but were not further increased by the higher level of supplementation. Rates of growth paralleled these changes. The poorer biological value of the unsupplemented diet 1 was shown also in a significantly higher excretion of urea N compared with diets 2 and 3. N digestibility was not markedly influenced by the level of lysine supplementation. Both whole-body protein synthesis and degradation increased markedly on 'adequate' supplementation of the diet with lysine, but did not increase further with an excess of lysine. It is concluded that the increase in protein accretion rate observed on supplementation of the diet with lysine was due to a greater increase in the rate of protein synthesis than of degradation, rather than a decrease in degradation rate.

Nasal turbinates were studied from 14 rhinitis patients following surgical turbinectomy, and from five subjects at autopsy. Mast cell counts on turbinectomy specimens were compared following staining with toluidine blue or Alcian blue and safranin after fixation in either paraformaldehyde or neutral buffered formalin. Mast cell numbers were significantly greater in the superficial submucosa than in the epithelium or deep submucosa in both the rhinitis group and the autopsy subjects. The combination of PFA fixation and ABS staining gave maximum mast cell counts, revealed two morphological mast cell sub-types and gave optimal demonstration of nasal tissue. Nasal mast cells are thus not uniformly distributed, appear heterogeneous under light microscopy, are present in large numbers even in the elderly, and are best demonstrated using PFA fixation and ABS staining.

Reliability of alcohol consumption reported on a self-administered questionnaire was examined in 73 gynecologic outpatients. The questionnaire included quantity-frequency questions on current beverage-specific alcohol use (wine, beer and liquor). The questions were replicated 5 years later for both the earlier period and for current drinking patterns. Results indicated that, in general, original and retrospective data were highly correlated. Only recall of wine, the least frequently drunk beverage, was more highly correlated with current than with original consumption. Frequency of drinking was typically recalled better than quantity per occasion. Beverage-specific absolute alcohol per day (AA) was less reliable than total AA. Retrospective AA values accounted for 86% of the variability in original scores. The heaviest drinkers, however, tended to report disproportionately greater alcohol intake in retrospect. Thus, almost twice as many heavy drinkers were identified on the basis of their retrospective reports compared to those identified by their original reports. Results from this study suggest that considerable confidence can be placed in retrospective reports of total alcohol consumption by nonalcoholic women over a relatively long-term interval and that heavy drinking may be reported more accurately retrospectively than currently.

The development of transgenic technology in poultry has lagged behind that in mammals because of the unique reproductive system of birds. Therefore, we chose to use wild-type and recombinant replication-competent avian leukosis viruses to determine whether these retroviruses could be artificially introduced into the germ line by injecting them near the blastoderm of fertile eggs just before incubation. We generated 23 proviral inserts that were stably inherited through two generations. Twenty-one inserts coded for complete avian leukosis virus. Two interesting inserts failed to produce complete virus. One coded for envelope glycoprotein only and the other coded for the group-specific antigen and envelope glycoprotein. Cell culture and animal studies showed that one of these inserts was very resistant to infection and oncogenesis by subgroup A field strains of avian leukosis virus. Therefore, this represents a model system for introducing genes from the pathogen into the host to induce host resistance to the pathogen. Future studies should be aimed at developing more efficient systems for introducing replication-defective retroviral vectors or cloned DNA into the germ line of poultry so that the regulation of gene expression can be studied and transgenic technology can be applied to the improvement of this highly reproductive group of farm animals.

Twelve patients in whom radial artery infections developed after catheterization in an intensive care unit over a 2-year period were reviewed. The incidence of local infection was 0.4%. An increased risk of infection was associated with prolonged catheterization (greater than 4 days). Aneurysms developed in five patients. Signs of septic emboli were present in two patients, including Osler's nodes, Janeway's lesions, and fingertip infarcts. In 6 of the 12 patients, the radial artery infection resolved with antibiotic treatment alone. The five patients with infected aneurysms were treated successfully with antibiotics and surgical excision. The radial artery was reconstructed by use of a vein graft in one patient. We believe that patients not responding promptly to antibiotics or patients with infected aneurysms are best treated by surgical excision.

Right ventricular (RV) failure is commonly treated with intravascular volume expansion to increase the RV-left atrial pressure gradient and improve left-sided filling. As RV pressure rises, chamber distention occurs and wall tension increases. These studies were designed to determine if increased wall tension might impede RV myocardial blood flow in the normal canine right ventricle and thus contribute to RV failure. Hemodynamic data, the septal-RV free wall dimension, and RV myocardial blood flow were obtained at low and high levels of preload and in both the autoregulated and vasodilated (adenosine, 2 mg per kilogram of body weight per minute) states. Elevated filling pressure decreased RV myocardial blood flow in both the autoregulated (0.85 +/- 0.18 to 0.67 +/- 0.15 ml/min/gm; p less than .05) and vasodilated (2.25 +/- 0.50 to 0.85 +/- 0.25 ml/min/gm; p less than .05) states but did not change the transmural distribution of blood flow to the right ventricle. Vasodilator reserve was markedly impaired in the high-preload state. These observations suggest that preload is an important determinant of RV myocardial blood flow. Volume loading to treat RV dysfunction may be limited by impairment of RV myocardial blood flow.

Sixty-five adenovirus isolates collected over a 3.5-year period were typed by both standard microneutralization techniques and restriction endonuclease digestion of viral DNA. Of the 65 isolates, 47 (72.3%) representing six adenovirus types could be typed by microneutralization. Eighteen isolates demonstrated partial neutralization with standard antisera to two or more adenovirus serotypes and thus could not be definitively typed. DNA analysis permitted typing of 64 of the 65 isolates (98.5%) (including four isolates which contained mixtures of two adenovirus types), and 12 different types were identified. Neutralization and DNA typing disagreed for five isolates, and in each case, digestion with multiple restriction endonucleases and DNA hybridization studies were consistent with the type assigned by DNA analysis. In addition, the DNA analysis method allowed the identification of genomic variants (genome types) of five adenovirus types. We conclude that typing clinical isolates of adenovirus by restriction endonuclease digestion of viral DNA can be done rapidly, provides additional epidemiological and typing information, and provides fewer ambiguous results than does typing by neutralization.

This report describes the unique biological properties of a transgenic chicken line that contains a defective avian leukosis virus (ALV) proviral insert that we call alv6. Chick embryo fibroblasts (CEF) containing this insert express subgroup A envelope glycoprotein since they yield focus-forming pseudotype virus when co-cultivated with transformed quail cells expressing envelope-defective Bryan high-liter Rous sarcoma virus (RSV). In addition, these cells display high interference to subgroup A RSV but not to subgroup B RSV infection. Chickens containing this insert are highly resistant to pathogenic subgroup A ALV infection, but show little immunological tolerance to subgroup B ALV infection. Thus we have artificially inserted a dominant gene for resistance to avian leukosis infection into the chicken germ line.

1. The influence of goat's-milk folate-binding protein (FBP) on the uptake of 5-methyltetrahydrofolate (MTHF) by brush-border-membrane vesicles prepared from the small intestine of the 6-d-old goat was investigated using a rapid-filtration assay. 2. Uptake of MTHF by the membrane vesicles was strongly enhanced by FBP within the pH range 4.5-6.5, with an optimum at pH 5-5.5. 3. Both the initial rate of MTHF uptake and uptake of MTHF at equilibrium were markedly increased in the presence of FBP. 4. Uptake of MTHF by brush-border-membrane vesicles was maximal when the molar ratio FBP:MTHF was 1.0-2.5. 5. The relation between pH and 125I-labelled FBP binding to the membranes was similar to that for uptake of MTHF, with an optimum at pH 5. 6. In experiments in which the osmotic pressure of the incubation medium was progressively increased with cellobiose, 125I-labelled FBP was found to be taken up primarily by binding to the brush-border-membrane surface. 7. Uptake of 125I-labelled FBP was time-dependent and saturable, with a Km of 0.39 (SE 0.07) microM and Vmax of 6.73 (SE 0.92) micrograms/mg protein. 8. Experiments in which various milk proteins (cow FBP, goat FBP, alpha-lactalbumin, beta-lactoglobulin, bovine serum albumin and lactoferrin) were allowed to compete in turn with 125I-labelled FBP for uptake by brush-border-membrane vesicles indicated that high-affinity binding was probably specific to FBP, although lactoferrin reduced uptake possibly by non-specific coating of the mucosal surface. 9. It was concluded that a folate transport mechanism mediated by the FBP in milk exists at the intestinal brush border of neonatal goats. It is suggested that this may reinforce the developing endogenous transport system.

1. Two young Friesian steers fitted with rumen cannulas were each given three different isonitrogenous and isoenergetic diets for successive periods of 2-3 weeks. The diets consisted mainly of straw and tapioca, with the nitrogen supplied mainly as decorticated groundnut meal(DCGM; diet A), in approximately equal amounts of DCGM and urea (diet B), or entirely as urea (diet C). 2. At the end of each period on a given diet, part of the dietary urea of a morning feed was replaced by a solution of [15N]urea which was infused into the rumen. Samples of rumen contents were removed just before giving the 15N dose and at 1,3,5,7 and 24 h afterwards, concentrations of ammonia and its 15N enrichment were determined and samples of mixed bacteria were prepared. Amino acids, ammonia derived mainly from amide groups, and hexosamines were prepared by ion-exchange chromatography of acid-hydrolysates of the bacteria and analysed for 15N. 3. Approximate estimates of net bacterial N synthesis were made from turnover data for rumen fluid and 15N enrichments in rumen fractions. From the determined efficiency of incorporation of urea-N into bacteria recovered at the duodenum, it was calculated that on diets A, B and C respectively 82%, 37% and 0% of the bacterial N was derived from dietary protein or other non-urea sources. 4. [15N]urea was converted rapidly to ammonia and the 15N then incorporated into bacterial amide-N; it appeared at a slower rate in total bacterial non-amide-N. Rates of incorporation into non-amide-N were highest for glutamic acid, aspartic acid and alanine, and generally lowest for proline (pro), histidine (his), phenylalanine(phe), arginine(arg), methionine(met) and galactosamine. A similar ranking was also generally observed for relative 15N abundances (15N atoms % excess in N component divided by 15N atoms % excess in total bacterial N) achieved after several hours. Relative 15N abundances in his, arg and pro increased with decreasing protein (DCGM) in the diet but those in the other protein amino acids, including the poorly labelled met, phe (and its derivative tyrosine) did not. 5. It was concluded that different extents of labelling of the amino acids (at least those present mainly in protein) indicated that different amounts of preformed units (amino acids or peptides) were used. When an adequate supply of such units was available (particularly on diet A) pro, arg, his, met and phe were derived in this way to a greater extent than the other amino acids, but whereas synthesis of pro, arg and his increased on the low-protein diet C, that of met and phe did not. Thus met and phe may be limiting for bacterial growth on diets low in protein and high in non-protein-N. 6. Differences in the extent of labelling of other bacterial N components may be due to different turnover rates.

Shedding and congenital transmission of endogenous avian leukosis viruses were studied in viremic White Leghorn hens exogenously infected with viruses with endogenous long terminal repeats (LTRs) and in four semicongenic lines of hens that naturally express infectious endogenous viruses (EVs). Relatively high titers of infectious virus EV7 (encoded at locus ev7), Rous-associated virus-0 (RAV-0), and recombinant 882/-16 RAV-0 were detected in blood cells and sera from exogenously infected hens, but marked differences were noted in the incidence of congenitally infected progeny. In enzyme immunoassays that detect viral group-specific antigen, little or no p27 was detected in albumens from dams infected with RAV-0. However, hatchmates infected with either EV7 or recombinant 882/-16 RAV-0, which was constructed with an RAV-0 LTR, shed high titers of p27. Similarly, semicongenic hens that expressed RAV-0 (EV2) (encoded at locus ev2) shed little or no p27 into albumens, but hens that harbored ev10, ev11, and ev12 shed high titers of p27. A slower electrophoretic mobility of p27, considered to be characteristic of EVs that are restricted in congenital transmission, was not associated with low levels of shedding or congenital transmission; p27 from other EVs and p27 from an avian leukosis virus field strain, all of which are shed at high levels, had mobilities identical to that of p27 from RAV-0. Although shedding and congenital transmission appear to be controlled by the viral genome, there was no correlation between low efficiency of shedding or congenital transmission and endogenous LTR or p27 sequences.

The accuracy of the results obtained from 2334 open breast biopsies performed during a 9-year period at Mount Sinai Hospital in Toronto are reviewed. With meticulous follow-up and the liberal use of needle aspiration, the senior author (A.A.B.) noted a progressive increase in his malignant to benign ratio, from 18% in 1970 to as high as 56% near the end of the study. In contrast, the overall hospital ratio of malignant to benign breast biopsies obtained over the same decade remained stationary at 25%. A low ratio implies unnecessary hospital admissions and biopsies, all adding to the patient's anxiety. The authors conclude that a currently acceptable malignant to benign ratio is 1 to 3 and that with the use of fine-needle aspiration the number of surgical biopsies can be reduced, minimizing patient anxiety and morbidity, and increasing the efficiency of hospital bed use.

Plantar fasciitis is a common cause of pain, particularly in runners and certain other athletic groups. This syndrome must be distinguished from certain other conditions, such as the tarsal tunnel syndrome and achillodynia. Conservative therapy including rest, orthotics, heel cups, anti-inflammatory agents, and icing reduce symptoms in most patients. A few athletes may need surgery to continue running. The authors released the plantar fascia and excised areas of mucinoid degeneration in 15 athletes. Fourteen returned to full athletic activity.

Experiments were carried out in vivo to investigate the pathways of ammonia incorporation into rumen bacteria, bacterial fractions and free amino acids within the bacteria. Steers were alternately given two isoenergetic, isonitrogenous diets containing the nitrogen mainly as either urea or decorticated groundnut meal (DCGM). At the end of each period on a given diet, a solution of 15NH4Cl was infused into the rumen and samples of rumen contents were removed at 2, 10, 20 and 90 min and 5, 10 and 24 h afterwards. Concentrations of ammonia and its 15N enrichment were determined and samples of mixed rumen bacteria were prepared. Bacteria were disrupted ultrasonically and separated into bacterial protein, cell wall and protein-free cell supernatant fractions. Amino acids were separated after hydrolysis and their 15N contents determined. A rumen fluid circulation pump was developed so that representative samples could be taken at very short time intervals after the introduction of the 15N label. Rumen pH changes, rumen fluid dilution rates and patterns of rumen ammonia concentrations were consistent with normal rumen metabolism. Net bacterial synthesis (as calculated from the net outflow of bacteria from the rumen) was significantly (P less than 0.05) greater with the DCGM diet (12.4 g bacterial N/d) than with the urea diet (9.24 g bacterial N/d). With both diets the 15N label rapidly left the rumen ammonia pool and entered the rumen bacteria. Analysis of the bacterial fractions indicated that the label appeared rapidly in the protein-free cell supernatant fraction and more slowly in the bacterial protein and cell wall fractions. With the DCGM diet bacteria apparently utilized intracellular label less efficiently than with the urea diet. The proportion of N in the protein-free cell supernatant was higher with the DCGM diet, suggesting increased levels of intracellular amino acids and peptides, following extracellular protein degradation. Levels of enrichment of the amino acids alanine and glutamate in the protein-free cell supernatant fraction suggested that the enzymes alanine dehydrogenase (EC 1.4.1.1) and glutamate dehydrogenase (EC 1.4.1.2 and 1.4.1.4) may be the major enzymes for assimilating ammonia when concentrations of soluble carbohydrate and rumen ammonia are high in the rumen. The high levels of intracellular alanine are discussed with reference to published work on the excretion of alanine by rumen bacteria.

Twenty-three subjects were administered three doses of inactivated herpes simplex virus (HSV) type 2 (HSV-2) glycoprotein-subunit vaccine, with doses 2 and 3 being given four and 22 weeks after dose 1. Both HSV-neutralizing antibody and antibody effective in antibody-dependent cell-mediated cytotoxicity were detected in serum samples of 12 of the 13 initially seronegative subjects by week 8. The geometric mean titers of both antibody types decreased between weeks 8 and 22 but increased one week after dose 3. HSV-neutralizing antibody remained detectable in serum samples of seven of the 10 initially seronegative subjects assayed seven months after dose 3. Cell-mediated immunity was detected by lymphocyte transformation responses to HSV-2 after vaccine administration in 12 of the 13 initially seronegative subjects. Unlike humoral antibody, which waned over time, in vitro cell-mediated immune responses remained stable over the seven-month follow-up period after dose 3. This HSV-2-subunit vaccine is well tolerated and elicits both humoral and cell-mediated immune responses to HSV.

15N-labelled mixed rumen bacteria, obtained from a steer that had received [15N]urea in its diet, were disrupted ultrasonically and freed from nucleic acids and their degradation products. Samples were subjected to a simulated abomasal digestion with pepsin. The digests were infused with a non-absorbable marker (polyethylene glycol) into the duodenum of four steers equipped with simple duodenal and re-entrant ileal cannulas and adapted to a diet of barley straw, flaked maize and urea. The outflow from the ileum was collected for 6-7 h. The mean value for the digestibility of 15N bacterial proteins in the small intestine was estimated to be 0.74. [14C]urea was administered intravenously during the infusion of the 15N-labelled protein into the duodenum. Urine and faeces were collected for the next 48 h and the proportion of urea-N produced, that was excreted in the urine, estimated from urine 14C excretion. Total urea 15N production was estimated from this value and the amount of 15N excreted in the urine. The mean proportion of 15N absorbed that was deposited in body protein, 0.70, was calculated by difference. The over-all efficiency of utilization of 15N in the infused rumen bacterial protein was 0.52. An approximate estimate of the mean rate of protein synthesis calculated from the data was 24 g/kg body-weight (W)0.75 per d and compared with an estimated net deposition of protein of 1.67 g/kg (W)0.75 per d. The importance of these values in factorial schemes for estimating ruminant N requirements is discussed.

Transformation by Rous sarcoma virus results in a dramatic increase in the rate at which the transformed cells transport glucose across the cell membrane. The increased transport rate is a consequence of an increased number of transporters in the transformed cells. Utilizing antibody raised against the purified human erythrocyte glucose transporter, we have identified the glucose transporter as a membrane glycoprotein with a monomer Mr of approximately 41,000. The increased rate of glucose transport is dependent on the activity of pp60src, the transforming protein of Rous sarcoma virus. This protein has been shown to be a protein kinase that phosphorylates on tyrosine residues. We have examined the tyrosine phosphorylation of a major cellular protein of Mr 36,000 in cells infected with a panel of partially transforming mutants of Rous sarcoma virus. One of these mutants (CU2) increases the rate of glucose transport only slightly and does not render the infected cells fully anchorage independent or tumorigenic (although other transformation parameters are fully induced). Cells infected with this mutant display a 36,000-dalton protein that is phosphorylated to a considerably lesser extent than cells infected with wild-type virus. Analyses of this sort may help to identify the cellular targets of pp60src whose phosphorylation is necessary for the increased glucose transport rate.

Sixty-nine patients with first episodes and 111 with recurrent episodes of genital herpes simplex virus (HSV) infection were enrolled in a double-blind trial comparing a 5 percent topical acyclovir ointment versus placebo, polyethylene glycol (PEG). Among acyclovir recipients with first episodes of genital herpes, the mean duration of viral shedding from genital lesions, 2.0 days, mean duration of local pain or itching, 3.6 days, and mean time to healing of lesions, 11.2 days, were less than in placebo recipients 4.6, 6.7, and 15.8 days, respectively (p less than 0.05 for each comparison). Among patients with recurrent genital herpes, the mean duration of viral shedding from genital lesions was 0.8 days in acyclovir recipients compared with 1.7 days in placebo recipients (p less than 0.001). Among men with recurrent genital herpes, the mean time to crusting and healing of lesions was 3.5 and 7.5 days in acyclovir recipients compared with 5.0 and 9.7 days in placebo recipients, p = 0.03 and 0.07, respectively. No significant differences in the duration of symptoms or healing times were noted between acyclovir- and placebo-treated women with recurrent genital herpes. Acyclovir therapy was not associated with a decrease in frequency of clinical recurrences or an increase in the time of the next recurrence in patients with either first or recurrent genital herpes. Topical acyclovir appears effective in shortening some of the clinical manifestations of genital HSV infections.

Forty-two men and 53 women patients at the Edinburgh Regional Poisoning Treatment Centre were interviewed, usually within 8-12 h of admission. The interview covered life events and difficulties from 6 months before admission. For 43 patients it was in 3 stages: 1) a list of life events and difficulties to be ticked, 2) standard probing questions about each situation ticked, 3) free flowing unstructured interviewing eliciting fuller contextual data about the situations. An independent rater scored the situations after each of the three stages, at each point being blind to information contained in subsequent stages. Four variables were scored designed to indicate the total number of life situations present, the number of situations containing either a long-term threat or personal loss element, an overall threat score and the total number of characteristics (1). The remaining 52 patients had a similar interview but containing an extra stage at the start. In this stage the patients were invited to tell the interviewer about any problems they had had in the last 6 months. Anything volunteered was probed freely before administration of the other three stages. The raters scored all four stages separately. No important differences in results from the two types of interview were found. For individual patients more than 80% of the life situation information found after the final free flow stage had been obtained by the end of the probe stage. Furthermore, the final stage took something between a third and a half the interview time. On the other hand, it was clear that it would be unreasonable to end the interview after either the first free flow or the list stages, and the gain in information from probe to final stage was highly significant and potentially important. For individual life situations 75% underwent no further change in rating after the probe stage. High though this figure is, it would not, in our view, warrant shortening the interview.

Two experiments are reported which showed that a stimulus suffix word, following eight words presented for immediate serial recall, affected recall performance differentially for the final list word: the target word. The observed difference depended on whether the target word and suffix were associated. It was concluded that both the target word and the redundant stimulus suffix were coded at the level of semantic coding as well as at the level of acoustic coding, and that an effect resulted where none had previously been found. There was no evidence to indicate that the coding of the semantic features required a switch in attention to the target word during the presentation of the list, and the coding for this was presumed to be autonomous. A model was described to explain the paradoxical effect of an associated stimulus suffix.

We have measured uptake of 3H-hexoses into diploid human cells by exposing them to brief pulses of isotopic sugar during the log-growth, subconfluent-growth, and confluent-growth (contact inhibited) phases of the strain HSWP derived from human skin. 3H-deoxyglucose appears to be taken up three times faster than 3H-glucose. After exposure to 3H-glucose for longer than one minute, the cells excrete approximately 70% of the isotope into the medium as lactate. If lactate production (and hence excretion) is abolished by treating the cellls with iodoacetic acid or dinitrofluorobenzene, neither of which inhibits transport, the uptake of 3H-glucose is found to be in fact somewhat larger than that of 3H-deoxyglucose. If cells are deprived of glucose for 24 hours, apparent uptake of 3H-glucose is enhanced 10-fold or more. This latter increase is accounted for by 2- to 3-fold enhancement of true transport plus retention of greater than 90% of the radioactivity, since little lactate is formed or excreted in glucose-deprived cells. Deoxyglucose, galactose, or pyruvate when present during glucose deprivation each have quantitatively different effects on the cells' capacity to produce lactate from a short pulse of glucose, but none of them prevents the enhancement of hexose transport. After restoration of 5 mM glucose to starved cells, their metabolsim returns to normal (in the sense that approximately 70% of the glucose taken up in a pulse is again excreted as lactate), with a half-time of 0.5 hour; but the transport of hexoses returns to control levels much more slowly, with a half-time of approximately 6 hours. The two processes appear to be independently regulated.

Relative risks for mortality due to various smoking related diseases were derived from a review of the literature on the epidemiology of smoking related illness. These were used, together with the New Zealand 1976 census data on smoking habits and the National Health Statistics mortality data, to derive the proportion of deaths which can be attributed to cigarette smoking. The results indicate that about 15 percent of deaths in New Zealand (3693 deaths annually) are attributable to smoking. This is comprised of 19 percent of all male deaths and 8 percent of all female deaths in 1976.

We injected chick syncytial strain of reticuloendotheliosis virus (CS-REV) and wild type and recombinant avian leukosis virus (ALV) near the blastoderm of unincubated fertilized embryos and CS-REV intra-abdominally at day of hatch, and we progeny tested the surviving ALV viremic males and REV viremic males and females for transmitted viral genetic material. A number of positive progeny were identified and their deoxyribonucleic acid (DNA) analyzed for restriction enzyme fragments that hybridized with viral genetic material. Most of the progeny had simple restriction enzyme patterns unlike the viremic parents or congenitally infected progeny. This is suggestive evidence that retroviral genetic information has been inserted into the germ line of chickens.

An improved affinity-chromatographic method for the preparation of folate-binding protein from cow's milk is described. Under dissociating conditions the protein appeared homogeneous in the ultracentrifuge, with a molecular weight of 35 000 +/- 1500, but it was heterogeneous on electrophoresis and ion-exchange chromatography and evidently consisted of several glycoproteins with similar molecular weights that all bound folic acid. Overall, the protein contained a high proportion of half-cystine (18 residues/molecule) and 10.3% of carbohydrate. At saturation it bound approx. 1 mol of folate/mol of protein at pH 7.2. Equilibrium-dialysis measurements of the binding of folic acid and 5-methyltetrahydrofolate to the purified protein gave non-linear Scatchard plots, the shapes of which depended on pH. The results were interpreted in terms of ligand binding to a polymerizing system in which the affinity of ligand for monomer was greater than its affinity for polymer. When the protein concentration was similar to that in cow's milk, dissociation constants (Kd) for folate and 5-methyltetrahydrofolate were 3 nM and 5 nM respectively at pH 7.2 and 37 degrees C, whereas Kd for the binding of folate to monomer was about 50 pM. The properties of the binding protein are discussed in relation to its possible role in folate absorption in the gut.

Fifty-two tibial shaft fractures in 50 patients were treated with flexible medullary nails (Ender type). In 32 cases the fracture was closed and in the remaining 28 cases the fracture was open. Forty-eight of the 52 fractures united in an average time of 16.8 weeks and there were no cases of deep infection or osteomyelitis. Nonunion in four patients required a secondary procedure to obtain union. Flexible medullary nailing is an excellent method for fixation of tibial shaft fractures because it combines the benefits of closed nailing and functional bracing while minimizing the disadvantages of each. Three-point fixation within the medullary canal maintains length alignment and avoids rotational problems. Nailing is done by closed methods without reaming. The technique allows early weight-bearing in a patellar tendon bearing cast or functional brace. Dynamic controlled motion at the fracture site leads to early callus formation which is biomechanically and biologically favorable. The procedure is relatively easy to perform, short in duration, and requires little specialized equipment. Flexible medullary nailing is an alternative treatment modality for selected open and closed displaced tibial shaft fractures.

Five cases of malignant histiocytosis of the intestine and one case of true histiocytic lymphoma were studied using immunohistological techniques. In paraffin sections tumour cells in all cases were shown to contain alpha-1-antitrypsin and to express the leucocyte common antigen. Four of the five cases of malignant histiocytosis of the intestine and the case of histiocytic lymphoma expressed the epithelial membrane antigen. Cryostat sections in four cases of malignant histiocytosis of the intestine showed that most tumour cells reacted with anti-T cell monoclonal antibodies. Only a minority expressed a typical monocyte macrophage phenotype.

1. The digestion of zinc present in human milk, cow's milk and a commercial babyfood was compared, using the piglet as a model for the human infant. 2. In piglets given human milk the pH of stomach contents was approximately 1 and 0.4 units lower than that of animals given respectively cow's milk and babyfood. The pH values of intestinal contents were approximately neutral and did not vary with the type of feed. 3. Hard casein curds were present throughout the stomachs and small intestines of animals fed on cow's milk or babyfood and between 55 and 70% Zn in these digesta samples were recovered in an insoluble form by centrifugation. In contrast, little solid material was observed in the digesta of animals fed on human milk, and 57 and 93% respectively of the Zn in digesta were recovered in a soluble form in the stomach and small intestine. 4. Soluble fractions prepared by centrifugation of digesta were analysed by filtration on Sephadex G-150. After any of the three feeds, soluble Zn in stomach contents was mainly in a low-molecular-weight form. In intestinal samples, however, Zn was present in low- and high-molecular-weight forms. Whilst there were similar amounts of Zn in the low-molecular-weight form in all samples, approximately three times as much of the total intestinal Zn was in a soluble high-molecular-weight form complexed to proteins in the animals fed on human milk compared with those fed on cow's milk or babyfood. 5. Analysis of protein-bound soluble Zn in intestinal samples on SDS-polyacrylamide gels resulted in a similar pattern of proteins for all feeds. Results indicated that at least some of these proteins were derived from intestinal secretions of the piglet. 6. Some implications of these results in respect of the mode of digestion of Zn and its biological availability to the human infant are discussed.

In an attempt to establish whether extended immuno-phenotyping allows more accurate definition of subgroups of B-cell non-Hodgkin's lymphoma (NHL) we have stained a series of 145 cases with a large panel of monoclonal antibodies that recognize B-cell differentiation and activation antigens. No antigen was expressed by all cases. The B-cell histogenesis in many cases could be confirmed only by using a panel of immunoglobulin and pan B-cell markers. There was marked phenotypic heterogeneity within and between major groups of B-cell NHL as delineated by the Kiel classification although the differentiation antigens CD5 (lymphocytic and centrocytic NHL) and OKT10 (plasma cell tumours) were more often expressed by certain morphological groups. The activation antigens 4F2 and transferrin receptor were expressed more strongly and more often by high grade NHL but other activation antigens (CD23 and CD25) were not more frequently associated with these tumours. Extended phenotyping may be of value in improving the understanding of biological abnormalities and processes involved in B-cell NHL, but we conclude that a limited panel of markers (CD3, CD5, CD22, CD45, IgM, kappa, and lambda) should be sufficient for routine diagnosis and classification of most cases.

The flavonol quercetin, a phloretin analog, inhibits transport of 2-deoxyglucose and 3-O-methylglucose in a cultured human diploid fibroblast. This inhibition is related to transport itself and not to the reported effects of flavonoids on membrane-bound ATPases. From concentration-inhibition curves at several pH's we conclude that uncharged (acid) quercetin (pK = 7.65) is the inhibitory form of the molecule (K1 = 10micron). Quercetin, unlike phloretin, is rapidly degraded in 0.1 N NaOH; the degradation products are weakly inhibitory to hexose transport.

We have artificially introduced 23 avian leukosis virus (ALV) proviral inserts into the chicken germ line by injection of wild-type and recombinant subgroup A ALV near the blastoderm of fertile eggs just before incubation. Eight viremic males were identified as germline mosaics because they transmitted proviral DNA to their generation 1 (G-1) progeny at a low frequency. Eleven female and 9 male G-1 progeny carried 23 distinct proviruses that had typical major clonal proviral-host DNA junction fragments detectable after digestion of their DNA with SacI, Southern blotting and hybridization with a probe representing the complete ALV genome. These proviruses, identified by their typical proviral-host DNA junction fragments, were transmitted to approximately 50% of their G-2 progeny after mating the G-1 parents to a line of chickens lacking endogenous ALV proviral inserts. One G-1 female carried 2 proviruses and another 3. The proviruses appeared to be scattered throughout the genome. One of the 14 proviruses carried by females was on the sex (Z) chromosome. Two of the 3 proviruses carried by a single G-1 female were linked with a recombination frequency of about 0.20. Twenty-one of the proviruses coded for infectious ALV. Two proviruses coded for envelope glycoprotein, and cell cultures carrying them were relatively resistant to subgroup A sarcoma virus, but failed to produce infectious ALV. One of these proviruses coded for internal gag proteins, had a deletion in pol, but produced non-infectious virus particles. The other failed to code for gag proteins and had no detectable internal deletions nor did it produce virus particles. Thus, we have shown that replication-competent ALV can artificially infect germ-line cells and that spontaneous defects in the inherited proviruses occur at a rather low rate.

Protein synthesis in liver and jejunal mucosa was measured in 19-d-old germ-free (GF) and conventional (CV) chicks fed on a semi-purified casein-gelatin (SCG) diet using a massive-dose single injection of [U-14C]phenylalanine. The effect of subsequent feeding for 9 d either a nitrogen-free (NF) diet or an NF diet supplemented with L-methionine (5 g/kg) and L-arginine hydrochloride (2 g/kg) (MA diet) was investigated in both types of chick. In the liver, apart from the amount of DNA, the values for wet weight, protein, RNA, fractional synthesis rate (FSR) and the amount of protein synthesized were reduced after feeding the NF diet and, to a lesser extent, the MA diet. Except that the total amount of liver DNA was higher in the CV chicks than in their GF counterparts (P less than 0.01), no environmental effect was significant. When expressed on a unit body-weight basis, liver weight, protein, RNA and DNA were significantly higher in the CV than in the GF chicks. In the jejunal mucosa, the values for wet weight, protein and RNA tended to be reduced after the NF treatment but increased after the MA treatment. Mucosal DNA and the amount of protein synthesized (microgram/mm per d) were significantly reduced after the NF diet but were less affected after the MA diet. Mucosal protein FSR and the amount of protein synthesized per mg RNA were significantly reduced after both dietary treatments. No difference was found among dietary treatments in the amount of protein synthesized per mg DNA in jejunal mucosa. Mucosal DNA was significantly higher in the CV chicks and the reverse was true for mucosal protein: DNA. It was suggested that the increased protein synthesis in jejunal mucosa and possibly in liver on supplementation of an NF diet with methionine and arginine would partly, if not completely, account for the N-sparing effect of these amino acids. Although the protein: DNA value was smaller in CV chicks, the FSR and the amount of protein synthesized tended to be higher than in their GF counterparts irrespective of nutritional status. This might imply that protein degradation rate is greater in the CV state.

Acute necrotizing pancreatitis developed in 5 of 405 patients who underwent renal transplantation. All five patients were taking immunosuppressive medication (azathioprine and steroids). Three patients also received rabbit antithymus serum. Alcohol ingestion or cholelithiasis did not play any causative role in the pancreatitis, which began between 7 days and 13 months after renal transplantation. The delay from the time of admission for pancreatitis to surgical exploration was a mean of 17 days. Operative findings included pancreatic necrosis, hemorrhage and abscess formation. All five patients died of the complications of necrotizing pancreatitis--persistent sepsis, respiratory and renal failure, upper gastrointestinal bleeding and disseminated intravascular coagulation. This review demonstrates that prolonged conservative therapy in renal transplant patients with necrotizing pancreatitis is associated with high mortality. The authors believe that earlier surgical intervention will lead to increased survival.

The reactivity of a new monoclonal antibody to the T-cell beta chain antigen receptor (beta F1) with routinely processed paraffin sections from patients with T-cell lymphoma is described. Staining of tumour cells was seen in 36/47 cases of T-cell lymphoma. No staining was seen in any cases of B-cell lymphoma (0/21 cases), nine of which had previously been shown to react with other T-cell antibodies (MT1/UCHL1). We conclude that beta F1 is a specific marker for demonstrating a T-cell histogenesis of lymphoma and with advantages over other currently available antibodies reactive with paraffin sections.